Pessimistic outcome expectancy does not explain ambiguity aversion in decision-making under uncertainty.

When faced with a decision, most people like to know the odds and prefer to avoid ambiguity. It has been suggested that this aversion to ambiguity is linked to people's assumption of worst possible outcomes. We used two closely linked behavioural tasks in 78 healthy participants to investigate whether such pessimistic prior beliefs can explain ambiguity aversion. In the risk-taking task, participants had to decide whether or not they place a bet, while in the beliefs task, participants were asked what they believed would be the outcome. Unexpectedly, we found that in the beliefs task, participants were not overly pessimistic about the outcome in the ambiguity condition and in fact closer to optimal levels of decision-making than in the risk conditions. While individual differences in pessimism could explain outcome expectancy, they had no effect on ambiguity aversion. Consequently, ambiguity aversion is more likely caused by general caution than by expectation of negative outcomes despite pessimism-dependent subjective weighting of probabilities

Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.

BACKGROUND: Appropriately formulated quantitative computational models can support researchers in understanding the dynamic behaviour of biological pathways and support hypothesis formulation and selection by "in silico" experimentation. An obstacle to widespread adoption of this approach is the requirement to formulate a biological pathway as machine executable computer code. We have recently proposed a novel, biologically intuitive, narrative-style modelling language for biologists to formulate the pathway which is then automatically translated into an executable format and is, thus, usable for analysis via existing simulation techniques. RESULTS: Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales. CONCLUSION: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself

Do Interventions Designed to Support Shared Decision-Making Reduce Health Inequalities? : A Systematic Review and Meta-Analysis

Copyright: © 2014 Durand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Increasing patient engagement in healthcare has become a health policy priority. However, there has been concern that promoting supported shared decision-making could increase health inequalities. Objective: To evaluate the impact of SDM interventions on disadvantaged groups and health inequalities. Design: Systematic review and meta-analysis of randomised controlled trials and observational studies.Peer reviewe

Groups without cultured representatives dominate eukaryotic picophytoplankton in the oligotrophic South East Pacific Ocean

Background: Photosynthetic picoeukaryotes (PPE) with a cell size less than 3 µm play a critical role in oceanic primary production. In recent years, the composition of marine picoeukaryote communities has been intensively investigated by molecular approaches, but their photosynthetic fraction remains poorly characterized. This is largely because the classical approach that relies on constructing 18S rRNA gene clone libraries from filtered seawater samples using universal eukaryotic primers is heavily biased toward heterotrophs, especially alveolates and stramenopiles, despite the fact that autotrophic cells in general outnumber heterotrophic ones in the euphotic zone. Methodology/Principal Findings: In order to better assess the composition of the eukaryotic picophytoplankton in the South East Pacific Ocean, encompassing the most oligotrophic oceanic regions on earth, we used a novel approach based on flow cytometry sorting followed by construction of 18S rRNA gene clone libraries. This strategy dramatically increased the recovery of sequences from putative autotrophic groups. The composition of the PPE community appeared highly variable both vertically down the water column and horizontally across the South East Pacific Ocean. In the central gyre, uncultivated lineages dominated: a recently discovered clade of Prasinophyceae (IX), clades of marine Chrysophyceae and Haptophyta, the latter division containing a potentially new class besides Prymnesiophyceae and Pavlophyceae. In contrast, on the edge of the gyre and in the coastal Chilean upwelling, groups with cultivated representatives (Prasinophyceae clade VII and Mamiellales) dominated. Conclusions/Significance: Our data demonstrate that a very large fraction of the eukaryotic picophytoplankton still escapes cultivation. The use of flow cytometry sorting should prove very useful to better characterize specific plankton populations by molecular approaches such as gene cloning or metagenomics, and also to obtain into culture strains representative of these novel groups

Observational study of lenalidomide in patients with mantle cell lymphoma who relapsed/progressed after or were refractory/intolerant to ibrutinib (MCL-004).

BACKGROUND: The observational MCL-004 study evaluated outcomes in patients with relapsed/refractory mantle cell lymphoma who received lenalidomide-based therapy after ibrutinib failure or intolerance. METHODS: The primary endpoint was investigator-assessed overall response rate based on the 2007 International Working Group criteria. RESULTS: Of 58 enrolled patients (median age, 71 years; range, 50-89), 13 received lenalidomide monotherapy, 11 lenalidomide plus rituximab, and 34 lenalidomide plus other treatment. Most patients (88%) had received ≥ 3 prior therapies (median 4; range, 1-13). Median time from last dose of ibrutinib to the start of lenalidomide was 1.3 weeks (range, 0.1-21.7); 45% of patients had partial responses or better to prior ibrutinib. Primary reasons for ibrutinib discontinuation were lack of efficacy (88%) and ibrutinib toxicity (9%). After a median of two cycles (range, 0-11) of lenalidomide-based treatment, 17 patients responded (8 complete responses, 9 partial responses), for a 29% overall response rate (95% confidence interval, 18-43%) and a median duration of response of 20 weeks (95% confidence interval, 2.9 to not available). Overall response rate to lenalidomide-based therapy was similar for patients with relapsed/progressive disease after previous response to ibrutinib (i.e., ≥PR) versus ibrutinib-refractory (i.e., ≤SD) patients (30 versus 32%, respectively). The most common all-grade treatment-emergent adverse events after lenalidomide-containing therapy (n = 58) were fatigue (38%) and cough, dizziness, dyspnea, nausea, and peripheral edema (19% each). At data cutoff, 28 patients have died, primarily due to mantle cell lymphoma. CONCLUSION: Lenalidomide-based treatment showed clinical activity, with no unexpected toxicities, in patients with relapsed/refractory mantle cell lymphoma who previously failed ibrutinib therapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02341781 . Date of registration: January 14, 2015

