Most donated organs in the United States come from brain dead donors, while a small percentage come from patients who die in “controlled,” or expected, circumstances, typically after the family or surrogate makes a decision to withdraw life support. The number of organs available for transplant could be substantially if donations were permitted in “uncontrolled” circumstances–that is, from people who die unexpectedly, often outside the hospital. According to projections from the Institute of Medicine, establishing programs permitting “uncontrolled donation after (...) circulatory determination of death,” or uDCDD, throughout the United States has the potential to provide 22,000 more donation opportunities annually. In contrast, U.S. controlled donation after circulatory determination of death, or cDCDD, cases have increased progressively over the past decade from 87 to 848 donors, but currently account for only 10.6 percent of all deceased donors. Following the IOM recommendations, several projects exploring the feasibility of uDCDD were funded by the federal government, including a grant from the Health Resources and Services Administration that supported a pilot project in New York City in which the authors of this article participated.A key feature of our protocol, and indeed of many uDCDD protocols, is the initiation of preservation methods such as chest compressions and extracorporeal membrane oxygenation shortly after death in order to perfuse and preserve the donor's organs. Critics of uDCDD argue that the means of determining death deviates from generally ascribed principles. They assert that reinstituting circulation in order to preserve organs has the effect of “undoing” the prior determination of death. The result is that cDCDD is widely accepted and practiced routinely even though it only marginally increases the number of organs available for transplantation, and uDCDD is widely considered unacceptable despite being ethically embraced and proven to significantly increase organ donation opportunities in other countries. This article explores the evolution of this counterintuitive state of affairs and calls for a policy that, in line with the IOM report, allows for both cDCDD and uDCDD protocols. (shrink)

Background: Lay persons’ judgements of the acceptability of the not uncommon practice of ending the life of a damaged neonate have not been studied. Methods: A convenience sample of 1635 lay people in France rated how acceptable it would be for a physician to end a neonate’s life—by withholding care, withdrawing care, or active euthanasia—in 54 scenarios in which the neonate was diagnosed either with perinatal asphyxia or a genetic abnormality. The scenarios were all combinations of four factors: three levels (...) of maturity or immaturity, three levels of severity of the health problem, three levels of parents’ preference concerning prolonging care and two levels of decision-making (with or without consulting the other caregivers). Analyses: Analyses of variance of the participants’ responses were performed to determine the importance of each factor; the interactions among factors, with methods of ending life and with other patient characteristics; and the differences between asphyxia and genetic abnormality. A cluster analysis was performed to look for groups with different patterns of responses. Results: Lay people assigned most importance to the parents’ request and to the severity of the problem. Except for a small group (12%) always opposed to ending life, they used a simple additive-type rule in integrating the information. Implications: Most of this sample of French lay people are not categorically for or against ending the life of a damaged neonate, but judge its degree of acceptability by adding up those factors that seem most salient to them. (shrink)

Background: Discussing treatment risks has become increasingly important in medical communication. Still, despite regulations, physicians must decide how much and what kind of information to present. Objective: To investigate patients’ preference for information about a small risk of a complication of colonoscopy, and whether medical and personal factors contribute to such preference. To propose a disclosure policy related to our results. Design: Vignettes study. Setting: Department of Gastroenterology, Academic Medical Centre, the Netherlands. Patients: 810 consecutive colonoscopy patients. Intervention: A (...) home-sent questionnaire containing three vignettes. Vignettes varied in the indication for colonoscopy, complication severity and level of risk. Patients were invited to indicate their wish to be informed and the importance of such information. In addition, sociodemograhic, illness-related and psychological characteristics were assessed. Main outcome measurements: Wish to be informed and importance of information. Results: Of 810 questionnaires, 68% were returned. Patients generally wished to be informed about low-risk complications, regardless of the indication for colonoscopy or the severity of the complication. The level of risk did matter, though (OR = 2.48, SE = 0.28, p = 0.001). The information was considered less important if done for population screening purposes or diagnosis of colon cancer, if the complication was less severe (bleeding) and if the risk was smaller (0.01% and 0.1%). Patients’ information preference was also related to age, mood and coping style. Limitations: Difficulty of vignettes. Conclusions: Patients generally wish to be informed about all possible risks. However, this might become uninformative. A stepwise approach is suggested. (shrink)

Intent and mitigating circumstances play a central role in moral and legal assessments in large-scale industrialized societies. Al- though these features of moral assessment are widely assumed to be universal, to date, they have only been studied in a narrow range of societies. We show that there is substantial cross-cultural variation among eight traditional small-scale societies (ranging from hunter-gatherer to pastoralist to horticulturalist) and two Western societies (one urban, one rural) in the extent to which intent and mitigating circumstances (...) influence moral judgments. Although participants in all societies took such factors into account to some degree, they did so to very different extents, varying in both the types of considerations taken into account and the types of violations to which such considerations were applied. The particular patterns of assessment characteristic of large-scale industrialized societies may thus reflect relatively recently culturally evolved norms rather than inherent features of human moral judgment. (shrink)

Daw-Nay N. R. Evans - Nietzsche and Rée: A Star Friendship - Journal of the History of Philosophy 44:4 Journal of the History of Philosophy 44.4 672-673 Muse Search Journals This Journal Contents Reviewed by Daw-Nay N. R. Evans, Jr. DePaul University Robin Small. Nietzsche and Rée: A Star Friendship. Oxford: Clarendon Press, 2005. Pp. xxiv + 247. Cloth, $45.00. Nietzsche attracts a wide range of scholarly enthusiasts. There are those who take Nietzsche seriously as a philosopher and study (...) his works for their own sake, while others seek to mine his works for philosophical gold to determine what he might have to offer their particular area of specialization . On the other hand, there are those who seek to sensationalize Nietzsche by making him.. (shrink)

The case study method offers a hands-on inquiry based method for teaching leadership traits. With this in mind, the case study method is used to provide opportunities for middle school students to analyze a situation and the actions of the case study charactcrs and to identify leadership behaviors. The use of the case study method allows instructors to teach character education to this group of middle school students by promoting the use of critical thinking skills through small group discussions (...) and reflections. The staff is confident by using this method that the students are able to analyze, discuss, and draw conclusions for discussions in small groups. (shrink)

In order to prepare bioethics and clinical ethics courses for clinicians in Turkey, we needed to know the attitudes of physicians when placed in ethically difficult care situations. We presented four cases to 207 physicians who are members of the Physicians’ Association in Kocaeli, Turkey. Depending on the decisions they made in each case, we determined whether they were aware of the ethical aspects of the cases and the principles they chose as a basis for their decisions. We aimed to (...) gain information about their ethical tendencies and moral sensitivity. A small number of physicians stated that they would ‘show respect for a patient’s living will’ in the first case, but more stated that they would ‘let the patient refuse the treatment’ in the second. In the third case, where medical confidentiality was the significant ethical issue, most of the physicians said that they would act in order to maintain confidentiality. For the last case, more than half the physicians chose to ‘tell the truth’ to the patient. The paternalism shown in the doctors’ decisions on the first two cases was no longer observed in those made for the last two cases. We concluded that the physicians who participated in our study have low sensitivity to living wills (or advance directives) and patients refusing treatment. However, when issues of medical confidentiality and truth-telling are concerned, they take care to protect the autonomy of the individual and are relatively more aware of the ethical aspects of these cases. (shrink)

