September 11 as A Turning Point In International Law Essay

September 11 as A Turning Point In International Law - Essay Example 2, para 4. cited in Schmitt 521) "as the events of 9/11 tragically demonstrated, domestic or international law enforcement may prove an insufficient tool in effectively defending against non-State actors, such as terrorists" (Schmitt 539). "the attack directly against the Taliban on October 7, 2001 challenged then-existing legal understandings of the quality and quantity of support necessary to attribute an armed attack by a non-State actor to its State sponsor" Schmitt (547). The United States approached the UN Security Council to determine the extent of military and non-military reaction to the September 11 attacks. The UN, in response, issued two new resolutions in the same month viz. Resolution 1368 and Resolution 1373. The latter explicitly declared those terrorist attacks as detrimental to international peace and security (McWhinney 280). "the administration blurs the distinction between "rouge states" and terrorists, essentially erasing the difference between terrorists and those states in which they reside. But these distinctions do indeed make a difference" (Crawford 31) Crawford (31) delineates four indispensable conditions in order for a pre-emptive action to be justified under international law. These conditions implicate that any country should not undertake such motives to advance their "imperial interests", they should be certain and be able to demonstrate potent evidence about the imminence of threat, pre-emptive strategies should be undertaken with sheer certainty that it would successfully reduce the threat and finally any intended military action against the threatening forces should be inevitable for a country to protect itself. Also, it is very important not to identify any state or organisation as imminent threat on the mere ground that it possesses the capability to harm another country. "a conception of self that justifies legitimate pre-emption in self-defence must be narrowly confined to immediate risks to life and health within borders or to life and health of citizens aboard" (Crawford 32) "not preemption, but paranoid aggression" (Crawford 32) "a preemptive-preventive doctrine moves us closer to a state of nature than to a state of international law" (Crawford 34) "When responding to a situation involves the use of force, it can

What are the products made from benzene Essay Example | Topics and Well Written Essays - 1000 words

What are the products made from benzene - Essay Example The utilization of this product is not linked with human being directly; this chemical is used in preparation of different human related products as indirect link with human beings (Wilcox and Greenbaum, 1965). So, people should be careful about the usage of those products which are prepared with participation of benzene chemical. This concentration is supportive for the health protection of people in the social and commercial way of life. Benzene is commonly used in different industrial programs which are linked with all people without any doubt. For example, this chemical is used in preparation of drugs, lubricants, detergents, nylon, wheels and various other significant products which are linked with human life (National Research Council & United States, 1984). It is mostly used in United Stated and this is also confirmed that latest researches are also performed about advantages and disadvantages of benzene are also related with western countries (Cavani, 2009). According to the professional persons, benzene is a colorless chemical which is used in product due to attractive smell of this element. Accordingly, the harms of this chemical are stated as the link of benzene with petroleum is certain without any reservation. Some products which are prepared with benzene chemical are enlisted as under; So, it can be stated that benzene is an important chemical element for the success of various industries. So, proper care is needed for making protection of human health certain and obvious in the communal and commercial way of life. Benzene is an important element to make painting products elegant and gorgeous in the community. This chemical is used in various departments and this utilization is helpful to gain success obvious in paint manufacturing programs. There are three major parts of paint industry which are mentioned as coloring, binding and solvent agents in the industry. These all parts are related with utilization of benzene chemical which is

Ethical Situation in Healthcare

Ethical Situation in Healthcare Azmir Bin Abdul Latiff ENQUIRY 3 Discuss the situation described from the perspective of the health and human services professional. What would be the most appropriate response to the situation? Include in your answer the: ethical frameworks, theories and principles appropriate to responding to the scenario relevant professional codes of ethics and codes of practice relevant legislation and guidelines, statute and common law, government guidelines. cultural and community values related to the issue, and comment on what would be appropriate and inappropriate responses of the health professional to the situation. Case Study Three Dr Simons was the new Surgical Consultant at a large public hospital. He was trained in the USA, and came with a reputation for being very fierce. Dr Simons regularly yelled at other staff, in particular Nurses, if his requests were not immediately met. He justified that if â€Å"Chefs could yell at staff in a kitchen, where nobody’s life is at stake, he could yell at incompetence when it is a life and death situation†. Although the Nursing staff disliked Dr Simons, they continued to work with him as they felt intimidated. One nurse, Clare, worked in Recovery where she looked after patients directly after they had surgery. She noticed that a very large proportion of Dr Simons’ patients were in considerable pain after surgery, and several patients had adverse outcomes such as heavy bleeding from the surgical site. Clare was concerned about this, but was scared to report it for fear of reprisal from Dr Simons. Eventually she was so worried about the patients’ health she made an official complaint to the Hospital management. She was called in to the Director of Nursing and told that if she ever made trouble like that again, a reason would be found to not continue her employment. She was told that Dr Simons was a senior staff member, and she had no right to make complaints about his medical conduct as she was â€Å"only a Nurse†. What should Clare’s response be? As healthcare professionals, Nurse Clare and Doctor Simons are bound by or influenced by professional codes of practice and ethics, Hippocraticoaths, statutes and laws and government guidelines. Clare was being responsible and professional by reporting and making an official complaint to the hospital management as she was concerned for the health and well being of her patients. It is her responsibility to report any suspicions of malpractice or substandard care to the higher authority if the senior staff members do not investigate and take actions to mitigate the suspicions. Considering that most of Doctor Simon’s patients were in a lot of pain and were exhibiting signs of heavy bleeding at the surgical site, Clare did raised her concerns to the hospital management and may have had exposed him to medical malpractice in the process. Instead of investigating the issue, the hospital management threatened to discontinue her employment. The fact that Doctor Simon is protected by the senior staff members despite his incompetence and medical malpractice is disturbing. Health professionals have codes of practice and guidelines to abide by. The National law requires Clare to report to a government body, AHPRA , if registered health practitioner knows of another practitioner’s destructive actions. AHPRA is a government body that focuses on serious cases of substandard practice or conduct by practitioners, or serious cases of impairment. This is to safeguard patients and to reduce or prevent the risk of potential harm from a result of medical malpract ice, negligence or impairment. A mandatory notification requirement helps to prevent the public from being placed at risk of harm. This shows that Clare have the right to report Doctor Simon’s attitude and actions to AHPRA if the senior staff members do not take action against Doctor Simon after the reported incidents as Doctor Simon have behaved in a way that poses a serious risk to the public. Ethics refers to standards of behaviors which are the best possible act in the many situations and issues that are raised as concerns. Ethics are not based on science, law, religion, accepted social norm, or feelings. It is viewed as approaches or processes such as, the utilitarian approach, an approach that is the one that provides the most good or does the least harm. The Utilitarian Approach deals with penalty; it tries both to increase the good done and to reduce the harm done. The Rights Approach is the one that best protects and respects the moral rights of those affected. This approach starts from the belief that humans have a dignity based on their human nature and their ability to choose freely what they do with their lives. TheJustice Approach, the idea that all people should be treated equally and fairly. Each of the approaches helps us determine what standards of behavior can be considered ethical. As there are still problems with the mentioned approaches, not all healthc are professionals agree to the specific approaches or the same set of human and civil rights. An ethical framework based on the approaches is to first recognize the ethical issue. After that, the healthcare professional must gather all the facts pertaining to the issue. He/she then must learn more about the situation and lay down the options available before acting on it. Subsequently, the next step would be to evaluate alternative approaches like the Utilitarian approach, Rights approach or Justice approach that best fits the situation. After considering the suitable approach needed to tackle the situation, he/she must act on the decided options. The end result must be reflected and evaluated if need be for further improvements. As a healthcare professional, Doctor Simon is to abide by the Ethics that is in the best interest of his patients. This means that he must provide the best healthcare and at the same time, reduce the amount of harm done on his patients. In Clare’s perspective, she viewed Doctor Simon’s actions as most harmful to the patients as he had caused a lot of pain and bleeding to his patients’ surgical site. As he did not abide by the Ethics in Clare’s viewpoint, she has the right to report him to the higher authority to protect the patients. The practice of Doctor Simon who caused pain and heavy bleedings to his patients was accepted by his peers may be due to the ‘Bolam’ test where traditionally, doctors were not said to have breached their duty of care if they acted in accordance with a practice accepted by their peers: Bolam v Friern Hospital Management Committee (1957). As their peers were the ones who set the standard, substandard care and malpractice were more prominent during those times as long as the practice conducted is accepted by the rest. However, this soon changed because of an incident whereby a patient was left almost blind when the doctor had failed in informing her on the risk of sympathetic ophthalmia. In this case, there were two opposing sides in which one would inform the patient and another would not inform. Due to this, the law was changed and the standard was set not by peers but by the court instead. Based on the Professional code of Ethics and Conduct, Ethical Frameworks, Theories and Principles, and Law and Guidelines, Clare should report to AHPRA if the higher authorities did not take any actions against Doctor Simon. By reporting to AHPRA also on the culture of the higher authority in her hospital, Clare would be able to break the inappropriate culture that is similar to ‘Bolam’ test. By doing so, Clare would be able to help stop the substandard practices and minimize the potential harm on the patients while maximizing the healthcare system to its optimum capabilities. This way, the patients would be able to receive better care with a methodological and ethical approach. References Dhai, A. (2008). Understanding professionalism in health care in the twenty first century.SADJ, 63, 174, 176-7 Faunce, T., Shat, K., Adams, C. (2008). Health the law. : Hot topics (Sydney, N.S.W.); no. 64. Retrieved on 30/5/2014 from: http://www.nursingmidwiferyboard.gov.au/Codes-Guidelines-Statements/Codes-Guidelines/Guidelines-for-mandatory-notifications.aspx M.Velasquez, D. Moberg, M. J. Meyer, T. Shanks, M. R. McLean, D. DeCosse, Claire Andre and Kirk O. Hanson. A Framework for Thinking Ethically (May 2009) retrieved from: http://www.scu.edu/ethics/practicing/decision/framework.html

Relationship of Washington Square to Henry Jamess Other Novels :: Washington Square Henry James

Relationship of Washington Square to Henry James's Other Novels According to Bette Howland in "Washington Square, the Family Plot," the idea that Henry James should leave Washington Square out of his New York Edition, is "a fitting irony" in that "like Dr. Sloper in the novel, James disinherited his heroine; [and] cut her out of his will" (1). Although James might have wished us to treat Washington Square as an orphan, an outcast, a black sheep as compared with its "better" relatives, Howland's essay quite clearly establishes a familial link between this and James's other, more famous works. As Howland says, "Not only is Washington Square, though disowned, a member of the family--it is the original, the mother lode" (1). Howland begins her analysis by looking at how James took an anecdote given to him one night at a dinner party and made the "tale purely American." To Howland, the very location of Washington Square stands for James' perception of "the stifling provincial life of America" in that it is "the object of Morris' aspirations; the prison of Catherine's confinement; the seat of the Doctor's power (sic)" (16). By confining the characters to the small world of Washington Square, says Howland, James created a "closed system" in which he could work his irony most effectively (5). She also notes how James changed the simple anecdote into an ironic contest of wills. He made the father the "heavy" rather than the fortune-hunter, and he made the father a scientist, a "scholarly doctor" so that he fit in with the American values of earning an income (or seeming to), and appreciating science (Howland 3). Howland also does an apt comparison of Washington Square in relationship to James's other novels by pointing out how he frequently talked about love in terms of the financial. As Howland says, "[With James], there's never enough [love] to go around; one person's gain is always another's loss" (7), and money is quite commonly involved in the equation. In addition, James has another system of economy that is always at work in his novels. As Howland says, "at the beginning, the good heroines are all in the dark," but "by the end, they are the only ones who see" (15).