Design of the Advance Directives Cohort: a study of end-of-life decision-making focusing on Advance Directives

<p>Abstract</p> <p>Background</p> <p>ADs are documents in which one can state one's preferences concerning end-of-life care, aimed at making someone's wishes known in situations where he/she is not able to do so in another manner. There is still a lot unclear about ADs. We designed a study aimed at investigating the whole process from the formulating of an AD to its actual use at the end of life.</p> <p>Methods/Design</p> <p>The study has mixed methods: it's longitudinal, consisting of a quantitative cohort-study which provides a framework for predominantly qualitative sub-studies. The members of the cohort are persons owning an AD, recruited through two Dutch associations who provide the most common standard ADs in the Netherlands, the NVVE (Right to Die-NL), of which 5561 members participate, and the NPV (Dutch Patient Organisation), of which 1263 members participate. Both groups were compared to a sample of the Dutch general public. NVVE-respondents are more often single, higher educated and non-religious, while amongst NPV-respondents there are more Protestants compared to the Dutch public. They are sent a questionnaire every 1,5 year with a follow-up of at least 7,5 years. The response rate after the second round was 88% respectively 90% for the NVVE and NPV. Participants were asked if we were allowed to approach close-ones after their possible death in the future. In this way we can get insight in the actual use of ADs at the end of life, also by comparing our data to that from the Longitudinal Aging Study Amsterdam, whose respondents generally do not have an AD.</p> <p>Discussion</p> <p>The cohort is representative for people with an AD as is required to study the main research questions. The longitudinal nature of the study as well as the use of qualitative methods makes it has a broad scope, focusing on the whole course of decision-making involving ADs. It is possible to compare the end of life between patients with and without an AD with the use of data from another cohort.</p

Family Influences on the Long Term Post-Disaster Recovery of Puerto Rican Youth

This study focused on characteristics of the family environment that may mediate the relationship between disaster exposure and the presence of symptoms that met DSM-IV diagnostic criteria for symptom count and duration for an internalizing disorder in children and youth. We also explored how parental history of mental health problems may moderate this meditational model. Approximately 18 months after Hurricane Georges hit Puerto Rico in 1998, participants were randomly selected based on a probability household sample using 1990 US Census block groups. Caregivers and children (N=1,886 dyads) were interviewed with the Diagnostic Interview Schedule for Children and other questionnaires in Spanish. Areas of the family environment assessed include parent-child relationship quality, parent-child involvement, parental monitoring, discipline, parents’ relationship quality and parental mental health. SEM models were estimated for parents and children, and by age group. For children (4–10 years old), parenting variables were related to internalizing psychopathology, but did not mediate the exposure-psychopathology relationship. Exposure had a direct relationship to internalizing psychopathology. For youth (11–17 years old), some parenting variables attenuated the relation between exposure and internalizing psychopathology. Family environment factors may play a mediational role in psychopathology post-disaster among youth, compared to an additive role for children. Hurricane exposure had a significant relation to family environment for families without parental history of mental health problems, but no influence for families with a parental history of mental health problems

Host-Species Transferrin Receptor 1 Orthologs Are Cellular Receptors for Nonpathogenic New World Clade B Arenaviruses

The ability of a New World (NW) clade B arenavirus to enter cells using human transferrin receptor 1 (TfR1) strictly correlates with its ability to cause hemorrhagic fever. Amapari (AMAV) and Tacaribe (TCRV), two nonpathogenic NW clade B arenaviruses that do not use human TfR1, are closely related to the NW arenaviruses that cause hemorrhagic fevers. Here we show that pseudotyped viruses bearing the surface glycoprotein (GP) of AMAV or TCRV can infect cells using the TfR1 orthologs of several mammalian species, including those of their respective natural hosts, the small rodent Neacomys spinosus and the fruit bat Artibeus jamaicensis. Mutation of one residue in human TfR1 makes it a functional receptor for TCRV, and mutation of four residues makes it a functional receptor for AMAV. Our data support an in vivo role for TfR1 in the replication of most, if not all, NW clade B arenaviruses, and suggest that with modest changes in their GPs the nonpathogenic arenaviruses could use human TfR1 and emerge as human pathogens

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death