Purpose The purpose of this paper is to understand the dark side of blockchain technology (BCT) adoption in small and mid-size enterprises. The focus of the authors is to decode the intricate relationship among the selected variables missing in the existing literature. Design/methodology/approach A focused group approach is initiated by the authors to identify the barriers. Total interpretive structural modeling, Matrice d'impacts croisés multiplication appliquée á un classment, that is, matrix multiplication applied to classification and decision-making trial and evaluation (...) laboratory are used to analyze the complex relationships among identified barriers. Findings This study finds that implementation of BCT reduces maintenance cost by withdrawing manual effort, as BCT has better capability to quantify the internal status of the system (observability characteristic). The observability characteristic of BCT provides high compatibility to the system. This study also finds that the compatibility of BCT with the organization reduces implementation cost and facilitates project management. The findings of this study recommend analyzing maintenance cost and compatibility of BCT before implementing it. Small and mid-size enterprises can select complex BCT depending on the sophistication level of IT usage and IT project management capabilities. Research limitations/implications This study comes with various limitations, where the model developed by the authors may not be conclusive, as it is based exclusively on expert opinion. The samples collected may not help in validating the model statistically. Though the model has its limitations, it can still be considered as a nascent initiative for further investigation using structural equation modeling. Originality/value The outcomes of the theoretical and managerial contributions of the study can be categorized into three levels. This study can be used both by the industrialists and researchers to understand the barriers and the recovery methods thereafter. Suggestions that serve as future directives are also discussed by the authors. (shrink)

The spiritual world of medieval Russia can be represented by the works of the most characteristic, brightest and most revered authors. Among them, undoubtedly, such as John Chrysostom, John Climacus, Isaac the Syrian, Basil the Great. The first place in popularity in Russia at all times is John Chrysostom. His Words, i.e. Some small works on this or that topic were compiled into special collections or textbooks by Zlatostruj, Zlatoust, Margarit, and sometimes the name of Zlatoust was signed by (...) works that did not belong to him. It is also popular in collections of mixed, composed of works by various authors, mainly the fathers of the church "Izmaragd", "Golden chain". The name Zlatoust became synonymous with all "book sweetness". What is so fond of Chrysostom in Russia? (shrink)

Introduction: The decision of “do not attempt resuscitation” in the event of cardiopulmonary arrest is usually made when the patients are critically ill and cannot make an informed choice. Although, various professional bodies have published guidelines, little is know about the patients’ own views regarding DNAR discussion.Aim: The aim of this study was to determine patients’ attitudes regarding discussing DNAR before they are critically ill.Methods: A prospective study was performed in a general out patients department. A questionnaire was distributed to (...) consecutive outpatients along with an explanatory leaflet in the adult outpatient clinic.Results: 364 patients completed the questionnaire . 90% of respondents wanted all patients to be asked regarding DNAR decision at some point during a hospital admission. The majority would not find a DNAR discussion distressing. Only 10% would find it upsetting, however, 48% of these still wanted a discussion. 37% of respondents wanted to discuss DNAR decisions on admission; 32% in outpatients; 17% at consent for surgery, 14% when they are critically ill. 87% of respondents would not object to their relatives being involved in making decisions about their resuscitation status. However, only 12% of the subjects in the study had been involved in discussing the resuscitation status of a relative and 21% would not be comfortable to discuss a relative’s resuscitation status. Although 33% of patients preferred their resuscitation status to simply be documented within their clinical notes, 77% wanted it to be more easily accessible.Conclusions: This study suggests that contrary to current practice most patients want to discuss their DNAR status prior to becoming critically ill. This includes half of the small number that find it distressing to discuss. Although most patients are comfortable with relatives being involved in discussing DNAR, a significant proportion do not want their relatives to be asked. Furthermore, once a decision has been made, the majority of patients want it to be more accessible than current practice allows. (shrink)

BackgroundSchool based running programmes, such as The Daily Mile™, positively impact pupils’ physical health, however, there is limited evidence on psychological health. Additionally, current evidence is mostly limited to examining the acute impact. The present study examined the longer term impact of running programmes on pupil cognition, wellbeing, and fitness.MethodData from 6,908 school pupils, who were participating in a citizen science project, was examined. Class teachers provided information about participation in school based running programmes. Participants completed computer-based tasks of inhibition, (...) verbal and visual-spatial working memory, as well as the Children’s Feeling scale and Felt arousal scale to determine subjective wellbeing. A multistage 20-m shuttle run test was used to estimate fitness.ResultsFrom our total sample of 6,908 school pupils, 474 participants had been taking part in a running programme for 3 months); and 5,430 did not take part in a running programme. The Longer Term participation group had higher fitness levels than both other groups and this remained significant when adjusted for age, sex and SES. Moderated regression analysis found that for the Shorter Term participation group, higher shuttle distance was associated with better visual-spatial working memory. Effect sizes were small though.ConclusionWe identified small and selective positive impact of participation in school based running programmes on fitness and cognition. While no long term benefit was identified for cognition or wellbeing, the impact on fitness and short term benefit suggest schools should consider participation. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Pyrrhonian Revival in Montaigne and NietzscheJessica N. BerryMichel de Montaigne occupies a unique place in Nietzsche's history of ideas. He is one of a very few figures for whom Nietzsche expresses deep admiration and about whom he has virtually nothing critical to say. This is a rare enough mark of distinction; but contrary to what it might lead us to expect, the relationship between Montaigne and Nietzsche has (...) seldom been carefully examined. There has yet to be a book-length study devoted solely to Montaigne and Nietzsche,1 and article-length treatments of the relationship between their works and thought have been surprisingly scarce. What discussions there have been tend to locate the connections between Nietzsche and Montaigne mainly in matters of either literary or personal style,2 but studies that examine Montaigne's influence on Nietzsche with an eye toward philosophical rather than literary or stylistic issues have been almost non-existent.3 This dearth of treatments can be explained, at least in part, by the fact that, while Montaigne is rightly recognized for the literary merits of his work and for its subsequent influence on later prose stylists (and not only in French), his work on the whole has seldom been appreciated as having any philosophical value in its own right. Small wonder, then, that the connection between Montaigne and Nietzsche has [End Page 497] appeared more significant to commentators on Montaigne who are interested in tracing his influence on later thinkers than to scholars of Nietzsche—even those Nietzsche scholars who take an acute interest in his intellectual heritage. What I will argue here is that Montaigne makes a more concrete and philosophically more substantive contribution to Nietzsche's thought than has generally been appreciated; specifically, by giving impetus to the naturalism that develops in Human, All Too Human as an antidote to Schopenhauer's pessimistic metaphysics of will.In this essay, I present a two-fold thesis about Montaigne's influence on Nietzsche's early work. First, I will argue that the "naturalistic turn" in Human, All Too Human reflects Nietzsche's engagement with Montaigne during a crucial moment in the development of his thought. Second, I will demonstrate that the naturalism Nietzsche adopts from Montaigne has roots in the tradition of Pyrrhonian skepticism that Montaigne carries forward into the Renaissance. In the end, a better understanding of the skeptical ancestry of Nietzsche's naturalism should help us make better sense of Human, All Too Human and its immediate successors in Nietzsche's oeuvre, which cultivate what otherwise seems to be an uneasy partnership between naturalism and skepticism.I. It is by now widely accepted that Nietzsche's estimation of the value of the techniques and methods of the natural sciences undergoes radical revision in the period culminating in the first volume of Human, All Too Human (HAH),4 a book sometimes described as inaugurating a "positivist" phase in Nietzsche's work. From the first of its nine major sections, "Of First and Last Things," HAH narrates a struggle between science on the one hand and philosophy on the other. It is important to note the breadth of the extension of the term "science" (Wissenschaft), which includes not only what we think of as the "hard" or physical sciences (physics, chemistry, and the like) but also areas of inquiry we now consider "behavioral sciences" such as psychology and sociology—and, Nietzsche would say, philology as well. "Philosophy," by contrast is specified more narrowly. As Nietzsche uses the term throughout HAH, "philosophy" is usually shorthand for "metaphysical philosophy" and singles out for criticism the discourse of metaphysics that has dominated the philosophical landscape at least since Plato.In the sense in which Nietzsche worries about it "metaphysical philosophy" promotes speculation about such supra-sensible entities as Platonic forms, Descartes's "immaterial substances," and Kantian things-in-themselves. That its contributions include, for instance, theories about the existence and immortality of the soul accounts for Nietzsche's grouping "metaphysical philosophy" [End Page 498] together with religion and art as "arts of narcosis."5 Consciously or not they endeavor to comfort us by assuaging our fear of death, our existential anxieties about the purposelessness of... (shrink)

