18th Edition HARRISON'S ® Principles of INTERNAL MEDICINE SELF- ASSESSMENT AND BOARD REVIEW Editorial Board DAN L. LONGO, md Professor of. Request PDF on ResearchGate | Harrison's Principles of Internal Medicine, 18th Edition | The most widely read textbook in the history of medicine -- made even. Director, Channing Laboratory, Department of Medicine, Brigham and Women's Harrison's Principles of Internal Medicine (HPIM) provides a comprehensive.
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Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events , most commonly protein phosphorylation catalyzed by protein kinases , which ultimately results in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors , although in some cases the term sensor is used. When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated, often by combinatorial signaling events. These molecular events are the basic mechanisms controlling cell growth , proliferation, metabolism and many other processes. Each component or node of a signaling pathway is classified according to the role it plays with respect to the initial stimulus. Ligands are termed first messengers , while receptors are the signal transducers , which then activate primary effectors. Such effectors are often linked to second messengers , which can activate secondary effectors , and so on.
Francis Sellers Collins born April 14, is an American physician - geneticist who discovered the genes associated with a number of diseases and led the Human Genome Project. Collins also has written a number of books on science, medicine, and religion, including the New York Times bestseller, The Language of God: A Scientist Presents Evidence for Belief. After leaving the directorship of NHGRI and before becoming director of the NIH, he founded and served as president of The BioLogos Foundation , which promotes discourse on the relationship between science and religion and advocates the perspective that belief in Christianity can be reconciled with acceptance of evolution and science, especially through the advancement of evolutionary creation.
Raised on a small farm in Virginia's Shenandoah Valley , Collins was home schooled until the sixth grade. Lee High School in Staunton, Virginia. Through most of his high school and college years he aspired to be a chemist, and he had little interest in what he then considered the "messy" field of biology. What he referred to as his "formative education" was received at the University of Virginia , where he earned a Bachelor of Science degree in Chemistry in He went on to graduate as a Doctor of Philosophy in physical chemistry at Yale University in After consulting with his mentor from the University of Virginia, Carl Trindle , he changed fields and enrolled in medical school at the University of North Carolina at Chapel Hill , earning a Doctor of Medicine degree there in From to , Collins served a residency and chief residency in internal medicine at North Carolina Memorial Hospital in Chapel Hill.
He then returned to Yale, where he was a Fellow in Human Genetics at the medical school from to Collins joined the University of Michigan faculty in , rising to the rank of professor in internal medicine and human genetics. His gene-hunting approach, which he named " positional cloning ",   developed into a powerful  component of modern molecular genetics. Several scientific teams worked in the s and s to identify genes and their loci as a cause of cystic fibrosis.
Progress was modest until , when Lap-Chee Tsui and colleagues at Toronto's Hospital for Sick Children identified the locus for the gene. The gene was identified in June ,   and the results were published in the journal Science on September 8, They included isolation of the genes for Huntington's disease ,  neurofibromatosis ,   multiple endocrine neoplasia type 1 ,  inv 16 AML  and Hutchinson—Gilford progeria syndrome.
As director, he oversaw the International Human Genome Sequencing Consortium,  which was the group that successfully carried out the Human Genome Project. In June Collins was joined by President Bill Clinton and biologist Craig Venter in making the announcement of a working draft of the human genome. Another major activity at NHGRI during his tenure as director was the creation of the haplotype map of the human genome.
This International HapMap Project produced a catalog of human genetic variations—called single-nucleotide polymorphisms —which is now being used to discover variants correlated with disease risk. Among the labs engaged in that effort is Collins' own lab at NHGRI, which has sought to identify and understand the genetic variations that influence the risk of developing type 2 diabetes. In addition to his basic genetic research and scientific leadership, Collins is known for his close attention to ethical and legal issues in genetics.
He has been a strong advocate for protecting the privacy of genetic information and has served as a national leader in securing the passage of the federal Genetic Information and Nondiscrimination Act, which prohibits gene-based discrimination in employment and health insurance. Building on his own experiences as a physician volunteer in a rural missionary hospital in Nigeria ,  Collins is also very interested in opening avenues for genome research to benefit the health of people living in developing nations.
For example, in , he helped establish an initiative called Human Heredity and Health in Africa H3Africa  to advance African capacity and expertise in genomic science. Science writer Jocelyn Kaiser opined that Collins was "known as a skilled administrator and excellent communicator," that Obama's nomination "did not come as a big surprise" and that the appointment "ignited a volley of flattering remarks from researchers and biomedical groups. Washington Post staffer David Brown wrote, however, that Collins' status as a " born-again Christian.
