The prelims comprise: Introduction 1 Should I Use Drugs? Is the State Justified in Punishing Drug Users? Conclusion References Further Reading.

Cell cycle arrest in M phase can be induced by the failure of a single chromosome to attach properly to the mitotic spindle. The same cell cycle checkpoint mediates M phase arrest when cells are treated with drugs that either disrupt or hyperstabilize spindle microtubules. Study of yeast mutants that fail to arrest in the presence of microtubule disruptors identified a set of genes important in this checkpoint pathway. Two recent papers report the cloning of human and Xenopus homologues of (...) one of these yeast genes, called MAD2 (for mitotic arrest deficient‐2)(1,2). Introduction of antibodies to the MAD2 protein into living mammalian cells or Xenopus egg extracts abrogates the M phase arrest induced by microtubule inhibitors. This and other recent developments suggest a model for the M phase checkpoint in which unattached kinetochores inhibit the ubiquitination of proteins whose proteolysis is necessary for chromatid separation and exit from mitosis. (shrink)

In this article a concept of non-local consciousness will be described, based on recent scientific research on near-death experiences . Since the publication of several prospective studies on NDEs in survivors of cardiac arrest, with strikingly similar results and conclusions, the phenomenon of the NDE can no longer be scientifically ignored. In the last thirty years several theories have been proposed to explain an NDE. The challenge to find a common explanation for the cause and content of an NDE is (...) complicated by the fact that an NDE can be experienced during various circumstances, such as severe injury of the brain as in cardiac arrest to conditions when the brain seems to function normally. The NDE is an authentic experience which cannot be simply reduced to imagination, fear of death, hallucination, psychosis, the use of drugs, or oxygen deficiency. Patients appear to be permanently changed by an NDE during a cardiac arrest of only some minutes duration. According to these aforementioned studies, the current materialistic view of the relationship between consciousness and the brain as held by most physicians, philosophers, and psychologists is too restricted for a proper understanding of this phenomenon. There are good reasons to assume that our consciousness does not always coincide with the functioning of our brain: enhanced or non-local consciousness can sometimes be experienced separately from the body. (shrink)

Two days following her arrest, a forty-four-year-old woman died in jail from aspiration pneumonia secondary to Untreated opiate withdrawal. The New York State Commission of Corrections concluded in its final report that had adequate medical evaluation and treatment been afforded, her death would have been prevented. A forty-six-year-old male with a history of alcohol dependence was arrested for trespassing and held in the county jail. Three days later he became agitated and aggressive. Following physician orders, deputies placed him in restraints. (...) He subsequently vomited and seized. Fifteen minutes later, he experienced respiratory arrest and died.These cases highlight a serious, but neglected problem in jails across the country: inadequate assessment and treatment of drug and alcohol withdrawal among arrestees. In this article, we show that untreated drug or alcohol withdrawal is associated with adverse outcomes including needless pain and suffering, medical morbidity, and in some instances, death. (shrink)

Two days following her arrest, a forty-four-year-old woman died in jail from aspiration pneumonia secondary to Untreated opiate withdrawal. The New York State Commission of Corrections concluded in its final report that had adequate medical evaluation and treatment been afforded, her death would have been prevented. A forty-six-year-old male with a history of alcohol dependence was arrested for trespassing and held in the county jail. Three days later he became agitated and aggressive. Following physician orders, deputies placed him in restraints. (...) He subsequently vomited and seized. Fifteen minutes later, he experienced respiratory arrest and died.These cases highlight a serious, but neglected problem in jails across the country: inadequate assessment and treatment of drug and alcohol withdrawal among arrestees. In this article, we show that untreated drug or alcohol withdrawal is associated with adverse outcomes including needless pain and suffering, medical morbidity, and in some instances, death. (shrink)

ON DECEMBER 10, 1991 Charles Shonubi, a Nigerian citizen but a resident of the USA, was arrested at John F. Kennedy International Airport for the importation of heroin into the United States.1 Shonubi's modus operandi was ``balloon swallowing.'' That is, heroin was mixed with another substance to form a paste and this paste was sealed in balloons which were then swallowed. The idea was that once the illegal substance was safely inside the USA, the smuggler would pass the balloons and (...) recover the heroin. On the date of his arrest, Shonubi was found to have swallowed 103 balloons containing a total of 427.4 grams of heroin. There was little doubt about Shonubi's guilt. In fact, there was considerable evidence that he had made at least seven prior heroin-smuggling trips to the USA (although he was not tried for these). In October 1992 Shonubi was convicted in a United States District Court for possessing and importing heroin. Although the conviction was only for crimes associated with Shonubi's arrest date of December 10, 1991, the sentencing judge, Jack B. Weinstein, also made a ®nding that Shonubi had indeed made seven prior drug-smuggling trips to the USA. The interesting part of this case was in the sentencing. According to the federal sentencing guidelines, the sentence in cases such as this should depend on the total quantity of heroin involved. This instruction was interpreted rather broadly.. (shrink)

