A call for transparent reporting to optimize the predictive value of preclinical research

The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress

A Cervid Vocal Fold Model Suggests Greater Glottal Efficiency in Calling at High Frequencies

Male Rocky Mountain elk (Cervus elaphus nelsoni) produce loud and high fundamental frequency bugles during the mating season, in contrast to the male European Red Deer (Cervus elaphus scoticus) who produces loud and low fundamental frequency roaring calls. A critical step in understanding vocal communication is to relate sound complexity to anatomy and physiology in a causal manner. Experimentation at the sound source, often difficult in vivo in mammals, is simulated here by a finite element model of the larynx and a wave propagation model of the vocal tract, both based on the morphology and biomechanics of the elk. The model can produce a wide range of fundamental frequencies. Low fundamental frequencies require low vocal fold strain, but large lung pressure and large glottal flow if sound intensity level is to exceed 70 dB at 10 m distance. A high-frequency bugle requires both large muscular effort (to strain the vocal ligament) and high lung pressure (to overcome phonation threshold pressure), but at least 10 dB more intensity level can be achieved. Glottal efficiency, the ration of radiated sound power to aerodynamic power at the glottis, is higher in elk, suggesting an advantage of high-pitched signaling. This advantage is based on two aspects; first, the lower airflow required for aerodynamic power and, second, an acoustic radiation advantage at higher frequencies. Both signal types are used by the respective males during the mating season and probably serve as honest signals. The two signal types relate differently to physical qualities of the sender. The low-frequency sound (Red Deer call) relates to overall body size via a strong relationship between acoustic parameters and the size of vocal organs and body size. The high-frequency bugle may signal muscular strength and endurance, via a ‘vocalizing at the edge’ mechanism, for which efficiency is critical

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.Published versionThe authors thank the UK MS Society for financial support (grant number: C008-16.1). DRO was funded by an MRC Clinician Scientist Award (MR/N008219/1). P.M.M. acknowledges generous support from Edmond J Safra Foundation and Lily Safra, the NIHR Senior Investigator programme and the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK. P.M.M. and D.R.O. thank the Imperial College Healthcare Trust-NIHR Biomedical Research Centre for infrastructure support and the Medical Research Council for support of TSPO studies (MR/N016343/1). E.A. was supported by the ALS Stichting (grant “The Dutch ALS Tissue Bank”). P.M. and B.B.T. are funded by the Swiss National Science Foundation (projects 320030_184713 and 310030_212322, respectively). S.T. was supported by an “Early Postdoc.Mobility” scholarship (P2GEP3_191446) from the Swiss National Science Foundation, a “Clinical Medicine Plus” scholarship from the Prof Dr. Max Cloëtta Foundation (Zurich, Switzerland), from the Jean et Madeleine Vachoux Foundation (Geneva, Switzerland) and from the University Hospitals of Geneva. This work was funded by NIH grants U01AG061356 (De Jager/Bennett), RF1AG057473 (De Jager/Bennett), and U01AG046152 (De Jager/Bennett) as part of the AMP-AD consortium, as well as NIH grants R01AG066831 (Menon) and U01AG072572 (De Jager/St George-Hyslop)

The 'ebb and flow' of transatlantic regulatory cooperation in banking

Do financial crises promote or hamper transatlantic regulatory cooperation in banking? This article argues that financial crises have an impact upon the alignment of regulatory preferences of the United States (US) and the European Union (EU), causing an 'ebb and flow' in transatlantic cooperation. When EU-US preferences are broadly aligned in periods of financial stability, transatlantic regulatory cooperation is intense. It is relatively easy for the EU and US to agree on market-friendly regulation promoted by banks. When preferences are different, especially in the context and aftermath of the exogenous shock of financial crises, transatlantic cooperation is more problematic because crises re-assert the importance of nationally embedded patterns of market organisation

Comparing different technologies for active TB case-finding among the homeless:a transmission-dynamic modelling study

Homeless persons have elevated risk of tuberculosis (TB) and are under-served by conventional health services. Approaches to active case-finding (ACF) and treatment tailored to their needs are required. A transmission-dynamic model was developed to assess the effectiveness and efficiency of screening with mobile Chest X-ray, GeneXpert, or both. Effectiveness of ACF depends upon the prevalence of infection in the population (which determines screening ‘yield’), patient willingness to wait for GeneXpert results, and treatment adherence. ACF is efficient when TB prevalence exceeds 78/100,000 and 46% of drug sensitive TB cases and 33% of multi-drug resistant TB cases complete treatment. This threshold increases to 92/100,000 if additional post-ACF enhanced case management (ECM) increases treatment completion to 85%. Generally, the most efficient option is one-step screening of all patients with GeneXpert, but if too many patients (>27% without ECM, >19% with ECM) are unwilling to wait the 90 minutes required then two-step screening using chest X-ray (which is rapid) followed by GeneXpert for confirmation of TB is the most efficient option. Targeted ACF and support services benefit health through early successful treatment and averting TB transmission and disease. The optimal strategy is setting-specific, requiring careful consideration of patients’ needs regarding testing and treatment