On October 1, , in the second of his four appearances on The Colbert Report , Collins discussed his leadership at the NIH and other topics such as personalized medicine and stem cell research. And, in November , Collins was included on The New Republic's list of Washington's most powerful, least famous people.
Collins appeared on the series finale of The Colbert Report , participating in a chorus with several other famous people singing " We'll Meet Again ".
Food and Drug Administration , 10 biopharmaceutical firms, and multiple non-profit organizations. The PMI Cohort Program will seek to extend precision medicine to all diseases by building a national research cohort of 1 million or more U.
In other precedent-setting actions during his time as NIH Director, Collins in June outlined plans to substantially reduce the use of chimpanzees in NIH-funded biomedical research.
Turning Discovery Into Health  was aimed at ensuring the agency remains well positioned to capitalize on new opportunities for scientific exploration and to address new challenges for human health.
Mention of Collins' love of guitar playing and motorcycle riding can often be found in articles about him. Sometimes the band, called "The Directors," dueled with a rock band from Johns Hopkins University , led by cancer researcher Bert Vogelstein. Lyrics of The Directors' songs included spoofs of rock and gospel classics re-written to address the challenges of contemporary biomedical research. He was a Kilby International Awards recipient in In he was presented with the Presidential Medal of Freedom.
By graduate school Collins considered himself an atheist. However, a conversation with a hospital patient led him to question his lack of religious views, and he investigated various faiths. He familiarized himself with the evidence for and against God in cosmology, and on the recommendation of a Methodist minister used Mere Christianity by C. Lewis as a foundation to develop his religious views.
He eventually came to a conclusion and became a Christian after a "leap of faith" when he saw a frozen waterfall during a hike on a fall afternoon. In his book The Language of God: A Scientist Presents Evidence for Belief , Collins wrote that scientific discoveries were an "opportunity to worship" and that he rejected both Young Earth creationism and intelligent design. His own belief, he wrote, was theistic evolution or evolutionary creation , which he preferred to call BioLogos.
He wrote that one can "think of DNA as an instructional script, a software program, sitting in the nucleus of the cell". Grothe on the Point of Inquiry podcast he said that the overall aim of the book was to show that "one can be intellectually in a rigorous position and argue that science and faith can be compatible", and that he was prompted to write the book because "most people are seeking a possible harmony between these worldviews [science and faith], and it seems rather sad that we hear so little about this possibility.
Collins is a critic of intelligent design , and for this reason he was not asked to participate in the documentary Expelled: No Intelligence Allowed. Walt Ruloff, a producer for the film, claimed that by rejecting intelligent design, Collins was "toeing the party line", a claim which Collins called "just ludicrous".
He served as the foundation's president until he was confirmed as director of the NIH.
Christopher Hitchens referred to Francis Collins as a 'Great American' and stated that Collins was one of the most devout believers he had ever met. In an interview with National Geographic in February , writer John Horgan criticized Collins' description of agnosticism as "a cop-out".
In response, Collins clarified his position on agnosticism so as to exclude. I was reacting to the agnosticism I see in the scientific community, which has not been arrived at by a careful examination of the evidence.
I went through a phase when I was a casual agnostic, and I am perhaps too quick to assume that others have no more depth than I did. In a interview with Scientific American , Collins stated that he is "intensely uncomfortable with abortion as a solution to anything" and does not "perceive a precise moment at which life begins other than the moment of conception".
However, in the same interview it was said that Collins also "does not advocate changing the law". From Wikipedia, the free encyclopedia. For other people named Francis Collins, see Francis Collins disambiguation. Retrieved The Biologos Foundation. Retrieved May 3, We embrace the historical Christian faith, upholding the authority and inspiration of the Bible.
We affirm evolutionary creation, recognizing God as Creator of all life over billions of years. We seek truth, ever learning as we study the natural world and the Bible.
Catholic News Agency. Yale University. Subscription required help. Collins; Sherman M. Weissman Nov Retrieved September 29, Rosenberg Collins ". Am J Hum Genet. University of Alberta, Department of Biological Science. Archived from the original PDF on April 25, Retrieved October 16, Let's not call it reverse anymore". Nature Genetics. Jun Curr Opin Genet Dev. Retrieved August 25, Howard Hughes Medical Institute.
Discovering the Gene for Cystic Fibrosis ". Rubin's Pathology: Clinicopathologic Foundation of Medicine 5th ed. Wolters Kluwer Health: Harrison's Principles of Internal Medicine Small textbook 16th ed.