Prominent tuberculosis (TB) actors are invoking solidarity to motivate and justify collective action to address TB, including through intensified development and implementation (D&I) of technologies such as drugs and diagnostics. We characterize the ethical challenges associated with D&I of new TB technologies by drawing on stakeholder perspectives from 23 key informant interviews and we articulate the ethical implications of solidarity for TB technology D&I. The fundamental ethical issue facing TB technological D&I is a failure within and beyond the TB community (...) to stand in solidarity with persons with TB in addressing the complex sociopolitical contexts of technological D&I. The failure in solidarity relates to two further ethical challenges raised by respondents: skewed power dynamics that hinder D&I and uncertainties around weighing risks and benefits associated with new technologies. Respondents identified advocacy and participatory research practices as necessary to address such challenges and to motivate sustained collective action to accelerate toward TB elimination. We present the first empirical examination of bioethical accounts of solidarity in public and global health. Our study suggests that solidarity allows us better to understand and address the ethical challenges that arrest the D&I of new TB technologies. Solidarity lends credence to policies and practices that address the relational nature of illness and health through collective action. (shrink)

Assessing social risks has proven difficult for IRBs. We undertook a novel effort to empirically investigate social risks before an HIV prevention trial among drug users in Thailand and China. The assessment investigated whether law, policies and enforcement strategies would place research subjects at significantly elevated risk of arrest, incarceration, physical harm, breach of confidentiality, or loss of access to health care relative to drug users not participating in the research. The study validated the investigator's concern that (...) class='Hi'>drug users were subject to serious social risks in the site localities, but also suggested that participation in research posed little or no marginal increase in risk and might even have a protective effect. Our experience shows that it is feasible to inform IRB deliberations with actual data on social risks, but also raises the question of whether and when such research is an appropriate use of scare research resources. (shrink)

In 2003, the South Carolina Supreme Court upheld the conviction of Regina McKnight, an African American woman who was convicted at the age of twenty‐two for committing “homicide by child abuse.” She became the first woman in the United States to be arrested, prosecuted, and convicted for experiencing a stillbirth. Rather than an outlier case in the annals of American jurisprudence that stretched law beyond reason while restraining compassion and justice, McKnight's conviction inspired similar prosecutions of other poor black women (...) and then of other women. More than one‐third of states consider pregnant women's illicit drug use a form of child abuse, resulting in unprecedented forms of criminal and civil punishment. Laws previously understood to protect pregnant women from domestic violence during pregnancy, such as fetal protection laws, now serve as the vehicles for prosecuting pregnant women. What these prosecutions and laws expose are the multitudinous ways in which the criminalization of poor pregnant women—and normalization of that criminalization, such that even doctors and nurses are expected to participate in it—serve to humiliate women, interfere with their reproductive health, and ultimately rob women of reproductive autonomy. (shrink)

Ribosome biogenesis includes the making and processing of ribosomal RNAs, the biosynthesis of ribosomal proteins from their mRNAs in the cytosol and their transport to the nucleolus to assemble pre‐ribosomal particles. Several stresses including cellular senescence reduce nucleolar rRNA synthesis and maturation increasing the availability of ribosome‐free ribosomal proteins. Several ribosomal proteins can activate the p53 tumor suppressor pathway but cells without p53 can still arrest their proliferation in response to an imbalance between ribosomal proteins and mature rRNA production. Recent (...) results on senescence‐associated ribogenesis defects (SARD) show that the ribosomal protein S14 (RPS14 or uS11) can act as a CDK4/6 inhibitor linking ribosome biogenesis defects to the main engine of cell cycle progression. This work offers new insights into the regulation of the cell cycle and suggests novel avenues to design anticancer drugs. (shrink)

This paper attends to the curious affair of Jacques Derrida in Prague when he was arrested by the Czechoslovakian police on charges of drug smuggling. It reads two images by Valerio Adami and Nicolas Poussin, entitled, ‘The Massacre of the Innocents’, Tom Stoppard's play, Professional Foul about dissident philosophers in Prague, and a section from Ken McMullen's film Ghost Dance on Kafka. It turns around the question of what ‘innocence’ might mean in politics and reading.

