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CLL evolution under the microscope – Medical Xpress

How do initially benign forms of cancer evolve to become aggressive? In a quest to answer this long-standing question, an EU project has studied the growth and clonal evolution of chronic lymphocytic leukaemia (CLL)a blood and bone marrow cancer that mostly starts asymptomatic but can become very aggressive over time.

Cancer evolution is a complex process. Whilst we know that tumour growth is enabled by a continuous process of clonal expansion, genetic diversification and clonal selection, there are still many open questions related to this process. Answering them could be the key to preventing tumour progression and relapses.

According to Dr Michaela Gruber, whose research was funded under the CLL_INCLONEL (Identification and functional dissection of key genetic events in early chronic lymphocytic leukaemia) project, CLL is a valuable model for studying this process due to its high prevalence, initially slow progression and easy access to samples.

Dr Gruber studied the clonal dynamics of a cohort of 21 CLL patients, who were recurrently sampled from diagnosis until the time of first treatment. Her objectives were to identify events leading to disease progression using next-generation sequencing of patient samples. She also developed in vitro models to assess the functional impact of these genetic events on B cell biology, studied their impact on CLL and gathered valuable information on the effects of drugs on potential CLL sub-populations.

Dr Gruber agreed to discuss the project's outcomes and how they could one day lead to individualised diagnostic and therapeutic management of CLL.

What kind of knowledge did you aim to gather from this project?

The key aim of this project was to gain a better understanding of the early dynamics of growth and clonal evolution, as cancer progresses from diagnosis to the need for treatment. CLL is a highly informative model system for studying such natural cancer growth patterns: It typically has a relatively indolent beginning, with potentially long timeframes (in the order of years) before treatment becomes necessary.

Why is it so important to better understand clonal evolution? How can it help prevent tumour progression and relapse?

Insights from recent cancer sequencing studies indicate that the occurrence and expansion of cancer-driving mutations follows a specific sequence. Certain mutations generally appear to occur early in the disease and could be cancer-initiating. Other mutations tend to occur late and appear to have variable impact on tumour expansion. Moreover, different cancer sub-types show different patterns of mutations.

Together, these findings indicate that it could be possible to anticipate the specific evolutionary potential (i.e. plasticity) of a patient's cancer, which actually fuels progression, treatment resistance and relapse. Based on such understanding, therapeutic strategies could be shaped directly against this plasticity of cancer. This would be a major milestone towards overcoming current obstacles to cancer cure.

What would you say were the most important findings from the project?

Our data show that key mutations driving the progression of CLL are established very early in the course of the disease, years before symptoms warrant treatment initiation. For the first time, we were also able to quantify the impact of individual sub-clonal driver mutations on in vivo tumour expansion.

Another important discovery is that of clearly distinguishable growth patterns among patients, both globally as well as on a sub-clonal level. Finally, our data indicate that different patients have different potentials for clonal evolution and growth, and that these patterns remain throughout the entire course of the disease up to the event of relapse.

Can you tell us more about the genome editing technologies you employed?

Suitable experimental models are much needed in order to test the functional impact of observations made in CLL sequencing studies. Thus, we employed novel genome editing strategies, initially using TALENs and then switching to the recently emerged and more easily programmable CRISPR/Cas9 technology. Thanks to the latter, we established an array of isogenic B cell lines, which are used to test the molecular impact of mutations on cellular biology andmost importanttreatment response.

What are your plans now that the project is completed?

We have initiated several follow-up projects in Vienna, which aim to integrate an understanding of epigenetic modifications and tumour microenvironments, as well as their role and dynamics in CLL evolution.

What do you hope will be the impact of the project on future diagnostics and treatments?

Our hope is to establish cancer evolution as a predictable process. With sufficient understanding of the forces that drive evolution and selective advantages of sub-clonal mutations, we hope to develop prognostic schemes that anticipate individuals' evolutionary trajectories.

Treatments based on these schemes would directly aim to target the cancer plasticity that underlies progression, treatment resistance or relapse. CLL provides us with a unique opportunity to better understand cancer evolution. The conceptual insights about cancer that can thus be gained from CLL would have a high potential for being translated across other haematologic and solid malignancies.

Explore further: Follicular lymphoma: A tale of two cancers

More information: Project page: cordis.europa.eu/project/rcn/186119

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CLL evolution under the microscope - Medical Xpress

New Microscope Technique Reveals Internal Structure of Live Embryos – Futurism

Advancing Science

University of Illinois researchers have developed a way to produce 3-D images of live embryos in cattle that could help determine embryo viability before in vitro fertilization in humans.

Infertility can be devastating for those who want children. Many seek treatment, and the cost of a single IVF cycle can be $20,000, making it desirable to succeed in as few attempts as possible. Advanced knowledge regarding the health ofembryoscould help physicians select those that are most likely to lead to successful pregnancies.

The newmethod, published in the journalNature Communications, brought together electrical and computer engineering professor Gabriel Popescu and animal sciences professor Matthew Wheeler in a collaborative project through the Beckman Institute for Advanced Science and Technology at the U. of I.

Called gradient light interference microscopy, the method solves a challenge that other methods have struggled withimaging thick, multicellular samples.

In many forms of traditional biomedical microscopy, light is shined through very thin slices of tissue to produce an image. Other methods use chemical or physical markers that allow the operator to find the specific object they are looking for within a thicksample, but those markers can be toxic to living tissue, Popescu said.

When looking at thick samples with other methods, your image becomes washed out due to the light bouncing off of all surfaces in the sample, said graduate student Mikhail Kandel, the co-lead author of the study. It is like looking into a cloud.

GLIM can probe deep into thick samples by controlling the path length over which light travels through the specimen. The technique allows the researchers to produce images from multiple depths that are then composited into a single 3-D image.

To demonstrate the new method, Popescus group joined forces with Wheeler and his team to examine cow embryos.

One of the holy grails of embryology is finding a way to determine which embryos are most viable, Wheeler said. Having a noninvasive way to correlate to embryo viability is key; before GLIM, we were taking more of an educated guess.

