Political legitimacy in decisions about experiments in solar radiation management

Some types of solar radiation management (SRM) research are ethically problematic because they expose persons, animals, and ecosystems to significant risks. In our earlier work, we argued for ethical norms for SRM research based on norms for biomedical research. Biomedical researchers may not conduct research on persons without their consent, but universal consent is impractical for SRM research. We argue that instead of requiring universal consent, ethical norms for SRM research require only political legitimacy in decision-making about global SRM trials. Using Allen Buchanan & Robert Keohane's model of global political legitimacy, we examine several existing global institutions as possible analogues for a politically legitimate SRM decision-making body

Effects of parietal lesions in humans on color and location priming

To determine whether the parietal lobes contribute to the selection of nonspatial features known to be processed in the ventral stream, the current study examined the effect of chronic unilateral parietal lobe lesions in humans on color and location priming. Patients and normal controls performed a go/no-go color discrimination task in which either the same color and different color pairs of stimuli (prime and probe) were projected sequentially either in the same hemifield or in opposite hemifields. Control subjects and patients both showed independent effects of color and location priming. In the patients, primes in either field produced color priming for target probes in the ipsilesional field but not for probes in the contralesional field. This observation implicates the parietal cortex in processing activated codes of stimulus attributes not only for spatial information but also for visual features processed in the ventral visual pathways

A Forty-Year-Old Woman with a History of Psychosis and a Seizure Disorder

In this issue of the Journal, we are introducing a new section. the Interdisciplinary Case Conference. Our goal will be to present psychiatric patients in whom pathology is demonstrable not only by interview, but also by physical examination,laboratory studies. and radiographic imaging techniques

Petition for a Writ of Certiorari. Sandifer v. United States Steel Corp., 134 S. Ct. 870 (2014) (No. 12-417), 2012 U.S. S. Ct. Briefs LEXIS 4304

QUESTIONS PRESENTED Under the Fair Labor Standards Act, the period of time during which a covered employee must be paid begins when the worker engages in a principal activity. Donning and doffing safety gear (including protective clothing) required by the employer is a principal activity when it is an integral and indispensable part of the activities for which the worker is employed. Such requirements are common in manufacturing firms. However, under section 203(o) of the Act an employer need not compensate a worker for time spent in “changing clothes” (even if it is a principal activity) if that time is expressly excluded from compensable time under a bona fide collective bargaining agreement applicable to that worker. The interrelated questions presented are: (1) What constitutes “changing clothes” within the meaning of section 203(o)? (2) If a worker’s actions are a principal activity but fall within the scope of the section 203(o) exemption, do those actions nonetheless commence the period of time during which (aside from the clothes-changing time) the worker must be compensated? (3) If a worker engages in a principal activity which is not exempted by section 203(o), but which involves only a de minimis amount of time, does the activity nonetheless commence the period of time during which the worker must be compensated

Cleft palate, Retrognathia and Congenital Heart Disease in Velo-Cardio-Facial Syndrome: A Phenotype Correlation Study

Objective: Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion of approximately 40 genes from one copy of chromosome 22. Expression of the syndrome is a variable combination of over 190 phenotypic characteristics. As of yet, little is known about how these phenotypes correlate with one another or whether there are predictable patterns of expression. Two of the most common phenotypic categories, congenital heart disease and cleft palate, have been proposed to have a common genetic relationship to the deleted T-box 1 gene (TBX1). The purpose of this study is to determine if congenital heart disease and cleft palate are correlated in a large cohort of human subjects with VCFS. Methods: This study is a retrospective chart review including 316 Caucasian non-Hispanic subjects with FISH or CGH microarray confirmed chromosome 22q11.2 deletions. All subjects were evaluated by the interdisciplinary team at the Velo-Cardio-Facial Syndrome International Center at Upstate Medical University, Syracuse, NY. Each combination of congenital heart disease, cleft palates, and retrognathia was analyzed by Chi square or Fisher exact test. Results: For all categories of congenital heart disease and cleft palate or retrognathia no significant associations were found, with the exception of submucous cleft palate and retrognathia (nominal p = 0.0325) and occult submucous cleft palate and retrognathia (nominal p = 0.000013). Conclusions: Congenital heart disease and cleft palate do not appear to be correlated in human subjects with VCFS despite earlier suggestions from animal models. Possible explanations include modification of the effect of TBX1 by genes outside of the 22q11.2 region that may further influence the formation of the palate or heart, or the presence of epigenetic factors that may effect genes within the deleted region, modifying genes elsewhere, or polymorphisms on the normal copy of chromosome 22. Lastly, it is possible that TBX1 plays a role in palate formation in some species, but not in humans. In VCFS, retrognathia is caused by an obtuse angulation of the skull base. It is unknown if the correlation between retrognathia and cleft palate in VCFS indicates a developmental sequence related to skull morphology, or direct gene effects of both anomalies. Much work remains to be done to fully understand the complex relationships between phenotypic characteristics in VCFS