Choir

Frisco High 2009 Coffeehouse: A Night in Manhattan The director of the Frisco High choir is Tracy Bradstreet. During the performance, I didn’t see her direct the choir while they were singing. All the songs were in English. The whole performance was a Broadway theme. The choir overall was really good; the acting was nice. Although, the guys need to project their voices more. They’re too quiet and too shy!! I think that everyone needs to open their mouths more wide so we can actually understand what they’re saying.During the concert, there were a lot of solo performances. In the song Vanilla Ice Cream from She Loves Me, Elison Willis was the soloist. She was awesome, and so was Kenneth West when he sang A Heart Full Of Love from Les Miserables along with Allison Behne and Rebecca Carrington. Allison Behne sang On My Own from Les Miserables. I absolutely love her voice. Her vibrato is awesome! She can’t really sing the high notes though. Bring Him Home from Les Miserables was sung by Alex Nelson. At the beginning of the song, he looked kind of scared.Although, he has a nice voice, very strong; great vibrato. L. O. V. E. was performed by Shachi Merchant. His dance was awesome! But he needs to sing louder; I could barely hear him even with the microphone. Heather Caton sang Part of Your World from The Little Mermaid. She was a little late for some parts; slow and fast here and there. I kind of heard a few flats. The ending was good, though. Pioneer Heritage Middle School Show Choir sang a song called It Don’t Mean a Thing If It Ain’t Got That Swing.The guys (even though there was only three of them, all the more reason) need to sing louder!! They got to project their voice more. Half of the time, they sang faster than what the CD played. Near the end of the first Act, the Frisco choir sang a medley of Wicked the Broadway musical. All choirs (excluding PHMS) sang No One Mourns the Wicked. One word: wow. They sound so totally awesome when they all sing together! The guys could still sing a little louder though. Next, two girls (Meghan Horstdaniel and Nicole Hathaway) sang What Is This Feeling.They need to add more feeling into that song because during that song, Elphaba and Galinda show how much they loathe each other. It felt like Meghan and Nicole didn’t add a lot of hatred towards their enemy character. In the song Popular, Ashley Romo was the soloist. She had a really pretty voice. But the choir sang too fast when they sang â€Å"you†¦will†¦be†¦Ã¢â‚¬  It just didn’t match the music. Dancing Through Life had two soloists: Taylor Duke and Frank Rosamond. Frank was really good with his solo.On the other hand, Taylor was okay. The choir rocked hard, though. Plus their dancing. Choir sang the song For Good and it was totally awesome! The last song they sang before intermission was Defying Gravity. The soloist, Jourdan Kolb had a pretty voice! Choir was great, once again and the ending of the song was magnifique! I wasn’t able to stay for the whole concert; just only the first Act. Overall though, Act I was really funny. They had cool props, but too many feedbacks with the microphone. They need to fix that.

Forward the Foundation Chapter 23

5 â€Å"Dad,† said Raych with some concern, â€Å"you look tired.† â€Å"I dare say,† said Hari Seldon, â€Å"I feel tired. But how are you?† Raych was forty-four now and his hair was beginning to show a bit of gray, but his mustache remained thick and dark and very Dahlite in appearance. Seldon wondered if he touched it up with dye, but it would have been the wrong thing to ask. Seldon said, â€Å"Are you through with your lecturing for a while?† â€Å"For a while. Not for long. And I'm glad to be home and see the baby and Manella and Wanda-and you, Dad.† â€Å"Thank you. But I have news for you, Raych. No more lecturing. I'm going to need you here.† Raych frowned. â€Å"What for?† On two different occasions he had been sent to carry out delicate missions, but those were back during the days of the Joranumite menace. As far as he knew, things were quiet now, especially with the overthrow of the junta and the reestablishment of a pale Emperor. â€Å"It's Wanda,† said Seldon. â€Å"Wanda? What's wrong with Wanda?† â€Å"Nothing's wrong with her, but we're going to have to work out a complete genome for her-and for you and Manella as well-and eventually for the new baby.† â€Å"For Bellis, too? What's going on?† Seldon hesitated. â€Å"Raych, you know that your mother and I always thought there was something lovable about you, something that inspired affection and trust.† â€Å"I know you thought so. You said so often enough when you were trying to get me to do something difficult. But I'll be honest with you. I never felt it.† â€Å"No, you won over me and†¦ and Dors.† (He had such trouble saying the name, even though four years had passed since her destruction.) â€Å"You won over Rashelle of Wye. You won over Jo-Jo Joranum. You won over Manella. How do you account for all that?† â€Å"Intelligence and charm,† said Raych, grinning. â€Å"Have you thought you might have been in touch with their-our-minds?† â€Å"No, I've never thought that. And now that you mention it, I think it's ridiculous. With all due respect, Dad, of course.† â€Å"What if I told you that Wanda seems to have read Yugo's mind during a moment of crisis?† â€Å"Coincidence or imagination, I should say.† â€Å"Raych, I knew someone once who could handle people's minds as easily as you and I handle conversation.† â€Å"Who was that?† â€Å"I can't speak of him. Take my word for it, though.† â€Å"Well-† said Raych dubiously. â€Å"I've been at the Galactic Library, checking on such matters. There is a curious story, about twenty thousand years old and therefore back to the misty origins of hyperspatial travel. It's about a young woman, not much more than Wanda's age, who could communicate with an entire planet that circled a sun called Nemesis.† â€Å"Surely a fairytale.† â€Å"Surely. And incomplete, at that. But the similarity with Wanda is astonishing.† Raych said, â€Å"Dad, what are you planning?† â€Å"I'm not sure, Raych. I need to know the genome and I have to find others like Wanda. I have a notion that youngsters are born-not often but occasionally-with such mental abilities, but that, in general, it merely gets them in trouble and they learn to mask it. And as they grow tip, their ability, their talent, is buried deep within their minds- sort of an unconscious act of self-preservation. Surely in the Empire or even just among Trantor's forty billion, there must be more of that sort, like Wanda, and if I know the genome I want, I can test those I think may be so.† â€Å"And what would you do with them if you found them, Dad?† â€Å"I have the notion that they are what I need for the further development of psychohistory.† Raych said, â€Å"And Wanda is the first of the type you know about and you intend to make a psychohistorian out of her?† â€Å"Perhaps.† â€Å"Like Yugo. Dad, no!† â€Å"Why no?† â€Å"Because I want her to grow up like a normal girl and become a normal woman. I will not have you sitting her before the Prime Radiant and make her into a living monument to psychohistorical mathematics.† Seldon said, â€Å"It may not come to that, Raych, but we must have her genome. You know that for thousands of years there have been suggestions that every human being have his genome on file. It's only the expense that's kept it from becoming standard practice; no one doubts the usefulness of it. Surely you see the advantages. If nothing else, we will know Wanda's tendencies toward a variety of physiological disorders. If we had ever had Yugo's genome, I am certain he would not now be dying. Surely we can go that far.† â€Å"Well, maybe, Dad, but no further. I'm willing to bet that Manella is going to be a lot firmer on this than I am.† Seldon said, â€Å"Very well. But remember, no more lecture tours. I need you at home.† â€Å"We'll see,† Raych said and left. Seldon sat there in a quandary. Eto Demerzel, the one person he knew who could handle minds, would have known what to do. Dors, with her nonhuman knowledge, might have known what to do. For himself, he had a dim vision of a new psychohistory-but nothing more than that. 6 It was not an easy task to obtain a complete genome of Wanda. To begin with, the number of biophysicists equipped to handle the genome was small and those that existed were always busy. Nor was it possible for Seldon to discuss his needs openly, in order to interest the biophysicists. It was absolutely essential, Seldon felt, that the true reason for his interest in Wanda's mental powers be kept secret from all the Galaxy. And if another difficulty was needed, it was the fact that the process was infernally expensive. Seldon shook his head and said to Mian Endelecki, the biophysicist he was now consulting, â€Å"Why so expensive, Dr. Endelecki? I am not an expert in the field, but it is my distinct understanding that the process is completely computerized and that, once you have a scraping of skin cells, the genome can be completely built and analyzed in a matter of days.† â€Å"That's true. But having a deoxyribonucleic acid molecule stretching out for billions of nucleotides, with every purine and pyrimidine in its place, is the least of it; the very least of it, Professor Seldon. There is then the matter of studying each one and comparing it to some standard. â€Å"Now, consider, in the first place, that although we have records of complete genomes, they represent a vanishingly small fraction of the number of genomes that exist, so that we don't really know how standard they are.† Seldon asked, â€Å"Why so few?† â€Å"A number of reasons. The expense, for one thing. Few people are willing to spend the credits on it unless they have strong reason to think there is something wrong with their genome. And if they have no strong reason, they are reluctant to undergo analysis for fear they will find something wrong. Now, then, are you sure you want your granddaughter genomed?† â€Å"Yes, I do. It is terribly important.† â€Å"Why? Does she show signs of a metabolic anomaly?† â€Å"No, she doesn't. Rather the reverse-if I knew the antonym of ‘anomaly.' I consider her a most unusual person and I want to know just what it is that makes her unusual.† â€Å"Unusual in what way?† â€Å"Mentally, but it's impossible for me to go into details, since I don't entirely understand it. Maybe I will, once she is genomed.† â€Å"How old is she?† â€Å"Twelve. She'll soon be thirteen.† â€Å"In that case, I'll need permission from her parents.† Seldon cleared his throat. â€Å"That may be difficult to get. I'm her grandfather. Wouldn't my permission be enough?† â€Å"For me, certainly. But, you know, we're talking about the law. I don't wish to lose my license to practice.† It was necessary for Seldon to approach Raych again. This, too, was difficult, as he protested once more that he and his wife, Manella, wanted Wanda to live a normal life of a normal girl. What if her genome did turn out to be abnormal? Would she be whisked away to be prodded and probed like a laboratory specimen? Would Hari, in his fanatical devotion to his Psychohistory Project, press Wanda into a life of all work and no play, shutting her off from other young people her age? But Seldon was insistent. â€Å"Trust me, Raych. I would never do anything to harm Wanda. But this must be done. I need to know Wanda's genome. If it is as I suspect it is, we may be on the verge of altering the course of psychohistory, of the future of the Galaxy itself!† And so Raych was persuaded and somehow he obtained Manella's consent, as well. And together, the three adults took Wanda to Dr. Endelecki's office. Mian Endelecki greeted them at the door. Her hair was a shining white, but her face showed no sign of age. She looked at the girl, who walked in with a look of curiosity on her face but with no signs of apprehension or fear. She then turned her gaze to the three adults who had accompanied Wanda. Dr. Endelecki said with a smile, â€Å"Mother, father, and grandfather-am I right?† Seldon answered, â€Å"Absolutely right.† Raych looked hang-dog and Manella, her face a little swollen and her eyes a little red, looked tired. â€Å"Wanda,† began the doctor. â€Å"That is your name, isn't it?† â€Å"Yes, ma'am,† said Wanda in her clear voice. â€Å"I'm going to tell you exactly what I'm going to do with you. You're right-handed, I suppose.† â€Å"Yes, ma'am.† â€Å"Very well, then, I'll spray a little patch on your left forearm with an anesthetic. It will just feel like a cool wind. Nothing else. I'll then scrape a little skin from you just a tiny bit. There'll be no pain, no blood, no mark afterward. When I'm done, I'll spray a little disinfectant on it. The whole thing will take just a few minutes. Does that sound all right to you?† â€Å"Sure,† said Wanda, as she held out her arm. When it was over, Dr. Endelecki said, â€Å"I'll put the scraping under the microscope, choose a decent cell, and put my computerized gene analyzer to work. It will mark off every last nucleotide, but there are billions of them. It will probably take the better part of a day. It's all automatic, of course, so I won't be sitting here watching it and there's no point in your doing so, either. â€Å"Once the genome is prepared, it will take an even longer time to analyze it. If you want a complete job, it may take a couple of weeks. That is why it's so expensive a procedure. The work is hard and long. I'll call you in when I have it.† She turned away, as if she had dismissed the family, and busied herself with the gleaming apparatus on the table in front of her. Seldon said, â€Å"If you come across anything unusual, will you get in touch with me instantly? I mean, don't wait for a complete analysis if you find something in the first hour. Don't make me wait.† â€Å"The chances of finding anything in the first hour are very slim, but I promise you, Professor Seldon that I will be in touch with you at once if it seems necessary.† Manella snatched Wanda's arm and led her off triumphantly. Raych followed, feet dragging. Seldon lingered and said, â€Å"This is more important than you know, Dr. Endelecki.† Dr. Endelecki nodded as she said, â€Å"Whatever the reason, Professor, I'll do my best.† Seldon left, his lips pressed tightly together. Why he had thought that somehow the genome would be worked out in five minutes and that a glance at it in another five minutes would give him an answer, he did not know. Now he would have to wait for weeks, without knowing what would be found. He ground his teeth. Would his newest brainchild, the Second Foundation, ever be established or was it an illusion that would remain always just out of reach? 7 Hari Seldon walked into Dr. Endelecki's office, a nervous smile on his face. He said, â€Å"You said a couple of weeks, Doctor. It's been over a month mow.† Dr. Endelecki nodded. â€Å"I'm sorry, Professor Seldon but you wanted everything exact and that is what I have tried to do.† â€Å"Well?† The look of anxiety on Seldon's face did not disappear. What did you find?† â€Å"A hundred or so defective genes.† â€Å"What! Defective genes. Are you serious, Doctor?† â€Å"Quite serious. Why not? There are no genomes without at least a hundred defective genes; usually there are considerably more. It's not as bad as it sounds, you know.† â€Å"No, I don't know. You're the expert, Doctor, not I.† Dr. Endelecki sighed and stirred in her chair. â€Å"You don't know anything about genetics, do you, Professor?† â€Å"No, I don't. A man can't know everything.† â€Å"You're perfectly right. I know nothing about this-what do you call it?-this psychohistory of yours.† Dr. Endelecki shrugged, then continued. â€Å"If you wanted to explain anything about it, you would be forced to start from the beginning and I would probably not understand it even so. â€Å"Now, as to genetics-â€Å" â€Å"Well?† â€Å"An imperfect gene usually means nothing. There are imperfect genes-so imperfect and so crucial that they produce terrible disorders. These are very rare, though. Most imperfect genes simply don't work with absolute accuracy. They're like wheels that are slightly out of balance. A vehicle will move along, trembling a bit, but it will move along.† â€Å"Is that what Wanda has?† â€Å"Yes. More or less. After all, if all genes were perfect, we would all look precisely the same, we would all behave precisely the same. It's the difference in genes that makes for different people.† â€Å"But won't it get worse as we grow older?† â€Å"Yes. We all get worse as we grow older. I noticed you limping when you came in. Why is that?† â€Å"A touch of sciatica,† muttered Seldon. â€Å"Did you have it all your life?† â€Å"Of course not.† â€Å"Well, some of your genes have gotten worse with time and now you limp.† â€Å"And what will happen to Wanda with time?† â€Å"I don't know. I can't predict the future, Professor; I believe that is your province. However, if I were to hazard a guess, I would say that nothing unusual will happen to Wanda-at least, genetically-except the gathering of old age.† Seldon said, â€Å"Are you sure?† â€Å"You have to take my word for it. You wanted to find out about Wanda's genome and you ran the risk of discovering things perhaps it is better not to know. But I tell you that, in my opinion, I can see nothing terrible happening to her.† â€Å"The imperfect genes-should we fix them? Can we fix them?† â€Å"No. In the first place, it would be very expensive. Secondly, the chances are that they would not stay fixed. And finally, people are against it. â€Å"But why?† â€Å"Because they're against science in general. You should know this as well as anyone, Professor. I'm afraid the situation is such, especially since Cleon's death, that mysticism has been gaining ground. People don't believe in fixing genes scientifically. They would rather cure things by the laying on of hands or by mumbo-jumbo of some sort or other. Frankly it is extremely difficult for me to continue with my job. Very little funding is coming in.† Seldon nodded. â€Å"Actually I understand this situation all too well. Psychohistory explains it, but I honestly didn't think the situation was growing so bad so rapidly. I've been too involved in my own work to see the difficulties all around me.† He sighed. â€Å"I've been watching the Galactic Empire slowly fall apart for over thirty years now-and now that it's beginning to collapse much more rapidly, I don't see how we can stop it in time.† â€Å"Are you trying to?† Dr. Endelecki seemed amused. â€Å"Yes, I am.† â€Å"Lots of luck. About your sciatica. You know, fifty years ago it could have been cured. Not now, though.† â€Å"Why not?† â€Å"Well, the devices used for it are gone; the people who could have handled them are working on other things. Medicine is declining.† â€Å"Along with everything else,† mused Seldon. â€Å"But let's get back to Wanda. I feel she is a most unusual young woman with a brain that is different from most. What do her genes tell you about her brain?† Dr. Endelecki leaned back in her chair. â€Å"Professor Seldon do you know just how many genes are involved in brain function?† â€Å"No. â€Å"I'll remind you that, of all the aspects of the human body, the brain function is the most intricate. In fact, as far as we know, there is nothing in the Universe as intricate as the human brain. So you won't be surprised when I tell you that there are thousands of genes that each play a role in brain function.† â€Å"Thousands?† â€Å"Exactly. And it is impossible to go through those genes and see anything specifically unusual. I will take your word for it, as far as Wanda is concerned. She is an unusual girl with an unusual brain, but I see nothing in her genes that can tell me anything about that brain-except, of course, that it is normal.† â€Å"Could you find other people whose genes for mental functioning are like Wanda's, that have the same brain pattern?† â€Å"I doubt it very much. Even if another brain were much like hers, there would still be enormous differences in the genes. No use looking for similarities. Tell me, Professor, just what is it about Wanda that makes you think her brain is so unusual?† Seldon shook his head. â€Å"I'm sorry. It's not something I can discuss.† â€Å"In that case, I am certain that I can find out nothing for you. How did you discover that there was something unusual about her brain-this thing you can't discuss?† â€Å"Accident,† muttered Seldon. â€Å"Sheer accident.† â€Å"In that case, you're going to have to find other brains like hers-also by accident. Nothing else can be done.† Silence settled over both of them. Finally Seldon said, â€Å"Is there anything else you can tell me?† â€Å"I'm afraid not. Except that I'll send you my bill.† Seldon rose with an effort. His sciatica hurt him badly. â€Å"Well then, thank you, Doctor. Send the bill and I'll pay it.† Hari Seldon left the doctor's office, wondering just what he would do next.