Those educated guesses are made by examining factors like the color of fluids inside the embryonic cells and the timing of development, among others, but there is no universal marker for determining embryo health, Wheeler said.

This method lets us see the whole picture, like a three-dimensional model of the entire embryo at one time, said Tan Nguyen, the other co-lead author of the study.

Choosing the healthiest embryo is not the end of the story, though. The ultimate test will be to prove that we have picked a healthy embryo and that it has gone on to develop a live calf, said Marcello Rubessa, a postdoctoral researcher and co-author of the study.

Illinois has been performing in vitro studies with cows since the 1950s, Wheeler said. Having the resources made available through Gabriels research and the other resources at Beckman Institute have worked out to be a perfect-storm scenario.

The team hopes to apply GLIM technology to human fertility research and treatment, as well as a range of different types of tissue research. Popescu plans to continue collaborating with other biomedical researchers and already has had success looking at thick samples of brain tissue in marine life for neuroscience studies.

This article was provided by University of Illinois of Urbana-Champaign (UIUC). Materials may have been edited for clarity and brevity. And make the name of the source a link back to their website.

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New Microscope Technique Reveals Internal Structure of Live Embryos - Futurism

World Elephant Day 2017: Milwaukee Zoo Steps Up Ivory Ban Drive – Patch.com

MILWAUKEE, WI Just how does an elephant walk? Thats one of the questions the staff at the Milwaukee County Zoo will answer during the Saturday, Aug. 2, observance of World Elephant Day, a day set aside to raise awareness of the soul-crushing plight of elephants in the wild.

The Milwaukee Zoo activities take place from 11 a.m-1 p.m. Besides trying to walk like an elephant and pick up food with their trunks, visitors will also be able to tour the elephants night quarters and learn more about their lives.

Sentient, gentle elephants lead rich emotional lives with values similar to humans, but have been driven to the brink of extinction by habitat destruction for cash crops and, more jarring, hunters who mercilessly rip out their ivory tusks while theyre still alive, then leave them to die excruciating, slow deaths from hemorrhage.

(For more local news, click here to sign up for real-time news alerts and newsletters from Milwaukee Patch, and click here to find your local Wisconsin Patch. If you have an iPhone, click here to get the free Patch iPhone app.)

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Conservationists warn that at the rate elephants are disappearing, their species could be wiped out in Asia and Africa with 12 years. Asian elephants number only about 40,000 and are classified as endangered on the IUCN Red List of Threatened Species. There are about 400,000 remaining in Africa, where they are classified as vulnerable.

A focus of the Milwaukee Zoo event will be to add more signatures to a petition for an ivory ban in Wisconsin. Last year, new rules announced by the Obama administration were a near-complete ban on the multi-billion-dollar ivory trade.

The rules outlawed ivory imports but had some exceptions for example, ivory legally imported before 1990, old ivory that is more than 100 years old, and ivory used in gun handles and musical instruments. Those rules prevent the trade of ivory between states but dont regulate the ivory trade in individual states.

Seven states have now added an extra layer of protection, and elephant advocates in a handful of others, including Wisconsin, are asking for similar legislation.

Ninety-six elephants die every day in Africa because of poaching, Milwaukee Zoo spokeswoman Jennifer Diliberti-Shea told Patch earlier this year, adding that the United States is one of the leading destinations for ivory imports. At that rate, an elephant dies every 15 minutes. Theyre dying at a higher rate than new calves are born the gestation period is 22 months and if the trend continues, African elephants will become extinct within 25 years.

Here are five things you can do right now to affect elephant survival rates:

1. Dont buy ivory, and if you have ivory heirlooms sitting around the house, crush them and have a burial ceremony with your kids in the back yard. Crushing events take place on massive scales just last week, state and federal environmental and conservation officials in Albany, New York, crushed a ton of illegal ivory trinkets worth a staggering $6 million and family-centered ivory disposals can help kids connect with a species that demonstrate what we consider the finest human traits: empathy, self-awareness and social intelligence, Vanity Fair Editor Graydon Carter said, adding: But the way we treat them puts on display the very worst of human behavior.

2. Support one of 10 elephant conservation projects in critical landscapes through The Bodhi Tree Foundations Power of 10 initiative. Each of the projects focuses on countering the forces that threaten elephants poaching, habitat loss, human-elephant conflict, and a lack of vital rehabilitation and veterinary care. Some of the projects are funded, but others are in dire need of support. The Bodhi Tree Foundation says 100 percent of donations go directly to the project of the donors choosing.

3. Be an informed consumer. Dont buy coffee that isnt fair-trade or shade-grown, and avoid products containing palm oil warning, thats going to be tough because its the most widely used vegetable oil in the world, but possible. Coffee and oil palm plantations have decimated elephant habitat. Also, make sure wood products are certified by the Forest Stewardship Council.

4. Adopt an elephant through organizations such as the World Wildlife Foundation, World Animal Foundation, Born Free and Defenders of Wildlife. Youll get pictures of your elephant, as well as the satisfaction that youre helping those organizations stop poaching and other threats to elephant survival.

5. If you want to experience elephants, be aware that many used for entertainment purposes are mistreated, sometime terribly so. Ringling Bros. and Barnum & Bailey Circus decision to retire its last working elephants reflected the publics growing understanding of elephant intelligence and distaste for activities that exploit them, and the travel website Trip Adviser is no longer booking excursions to attractions with captive animals, including elephant rides, but exploitation still happens. If youre planning on experiencing elephants in the wild, make sure you choose eco-friendly tourism options.

If you want to know more about how human behavior is altering elephant behavior, check out the fascinating read published in 2006 by The New York Times titled An Elephant Crackup?

Among the conclusions: Young male elephants are running amuck across Africa, India and Asia, goring children in villages where they once peacefully co-existed with humans, because decades of ivory poaching, habitat loss and other threats have disrupted the fabric of elephant life and the societal and familial structures under which young elephants are raised and, essentially, kept in line.