Monica Colvin-Adams,1 Nonyelum Harcourt,1 Robert LeDuc,2 Ganesh Raveendran,1 Yassir Sonbol,3 Robert Wilson,1 Daniel Duprez11Cardiovascular Division, University of Minnesota, Minneapolis, MN, USA; 2Division of Biostatistics University of Minnesota, Minneapolis, MN, USA; 3Cardiovascular Division, St Luke's Hospital System, Sugar Land, TX, USAObjective: Arterial elasticity is a functional biomarker that has predictive value for cardiovascular morbidity and mortality in nontransplant populations. There is little information regarding arterial elasticity in heart transplant recipients. This study aimed to characterize small and large artery elasticity in (...) heart transplant recipients in comparison with an asymptomatic population free of overt cardiovascular disease. A second goal was to identify demographic and clinical factors associated with arterial elasticity in this unique population.Methods: Arterial pulse waveform was registered noninvasively at the radial artery in 71 heart transplant recipients between 2008 and 2010. SAEs and LAEs were derived from diastolic pulse contour analysis. Comparisons were made to a healthy cohort of 1,808 participants selected from our prevention clinic database. Multiple regression analyses were performed to evaluate associations between risk factors and SAE and LAE within the heart transplant recipients.Results: LAE and SAE were significantly lower in heart transplant recipients than in the normal cohort. Female sex and history of ischemic cardiomyopathy were significantly associated with reduced LAE and SAE. Older age and the presence of moderate cardiac allograft vasculopathy were also significantly associated with reduced SAE. Transplant duration was associated with increased SAE.Conclusion: Heart transplants are associated with peripheral endothelial dysfunction and arterial stiffness, as demonstrated by a significant reduction in SAE and LAE when compared with a healthy population. Furthermore, cardiac allograft vasculopathy is associated with a significant reduction in SAE, suggesting a potential use in screening heart transplant recipients at risk for developing this complication.Keywords: heart transplant, endothelial function, arterial elasticity, cardiac allograft vasculopathy. (shrink)

Of all the distinctive features of the Buddhist religion, one of the most neglected is the sangha . Scholars give much attention to the study of texts and commentaries, the analysis of doctrines and the classification of schools. But the core of the Buddhist religion is the sangha , the community of bhikkhus around whose corporate life the religion is moulded. It is the existence and structure of the sangha which has shaped the history of Buddhism, enabled it to take (...) root in new countries, and given it the customs and rituals which have made it a religion rather than a small sect. (shrink)

Japan is a country largely lacking supplies of many essential natural resources including petroleum, coal, and iron ore. As her industrial base and economy expanded during the 1920s and 1930s, Japan's dependence on imports of these resources became increasingly evident. The onset of the Depression in the 1930s further threatened Japan's lifeline, and, in an effort to become economically independent and self-sufficient in natural resources , Japan's militaristic government pursued a policy of territorial expansion. Beginning in 1937, Japan's military forces (...) swept out of Manchuria into China and then into Southeast Asia in search of strategic materials such as petroleum, coal, copper, zinc, and rubber. To achieve independence in petroleum, the Japanese developed a dual approach: they would acquire natural petroleum sources in Southeast Asia and at the same time establish a synthetic fuel industry for the conversion of coal to oil. Actually, the Japanese had begun research on synthetic fuel in the 1920s, only a few years after other countries, such as Germany and Britain, that lacked sources of natural petroleum. They did excellent laboratory research on the coal hydrogenation and Fischer-Tropsch conversion processes, but in their haste to construct large synthetic fuel plants they bypassed the intermediated pilot-plant stage and failed to make a successful transition from small- to large-scale production. Unable to synthesize liquid fuels from coal, they instead derived significant quantities from the technologically simpler coal carbonization and shale oil distillation processes. In the last year of World War II, the Japanese attempted to revive their synthetic fuel industry and entered into an agreement with IG Farben for technical assistance. Germany's defeat ended this final effort. The Japanese synthetic fuel industry presents a good case study of technological failure. It shows that high-quality basic scientific research does not necessarily translate into large-scale technological success. (shrink)

Many researchers have identified a process they call ‘deskilling’, which they use to describe the daily experience of teachers who have been gradually losing control of their own labour within ‘low‐trust’ workplaces. Conversely, other scholars have found that under similar conditions, some teachers have their own ways of dealing with it which leads them towards a process of ‘reskilling’. This study is an attempt to explore the actual teachers’ perceptions towards their daily practice within the context of educational decentralization, a (...) neglected area of research which needs to be further discussed and explored. This paper uses data gathered from seven schools in Guangdong Province, China as a case study to show that educational decentralization in China not only results in teachers being deskilled because indirect control is still being maintained, but also provides a small number of teachers with a competitive working environment to reskill their pedagogical techniques and educational knowledge, and to pursue good practices in teaching under the pressure of competition. All in all, educational decentralization provides a context in which teachers can experience either deprofessionalization or reprofessionalization. (shrink)

The goal of this small book and accompanying DVD is to help you to have a better experience in your laboratory by getting you to step back and take a global look at what is involved in making progress in the laboratory.

