Saturday, January 23, 2010

In Guns, Germs, and Steel, Jared Diamond suggests that more research needs to be done on how cultural factors influenced the distribution of...

The answer to this question is, of course, a matter of personal opinion, as we do not have the ability to go out and do rigorous research on this issue. My own view is that culture can affect the distribution of wealth and power.  However, I would say that culture can affect this distribution within regions much more than it can affect the distribution between regions. In other words, I would argue that culture could cause differences in wealth and power between Germany and Poland, for example, much more than it could have caused differences in wealth and power between Germany and Angola.


If culture causes differences in wealth and power, it does so because it affects how the degree to which people are open to change and how they think about things like work.  For example, imagine that you have a culture that is strongly opposed to change. It might prevent women from getting educated and/or entering the workforce because that is not how things have always been done. This society will likely end up poorer and weaker than one that is open to change.  In the second society, women would end up working and would increase the country’s economic potential. As another example, people in one society might think that work for its own sake is morally good. Those people would work hard for long hours because they thought that is what good people do. That society would end up richer and stronger than one where people felt that it was okay to work only as much as necessary.


While it is (in my view) possible that culture can affect wealth and power, I would argue that this is more likely to matter within a region than between regions.  I say this mainly because Diamond seems to prove very convincingly in Guns, Germs, and Steel, that the environment caused the differences between regions that we saw when the Europeans dominated the world.  It is hard to argue that he is wrong in any particular circumstance.  I cannot refute his arguments, for example, about why Australia remained poor and weak until Europeans came.  Therefore, I am inclined to believe that culture does not cause differences between regions. Furthermore, I am more inclined to believe that the environment is very different between regions than within a region.  Germany and Angola were clearly very different environments where Germany and Poland were not.  Therefore, it seems logical that something else must have caused the differences between Germany and Poland. 

What is the human papillomavirus (HPV) vaccine?


Definition

Two brands of the human papillomavirus (HPV) vaccine, Cervarix and Gardasil, have been approved by the US Food and Drug Administration. Both brands can prevent most cases of cervical cancer if the vaccine is given before exposure to HPV. Gardasil can also prevent genital warts in both females and males.




More than forty types of HPV can infect the genital areas of both males and females. Most HPV types cause no symptoms and resolve on their own. Some types of HPV, however, cause cervical cancer and other, less common, genital cancers (of the penis, anus, vagina, and vulva). The Centers for Disease Control and Prevention (CDC) estimate that 17,500 women and 9,300 men are affected by cancers caused by HPV each year. Some types of HPV can cause genital warts. Because the HPV vaccine does not prevent all kinds of cervical cancer, females who receive the HPV vaccine still need to have regular Pap tests.




Candidates for Vaccination

The HPV vaccine should be given before beginning sexual activity with another person. The vaccine is most effective in persons who have not been exposed to HPV.


The vaccine is recommended for children age eleven and twelve. However, the vaccines can be administered in children as young as nine years of age. Also, people through age twenty-six years can receive the vaccine if they did not receive any or all of the shots when they were younger.




Dosage

The HPV vaccine is given as a three-dose series. Each dose is 0.5 milliliters, administered intramuscularly, preferably in a deltoid muscle. It is best to use the same vaccine brand for all three doses. The minimum time between dose one and dose two of the vaccine is four weeks; between does two and dose three is twelve weeks. The minimum time between dose one and dose three is twenty-four weeks. Doses that were received after a shorter-than-recommended time interval should be given again.




Risks

Generally, the HPV vaccine is very safe, but mild to moderate reactions have been reported. Reactions include pain, redness, itching, bruising, or swelling at the injection site; mild to moderate fever; headache; nausea; vomiting; dizziness; and fainting. Persons who are allergic to the ingredients of the vaccines, including yeast, should not receive the vaccine, nor should pregnant persons.