How actions portray the personality of the characters essays

How actions portray the personality of the characters essays The way a person reacts to another can sometimes give a little idea as to what their personality is like. In Pride and Prejudice by Jane Austen, this is displayed by the presence of Mr. Collins. Mrs. Bennet, Mrs. Philips, Mr. Darcy, Elizabeth and Lady Catherine de Bourgh all reacted to the arrival of Mr. Collins. Mrs. Bennet, Mrs. Philips and Elizabeth are all part of the same family and they all reacted to the arrival of Mr. Collins. ...Pray do not talk of that odious man. I do think it is the hardest thing in the world, that your estate should be entailed away from your own children... (60) This quote represents how Mrs. Bennet reacted to Mr. Collinss visit. She is worried about the estate being taken out of the family. It shows that she is the kind of person to hold a grudge and to be hateful towards people whether it be their fault or not. It is not Mr. Collinss fault that the estate will be handed over to him, but Mrs. Bennet only sees what she wants to see. In describing to her all the grandeur of Lady Catherine and her mansion, with occasional digressions in praise of his own humble abode, and the improvements it was receiving, he was happily employed until the gentleman joined them; and he found in Mrs. Philips a very attentive listener, whose opinion of his consequence increa sed with what she heard, and who was resolving to retail it all among her neighbors as soon as she could. (73) This quote describes Mrs. Philips in a way that she is easily flattered and she likes to be complimented. She feels very honored that her house is compared with that of Lady Catherines and cant wait to brag to the other people of the community. I cannot make him out. There is something very pompous in his style. And what can he mean by apologizing for being next in the entail? We cannot suppose he would help it, if he could. Can he be a sensible man, sir? (62) When Eliz...

A Person Who Had a Big Influence on My Life Essays

A Person Who Had a Big Influence on My Life Essays A Person Who Had a Big Influence on My Life Essay A Person Who Had a Big Influence on My Life Essay It was a stormy night. The atmosphere was heavy and the environment was clouded with darkness. Rain was pouring like cats and dogs. I had been an orphan since the day I was born and now the orphanage had abandoned me. Lying in the dark, stormy streets I was getting wet head to toe. There was no one walking around, or at least thats what I thought . My eyesight barely managed to let me detect that sevven men in black coats, black shoes, black mask and black gloves were heading my way. I was filled with terror. I wished that they didnt detect me.However, my luck, as usual, had always been cursed. So it decided to side with the devil. I managed to get up but I was too frightened to move. Then I suddenly heard a loud noise. That is when I felt someone pushing me and a moment later I realized that I had bumped into a wall. I also, now having regained my senses understood that it was a gunshot. I saw a man lying on the floor. He was shot dead. However, that was all only in my imagination of my own creation. I realized that when he suddenly stood up. He held my hand and looked at me for a second.His look was one of concern and his grasp was one which seemed to reassure my safety. It felt like he would not let go. We started running and he quickly pushed me into his house. He locked the doors and shouted to everyone that he had returned. Abruptly, many children came rushing down the stairs and from the kitchen came a woman who gave me a cheerful smile. The man introduced me to the kids and the woman. Not only did he save me and give me a new life, but he also gave me a family and he took away my loneliness.

How to Format Block Quotations

How to Format Block Quotations How to Format Block Quotations How to Format Block Quotations By Mark Nichol A block quotation is a distinct body of type set off from the default text (also called the running text), usually distinguished by insertion of line spaces above and below and formatting of a narrower margin (and sometimes even type of a different point size or a distinct font). When reproducing written text from another source, consider setting the quoted material off from the rest of the content in a block quotation if it is more than a hundred words long. consists of more than one paragraph. is made up of a number of shorter passages (so that it would resemble an indented list without numbers or bullets). constitutes a letter or other correspondence, complete with salutation, signature, and the like, or another type of templated form. requires any special formatting. However, determine whether it might be better to simply paraphrase a long quotation in one or more normal paragraphs with perhaps some partial quotations when phrases should be reproduced verbatim. When the first line of each paragraph in the running text is indented, block quotations of a single paragraph, and the first of multiple paragraphs, are not indented, but subsequent ones should be. When paragraphs in running text are distinguished not by indentation but by line spaces, follow the same format in block quotations. If the block quotation is inserted in a framing paragraph that continues after the quotation, do not indent the first line of the rest of the paragraph. If paragraphs are set off by line spaces, a new paragraph that immediately follows a block quotation should be separated from the quotation by two line spaces so that the new paragraph is not mistaken for a continuation of the paragraph in which the quotation is inserted. When a block quotation is the continuation of an introductory sentence, use punctuation or capitalization (or a lack thereof) accordingly. In this case, the quotation is a continuation of the introduction, so no punctuation or capitalization is necessary: â€Å"The writer described the apparition as a tall, thin wraith of diaphanous constitution, as if made of smoke . . . .† (Note also that a block quotation is not enclosed in quotation marks; it is assumed that such an excerpt is quoted material.) If the first word of the quoted material had originally been capitalized (â€Å"A tall, thin wraith . . .†), silently correct it, as above; it’s not necessary to call attention to the change, as is sometimes done in specialized contexts (â€Å"[a] tall, thin wraith . . .†). A lead-in line consisting of a complete clause, and the first word of the following quotation, should be treated otherwise: â€Å"The writer described the apparition as follows: It was a tall, thin wraith of diaphanous constitution, as if made of smoke . . . .† The same rules hold for run-in quotations (those that are assimilated into the running text): â€Å"The sage says that ‘a fool and his money are soon parted.’† (Though the adage, standing alone, would begin with an uppercase a, it is part of the framing sentence here and must be lowercased; alternatively, you could write, â€Å"The sage says, ‘A fool and his money are soon parted.’†) If the writer wishes to amend or comment on a quotation, several strategies are available: To clarify that a typographical error is in the original, insert sic (Latin for â€Å"thus,† or â€Å"so,† and meaning â€Å"as originally published†), italicized and in brackets, after the offense. Take care, however, not to employ this term as a textual smirk, and if the quotation is full of unconventional, outdated, or variant spelling, an explanatory note before the quotation is preferable to a quotation repeatedly interrupted by [sic]. When you don’t need the entire quotation to illustrate a point, you may delete irrelevant passages and indicate the elision with ellipsis points. However, it is not necessary to precede or follow a passage with ellipses to indicate that you are not reproducing the entire text from which the excerpt is derived; the reader will assume this. If you must make comment or clarify a point, enclose the note in brackets, but be as concise as possible, or provide a longer explanatory note outside the quotation. If you wish to emphasize one or more words or phrases, follow the quotation with the parenthesized note â€Å"Italics added† or â€Å"Emphasis mine,† or vice versa. But a quotation with extant italicization should be treated differently: Insert the comment in brackets immediately following your emphasis. Want to improve your English in five minutes a day? Get a subscription and start receiving our writing tips and exercises daily! Keep learning! Browse the Style category, check our popular posts, or choose a related post below:16 Substitutes for â€Å"Because† or â€Å"Because Of†How to Punctuate Descriptions of ColorsTitled versus Entitled

The implications of Tudor-Stuart polices on Ireland Research Proposal

The implications of Tudor-Stuart polices on Ireland - Research Proposal Example Hence, â€Å"...obeyeth to no other person, English, Irish except only to such persons...† that could subdue them in the battlefield in case of invasion with a sword2. However, this did not last long before Tudors and later Stuarts showing interest in subduing them though encountered severe resistance from some of the then uncooperative chieftains but eventually complied with English king’s laws. This was contrary to earlier times when they were not under the subject of any King’s laws except their Gaelic chiefs doing what they wished3. However, the imposition of Tudor-Stuart policies on Ireland aimed at subduing Ireland as well as bringing the entire state under complete control. This included even the then powerful Irish Landlords who later after the conquest turned into mere chiefs subject to Henry VIII as per the Pope Andrian IV’s wish who had given king that title4. Despite strong resistance waged by some of the then powerful proprietors like Oâ€℠¢Donell and O’Neil supported by Philip of Spain (Elizabeth’s enemy), they gave in to Henry’s regime after a miserable defeat5. Hence, they both recognized and accepted Henry III as king whereas in their capacity remained only as Anglo-Irish Nobles6. Henry VIII after subduing powerful Irish land Landlords especially in Ulster and more agreeing to give in their full compliance, he resulted to autocratic rule. This constituted torture especially to those who showed any disobedience besides bringing English settlers in Ireland7.