Introduction: The decision of “do not attempt resuscitation” in the event of cardiopulmonary arrest is usually made when the patients are critically ill and cannot make an informed choice. Although, various professional bodies have published guidelines, little is know about the patients’ own views regarding DNAR discussion.Aim: The aim of this study was to determine patients’ attitudes regarding discussing DNAR before they are critically ill.Methods: A prospective study was performed in a general out patients department. A questionnaire was distributed to (...) consecutive outpatients along with an explanatory leaflet in the adult outpatient clinic.Results: 364 patients completed the questionnaire . 90% of respondents wanted all patients to be asked regarding DNAR decision at some point during a hospital admission. The majority would not find a DNAR discussion distressing. Only 10% would find it upsetting, however, 48% of these still wanted a discussion. 37% of respondents wanted to discuss DNAR decisions on admission; 32% in outpatients; 17% at consent for surgery, 14% when they are critically ill. 87% of respondents would not object to their relatives being involved in making decisions about their resuscitation status. However, only 12% of the subjects in the study had been involved in discussing the resuscitation status of a relative and 21% would not be comfortable to discuss a relative’s resuscitation status. Although 33% of patients preferred their resuscitation status to simply be documented within their clinical notes, 77% wanted it to be more easily accessible.Conclusions: This study suggests that contrary to current practice most patients want to discuss their DNAR status prior to becoming critically ill. This includes half of the small number that find it distressing to discuss. Although most patients are comfortable with relatives being involved in discussing DNAR, a significant proportion do not want their relatives to be asked. Furthermore, once a decision has been made, the majority of patients want it to be more accessible than current practice allows. (shrink)

The similarity of documents in a large database of published Fractals articles was examined for redundancy. Three different text matching techniques were used on published Abstracts to identify redundancy candidates, and predictions were verified by reading full text versions of the redundancy candidate articles. A small fraction of the total articles in the database was judged to be redundant. This was viewed as a lower limit, because it excluded cases where the concepts remained the same, but the text was (...) altered substantially. Far more pervasive than redundant publications were publications that did not violate the letter of redundancy but rather violated the spirit of redundancy. There appeared to be widespread publication maximization strategies. Studies that resulted in one comprehensive paper decades ago now result in multiple papers that focus on one major problem, but are differentiated by parameter ranges, or other stratifying variables. This ‘paper inflation’ is due in large part to the increasing use of metrics (publications, patents, citations, etc) to evaluate research performance, and the researchers’ motivation to maximize the metrics. (shrink)

The similarity of documents in a large database of published Fractals articles was examined for redundancy. Three different text matching techniques were used on publisheds to identify redundancy candidates, and predictions were verified by reading full text versions of the redundancy candidate articles. A small fraction of the total articles in the database was judged to be redundant. This was viewed as a lower limit, because it excluded cases where the concepts remained the same, but the text was altered (...) substantially.Far more pervasive than redundant publications were publications that did not violate the letter of redundancy but rather violated the spirit of redundancy. There appeared to be widespread publication maximization strategies. Studies that resulted in one comprehensive paper decades ago now result in multiple papers that focus on one major problem, but are differentiated by parameter ranges, or other stratifying variables. This ‘paper inflation’ is due in large part to the increasing use of metrics (publications, patents, citations, etc) to evaluate research performance, and the researchers’ motivation to maximize the metrics. (shrink)

The similarity of documents in a large database of published Fractals articles was examined for redundancy. Three different text matching techniques were used on published Abstracts to identify redundancy candidates, and predictions were verified by reading full text versions of the redundancy candidate articles. A small fraction of the total articles in the database was judged to be redundant. This was viewed as a lower limit, because it excluded cases where the concepts remained the same, but the text was (...) altered substantially.Far more pervasive than redundant publications were publications that did not violate the letter of redundancy but rather violated the spirit of redundancy. There appeared to be widespread publication maximization strategies. Studies that resulted in one comprehensive paper decades ago now result in multiple papers that focus on one major problem, but are differentiated by parameter ranges, or other stratifying variables. This ‘paper inflation’ is due in large part to the increasing use of metrics (publications, patents, citations, etc) to evaluate research performance, and the researchers’ motivation to maximize the metrics. (shrink)

Western scholarly literature suggests that (1) weaning is initiated by mothers; (2) weaning takes place within a few days once mothers decide to stop nursing; (3) mothers employ specific techniques to terminate nursing; (4) semi-solid foods (gruels and mashed foods) are essential when weaning; (5) weaning is traumatic for children (it leads to temper tantrums, aggression, etc.); (6) developmental stages in relationships with mothers and others can be demarcated by weaning; and (7) weaning is a process that involves mothers and (...) children exclusively, with weaned children moving from close relationships with their mothers to strengthened relationships with other children. In many respects, these presumptions are consistent with contemporary Euroamerican practices: nursing stops early (usually before six months) relative to other cultures and takes place over a few days or weeks with the help of bottles and baby foods. Because bottles are available, weaning seldom appears traumatic, but it is seen as an important step in the establishment of independence between mothers and infants. By contrast, weaning from the bottle is often perceived as traumatic. Despite considerable academic and popular interest, weaning has seldom been studied systematically, especially in small-scale cultures. Qualitative and quantitative data from a study of Bofi foragers in Central Africa are used here to evaluate the cross-cultural applicability of the assumptions summarized above. (shrink)

Clinical Pharmacology is a specialty with many attributes and our association with the subject has allowed us to acquire, apply and disseminate myriad aspects of research and practice. Though clinical pharmacologists are conspicuous by virtue of their small number, recent years have shown a growing need for the course. In the review below we navigate through several aspects of the subject as we encountered them from time to time. From critical appraisal of literature, to application of knowledge of drugs, (...) to clinical practice; moving on to clinical and basic research, to drug development process, to policy making - these are but a few of the many fields which constitute the scope of clinical pharmacology. The importance of the subject lies in allowing a trainee to develop a broad overview of the entire process, from drug generation to drug distribution to drug utilization, a process meant for the greater common goal of better health for all. We foresee a bright future for the subject though with a slight skepticism thrown in. In the present article, we make use of personal experiences and reference from literature to help you get a broad view of what clinical pharmacology means to us. (shrink)