Impact

The HPV vaccine is the first preventive cancer vaccine. Initially, the vaccine was controversial because some parents and religious groups claimed it would make casual sex more acceptable, especially among girls, although studies by both Merck (the manufacturer of Gardasil) and independent researchers show no link between receiving the vaccine and increased sexual activity. Lawmakers are debating whether to make this vaccine mandatory; as of December 2015 it was mandatory only in Rhode Island, Virginia, and Washington, DC, and many teenagers were still not receiving it. According to the CDC, in 2014 60 percent of adolescent girls and 42 percent of boys had received at least one dose of the vaccine, an increase over the previous year but still a lower percentage than those receiving other vaccines recommended for eleven- and twelve-year-olds, such as the Tdap (tetanus, diphtheria, and pertussis) and meningitis vaccines.




Bibliography


Boston Women’s Health Collective. Our Bodies, Ourselves: A New Edition for a New Era. 35th anniversary ed. New York: Simon, 2005. Print.



Centers for Disease Control and Prevention. “FDA Licensure of Bivalent Human Papillomavirus Vaccine (HPV2, Cervarix) for Use in Females: Recommendations of the Advisory Committee on Immunization Practices (ACIP).” Morbidity and Mortality Weekly Report 28 May 2010: 626–29. Print.



Centers for Disease Control and Prevention. “FDA Licensure of Quadrivalent Human Papillomavirus Vaccine (HPV4, Gardasil) for Use in Males: Recommendations of the Advisory Committee on Immunization Practices (ACIP).” Morbidity and Mortality Weekly Report 28 May 2010: 630–32.



Centers for Disease Control and Prevention. “HPV Vaccine Information for Young Women.” Centers for Disease Control and Prevention. Dept. of Health and Human Services, 26 Mar. 2015. Web. 30 Dec. 2015.



Daniel, Jennifer. “Good Talks Needed to Combat HPV Vaccine Myth.” New York Times. New York Times, 9 Nov. 2015. Web. 30 Dec. 2015.



Dunne, E. F., and L. E. Markowitz. “Genital Human Papillomavirus Infection.” Clinical Infectious Diseases 43 (2006): 624. Print.



“Human Papillomavirus (HPV) Vaccines.” National Cancer Institute. Natl. Inst. of Health, 19 Feb. 2015. Web. 30 Dec. 2015.



Larsen, Laura. Sexually Transmitted Diseases Sourcebook. Detroit: Omnigraphics, 2009. Print.



McCance, Dennis J., ed. Human Papilloma Viruses. New York: Elsevier Science, 2002. Print.



Plotkin, Stanley A., Walter A. Orenstein, and Paul A. Offit. Vaccines. 5th ed. Philadelphia: Saunders, 2008. Print.



“Quadrivalent Vaccine Against Human Papillomavirus to Prevent High-Grade Cervical Lesions.” New England Journal of Medicine 356 (2007): 1915–927. Print.



Thompson, Dennis. "CDC Says Too Few US Teens Getting HPV Vaccine." CBS News. CBS, 30 July 2015. Web. 30 Dec. 2015.



Trottier, H., and E. L. Franco. “The Epidemiology of Genital Human Papillomavirus Infection.” Vaccine 24 suppl. 1 (2006): S1–S15. Print.

Friday, January 22, 2010

What is attention?


Introduction

Attention usually refers to concentration on a particular aspect of the external environment, although it is possible to attend to one’s own thoughts and other internal states. The flavor of the typical use of the term is captured in a statement by nineteenth-century German physiologist Hermann von Helmholtz, who noted that an observer who is steadily gazing at a fixation mark can, at the same time, concentrate attention on any given part of the visual field. The point in space to which one is directing one’s eyes and the point to which one is attending thus are not necessarily the same, and one does not have to move the eyes to shift visual attention.





Attention has been of interest for a long time. Helmholtz wrote about attention in an 1850 book on physiological optics. William James, a pioneer in the study of psychology, devoted much space to attention in his book
The Principles of Psychology
(1890), noting that it can be either involuntary and effortless or voluntary and effortful. According to James, attention allows people to perceive, conceive, distinguish, and remember better than they otherwise could. Edward Titchener, in his Lectures on the Elementary Psychology of Feeling and Attention (1908), reinforced this point by stating that attention determines what people are conscious of as well as the clarity of their conscious experience.


