Adjusting for Confounding by Neighborhood Using a Proportional Odds Model and Complex Survey Data

In social epidemiology, an individual\u27s neighborhood is considered to be an important determinant of health behaviors, mediators, and outcomes. Consequently, when investigating health disparities, researchers may wish to adjust for confounding by unmeasured neighborhood factors, such as local availability of health facilities or cultural predispositions. With a simple random sample and a binary outcome, a conditional logistic regression analysis that treats individuals within a neighborhood as a matched set is a natural method to use. The authors present a generalization of this method for ordinal outcomes and complex sampling designs. The method is based on a proportional odds model and is very simple to program using standard software such as SAS PROC SURVEYLOGISTIC (SAS Institute Inc., Cary, North Carolina). The authors applied the method to analyze racial/ethnic differences in dental preventative care, using 2008 Florida Behavioral Risk Factor Surveillance System survey data. The ordinal outcome represented time since last dental cleaning, and the authors adjusted for individual-level confounding by gender, age, education, and health insurance coverage. The authors compared results with and without additional adjustment for confounding by neighborhood, operationalized as zip code. The authors found that adjustment for confounding by neighborhood greatly affected the results in this example

Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior.

Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing. To explore how altered SC neuron physiology might impact behavior, we took advantage of the fact that in deep layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics. We found that social exploration preferentially recruits mPFC D2R+ cells, but that this recruitment is attenuated in VPA-exposed mice. Stimulating mPFC D2R+ neurons disrupts normal social interaction. Conversely, inhibiting these cells enhances social behavior in VPA-exposed mice. Importantly, this effect was not reproduced by nonspecifically inhibiting mPFC neurons in VPA-exposed mice, or by inhibiting D2R+ neurons in wild-type mice. These findings suggest that multiple forms of autism may alter the physiology of specific deep-layer prefrontal neurons that project to subcortical targets. Furthermore, a highly overlapping population-prefrontal D2R+ neurons-plays an important role in both normal and abnormal social behavior, such that targeting these cells can elicit potentially therapeutic effects

A possible phase dependent absorption feature in the transient X-ray pulsar SAX J2103.5+4545

We present an X-ray spectral and timing analysis of two $NuSTAR$ observations of the transient Be X-ray binary SAX J2103.5+4545 during its April 2016 outburst, which was characterized by the highest flux since $NuSTAR$'s launch. These observations provide detailed hard X-ray spectra of this source during its bright precursor flare and subsequent fainter regular outburst for the first time. In this work, we model the phase-averaged spectra for these observations with a negative and positive power law with an exponential cut-off (NPEX) model and compare the pulse profiles at different flux states. We found that the broad-band pulse profile changes from a three peaked pulse in the first observation to a two peaked pulse in the second observation, and that each of the pulse peaks has some energy dependence. We also perform pulse-phase spectroscopy and fit phase-resolved spectra with NPEX to evaluate how spectral parameters change with pulse phase. We find that while the continuum parameters are mostly constant with pulse phase, a weak absorption feature at ~12 keV that might, with further study, be classified as a cyclotron line, does show strong pulse phase dependence.Comment: 10 pages, 7 figures, accepted by ApJ, acknowledgements update

The impact of a school-based water supply and treatment, hygiene, and sanitation programme on pupil diarrhoea: a cluster-randomized trial.

The impact of improved water, sanitation, and hygiene (WASH) access on mitigating illness is well documented, although impact of school-based WASH on school-aged children has not been rigorously explored. We conducted a cluster-randomized trial in Nyanza Province, Kenya to assess the impact of a school-based WASH intervention on diarrhoeal disease in primary-school pupils. Two study populations were used: schools with a nearby dry season water source and those without. Pupils attending 'water-available' schools that received hygiene promotion and water treatment (HP&WT) and sanitation improvements showed no difference in period prevalence or duration of illness compared to pupils attending control schools. Those pupils in schools that received only the HP&WT showed similar results. Pupils in 'water-scarce' schools that received a water-supply improvement, HP&WT and sanitation showed a reduction in diarrhoea incidence and days of illness. Our study revealed mixed results on the impact of improvements to school WASH improvements on pupil diarrhoea

Critical-Sized Bone Defects: Sequence and Planning.