In lieu of an abstract, here is a brief excerpt of the content:To Be or Not to Be:Waiving Informed Consent in Emergency ResearchCharles R. McCarthy (bio)The requirements for prior, legally authorized informed consent constitute a necessary condition for recruiting subjects into biomedical or behavioral research. However, informed consent requirements pose a serious problem for most research conducted in emergency care settings. For this reason, the Food and Drug Administration's (FDA) regulations governing investigational devices and the Department of Health and (...) Human Services' (HHS) regulations for the protection of human subjects allow narrow exceptions to the general requirements of informed consent. In a joint effort to clarify the applicability of the current FDA regulations and to better understand the intent of the HHS regulations as they apply to emergency research, the FDA and the National Institutes of Health (NIH) cosponsored a public forum on the ethical conduct of emergency research in January 1995.Although the forum was not designed as a consensus conference and participants vigorously disagreed on some of the details, a broad consensus emerged on several major points: (1) both HHS and FDA regulations should, in the immediate future, be interpreted to allow for randomized clinical trials in emergency situations so long as the subjects are carefully protected; and (2) consideration should be given to producing new, closely harmonized regulations from both agencies that will provide greater clarity concerning what kinds of emergency research may be allowed without obtaining prior informed consent.The FDA-NIH forum in January was occasioned primarily by controversy about the hypothermia research protocol described below, but it is obvious that many other kinds of emergency research also await the outcome of deliberations concerning waiver of informed consent in emergency situations. These include research into the care and treatment of: occlusive stroke; subarachnoid hemorrhage due to intracranial aneurysm; metabolic coma; status epilepticus; cardiac arrest; myocardial infarction; cardiac arrhythmia; hemorrhagic shock; pulmonary embolism; acute asthmatic attack; and poisoning. All of these conditions [End Page 155] are encountered in emergency settings where obtaining informed consent from the patient-subjects to participate in research is seldom possible, and obtaining consent from legally authorized representatives of the subjects is either not feasible, or, if obtained, is of doubtful validity.The Hypothermia Research Case and HHS RegulationsA $7.2 million grant for research on the use of hypothermia in the treatment of severe head trauma, the largest award ever made to the University of Texas Health Sciences Center at Houston, is in danger of expiring before the study is completed. The protocol, which involves the use of cooling blankets to induce hypothermia in patients suffering from severe head injuries, is designed to test the hypothesis that: "Early lowering of the body temperature of patients suffering from severe head trauma to approximately 91 degrees Fahrenheit will slow patients' metabolism and will/will not, as a consequence, reduce the rates of both morbidity and mortality in these patients." The protocol was approved by seven Institutional Review Boards (IRBs), each of which waived the requirement to obtain informed consent from research subjects in accordance with Sec. 46. 116(d) of the HHS Regulations for the Protection of Human Subjects.1However, NIH's Office for Protection from Research Risks (OPRR), which is responsible for assuring compliance with the HHS regulations, has taken a controversial regulatory position by requiring informed consent from a legally authorized representative of each subject to be entered in the hypothermia trial. Because the obtaining of surrogate consent has proved to be very difficult, OPRR's position has slowed the research to a point where it may have to be terminated.At issue in the controversy is a fundamental question of ethics and public policy. Is it ever permissible to involve incompetent subjects in research without either their consent, or the consent of their legally authorized representatives? Pertinent HHS regulations for the protection of human subjects seem to answer the question affirmatively by allowing local IRBs to waive some or all of the elements of informed consent under carefully limited circumstances (45 CFR 46 116(d)). Nevertheless, OPRR has signalled the research community that use of the informed consent waiver provision for the Houston hypothermia study is not permitted under the regulations. OPRR judged that the risks... (shrink)

Objectives: To examine the willingness of patients to participate in a resuscitation study that requires exception from informed consent and to determine if willingness to participate is associated with demographic and other characteristics.Methods: Adult patients in an emergency department and in a geriatric outpatient clinic were surveyed. Patients were asked to imagine that they presented to an emergency department with cardiac arrest and asked about their willingness to receive a new drug outside of a study, receive a new (...) class='Hi'>drug as part of a study and participate in a randomised controlled trial for a new drug. Patients were also asked about participation in studies of invasive procedures.Results: 213 patients from a geriatric clinic and 207 from an emergency department were surveyed. Two thirds of patients from the geriatric clinic and 83% from the emergency department were willing to receive an experimental drug outside of a study. Patients were less willing to participate in a study of the new drug and even less likely to participate in an RCT for the new drug . Patients were less likely to participate in a study of thoracotomy than in a study that required placement of a femoral catheter . Willingness to participate was not associated with trust in the doctors.Conclusions: Study design and invasiveness of the intervention were associated with the willingness of patients to participate in resuscitation studies that require exception from informed consent. (shrink)

Internal misconduct is a universal problem in prisons and affects the maintenance of social order. Consequently, correctional institutions often develop rehabilitation programs to reduce the likelihood of inmates committing internal offenses and criminal recidivism after release. Therefore, it is necessary to identify the profile of each offender, both for the appropriate indication of a rehabilitation program and the level of internal security to which he must be submitted. In this context, this work aims to discover the most significant characteristics in (...) predicting inmate misconduct from ML methods and the SHAP approach. A database produced in 2004 through the Survey of Inmates in State and Federal Correctional Facilities in the United States of America was used, which provides nationally representative data on prisoners from state and federal facilities. The predictive model based on Random Forest performed the best, thus, we applied the SHAP to it. Overall, the results showed that features related to victimization, type of crime committed, age and age at first arrest, history of association with criminal groups, education, and drug and alcohol use are most relevant in predicting internal misconduct. Thus, it is expected to contribute to the prior classification of an inmate on time, to use programs and practices that aim to improve the lives of offenders, their reintegration into society, and consequently, the reduction of criminal recidivism. (shrink)