Other leading figures from the early history of psychology, such as Wilhelm Wundt, agreed with James that the issue of attention was of great importance. Titchener regarded the prominence of the topic as one of the major achievements of experimental psychology. Interest was maintained through the period following World War I; Karl Dallenbach noted in the late 1920s that more studies had been reported on attention in the preceding three years than in any comparable period in history. After World War II, the study of attention received an even greater boost with the increasing concern over human-machine interactions, especially in the military.


Attention can be drawn automatically (involuntarily and effortlessly) by certain characteristics of stimuli in the environment. These include abrupt brightness changes or vivid colors at particular locations; both intensity and clarity are important. Auditory attention is automatically drawn by changes in pitch or location. Such automatic attentional capture is often termed “bottom-up” or “data-driven.” A person readily attends to familiar stimuli, although these more often invoke voluntary and effortful processing, which is “top-down” or “internally driven.” A person can voluntarily attend to any aspect of the environment he or she chooses.




Attention Selection

How does a person select the things to which to attend? This question leads to a consideration of “early” (before meaning is analyzed) versus “late” selection. In 1958, Donald Broadbent championed the view that selection is made early through a process analogous to filtering incoming information according to its sensory properties. After a brief glimpse, a person can report the identity of items in the environment accurately if a cue indicating which items to report refers to their spatial location, but that person is much less accurate if the cue refers to semantic properties—for example, if it asks for only the letters from a display of several letters and digits intermixed.


Other researchers, such as J. Anthony Deutsch and Diana Deutsch, have argued that people unconsciously analyze all incoming information for its meaning, although selection cannot be made on this basis as easily as on a sensory basis. Support for this process, termed late selection, can be seen in tasks such as naming the ink colors of printed letters. J. Ridley Stroop
found that if a word that is the name of a color is printed in ink that is a different color from the one it names—for example, the word “blue” written in red ink—it takes much longer to name the ink color than if the combination of letters is meaningless, such as a row of red Xs. People cannot avoid reading the word, no matter how hard they try. Thus, word meaning appears to be activated automatically, and a person cannot selectively attend to the color. Nevertheless, if the color to be named appears as a patch, separated in space from the inconsistent color word, color naming is not slowed. Selection of what to attend to thus can be made easily on the basis of location, color, or brightness but not on the basis of meaning.




Visual, Sensory, and Spatial Attention

Attention is necessary because people do not have the capacity to be conscious of all aspects of their environment at once. Questions arise concerning the extent to which people can be conscious of more than one aspect simultaneously and of what aspects they can be simultaneously conscious. Because what is to be attended to can so easily be selected on the basis of its location, these questions often have been posed in relation to whether people can attend to nonadjacent areas simultaneously.


It is important first to point out that the observations of Helmholtz, James, and Titchener have been verified in sensitive laboratory experiments. Subjects gazing at the center of a computer screen were first given information about the spatial location on the screen of a target that would later appear away from fixation. The correct location usually was indicated, but sometimes an incorrect location was indicated. In comparison with instances when no location information was shown, detection of the target was aided by valid information but harmed by invalid information. If the target did not appear in the indicated location, however, detection was better when it appeared near the indicated location than when it appeared farther away. The edges of the attended area are thus vaguely rather than sharply defined. Yet can attention be split between nonadjacent locations? Most research has shown that this is not possible; people cannot attend to two separate areas simultaneously, although a few studies have indicated that they can attend to ringlike areas with attention devoted to the ring but not the surrounding area or the center.


In contrast to splitting visual attention between two separate locations, dividing attention between two different senses is possible. People can, for example, listen (attend) to a conversation while watching (attending to) the road when driving. Nevertheless, unless one of the tasks is very easy or highly practiced, performance still suffers in comparison to when attention is dedicated to one sense.


Directing attention on the basis of spatial location appears to be very important. Ulric Neisser described the visual determination of what is present as occurring rapidly in two stages. The first he called “preattentive” because it involves only a rough global analysis of information in the entire visual field, before attention is directed to any one location. People can detect simple visual features such as color, brightness, and the direction in which a straight line points on the basis of preattentive analysis. More precise determination of combinations of these simple features requires what is called focal attention, in which attention is focused on particular spatial locations containing the preattentively detected simple features. For example, seeing that a line in a particular orientation is of a certain color requires focal attention. Without it, a person could tell that the color is present somewhere, and that a line of that orientation is present somewhere, but not that the line is of that color. Focal attention is required to combine simple features. This process has been termed feature integration theory, and focused attention is described as the metaphorical glue that binds separate features into a unitary object.