The slaughter is traumatic for young elephants and profoundly changes them, psychologist Gay Bradshaw told The Times.

The loss of elephant elders and the traumatic experience of witnessing the massacres of their family, impairs normal brain and behavior development in young elephants, said Bradshaw, who at the time was doing research for what became the Pulitzer Prize-nominated Elephants on the Edge: What Animals Teach Us about Humanity.

Photo by Ian Walton/Getty Images News/Getty Images

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Originally published August 11, 2017.

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World Elephant Day 2017: Milwaukee Zoo Steps Up Ivory Ban Drive - Patch.com

Saturday letters: Different beliefs – Houston Chronicle

August 11, 2017

The Texas Legislature's just-ended 85th session included bills that allow religion-based exemptions to certain laws, leading some to wonder how the term "sincerely held religious beliefs" is defined. Ultimately, we rely far more on general cultural norms as to what we wish to tolerate at a given time.

The Texas Legislature's just-ended 85th session included bills that...

Outmoded ideas

Regarding letter to the editor "Christian faith" (Page A13, Tuesday), no one is asking the Rev. F.N. Williams to abandon his apparently fervently-held beliefs; he's just being asked to not use them as a reason to discriminate against people who don't meet his rigid standards for "appropriate" behavior, including transgender folks.

As for showing your birth certificate before being allowed to use the restroom; who's going to enforce that? As far as I know, there is no Department of Potty Police, nor should there be. Rev. Williams, you are not being "classed" as a bigot because, as you state, "I will not allow transgenders....to change my faith and practices." You are being classed as a bigot because you fail to see the difference between belief and behavior. Beliefs are simply that: beliefs. They should not be used as WMDs because you disagree with another person's behavior. The reverend's narrow concept of human behavior is a dangerous precursor to imposing disconnected standards of behavior to outmoded ideas.

Neal Massey, Houston

To read this article in one of Houston's most-spoken languages, click on the button below.

Life choices

Rev. Williams states "The highest law of the land is God's law; not national, not state, not local laws..."

Believers of all faiths will agree that ultimately, God's law is supreme. However, because our varying faiths understand God's laws differently, it is left to our nation of men and women to create laws that recognize that diversity in our faith traditions. It is up to each individual to follow their own religious teachings about God's law in his or her own life choices and actions; however, it is up to our government to protect each individual's rights regarding those choices and actions.

Nancy Pryzant Picus, Houston

Secular laws rule

The highest law of this land is the U.S. Constitution. As the United States is a democratic republic, I do not have to follow any religious laws (Christian, Judaic, Islamic or any other faith) unless I subscribe to that faith and its tenets. On the other hand, I must obey all the secular laws (federal, state or local - whichever jurisdiction applies to me) or I can be sanctioned. No such sanctions can be imposed on me should I not following some specific religious law. This country is not now, nor has ever been, a theocracy.

Len Denney, Houston

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Saturday letters: Different beliefs - Houston Chronicle

Neuroscience majors TURN to research – News from Tulane

Emily Kaminski, right, fields questions from neuroscience PhD students Amy Feehan, left, and Christopher Jones, center, about her summer research project during the annual Tulane Undergraduate Research in Neuroscience (TURN) program poster session at the Lavin-Bernick Center on Friday (August 4). (Photo by Paula Burch-Celentano)

For 10 years, the Tulane Undergraduate Research in Neuroscience (TURN) programhas provided promising students with an in-depth introduction to brain research.

The summer program was founded by professor of psychology Gary Dohanich, professor of cell and molecular biology Jeff Tasker, and Beth Wee, associate dean for undergraduate programs in the School of Science and Engineering. It was created as an opportunity for undergraduates to gain hands-on lab experience with guidance from graduate students and faculty members.

Working side-by-side with neuroscientists, participants developed essential skills, including data analysis and experimental design, while receiving feedback from peers and advisers in weekly group sessions.

They are part of a cohort that shares the frustrations, concerns and joys that come from doing research.

Beth Wee, associate dean for undergraduate programs in the School of Science & Engineering

Our students gain valuable experience conducting empirical research and giving oral and poster presentations, said Wee. They are part of a cohort that shares the frustrations, concerns and joys that come from doing research.

The experience culminated in a poster session modeled after a formal academic conference, where students like Tulane senior Matthew Coleman presented their findings to an audience of peers, faculty, graduate students and program alumni.

Coleman, a neuroscience major, was mentored by assistant professor of psychology Julie Markantwhile developing his project, titled The Interaction of Positive Prediction Error and Active Learning on Memory.

Coleman says that active learning is defined by control over ones learning environment. He is studying how the concept works in tune with prediction error the primary mechanism in which the brain encodes rewards.

His project builds upon a visual memorization test developed years ago by Markants brother, Doug Markant, an assistant professor of psychology at the University of North Carolina at Charlotte.

The experiment requires participants to memorize images in different locations on a computer screen, said Coleman. Participants are divided into two groups to compare different forms of learning.

Coleman is hypothesizing that positive prediction error will facilitate the benefits of active learning on memory.

Like this article? Keep reading: No problem is too big for Tulane students to solve

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Neuroscience majors TURN to research - News from Tulane

Obedience (human behavior) – Wikipedia

Obedience, in human behavior, is a form of "social influence in which a person yields to explicit instructions or orders from an authority figure".[1] Obedience is generally distinguished from compliance, which is behavior influenced by peers, and from conformity, which is behavior intended to match that of the majority. Depending on context, obedience can be seen as immoral, amoral or moral.

Humans have been shown to be obedient in the presence of perceived legitimate authority figures, as shown by the Milgram experiment in the 1960s, which was carried out by Stanley Milgram to find out how the Nazis managed to get ordinary people to take part in the mass murders of the Holocaust. The experiment showed that obedience to authority was the norm, not the exception. Regarding obedience, Milgram said that "Obedience is as basic an element in the structure of social life as one can point to. Some system of authority is a requirement of all communal living, and it is only the man dwelling in isolation who is not forced to respond, through defiance or submission, to the commands of others."[2] A similar conclusion was reached in the Stanford prison experiment.

