Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial

<p><b>Background and Purpose:</b>Although magnesium is neuroprotective in animal stroke models, no clinical benefit was confirmed in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial of acute stroke patients. The Magnetic Resonance in IMAGES (MR IMAGES) substudy investigated the effects of magnesium on the imaging surrogate outcome of infarct growth.</p> <p><b>Methods:</b> IMAGES trial patients in participating centers were randomized to receive either intravenous magnesium or placebo within 12 hours of stroke onset. Infarct growth was defined as volume difference between baseline diffusion-weighted imaging and day 90 fluid-attenuated inversion recovery image lesions. Patients who died were imputed the largest infarct growth observed.</p> <p><b>Results:</b> Among the 90 patients included in the primary analysis, there was no difference in infarct growth (median absolute growth, P=0.639; median percentage growth, P=0.616; proportion with any growth, P=0.212) between the 46 treated with magnesium and 44 with placebo. Infarct growth correlated with NIHSS score change from baseline to day 90. There was a trend showing baseline serum glucose correlated with infarct growth with magnesium treatment, but not in the placebo group. The mismatch frequency was reduced from 73% to 47% by increasing the mismatch threshold from >20% to >100% of core volume.</p> <p><b>Conclusions:</b> Infarct growth, confirmed here as a surrogate for clinical progression, was similar between magnesium and placebo treatment, paralleling the main IMAGES trial clinical outcomes. Glucose was a covariate for infarct growth with magnesium treatment. A more stringent mismatch threshold to define penumbra more appropriately would have excluded half of the patients in this 12-hour time window stroke study.</p&gt

Why Are People's Decisions Sometimes Worse with Computer Support?

In many applications of computerised decision support, a recognised source of undesired outcomes is operators' apparent over-reliance on automation. For instance, an operator may fail to react to a potentially dangerous situation because a computer fails to generate an alarm. However, the very use of terms like "over-reliance" betrays possible misunderstandings of these phenomena and their causes, which may lead to ineffective corrective action (e.g. training or procedures that do not counteract all the causes of the apparently "over-reliant" behaviour). We review relevant literature in the area of "automation bias" and describe the diverse mechanisms that may be involved in human errors when using computer support. We discuss these mechanisms, with reference to errors of omission when using "alerting systems", with the help of examples of novel counterintuitive findings we obtained from a case study in a health care application, as well as other examples from the literature

Germline DNA Repair Gene Mutations in Young-onset Prostate Cancer Cases in the UK: Evidence for a More Extensive Genetic Panel

Background Rare germline mutations in DNA repair genes are associated with prostate cancer (PCa) predisposition and prognosis. Objective To quantify the frequency of germline DNA repair gene mutations in UK PCa cases and controls, in order to more comprehensively evaluate the contribution of individual genes to overall PCa risk and likelihood of aggressive disease. Design, setting, and participants We sequenced 167 DNA repair and eight PCa candidate genes in a UK-based cohort of 1281 young-onset PCa cases (diagnosed at ≤60 yr) and 1160 selected controls. Outcome measurements and statistical analysis Gene-level SKAT-O and gene-set adaptive combination of p values (ADA) analyses were performed separately for cases versus controls, and aggressive (Gleason score ≥8, n = 201) versus nonaggressive (Gleason score ≤7, n = 1048) cases. Results and limitations We identified 233 unique protein truncating variants (PTVs) with minor allele frequency <0.5% in controls in 97 genes. The total proportion of PTV carriers was higher in cases than in controls (15% vs 12%, odds ratio [OR] = 1.29, 95% confidence interval [CI] 1.01–1.64, p = 0.036). Gene-level analyses selected NBN (pSKAT-O = 2.4 × 10−4) for overall risk and XPC (pSKAT-O = 1.6 × 10−4) for aggressive disease, both at candidate-level significance (p < 3.1 × 10−4 and p < 3.4 × 10−4, respectively). Gene-set analysis identified a subset of 20 genes associated with increased PCa risk (OR = 3.2, 95% CI 2.1–4.8, pADA = 4.1 × 10−3) and four genes that increased risk of aggressive disease (OR = 11.2, 95% CI 4.6–27.7, pADA = 5.6 × 10−3), three of which overlap the predisposition gene set. Conclusions The union of the gene-level and gene-set-level analyses identified 23 unique DNA repair genes associated with PCa predisposition or risk of aggressive disease. These findings will help facilitate the development of a PCa-specific sequencing panel with both predictive and prognostic potential. Patient summary This large sequencing study assessed the rate of inherited DNA repair gene mutations between prostate cancer patients and disease-free men. A panel of 23 genes was identified, which may improve risk prediction or treatment pathways in future clinical practice