Feature integration theory has received experimental confirmation in the work of Anne Treisman and her colleagues. They found that when focal attention is diverted or cannot be applied because of an interfering task, simple features are often matched incorrectly to produce what they termed “illusory conjunctions.” For example, when a red horizontal line and a green vertical one are shown, in the absence of focal attention, a subject is likely to be conscious of the horizontal line as green and the vertical line as red.




Use of Schemata

A person can direct attention on bases other than a spatial one. That is, even overlapping shapes can be selectively attended. Neisser has described a study in which a basketball game and a hand-slapping game were shown simultaneously in outline form in the same location on a television screen. Observers could attend to only one game and were largely unaware of events occurring in the unattended game, but they were just as able to indicate each occurrence of some event in the game being attended, such as a throw of the ball from one player to another, as they were when that game was shown alone. The inability to divide attention between two games is due to expectations inherent in the way people understand and mentally represent each game. These mental representations are called schemata. Through them, attention has its effects as an alerting and sustaining process whereby receptivity to certain information can be maintained over the short or long term.


One additional phenomenon involves what Colin Cherry referred to as the “cocktail party phenomenon.” The setting is a cocktail party or any gathering where people are engaged simultaneously in different conversations. A person can listen selectively to one conversation and apparently not be conscious of others. Auditory attention therefore seems fully focused on only one conversation. However, the listener might hear his or her name mentioned in any one of a number of other conversations and immediately shift attention to it. How can people attend fully to one source of information, yet simultaneously be sensitive to important information from other sources? Can their attention be focused and yet divided among a number of possible sources of information at the same time? The answer lies in the fact that stimuli outside the focus of attention are sometimes processed to the level of meaning, especially if they correspond to active and important schemata such as one’s name.




Practical Uses of Research

Understanding how attention operates makes it possible to design environments that enable people to better attend to important characteristics. For example, hunters often are cautioned to wear a piece of clothing colored “blaze orange.” A bright color is a simple feature that draws attention automatically. Another hunter’s attention will be drawn to the blaze orange, and focusing attention on the color will allow it to be conjoined with other simple features, such as shape. The second hunter thus will almost immediately be conscious of the hunter wearing the blaze orange as a hunter and will be unlikely to misperceive this hunter as game (in addition, the color of game is never blaze orange). The same principle is applied when emergency vehicles such as fire trucks are painted bright red or yellow.


Principles stemming from basic research on attention have been applied in the development of what is known as head-up displays (HUDs) in aircraft such as helicopters. Typically, a pilot faces a windscreen through which the environment can be seen, with a cluster of instruments designating altitude, speed, and so on nearby. With this configuration, the pilot must look away from the windscreen and at the instruments to check them. As helicopters are capable of traveling at high speeds and often are flown close to the earth and to objects into which they might crash, it is important that looking away from the windscreen be minimized. In a HUD, the data from the instruments is projected onto the windscreen so that the pilot can see the information without having to divert his or her eyes from the windscreen.


Can the pilot attend to the instruments and the environment outside the windscreen simultaneously? They spatially overlap and thus are visible at the same time, yet studies of attention indicate that the pilot cannot attend to them both at once. The experiment described by Neisser in which two games were superimposed on a screen is relevant here. An observer could attend to one game or the other but not to both at the same time. This does not mean that HUDs are without value. Attention can be directed from the instruments to the environment or vice versa without the pilot moving his or her head or eyes, and either type of physical movement is much more time consuming than a relatively rapid shift of attention.




Shadowing

One popular laboratory task is to have listeners “shadow” material presented to them. In shadowing, the listener hears a series of words spoken at a normal conversational rate and tries to repeat aloud each word as it is heard. The task is difficult, and subjects must devote considerable attention to the shadowing. Often a listener is asked to shadow material played with a tape recorder to one ear while different material is played by another tape recorder to the other ear (earphones are used). Certain characteristics of the material not being shadowed can be varied. After the task, the listener can be asked a number of questions regarding what he or she was conscious of in the unshadowed message.