A rule- utilitarian appraisal of criminal law requires that the total system, including punishments, is justified only if it will expectably maximize public benefit, including its stigmatizing some behaviors as "offenses" and its prescribed punishment of these, such as imprisonment, with (possible) deterrent effects. In view of the paucity of evidence about the deterrent effect of prison sentences, some changes seem to be in order: reduction in the length of incarceration, replacement of prison by fines or restrictions on the convicted (...) such as house arrest for many hours of a day, intensive supervision, required community service (say thirty hours in place of a month in prison), enrollment in a drug program or therapy in the case of sex offenses, and so on. An evaluation of such proposals should be based on statistics and the psychology of criminal behavior. (shrink)

Assessing social risks has proven difficult for IRBs. We undertook a novel effort to empirically investigate social risks before an HIV prevention trial among drug users in Thailand and China. The assessment investigated whether law, policies and enforcement strategies would place research subjects at significantly elevated risk of arrest, incarceration, physical harm, breach of confidentiality, or loss of access to health care relative to drug users not participating in the research. The study validated the investigator's concern that (...) class='Hi'>drug users were subject to serious social risks in the site localities, but also suggested that participation in research posed little or no marginal increase in risk and might even have a protective effect. Our experience shows that it is feasible to inform IRB deliberations with actual data on social risks, but also raises the question of whether and when such research is an appropriate use of scare research resources. (shrink)

The dinoflagellates, a diverse sister group of the malaria parasites, are the major agents causing harmful algal blooms and are also the symbiotic algae of corals. Dinoflagellate nuclei differ significantly from other eukaryotic nuclei by having extranuclear spindles, no nucleosomes and enormous genomes in liquid crystal states. These cytological characteristics were related to the acquisition of prokaryotic genes during evolution (hence Mesokaryotes), which may also account for the biochemical diversity and the relatively slow growth rates of dinoflagellates. The fact that (...) the proliferation of many dinoflagellates is sensitive to turbulence may be due to the physiological requirements of the genome's liquid crystal states. Mechanical stress and anti‐microtubule drugs induce cell cycle arrest mainly in G1, implicating a role for the permanent cortical microtubular cytoskeleton in mechanotransduction. The cell cycles of photosynthetic dinoflagellates are also gated by the circadian rhythm, with cell division occurring mainly at the end of the dark phase. Cell growth and the biosynthesis of many toxins occur during the light phase, corresponding to G1 in the cell cycle. The dinoflagellates also embody several options for coupling cell cycle progression to cell growth, enabling them to make the best use of available resources and possibly preparing them for a symbiotic existence. BioEssays 27:730–740, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The police are one of the most powerful and important forces for any country. The main task of the police is to install a sense of security in the ordinary citizens and to protect their life and property when they are in danger. Bangladeshi Police have a glorious past with tremendous achievement. Especially in our great liberation war in 1971, they played an important role in achieving our liberation. Eliminating terrorism & militancy and others several operation that leads with the (...) risk of their life. But there are still a lot of accusations against the police force. Like- abusing of power, Misconducting with the people, Committing crossfire defying the high-court order, Wearing white dress when they move to detain criminals, Arresting without warrant, and many other including Bribery, Extortion, Trading Drug and Yaba, Playing partisan role, keeping Bad association, Filing case against deceased man, Charging sheet against the infant who has not been born yet, Enforcing disappearance, Suppressing the freedom of express, Violating Human rights, Doing anti-social activities such as rape, forcible extortion, drinking alcohol, etc. are the real scenario of Bangladesh Police. Policing ethics or related unethical behaviors, in particular, are shaped by both societal perceptions and organizational socialization of the police personnel on how authority should be exercised, as well as the latter's relationship with the socio-political and economic structures overtime. This paper proposes to explain the role of police as the main law enforcement agency in any democratic country. An Attempt has been made to bring different perspectives of ethics which comprises views of Aristotle, Machiavelli, Immanuel Kant, J S Mill and John Rawls. The paper focuses on police Ethics. Police ethics’ reflects the society and the regulations that shape the policing system. Discuss the results and analysis of the consequences of moral degradation caused by the Police. Explore the police brutality because of the lack of Ethics to highlight the public's attitude towards police. The ethical standards and the code of conduct Police practitioners should actually abide by is an ongoing debate. (shrink)

Current health care standards, in many countries, Australia included, are regrettably poor. Surprisingly, practitioners and treating teams alike in mental health and disability sectors, in particular, make far too many basic care-related mistakes, in addition to the already abundant diagnostic mistakes that cause and amplify great harm. In part, too many practitioners also fail to distinguish adverse effects for what they are and all too often treat adverse effects, instead, as comorbidities. Diagnostic failures are dangerous, the result of which generates (...) and perpetuates harms that are extremely costly in terms of patient welfare, in addition to the financial burden placed on everyone. In this essay, I contend that the authority bestowed upon psychiatry is misplaced. Subsequently, this misplaced authority affects the governing and investigatory institutions reliant and informed by psychiatry. The examination process undertaken in this investigation traces the metaphysics of psychiatric disorders relative to the Diagnostic-Statistical-Manual (DSM) in all its iterations and to the epistemological construction process that serves to underpin the fundamentals of psychiatric practice. There exists a crisis of confidence in psychiatric practice and I urge drastic reform be undertaken to arrest the damage. (shrink)