Qatar Balance of Payments Analysis Assignment Example | Topics and Well Written Essays - 250 words

Qatar Balance of Payments Analysis - Assignment Example The fact that Qatar relied to very solely on investments in the oil sector lead to very low investment inflows which then kept the income balance of Qatar very low. The income from foreign direct investment was generally low in comparison with that of other countries. The deficit in the income balance of Qatar in 1997-2007 estimated to have averagely $ 2 billion which is responsible for the deficit in balance of payment during that period. According to CIA World Factbook (2013), statistics on the economy of Qatar shows that the country imports more service than what they export. Since 1997 to 2007 the general amount of exports from Qatar were estimated to be about $12 billion while their imports were estimated to be about $38 billion. However, their major exports were goods while the service industry contributed small portion of their exports. This therefore led to more imports on the service which then amounted to deficit balance on the services. This then shows that the general services balance of Qatar had been in a deficit before the country took a step to diversify their economy in 2008. The external borrowings of Qatar have also been increasing between the years 1997 and 2007 which was an estimate of about $ 1 billion increase. The increase in the borrowings of Qatar was from both the private and foreign sources. These needed to develop the natural gas in Qatar. This therefore led to the increase in the current transfers of the country of Qatar between 1997 and 2007. With increased current transfers and unfavourable balance of trade on services and income, the country of Qatar has persistently registered a deficit in its balance of payment in

Key Motivating Factors for CSR reporting Essay Example | Topics and Well Written Essays - 1250 words

Key Motivating Factors for CSR reporting - Essay Example This research tells that the role of sustainable business practices has become the key component of corporate governance that incorporates social aspect within the broader framework of business goals and objectives. GRI is the important institution that helps to develop the framework of sustainability reporting that has the major impact on people. The various imperatives and drivers of changes motivate business to develop corporate social responsibility and sustainability report an intrinsic part of business strategy. Jones and Jones state that CSR actions are initiatives of companies to ‘further some social good beyond its own interests’ that have the long-term impact on their performance. Globalization influenced business decisions. Sirgy asserts that globalization is ‘the diffusion of goods, services, capital, technology, and people (workers) across national borders’. This has resulted in more competition and require the good image of companies. To stop s candals like Enron and WorldCom, transparency in corporate governance is needed. Corporate governance emphasizes accountability, responsibility, and transparency through good practice in business. Turnbull Report also says that risk management, internal control etc. are extremely important issues as they reflect ‘sound business practices’. Nature has limited resources like air, water, land and mineral resources. The indiscriminate use of natural resources resulted in fast depletion and therefore businesses must use technology and processes that promote environmental conservation and preservation. In the current times, people have become more aware of the environment, social issues and about other brands. Companies need become more active in responding to social issues like environment, diversity and contribute towards the socio-economic development of the society which is helping them to do business.

Edit my summary Essay Example | Topics and Well Written Essays - 750 words

Edit my summary - Essay Example udy where the researchers focus mainly on how twitter helped public relation specialists in building relationships by having followers on twitter who helped in reaching out to other effective individuals or organizations. The communication on twitter can be bilateral if the two parties are following each other and it can be unilateral if only one party is following. Khalid Al†Shohaib, Ali A. J. Al†Kandari, & Masaud A. Abdulrahim (2009) mention the role of the Internet in facilitating the public relations practitioner tasks especially when the organization is facing competition. This study will be analyzing the usage of the Internet by Saudi public relations practitioners and that their Internet existence is tied to religious and political values. Diffusion of innovation theory is used to show Internet’s role in public relations in Saudi Arabia by sending surveys to the main three metropolitan regions in Saudi Arabia divided between public and private organizations. The findings highlighted that only 46 per cent of public relation practitioners are using the Internet to facilitate their tasks. Al-Enad (1992) discussed how public relations operate in different settings using public relation models. He used the critical theory and the ethical theory. The public relations practitioners are the link between the organization and the stakeholders. The focus to public relations focus can be divided into several categories that include organizational PR where the practitioners’ focus is the organizations goals, responsible PR where the needs of stakeholders come first, and balanced PR, which is based on dialog as well as considering the needs of organization and the stakeholders. The result of this study showed that the majority of organizations are trying to meet the needs of both parties. Saxton, G. D. & Waters, R. D. (2014). What do Stakeholders Like on Facebook? Examining Public Reactions to Nonprofit Organizations’ Informational, Promotional, and

Economic analysis of the current residential housing market in Houston Essay

Economic analysis of the current residential housing market in Houston - Essay Example Houston realtor’s housing data indicates that demand for houses increased by 29% as January 2013 representing a sales increase of 4680 units as compared to the previous year. Additionally, the housing prices were ranging from $500,000 on January 2012 to million dollars. For instance, the highest price were recorded on January 2012 was $200296 (Bivins, paras7-8). The data further indicates that prices of single family houses increased by 9.6% between 2012 and 2013. This indicates that there was a 22.45% increase in housing prices this year as compared to the last year. Additionally, the sale of condominiums was reported to be 422 residential units as at February this year while on February last year the sales of condominiums was 313 units. This indicates that there was an increase in demand for condominiums and mansions by 109 units as at February 2013. According to Eaton, Paras 2-4, higher demand for houses caused an increase in demand for mortgages. For example, demand for mortgage loans increased from 11.4% on January 2009 to 18.6% on January 2011.Therefore, study aims to explain three factors that increase or decrease demands for residential housing in Houston as well as those factors that increase or decrease supply of residential housing. In above connection, the study will put forth demand three examples that explain areas where demand or supply based market failure can be anticipated. Additionally, the study will put forth three examples that explain demand or supply based market failures and how the government can address such failures in a free market. Connectively, graphs will utilize to explain the concepts that are going to be discussed. Economic analysis of the current residential housing market in Houst on Numerous factors have been attributed to an increases demand for housing in Houston, among those factors includes: change in consumer’s disposable income, change in demographic, availability of substitutes to mention just but a few (Arnold p.65). Changes in consumer’s disposable income may involve increase or a decrease in income. Whereby, an increase income caused an increase in demand for houses in Houston as many consumers could afford to pay for houses despite having a higher price. This in turn caused a movement from point A to point B causing a right ward shift demand curve from D1D1 to D2D2 as indicated in 1.1. Additionally, change in population demographics such; as increase in population, could have contributed to an increase in demand for houses (Gwartney p.61). Whereby, as birth rates increases, demand for houses increase causing a rightward shift in demand curve as indicated in diagram 1.1. In above connection, availability of houses that could have been used as substitute contributed significantly to a high demand of houses in Houston. This means that better houses were readily available and therefore, most people were able to substitute their old houses with a new and better residential house depending on their needs. On the other hand, those factors that decrease demand for housing include: changes in consumers future expectations. Whereby, future anticipations that houses prices might fall in the future they may make consumers postpone their current demand for houses in order to purchases those houses in the future at a lower price (Hall p.60). This in turn leads to a decrease in demand for houses and hence causing a leftward shift in demand curve as indicated in diagram 1.2 at the end of the essay. Additionally, a fall in consumer’

Pandemic Flu plan Case Study Example | Topics and Well Written Essays - 750 words

Pandemic Flu plan - Case Study Example that has seen heath experts and governments come together to formulate policies and plans on how to curb and mange influenza so as to reduce loss of life through such pandemic. Communities at their local levels have come up with ways to handle influenza so to protect the community members from suffering and deaths. This paper indicates a community plan outlines strategies to curb influenza in Glen Falls in New York. To enhance influenza review in Glen Falls, the plan shall initiate measures to protect community members from attacks and loss of lives as a result of flu. They include; This shall be meant to promote and boost the immunity of villagers through anti viral drugs and vaccine. Parents shall be advised to take their children fro vaccine so as to enable them withstand the effects of influenza. Immunization awareness shall be carried out to educate the people on the need to consider immunization as the possible solution for this challenge. Expectant mothers shall be advised to attend prenatal and antenatal care program in which vaccination and immunization for the unborn baby and the mother shall be done to offer remedy for this problem. To educate the community, seminars and workshops shall be carried out in the community to enlighten the people. Cultural dances and performances where by communal artists shall be used to perform and make skits more so in the evenings which shall bring together members of the community to learn on the need to take on immunization program to remedy influenza. Influenza pandemic requires proper planning that involves partie s of every level such as communities and families and individuals so as to slow and respond so as to recover from this disaster. This is because influenza has been identified to cause loss of life through illness making it a public threat. The plan will involve health care providers in advocating the control of influenza in the community. Hospitals shall print leaflets which shall have the information

Economic analysis of the current residential housing market in Houston Essay

Economic analysis of the current residential housing market in Houston - Essay Example Houston realtor’s housing data indicates that demand for houses increased by 29% as January 2013 representing a sales increase of 4680 units as compared to the previous year. Additionally, the housing prices were ranging from $500,000 on January 2012 to million dollars. For instance, the highest price were recorded on January 2012 was $200296 (Bivins, paras7-8). The data further indicates that prices of single family houses increased by 9.6% between 2012 and 2013. This indicates that there was a 22.45% increase in housing prices this year as compared to the last year. Additionally, the sale of condominiums was reported to be 422 residential units as at February this year while on February last year the sales of condominiums was 313 units. This indicates that there was an increase in demand for condominiums and mansions by 109 units as at February 2013. According to Eaton, Paras 2-4, higher demand for houses caused an increase in demand for mortgages. For example, demand for mortgage loans increased from 11.4% on January 2009 to 18.6% on January 2011.Therefore, study aims to explain three factors that increase or decrease demands for residential housing in Houston as well as those factors that increase or decrease supply of residential housing. In above connection, the study will put forth demand three examples that explain areas where demand or supply based market failure can be anticipated. Additionally, the study will put forth three examples that explain demand or supply based market failures and how the government can address such failures in a free market. Connectively, graphs will utilize to explain the concepts that are going to be discussed. Economic analysis of the current residential housing market in Houst on Numerous factors have been attributed to an increases demand for housing in Houston, among those factors includes: change in consumer’s disposable income, change in demographic, availability of substitutes to mention just but a few (Arnold p.65). Changes in consumer’s disposable income may involve increase or a decrease in income. Whereby, an increase income caused an increase in demand for houses in Houston as many consumers could afford to pay for houses despite having a higher price. This in turn caused a movement from point A to point B causing a right ward shift demand curve from D1D1 to D2D2 as indicated in 1.1. Additionally, change in population demographics such; as increase in population, could have contributed to an increase in demand for houses (Gwartney p.61). Whereby, as birth rates increases, demand for houses increase causing a rightward shift in demand curve as indicated in diagram 1.1. In above connection, availability of houses that could have been used as substitute contributed significantly to a high demand of houses in Houston. This means that better houses were readily available and therefore, most people were able to substitute their old houses with a new and better residential house depending on their needs. On the other hand, those factors that decrease demand for housing include: changes in consumers future expectations. Whereby, future anticipations that houses prices might fall in the future they may make consumers postpone their current demand for houses in order to purchases those houses in the future at a lower price (Hall p.60). This in turn leads to a decrease in demand for houses and hence causing a leftward shift in demand curve as indicated in diagram 1.2 at the end of the essay. Additionally, a fall in consumer’

The Many Uses of Adobe Illustrator Essay Example for Free

The Many Uses of Adobe Illustrator Essay With Adobe Illustrator, I can create drawings or pictures for my automotive class. We have a thing where when we are seniors we get a shirt with someone’s drawing on it. In college I can use Illustrator to do basically the same thing, but with different classes. I can use Illustrator in the work force if I decide to be a computer graphic designer; this will be really useful for me to know all the skills in order for me to be able to do a good job at that job. With Adobe Photoshop, I can create different posters, or change pictures, or even create drawings as well. I can use this in school when I again, create the drawings in my automotive class. In college, I can use it, if I take some graphics classes, I can show that I have some experience with Photoshop, and that will probably give me some points in getting accepted to the class. In the work force, I could be a photographer and edit the pictures to my liking and make sure everything looks nice. With Adobe InDesign, I can create posters, flyers, brochures, magazines etc. This will be really useful in High School if I need to create a poster or magazine for a project or for the school itself. In College, I can use it to maybe make a few books or newspapers for the teachers and also maybe for projects. In the work force, I can become a newspaper writer, maybe for the Las Vegas Review Journal. Using Adobe InDesign will be really useful for a newspaper writer, because of all the cool things it can do. With Adobe Flash Professional, I can create animations and videos. In High School this will be really useful if I need to make a video for a project. In college this will be equally important and useful because I can again make videos or animations for some of my classes that may require that. In the work force, I can become a video editor for movies. I can use Adobe Flash to edit the movies and change them how I like them. All these programs relate to each other in different ways. You can upload Adobe Illustrator projects into Adobe Photoshop, Adobe InDesign, or Adobe Flash Professional. Each one can be used with other ones. Adobe Photoshop projects can be uploaded to Adobe Flash Professional or Adobe InDesign. They all have an important part in making up the Adobe Creative Suite CS5 because they are equally important. Each one has its own part in helping out people to have creative ideas and make them come to life on the screen.