Consistent with Cherry’s cocktail party phenomenon, listeners are conscious of the presence of the unshadowed message and of whether there is an abrupt change of pitch (as in a change of voice from a man’s to a woman’s, or the introduction of a whistle). These global physical characteristics of the unshadowed message can be determined preattentively. Listeners are not conscious, however, of the contents or the language of the unshadowed message, of whether the language changed during the message, or even of whether speech or nonsense sounds were presented, unless a change of pitch occurred. Many variations of this experiment have been performed, and all have produced the same results: consciousness of the unshadowed material is limited to information that could be detected preattentively. There is no consciousness of the meaning of the unshadowed message, except that listeners sometimes are conscious of their own name if it appears, as a result of powerful schemata for something as important as one’s own name. The results are exactly what would be expected from what has been shown to be true of attention thus far and from the original description of the cocktail party problem.




Emergence of Attention Theories

The first complete theory of attention was not proposed until 1958, when Broadbent introduced his concept of attention as a filter that admitted only certain information, selected on the basis of sensory characteristics, into the limited-capacity system. This marked the continuation of interest in attention by researchers in England, beginning with Cherry in 1953. In 1963, J. Anthony and Diana Deutsch proposed that all incoming information is analyzed to the level of meaning.


Many of the fundamental issues in attention have been recast somewhat in an information-processing mode, beginning in the late 1960s. For example, attention is described in terms of “selection,” “resources,” “features,” “input,” and so on. Whereas the emphasis had previously been on hearing, visual attention began to receive more emphasis. Many of the findings were like those on hearing, although factors such as color and brightness were considered.


Attention remains central to the study of consciousness and cognitive psychology. As Michael Posner noted in 1975, “Attention is not a single concept, but the name of a complex field of study.” Accordingly, questions about early versus late selection, automatic processing, and other issues in the control of attention have not yet been fully answered.




Bibliography


Gazzaniga, Michael S. The Cognitive Neurosciences. Cambridge: MIT P, 2004. Print.



Gopher, Daniel, and Asher Koriat, eds. Attention and Performance XVII. Cambridge: MIT P, 1999. Print.



Humphreys, Glyn, John Duncan, and Anne Treisman, eds. Attention, Space, and Action: Studies in Cognitive Neuroscience. New York: Oxford UP, 2003. Print.



Johnston, William A., and Veronica J. Dark. “Selective Attention.” Annual Review of Psychology 37 (1986): 43–75. Print.



Lehmann, Alexandre, and Marc Schönwiesner. "Selective Attention Modulates Human Auditory Brainstem Responses: Relative Contributions of Frequency and Spatial Cues." PLOS ONE 9.1 (2014): 1–10. Web. 18 Feb. 2014.



McColeman, Caitlyn M., et al. "Learning-Induced Changes in Attentional Allocation during Categorization: A Sizable Catalog of Attention Change As Measured by Eye Movements." PLOS ONE 9.1 (2014): 1–22. Web. 18 Feb. 2014.



West, Greg L., Jay Pratt, and Mary A. Peterson. "Attention Is Biased to Near Surfaces." Psychonomic Bulletin & Review 20.6 (2013): 1213–20. Print.

Thursday, January 21, 2010

What do Cassius and Brutus discuss at the end of Act 1, Scene 2 in Julius Caesar? Which "side" will Brutus ultimately choose?

Brutus and Cassius are discussing Caesar’s ambition and what to do about it.


Cassius seeks out Brutus and asks him what he thinks about Caesar.  He knows that Brutus and Caesar are close.  However, he still wants Brutus to join in their conspiracy because his name and reputation will help lend them legitimacy.  Brutus tells him he is indeed concerned about Caesar’s ambition.


Brutus promises to consider Cassius’s arguments, but does not make a promise to join them.  He tells Cassius that he does not want to live under Caesar’s thumb, however.



