The IPCC AR5 guidance note on consistent treatment of uncertainties: A common approach across the working groups

Evaluation and communication of the relative degree of certainty in assessment findings are key cross-cutting issues for the three Working Groups of the Intergovernmental Panel on Climate Change. A goal for the Fifth Assessment Report, which is currently under development, is the application of a common framework with associated calibrated uncertainty language that can be used to characterize findings of the assessment process. A guidance note for authors of the Fifth Assessment Report has been developed that describes this common approach and language, building upon the guidance employed in past Assessment Reports. Here, we introduce the main features of this guidance note, with a focus on how it has been designed for use by author teams. We also provide perspectives on considerations and challenges relevant to the application of this guidance in the contribution of each Working Group to the Fifth Assessment Report. Despite the wide spectrum of disciplines encompassed by the three Working Groups, we expect that the framework of the new uncertainties guidance will enable consistent communication of the degree of certainty in their policy-relevant assessment findings

Bayesian estimation of genetic parameters for multivariate threshold and continuous phenotypes and molecular genetic data in simulated horse populations using Gibbs sampling

<p>Abstract</p> <p>Background</p> <p>Requirements for successful implementation of multivariate animal threshold models including phenotypic and genotypic information are not known yet. Here simulated horse data were used to investigate the properties of multivariate estimators of genetic parameters for categorical, continuous and molecular genetic data in the context of important radiological health traits using mixed linear-threshold animal models via Gibbs sampling. The simulated pedigree comprised 7 generations and 40000 animals per generation. Additive genetic values, residuals and fixed effects for one continuous trait and liabilities of four binary traits were simulated, resembling situations encountered in the Warmblood horse. Quantitative trait locus (QTL) effects and genetic marker information were simulated for one of the liabilities. Different scenarios with respect to recombination rate between genetic markers and QTL and polymorphism information content of genetic markers were studied. For each scenario ten replicates were sampled from the simulated population, and within each replicate six different datasets differing in number and distribution of animals with trait records and availability of genetic marker information were generated. (Co)Variance components were estimated using a Bayesian mixed linear-threshold animal model via Gibbs sampling. Residual variances were fixed to zero and a proper prior was used for the genetic covariance matrix.</p> <p>Results</p> <p>Effective sample sizes (ESS) and biases of genetic parameters differed significantly between datasets. Bias of heritability estimates was -6% to +6% for the continuous trait, -6% to +10% for the binary traits of moderate heritability, and -21% to +25% for the binary traits of low heritability. Additive genetic correlations were mostly underestimated between the continuous trait and binary traits of low heritability, under- or overestimated between the continuous trait and binary traits of moderate heritability, and overestimated between two binary traits. Use of trait information on two subsequent generations of animals increased ESS and reduced bias of parameter estimates more than mere increase of the number of informative animals from one generation. Consideration of genotype information as a fixed effect in the model resulted in overestimation of polygenic heritability of the QTL trait, but increased accuracy of estimated additive genetic correlations of the QTL trait.</p> <p>Conclusion</p> <p>Combined use of phenotype and genotype information on parents and offspring will help to identify agonistic and antagonistic genetic correlations between traits of interests, facilitating design of effective multiple trait selection schemes.</p

Threat captures attention, but not automatically: Top-down goals modulate attentional orienting to threat distractors

The rapid orienting of attention to potential threats has been proposed to proceed outside of top-down control. However, paradigms that have been used to investigate this have struggled to separate the rapid orienting of attention (i.e. capture) from the later disengagement of focal attention that may be subject to top-down control. Consequently, it remains unclear whether and to what extent orienting to threat is contingent on top-down goals. The current study manipulated the goal-relevance of threat distractors (spiders), whilst a strict top-down attentional set was encouraged by presenting the saliently colored target and the threat distracter simultaneously for a limited time. The goal-relevance of threatening distractors was manipulated by including a spider amongst the possible target stimuli (Experiment 1: spider/cat targets) or excluding it (Experiment 2: bird/fish targets). Orienting and disengagement were disentangled by cueing attention away from or towards the threat prior to its onset. The results indicated that the threatening spider distractors elicited rapid orienting of attention when spiders were potentially goal-relevant (Experiment 1) but did so much less when they were irrelevant to the task goal (Experiment 2). Delayed disengagement from the threat distractors was even more strongly contingent on the task goal and occurred only when a spider was a possible target. These results highlight the role of top-down goals in attentional orienting to and disengagement from threat. © 2016 The Psychonomic Society, Inc