Gender Differences in Neurotoxicity

Gender Differences in Neurotoxicity Abstract Neurotoxicity is damage to the structure and/or function of the peripheral and central nervous systems. It is a common outcome of exposure to hundreds of environmental chemicals, which act via a wide range of mechanisms. Due to the fundamental importance of the nervous system to a fully functioning body, the neurotoxic effects of many chemicals have been well investigated. There is evidence from a number of studies of a difference in susceptibility to environmental neurotoxins between genders. Males appear to be more vulnerable than females. There may be many reasons for this difference, a key one being the neuroprotective activities of the gonadal (sex) hormones, which differ between males and females. The female hormone, oestrogen, is thought to have greater protective activity, from a wide range of chemicals than the male hormone, testosterone. This report will examine the available evidence of a gender difference in susceptibility to environmental neurotoxins, and look into the actions of hormones within the nervous system as one of the main reasons for this difference. Introduction The nervous system (NS) is a fundamental component of a fully functioning human body. Due to the immense importance of the NS, any damage that occurs to this system will have huge repercussions throughout the whole body. Unfortunately, the NS is extremely vulnerable, and neurons, with their unique shape, and long, thin extensions protruding from their cell bodies, are highly susceptible to degeneration, from ageing and from exogenous substances (1, 2). It has been observed that exposure to a range of different environmental chemicals can have adverse effects on the NS, resulting in degeneration of neurons, and leading to onset of various neurological diseases (2, 3). The developing NS in particular is extremely sensitive to the effects of such chemicals (2, 4). Prenatal, and early postnatal, exposure to environmental chemicals, such as lead and those in tobacco smoke, can affect the developmental process within the Central Nervous System (CNS). This can lead to slowed and incorrect development, and neurological problems in the early years of life (4). From both animal studies, and human case reports of inadvertent exposures, there is also evidence to suggest a difference between males and females in their susceptibilities to neurotoxicity of some environmental chemicals (5). There are a number of reasons why this may be, including differences in amounts and activities of metabolic enzymes, differences in rates of absorption between the sexes, different rates of clearance of exogenous substances from the body, and differences in exposure to neurotoxic chemicals; diet, hobbies, occupations, etc (6). However, a key reason may be the neuroprotection that is conferred by gonadal hormones, and their metabolites, within the NS (5). The aim of this report is to research evidence of sex differences in responses to environmental chemicals, and investigate hormonal influences as one of the reasons for this difference. Neurotoxicity of Environmental Chemicals Neurotoxicity is a term used to describe damage to the structure and/or function of the peripheral NS (PNS) and CNS, brought about by exposure to particular exogenous substances (7, 8), which act via a range of mechanisms to induce cellular changes, and often cell death (7). Neurotoxicity can be seen in all ages of individuals exposed to hazardous chemicals, however, the developing NS is particularly vulnerable to their effects (2, 4, 7). Development of the NS involves a series of very specific steps, over a prolonged time period, each one occurring only when the previous is finished, and disruption to these events leads to incorrect development and neurological problems (4). The blood-brain barrier (BBB), which prevents many substances from passing to the brain, is not fully complete until several months of age, leaving the NS susceptible to damage (7). The entire NS is not fully mature until puberty (4). A great number of the reports published concerning neurotoxic effects of chemi cals have reported observations on child subjects. This is due to the fact that the developing NS is much more vulnerable, and so the neurotoxic effects may be more easily noticed. There are over 200 chemicals that have been confirmed as neurotoxic to humans (and other animals)as a result of exposure to them (3). A number of these chemicals are identified in Panel 1 (3), and can be divided into groups; metals, organic solvents, pesticides, and other neurotoxic chemicals. Panel 1. There are over 200 chemicals known to cause neurotoxicity in humans. This list identifies some common ones. Adapted from (3). Chemicals in bold and red are those identified within this report. Different toxins have distinct mechanisms through which they influence the NS. This depends on dose, route and duration of exposure (9). Those chemicals which are most widespread in the environment, and those which cause the most drastic effects, have been extensively investigated, and many of the mechanisms causing neurotoxicity have been identified (9). Given the knowledge of these effects, it is important to investigate the possible neurotoxic influences of the large number of other chemicals prevalent in the environment. Mechanisms of neurotoxicity The main mechanisms encompassed by the afore-mentioned groups of substances include; induction of oxidative stress, alterations to neurotransmitter synthesis including inhibition of synaptic signalling, accumulation of the substance within mitochondria leading to dysfunction, alterations to the flow of ions across neuronal membranes, activation of second messengers to induce apoptosis or inhibit neurogenesis, disruption of DNA/RNA, affecting the differentiation and functioning of glial cells, to indirectly influence neuronal cells, alterations to membrane fluidity, abnormal expression of neurotrophic factors (7, 10-20). There is a requirement for metals in many body processes, including within the NS, providing an additional mechanism by which exogenous metals can induce neurotoxicity (17). They can compete with essential metals for protein binding sites and influence cellular processes (17). For example, lead competes with zinc, which is known to have binding sites present in many important receptor channels, such as the N-methyl-D-aspartate (NMDA) receptor involved in glutamate signalling at the synapse. Lead can displace zinc, and therefore alter functioning of these channels, and so influence glutamatergic functions in the NS (13, 14, 17). A relatively recently proposed mechanism thought to induce neurotoxicity via environmental chemicals, is endocrine disruption. Endocrine disruption is believed to be a crucial mechanism of most neurotoxicants, including metals, solvents, pesticides, Polychlorinated Biphenyls (PCBs), Diethylstilbesterol (DES), etc (21-25). Endocrine disrupting chemicals act by mimicking, enhancing, or antagonising the effects of endogenous oestrogens and androgens (21, 22). Their actions can result in alterations to hormone synthesis and/or release, altered transport and clearance of hormones, altered binding of hormones to their receptors (by binding themselves, thereby either mimicking hormone response, or blocking hormonal activation (24)), or altering components of pathways following receptor activation (22). An example of an endocrine disrupting mechanism is one used by lead, which lowers blood levels of testosterone, thereby de-masculinising certain areas of the male brain, and PCBs, which both mimic and antagonise various oestrogenic functions, and disturb production of androgens (21). As hormones are known to have a role in the development of the CNS, including sexual differentiation (26), disruption to their activities may result in disruption to the development of some brain areas, and the possibility of feminisation or masculinisation of particular brain areas (21-25). The neuroprotective function of hormones (discussed later) may also be hindered due to the endocrine disrupting actions of certain chemicals, allowing for their other neurotoxic mechanisms to have greater damaging effects. Neurotoxic investigations Carrying out investigations into the effects of neurotoxic chemicals is much more difficult in humans than it is in other animals, due to the greater difficulty in controlling the surrounding environment and its influences, and there are many potential variables that can have an effect on the overall result, in particular exposure to other environmental chemicals, drugs, alcohol, tobacco, education, culture, etc (27-31). All the potential confounding factors must be taken into consideration in order to analyse the neurotoxic effects only of the chemical in question (32). Often, environmental chemicals induce delayed neurotoxicity, whereby a patient does not present with symptoms until well after exposure to the chemical has ended, providing another problem to investigators (4). There are many different symptoms that can present upon neurotoxicity; migraines or headaches, confusion, memory loss, Multiple Sclerosis (MS)-like symptoms, problems with sleep, balance and hearing, attention impairment and trouble concentrating, anxiety and depression (8). Alterations to cognitive function, motor function and behaviour are common outcomes of neurotoxicity, and are a useful assessment of the effects of exposure to chemicals (32, 33). There are a wide range of different tests commonly used to assess neurotoxicity to the PNS and CNS (4, 32, 33). Measurements of functions such as motor reflexes, insensitivity to pinpricks on the skin, or impairment of sensitivity to temperature and vibration, provide evidence of PNS toxicity (4, 32, 33). Other functional tests, including IQ (Intelligence Quotient) tests, memory tests, assessment of mood and personality, and behavioural questionnaires, are used to assess toxicity to the CNS (4, 32, 33). Damage to the Nervous System can also be established by use of various brain imaging techniques (e.g. Computed Tomography, Magnetic Resonance Imaging) (9). These are useful in observing physical alterations to brain size and appearance caused by brain tissue atrophy following neurotoxic exposure (9). It is also possible, using these images, to ascertain which regions of the brain are particularly affected (9, 33-35). Despite the large quantity of literature outlining investigations concerning exposure to different neurotoxic chemicals, there are relatively few publications available that have identified a difference in response between males and females. Differences between susceptibilities of a range of age groups, and groups with varying levels of exposure, have been acknowledged frequently (27, 36-38), however reports are rare in which results for men and women are assessed independently, therefore it is often difficult to determine any differences in susceptibility between the sexes. Many reports record numbers of each sex taking part in the study, and match controls accordingly, then proceed to analyse results as a whole (27, 28, 39-45). Others exclude female subjects altogether, rather than including analysis of female results, but separate from the male (29, 30, 46-51). This is often the case when the number of female subjects is small compared to men. However, the results could still be analysed, and any differences between them could be noted. Some fail to establish which sexes have been used at all (52-54). Nevertheless, there is evidence from a number of reports, of a difference between genders in neurological functioning following exposure to neurotoxic chemicals. An extensive search using MEDLINE and EMBASE, of published studies and case reports into neurotoxicity of environmental chemicals, identified a number of studies which observed differences between males and females. For the purpose of this report, only those chemicals with gender differences have been mentioned. Evidence of Gender Differences in neurological outcomes of exposure to Neurotoxic Chemicals Metals There are roughly 40 different metals that exist in the environment, some of which are essential for life to occur (e.g. copper, zinc, etc), others which arent (e.g. mercury, lead, etc) (9). Exposure to metals in the environment has been known to cause adverse effects to both the adult and child human NS for many years (3). The neurotoxic effects of these metals are particularly well characterised, and have been well investigated. Included in this report are three of the major neurotoxic metals, of which there has been much exposure to in the environment, and of which there has been some indication of a sex difference in susceptibility to neurotoxic effects; mercury, lead and manganese. These three metals have been more extensively investigated than others, and therefore sex differences observed should not be ruled out of others, and may also be noted if they are as well examined. Mercury Mercury can take various different forms, each of which has distinct effects on human systems (18). Methylmercury (e.g. contaminated seafood), ethylmercury (e.g. Thimerosol, a component of some vaccines), elemental Mercury (present in industrial vapours), and inorganic mercury compounds (e.g. skin lightening creams) (18). Of these forms, methylmercury has been acknowledged as having the greatest detrimental effect on the correct functioning of the human NS, and in particular, the developing nervous system of children (18). In adults, methylmercury is thought to damage specific brain regions, such as the visual cortex, and parts of the cerebellum, whereas in children, as the NS is not completely developed, the effects are thought to be more widespread (7). It has been observed in a number of studies that male children show greater impairments in NS functioning following exposure than female children. In certain neurological tests, which have an association with methylmercury exposure, namely those assessing finger tapping, tendon reflexes, and leg coordination ability, males achieve poorer results (8, 36, 37, 55-57). As the majority of studies reporting results individually for male and female subjects are those carried out in children, the main sex differences reported here have been observed in children. However, similar results are noted in those adult investigations where males and females were analysed separately (27). McKeowyn-Eyssen et al. (1983), Cordier et al. (2002), Myers et al. (2003), Grandjean et al. (1998), and Marsh et al. (1987), all carried out numerous different tests on school children exposed to methylmercury at varying concentrations, pre- and post-natally. Each of these groups identified that, for those tests which have been shown to be more affected by increasing methylmercury levels, including finger-tapping, abnormal muscle tone, tendon reflexes, and leg coordination, male children showed poorer results (19, 57-60). McKeowyn-Eyssen et al. (1983) carried out the same tests on adults, and found an indication of a similar sex difference, with men being more likely than women to develop neurological disorders, following increases in methylmercury levels (37). Davidson et al. (2000) found that male, but not female, responses in neurological tests increased with methylmercury exposure, which is the opposite of the expected results, however, numerous unexamined variables were identified, which could have had influences on the results of the tests (31). Holmes et al. (2003) identified a link between mercury exposure and autism in children. Higher mercury levels in the hair were found to be associated with milder autistic symptoms (61). Perhaps because those children with milder symptoms were more able to excrete the mercury through their hair, before too much damage