What you have said
I will consider; what you have to say
I will with patience hear, and find a time
Both meet to hear and answer such high things.
Till then, my noble friend, chew upon this:
Brutus had rather be a villager
Than to repute himself a son of Rome
Under these hard conditions as this time
Is like to lay upon us. (Act 1, Scene 2)



Casca comes and tells them that Caesar was offered a crown three times by Mark Antony.  This seems to reinforce their fear that Caesar is making a play for becoming King of Rome.  Brutus and Cassius do not approve of kings.  Rome hasn’t had a king in a long time.  Caesar is dictator, which is bad enough.  They do not want to risk him getting more power.


After Brutus leaves, Cassius tells us his plan for making Brutus agree to join their conspiracy.  He will trick him into thinking that all of the people of Rome want Brutus as their leader.



If I were Brutus now and he were Cassius,
He should not humour me. I will this night,
In several hands, in at his windows throw,
As if they came from several citizens,
Writings all tending to the great opinion
That Rome holds of his name … (Act 1, Scene 2)



Cassius hopes that Brutus will find all of these letters, supposedly from many Romans, begging him to take care of Caesar.  He thinks that Brutus is on the edge, but this will give him the extra push to agree to join them.  Cassius already has a group going, but he wants Brutus’s clout.


At this point, the reader or audience can make a prediction that Brutus will join the conspiracy.  He has said that he is concerned about Caesar’s power and ambition, and he told Cassius to come see him to talk to him again.  We also know that Cassius has a plan to convince Brutus that the people of Rome are on his side.

What are inborn errors of metabolism?


Early Observations

In 1902, Sir Archibald Garrod, a British physician, presented a classic paper in which he summarized his observations and analyses of a condition known as alkaptonuria. The condition is easily diagnosed because the initial major symptom is dark urine caused by the excretion of homogentisic acid. Other symptoms that occur later in life include pigmentation of the connective tissue, spine and joint deterioration, coronary artery calcifications, and cardiac valve deterioration.










Garrod reasoned that individuals with alkaptonuria had a defect in the utilization of amino acids, because homogentisic acid is not normally found in urine and is a by-product of certain amino acids with particular ring structures. Today it is known that alkaptonuria is linked to mutations of the HGD gene, which was mapped to chromosome 3q21-q23. These mutations cause an absence of the enzyme homogentisic acid oxidase. Without the presence of this enzyme, homogentisic acid accumulates and causes the aforementioned symptoms.


Scientists were only beginning to discover the genetic causes of disease at this time. Garrod noted that the condition is often found in two or more siblings and postulated that the occurrence of this condition may be explained by the mechanism of inheritance. In 1908, in “Inborn Errors of Metabolism,” Garrod extended his observations on alkaptonuria to other diseases such as albinism and cystinuria. In each case, he argued that the abnormal or disease condition was caused by a defect in metabolism that resulted in a block of an important metabolic pathway. He speculated that when such a pathway is blocked, there would be an accumulation of products that are not seen in normal individuals, or important substances would be missing or abnormal. He traced the inheritance of these conditions and discovered that they could be passed on from one generation to the next. He was the first to use the term “inborn errors of metabolism” to describe these conditions.


Other investigators have studied more than three thousand additional diseases that can be included in this category. A few of these conditions occur at relatively high frequency in humans. In the U.S. Caucasian population, cystic fibrosis occurs in about 1 in 2,000 births. Some conditions, such as phenylketonuria (PKU), are seen at moderate frequency, about 1 in 10,000. Many of the inborn errors are rare, with frequencies less than 1 in 100,000. A generally accepted definition of an inborn error of metabolism is any condition with actual or potential health consequences that can be inherited in the fashion described by Gregor Mendel in the nineteenth century.




Malfunctioning Proteins and Enzymes

The biochemical causes of the inborn errors of metabolism were discovered many years after Garrod presented his ideas. In 1952, Von Gierke disease was found to be caused by the defective enzyme glucose-6 phosphatase. After this discovery, many inborn errors of metabolism were traced to defects in other enzymes. Enzymes are proteins that catalyze biochemical reactions. They are responsible for increasing the rates of reactions that occur in all cells. These reactions are important steps in metabolic pathways that are responsible for processes such as utilization of nutrients, generation of energy, cell division, and biosynthesis of substances that are needed by organisms. There are many metabolic pathways that can be affected if one of the enzymes in the pathway is missing or malfunctions. In addition to enzymes, defective proteins with other functions may also be considered as candidates for inborn errors of metabolism. For example, there are many types of defective hemoglobin, the protein responsible for oxygen transport. These defective hemoglobins
are the causes of diseases such as sickle-cell disease and thalassemia.