BackgroundThe potential contribution of community engagement to addressing ethical challenges for international biomedical research is well described, but there is relatively little documented experience of community engagement to inform its development in practice. This paper draws on experiences around community engagement and informed consent during a genetic cohort study in Kenya to contribute to understanding the strengths and challenges of community engagement in supporting ethical research practice, focusing on issues of communication, the role of field workers in 'doing ethics' on (...) the ground and the challenges of community consultation.MethodsThe findings are based on action research methods, including analysis of community engagement documentation and the observations of the authors closely involved in their development and implementation. Qualitative and quantitative content analysis has been used for documentation of staff meetings and trainings, a meeting with 24 community leaders, and 40 large public and 70 small community group meetings. Meeting minutes from a purposive sample of six community representative groups have been analysed using a thematic framework approach.ResultsField workers described challenges around misunderstandings about research, perceived pressure for recruitment and challenges in explaining the study. During consultation, leaders expressed support for the study and screening for sickle cell disease. In community meetings, there was a common interpretation of research as medical care. Concerns centred on unfamiliar procedures. After explanations of study procedures to leaders and community members, few questions were asked about export of samples or the archiving of samples for future research.ConclusionsCommunity engagement enabled researchers to take account of staff and community opinions and issues during the study and adapt messages and methods to address emerging ethical challenges. Field workers conducting informed consent faced complex issues and their understanding, attitudes and communication skills were key influences on ethical practice. Community consultation was a challenging concept to put into practice, illustrating the complexity of assessing information needs and levels of deliberation that are appropriate to a given study. (shrink)

This study compares corporate social performance in terms of charitable contributions of minority-owned and nonminority-owned small businesses. In this sample, minority-owned small businesses are younger, have less full-time employees, and lower annual sales. Minority-owned small businesses donate more funds to religious organizations than nonminority-owned small businesses. When annual sales are accounted for, minority-owned businesses contribute more total dollars to all charitable organizations than nonminority-owned firms. Suggestions for future research in this area are delineated.

The human intestines are constantly under the influence of numerous pathological factors: enteropathogenic microorganisms, food antigens, physico‐chemical stress associated with digestion and bacterial metabolism, therefore it must be provided with a system of protection against adverse impact. Recent studies have shown that Paneth cells play a crucial role in maintaining homeostasis of the small intestines. Paneth cells perform many vital functions aimed at maintaining a homeostatic balance between normal microbiota, infectious pathogens and the human body, regulate the qualitative (...) composition and number of intestinal microorganisms, prevent the introduction of potentially pathogenic species, and protect stem cells from damage. Paneth cells take part in adaptive and protective‐inflammatory reactions. Paneth cells maintain dynamic balance between microbial populations, and the macroorganism, preventing the development of intestinal infections and cancer. They play a crucial role in gastrointestinal homeostasis and may be key factors in the etiopathological progression of intestinal diseases. (shrink)

Purpose Many of the ethical issues of additive manufacturing are not well known or understood, and there remains a policy vacuum that needs to be addressed. This paper aims to describe an approach that has been applied successfully to other emerging technologies, referred to as the responsible research and innovation framework programme. A case is then made for the application of this approach in the AM industry with an illustration of how it might be used. Design/methodology/approach The research uses an (...) RRI approach referred to as AREA, an acronym for Anticipate, Reflect, Engage and Act, to assess the ethical implications of AM. For the anticipation phase, horizon scanning was done to explore the ethical issues of AM based on extant literature, while reflective analysis was carried out all through the work to reflect on the data being collected and the research process. The engage phase involved interviews with five participants from small- and medium-sized enterprises involved in 3D printing. Findings The findings indicate that although AM appears to pose a threat to intellectual property rights, many in the industry do not care about this issue. As AM becomes mainstream, intellectual property will likely become a big problem. Also, very little is known about the health impacts of AM. This study shows that AM can be hazardous. Research limitations/implications Only users at SME level were sampled. Other researchers might test the usefulness of AREA at the enterprise level. Practical implications The research demonstrates how the AREA framework may be useful in information systems and social science research by enabling a more anticipatory and reflective research process. Originality/value The paper responds to the need for a novel approach to identifying ethical issues of AM. (shrink)

Background Moral distress is a common challenge among professional nurses when caring for their patients, especially when they need to make rapid decisions. Therefore, leaving moral distress unconsidered may jeopardize patient quality of care, safety, and satisfaction. Aim To estimate moral distress among nurses. Methods This systematic review and meta-analysis conducted systematic search in Scopus, PubMed, ProQuest, ISI Web of Knowledge, and PsycInfo up to end of February 2022. Methodological quality of included studies was assessed using the Newcastle Ottawa (...) checklist. Data from included studies were pooled by meta-analysis with random effect model in STATA software version 14. The selected key measure was mean score of moral distress total score with its’ 95% Confidence Interval was reported. Subgroup analyses and meta-regressions were conducted to identify possible sources of heterogeneity and potentially influencing variables on moral distress. Funnel plots and Begg’s Tests were used to assess publication bias. The Jackknife method was used for sensitivity analysis. Ethical consideration The protocol of this project was registered in the PROSPERO database under decree code of CRD42021267773. Results Eighty-six manuscripts with 19,537 participants from 21 countries were included. The pooled estimated mean score of moral distress was 2.55 on a 0–10 scale [95% Confidence Interval: 2.27–2.84, I2: 98.4%, Tau2:0.94]. Publication bias and small study effect was ruled out. Moral distress significantly decreased in the COVID-19 pandemic versus before. Nurses working in developing countries experienced higher level of moral distress compared to their counterparts in developed countries. Nurses' workplace (e.g., hospital ward) was not linked to severity of moral disturbance. Conclusion The results of the study showed a low level of pooled estimated score for moral distress. Although the score of moral distress was not high, nurses working in developing countries reported higher levels of moral distress than those working in developed countries. Therefore, it is necessary that future studies focus on creating a supportive environment in hospitals and medical centers for nurses to reduce moral distress and improve healthcare. (shrink)

Since Seligman's 1971 statement that the vast majority of phobias are about objects essential to the survival of a species, a multitude of laboratory studies followed, supporting the finding that humans learn to fear and detect snakes (and other animals) faster than other stimuli. Most of these studies used schematic drawings, images, or pictures of snakes, and only a small amount of fieldwork in naturalistic environments was done. We address fear preparedness theories, and automatic fast detection data (...) from mainstream laboratory data and compares it with ethobehavioural information relative to snakes, predator-prey interaction, and snakes’ defensive kinematics strikes in order to analyse their potential matching. From this analysis four main findings arose, namely that: 1) Snakebites occur when people are very close to the snake and are unaware or unable to escape the bite; 2) Human visual detection and escape response is slow compared to the speed of snake strikes; 3) In natural environments, snake experts are often unable to see snakes existing nearby; 4) animate objects in general capture more attention over other stimuli and dangerous but recent objects in evolutionary terms are also able to be detected fast. The issues mentioned above pose several challenges to evolutionary psychology-based theories expecting to find special-purpose neural modules. The older selective habituation hypothesis (Schleidt, 1961), that prey animals start with a rather general predator image from which specific harmless cues are removed by habituation might deserve reconsideration. (shrink)