Ted; Gordon, Leslie B. Retrieved March 29, Collins, M. Biography and Interview". American Academy of Achievement. Los Angeles Times. God's Undertaker: Has Science Buried God? Lion Books.
At the public announcement of the completion of the Human Genome Project, its director, Francis Collins, said: June 26, An Agreement on Privacy and Access". June 13, Francis S. Collins; unlocking the secrets of the Genome". The New York Times. Nov Archived from the original on September 21, Washington Post.
July 8, Chief, Issues of Identity and Culture". Retrieved May 2, The New Republic.
Retrieved October 25, CS1 maint: Extra text: The Colbert Report. October 1, Retrieved October 18, September 18, Archived from the original on March 26, Retrieved August 30, Rare blood types can cause supply problems for blood banks and hospitals. For example, Duffy -negative blood occurs much more frequently in people of African origin,  and the rarity of this blood type in the rest of the population can result in a shortage of Duffy-negative blood for these patients.
Similarly for RhD negative people, there is a risk associated with travelling to parts of the world where supplies of RhD negative blood are rare, particularly East Asia , where blood services may endeavor to encourage Westerners to donate blood.
Pregnant women may carry a fetus with a blood type which is different from their own. In those cases, the mother can make IgG blood group antibodies. This can happen if some of the fetus' blood cells pass into the mother's blood circulation e. Sometimes this is lethal for the fetus; in these cases it is called hydrops fetalis. To provide maximum benefit from each blood donation and to extend shelf-life, blood banks fractionate some whole blood into several products.
The most common of these products are packed RBCs, plasma , platelets , cryoprecipitate , and fresh frozen plasma FFP. FFP is quick-frozen to retain the labile clotting factors V and VIII , which are usually administered to patients who have a potentially fatal clotting problem caused by a condition such as advanced liver disease, overdose of anticoagulant , or disseminated intravascular coagulation DIC.
Units of packed red cells are made by removing as much of the plasma as possible from whole blood units. Clotting factors synthesized by modern recombinant methods are now in routine clinical use for hemophilia , as the risks of infection transmission that occur with pooled blood products are avoided. Table note 1. Assumes absence of atypical antibodies that would cause an incompatibility between donor and recipient blood, as is usual for blood selected by cross matching.
An Rh D-negative patient who does not have any anti-D antibodies never being previously sensitized to D-positive RBCs can receive a transfusion of D-positive blood once, but this would cause sensitization to the D antigen, and a female patient would become at risk for hemolytic disease of the newborn.
If a D-negative patient has developed anti-D antibodies, a subsequent exposure to D-positive blood would lead to a potentially dangerous transfusion reaction. Rh D-positive blood should never be given to D-negative women of child-bearing age or to patients with D antibodies, so blood banks must conserve Rh-negative blood for these patients. In extreme circumstances, such as for a major bleed when stocks of D-negative blood units are very low at the blood bank, D-positive blood might be given to D-negative females above child-bearing age or to Rh-negative males, providing that they did not have anti-D antibodies, to conserve D-negative blood stock in the blood bank.
The converse is not true; Rh D-positive patients do not react to D negative blood. This same matching is done for other antigens of the Rh system as C, c, E and e and for other blood group systems with a known risk for immunization such as the Kell system in particular for females of child-bearing age or patients with known need for many transfusions.
Blood plasma compatibility is the inverse of red blood cell compatibility. Type O carries both antibodies, so individuals of blood group O can receive plasma from any blood group, but type O plasma can be used only by type O recipients.
Assumes absence of strong atypical antibodies in donor plasma. Rh D antibodies are uncommon, so generally neither D negative nor D positive blood contain anti-D antibodies. If a potential donor is found to have anti-D antibodies or any strong atypical blood group antibody by antibody screening in the blood bank, they would not be accepted as a donor or in some blood banks the blood would be drawn but the product would need to be appropriately labeled ; therefore, donor blood plasma issued by a blood bank can be selected to be free of D antibodies and free of other atypical antibodies, and such donor plasma issued from a blood bank would be suitable for a recipient who may be D positive or D negative, as long as blood plasma and the recipient are ABO compatible.
In transfusions of packed red blood cells, individuals with type O Rh D negative blood are often called universal donors. Those with type AB Rh D positive blood are called universal recipients.
However, these terms are only generally true with respect to possible reactions of the recipient's anti-A and anti-B antibodies to transfused red blood cells, and also possible sensitization to Rh D antigens. One exception is individuals with hh antigen system also known as the Bombay phenotype who can only receive blood safely from other hh donors, because they form antibodies against the H antigen present on all red blood cells.
