Switching genders: identifying the evaluator in stereotype threat for men and women in a math context

The current study seeks to identify the source of evaluation that causes stereotype threat for men and women in a math context. In a 2 (participant gender: male vs. female) X 3 (gender label: Match, Mismatch, Control) factorial design, male and female participants that identified highly with math were asked to take a math test. Throughout the test, participants\u27 ostensible gender was displayed on the computer screen. The displayed gender was either the correct gender, the opposite gender, or Alabama. Although our results were unable to determine if stereotype threat is a self- or an outside evaluator-threat, we did observe a strong gender-math relationship in which being labeled with the opposite gender disrupted both men and women\u27s math performance. However, women were more affected in that they not only performed significantly lower on the math test, but also took a longer time, attempted fewer problems, and significantly disidentified from math

NXY-059, a Failed Stroke Neuroprotectant, Offers No Protection to Stem Cell-Derived Human Neurons

Background: Developing new medicines is a complex process where understanding the reasons for both failure and success takes us forward. One gap in our understanding of most candidate stroke drugs before clinical trial is whether they have a protective effect on human tissues. NXY-059 is a spin-trap reagent hypothesized to have activity against the damaging oxidative biology which accompanies ischemic stroke. Re-examination of the preclinical in vivo dataset for this agent in the wake of the failed SAINT-II RCT highlighted the presence of a range of biases leading to overestimation of the magnitude of NXY-059\u27s effects in laboratory animals. Therefore, NXY-059 seemed an ideal candidate to evaluate in human neural tissues to determine whether human tissue testing might improve screening efficiency. Materials and Methods: The aim of this randomized and blinded study was to assess the effects of NXY-059 on human stem cell-derived neurons in the presence of ischemia-like injury induced by oxygen glucose deprivation or oxidative stress induced by hydrogen peroxide or sodium nitroprusside. Results: In MTT assays of cell survival, lactate dehydrogenase assays of total cell death and terminal deoxynucleotidyl transferase dUTP nick end labeling staining of apoptotic-like cell death, NXY-059 at concentrations ranging from 1 µm to 1 mm was completely without activity. Conversely an antioxidant cocktail comprising 100 µm each of ascorbate, reduced glutathione, and dithiothreitol used as a positive control provided marked neuronal protection in these assays. Conclusion: These findings support our hypothesis that stroke drug screening in human neural tissues will be of value and provides an explanation for the failure of NXY-059 as a human stroke drug

Coordinated TSO and DSO network development plan on the islands of Cres and Lošinj

The paper presents an example of coordinated transmission and distribution network planning based on analyses conducted as part of the study on long term distribution network development plan for islands of Cres and Lošinj in Croatia. The observed area of two large and several smaller islands is supplied with electricity by one long radial 110 kV TSO owned line and parallel radial 35 kV DSO owned line. Due to transmission capacity of 35 kV line limited to 40% of the area peak demand, which is highly conditioned by tourism, the (N-1) criteria is not complied with in case of unavailability of 110 kV line during the two-month period in summer high season. Construction of the second 110 kV line as a common solution is extremely costly, due to necessity of laying down several kilometres of submarine cables. The paper provides the cost benefit analyses of this basic scenario and other possible alternative scenarios, including also investments in DSO network, to determine the most cost-effective solution. Due to the values of the demands and networks lengths, the presented example is close to a worst case scenario concerning the reliability of supply requirement, requesting thus some atypical distribution network analyses, elements and even conducted field tests of operation. The results clearly show that coordination of TSO and DSO planning is beneficiary concerning efficiency of investments in the networks. However, further analyses are recommended presuming contribution to satisfying the (N-1) criteria by use of non-traditional (“non-network” or “third party”) solutions

Investigation of the reactivity of AlCl3 and CoCl2 toward molten alkali-metal nitrates in order to synthesize CoAl2O4

Cobalt aluminate CoAl2O4 powder, constituted of nano-sized crystallites, is prepared, involving the reactivity of AlCl3 and CoCl2 with molten alkali-metal nitrates. The reaction at 450 °C for 2 h leads to a mixture of spinel oxide Co3O4 and amorphous γ-Al2O3. It is transformed into the spinel oxide CoAl2O4 by heating at 1000 °C. The powders are mainly characterized by XRD, FTIR, ICP, electron microscopy and diffraction, X-EDS and diffuse reflection. Their properties are compared to those of powders obtained by solid state reactions of a mechanical mixture of chlorides or oxides submitted to the same thermal treatment

Derivation of phenotypically diverse neural culture from hESC by combining adherent and dissociation methods

Background:Differentiation of human embryonic stem cells (hESCs) into distinct neural lineages has been widely studied. However, preparation of mixed yet neurochemically mature populations, for the study of neurological diseases involving mixed cell types has received less attention.New method:We combined two commonly used differentiation methods to provide robust and reproducible cultures in which a mixture of primarily GABAergic and Glutamatergic neurons was obtained. Detailed characterisation by immunocytochemistry (ICC) and quantitative real-time PCR (qPCR) assessed the neurochemical phenotype, and the maturation state of these neurons.Results:We found that once neurospheres (NSs) had attached to the culture plates, proliferation of neural stem cell was suppressed. Neuronal differentiation and synaptic development then occurred after 21 days in vitro (DIV). By 49DIV, there were large numbers of neurochemically and structurally mature neurons. The qPCR studies indicated that expression of GABAergic genes increased the most (93.3-fold increase), followed by glutamatergic (51-fold increase), along with smaller changes in expression of cholinergic (3-fold increase) and dopaminergic genes (6-fold increase), as well as a small change in glial cell marker expression (5-fold increase).Comparison with existing method (s):Existing methods isolate hESC-derived neural progenitors for onward differentiation to mature neurons using either migration or dissociative paradigms. These give poor survival or yield. By combining these approaches, we obtain high yields of morphologically and neurochemically mature neurons. These can be maintained in culture for extended periods.Conclusion:Our method provides a novel, effective and robust neural culture system with structurally and neurochemically mature cell populations and neural networks, suitable for studying a range of neurological diseases from a human perspective

A systematic review and meta-analysis of gene therapy in animal models of cerebral glioma:why did promise not translate to human therapy?