In The Ethics of Food, Gregory E. Pence brings together a collection of voices who share the view that the ethics of genetically modified food is among the most pressing societal questions of our time. This comprehensive collection addresses a broad range of subjects, including the meaning of food, moral analyses of vegetarianism and starvation, the safety and environmental risks of genetically modified food, issues of global food politics and the food industry, and the relationships among food, evolution, and human (...) history. (shrink)

Children who experience well-being are engaging more confidently and positively with their caregiver and peers, which helps them to profit more from available learning opportunities and support current and later life outcomes. The goodness-of-fit theory suggests that children’s well-being might be a result of the interplay between their temperament and the environment. However, there is a lack of studies that examined the association between children’s temperament and well-being in early childhood education and care, and whether this association is affected by (...) ECEC process quality. Using a multilevel random coefficient approach, this study examines the association between toddlers’ temperament and well-being in Norwegian ECEC and investigates whether process quality moderates this association. Results reveal an association between temperament and well-being. Staff-child conflict moderates the association between shyness and well-being, and between activity and well-being. Moreover, high emotional behavioral support moderates the association between activity and well-being. Extra attention should be paid by the staff to these children’s needs. (shrink)

There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED)”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa (...) opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On the other hand, it suggests that ordinary conscious experience might involve a minimal kind of self-awareness rooted in multisensory processing, which is what appears to fade away during DIED. (shrink)

The promises of nanotechnology have been framed by a variety of metaphors, that not only channel the attention of the public, orient the questions asked by researchers, and convey epistemic choices closely linked to ethical preferences. In particular, the image of the ‘therapeutic missile’ commonly used to present targeted drug delivery devices emphasizes precision, control, surveillance and efficiency. Such values are highly praised in the current context of crisis of pharmaceutical innovation where military metaphors foster a general mobilization of (...) resources from multiple fields of cutting-edge research. The missile metaphor, reminiscent of Paul Ehrlich’s ‘magic bullet’, has framed the problem in simple terms: how to deliver the right dose in the right place at the right moment? Chemists, physicists and engineers who design multi-functional devices operating in vitro can think in such terms, as long as the devices are not actually operating through the messy environment of the body. A close look at what has been done and what remains to be done suggests that the metaphor of the “therapeutic missile” is neither sufficient, nor even necessary. Recent developments in nanomedicine suggest that therapeutic efficacy cannot be obtained without negotiating with the biological milieu and taking advantage of what it affords. An ‘oikological’ approach seems more appropriate, more heuristic and more promising than the popular missile. It is based on the view of organism as an oikos that has to be carefully managed. The dispositions of nanocapsules have to be coupled with the affordances of the environment. As it requires dealing with nanoparticles as relational entities (defined by their potential for interactions) rather than as stable substances (defined by intrinsic properties) this metaphor eventually might well change research priorities in nanotechnology in general. (shrink)

Regulators rely on clinical trials for drug approval and labeling decisions. Health systems and clinicians rely on the evidence from trials to determine treatment, and patients rely on it to decide which courses of care to undertake. Many of these stakeholders presume that the careful review of individual studies is enough to address the ethical and scientific questions that arise in clinical trials. In what follows, however, we demonstrate that explicit consideration of trial portfolios—series of trials that are interrelated (...) by a common set of objectives—is crucial. the ethical acceptability and evidentiary probity of individual trials can change depending on the characteristics of the portfolios in which they are embedded. Second, how trial portfolios are composed, how well they are coordinated, and how efficiently they use information determines the balance of risks and benefits they present as well as their different prospects for generating socially valuable information; these three factors also raise distinct questions of justice. (shrink)

BackgroundThe U.S. Food and Drug Administration traditionally has kept confidential significant amounts of information relevant to the approval or non-approval of specific drugs, devices, and biologics and about the regulatory status of such medical products in FDA’s pipeline.ObjectiveTo develop practical recommendations for FDA to improve its transparency to the public that FDA could implement by rulemaking or other regulatory processes without further congressional authorization. These recommendations would build on the work of FDA’s Transparency Task Force in 2010.MethodsIn 2016-2017, we (...) convened a team of academic faculty from Harvard Medical School, Brigham and Women’s Hospital, Yale Medical School, Yale Law School, and Johns Hopkins Bloomberg School of Public Health to develop recommendations through an iterative process of reviewing FDA’s practices, considering the legal and policy constraints on FDA in expanding transparency, and obtaining insights from independent observers of FDA.ResultsThe team developed 18 specific recommendations for improving FDA’s transparency to the public. FDA could adopt all these recommendations without further congressional action.FundingThe development of the Blueprint for Transparency at the U.S. Food and Drug Administration was funded by the Laura and John Arnold Foundation. (shrink)

Pharmacogenetics is the study of inherited variations in drug response Pharmacogenetics uses the techniques of pharmacology, population genetics, biochemical genetics and, most recently, molecular biology, to study the biological basis for individual variation in therapeutic response and in the occurrence of adverse reactions to medications. Most pharmacogenetic experiments deal with inherited differences in drug metabolism. The discussion here will review inherited variation in the activity of thiopurine methyltransferase, an enzyme that catalyzes the methyl conjugation of an important group (...) of drugs, the thiopurines. (shrink)

Why are people interested in money? Specifically, what could be the biological basis for the extraordinary incentive and reinforcing power of money, which seems to be unique to the human species? We identify two ways in which a commodity which is of no biological significance in itself can become a strong motivator. The first is if it is used as a tool, and by a metaphorical extension this is often applied to money: it is used instrumentally, in order to obtain (...) biologically relevant incentives. Second, substances can be strong motivators because they imitate the action of natural incentives but do not produce the fitness gains for which those incentives are instinctively sought. The classic examples of this process are psychoactive drugs, but we argue that the drug concept can also be extended metaphorically to provide an account of money motivation. From a review of theoretical and empirical literature about money, we conclude that (i) there are a number of phenomena that cannot be accounted for by a pure Tool Theory of money motivation; (ii) supplementing Tool Theory with a Drug Theory enables the anomalous phenomena to be explained; and (iii) the human instincts that, according to a Drug Theory, money parasitizes include trading (derived from reciprocal altruism) and object play. (Published Online April 5 2006) Key Words: economic behaviour; evolutionary psychology; giving; incentive; money; motivation; play; reciprocal altruism. (shrink)

Over the last decade, philosophers of science have extensively criticized the epistemic superiority of randomized controlled trials for testing safety and effectiveness of new drugs, defending instead various forms of evidential pluralism. We argue that scientific methods in regulatory decision-making cannot be assessed in epistemic terms only: there are costs involved. Drawing on the legal distinction between rules and standards, we show that drug regulation based on evidential pluralism has much higher costs than our current RCT-based system. We analyze (...) these costs and advocate for evaluating any scheme for drug regulatory tests in terms of concrete empirical benchmarks, like the error rates of regulatory decisions. (shrink)

In this article, I examine children's reported experiences with stimulant drug treatments for attention deficit hyperactivity disorder in light of bioethical arguments about the potential threats of psychotropic drugs to authenticity and moral agency. Drawing on a study that involved over 150 families in the USA and the UK, I show that children are able to report threats to authenticity, but that the majority of children are not concerned with such threats. On balance, children report that stimulants improve their (...) capacity for moral agency, and they associate this capacity with an ability to meet normative expectations. I argue that although under certain conditions stimulant drug treatment may increase the risk of a threat to authenticity, there are ways to minimise this risk and to maximise the benefits of stimulant drug treatment. Medical professionals in particular should help children to flourish with stimulant drug treatments, in good and in bad conditions. (shrink)

In public health and the social sciences, there is growing recognition of the role that social context plays in determining health. Frequently, social relations of inequality are among the most important features of social context identified in this work, and emphasis is placed on identifying and addressing these inequalities in order to improve health. Within the field of HIV/AIDS prevention as well, researchers have begun to look beyond individuals for an understanding of the structural causes of HIV-related risk. This research (...) demands that greater attention be paid to the social mechanisms and contextual factors that lead to HIV risk. Among these factors are law and social policy, which form a part of the context in which risk-taking occurs and which can promote both HIV transmission and prevention. On the one hand, laws limiting access to sterile injection equipment have contributed to HIV-related risk behavioxs among injection drug users. (shrink)

This article critically examines current responses to multi-drug resistant tuberculosis and argues that bioethics needs to be willing to engage in a more radical critique of the problem than is currently offered. In particular, we need to focus not simply on market-driven models of innovation and anti-microbial solutions to emergent and re-emergent infections such as TB. The global community also needs to address poverty and the structural factors that entrench inequalities—thus moving beyond the orthodox medical/public health frame of reference.

The unprecedented outbreak of Ebola virus disease in West Africa has raised several novel ethical issues for global outbreak preparedness. It has also illustrated that familiar ethical issues in infectious disease management endure despite considerable efforts to understand and mitigate such issues in the wake of past outbreaks. To improve future global outbreak preparedness and response, we must examine these shortcomings and reflect upon the current state of ethical preparedness. To this end, we focus our efforts in this article on (...) the examination of one substantial area: ethical guidance in pandemic plans. We argue that, due in part to their focus on considerations arising specifically in relation to pandemics of influenza origin, pandemic plans and their existing ethical guidance are ill-equipped to anticipate and facilitate the navigation of unique ethical challenges that may arise in other infectious disease pandemics. We proceed by outlining three reasons why this is so, and situate our analysis in the context of the EVD outbreak and the threat posed by drug-resistant tuberculosis: different infectious diseases have distinct characteristics that challenge anticipated or existing modes of pandemic prevention, preparedness, response, and recovery, clear, transparent, context-specific ethical reasoning and justification within current influenza pandemic plans are lacking, and current plans neglect the context of how other significant pandemics may manifest. We conclude the article with several options for reflecting upon and ultimately addressing ethical issues that may emerge with different infectious disease pandemics. (shrink)