Genetic Basis of Inborn Errors

The cause of these defects in enzymes and proteins has been traced to mutations in the genes that code for them. Alterations in the structure or nucleotide composition of DNA can have various consequences for the structure of the protein coded for by the DNA. Some of the genetic alterations affecting metabolism simply represent normal variation within the population and are asymptomatic. An example of such a genetic alteration is the ability of some individuals to experience a bitter taste after exposure to chemical derivatives of thiourea.


Some asymptomatic variations in genetic coding may lead to complications only after environmental conditions are changed. There are a few “inborn errors” that can be induced by certain drugs. Another class of alterations may be minor, with the resulting protein having some degree of function. Individuals with such alterations may live long lives but will occasionally experience a range of problems associated with their conditions. Depending on the exact nature of the mutation, some of the alterations in the resulting protein structure can lead to a completely nonfunctional protein or enzyme. Consequences of this type of mutation can be quite severe and may result in death.


Many of the inborn errors of metabolism are inherited as autosomal recessive traits. Individuals are born with two copies of the gene. If one copy is defective and the second copy is normal, enough functioning protein or enzyme can be made to prevent the individual from exhibiting any symptoms of the disease. Such individuals will be classified as carriers for the defect since they can pass on the defective gene to their offspring. About one in twenty Caucasians in the United States is a carrier for the cystic fibrosis gene, and about one in thirty individuals of Eastern Jewish descent carries the gene for the lethal Tay-Sachs disease. When an individual inherits two defective copies of the gene, the manifestations of the disease can be much more severe.


Some inborn errors of metabolism, such as Huntington’s disease, are manifested as dominant genetic traits. This means that only one copy of the defective gene is necessary for manifestations of the abnormal condition. Huntington’s disease is linked to mutations in the IT15 gene, and it causes severe neurodegenerative symptoms. Researchers are currently looking into treatments for Huntington’s disease that would actually turn off certain genes instead of adding new ones.


There are some inborn errors of metabolism that are sex-linked. Diseases that involve mutations carried on the X chromosome may be severe in males because they have only one X chromosome but less severe or nonexistent in females because females carry two X chromosomes.




Diagnosis and Treatment

Significant progress has been made in the diagnosis of inborn errors of metabolism. Prior to 1980, clinical examination was the primary tool used to diagnose metabolic defects. Biochemical tests detect various substances that accumulate, or are missing, when an enzymatic defect is present. The commonly used screening for phenylketonuria (PKU) relies on detection of phenylketones in the blood of newborns. PKU is caused by a mutation in the phenylalanine hydroxylase gene, which is responsible for encoding the enzyme L-phenylalanine hydroxylase. Hyperphenylalaninemia, or an elevated blood level of phenylalanine, occurs without the presence of the enzyme L-phenylalanine.


For cases in which the genetic defect is known, DNA can often be used for the purpose of genetic testing. Genetic counselors will help parents determine their chances of having a child with a severe defect when parents are identified as carriers. Small samples of cells can be used as a source of DNA, and such cells may even be obtained from amniotic fluid by amniocentesis. This allows diagnosis to be made prenatally. Some parents choose abortion when their fetus is diagnosed with a lethal or debilitating defect.


Although strides have been made in diagnosis, the problem of treatment still remains. For some inborn errors of metabolism such as PKU, dietary modification will often prevent the serious symptoms of the disease condition. Individuals with PKU must limit their intake of the amino acid phenylalanine during the critical stages of brain development, generally the first eight years of life.


Treatment of other inborn errors may involve avoidance of certain environmental conditions. For example, individuals suffering from albinism, a lack of pigment production, must avoid the sun. For other inborn errors of metabolism, there are no simple cures on the horizon. Since the early 1990’s, some medical pioneers have been involved in clinical trials of gene therapy.