Objectives To conduct an independent evaluation of the first phase of the Health Foundation’s Safer Patients Initiative (SPI), and to identify the net additional effect of SPI and any differences in changes in participating and non-participating NHS hospitals. Design Mixed method evaluation involving five substudies, before and after design. Setting NHS hospitals in the United Kingdom. Participants Four hospitals (one in each country in the UK) participating in the first phase of the SPI (SPI1); 18 control hospitals. Intervention The SPI1 (...) was a compound (multi-component) organisational intervention delivered over 18 months that focused on improving the reliability of specific frontline care processes in designated clinical specialties and promoting organisational and cultural change. Results Senior staff members were knowledgeable and enthusiastic about SPI1. There was a small (0.08 points on a 5 point scale) but significant (P<0.01) effect in favour of the SPI1 hospitals in one of 11 dimensions of the staff questionnaire (organisational climate). Qualitative evidence showed only modest penetration of SPI1 at medical ward level. Although SPI1 was designed to engage staff from the bottom up, it did not usually feel like this to those working on the wards, and questions about legitimacy of some aspects of SPI1 were raised. Of the five components to identify patients at risk of deterioration—monitoring of vital signs (14 items); routine tests (three items); evidence based standards specific to certain diseases (three items); prescribing errors (multiple items from the British National Formulary); and medical history taking (11 items)—there was little net difference between control and SPI1 hospitals, except in relation to quality of monitoring of acute medical patients, which improved on average over time across all hospitals. Recording of respiratory rate increased to a greater degree in SPI1 than in control hospitals; in the second six hours after admission recording increased from 40% (93) to 69% (165) in control hospitals and from 37% (141) to 78% (296) in SPI1 hospitals (odds ratio for “difference in difference” 2.1, 99% confidence interval 1.0 to 4.3; P=0.008). Use of a formal scoring system for patients with pneumonia also increased over time (from 2% (102) to 23% (111) in control hospitals and from 2% (170) to 9% (189) in SPI1 hospitals), which favoured controls and was not significant (0.3, 0.02 to 3.4; P=0.173). There were no improvements in the proportion of prescription errors and no effects that could be attributed to SPI1 in non-targeted generic areas (such as enhanced safety culture). On some measures, the lack of effect could be because compliance was already high at baseline (such as use of steroids in over 85% of cases where indicated), but even when there was more room for improvement (such as in quality of medical history taking), there was no significant additional net effect of SPI1. There were no changes over time or between control and SPI1 hospitals in errors or rates of adverse events in patients in medical wards. Mortality increased from 11% (27) to 16% (39) among controls and decreased from 17% (63) to 13% (49) among SPI1 hospitals, but the risk adjusted difference was not significant (0.5, 0.2 to 1.4; P=0.085). Poor care was a contributing factor in four of the 178 deaths identified by review of case notes. The survey of patients showed no significant differences apart from an increase in perception of cleanliness in favour of SPI1 hospitals. Conclusions The introduction of SPI1 was associated with improvements in one of the types of clinical process studied (monitoring of vital signs) and one measure of staff perceptions of organisational climate. There was no additional effect of SPI1 on other targeted issues nor on other measures of generic organisational strengthening. (shrink)

Downsizing is a process whereby human relations management emerges as a critical skill in its effective management. This paperis about perceptions of employees of a small-sized Turkish firm who survived successive downsizing decisions. It was found that downsizing affected the organizational justice-related perceptions of survivors. The questionnaire used to explore organizational justice-related perceptions involved three dimensions and was developed by Saunders and Thornhill (1999). Procedural, interactional and distributive justice-related perceptions of survivors were influenced by the way management handled the (...) process. Management credibility, communication and commitment were other variables studied. The findings supported the view that downsizing not only affects the victims but also the survivors. (shrink)

This article addresses five research questions: What specific behaviors are described in the literature as ethical or unethical? What percentage of business people are believed to be guilty of unethical behavior? What specific unethical behaviors have been observed by bank employees? How serious are the behaviors? Are experiences and attitudes affected by demographics? Conclusions suggest: There are seventeen categories of behavior, and that they are heavily skewed toward internal behaviors. Younger employees have a higher level of ethical consciousness than older (...) employees. The longer one works for a company, the more one may look to job security as a priority; this can lead to rationalizing or overlooking apparently unethical behaviors. More emphasis is needed on internal behaviors with particular attention on the impact that external behaviors have on internal behaviors. (shrink)

The use of upper limb vibration during exercise and rehabilitation continues to gain popularity as a modality to improve function and performance. Currently, a lack of knowledge of the pathways being altered during ULV limits its effective implementation. Therefore, the aim of this study was to investigate whether indirect ULV modulates transmission along spinal and corticospinal pathways that control the human forearm. All measures were assessed under CONTROL and ULV conditions while participants maintained a small contraction of the right (...) flexor carpi radialis muscle. To assess spinal pathways, Hoffmann reflexes elicited by stimulation of the median nerve were recorded from FCR with motor response amplitudes matched between conditions. An H-reflex conditioning paradigm was also used to assess changes in presynaptic inhibition by stimulating the superficial radial nerve 37 ms prior to median nerve stimulation. Cutaneous reflexes in FCR elicited by stimulation of the SR nerve at the wrist were also recorded. To assess corticospinal pathways, motor evoked potentials elicited by transcranial magnetic stimulation of the contralateral motor cortex were recorded from the right FCR and biceps brachii. ULV significantly reduced H-reflex amplitude by 15.7% for both conditioned and unconditioned reflexes. Therefore, ULV inhibits cutaneous and H-reflex transmission without influencing corticospinal excitability of the forearm flexors suggesting increased presynaptic inhibition of afferent transmission as a likely mechanism. A general increase in inhibition of spinal pathways with ULV may have important implications for improving rehabilitation for individuals with spasticity. (shrink)

The study aimed at identifying the personal variables and their effect in promoting job creation in Gaza Strip through business incubators. The researchers used the descriptive analytical approach to achieve the study objectives. The study population consisted of 92 of the pilot projects benefiting from the three business incubators in Gaza Strip (Palestinian Information Technology Incubator, UCAS Technology Incubator and Business and Technology Incubator). The study reached a number of results, the most important of which are the existence of statistically (...) significant differences on entrepreneurship attributed to each age as most of them are between the ages of 22-30, Gender for males, business incubator, scientific qualification for the specialties of information technology and engineering, and years of experience. Based on the findings, the researchers recommend focusing on university students in guiding them towards entrepreneurship and helping new graduates to start entrepreneurship. And to guide students to scientific disciplines that help them in entrepreneurship after graduation, whether starting a small business or self-employment, support females to entrepreneurship as most of the entrepreneurs are male, in addition to stimulating males as well. (shrink)