Although other fields have studied obedience, social psychology has been primarily responsible for the advancement of research on obedience. It has been studied experimentally in several different ways.

In one classical study, Stanley Milgram (as part of the Milgram experiment) created a highly controversial yet often replicated study. Like many other experiments in psychology, Milgram's setup involved deception of the participants. In the experiment, subjects were told they were going to take part in a study of the effects of punishment on learning. In reality, the experiment focuses on people's willingness to obey malevolent authority. Each subject served as a teacher of associations between arbitrary pairs of words. After meeting the "teacher" at the beginning of the experiment, the "learner" (an accomplice of the experimenter) sat in another room and could be heard, but not seen. Teachers were told to give the "learner" electric shocks of increasing severity for each wrong answer. If subjects questioned the procedure, the "researcher" (again, an accomplice of Milgram) would encourage them to continue. Subjects were told to ignore the agonized screams of the learner, his desire to be untied and stop the experiment, and his pleas that his life was at risk and that he suffered from a heart condition. The experiment, the "researcher" insisted, had to go on. The dependent variable in this experiment was the voltage amount of shocks administered.[2]

The other classical study on obedience was conducted at Stanford University during the 1970s. Phillip Zimbardo was the main psychologist responsible for the experiment. In the Stanford Prison Experiment, college age students were put into a pseudo prison environment in order to study the impacts of "social forces" on participants behavior.[3] Unlike the Milgram study in which each participant underwent the same experimental conditions, here using random assignment half the participants were prison guards and the other half were prisoners. The experimental setting was made to physically resemble a prison while simultaneously inducing "a psychological state of imprisonment".[3]

The Milgram study found that most participants would obey orders even when obedience posed severe harm to others. In fact, about 2/3 of the subjects carried the procedure to its bitter end, fully realizing that they were posing a serious threat to the life and well being of the "learner." This result was surprising to Milgram because he thought that "subjects have learned from childhood that it is a fundamental breach of moral conduct to hurt another person against his will".[2]

Zimbardo obtained similar results as the guards in the study obeyed orders and turned aggressive. Prisoners likewise were hostile to and resented their guards. The cruelty of the "guards" and the consequent stress of the "prisoners," forced Zimbardo to terminate the experiment prematurely, after 6 days.[3]

The previous two studies greatly influenced how modern psychologists think about obedience. Milgram's study in particular generated a large response from the psychology community. In a modern study, Jerry Burger replicated Milgram's method with a few alterations. Burger's method was identical to Milgram's except when the shocks reached 150 volts, participants decided whether or not they wanted to continue and then the experiment ended (base condition). To ensure the safety of the participants, Burger added a two-step screening process; this was to rule out any participants that may react negatively to the experiment. In the modeled refusal condition, two confederates were used, where one confederate acted as the learner and the other was the teacher. The teacher stopped after going up to 90 volts, and the participant was asked to continue where the confederate left off. This methodology was considered more ethical because many of the adverse psychological effects seen in previous studies' participants occurred after moving past 150 volts. Additionally, since Milgram's study only used men, Burger tried to determine if there were differences between genders in his study and randomly assigned equal numbers of men and women to the experimental conditions.[4]

Using data from his previous study, Burger probed participant's thoughts about obedience. Participants' comments from the previous study were coded for the number of times they mentioned "personal responsibility and the learner's well being".[5] The number of prods the participants used in the first experiment were also measured.

Another study that used a partial replication of Milgram's work changed the experimental setting. In one of the Utrecht University studies on obedience, participants were instructed to make a confederate who was taking an employment test feel uncomfortable. Participants were told to make all of the instructed stress remarks to the confederate that ultimately made him fail in the experimental condition, but in the control condition they were not told to make stressful remarks. The dependent measurements were whether or not the participant made all of the stress remarks (measuring absolute obedience) and the number of stress remarks (relative obedience).[6]

Following the Utrecht studies, another study used the stress remarks method to see how long participants would obey authority. The dependent measures for this experiment were the number of stress remarks made and a separate measure of personality designed to measure individual differences.[7]

Burger's first study had results similar to the ones found in Milgram's previous study. The rates of obedience were very similar to those found in the Milgram study, showing that participants' tendency to obey has not declined over time. Additionally, Burger found that both genders exhibited similar behavior, suggesting that obedience will occur in participants independent of gender. In Burger's follow-up study, he found that participants that worried about the well being of the learner were more hesitant to continue the study. He also found that the more the experimenter prodded the participant to continue, the more likely they were to stop the experiment. The Utrecht University study also replicated Milgram's results. They found that although participants indicated they did not enjoy the task, over 90% of them completed the experiment.[6] The Bocchiaro and Zimbardo study had similar levels of obedience compared to the Milgram and Utrecht studies. They also found that participants would either stop the experiment at the first sign of the learner's pleas or would continue until the end of the experiment (called "the foot in the door scenario").[7] In addition to the above studies, additional research using participants from different cultures (including Spain,[8] Australia,[9] and Jordan)[10] also found participants to be obedient.

One of the major assumptions of obedience research is that the effect is caused only by the experimental conditions, and Thomas Blass' research contests this point, as in some cases participant factors involving personality could potentially influence the results.[11] In one of Blass' reviews on obedience, he found that participant's personalities can impact how they respond to authority,[11] as people that were high in authoritarian submission were more likely to obey.[12] He replicated this finding in his own research, as in one of his experiments, he found that when watching portions of the original Milgram studies on film, participants placed less responsibility on those punishing the learner when they scored high on measures of authoritarianism.[13]

In addition to personality factors, participants who are resistant to obeying authority had high levels of social intelligence.[14]

Obedience can also be studied outside of the Milgram paradigm in fields such as economics or political science. One economics study that compared obedience to a tax authority in the lab versus at home found that participants were much more likely to pay participation tax when confronted in the lab.[15] This finding implies that even outside of experimental settings, people will forgo potential financial gain to obey authority.