Blood donors with exceptionally strong anti-A, anti-B or any atypical blood group antibody may be excluded from blood donation. In general, while the plasma fraction of a blood transfusion may carry donor antibodies not found in the recipient, a significant reaction is unlikely because of dilution. Additionally, red blood cell surface antigens other than A, B and Rh D, might cause adverse reactions and sensitization, if they can bind to the corresponding antibodies to generate an immune response.
Transfusions are further complicated because platelets and white blood cells WBCs have their own systems of surface antigens, and sensitization to platelet or WBC antigens can occur as a result of transfusion.
For transfusions of plasma , this situation is reversed. Type O plasma, containing both anti-A and anti-B antibodies, can only be given to O recipients. The antibodies will attack the antigens on any other blood type. Typically, blood type tests are performed through addition of a blood sample to a solution containing antibodies corresponding to each antigen.
The presence of an antigen on the surface of the blood cells is indicated by agglutination. An alternative system for blood type determination involving no antibodies was developed in at Imperial College London which makes use of paramagnetic molecularly imprinted polymer nanoparticles with affinity for specific blood antigens.
In addition to the current practice of serologic testing of blood types, the progress in molecular diagnostics allows the increasing use of blood group genotyping. In contrast to serologic tests reporting a direct blood type phenotype, genotyping allows the prediction of a phenotype based on the knowledge of the molecular basis of the currently known antigens. This allows a more detailed determination of the blood type and therefore a better match for transfusion, which can be crucial in particular for patients with needs for many transfusions to prevent allo-immunization.
In , he found that blood sera from different persons would clump together agglutinate when mixed in test tubes, and not only that some human blood also agglutinated with animal blood. The serum of healthy human beings not only agglutinates animal red cells, but also often those of human origin, from other individuals. It remains to be seen whether this appearance is related to inborn differences between individuals or it is the result of some damage of bacterial kind.
This was the first evidence that blood variation exists in humans. The next year, in , he made a definitive observation that blood serum of an individual would agglutinate with only those of certain individuals. Based on this he classified human bloods into three groups, namely group A, group B, and group C. He defined that group A blood agglutinates with group B, but never with its own type. Similarly, group B blood agglutinates with group A. Group C blood is different in that it agglutinates with both A and B.
C was later renamed to O after the German Ohne , meaning without, or zero, or null. A popular pseudoscientific belief in Japan known as "ketsueki-gata" and South Korea  is that a person's ABO blood type is predictive of their personality , character , and compatibility with others.
From Wikipedia, the free encyclopedia. For other uses, see Blood type disambiguation. It is not to be confused with type 0. Main article: ABO blood group system. In , Lerner and his colleagues began a series of experiments that used shock paradigms to investigate observer responses to victimization. In the first of these experiments conducted at the University of Kansas , 72 female subjects were made to watch a confederate receiving electrical shocks under a variety of conditions.
Initially, subjects were upset by observing the apparent suffering. But as the suffering continued and observers remained unable to intervene, the observers began to derogate the victim. Derogation was greater when the observed suffering was greater. But when subjects were told the victim would receive compensation for her suffering, subjects did not derogate the victim. To explain these studies' findings, Lerner theorized that there was a prevalent belief in a just world. A just world is one in which actions and conditions have predictable, appropriate consequences.
These actions and conditions are typically individuals' behaviors or attributes. The specific conditions that correspond to certain consequences are socially determined by a society's norms and ideologies.
Lerner presents the belief in a just world as functional: Belief in a just world functions as a sort of "contract" with the world regarding the consequences of behavior.
This allows people to plan for the future and engage in effective, goal-driven behavior. Lerner summarized his findings and his theoretical work in his monograph The Belief in a Just World: A Fundamental Delusion. Lerner hypothesized that the belief in a just world is crucially important for people to maintain for their own well-being. But people are confronted daily with evidence that the world is not just: Lerner explained that people use strategies to eliminate threats to their belief in a just world.
These strategies can be rational or irrational. Rational strategies include accepting the reality of injustice, trying to prevent injustice or provide restitution, and accepting one's own limitations. Non-rational strategies include denial , withdrawal , and reinterpretation of the event. There are a few modes of reinterpretation that could make an event fit the belief in a just world. In the case of observing the injustice of the suffering of innocent people, one major way to rearrange the cognition of an event is to interpret the victim of suffering as deserving.
An additional effect of this thinking is that individuals experience less personal vulnerability because they do not believe they have done anything to deserve or cause negative outcomes. Many researchers have interpreted just-world beliefs as an example of causal attribution.