The human genome is basically the set of instructions used to create a human being. Scientists are now able to compare the genome of a healthy individual to that of a person with an inborn disease. It is now possible to locate an inborn error on the human genome. The possibility, and future probability, of gene therapy is based on this new information. Diseased cells may one day be replaced with cells that contain the correct version of genetic instructions. This may allow healthy cells to grow in the place of diseased ones.


Researchers have seen some efficacy in treating mice affected with PKU using gene therapy. In addition, embryonic or genetically modified cells are being studied for the treatment of Huntington’s disease. Gene therapy is expected to one day prolong the lives of those suffering from cystic fibrosis, who are currently expected to live only forty years. In general, gene therapies for inborn errors of metabolism are expected, but not yet in practice. Many ethical issues are raised when gene therapy trials are proposed. Nevertheless, scientists are looking more and more toward genetic cures to genetic problems such as those manifested as inborn errors of metabolism.




Key terms



metabolic pathway

:

enzyme-mediated reactions that are connected in a series




metabolism

:

the collection of biochemical reactions occurring in an organism





Bibliography


Econs, Michael J., ed. The Genetics of Osteoporosis and Metabolic Bone Disease. Totowa, N.J.: Humana Press, 2000. International experts discuss the genetic and molecular dimensions of their own research into various aspects of the clinical features and pathophysiology of metabolic bone disease.



Fernandes, John, et al., eds. Inborn Metabolic Diseases: Diagnosis and Treatment. 4th rev. ed. Heidelberg, Germany: Springer Medizin Verlag, 2006. Inborn errors of metabolism are discussed thoroughly along with their diagnoses and their treatments in a manner that is aimed at informing the medical community.



Lee, Thomas F. The Human Genome Project: Cracking the Genetic Code of Life. New York: Plenum Press, 1991. The diagnosis of inborn errors of metabolism, development of molecular methods for diagnosis of these genetic defects, and prospects for treatment of these conditions by gene therapy are highlighted within the context of the Human Genome Project.



O’Rahilly, S., and D. B. Dunger, eds. Genetic Insights in Pediatric Endocrinology and Metabolism. Bristol, England: BioScientifica, 1999. Examines endocrine and metabolic diseases among infants, children, and adolescents. Illustrated.



Pacifici, O. G. M., Julio Collado-Vides, and Ralf Hofestadt, eds. Gene Regulation and Metabolism: Postgenomic Computational Approaches. Cambridge, Mass.: MIT Press, 2002. Explores current computational approaches to understanding the complex networks of metabolic and gene regulatory capabilities of the cell.



Sarafoglou, Kyriakie, ed. Pediatric Endocrinology and Inborn Errors of Metabolism. New York: McGraw-Hill, 2009. An international project aimed at helping physicians to diagnose inborn errors of metabolism in children. Well illustrated and easy to navigate.



Scriver, Charles, et al., eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. 4 vols. New York: McGraw-Hill, 2001. These authoritative volumes on genetic inheritance, by some of the biggest names in the field, survey all aspects of genetic disease, including metabolic disorders. The eighth edition has been thoroughly updated; more than half of the content is new.

How does Portia in The Merchant of Venice display mercy in three different ways (with examples)?

Wednesday, January 20, 2010

How could a student write a monologue about Okonkwo's exile in Things Fall Apart?

To write a monologue about Chinua Achebe's protagonist Okonkwo from the novel Things Fall Apart, one would have to consider not only the events surrounding the exile but Okonkwo himself and the major themes and conflicts that affect his characterization. 


Okonkwo is exiled following the accidental death of a clansman. According to tribal tradition, this is a crime against the earth goddess. As such, Okonkwo and his family must leave the village for seven years to atone for his sins. In such a monologue, it would be vital to determine when in the process of this exile the monologue appeared. Does it take place immediately after the crime? During the deliberation of the elders? After the banishment? Such questions will determine much of the content of the monologue. 


Likewise, one must write in Okonkwo's voice -- a man who considers himself the paradigm of Igbo masculinity, but who chafes against this traditional Igbo ruling of justice. It would be important to emphasize the paradox in this situation and how conflicted Okonkwo must feel in this moment. 

What are hearing tests?

Indications and Procedures Hearing tests are done to establish the presence, type, and sever...