The complex hexaploid wheat genome offers many challenges for genomics research. Expressed sequence tags facilitate the analysis of gene-coding regions and provide a rich source of molecular markers for mapping and comparison with model organisms. The objectives of this study were to construct a high-density EST chromosome bin map of wheat homoeologous group 2 chromosomes to determine the distribution of ESTs, construct a consensus map of group 2 ESTs, investigate synteny, examine patterns of duplication, and assess the colinearity with rice (...) of ESTs assigned to the group 2 consensus bin map. A total of 2600 loci generated from 1110 ESTs were mapped to group 2 chromosomes by Southern hybridization onto wheat aneuploid chromosome and deletion stocks. A consensus map was constructed of 552 ESTs mapping to more than one group 2 chromosome. Regions of high gene density in distal bins and low gene density in proximal bins were found. Two interstitial gene-rich islands flanked by relatively gene-poor regions on both the short and long arms and having good synteny with rice were discovered. The map locations of two ESTs indicated the possible presence of a small pericentric inversion on chromosome 2B. Wheat chromosome group 2 was shown to share syntenous blocks with rice chromosomes 4 and 7. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Nietzsche and Rée: A Star FriendshipDaw-Nay N. R. Evans Jr.Robin Small. Nietzsche and Rée: A Star Friendship. Oxford: Clarendon Press, 2005. Pp. xxiv + 247. Cloth, $45.00.Nietzsche attracts a wide range of scholarly enthusiasts. There are those who take Nietzsche seriously as a philosopher and study his works for their own sake, while others seek to mine his works for philosophical gold to determine what he might (...) have to offer their particular area of specialization (and sometimes these objectives overlap). On the other hand, there are those who seek to sensationalize Nietzsche by making him out to be a caricature or buffoon of sorts—far less deserving of the kind of seriousness we reserve for other figures such as Descartes or Kant. Instead, Nietzsche's philosophical legacy is colored by his ill health, alleged homosexuality, or "madness." Some recent biographies have only perpetuated the caricature. Fortunately, Small's book is not one of them.Small aims to explain the philosophical relationship between Nietzsche and Rée. Nietzsche's background is well known, while Rée's life has received only slight attention from scholars. Although he did not self-identify as Jewish, Rée was born into a wealthy Jewish family, which afforded him the luxury of attending several different German universities. After studying law, psychology, and physiology, he finally settled on philosophy. By the time Rée met Nietzsche, he had already defended a dissertation on Aristotle's ethics and published his first book, Psychological Observations, in 1875.Throughout the book, Small subtly fuses the personal with the philosophical without weakening the philosophical substance of Nietzsche's or Rée's ideas. In explaining Rée's influence on Nietzsche during the seven years of their friendship, Small accomplishes several objectives.First and foremost, Small illuminates the development of Nietzsche's thought from 1875 until 1882. It was during these years that Nietzsche published Human, All Too Human (1878; the first supplement to the book was published in 1879 and the second in 1880), Daybreak (1881), and The Gay Science (1882). More importantly, Small demonstrates the nexus between these works and Rée's Psychological Observations (1875) and The Origin of Moral Sensations.During the winter of 1876–77, Nietzsche and Rée lived together. At this time Nietzsche began writing Human, All Too Human, while Rée wrote The Origin of Moral Sensations. Nietzsche turned to Rée's Psychological Observations for headings for his own Human, All Too Human. Thus, "'On Religious Things' became 'The Religious Life,' while 'On Woman, Love and Marriage' became 'Woman and Child'" (28). As Nietzsche continued work on Human, All Too Human, Rée's The Origin of Moral Sensations was published and Nietzsche drew inspiration from this book as well. In section 40 of The Wanderer and His Shadow (the second supplement to Human, All Too Human), Nietzsche provides an abbreviated version of the core argument of that work, namely that the move away from utility and towards socially accepted norms as the determining factor in behavior is what led to morality. For these reasons, it is no surprise that Nietzsche referred to the "Rée-ness" of his work, and dubbed books like Human, All Too Human as "Réealism" (x, 33, 65). [End Page 672]Second, Small makes clear the shared philosophical sympathies that made their relationship possible. Their mutual admiration for Schopenhauer, denial of free will, skepticism about morality and metaphysics, and adherence to philosophical naturalism created a friendship that nurtured their philosophical development generally and their philosophical projects more specifically.Third, Small sheds light on how Nietzsche integrated Rée's aphoristic style into his own philosophical writings. This is helpful because it contextualizes Nietzsche's writing style during the time when his strict preoccupation with philological matters had ended and he began exhibiting contempt for morality and extolling the virtues of scientific knowledge.Fourth, Small discusses Nietzsche's break with Rée, the central tension of which he locates in Nietzsche's willingness to move beyond Rée's merely descriptive approach to moral phenomena towards a life-affirming philosophy. To be sure, Nietzsche envisioned Human, All Too... (shrink)

Testosterone fluctuates in response to competitive social interactions, with the direction of change typically depending on factors such as contest outcome. Watching a competition may be sufficient to activate T among fans and others who are invested in the outcome. This study explores the change in T associated with vicarious experiences of competition among combat sport athletes viewing a teammate win or lose and assesses how individual differences in social identification with one’s team relates to these patterns of T reactivity. (...) Twenty-six male combat athletes completed a social identity questionnaire on a neutral day. Later, salivary samples were obtained before and after athletes viewed a video of a teammate engaged in a formal contest. T reactivity to viewing a teammate compete varied among participants in both the magnitude and direction of change, independent of contest outcome. Individual differences in cognitive centrality, a core feature of social identification, showed a strong positive relationship with T reactivity, particularly if their teammate won. Initial findings suggest that dominance-linked androgen responses associated with watching a teammate win a competition might depend on the belief that team membership is central to one’s own identity. These exploratory results in a small sample of combat athletes should be interpreted with caution. Uncovering the role of social group dynamics in influencing T responses to competition is particularly important in light of the evolutionary history of coalitional combat in humans. (shrink)

This book is a comparative study of the sociological theory of such founding American sociologists as Ward, Sumner, Keller, Giddings, Ross, Small, and Cooley. The work is divided into chapters such as the one on "Social Origins" in which the contributions of these sociologists are delineated and compared. Hinkle attempts to characterize the fundamental working assumptions of these men by relating their work to the materials of American history and to the structures of American society and academia around 1880-1915. (...) Thus Hinkle claims that his book is "a contribution to the sociology of the history of sociological theory.". (shrink)

BACKGROUND: Serotonin transporter promoter genotype appears to increase risk for depression in the context of stressful life events. However, the effects of this genotype on measures of stress sensitivity are poorly understood. Therefore, this study examined whether 5-HTTLPR genotype was associated with negative information processing biases in early childhood. METHOD: Thirty-nine unselected seven-year-old children completed a negative mood induction procedure and a Self-Referent Encoding Task designed to measure positive and negative schematic processing. Children were also genotyped for the 5-HTTLPR gene. (...) RESULTS: Children who were homozygous for the short allele of the 5-HTTLPR gene showed greater negative schematic processing following a negative mood prime than those with other genotypes. 5-HTTLPR genotype was not significantly associated with positive schematic processing. LIMITATIONS: The sample size for this study was small. We did not analyze more recently reported variants of the 5-HTTLPR long alleles. CONCLUSIONS: 5-HTTLPR genotype is associated with negative information processing styles following a negative mood prime in a non-clinical sample of young children. Such cognitive styles are thought to be activated in response to stressful life events, leading to depressive symptoms; thus, cognitive styles may index the "stress-sensitivity" conferred by this genotype. (shrink)