occurred. There was a greater number of females showing milder autistic symptoms, and a greater number of males showing severe autistic symptoms (61). From the evidence put forward here, there is a definite implication of a greater susceptibility for males than females to the neurotoxic effects of methylmercury exposure. There is an increased risk of neurotoxicity for children of women with increased levels of mercury in the hair (61). Hair mercury levels in subjects themselves, following equal exposure between the sexes, has been observed on numerous occasions as being lower in males than females, when associated with neurological problems (37, 61, 62). It may be that females have a better ability to excrete mercury through the hair than males, so less is present in body tissues. Lead Lead has long been known as a neurotoxicant, and its widespread release into the environment over the years has resulted in many neurological problems, mainly linked to learning difficulties (17), that have been well studied and characterised (3). Lead toxicity is thought to occur mainly in the hippocampus, cerebellum, and prefrontal cerebral cortex and again, it is thought that children, with their NS still developing, are at greatest risk to the neurotoxic insults of lead (7), so the majority of reports found here have been carried out in children. The elimination of lead from many environmental sources, such as motor vehicle petrol, and paints, has seen a decline in the amount of toxic lead exposure (7). However, it is still a problem in many areas, for example those homes where lead paint has been used in decoration (17). There are a number of studies that have reported a difference in cognitive impairments between male and female children. Tests carried out on school children, in South America, the UK and USA (38, 63-66), all identify a larger correlation between lead levels in the blood and poor cognitive ability in males than in females, while Wasserman et al. (1998) state that mothers reported behavioural problems with male children exposed to lead, more often than with exposed female children (67). An assessment of behavioural problems associated with lead exposure in American children (68) and an assessment of intelligence of children following lead exposure in Port Pirie (69), identified no difference between males and females in the results of their tests, while an assessment of the capabilities of children in school, and association with lead exposure (70), along with another investigation of child IQ by Needleman et al. (71), observed results to suggest females were more susceptible to lead neurotoxicity than male subjects, as they appeared to have greater prevalence of learning difficulties associated with lead. So, there appears to be a significant amount of evidence implying a gender difference in neurotoxicity associated with lead exposure. The majority of reports imply an increased susceptibility for males; however it is important for groups to look at sex differences in future studies, in order to ascertain conclusive results. This evidence also provides a need for investigation of sex differences in effects of lead exposure in adults. Manganese Manganese is another commonly used metal that can cause a toxic effect the NS upon exposure (20, 29, 40, 46, 47). There is a risk of manganese toxicity in various professions, in particular, welding (29, 46), but also through drinking or washing in water containing extraordinarily high levels of manganese (20, 40). There are a large number of reports confirming the neurotoxicity of manganese (20). Investigations have shown decreased intellectual ability in children over-exposed to manganese (40), and mood disturbances in men exposed occupationally (e.g. welders, factory workers.) (29, 40, 46, 47). In children, a report into an association between hair manganese levels and prevalence of hyperactivity, found that while there was a higher amount of manganese present in girls than boys, no difference was found between the sexes in assessment of neurological behaviour tests (72). Perhaps female brains are better able to cope with a higher amount of manganese. In adults, Dietz et al. (2001) found that a relationship between levels of manganese exposure and its effect on the Globus Pallidus area of the brain was seen only in men. These investigators give the reason that female workers have lower blood concentrations of manganese, and have a lower cumulative exposure index (73). However, they do not state whether there was a difference in actual exposure between sexes. If the exposure levels were the same, this could be an indication of increased susceptibility to males. In another study, results of neurological tests following manganese exposure were poorer for men than for women (74). As the majority of studies on manganese actually exclude females from results, or do not give separate results for each sex, it is difficult to make any definite assumptions about gender differences in neurotoxicity susceptibility. Implications from the three studies above provide a suggestion of a sex differences in manganese toxicity, with a greater effect within males. However, in future studies, where possible, females should be included, and the results analysed separately, in order to establish conclusive evidence for sex differences in neurotoxicity to manganese. Solvents There is a vast array of solvents that are used in many different industries and work places, meaning daily exposure for many different workers, including hairdressers, laboratory workers, painters, dry cleaners, and carpet layers, among others (33, 75-78). Due to the composition of solvents, they are particularly dangerous to the tissues of the NS. They are lipophillic compounds, and therefore have strong affinity for tissues rich in lipids, including the brain (33, 79). It is thought that psychomotor performance is the most common deficit (51) of solvent exposure, and prolonged exposure can cause permanent damage (15). Other symptoms include anxiety, insomnia, irritability, memory loss, fatigue and seizures (15, 33, 75). Solvent substances most often consist of a mixture of different chemicals, which can affect different regions of the brain. This can result in difficulties determining the toxic effects of a particular chemical (9). There have been many studies published that report clear association between solvent exposure and neurological deficits. Nelson et al. (1994) report that solvent exposure in workers at an automobile assembly plant, correlates with increased neurological disease, and, noticed in particular, an association with increased prevalence of a condition closely resembling MS (52). Cavalleri et al. (1994) obtained results to indicate deterioration of colour vision in factory workers following perchloroethylene exposure, even at low levels (53), and Boor et al. (1977) confirm a damaging effect of toluene on the CNS (54), a chemical that is also known to effect CNS development prenatally (3). Alcohol (Ethanol) is a major environmental solvent, although exposure rarely occurs occupationally, and it is most often taken in voluntarily (3). Hommer et al. (2001) studied the brain volumes of alcoholic and non-alcoholic men and women, and found that alcoholics had a much smaller volume of grey matter than non-alcoholics. This difference was found to be much more significant in females than males, suggesting an increased susceptibility of females to neurotoxic effects of alcoholism (34). In contrast, Pfefferbaum et al. (2001), in the same journal publication, indicated that the results of their study into alcohol effects on brain structure, show larger cortical sulci and lateral and third ventricles found in the alcoholics compared to non-alcoholics, which was a much greater and more significant difference in male subjects than female subjects. They also note that female brains show quicker and more effective recovery than those of males during abstinence (35). Jacobson (1986) ca rried out a study examining the brains of male and female alcoholics compared to non-alcoholic controls. It was noticed that the appearance of the brains on a CT scan was different between alcoholics and controls. Also observed was the fact that females appear more susceptible to structural changes in the brain following chronic alcohol intake, but are much more effective at recovering following cessation of intake, and the recovery occurs much quicker (80). Taking these 3 reports into consideration, there may be a difference in susceptibility of particular brain areas in males and females; however, females consistently recover more quickly from damage than males, indicating perhaps, a decreased susceptibility to long term damage. Neurophysiological deficits have also been reported in numerous studies of children exposed to alcohol pre-natally (81-83). However, few have noted results separately for male and female children. Nanson and Hiscock (1990) observed that female Fetal Alcohol Syndrome (FAS) children appear to have a higher IQ than males with FAS (83). As mentioned above, the majority of studies into other solvents, such as toluene, trichloroethene, n-hexane, chlorinated solvents (84), and solvent mixtures (49, 50, 76, 78, 85) in the workplace, report an obvious detrimental effect on the CNS, PNS, or both, following exposure. However, the majority included only men in the reports, or male and female results were analysed together. Again, it has been observed that the developing NS is especially susceptible to the neurotoxic effects of solvents, due to their high affinities for the brains lipid tissues (33, 79), and the BBB not being fully formed (7). Laslo-Baker et al. (2004) and Till et al. (2001) carried out studies on organic solvent exposure in pregnant women, taken in accidentally from occupational exposure, and the effects on neurodevelopment of their offspring. Both groups confirmed that children exposed pre-natally had poorer cognitive functioning than those not exposed, with lower results in neurological tests (75, 86). Again, no distinction was made between results for female and male children. Considering the obvious effects of solvents, including alcohol and toluene, on the NS, and the observations of sex differences from other neurotoxins, and the implications of sex differences in effects of alcohol mentioned here, it should be suggested that future studies automatically investigate male and female results separately, and allow for observation of any differences in results. Pesticides The term pesticides encompasses a wide range of chemicals, commonly used within a wide range of industries, particularly agriculture (87, 88). Included are the sub-groups; organophosphates, organochlorines, fumigants, and herbicides, all of which act to damage the NS of an organism, either directly, or via alteration of the cellular mechanisms that support it (87). Pesticides cause concern for human health as they are extremely widely used, and so readily released into the environment (88). It has been known for a long time that exposure to certain levels of these chemicals will adversely affect the human NS, as well as those organisms they are designed against (87, 88). Indeed, numerous studies have linked exposure to various pesticides with a number of neurological disorders, including Parkinsons disease (87, 89). In a similar situation to that for metals and solvents, there are many publications from groups investigating the effects of pesticide exposure on the human Nervous System, using an array of cognitive and neurobehavioural tests, with almost every study confirming the presence of some form of Neurotoxicity in subjects exposed to a range of doses. The following reports have identified separate results for neurological effects of pesticide exposure on male and female subjects, and an apparent greater effect on males. A report investigating the influence on the onset of Parkinsons and Alzheimers Diseases in elderly people living in the south of France, where pesticides are used daily in vineyards, noted a significant association between these disorders and pesticide exposure, in males only (90), suggesting a potentially increased susceptibility to males. Stallones et al. (2002) acknowledge males being at increased risk of developing neurological problems related to pesticide exposure than females, in an investigation into farmers, and their families in Colorado, USA (91), with the percentage of illnesses caused by exposure to pesticides almost three times greater in males. An assessment of neurobehavioural activity of Hispanic agricultural workers (92) identified a significant difference between the genders on results for 2 out of 10 tests, with females scoring lower than males. In the remaining tests, no significant differences were found between the sexes, although all exposed subjects faired worse than control, non-exposed (92). Similarly, pesticide-exposed Ecuadorians achieved lower outcomes in neurobehavioural tasks set by Cole et al. than did non-rural, unexposed Ecuadorians, and females were found to respond better in one task, with no significant difference between genders in others (93, 94). Guillette et al. (1998), carried out an assessment of Preschool children in Mexico, exposed to pesticides through living in close proximity of farm land. They identified a significant difference between those exposed and those living further away from the farm lands, with females performing better than males in several of the neurological tests (95). It appears that when there is a gender difference observed in the neurotoxic effects of pesticides, females tend to fair better than males, implying an increased susceptibility of males to the influences of pesticides on the NS. As it is more commonly males that are in the closest proximity to pesticides, within farming industries in particular, this could have some influence on this hypothesis. However, as the differences are also apparent in male and female children, with equal exposure, it does indicate a greater risk for males. The finding that there was only a significant difference in some tests may indicate an increased susceptibility of some brain areas in males over others, which correlates with results of studies of alcohol and tobacco smoke (below). Other Sources of Environmental Neurotoxicity Tobacco Smoke The chemicals contained in tobacco smoke, particularly nicotine, are now known to cause a variety of neurological problems, in addition to their other effects, including behavioural and cognitive problems during development, tremor, and an increased risk of stroke, from both smoking directly, and through passive smoke; inhalation or exposure prenatally (96-100). Various groups investigating toxicity caused by intake of tobacco smoke have described minor sex difference in the neurological outcome. Louis (2007) reports that, when looking into hand tremor as an outcome of tobacco smoking, the difference in score between smokers and non-smokers is greater in women than in men, which would indicate more of a susceptibility to women, rather than men (96). Jacobsen et al. (2007) investigated auditory and visual attention in adolescent smokers and non-smokers, with and without prenatal exposure to tobacco (101). They observed that different areas of the brain are apparently affected differently in male and female subjects exposed to tobacco smoke. In females, both auditory and visual attentions appear equally vulnerable, performing slightly more poorly in visual tests than males, while in males, auditory attention seems significantly more affected than visual attention, and in this auditory test, males performed substantially worse than females (101). The results of this investigation, put together with those from the Louis (2007) report, point towards sex-specific variation