A systematic review evaluating the psychometric properties of measures of social inclusion

Introduction: Improving social inclusion opportunities for population health has been identified as a priority area for international policy. There is a need to comprehensively examine and evaluate the quality of psychometric properties of measures of social inclusion that are used to guide social policy and outcomes. Objective: To conduct a systematic review of the literature on all current measures of social inclusion for any population group, to evaluate the quality of the psychometric properties of identified measures, and to evaluate if they capture the construct of social inclusion. Methods: A systematic search was performed using five electronic databases: CINAHL, PsycINFO, Embase, ERIC and Pubmed and grey literature were sourced to identify measures of social inclusion. The psychometric properties of the social inclusion measures were evaluated against the COSMIN taxonomy of measurement properties using pre-set psychometric criteria. Results: Of the 109 measures identified, twenty-five measures, involving twenty-five studies and one manual met the inclusion criteria. The overall quality of the reviewed measures was variable, with the Social and Community Opportunities Profile-Short, Social Connectedness Scale and the Social Inclusion Scale demonstrating the strongest evidence for sound psychometric quality. The most common domain included in the measures was connectedness (21), followed by participation (19); the domain of citizenship was covered by the least number of measures (10). No single instrument measured all aspects within the three domains of social inclusion. Of the measures with sound psychometric evidence, the Social and Community Opportunities Profile-Short captured the construct of social inclusion best. Conclusions: The overall quality of the psychometric properties demonstrate that the current suite of available instruments for the measurement of social inclusion are promising but need further refinement. There is a need for a universal working definition of social inclusion as an overarching construct for ongoing research in the area of the psychometric properties of social inclusion instruments

Hábito de assistir à televisão e sua relação com a alimentação: resultados do período de 2006 a 2014 em capitais brasileiras

Resumo: O objetivo foi analisar a evolução da frequência do hábito de assistir à TV no Brasil e identificar a associação entre este hábito e o consumo alimentar na população adulta do Brasil entre os anos de 2006 e 2014. Dados do sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico (VIGITEL) entre os anos de 2006 e 2014 foram utilizados. O hábito diário de assistir à TV e o consumo alimentar de frutas, hortaliças, feijão, carnes, leite, refrigerantes e/ou bebidas adoçadas foram analisados ao longo dos anos, sendo sua associação investigada por meio de modelos de regressão. A frequência de adultos referindo assistir à televisão por ao menos 3 horas por dia não variou significativamente ao longo dos anos, porém, nestes indivíduos, foi possível verificar um menor consumo de alimentos saudáveis, e maior, daqueles não saudáveis. Essa situação foi verificada em ambos os sexos e em todas as faixas de idade e escolaridade pesquisadas. O hábito de assistir à TV está associado ao consumo alimentar não saudável

Cross-correlation of gravitational lensing from DES Science Verification data with SPT and Planck lensing

We measure the cross-correlation between weak lensing of galaxy images and of the cosmic microwave background (CMB) on the same patch of sky. The effects of gravitational lensing on different sources will be correlated if the lensing is caused by the same mass fluctuations. We use galaxy shape measurements from 139 deg2 of the Dark Energy Survey (DES) Science Verification data and overlapping CMB lensing from the South Pole Telescope (SPT) and Planck. The DES source galaxies have a median redshift of zmed∼0.7, while the CMB lensing kernel is broad and peaks at z∼2. The resulting cross-correlation is maximally sensitive to mass fluctuations at z∼0.44. Assuming the Planck 2015 best-fit cosmology, the amplitude of the DES×SPT cross-power is found to be ASPT = 0.88 ± 0.30 and that from DES×Planck to be APlanck = 0.86±0.39, where A = 1 corresponds to the theoretical prediction and the errors are 68% confidence limits. These are consistent with the expected signal and correspond to significances of 2.9σ and 2.2σ respectively. We demonstrate that our results are robust to a number of important systematic effects including the shear measurement method, estimator choice, photometric redshift uncertainty and CMB lensing systematics. Significant intrinsic alignment of galaxy shapes would increase the cross-correlation signal inferred from the data; we calculate a value of A = 1.08±0.36 for DES×SPT when we correct the observations with a simple IA model. With three measurements of this cross-correlation now existing in the literature, there is not yet reliable evidence for any deviation from the expected LCDM level of cross-correlation, given the size of the statistical uncertainties and the significant impact of systematic errors, particularly IAs. Future data sets, including those from upcoming releases of DES and SPT, will cover more sky area and provide both greater depth and higher resolution, making this correlation a potentially very powerful cosmological tool. We provide forecasts for the expected signal-to-noise of the combination of the five-year DES survey and SPT-3G