Pleiotropically acting eukaryotic corepressors such as retinoblastoma and SIN3 have been found to physically interact with many widely expressed “housekeeping” genes. Evidence suggests that their roles at these loci are not to provide binary on/off switches, as is observed at many highly cell‐type specific genes, but rather to serve as governors, directly modulating expression within certain bounds, while not shutting down gene expression. This sort of regulation is challenging to study, as the differential expression levels can be small. We (...) hypothesize that depending on context, corepressors mediate “soft repression,” attenuating expression in a less dramatic but physiologically appropriate manner. Emerging data indicate that such regulation is a pervasive characteristic of most eukaryotic systems, and may reflect the mechanistic differences between repressor action at promoter and enhancer locations. Soft repression may represent an essential component of the cybernetic systems underlying metabolic adaptations, enabling modest but critical adjustments on a continual basis. (shrink)

There is a scarcity of research on men’s experience of bereavement (Reiniche, 2006), particularly in relation to qualitative research that focuses on the meaning of such an experience. This paper seeks to address this scarcity by presenting the findings from a phenomenological study of the lifeworlds of a small number of bereaved men. The study looked specifically at how the loss of a spouse influences men’s experience of meaning, grief and loss. Three men aged between 32 and 54 years (...) old who had all lost their partners to cancer between 3 and 7 years ago were interviewed. The hermeneutic phenomenological method of Van Manen (1990) was used to uncover three key themes, labelled grief and self-reflection, meaning of life and loss, and refiguring the life-world. These themes are discussed in the light of broader existential concerns and the extant literature. (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 (...) was suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags accounting for 2266 restriction fragments on the homoeologous group 3 chromosomes of hexaploid wheat. Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the (...) chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes ∼21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. (shrink)

The experience of the use of applied containerized biomedical software tools in cloud environment is summarized. The reproducibility of scientific computing in relation with modern technologies of scientific calculations is discussed. The main approaches to biomedical data preprocessing and integration in the framework of the intelligent analytical system are described. At the conditions of pandemic, the success of health care system depends significantly on the regular implementation of effective research tools and population monitoring. The earlier the risks of disease can (...) be identified, the more effective process of preventive measures or treatments can be. This publication is about the creation of a prototype for such a tool within the project «Development of methods, algorithms and intelligent analytical system for processing and analysis of heterogeneous clinical and biomedical data to improve the diagnosis of complex diseases», implementted by the V.M. Glushkov Institute of Cybernetics, National Academy of Sciences of Ukraine, together with the United Institute of Informatics Problems, National Academy of Sciences of Belarus. The insurers, entering the market, can insure mostly low risks by facilitating more frequent changes of insurers by consumers and mixing the overall health insurance market. Socio-demographic variables can be risk adjusters. Since age and gender have a relatively small explanatory power, other socio-demographic variables were studied – marital status, retirement status, disability status, educational level, income level. Because insurers have an interest in beneficial diagnoses for their policyholders, they are also interested in the ability to interpret relevant information – upcoding: insurers can encourage their policyholders to consult with doctors more often to select as many diagnoses as possible. Many countries and health care systems use diagnostic information to determine the reimbursement to a service provider, revealing the necessary data. For processing and analysis of these data, software implementations of construction for classifiers, allocation of informative features, processing of heterogeneous medical and biological variables for carrying out scientific research in the field of clinical medicine are developed. The experience of the use of applied containerized biomedical software tools in cloud environment is summarized. The reproducibility of scientific computing in relation with modern technologies of scientific calculations is discussed. Particularly, attention is paid to containerization of biomedical applications, this permits to get reproducibility of the conditions in which the calculations took place, technologies of software pipelining of calculations, that allows to organize flow calculations, and technologies for parameterization of software environment, that allows to reproduce, if necessary, an identical computing environment. The main approaches to biomedical data preprocessing and integration in the framework of the intelligent analytical system are described. The experience of using the developed linear classifier, gained during its testing on artificial and real data, allows us to conclude about several advantages provided by the containerized form of the created application: it permits to provide access to real data located in cloud environment; it is possible to perform calculations to solve research problems on cloud resources both with the help of developed tools and with the help of cloud services; such a form of research organization makes numerical experiments reproducible, i.e. any other researcher can compare the results of their developments on specific data that have already been studied by others, in order to verify the conclusions and technical feasibility of new results; there exists a universal opportunity to use the developed tools on technical devices of various classes from a personal computer to powerful cluster. (shrink)

A literature search was conducted on studies of new drugs used with patients with schizophrenia reported by U.S. and non-U.S. researchers from 1966–1993, yielding 41 U.S., and a total of 24 other non-U.S. studies, among them 11 British studies. Results of the U.S. and non-U.S. studies were pooled separately and compared. Among several comparable conditions discussed, the lack of any data on suicides in the U.S. studies was observed. For a second statistical analysis of suicide (...) rates ‘person-years’ were calculated to adjust for differing washout durations. The results obtained include findings that the percentage of patients relapsing in U.S. studies was slightly lower than in non-U.S. studies ; the percentage of patients dropping out in U.S. studies was higher than in non-U.S. studies ; known location of dropout patients in U.S. studies was 1.7%, compared to 2.6% in non-U.S. studies. The most interesting finding was that no suicides were reported in U.S. studies, compared to 0.6% of patients reported in British studies. Some U.S. studies used ‘challenge doses’, such as amphetamines or L-dopa; no non-U.S. studies reported their use. Compared to U.S. studies, those by non-U.S., and particularly British, researchers appeared to report adverse events in their studies. ‘Challenge’ drugs were not used; suicides were reported. It is estimated that the probability that no patients suicided who participated in the U.S. is small—one in 500. (shrink)

This text examines the intellectual partnership of Friedrich Nietzsche (1844-1900) and Paul Rée (1849-1901), combining biography with philosophy to give an account of a friendship that made major contributions to modern thought"--Provided by publisher.

Exclusionary defeat is Joseph Raz’s proposal for understanding the more complex, layered structure of practical reasoning. Exclusionary reasons are widely appealed to in legal theory and consistently arise in many other areas of philosophy. They have also been subject to a variety of challenges. I propose a new account of exclusionary reasons based on their justificatory role, rejecting Raz’s motivational account and especially contrasting exclusion with undercutting defeat. I explain the appeal and coherence of exclusionary reasons by appeal to commonsense (...) value pluralism and the intermediate space of public policies, social roles, and organizations. We often want our choices to have a certain character or instantiate a certain value and in order to do so, that choice can only be based on a restricted set of reasons. Exclusion explains how pro tanto practical reasons can be disqualified from counting towards a choice of a particular kind without being outweighed or undercut. (shrink)