Gender Differences in Neurotoxicity Gender Differences in Neurotoxicity Abstract Neurotoxicity is damage to the structure and/or function of the peripheral and central nervous systems. It is a common outcome of exposure to hundreds of environmental chemicals, which act via a wide range of mechanisms. Due to the fundamental importance of the nervous system to a fully functioning body, the neurotoxic effects of many chemicals have been well investigated. There is evidence from a number of studies of a difference in susceptibility to environmental neurotoxins between genders. Males appear to be more vulnerable than females. There may be many reasons for this difference, a key one being the neuroprotective activities of the gonadal (sex) hormones, which differ between males and females. The female hormone, oestrogen, is thought to have greater protective activity, from a wide range of chemicals than the male hormone, testosterone. This report will examine the available evidence of a gender difference in susceptibility to environmental neurotoxins, and look into the actions of hormones within the nervous system as one of the main reasons for this difference. Introduction The nervous system (NS) is a fundamental component of a fully functioning human body. Due to the immense importance of the NS, any damage that occurs to this system will have huge repercussions throughout the whole body. Unfortunately, the NS is extremely vulnerable, and neurons, with their unique shape, and long, thin extensions protruding from their cell bodies, are highly susceptible to degeneration, from ageing and from exogenous substances (1, 2). It has been observed that exposure to a range of different environmental chemicals can have adverse effects on the NS, resulting in degeneration of neurons, and leading to onset of various neurological diseases (2, 3). The developing NS in particular is extremely sensitive to the effects of such chemicals (2, 4). Prenatal, and early postnatal, exposure to environmental chemicals, such as lead and those in tobacco smoke, can affect the developmental process within the Central Nervous System (CNS). This can lead to slowed and incorrect development, and neurological problems in the early years of life (4). From both animal studies, and human case reports of inadvertent exposures, there is also evidence to suggest a difference between males and females in their susceptibilities to neurotoxicity of some environmental chemicals (5). There are a number of reasons why this may be, including differences in amounts and activities of metabolic enzymes, differences in rates of absorption between the sexes, different rates of clearance of exogenous substances from the body, and differences in exposure to neurotoxic chemicals; diet, hobbies, occupations, etc (6). However, a key reason may be the neuroprotection that is conferred by gonadal hormones, and their metabolites, within the NS (5). The aim of this report is to research evidence of sex differences in responses to environmental chemicals, and investigate hormonal influences as one of the reasons for this difference. Neurotoxicity of Environmental Chemicals Neurotoxicity is a term used to describe damage to the structure and/or function of the peripheral NS (PNS) and CNS, brought about by exposure to particular exogenous substances (7, 8), which act via a range of mechanisms to induce cellular changes, and often cell death (7). Neurotoxicity can be seen in all ages of individuals exposed to hazardous chemicals, however, the developing NS is particularly vulnerable to their effects (2, 4, 7). Development of the NS involves a series of very specific steps, over a prolonged time period, each one occurring only when the previous is finished, and disruption to these events leads to incorrect development and neurological problems (4). The blood-brain barrier (BBB), which prevents many substances from passing to the brain, is not fully complete until several months of age, leaving the NS susceptible to damage (7). The entire NS is not fully mature until puberty (4). A great number of the reports published concerning neurotoxic effects of chemi cals have reported observations on child subjects. This is due to the fact that the developing NS is much more vulnerable, and so the neurotoxic effects may be more easily noticed. There are over 200 chemicals that have been confirmed as neurotoxic to humans (and other animals)as a result of exposure to them (3). A number of these chemicals are identified in Panel 1 (3), and can be divided into groups; metals, organic solvents, pesticides, and other neurotoxic chemicals. Panel 1. There are over 200 chemicals known to cause neurotoxicity in humans. This list identifies some common ones. Adapted from (3). Chemicals in bold and red are those identified within this report. Different toxins have distinct mechanisms through which they influence the NS. This depends on dose, route and duration of exposure (9). Those chemicals which are most widespread in the environment, and those which cause the most drastic effects, have been extensively investigated, and many of the mechanisms causing neurotoxicity have been identified (9). Given the knowledge of these effects, it is important to investigate the possible neurotoxic influences of the large number of other chemicals prevalent in the environment. Mechanisms of neurotoxicity The main mechanisms encompassed by the afore-mentioned groups of substances include; induction of oxidative stress, alterations to neurotransmitter synthesis including inhibition of synaptic signalling, accumulation of the substance within mitochondria leading to dysfunction, alterations to the flow of ions across neuronal membranes, activation of second messengers to induce apoptosis or inhibit neurogenesis, disruption of DNA/RNA, affecting the differentiation and functioning of glial cells, to indirectly influence neuronal cells, alterations to membrane fluidity, abnormal expression of neurotrophic factors (7, 10-20). There is a requirement for metals in many body processes, including within the NS, providing an additional mechanism by which exogenous metals can induce neurotoxicity (17). They can compete with essential metals for protein binding sites and influence cellular processes (17). For example, lead competes with zinc, which is known to have binding sites present in many important receptor channels, such as the N-methyl-D-aspartate (NMDA) receptor involved in glutamate signalling at the synapse. Lead can displace zinc, and therefore alter functioning of these channels, and so influence glutamatergic functions in the NS (13, 14, 17). A relatively recently proposed mechanism thought to induce neurotoxicity via environmental chemicals, is endocrine disruption. Endocrine disruption is believed to be a crucial mechanism of most neurotoxicants, including metals, solvents, pesticides, Polychlorinated Biphenyls (PCBs), Diethylstilbesterol (DES), etc (21-25). Endocrine disrupting chemicals act by mimicking, enhancing, or antagonising the effects of endogenous oestrogens and androgens (21, 22). Their actions can result in alterations to hormone synthesis and/or release, altered transport and clearance of hormones, altered binding of hormones to their receptors (by binding themselves, thereby either mimicking hormone response, or blocking hormonal activation (24)), or altering components of pathways following receptor activation (22). An example of an endocrine disrupting mechanism is one used by lead, which lowers blood levels of testosterone, thereby de-masculinising certain areas of the male brain, and PCBs, which both mimic and antagonise various oestrogenic functions, and disturb production of androgens (21). As hormones are known to have a role in the development of the CNS, including sexual differentiation (26), disruption to their activities may result in disruption to the development of some brain areas, and the possibility of feminisation or masculinisation of particular brain areas (21-25). The neuroprotective function of hormones (discussed later) may also be hindered due to the endocrine disrupting actions of certain chemicals, allowing for their other neurotoxic mechanisms to have greater damaging effects. Neurotoxic investigations Carrying out investigations into the effects of neurotoxic chemicals is much more difficult in humans than it is in other animals, due to the greater difficulty in controlling the surrounding environment and its influences, and there are many potential variables that can have an effect on the overall result, in particular exposure to other environmental chemicals, drugs, alcohol, tobacco, education, culture, etc (27-31). All the potential confounding factors must be taken into consideration in order to analyse the neurotoxic effects only of the chemical in question (32). Often, environmental chemicals induce delayed neurotoxicity, whereby a patient does not present with symptoms until well after exposure to the chemical has ended, providing another problem to investigators (4). There are many different symptoms that can present upon neurotoxicity; migraines or headaches, confusion, memory loss, Multiple Sclerosis (MS)-like symptoms, problems with sleep, balance and hearing, attention impairment and trouble concentrating, anxiety and depression (8). Alterations to cognitive function, motor function and behaviour are common outcomes of neurotoxicity, and are a useful assessment of the effects of exposure to chemicals (32, 33). There are a wide range of different tests commonly used to assess neurotoxicity to the PNS and CNS (4, 32, 33). Measurements of functions such as motor reflexes, insensitivity to pinpricks on the skin, or impairment of sensitivity to temperature and vibration, provide evidence of PNS toxicity (4, 32, 33). Other functional tests, including IQ (Intelligence Quotient) tests, memory tests, assessment of mood and personality, and behavioural questionnaires, are used to assess toxicity to the CNS (4, 32, 33). Damage to the Nervous System can also be established by use of various brain imaging techniques (e.g. Computed Tomography, Magnetic Resonance Imaging) (9). These are useful in observing physical alterations to brain size and appearance caused by brain tissue atrophy following neurotoxic exposure (9). It is also possible, using these images, to ascertain which regions of the brain are particularly affected (9, 33-35). Despite the large quantity of literature outlining investigations concerning exposure to different neurotoxic chemicals, there are relatively few publications available that have identified a difference in response between males and females. Differences between susceptibilities of a range of age groups, and groups with varying levels of exposure, have been acknowledged frequently (27, 36-38), however reports are rare in which results for men and women are assessed independently, therefore it is often difficult to determine any differences in susceptibility between the sexes. Many reports record numbers of each sex taking part in the study, and match controls accordingly, then proceed to analyse results as a whole (27, 28, 39-45). Others exclude female subjects altogether, rather than including analysis of female results, but separate from the male (29, 30, 46-51). This is often the case when the number of female subjects is small compared to men. However, the results could still be analysed, and any differences between them could be noted. Some fail to establish which sexes have been used at all (52-54). Nevertheless, there is evidence from a number of reports, of a difference between genders in neurological functioning following exposure to neurotoxic chemicals. An extensive search using MEDLINE and EMBASE, of published studies and case reports into neurotoxicity of environmental chemicals, identified a number of studies which observed differences between males and females. For the purpose of this report, only those chemicals with gender differences have been mentioned. Evidence of Gender Differences in neurological outcomes of exposure to Neurotoxic Chemicals Metals There are roughly 40 different metals that exist in the environment, some of which are essential for life to occur (e.g. copper, zinc, etc), others which arent (e.g. mercury, lead, etc) (9). Exposure to metals in the environment has been known to cause adverse effects to both the adult and child human NS for many years (3). The neurotoxic effects of these metals are particularly well characterised, and have been well investigated. Included in this report are three of the major neurotoxic metals, of which there has been much exposure to in the environment, and of which there has been some indication of a sex difference in susceptibility to neurotoxic effects; mercury, lead and manganese. These three metals have been more extensively investigated than others, and therefore sex differences observed should not be ruled out of others, and may also be noted if they are as well examined. Mercury Mercury can take various different forms, each of which has distinct effects on human systems (18). Methylmercury (e.g. contaminated seafood), ethylmercury (e.g. Thimerosol, a component of some vaccines), elemental Mercury (present in industrial vapours), and inorganic mercury compounds (e.g. skin lightening creams) (18). Of these forms, methylmercury has been acknowledged as having the greatest detrimental effect on the correct functioning of the human NS, and in particular, the developing nervous system of children (18). In adults, methylmercury is thought to damage specific brain regions, such as the visual cortex, and parts of the cerebellum, whereas in children, as the NS is not completely developed, the effects are thought to be more widespread (7). It has been observed in a number of studies that male children show greater impairments in NS functioning following exposure than female children. In certain neurological tests, which have an association with methylmercury exposure, namely those assessing finger tapping, tendon reflexes, and leg coordination ability, males achieve poorer results (8, 36, 37, 55-57). As the majority of studies reporting results individually for male and female subjects are those carried out in children, the main sex differences reported here have been observed in children. However, similar results are noted in those adult investigations where males and females were analysed separately (27). McKeowyn-Eyssen et al. (1983), Cordier et al. (2002), Myers et al. (2003), Grandjean et al. (1998), and Marsh et al. (1987), all carried out numerous different tests on school children exposed to methylmercury at varying concentrations, pre- and post-natally. Each of these groups identified that, for those tests which have been shown to be more affected by increasing methylmercury levels, including finger-tapping, abnormal muscle tone, tendon reflexes, and leg coordination, male children showed poorer results (19, 57-60). McKeowyn-Eyssen et al. (1983) carried out the same tests on adults, and found an indication of a similar sex difference, with men being more likely than women to develop neurological disorders, following increases in methylmercury levels (37). Davidson et al. (2000) found that male, but not female, responses in neurological tests increased with methylmercury exposure, which is the opposite of the expected results, however, numerous unexamined variables were identified, which could have had influences on the results of the tests (31). Holmes et al. (2003) identified a link between mercury exposure and autism in children. Higher mercury levels in the hair were found to be associated with milder autistic symptoms (61). Perhaps because those children with milder symptoms were more able to excrete the mercury through their hair, before too much damage