Another study involving political science measured public opinion before and after a Supreme Court case debating whether or not states can legalize physician assisted suicide. They found that participants' tendency to obey authorities was not as important to public opinion polling numbers as religious and moral beliefs.[16] Although prior research has demonstrated that the tendency to obey persists across settings, this finding suggests that at personal factors like religion and morality can limit how much people obey authority.

Both the Milgram and Stanford experiments were conducted in research settings. In 1966, psychiatrist Charles K. Hofling published the results of a field experiment on obedience in the nursephysician relationship in its natural hospital setting. Nurses, unaware they were taking part in an experiment, were ordered by unknown doctors to administer dangerous doses of a (fictional) drug to their patients. Although several hospital rules disallowed administering the drug under the circumstances, 21 out of the 22 nurses would have given the patient an overdose.[17]

Many traditional cultures regard obedience as a virtue; historically, societies have expected children to obey their elders (compare patriarchy, slaves their owners, serfs their lords in feudal society, lords their king, and everyone God. Even long after slavery ended in the United States, the Black codes required black people to obey and submit to whites, on pain of lynching. Compare the religious ideal of surrender and its importance in Islam (the word Islam can literally mean "surrender").[18]

In some Christian weddings, obedience was formally included along with honor and love as part of a conventional bride's (but not the bridegroom's) wedding vow. This came under attack with women's suffrage[citation needed] and the feminist movement. As of 2014[update] the inclusion of a promise to obey in marriage vows has become optional in some denominations.

Some animals can easily be trained to be obedient by employing operant conditioning, for example obedience schools exist to condition dogs to obey the orders of human owners.

Learning to obey adult rules is a major part of the socialization process in childhood, and many techniques are used by adults to modify the behavior of children. Additionally, extensive training is given in armies to make soldiers capable of obeying orders in situations where an untrained person would not be willing to follow orders. Soldiers are initially ordered to do seemingly trivial things, such as picking up the sergeant's hat off the floor, marching in just the right position, or marching and standing in formation. The orders gradually become more demanding, until an order to the soldiers to place themselves into the midst of gunfire gets an instinctively obedient response.

When the Milgram experimenters were interviewing potential volunteers, the participant selection process itself revealed several factors that affected obedience, outside of the actual experiment.

Interviews for eligibility were conducted in an abandoned complex in Bridgeport, Connecticut.[2][19] Despite the dilapidated state of the building, the researchers found that the presence of a Yale professor as stipulated in the advertisement affected the number of people who obeyed. This was not further researched to test obedience without a Yale professor because Milgram had not intentionally staged the interviews to discover factors that affected obedience.[2] A similar conclusion was reached in the Stanford prison experiment.[19]

In the actual experiment, prestige or the appearance of power was a direct factor in obedienceparticularly the presence of men dressed in gray laboratory coats, which gave the impression of scholarship and achievement and was thought to be the main reason why people complied with administering what they thought was a painful or dangerous shock.[2] A similar conclusion was reached in the Stanford prison experiment.

Raj Persaud, in an article in the BMJ,[20] comments on Milgram's attention to detail in his experiment:

The research was also conducted with amazing verve and subtletyfor example, Milgram ensured that the "experimenter" wear a grey lab coat rather than a white one, precisely because he did not want subjects to think that the "experimenter" was a medical doctor and thereby limit the implications of his findings to the power of physician authority.

Despite the fact that prestige is often thought of as a separate factor, it is, in fact, merely a subset of power as a factor. Thus, the prestige conveyed by a Yale professor in a laboratory coat is only a manifestation of the experience and status associated with it and/or the social status afforded by such an image.

According to Milgram, "the essence of obedience consists in the fact that a person comes to view himself as the instrument for carrying out another person's wishes, and he therefore no longer sees himself as responsible for his actions. Once this critical shift of viewpoint has occurred in the person, all of the essential features of obedience follow." Thus, "the major problem for the subject is to recapture control of his own regnant processes once he has committed them to the purposes of the experimenter."[21] Besides this hypothetical agentic state, Milgram proposed the existence of other factors accounting for the subject's obedience: politeness, awkwardness of withdrawal, absorption in the technical aspects of the task, the tendency to attribute impersonal quality to forces that are essentially human, a belief that the experiment served a desirable end, the sequential nature of the action, and anxiety.

Another explanation of Milgram's results invokes belief perseverance as the underlying cause. What "people cannot be counted on is to realize that a seemingly benevolent authority is in fact malevolent, even when they are faced with overwhelming evidence which suggests that this authority is indeed malevolent. Hence, the underlying cause for the subjects' striking conduct could well be conceptual, and not the alleged 'capacity of man to abandon his humanity... as he merges his unique personality into larger institutional structures."'[22]

In humans:

In animals:

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Obedience (human behavior) - Wikipedia

After the dark days of the financial crisis, RBS wants to regain its customers’ trust – CNBC

The Royal Bank of Scotland (RBS) has seen its reputation take a battering over the last ten years or so. Bailed out by the U.K. government during the global financial crisis in 2008, nearly 73 percent is still owned by the taxpayer.

Almost ten years on, the bank is focusing on the future. "RBS is probably the poster child of the financial crisis and we're well aware of the mistakes we made in the past," David Wheldon, chief marketing officer of RBS, told CNBC's Marketing Media Money on Thursday evening. "We're well aware of the legacy issues, but that was the bank that we once were," he added. "We're focussing on the bank we are today and the bank we want to be in the future. And what we want to be is the 'most preferred' bank."

RBS, Wheldon added, was focussed full square on the customer and its customer facing brands.

Wheldon said that RBS wanted to become number one for customer service, trust and advocacy by 2020. Is the ambition of becoming the most trusted bank an achievable one? Wheldon said it was, although challenges clearly remained.