Bone defects associated with open fractures require a careful approach and planning. At initial presentation, an emergent irrigation and debridement is required. Immediate definitive fixation is frequently safe, with the exception of those injuries that normally require staged management or very severe type IIIB and IIIC injuries. Traumatic wounds that can be approximated primarily should be closed at the time of initial presentation. Wounds that cannot be closed should have a negative pressure wound therapy dressing applied. The need for subsequent debridements remains a clinical judgment, but all nonviable tissue should be removed before definitive coverage. Cefazolin remains the standard of care for all open fractures, and type III injuries also require gram-negative coverage. Both induced membrane technique with staged bone grafting and distraction osteogenesis are excellent options for bony reconstruction. Soft tissue coverage within 1 week of injury seems critical

Late systolic central hypertension as a predictor of incident heart failure : the Multi-Ethnic Study of Atherosclerosis

Background: Experimental studies demonstrate that high aortic pressure in late systole relative to early systole causes greater myocardial remodeling and dysfunction, for any given absolute peak systolic pressure. Methods and Results: We tested the hypothesis that late systolic hypertension, defined as the ratio of late (last one third of systole) to early (first two thirds of systole) pressure-time integrals (PTI) of the aortic pressure waveform, independently predicts incident heart failure (HF) in the general population. Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 6124 adults. The late/early systolic PTI ratio (L/ESPTI) was assessed as a predictor of incident HF during median 8.5 years of follow-up. The L/ESPTI was predictive of incident HF (hazard ratio per 1% increase= 1.22; 95% CI= 1.15 to 1.29; P58.38%) was more predictive of HF than the presence of hypertension. After adjustment for each other and various predictors of HF, the HR associated with hypertension was 1.39 (95% CI= 0.86 to 2.23; P=0.18), whereas the HR associated with a high L/E was 2.31 (95% CI=1.52 to 3.49; P<0.0001). Conclusions: Independently of the absolute level of peak pressure, late systolic hypertension is strongly associated with incident HF in the general population

Nonparametric Covariate Adjustment for Receiver Operating Characteristic Curves

The accuracy of a diagnostic test is typically characterised using the receiver operating characteristic (ROC) curve. Summarising indexes such as the area under the ROC curve (AUC) are used to compare different tests as well as to measure the difference between two populations. Often additional information is available on some of the covariates which are known to influence the accuracy of such measures. We propose nonparametric methods for covariate adjustment of the AUC. Models with normal errors and non-normal errors are discussed and analysed separately. Nonparametric regression is used for estimating mean and variance functions in both scenarios. In the general noise case we propose a covariate-adjusted Mann-Whitney estimator for AUC estimation which effectively uses available data to construct working samples at any covariate value of interest and is computationally efficient for implementation. This provides a generalisation of the Mann-Whitney approach for comparing two populations by taking covariate effects into account. We derive asymptotic properties for the AUC estimators in both settings, including asymptotic normality, optimal strong uniform convergence rates and MSE consistency. The usefulness of the proposed methods is demonstrated through simulated and real data examples

Discovery of Pulsation Dropout and Turn-on during the High State of the Accreting X-Ray Pulsar LMC X-4

Two Nuclear Spectroscopic Telescope Array (NuSTAR) observations of the luminous X-ray pulsar LMC X-4 in 2015 October and November captured several bright accretion flares from this source, which has a long history of stable pulse and superorbital behavior. We present a timing analysis of these data in which we detect a rapid pulse "turn-on" in association with the accretion flares, during which the source reaches super-Eddington luminosities. Pulsations, which are normally seen from this source, are found to only occur for approximately one hour before and during the bright flares. Beyond one hour before and after the flares, we find pulsations to be weak or nonexistent, with fractional rms amplitudes of less than 0.05. At the onset of the flare, the pulse profiles exhibit a phase shift of 0.25 cycles that could be associated with a change in the emission geometry. This increase in pulse strength occurring well before the flare cannot be explained by the propeller effect, and potentially offers a connection between the magnetic properties of pulsars that accrete close to their Eddington limits and ultra-luminous X-ray pulsars

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis

BACKGROUND: The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. METHODS: Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. RESULTS: Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). CONCLUSIONS: iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials