Participants in clinical research sometimes view participation as therapy or exaggerate potential benefits, especially in phase I or phase II trials. We conducted this study to discover what methods might improve cancer patients’ understanding of early-phase clinical trials. We randomly assigned 130 cancer patients from three U.S. medical centers who were considering enrollment in a phase I or phase II cancer trial to receive either a multimedia intervention or a National Cancer Institute pamphlet explaining the trial and its purpose. Intervention (...) participants were 32 times more likely to believe that the trial’s purpose was to examine safety and 60 % less likely to believe they would experience long-term benefit or cure. There was no difference in enrollment decision. However, while patients’ understanding of the trial’s purpose improved and expectations of long-term benefit diminished, half the respondents still believed they would experience long-term benefit or cure from participation. Therefore, we conclude that multimedia interventions such as this one may help oncologists to explain the risks and benefits of early-phase cancer trials in a way that patients can more easily understand, helping them to make more informed decisions about participation. But further research into other factors that influence patients’ beliefs about the outcome of enrollment is needed, both to modify the interventions and to determine how malleable patient beliefs are. (shrink)

Substantial evidence implicates fast axonal transport (FAT) defects in neurodegeneration. In Alzheimer's disease (AD), it is controversial whether transport defects cause or arise from amyloid‐β (Aβ)‐induced toxicity. Using a novel, unbiased genetic screen, Morihara et al. identified kinesin light chain‐1 splice variant E (KLC1vE) as a modifier of Aβ accumulation. Here, we propose three mechanisms to explain this causal role. First, KLC1vE reduces APP transport, leading to Aβ accumulation. Second, reduced transport of APP by KLC1vE triggers an ER stress response (...) that activates the amyloidogenic pathway. Third, KLC1vE impairs transport of other KLC1 cargos that regulate amyloidogenesis, promoting Aβ retention within the secretory pathway. Collectively, KLC1vE perpetuates a vicious cycle of Aβ generation, kinase dysregulation, and global FAT impairment that inevitably leads to cellular toxicity. These concepts implicate alternative splicing of KLC1 in AD and suggest that the reciprocal influence of transport mechanisms on disease states contributes to neurodegeneration. (shrink)

ObjectivePhysical isolation measures, known as lockdown or shelter-in-place, experienced during coronavirus disease 2019 have the potential to cause psychological distress. This study was conducted to examine parents’ perceived stress and whether reports of rewards and challenges during lockdown impact stress.MethodsData were collected using a cross-sectional online survey in New South Wales, Australia, across the 4-week lockdown. The survey was completed by 158 parents of children aged under 6 years. Stress was measured using the short form of the Perceived Stress Scale. (...) Rewards and challenges were reported in response to two open-ended questions.ResultsThere was a weak negative correlation between PSS-4 scores and days in isolation, with parents who had spent longer in isolation reporting fewer stress symptoms. The relationship between time in isolation and stress was moderated by the degree to which parents described more rewards than challenges: parents who perceived high rewards and low challenges reported lower PSS-4 scores with more days in lockdown, whereas parents who perceived low rewards and high challenges reported higher PSS-4 scores with more days in lockdown. The moderation model examining associations between time in isolation and rewards ratio explained 13% of the variance in PSS-4 scores.ConclusionLockdowns are not uniformly or consistently negative experiences for parents. Identifying positive aspects of the experience may serve to buffer negative mental health risks across time. Understanding resilience strategies is critical for supporting current psychological wellbeing and to adequately prepare for future pandemic experiences. (shrink)