The Art of Struggle and the Struggle for Art: Let SCA Stay and the fight against the neoliberal university

Student movements are popularly considered as phenomena of the past. The history of Let SCA Stay, 2016, lays waste to this pessimistic stereotype and announces a developing history of student struggles against neoliberal universities. The campaign’s record-breaking 65-day occupation and associated student strikes at the University of Sydney reveal the reality of radical student movements in a post-Voluntary Student Unionism era. This thesis suggests that students’ embodied learning in the struggle elucidated potentialities for education beyond neoliberal universities. This history behoves historians to understand emerging student movements and involve themselves directly in the development of liberation struggles

Artificial Intelligence as a Means to Moral Enhancement

This paper critically assesses the possibility of moral enhancement with ambient intelligence technologies and artificial intelligence presented in Savulescu and Maslen (2015). The main problem with their proposal is that it is not robust enough to play a normative role in users’ behavior. A more promising approach, and the one presented in the paper, relies on an artifi-cial moral reasoning engine, which is designed to present its users with moral arguments grounded in first-order normative theories, such as Kantianism or utilitarianism, that reason-responsive people can be persuaded by. This proposal can play a normative role and it is also a more promising avenue towards moral enhancement. It is more promising because such a system can be designed to take advantage of the sometimes undue trust that people put in automated technologies. We could therefore expect a well-designed moral reasoner system to be able to persuade people that may not be persuaded by similar arguments from other people. So, all things considered, there is hope in artificial intelli-gence for moral enhancement, but not in artificial intelligence that relies solely on ambient intelligence technologies

Women Organizing Women –‘Doing it Backwards and in High Heels’

Summary This article looks at the formative stages of a Zimbabwean NGO, the Musasa Project. The process of arriving at a particular organizational model is examined. Particular attention is paid to two aspects of this process i) problems experienced in an organization run by women for women, in particular, the issue of gendered ‘dis?ease’ in the public sphere of work and how it affects performance, and ii) the impact of increased external funding on the organizational model and on the relative importance of members of the organization. The final section of the article poses questions about ‘scaling?up’ of NGOs, how it can affect organizational priorities, and how the accompanying ‘professionalization’ can marginalize less well?educated staff. A model of scaling?up is proposed which, by setting up structures to enhance the ‘voice’ of the constituency, ensures that their views continue to be heard. RESUME Comment s'y prendre à reculons, en chaussures à hauts talons Cet article examine les stades formateurs d'une ONG au Zimbabwe, le Projet de Musasa. Il examine le processus par lequel un model d'organisation particulier a été atteint. Deux aspects spécifiques sont examinés: tout d'abord les problèmes qui se sont soulevés dans une organisation menée par des femmes pour des femmes et notamment, la question des conditions défavorables au genre dans le secteur du service public et l'effet de ces conditions sur la performance; et deuxièmement, l'impact de l'augmentation des financements de provenance extérieure sur le modèle organisationnel adopté, et la question de l'importance relative des membres de l'organisation. La dernière section de l'article pose des questions sur la croissance des ONG et comment celle?ci peut affecter les priorités organisationnelles, ainsi que la manière dans laquelle la “professionalisation” qui l'accompagne peut servir à marginaliser les membres du personnel les moins bien éduqués. Un modèle de croissance est proposé et celui?ci, grâce à la mise en place de structures qui puisssent accentuer la “voix” des représenté(e)s, garantit que leurs opinions ne cesseront d'être entendus. RESUMEN Al revés y en tacos altos El artículo explora las fases formativas de una NGO en Zimbabwe, el proyecto Musasa. Se examina el proceso de llegada a un modelo organizativo particular, especialmente en dos aspectos: a) los problemas existentes en una organización manejada por mujeres para mujeres, en particular es asunto de la ‘incómodidad práctica’ del género en las esferas de actuación pública y cómo ésta afecta los resultados, y b) el impacto del aumento de la financiación externa en el modelo organizativo y en la importancia relativa de los miembros de la organización. Finalmente, el artículo plantea un serie de interrogantes relativos a la ‘ampliación’ de las NGOs, cómo ésta puede afectar prioridades de organización, y cómo la profesionalización que la acompaña puede marginalizar al personal con menos educación. Se propone un modelo de ‘ampliación’ que establece las estructuras para estimular las voces del distrito, y asegurar que sus opiniones sean escuchadas