Resample-smoothing of Voronoi intensity estimators

Voronoi estimators are non-parametric and adaptive estimators of the intensity of a point process. The intensity estimate at a given location is equal to the reciprocal of the size of the Voronoi/Dirichlet cell containing that location. Their major drawback is that they tend to paradoxically under-smooth the data in regions where the point density of the observed point pattern is high, and over-smooth where the point density is low. To remedy this behaviour, we propose to apply an additional smoothing operation to the Voronoi estimator, based on resampling the point pattern by independent random thinning. Through a simulation study we show that our resample-smoothing technique improves the estimation substantially. In addition, we study statistical properties such as unbiasedness and variance, and propose a rule-of-thumb and a data-driven cross-validation approach to choose the amount of smoothing to apply. Finally we apply our proposed intensity estimation scheme to two datasets: locations of pine saplings (planar point pattern) and motor vehicle traffic accidents (linear network point pattern)

Group mindfulness based cognitive therapy vs group support for self-injury among young people: Study protocol for a randomised controlled trial

Background: Non-suicidal self-injury (NSSI) is a transdiagnostic behaviour that can be difficult to treat; to date no evidence based treatment for NSSI exists. Mindfulness Based Cognitive Therapy (MBCT) specifically targets the mechanisms thought to initiate and maintain NSSI, and thus appears a viable treatment option. The aims of the current study are to test the ability of MBCT to reduce the frequency and medical severity of NSSI, and explore the mechanisms by which MBCT exerts its effect. Methods/Design: We will conduct a parallel group randomised controlled trial of Mindfulness Based Cognitive Therapy (MBCT) versus Supportive Therapy (ST) in young people aged 18-25 years. Computerised block randomisation will be used to allocate participants to groups. All participants will meet the proposed DSM-5 criteria for NSSI (i.e. five episodes in the last twelve months). Participants will be excluded if they: 1) are currently receiving psychological treatment, 2) have attempted suicide in the previous 12 months, 3) exhibit acute psychosis, 4) have a diagnosis of borderline personality disorder, or 5) have prior experience of MBCT. Our primary outcome is the frequency and medical severity of NSSI. As secondary outcomes we will assess changes in rumination, mindfulness, emotion regulation, distress tolerance, stress, and attentional bias, and test these as mechanisms of change. Discussion: This is the first randomised controlled trial to test the efficacy of MBCT in reducing NSSI. Evidence of the efficacy of MBCT for self-injury will allow provision of a brief intervention for self-injury that can be implemented as a stand-alone treatment or integrated with existing treatments for psychiatric disorders

Nck adapter proteins: functional versatility in T cells

Nck is a ubiquitously expressed adapter protein that is almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins of Nck are functionally redundant in many aspects and differ in only few amino acids that are mostly located in the linker regions between the interaction modules. Nck proteins connect receptor and non-receptor tyrosine kinases to the machinery of actin reorganisation. Thereby, Nck regulates activation-dependent processes during cell polarisation and migration and plays a crucial role in the signal transduction of a variety of receptors including for instance PDGF-, HGF-, VEGF- and Ephrin receptors. In most cases, the SH2 domain mediates binding to the phosphorylated receptor or associated phosphoproteins, while SH3 domain interactions lead to the formation of larger protein complexes. In T lymphocytes, Nck plays a pivotal role in the T cell receptor (TCR)-induced reorganisation of the actin cytoskeleton and the formation of the immunological synapse. However, in this context, two different mechanisms and adapter complexes are discussed. In the first scenario, dependent on an activation-induced conformational change in the CD3ε subunits, a direct binding of Nck to components of the TCR/CD3 complex was shown. In the second scenario, Nck is recruited to the TCR complex via phosphorylated Slp76, another central constituent of the membrane proximal activation complex. Over the past years, a large number of putative Nck interactors have been identified in different cellular systems that point to diverse additional functions of the adapter protein, e.g. in the control of gene expression and proliferation