In the last decade, the organization of pharmaceutical research on neglected tropical diseases has undergone transformative change. In a context of perceived “market failure,” the development of new medicines is increasingly handled by public-private partnerships. This shift toward hybrid organizational models depends on a particular form of exchange: the sharing of proprietary assets in general and of intellectual property rights in particular. This article explores the paradoxical role of private property in this new configuration of global health research and development. (...) Rather than a tool to block potential competitors, proprietary assets function as a lever to attract others into risky collaborative ventures; instead of demarcating public and private domains, the sharing of property rights is used to increase the porosity of that boundary. This reimagination of the value of property is connected to the peculiar timescape of global health drug development, a promissory orientation to the future that takes its clearest form in the centrality of “virtual” business models and the proliferation of strategies of deferral. Drawing on the anthropological literature on inalienable possessions, we reconsider property’s traditional exclusionary role and discuss the possibility that the new pharmaceutical “commons” proclaimed by contemporary global health partnerships might be the precursor of future enclosures. (shrink)

The contributions of adolescent and parent perspectives to ethical planning of survey research on youth drug use and suicide behaviors are highlighted through an empirical examination of 322 7th-12th graders' and 160 parents' opinions on questions related to 4 ethical dimensions of survey research practice: evaluating research risks and benefits, establishing guardian permission requirements, developing confidentiality and disclosure policies, and using cash incentives for recruitment. Generational and ethnic variation in response to questionnaire items developed from discussions within adolescent and (...) parent focus groups are described. The article concludes with a discussion of the potential contributions and challenges of adolescent and parent perspectives for planning scientifically valid and ethically responsible youth risk survey research. (shrink)

Do terminally ill patients who have exhausted all other available, government-approved treatment options have a constitutional right to experimental treatment that may prolong their lives? On May 2, 2006, a divided panel of the U.S. Court of Appeals for the District of Columbia, in a startling opinion, Abigail Alliance for Better Access to Developmental Drugs v. Von Eschenbach, held “Yes.” The plaintiffs, Abigail Alliance for Better Access to Developmental Drugs and Washington Legal Foundation, sought to enjoin the Food and (...) class='Hi'>Drug Administration from refusing to allow the sale of investigational new drugs that had not yet received FDA approval. The terminally ill plaintiffs contended that they quite literally could not wait that long for the drugs. With no other treatment options available, the plaintiffs urged the court to recognize a fundamental, constitutional right to take potentially life-saving or life-prolonging drugs, even though the treatment had not been fully tested through human trials for safety and effectiveness and could not be legally marketed to the public. (shrink)

BackgroundThis study aimed to determine the elements and the extent of information that child participants and their parents would like to read in an informed assent form /informed consent form of a pediatric drug trial.MethodsA descriptive survey was conducted to determine the perceived importance of each element of the ICF content from child participants and their parents who underwent informed assent/consent of a multi-center pediatric drug trial. The respondents were asked to indicate the level of importance of each (...) item in a questionnaire, by giving a rating scale from 1 to 5.ResultsA total of 22 families, 17 child participants with the diagnosis of hematology or oncology diseases and 27 parents, were enrolled. Among 30 items, risk–benefit aspects were perceived to be of most concerning items from both child participants’ and parents’ viewpoint. None of the items were considered ‘slightly important’ or lower by more than 20% of the respondents.ConclusionsFor pediatric drug trials, risk–benefit information should be made a salient feature of an IAF/icf. This empirical data could help related stakeholders arrange essential information in order of importance and tailor an IAF/icf to better suit child participants’ and parents’ needs, particularly for pediatric drug trials involving children with the diagnosis of hematology or oncology diseases. (shrink)

Dramatic events involving dangerous microbes often focus attention on isolation and quarantine as policy instruments. The incident in May-June 2007 involving Andrew Speaker and drug-resistant tuberculosis joins other communicable disease crises that have forced contemplation or actual application of quarantine powers. Implementation of quarantine powers, which encompasses authority for both isolation and quarantine actions, is important not only for the handling of a specific event but also because the use of such authority provides a window on broader issues of (...) public health and the legal rules, ethical principles, and governance systems that support it. Debates about quarantine powers reflect political and social attitudes about public health that often tell us more about this policy endeavor than acts of isolation and quarantine themselves. (shrink)