BACKGROUND: The development of therapeutics is often characterized by promising animal research that fails to translate into clinical efficacy; this holds for the development of gene therapy in glioma. We tested the hypothesis that this is because of limitations in the internal and external validity of studies reporting the use of gene therapy in experimental glioma. METHOD: We systematically identified studies testing gene therapy in rodent glioma models by searching three online databases. The number of animals treated and median survival were extracted and studies graded using a quality checklist. We calculated median survival ratios and used random effects meta‐analysis to estimate efficacy. We explored effects of study design and quality and searched for evidence of publication bias. RESULTS: We identified 193 publications using gene therapy in experimental glioma, including 6,366 animals. Overall, gene therapy improved median survival by a factor of 1.60 (95% CI 1.53–1.67). Study quality was low and the type of gene therapy did not account for differences in outcome. Study design characteristics accounted for a significant proportion of between‐study heterogeneity. We observed similar findings in a data subset limited to the most common gene therapy. CONCLUSION: As the dysregulation of key molecular pathways is characteristic of gliomas, gene therapy remains a promising treatment for glioma. Nevertheless, we have identified areas for improvement in conduct and reporting of studies, and we provide a basis for sample size calculations. Further work should focus on genes of interest in paradigms recapitulating human disease. This might improve the translation of such therapies into the clinic

Evolution of metabolic divergence in <i>Pseudomonas aeruginosa</i> during long-term infection facilitates a proto-cooperative interspecies interaction

The effect of polymicrobial interactions on pathogen physiology and how it can act either to limit pathogen colonization or to potentiate pathogen expansion and virulence are not well understood. Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens commonly found together in polymicrobial human infections. However, we have previously shown that the interactions between these two bacterial species are strain dependent. Whereas P. aeruginosa PAO1, a commonly used laboratory strain, effectively suppressed S. aureus growth, we observed a commensal-like interaction between the human host-adapted strain, DK2-P2M24-2003, and S. aureus. In this study, characterization by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) imaging mass spectrometry (IMS) and mass spectral (MS) molecular networking revealed a significant metabolic divergence between P. aeruginosa PAO1 and DK2-P2M24-2003, which comprised several virulence factors and signaling 4-hydroxy-2-alkylquinoline (HAQ) molecules. Strikingly, a further modulation of the HAQ profile was observed in DK2-P2M24-2003 during interaction with S. aureus, resulting in an area with thickened colony morphology at the P. aeruginosa–S. aureus interface. In addition, we found an HAQ-mediated protection of S. aureus by DK2-P2M24-2003 from the killing effect of tobramycin. Our findings suggest a model where the metabolic divergence manifested in human host-adapted P. aeruginosa is further modulated during interaction with S. aureus and facilitate a proto-cooperative P. aeruginosa–S. aureus relationship

Human Ischaemic Cascade Studies Using SH-SY5Y Cells: a Systematic Review and Meta-Analysis

Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic responses is confirmed by systematic review and meta-analysis revealing that data for the most commonly used SH-SY5Y human cells comprises only 84 papers. Oxygen-glucose deprivation, H2O2, hypoxia, glucose-deprivation and glutamate excitotoxicity yielded − 58, − 61, − 29, − 45 and − 49% injury, respectively, with a dose-response relationship found only for H2O2 injury (R2 = 29.29%, p I2 = 99.36%, df = 132, p R2 = 44.77%, p R2 = 28.64%, p R2 = 4.13%, p p 2O2 injury reported only improvement. In studies using glucose deprivation, intervention generally worsened outcome. There was insufficient data to rank individual interventions, but of the studies reporting greatest improvement (> 90% effect size), 7/13 were of herbal medicine constituents (24.85% of the intervention dataset). We conclude that surprisingly little is known of the human neuronal response to ischaemic injury, and that the large impact of methodology on outcome indicates that further model validation is required. Lack of evidence for randomisation, blinding or power analysis suggests that the intervention data is at substantial risk of bias

Symptomatic benefits of testosterone treatment in patient subgroups : a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

Acknowledgments This work was supported by the UK National Institute for Health and Care Research (NIHR)'s Health Technology Assessment Programme (project number 17/68/01). The views expressed herein are those of the authors and not necessarily those of the National Health Service, the NIHR Health Technology Assessment Programme, or the UK Department of Health and Social Care. The Health Services Research Unit at the University of Aberdeen is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The Section of Endocrinology and Investigative Medicine at Imperial College London is funded by grants from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award, and an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Biomedical Research Centre Funding Scheme. WSD is funded by an NIHR Research Professorship. CNJ is funded by an NIHR Post-Doctoral Fellowship. ShB receives NIH research grant funding. The authors are grateful to the clinical and methodological experts and patient partners who contributed to the advisory group for this study.Peer reviewedPublisher PD