Higher education is starting to embrace its role in promoting student wellbeing and life skills, especially given the concerning levels of poor mental health and uncertainties in the future job market. Yet, many of the published studies evaluating positive educational teaching methods thus far are limited to interventions delivered to small student cohorts and/or imbedded within elective wellbeing courses, and are focussed on developed Western countries. This study addressed this gap by investigating the effectiveness of an institution-wide compulsory course informed (...) by the principles of Seligman’s Wellbeing Theory. The course was delivered at a British university in a developing country in Southeast Asia. It purposefully sought to nurture growth-oriented outcomes and was taken by an entire cohort of year one undergraduate students. We tested the effectiveness of the curriculum content and staff coaching style in achieving life skills, and evaluated how these perceptions influenced students’ subjective wellbeing. A convergent mixed-methods design was used with 350 survey respondents and 11 interviewees. Perceived life skills scores showed a 2.5% improvement at the end of the course. Partial Least Squares Structural Equation Modelling tested the predicted relationships between variables. All relationships were statistically significant, but the influence of course design and educators’ style on life skills acquisition was moderate, while the effect on subjective happiness and life satisfaction was very weak. Qualitative data indicated that while quantifiable benefits to wellbeing might not be immediate, students did anticipate longer-term benefits for happiness and life satisfaction. This finding suggests that such a novel educational approach is well-received by Asian students and may sow the seeds for future benefit by positively impacting on their skills, behaviours, attitudes, and values. To achieve optimal flourishing at university, we recommend exploring teaching practises that combine positive education with coaching psychology practises. (shrink)

With lost credibility, ratings, and circulation, journalism faces a crisis of conscience. One answer is participatory community journalism; journalists become activists on behalfofthe process of self-government. A veteran journalist and author of Agents of Power, Altschull questions the press's arrogance, its faith in objectivity, and its unvarying insistence on its First Amendment rights, and asks instead that the public interest be put ahead of the maximization of profit, that media help to mediate public issues, and that the public be allowed (...) to play a bigger role in the news decision making process. (shrink)

Individuals higher on avoidant coping may remember fewer specific autobiographical memories and more nonspecific memories on the Autobiographical Memory Test in order to protect themselves from the painful emotions accompanying some specific memories. Habitually remembering this way may be a risk factor for depression. In Studies 1 and 2, avoidant coping was associated with more specific memories and fewer overgeneral memories, at odds with the functional avoidance view. In Study 3, there were no significant relationships between AMT indices and avoidant (...) coping. Results are discussed in light of ironic process theory. (shrink)

What sets off the termination of analysis and psychodynamic therapy from the variety of endings that enter into all human relationships? So asks Herbert J. Schlesinger in _Endings and Beginnings: On Terminating Psychotherapy and Psychoanalysis_, a work of remarkable clarity, conceptual rigor, and ingratiating readability. Schlesinger situates termination - which he understands, variously, as a phase of treatment, a treatment process, and a state of mind - within the family of "beginnings and endings" that permeate one another throughout the (...) course of therapy. For Schlesinger, therapeutic endings cannot be aligned with the final phase of treatment; ending-phase phenomena are ongoing accompaniments of therapeutic work. They occur whenever patients achieve some portion of their treatment goals and supervene when therapy stagnates. Small wonder that an assessment of the patient's relationship to time and capacity to end therapy are key aspects of diagnostic evaluation. By linking beginning and ending phases not to the chronology of treatment but to the patient’s experience of it, Schlesinger brings revivifying insight to a host of psychodynamic concepts. Nor does he shy away from a trenchant critique of the instrumental “medical model” of psychiatric and psychotherapeutic training, which militates against the therapeutic exploration of treatment endings. Schlesinger's exemplification of how to begin treatment from the point of view of ending; his sensitive delineation of the mid-treatment "ending" crises characteristic of "vulnerable patients"; his richly woven case vignettes illustrating various "ending" contingencies and permutations - these inquiries are gems of pragmatic clinical wisdom. _Endings and Beginnings_ distills lessons learned over the course of a half century of practicing, teaching, and supervising psychotherapy and psychoanalysis and is a gift to the profession. (shrink)