A doubly-refined enumeration of alternating sign matrices and descending plane partitions

It was shown recently by the authors that, for any n, there is equality between the distributions of certain triplets of statistics on nxn alternating sign matrices (ASMs) and descending plane partitions (DPPs) with each part at most n. The statistics for an ASM A are the number of generalized inversions in A, the number of -1's in A and the number of 0's to the left of the 1 in the first row of A, and the respective statistics for a DPP D are the number of nonspecial parts in D, the number of special parts in D and the number of n's in D. Here, the result is generalized to include a fourth statistic for each type of object, where this is the number of 0's to the right of the 1 in the last row of an ASM, and the number of (n-1)'s plus the number of rows of length n-1 in a DPP. This generalization is proved using the known equality of the three-statistic generating functions, together with relations which express each four-statistic generating function in terms of its three-statistic counterpart. These relations are obtained by applying the Desnanot-Jacobi identity to determinantal expressions for the generating functions, where the determinants arise from standard methods involving the six-vertex model with domain-wall boundary conditions for ASMs, and nonintersecting lattice paths for DPPs.Comment: 28 pages; v2: published versio

Lassoing and corraling rooted phylogenetic trees

The construction of a dendogram on a set of individuals is a key component of a genomewide association study. However even with modern sequencing technologies the distances on the individuals required for the construction of such a structure may not always be reliable making it tempting to exclude them from an analysis. This, in turn, results in an input set for dendogram construction that consists of only partial distance information which raises the following fundamental question. For what subset of its leaf set can we reconstruct uniquely the dendogram from the distances that it induces on that subset. By formalizing a dendogram in terms of an edge-weighted, rooted phylogenetic tree on a pre-given finite set X with |X|>2 whose edge-weighting is equidistant and a set of partial distances on X in terms of a set L of 2-subsets of X, we investigate this problem in terms of when such a tree is lassoed, that is, uniquely determined by the elements in L. For this we consider four different formalizations of the idea of "uniquely determining" giving rise to four distinct types of lassos. We present characterizations for all of them in terms of the child-edge graphs of the interior vertices of such a tree. Our characterizations imply in particular that in case the tree in question is binary then all four types of lasso must coincide

A glimpse of the future in animal nutrition science. 1. Past and future challenges

ABSTRACT If the world population continues to increase exponentially, wealth and education inequalities might become more pronounced in the developing world. Thus, offering affordable, high-quality protein food to people will become more important and daunting than ever. Past and future challenges will increasingly demand quicker and more innovative and efficient solutions. Animal scientists around the globe currently face many challenging issues: from ensuring food security to prevent excess of nutrient intake by humans, from animal welfare to working with genetic-engineered animals, from carbon footprint to water footprint, and from improved animal nutrition to altering the rumen microbiome. Many of these issues are most likely to continue (or to exacerbate further) in the coming years, but animal scientists have many options to surmount the obstacles posed to the livestock industry through tools that are presently available. The frequency, interval, and intensity of livestock impacts, however, differ across regions, production systems, and among livestock species. These differences are such that the generalization of these issues is impossible and dangerous. For instance, when we discuss domesticated ruminant nutrition in the human food context, we look for the most efficient ruminant feeds that complement, rather than compete with, grains grown for direct human nutrition. Greater scrutiny and standardization are needed when developing and validating methodologies to assess short- and long-term impacts of livestock production. Failure in correctly quantifying these impacts may lead to disregard and disbelief by the livestock industry, increased public confusion, and the development of illusionary solutions that may amplify the impacts, thereby invalidating its original intent

Cerebellar plasticity and associative memories are controlled by perineuronal nets.

Perineuronal nets (PNNs) are assemblies of extracellular matrix molecules, which surround the cell body and dendrites of many types of neuron and regulate neural plasticity. PNNs are prominently expressed around neurons of the deep cerebellar nuclei (DCN), but their role in adult cerebellar plasticity and behavior is far from clear. Here we show that PNNs in the mouse DCN are diminished during eyeblink conditioning (EBC), a form of associative motor learning that depends on DCN plasticity. When memories are fully acquired, PNNs are restored. Enzymatic digestion of PNNs in the DCN improves EBC learning, but intact PNNs are necessary for memory retention. At the structural level, PNN removal induces significant synaptic rearrangements in vivo, resulting in increased inhibition of DCN baseline activity in awake behaving mice. Together, these results demonstrate that PNNs are critical players in the regulation of cerebellar circuitry and function