Observational constraints on the curvaton model of inflation

Simple curvaton models can generate a mixture of of correlated primordial adiabatic and isocurvature perturbations. The baryon and cold dark matter isocurvature modes differ only by an observationally null mode in which the two perturbations almost exactly compensate, and therefore have proportional effects at linear order. We discuss the CMB anisotropy in general mixed models, and give a simple approximate analytic result for the large scale CMB anisotropy. Working numerically we use the latest WMAP observations and a variety of other data to constrain the curvaton model. We find that models with an isocurvature contribution are not favored relative to simple purely adiabatic models. However a significant primordial totally correlated baryon isocurvature perturbation is not ruled out. Certain classes of curvaton model are thereby ruled out, other classes predict enough non-Gaussianity to be detectable by the Planck satellite. In the appendices we review the relevant equations in the covariant formulation and give series solutions for the radiation dominated era.Comment: Minor changes and corrections to match version accepted by PR

Portrait of blood-derived extracellular vesicles in patients with Parkinson's disease.

The production of extracellular vesicles (EV) is a ubiquitous feature of eukaryotic cells but pathological events can affect their formation and constituents. We sought to characterize the nature, profile and protein signature of EV in the plasma of Parkinson's disease (PD) patients and how they correlate to clinical measures of the disease. EV were initially collected from cohorts of PD (n = 60; Controls, n = 37) and Huntington's disease (HD) patients (Pre-manifest, n = 11; manifest, n = 52; Controls, n = 55) - for comparative purposes in individuals with another chronic neurodegenerative condition - and exhaustively analyzed using flow cytometry, electron microscopy and proteomics. We then collected 42 samples from an additional independent cohort of PD patients to confirm our initial results. Through a series of iterative steps, we optimized an approach for defining the EV signature in PD. We found that the number of EV derived specifically from erythrocytes segregated with UPDRS scores corresponding to different disease stages. Proteomic analysis further revealed that there is a specific signature of proteins that could reliably differentiate control subjects from mild and moderate PD patients. Taken together, we have developed/identified an EV blood-based assay that has the potential to be used as a biomarker for PD

Cosmopolitan Sentiment: Politics, Charity, and Global Poverty

Duties to address global poverty face a motivation gap. We have good reasons for acting yet we do not, at least consistently. A ‘sentimental education’, featuring literature and journalism detailing the lives of distant others has been suggested as a promising means by which to close this gap (Nussbaum in Upheavals of Thought: The Intelligence of Emotions, CUP, Cambridge, 2001; Rorty in Truth and Progress: Philosophical Papers, vol. 3, CUP, Cambridge, 1998). Although sympathetic to this project, I argue that it is too heavily wed to a charitable model of our duties to address global poverty—understood as requiring we sacrifice a certain portion of our income. However, political action, aimed at altering institutions at both a global and a local level is likely to be necessary in order to provide effective long-term solutions to poverty globally. To rectify this, the article develops an alternative dialogical account of sentimental education, suitable for motivating support for political action to address global poverty

Level of RUNX1 activity is critical for leukemic predisposition but not for thrombocytopenia

International audienceA half loss of RUNX1 activity leads to defects in primitive erythropoiesis, megakaryopoiesis, and proplatelet formation. • An almost complete loss of RUNX1 activity leads to the amplification of the granulomonocytic compartment with increased genomic instability. To explore how RUNX1 mutations predispose to leukemia, we generated induced plu-ripotent stem cells (iPSCs) from 2 pedigrees with germline RUNX1 mutations. The first, carrying a missense R174Q mutation, which acts as a dominant-negative mutant, is associated with thrombocytopenia and leukemia, and the second, carrying a monoallelic gene deletion inducing a haploinsufficiency, presents only as thrombocytopenia. Hema-topoietic differentiation of these iPSC clones demonstrated profound defects in eryth-ropoiesis and megakaryopoiesis and deregulated expression of RUNX1 targets. iPSC clones from patients with the R174Q mutation specifically generated an increased amount of granulomonocytes, a phenotype reproduced by an 80% RUNX1 knockdown in the H9 human embryonic stem cell line, and a genomic instability. This phenotype, found only with a lower dosage of RUNX1, may account for development of leukemia in patients. Altogether, RUNX1 dosage could explain the differential phenotype according to RUNX1 mutations, with a haploinsufficiency leading to thrombocytopenia alone in a majority of cases whereas a more complete gene deletion predisposes to leukemia

Global evidence of gender inequity in academic health research: a living scoping review protocol

Objective: The objective of this review is to describe the global evidence of gender inequity among individuals with appointments at academic institutions that conduct health research, and examine how gender intersects with other social identities to influence outcomes. Introduction: The gender demographics of universities have shifted, yet the characteristics of those who lead academic health research institutions have not reflected this change. Synthesized evidence will guide decision-making and policy development to support the progress of gender and other under-represented social identities in academia. Inclusion Criteria: This review will consider any quantitative, qualitative, or mixed methods primary research that reports outcome data related to gender equity and other social identities among individuals affiliated with academic or research institutions that conduct health research, originating from any country. Methods: The JBI Manual for Evidence Synthesis and the Cochrane Collaboration's guidance on living reviews will inform the review methods. Information sources will include electronic databases, unpublished literature sources, reference scanning of relevant systematic reviews, and sources provided by experts on the research team. Searches will be run regularly to monitor the development of new literature and determine when the review will be updated. Study selection and data extraction will be conducted by two reviewers working independently, and all discrepancies will be resolved by discussion or a third reviewer. Data synthesis will summarize information using descriptive frequencies and simple thematic analysis. Results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension to scoping reviews.</p