occurred. There was a greater number of females showing milder autistic symptoms, and a greater number of males showing severe autistic symptoms (61). From the evidence put forward here, there is a definite implication of a greater susceptibility for males than females to the neurotoxic effects of methylmercury exposure. There is an increased risk of neurotoxicity for children of women with increased levels of mercury in the hair (61). Hair mercury levels in subjects themselves, following equal exposure between the sexes, has been observed on numerous occasions as being lower in males than females, when associated with neurological problems (37, 61, 62). It may be that females have a better ability to excrete mercury through the hair than males, so less is present in body tissues. Lead Lead has long been known as a neurotoxicant, and its widespread release into the environment over the years has resulted in many neurological problems, mainly linked to learning difficulties (17), that have been well studied and characterised (3). Lead toxicity is thought to occur mainly in the hippocampus, cerebellum, and prefrontal cerebral cortex and again, it is thought that children, with their NS still developing, are at greatest risk to the neurotoxic insults of lead (7), so the majority of reports found here have been carried out in children. The elimination of lead from many environmental sources, such as motor vehicle petrol, and paints, has seen a decline in the amount of toxic lead exposure (7). However, it is still a problem in many areas, for example those homes where lead paint has been used in decoration (17). There are a number of studies that have reported a difference in cognitive impairments between male and female children. Tests carried out on school children, in South America, the UK and USA (38, 63-66), all identify a larger correlation between lead levels in the blood and poor cognitive ability in males than in females, while Wasserman et al. (1998) state that mothers reported behavioural problems with male children exposed to lead, more often than with exposed female children (67). An assessment of behavioural problems associated with lead exposure in American children (68) and an assessment of intelligence of children following lead exposure in Port Pirie (69), identified no difference between males and females in the results of their tests, while an assessment of the capabilities of children in school, and association with lead exposure (70), along with another investigation of child IQ by Needleman et al. (71), observed results to suggest females were more susceptible to lead neurotoxicity than male subjects, as they appeared to have greater prevalence of learning difficulties associated with lead. So, there appears to be a significant amount of evidence implying a gender difference in neurotoxicity associated with lead exposure. The majority of reports imply an increased susceptibility for males; however it is important for groups to look at sex differences in future studies, in order to ascertain conclusive results. This evidence also provides a need for investigation of sex differences in effects of lead exposure in adults. Manganese Manganese is another commonly used metal that can cause a toxic effect the NS upon exposure (20, 29, 40, 46, 47). There is a risk of manganese toxicity in various professions, in particular, welding (29, 46), but also through drinking or washing in water containing extraordinarily high levels of manganese (20, 40). There are a large number of reports confirming the neurotoxicity of manganese (20). Investigations have shown decreased intellectual ability in children over-exposed to manganese (40), and mood disturbances in men exposed occupationally (e.g. welders, factory workers.) (29, 40, 46, 47). In children, a report into an association between hair manganese levels and prevalence of hyperactivity, found that while there was a higher amount of manganese present in girls than boys, no difference was found between the sexes in assessment of neurological behaviour tests (72). Perhaps female brains are better able to cope with a higher amount of manganese. In adults, Dietz et al. (2001) found that a relationship between levels of manganese exposure and its effect on the Globus Pallidus area of the brain was seen only in men. These investigators give the reason that female workers have lower blood concentrations of manganese, and have a lower cumulative exposure index (73). However, they do not state whether there was a difference in actual exposure between sexes. If the exposure levels were the same, this could be an indication of increased susceptibility to males. In another study, results of neurological tests following manganese exposure were poorer for men than for women (74). As the majority of studies on manganese actually exclude females from results, or do not give separate results for each sex, it is difficult to make any definite assumptions about gender differences in neurotoxicity susceptibility. Implications from the three studies above provide a suggestion of a sex differences in manganese toxicity, with a greater effect within males. However, in future studies, where possible, females should be included, and the results analysed separately, in order to establish conclusive evidence for sex differences in neurotoxicity to manganese. Solvents There is a vast array of solvents that are used in many different industries and work places, meaning daily exposure for many different workers, including hairdressers, laboratory workers, painters, dry cleaners, and carpet layers, among others (33, 75-78). Due to the composition of solvents, they are particularly dangerous to the tissues of the NS. They are lipophillic compounds, and therefore have strong affinity for tissues rich in lipids, including the brain (33, 79). It is thought that psychomotor performance is the most common deficit (51) of solvent exposure, and prolonged exposure can cause permanent damage (15). Other symptoms include anxiety, insomnia, irritability, memory loss, fatigue and seizures (15, 33, 75). Solvent substances most often consist of a mixture of different chemicals, which can affect different regions of the brain. This can result in difficulties determining the toxic effects of a particular chemical (9). There have been many studies published that report clear association between solvent exposure and neurological deficits. Nelson et al. (1994) report that solvent exposure in workers at an automobile assembly plant, correlates with increased neurological disease, and, noticed in particular, an association with increased prevalence of a condition closely resembling MS (52). Cavalleri et al. (1994) obtained results to indicate deterioration of colour vision in factory workers following perchloroethylene exposure, even at low levels (53), and Boor et al. (1977) confirm a damaging effect of toluene on the CNS (54), a chemical that is also known to effect CNS development prenatally (3). Alcohol (Ethanol) is a major environmental solvent, although exposure rarely occurs occupationally, and it is most often taken in voluntarily (3). Hommer et al. (2001) studied the brain volumes of alcoholic and non-alcoholic men and women, and found that alcoholics had a much smaller volume of grey matter than non-alcoholics. This difference was found to be much more significant in females than males, suggesting an increased susceptibility of females to neurotoxic effects of alcoholism (34). In contrast, Pfefferbaum et al. (2001), in the same journal publication, indicated that the results of their study into alcohol effects on brain structure, show larger cortical sulci and lateral and third ventricles found in the alcoholics compared to non-alcoholics, which was a much greater and more significant difference in male subjects than female subjects. They also note that female brains show quicker and more effective recovery than those of males during abstinence (35). Jacobson (1986) ca rried out a study examining the brains of male and female alcoholics compared to non-alcoholic controls. It was noticed that the appearance of the brains on a CT scan was different between alcoholics and controls. Also observed was the fact that females appear more susceptible to structural changes in the brain following chronic alcohol intake, but are much more effective at recovering following cessation of intake, and the recovery occurs much quicker (80). Taking these 3 reports into consideration, there may be a difference in susceptibility of particular brain areas in males and females; however, females consistently recover more quickly from damage than males, indicating perhaps, a decreased susceptibility to long term damage. Neurophysiological deficits have also been reported in numerous studies of children exposed to alcohol pre-natally (81-83). However, few have noted results separately for male and female children. Nanson and Hiscock (1990) observed that female Fetal Alcohol Syndrome (FAS) children appear to have a higher IQ than males with FAS (83). As mentioned above, the majority of studies into other solvents, such as toluene, trichloroethene, n-hexane, chlorinated solvents (84), and solvent mixtures (49, 50, 76, 78, 85) in the workplace, report an obvious detrimental effect on the CNS, PNS, or both, following exposure. However, the majority included only men in the reports, or male and female results were analysed together. Again, it has been observed that the developing NS is especially susceptible to the neurotoxic effects of solvents, due to their high affinities for the brains lipid tissues (33, 79), and the BBB not being fully formed (7). Laslo-Baker et al. (2004) and Till et al. (2001) carried out studies on organic solvent exposure in pregnant women, taken in accidentally from occupational exposure, and the effects on neurodevelopment of their offspring. Both groups confirmed that children exposed pre-natally had poorer cognitive functioning than those not exposed, with lower results in neurological tests (75, 86). Again, no distinction was made between results for female and male children. Considering the obvious effects of solvents, including alcohol and toluene, on the NS, and the observations of sex differences from other neurotoxins, and the implications of sex differences in effects of alcohol mentioned here, it should be suggested that future studies automatically investigate male and female results separately, and allow for observation of any differences in results. Pesticides The term pesticides encompasses a wide range of chemicals, commonly used within a wide range of industries, particularly agriculture (87, 88). Included are the sub-groups; organophosphates, organochlorines, fumigants, and herbicides, all of which act to damage the NS of an organism, either directly, or via alteration of the cellular mechanisms that support it (87). Pesticides cause concern for human health as they are extremely widely used, and so readily released into the environment (88). It has been known for a long time that exposure to certain levels of these chemicals will adversely affect the human NS, as well as those organisms they are designed against (87, 88). Indeed, numerous studies have linked exposure to various pesticides with a number of neurological disorders, including Parkinsons disease (87, 89). In a similar situation to that for metals and solvents, there are many publications from groups investigating the effects of pesticide exposure on the human Nervous System, using an array of cognitive and neurobehavioural tests, with almost every study confirming the presence of some form of Neurotoxicity in subjects exposed to a range of doses. The following reports have identified separate results for neurological effects of pesticide exposure on male and female subjects, and an apparent greater effect on males. A report investigating the influence on the onset of Parkinsons and Alzheimers Diseases in elderly people living in the south of France, where pesticides are used daily in vineyards, noted a significant association between these disorders and pesticide exposure, in males only (90), suggesting a potentially increased susceptibility to males. Stallones et al. (2002) acknowledge males being at increased risk of developing neurological problems related to pesticide exposure than females, in an investigation into farmers, and their families in Colorado, USA (91), with the percentage of illnesses caused by exposure to pesticides almost three times greater in males. An assessment of neurobehavioural activity of Hispanic agricultural workers (92) identified a significant difference between the genders on results for 2 out of 10 tests, with females scoring lower than males. In the remaining tests, no significant differences were found between the sexes, although all exposed subjects faired worse than control, non-exposed (92). Similarly, pesticide-exposed Ecuadorians achieved lower outcomes in neurobehavioural tasks set by Cole et al. than did non-rural, unexposed Ecuadorians, and females were found to respond better in one task, with no significant difference between genders in others (93, 94). Guillette et al. (1998), carried out an assessment of Preschool children in Mexico, exposed to pesticides through living in close proximity of farm land. They identified a significant difference between those exposed and those living further away from the farm lands, with females performing better than males in several of the neurological tests (95). It appears that when there is a gender difference observed in the neurotoxic effects of pesticides, females tend to fair better than males, implying an increased susceptibility of males to the influences of pesticides on the NS. As it is more commonly males that are in the closest proximity to pesticides, within farming industries in particular, this could have some influence on this hypothesis. However, as the differences are also apparent in male and female children, with equal exposure, it does indicate a greater risk for males. The finding that there was only a significant difference in some tests may indicate an increased susceptibility of some brain areas in males over others, which correlates with results of studies of alcohol and tobacco smoke (below). Other Sources of Environmental Neurotoxicity Tobacco Smoke The chemicals contained in tobacco smoke, particularly nicotine, are now known to cause a variety of neurological problems, in addition to their other effects, including behavioural and cognitive problems during development, tremor, and an increased risk of stroke, from both smoking directly, and through passive smoke; inhalation or exposure prenatally (96-100). Various groups investigating toxicity caused by intake of tobacco smoke have described minor sex difference in the neurological outcome. Louis (2007) reports that, when looking into hand tremor as an outcome of tobacco smoking, the difference in score between smokers and non-smokers is greater in women than in men, which would indicate more of a susceptibility to women, rather than men (96). Jacobsen et al. (2007) investigated auditory and visual attention in adolescent smokers and non-smokers, with and without prenatal exposure to tobacco (101). They observed that different areas of the brain are apparently affected differently in male and female subjects exposed to tobacco smoke. In females, both auditory and visual attentions appear equally vulnerable, performing slightly more poorly in visual tests than males, while in males, auditory attention seems significantly more affected than visual attention, and in this auditory test, males performed substantially worse than females (101). The results of this investigation, put together with those from the Louis (2007) report, point towards sex-specific variation