Objective: The dopamine hypothesis is one of the most influential theories of the neurobiological background of schizophrenia (SCZ). However, direct evidence for abnormal dopamine-related subcortical-cortical circuitry disconnectivity is still lacking. The aim of this study was therefore to test dopamine-related substantia nigra (SN)-based striato-thalamo-cortical resting-state functional connectivity (FC) in SCZ. Method: Based on our a priori hypothesis, we analyzed a large sample resting-state functional magnetic resonance imaging (fMRI) dataset from first-episode drug-naïve SCZ patients (n = 112) and healthy controls (...) (n = 82) using the SN as the seed region for an investigation of striato-thalamo-cortical FC. This was done in the standard band of slow frequency oscillations and then in its subfrequency bands (Slow4 and Slow5). Results: The analysis showed in SCZ: (1) reciprocal functional hypo-connectivity between SN and striatum, with differential patterns for Slow5 and Slow4; (2) functional hypo-connectivity between striatum and thalamus, as well as functional hyper-connectivity between thalamus and sensorimotor cortical areas, specifically in Slow4; (3) correlation of thalamo-sensorimotor functional hyper-connectivity with psychopathological symptoms. Conclusions: We demonstrate abnormal dopamine-related SN-based striato-thalamo-cortical FC in slow frequency oscillations in first-episode drug-naive SCZ. This suggests that altered dopaminergic function in the SN leads to abnormal neuronal synchronization (as indexed by FC) within subcortical-cortical circuitry, complementing the dopamine hypothesis in SCZ on the regional level of resting-state activity. (shrink)

The U.S. Food and Drug Administration (FDA) announced recently that food products derived from some animal clones and their offspring are safe for human consumption. In response to criticism that it had failed to engage with ethical, social, and economic concerns raised by livestock cloning, the FDA argued that addressing normative issues prior to issuing a final ruling on animal cloning is not part of its mission. In this article, the authors reject the FDA's claim that its mission to (...) protect and advance public health can be accomplished without considering ethical issues or without making value judgments. The authors offer two arguments in support of their position. First, the agency's mission statement presupposes significant normative commitments and judgments. Second, the FDA's risk assessment of food products from cloned animals and their offspring is itself clearly shaped by a variety of normative commitments. (shrink)

Gliomas are diffuse and invasive brain tumors with the nefarious ability to evade even seemingly draconian treatment measures. Here we introduce a simple mathematical model for drug delivery of chemotherapeutic agents to treat such a tumor. The model predicts that heterogeneity in drug delivery related to variability in vascular density throughout the brain results in an apparent tumor reduction based on imaging studies despite continual spread beyond the resolution of the imaging modality. We discuss a clinical example for (...) which the model-predicted scenario is relevant. The analysis and results suggest an explanation for the clinical problem of the long-standing confounding observation of shrinkage of the lesion in certain areas of the brain with continued growth in other areas. (shrink)

Introducción: Se presenta un análisis cualitativo del acompañamiento psicosocial a jóvenes en condiciones de vulnerabilidad desde la ecología humana durante 12 meses entre 2010 a 2011; utilizando técnicas pedagógicas evaluativas participativas. Éstas, son una alternativa para crear espacios reflexivos con el propósito de potenciar la resiliencia en las relaciones comunicativas y formar en el respeto. Objetivo: Generar bienestar, prevenir la farmacodependencia y contribuir a la promoción de la salud. Material y Métodos: Se revisaron los antecedentes temáticos, fueron seleccionados 100 estudiantes (...) entre 11 y 19 años de dos instituciones educativas públicas en condiciones vulnerables;se desarrollaron cuatro talleres reflexivos y cuatro prácticas lúdicas y se realizaron tres grupos focales con estudiantes, profesores y padres de familia. Resultados y Discusión: El contexto social de la población intervenida, revela problemas de abuso sexual, violencia intrafamiliar y eventos violentos en el vecindario por grupos armados ilegales, entre otros, que constituyen factores de riesgo importantes para la farmacodependencia. Conclusión: Se infiere que lo psicosocial incide en la farmacodependencia, afectando la convivencia de la población estudiada por múltiples causas del orden psicoafectivo, sociocultural, económico y político que van desde el consumo cultural hasta la seguridad alimentaria. Introduction: A qualitative analysis of the psycho-social support to young people in situations of vulnerability from human ecology is presented for 12 months between 2010 to 2011; using participatory evaluative pedagogical techniques. These are an alternative to create reflective spaces with the purpose of enhancing resilience in communicative relationships and working in respect. Objective: to generate well-being, prevent drug abuse and contribute to the health promotion. Material aids and methods: the thematic background was reviewed, 100 students between 11 and 19 years of two public schools in vulnerable conditionswere selected; four reflective workshops and four playful practices were developed and three focus groups with students, teachers and parentswere conducted. Results and discussion: the social context of the manipulated population reveals sexual abuse problems, domestic violence and violent events in the neighborhood by illegal armed groups, among others, which constitutemajor risk factors for drug abuse. Conclusion: It can be inferred that the psychosocial factors impact on drug dependence, affecting the coexistence of the population studied by multiple causes of the psychological, socio-cultural, economic and political order, ranging from cultural consumption to food security. (shrink)