"It's certainly a stretching target becauseif you look at RBS, it is still the least trusted brand in the least trusted sector," he explained. Focusing on customer facing brands such as NatWest and Ulster Bank was an important part of the process.

"By doing this we've really been able to get our staff focussed again on customer facing brands, leaving RBS behind us, because that was the global brand that we were attempting to build before it went wrong."

A recent ad campaign for NatWest, for example, used the slogan "we are what we do." A black and white film showed various types of human behavior, from the caring nature of a parent carrying a sleeping child to hooligans kicking tables and chairs.

The ad was something of a mea culpa for the bank and, according to Wheldon, a way of getting permission to be heard again.

"Inside there as well is the human truth: we're all what we have done, we're all what we will do," he said. "We're no different," he added. "We are what we do, so it was an admission of fault and an invitation to hold us to account, and our customers do exactly that."

Looking to the future, Wheldon said he wanted RBS to be trusted again.

"We've rebuilt pride internally and that's a really important thing for us because at its heart our strategy is... (to) engage our colleagues," he added.

"If we engage our colleagues and motivate them they'll service our customers well. If we do that well enough, our customers will advocate us. And there's a beautiful virtuous circle there that will lead us to number one."

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After the dark days of the financial crisis, RBS wants to regain its customers' trust - CNBC

Study Aims to Develop Hybrid Gross Anatomy Curriculum – UB School of Medicine and Biomedical Sciences News

Stuart D. Inglis, PhD, left, and Scott T. Doyle, PhD, are developing a model for a hybrid gross anatomy curriculum that integrates digital scans with cadaveric dissection.

Published August 10, 2017

Department ofPathology and Anatomical Sciences researchers are studying waysto develop a hybrid gross anatomy curriculum that fuses digitizedCT scans with actual cadaveric dissection.

Hybrid Program Offers Best of Both Worlds

Gross anatomy programs are expensive and extremelyresource-intensive, requiring a lot of infrastructure to set up andoperate.

The Jacobs School of Medicineand Biomedical Sciences is fortunate to have a productive andgenerous AnatomicalGift Program, but many institutions do not have the necessaryresources and are looking at replacing their cadaver programs withan entire digital way of learning using standard CT datasets or downloads from the Internet as a way of learning humangross anatomy.

Students benefit from a tactile and kinesthetic mode oflearning, says ScottT. Doyle, PhD, assistant professor of pathology and anatomicalsciences. Dissection, the process of learning through doing,is really important and we think its critical for studentsto learn that while they are going through theirtraining.

The amount of raw data that digital scans provide can be used tobuild upon the inherent value that exists in cadaveric dissection,he says.

Scans Help Students Learn About Human Variation

Doyle and StuartD. Inglis, PhD, instructor of pathology and anatomicalsciences, are co-principal investigators on a 2017 SeedGrant for Promoting Pedagogical Innovation through the Center for EducationInnovation, that will study the best ways to integrate the datafrom CT scans into a gross anatomy curriculum.

The medical school receives about 600 donations a year throughits anatomical donation gifts program, and initiated a CT scanproject in 2014 in order to create a database.

RaymondP. Dannenhoffer, PhD, director of the anatomical gift program,felt that high-resolution scans of some of the cadavers comingthrough the gross anatomy program would be useful for teachingstudents not only about the human form, but also about humanvariation.

That often doesnt come through if you are using aclassic textbook example because in that instance you get oneexample of what the human form is like and you dont reallyget an appreciation for all the things you might see in clinicalpractice or the real world, Doyle says.

Digital Images Provide Useful Roadmaps

As part of their gross anatomy lab, medical students are givenCT scans on USB drives to refer back to throughout the course.

Inglis notes there are several advantages to using CT scans in agross anatomy setting.

Being able to look at scans prior to dissection, studentscan identify some interesting pathologies, he says.They can see kidney stones, pacemaker units or jointreplacements. When they are about to dissect, it gives them abetter perspective on what they are about to find.

Inglis says it also allows students to start to make directcomparisons between the dissected body and the radiologicalimages.

Its one experience to dissect, but as they move onin their careers they will be looking at digital representations ofproblems they see in MRIs and CT scans, he adds.

Visualizing Data in 3-D Space Extremely Useful

In its gross anatomy labs, the medical school utilizes a devicecalled a visualization table that is manufactured by Sectra, aSwedish company.

It has a giant touchscreen, a computer inside it and USBports on the side. Students can plug in a USB drive and uploadtheir scan, Doyle says. It allows you to visualizethe CT scans in 3-D. It takes a certain range of CT values andmakes them look solid, and then renders them, so you can spin itaround and zoom in and look at the data that way.

Inglis says the best analogy is thinking of the CT scans asslices of bread and the visualization table putting them togetherto present the whole picture.

When you look at the literature on replacing cadavericdissection with digital models, you see the students find thedigital models more convenient because they dont have tocome to a physical lab and deal with all of the technicalities ofperforming a dissection, but they value the education they get fromactual dissection, Doyle says.

There is inherent value in both of these modes ofteaching and that is why we are thinking about this as a hybridprogram that uses traditional cadaveric dissection as well asdigital modeling of the CT scans.

For this project I am interested in looking at thevariation structure from a quantitative standpoint, Doyleadds. From an engineering standpoint, all the data for these3-D models is contained in these grayscale images and the questionis how best to represent them in 3-D space.

User Feedback Key Component of Study

As part of the study, the researchers plan to seek studentfeedback, Doyle says.

We definitely want to know how they are using it.Students are very good at prioritizing what they are going to spendtheir time on, he says. They want to excel in thecourse so they are going to find the most efficient way of usingthe data.

One of the big concerns we have is to make sure we aredoing this in a way that is not going to inconvenience them or notgoing to hamper their ability to learn.

Diverse Data Set Most Desirable

Inglis notes that many institutions that are thinking aboutadopting the digital-only model intend to use a single, unifiedbody for teaching purposes.

In recent years, there have been scans of two bodies thathave been used from school to school, but it has been documented inthe literature that in those cases, there have been a number ofanatomical variations identified in these bodies that are now beingpresented as the norm, which is problematic.