In victim blaming, the causes of victimization are attributed to an individual rather than to a situation. Thus, the consequences of belief in a just world may be related to or explained in terms of particular patterns of causal attribution.
Others have suggested alternative explanations for the derogation of victims. One suggestion is that derogation effects are based on accurate judgments of a victim's character. In particular, in relation to Lerner's first studies, some have hypothesized that it would be logical for observers to derogate an individual who would allow himself to be shocked without reason. Another alternative explanation offered for the derogation of victims early in the development of the just-world hypothesis was that observers derogate victims to reduce their own feelings of guilt.
Observers may feel responsible , or guilty, for a victim's suffering if they themselves are involved in the situation or experiment. In order to reduce the guilt, they may devalue the victim. They conducted one study that found derogation of victims occurred even by observers who were not implicated in the process of the experiment and thus had no reason to feel guilty.
Alternatively, victim derogation and other strategies may only be ways to alleviate discomfort after viewing suffering. This would mean that the primary motivation is not to restore a belief in a just world, but to reduce discomfort caused by empathizing.
Studies have shown that victim derogation does not suppress subsequent helping activity and that empathizing with the victim plays a large role when assigning blame. According to Ervin Staub ,  devaluing the victim should lead to lesser compensation if restoring belief in a just world was the primary motive; instead, there is virtually no difference in compensation amounts whether the compensation precedes or follows devaluation.
Psychopathy has been linked to the lack of just-world maintaining strategies, possibly due to dampened emotional reactions and lack of empathy. After Lerner's first studies, other researchers replicated these findings in other settings in which individuals are victimized.
This work, which began in the s and continues today, has investigated how observers react to victims of random calamities like traffic accidents, as well as rape and domestic violence , illnesses, and poverty. Observers thus maintain their belief in a just world by changing their cognitions about the victims' character. In the early s, social psychologists Zick Rubin and Letitia Anne Peplau developed a measure of belief in a just world. These studies on victims of violence , illness , and poverty and others like them have provided consistent support for the link between observers' just-world beliefs and their tendency to blame victims for their suffering.
Researchers have looked at how observers react to victims of rape and other violence. In a formative experiment on rape and belief in a just world by Linda Carli and colleagues, researchers gave two groups of subjects a narrative about interactions between a man and a woman. The description of the interaction was the same until the end; one group received a narrative that had a neutral ending and the other group received a narrative that ended with the man raping the woman.
Subjects judged the rape ending as inevitable and blamed the woman in the narrative for the rape on the basis of her behavior, but not her characteristics. Other researchers have found a similar phenomenon for judgments of battered partners. One study found that observers' labels of blame of female victims of relationship violence increase with the intimacy of the relationship. Observers blamed the perpetrator only in the most significant [ clarification needed ] case of violence, in which a male struck an acquaintance.
Researchers have employed the just-world hypothesis to understand bullying. Given other research on beliefs in a just world, it would be expected that observers would derogate and blame bullying victims, but the opposite has been found: Other researchers have found that observers judge sick people as responsible for their illnesses.
One experiment showed that persons suffering from a variety of illnesses were derogated on a measure of attractiveness more than healthy individuals were. In comparison to healthy people, victim derogation was found for persons presenting with indigestion, pneumonia, and stomach cancer.
Moreover, derogation was found to be higher for those suffering from more severe illnesses, except for those presenting with cancer.
More recently, researchers have explored how people react to poverty through the lens of the just-world hypothesis. Strong belief in a just world is associated with blaming the poor, with weak belief in a just world associated with identifying external causes of poverty including world economic systems, war , and exploitation.
Some research on belief in a just world has examined how people react when they themselves are victimized. An early paper by Dr. Ronnie Janoff-Bulman found that rape victims often blame their own behavior, but not their own characteristics, for their victimization. Subsequent work on measuring belief in a just world has focused on identifying multiple dimensions of the belief. This work has resulted in the development of new measures of just-world belief and additional research.
These distinct beliefs are differentially associated with positive mental health. Researchers have used measures of belief in a just world to look at correlates of high and low levels of belief in a just world.
Limited studies have examined ideological correlates of the belief in a just world. These studies have found sociopolitical correlates of just-world beliefs, including right-wing authoritarianism and the protestant work ethic. Studies of demographic differences, including gender and racial differences, have not shown systematic differences, but do suggest racial differences, with blacks and African Americans having the lowest levels of belief in a just world.
The development of measures of just-world beliefs has also allowed researchers to assess cross-cultural differences in just-world beliefs. Much research conducted shows that beliefs in a just world are evident cross-culturally.