Considering that getting along in civil society is based on the expectation that people will do what they say they will do, i.e., essentially live up to their explicit or implicit promises, it is amazing that so little scientific attention has been given to the act of promising. A great deal of research has been done on the moral development of children, for example, but not on the child’s ability to make and keep a promise, one of the highest moral (...) achievements. What makes it possible developmentally, cognitively, and emotionally to make a promise in the first place? And on the other hand, what compels one to keep a promise when there seems to be no personal advantage in doing so, and even when harm can be predicted? How do we know when a promise is offered seriously to be taken at face value, and how do we understand that another is only a polite gesture, not to be taken seriously? In _Promises, Oaths, and Vows: On the Psychology of Promising_, Herbert Schlesinger addresses these questions, drawing on the literature of moral development in children; the psychotherapy of a patient who regularly broke promises that were unnecessary in the first place; those who were regarded as "promising youngsters" who did not fulfill their "promise"; and those who feared making a promise, a commitment, or a threat out of fear that, once made, the utterance would take on a life of its own and could never be taken back. Furthermore, he illustrates his conclusions by examining the widespread use of promising in classical literature, such as Greek drama and the plays of Shakespeare, as well as the motivating and reifying power of the promise in Western religious traditions. With a style honed over the penning of two previous books, Schlesinger once again produces a work grounded in a firm analytic sensibility, but which also retains the wit and candor of the seasoned analyst. His seminal investigation of this all but neglected topic in the clinical literature is as timely as it is scholarly, and – with the title firmly in mind – _Promises, Oaths, and Vows_ is assured to be a worthy addition to any clinician’s library and a provoking investigation into Nietzsche’s notion of man as "the animal who makes promises.". (shrink)

The participation of vulnerable patients in clinical research poses apparent ethical dilemmas. Depending on the nature of the vulnerability, their participation may challenge the ethical principles of autonomy, non-maleficence, or justice. On the other hand, non-participation may preclude the building of a knowledge base that is a prerequisite for defining the optimal clinical management of vulnerable patients. Such clinical uncertainty may also incur substantial economic costs. We present the participation of pre-menopausal women with atrial fibrillation in trials of novel oral (...) anticoagulant drugs as a case study. Due to their non-participation in pivotal trials, it is uncertain whether for them, the risks that are associated with these drugs are outweighed by the advantages compared with conventional treatment. We addressed the question whether research of this new class of drugs in this subgroup would be appropriate from both, an ethical as well an economic perspective. We used the method of specifying norms as a wider framework to resolve the apparent ethical dilemma, while incorporating the question whether research of oral anticoagulants in premenopausal women with atrial fibrillation can be justified on economic grounds. For the latter, the results of a value-of-information analysis were used. Further clinical research on NOACs in premenopausal women with atrial fibrillation can be justified on both, ethical and economic grounds. Addressing apparent ethical dilemmas by invoking a method such as specifying norms can improve the quality of public practical reasoning. As such, the method should also prove valuable to committees that have formally been granted the authority to review trial protocols and proposals for scientific research. (shrink)

Evidence is summarized which indicates that the DNA loop anchoring proteins in chromosomes are effectively heterodimers that stack and are fastened into a bilaterally symmetrical array along the chromonemal axis. The evidence consists primarily of the observations made twenty five to thirty years ago on the pattern of sister chromatid exchanges and the way the DNA chains are sorted in the formation of diplochromosomes in cells that have undergone endoreduplication. The evidence indicates that each chain of DNA in the single (...) duplex, which is assumed to run the length of a chromosome, is anchored to a bilaterally symmetrical axis of heterodimers that sort the two original chains among the four derived chromatids of each diplochromosome in a very precise way. These observations are considered in the context of investigations on the nature of scaffold proteins and the loop anchorage sequences, as well as the advances being made on the nature of DNA binding proteins and the roles of topoisomerase II. (shrink)

In this paper certain basic assumptions about causation will be made explicit and then an attempt will be made to show, on the basis of those assumptions, that causation must be supplemented by an extra-causal operation of a selective nature. It is hoped that our assumptions will have in their own right a certain general acceptability, but since assumptions or “postulate sets”, whether antecedently acceptable or not are usually chosen for the purpose of proving something already deemed desirable, a word (...) should be said as to why it was thought desirable to argue for selectivity. (shrink)

Multiple accounts of how theories of human psychology and of image-making influenced each other in a decisive period in the history of philosophy and art.