Parmodulins Inhibit Thrombus Formation Without Inducing Endothelial Injury Caused by Vorapaxar

Protease-activated receptor-1 (PAR1) couples the coagulation cascade to platelet activation during myocardial infarction and to endothelial inflammation during sepsis. This receptor demonstrates marked signaling bias. Its activation by thrombin stimulates prothrombotic and proinflammatory signaling, whereas its activation by activated protein C (APC) stimulates cytoprotective and antiinflammatory signaling. A challenge in developing PAR1-targeted therapies is to inhibit detrimental signaling while sparing beneficial pathways. We now characterize a novel class of structurally unrelated small-molecule PAR1 antagonists, termed parmodulins, and compare the activity of these compounds to previously characterized compounds that act at the PAR1 ligand–binding site. We find that parmodulins target the cytoplasmic face of PAR1 without modifying the ligand-binding site, blocking signaling through Gαq but not Gα13 in vitro and thrombus formation in vivo. In endothelium, parmodulins inhibit prothrombotic and proinflammatory signaling without blocking APC-mediated pathways or inducing endothelial injury. In contrast, orthosteric PAR1 antagonists such as vorapaxar inhibit all signaling downstream of PAR1. Furthermore, exposure of endothelial cells to nanomolar concentrations of vorapaxar induces endothelial cell barrier dysfunction and apoptosis. These studies demonstrate how functionally selective antagonism can be achieved by targeting the cytoplasmic face of a G-protein–coupled receptor to selectively block pathologic signaling while preserving cytoprotective pathways

A realist synthesis of randomised control trials involving use of community health workers for delivering child health interventions in low and middle income countries

<p>Abstract</p> <p>Background</p> <p>A key constraint to saturating coverage of interventions for reducing the burden of childhood illnesses in Low and Middle Income Countries (LMIC) is the lack of human resources. Community health workers (CHW) are potentially important actors in bridging this gap. Evidence exists on effectiveness of CHW in management of some childhood illnesses (IMCI). However, we need to know how and when this comes to be. We examine evidence from randomized control trials (RCT) on CHW interventions in IMCI in LMIC from a realist perspective with the aim to see if they can yield insight into the working of the interventions, when examined from a different perspective.</p> <p>Methods</p> <p>The realist approach involves educing the mechanisms through which an intervention produced an outcome in a particular context. 'Mechanisms' are reactions, triggered by the interaction of the intervention and a certain context, which lead to change. These are often only implicit and are actually hypothesized by the reviewer. This review is limited to unravelling these from the RCTs; it is thus a hypothesis generating exercise.</p> <p>Results</p> <p>Interventions to improve CHW performance included 'Skills based training of CHW', 'Supervision and referral support from public health services', 'Positioning of CHW in the community'. When interventions were applied in context of CHW programs embedded in local health services, with beneficiaries who valued services and had unmet needs, the interventions worked if following mechanisms were triggered: anticipation of being valued by the community; perception of improvement in social status; sense of relatedness with beneficiaries and public services; increase in self esteem; sense of self efficacy and enactive mastery of tasks; sense of credibility, legitimacy and assurance that there was a system for back-up support. Studies also showed that if context differed, even with similar interventions, negative mechanisms could be triggered, compromising CHW performance.</p> <p>Conclusion</p> <p>The aim of this review was to explore if RCTs could yield insight into the working of the interventions, when examined from a different, a realist perspective. We found that RCTs did yield some insight, but the hypotheses generated were very general and not well refined. These hypotheses need to be tested and refined in further studies.</p