In some cases, there are advantages to all medicalstudents from around the country learning from the same sort ofcontent map, but at the same time there are also some very seriousissues with that, he says.

Whereas, if a more diverse data set were available, studentscould gain a better sense of appreciation for variation, Inglissays.

3-D Models Aid in Finding Anatomical Landmarks

Looking at the human body in 3-D form is extremely helpful forstudents trying to find different anatomical landmarks oranatomical structures they need to know, Doyle says.

A good example that is a problem for students are cranialnerves, which tend to have loops and insert into the skull indifferent ways so they are often difficult to see, both on a flatCT scan and during dissection, he adds.

Having a 3-D model where they can identify those nervesand where they enter the skull and how they move is going to bevery useful.

Potential Applications in Surgical Planning Procedures

While the grant is focused on the educational side of theequation, Doyle notes other researchers working in areas such as3-D printing and surgical planning are interested in the study.

In the course of figuring out how to work with this data,we anticipate there are different directions this could go from aresearch standpoint, he says.

One example is a project they are undertaking with a hepaticsurgeon who is interested in the biliary tree that lies between thegallbladder and the liver.

The way in which the ducts connect the gallbladder to the maintrunk of the biliary tree can have implications for how a surgeongoes in to remove a tumor.

In about two-thirds of individuals, the artery to thegallbladder lies behind the duct that needs to be cut, which meansthat in one-third it lies in front, Inglis says.

If you go in and are not precise as to where it is and ifthe artery is severed first, that becomes a medical emergencybecause that creates a massive internal hemorrhage.

Being able to take a scan of a patient and reconstructing a 3-Dstructure before printing it out to provide to a surgeon is goingto be very useful in terms of planning, Doyle says.

At the end of the day, what we are trying to do isimprove patient care by making better doctors on the education sideor by using the data in a way to help practicing physicians treattheir patients better, he says.

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Study Aims to Develop Hybrid Gross Anatomy Curriculum - UB School of Medicine and Biomedical Sciences News

Anatomy of a suddenly sick Obamacare insurer – CBS News

Headlines have been screaming for months about big insurers such as Aetna (AET), United Healthcare (UNH) and Humana (HUM) pulling out of the Obamacare marketplaces because they couldn't make the exchange business profitable. As a result, dozens of counties throughout the country have been left with only one or no insurance choice on their exchange.

Against that backdrop, two smaller insurers that focus primarily on the Medicaid market -- Molina Healthcare (MOH) and Centene (CNC) -- were frequently noted as companies that can successfully navigate the uncertain and complicated exchange business. Many states looked to them and small regional or local insurers to help fill the increasing gaps the big names were leaving behind.

So it came as a bit of shock when Molina announced on Aug. 2 it would exit the exchanges in Wisconsin and Utah, scale back its exchange business in Washington state and leave the door open to pull out of other exchanges in the near future.

What's more, in marketplaces where it will continue to operate, Molina has submitted an average 55 percent premium increase to state regulators, partly due to the uncertainty over the future of federal cost sharing payments.

The news came amid Molina's report of a steep second-quarter earnings loss of $4.10 a share, compared to a 58 cent per share gain during the same period a year earlier. It also followed the ouster in May of Chief Executive Mario Molina and Chief Financial Officer John Molina, brothers who are sons of company founder David Molina. In the earnings report, Molina also announced a major restructuring, which includes about 1,500 layoffs, approximately 7 percent of its workforce.

Until all this bad news broke, Molina was one of the prime examples of an insurer that could actually make the exchanges work. (Centene still does and is expanding its exchange business.) Major insurers like Aetna and United Health, accustomed to the more stable employer-sponsored health insurance market, racked up losses in the exchange business in part because they were surprised by the large number of high-cost patients who signed up.

Molina's business focuseson administering Medicaid health plans for low-income and disabled patients. As a result, the company has experience with managing narrow networks of lower-cost health care providers. "The idea is to arbitrage low-reimbursement providers into exchanges where the competition is paying a lot more," explained Robert Laszewski, president of consulting firm Health Policy and Strategy Associates. "There's an opportunity for profit there."

Molina found it could compete for the no-frills end of the exchange market and enjoy a robust volumne of patient sign-ups. According to Laszewski's estimates, Molina had a track record of enrolling as much as 70 percent of eligible participants in the various markets it participated in. A pool that big offers enough healthy individuals to help stabilize risk, he added.

What went wrong?

According to Joseph White, interim CEO of Molina, the company became overwhelmed with its ACA business, including unexpected increases in medical costs and claims. "We did not adjust for growth in the ACA marketplace," White told analysts in a conference call last week. He explained that the company focused resources on existing processes and technologies instead of a full redesign that would have helped it better deal with ACA growth.

"That was a mistake," said White. "The marketplace shares fundamentals of the Medicaid market, but it's also very different," he added.

In addition, speculated Laszewski, as Molina expanded into new markets and became a more dominant player in others, it may have strayed from its core base of low-income customers, adding costs and risks it couldn't deal with.

"Every company has to analyze every market to make sure they're making money in every market," said Dan Mendelson, chief executive of Avalere Health. Say a plan with bad risk drops out of the market, he added. "You may get saddled with that risk as you pick up those customers."

Molina's bad news leaves exchange consumers with even less choice and more uncertainty than they were already facing in light of failed GOP efforts to repeal and replace Obamacare and the Trump administration's threats to discontinue support for the system.

As commitment deadlines for insurers approach, state insurance commissioners are working hard to convince them to stay in the exchanges and keep at least a bare minimum of coverage. In addition, small, local, often nonprofit players such as L.A. Care Health Plan are trying to fill gaps where they can, while heeding the lessons from Molina's recent mess.

Will these efforts be enough? Consumers may have to wait until open enrollment begins on Nov. 1 to find out.

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Anatomy of a suddenly sick Obamacare insurer - CBS News

Spoiler Room: Scoop on Blindspot, Brooklyn Nine-Nine, Grey’s Anatomy, and more – EW.com (blog)

Welcome to the Spoiler Room, a safe place for spoiler addicts to come on a weekly basis to learn whats coming next on their favorite shows and, hopefully, get a few of their own questions answered. If you want scoop on a specific show, send your questions to spoilerroom@ew.com.

Anything new to tease for season 3 of Blindspot? TonyIf youre wondering what has happened to the team over the last 18 months thats the exact amount of time that has passed when we pick back up with Jane and Weller answers will come very quickly this season. Youll see flashbacks, EP Martin Gero promises. We hope to fill in a lot of it right away in the first two or three minutes of the show. No fan of the show will want to miss the opening of the season that will endeavor to fill in a lot of what the hell is going on. Why did she run away? Are Jane and Weller married? All those questions will be answered in the first few minutes.

How long will Jake and Rosa be in jail on Brooklyn Nine-Nine? JessicaIf Boyle has his way, not long! Hes determined to make sure that his friends innocence is known to the rest of the world, Joe Lo Truglio tells me. So hes doing everything he can, hes tailing Hawkins and hes trying to take advantage of her making a mistake. But expect to find a very different Boyle in Jakes absence when the show returns. Theyve got a wonderful cold open to show his depression, which rivals and dare I say surpasses him breaking up with Vivian in the Matrix leather coat cold open.

Where is the new season of Greys Anatomy picking up? KarolineRight where we left off, so everyone is still reeling in the wake of the finale explosion. But it wont be long before theres a shakeup at Grey Sloan. Theres obviously some damage to the hospital, Kelly McCreary says. But it is, in true Greys Anatomy style, a completely surmountable obstacle, because we are superhuman doctors. It serves more as a metaphor of the transformation that the show is going to go through tonally. Its lighter this season. The hospital definitely is undergoing some changes in the form of a new crop of students coming in. Itll look a bit different in certain areas, and some relationships have come to an end or are blossoming, so repairing the damage is more of a metaphor.

Any Chicago P.D. news would be great. MarAntonio is back in Intelligence, as a case in the premiere reconnects him with his former family. The suspect that theyre going after, they hit a bump in the road and they need someone to come in that this guy has never seen and can do a great job undercover, and thats where Antonio comes in, Jon Seda tells me, teasing that Antonio will bump heads with Voight over certain new policies within Intelligence this year.

Will Kuasa crossing paths with Ray on Vixen be addressed on Legends of Tomorrow? ColemanYes, and his knowledge of Kuasa just may help the Legends version of Vixen. If you go back and look at Vixen season 2, I wouldnt exactly call her fighting alongside Ray, shes always been morally questionable, EP Marc Guggenheim says. But I think thats what makes it interesting as far as Amaya is concerned is that Ray, at the appropriate moment, will accurately tell her that there were moments where Kuasa was capable of selfless good, so I think that gives Amaya a little bit of hope.

Do you know anything more about Reginas alter-ego on Once Upon a Time? BradenBar owner Roni is very, very different from Regina, so prepare yourselves. Shes given up a little bit on life, Lana Parrilla tells me. She seems a little hopeless when we first meet her, and then Henry comes to town and things start to shift a little bit. But dont expect his arrival to immediately spark Reginas memories. No, theres nothing there, and I like that. Shes just asleep. Shes not quite in touch with all that stuff yet. A few more things need to happen before she starts getting that feeling. Although, she is inspired by a character, and it shifts her a bit, at the end of the first episode.

Anything on the Hawaii Five-0 team in season 8? ElizabethI hear theres going to be another new member of the team but its definitely not who (or what!) youre expecting. There is a story thats coming up, it actually was Alex OLoughlins idea, EP Peter Lenkov says. I wanted to do a story where the victim left in the wake of a tragedy was a dog who lost its owner. Its a very emotional, really great story. Its a dog thats a drug sniffing service dog that McGarrett ends up adopting. Its a really emotional journey, but it was his idea to keep the dog, and I thought that was a great one.

Hand over some Scandal scoop! DangerWaveWith Cyrus sliding into the White House as VP to Mellies POTUS, Jake will somewhat be sidelined but his continued role in the White House will put some pressure on the dynamic between Jake and Olivia. The interesting thing for Jake is that hes still the head of the NSA, but Olivia being Chief of Staff is sort of his boss, which is a position theyve never really find themselves in and a dynamic we have yet to explore, Scott Foley says. Its going to cause some waves in the water of love.

How will Gretchen be handling Jimmys disappearing act on Youre the Worst this season? MalloyNot well. Not well at all. Believe me, Gretchen does something so shocking in the premiere and enlists Lindsay to do it, too that you will have to remind yourself of the title of the show before you fall down a rabbit hole. And it only gets worse from there. Theres some weird sh that goes down, Aya Cash says. There are so many different kinds of bad, let me put it that way. Even so, Cash has hopes that Gretchen and Jimmy will eventually reconcile. I do because this show is about them and theyre going to have to figure it out, she says. I feel like were heading toward something positive. They start to work out how to be around each other and how to engage in a healthier way. But will she get payback on Jimmy for abandoning her? Yes, Cash says with a smirk.

Any scoop on the season finale of Shadowhunters? TaylorA. lot. happens. Youll find out whether weve seen the last of Jonathan within the finales first minute, but regardless of what happens there, theres still the matter of stopping Valentine. And lets just say that battle is filled with big decisions for Clary, none of which shell be able to take back, and the consequences of which will play heavily into next season. That cryptic enough?

This week in TV: TCA is finally over! You can read all the coverage from our incredibly hard-working TV team here.

Thats a wrap on this weeks Spoiler Room. Be sure to email your questions to spoilerroom@ew.com or tweet them to @NatalieAbrams.

Additional reporting by Samantha Highfill.

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Spoiler Room: Scoop on Blindspot, Brooklyn Nine-Nine, Grey's Anatomy, and more - EW.com (blog)