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

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

Theoretical Properties of Projection Based Multilayer Perceptrons with Functional Inputs

Many real world data are sampled functions. As shown by Functional Data Analysis (FDA) methods, spectra, time series, images, gesture recognition data, etc. can be processed more efficiently if their functional nature is taken into account during the data analysis process. This is done by extending standard data analysis methods so that they can apply to functional inputs. A general way to achieve this goal is to compute projections of the functional data onto a finite dimensional sub-space of the functional space. The coordinates of the data on a basis of this sub-space provide standard vector representations of the functions. The obtained vectors can be processed by any standard method. In our previous work, this general approach has been used to define projection based Multilayer Perceptrons (MLPs) with functional inputs. We study in this paper important theoretical properties of the proposed model. We show in particular that MLPs with functional inputs are universal approximators: they can approximate to arbitrary accuracy any continuous mapping from a compact sub-space of a functional space to R. Moreover, we provide a consistency result that shows that any mapping from a functional space to R can be learned thanks to examples by a projection based MLP: the generalization mean square error of the MLP decreases to the smallest possible mean square error on the data when the number of examples goes to infinity

Prognostic value of NT-proBNP levels in the acute phase of sepsis on lower long-term physical function and muscle strength in sepsis survivors

Background: Sepsis survivors often develop chronic critical illness (CCI) and demonstrate the persistent inflammation, immunosuppression, and catabolism syndrome predisposing them to long-term functional limitations and higher mortality. There is a need to identify biomarkers that can predict long-term worsening of physical function to be able to act early and prevent mobility loss. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-accepted biomarker of cardiac overload, but it has also been shown to be associated with long-term physical function decline. We explored whether NT-proBNP blood levels in the acute phase of sepsis are associated with physical function and muscle strength impairment at 6 and 12 months after sepsis onset. Methods: This is a retrospective analysis conducted in 196 sepsis patients (aged 18-86 years old) as part of the University of Florida (UF) Sepsis and Critical Illness Research Center (SCIRC) who consented to participate in the 12-month follow-up study. NT-proBNP was measured at 24 h after sepsis onset. Patients were followed to determine physical function by short physical performance battery (SPPB) test score (scale 0 to12-higher score corresponds with better physical function) and upper limb muscle strength by hand grip strength test (kilograms) at 6 and 12 months. We used a multivariate linear regression model to test an association between NT-proBNP levels, SPPB, and hand grip strength scores. Missing follow-up data or absence due to death was accounted for by using inverse probability weighting based on concurrent health performance status scores. Statistical significance was set at p ≤ 0.05. Results: After adjusting for covariates (age, gender, race, Charlson comorbidity index, APACHE II score, and presence of CCI condition), higher levels of NT-proBNP at 24 h after sepsis onset were associated with lower SPPB scores at 12 months (p < 0.05) and lower hand grip strength at 6-month (p < 0.001) and 12-month follow-up (p < 0.05). Conclusions: NT-proBNP levels during the acute phase of sepsis may be a useful indicator of higher risk of long-term impairments in physical function and muscle strength in sepsis survivors

MAXI and NuSTAR observations of the faint X-ray transient MAXI J1848-015 in the GLIMPSE-C01 Cluster

We present the results of MAXI monitoring and two NuSTAR observations of the recently discovered faint X-ray transient MAXI J1848-015. Analysis of the MAXI light-curve shows that the source underwent a rapid flux increase beginning on 2020 December 20, followed by a rapid decrease in flux after only $\sim5$ days. NuSTAR observations reveal that the source transitioned from a bright soft state with unabsorbed, bolometric ($0.1$-$100$ keV) flux $F=6.9 \pm 0.1 \times 10^{-10}\,\mathrm{erg\,cm^{-2}\,s^{-1}}$, to a low hard state with flux $F=2.85 \pm 0.04 \times 10^{-10}\,\mathrm{erg\,cm^{-2}\,s^{-1}}$. Given a distance of $3.3$ kpc, inferred via association of the source with the GLIMPSE-C01 cluster, these fluxes correspond to an Eddington fraction of order $10^{-3}$ for an accreting neutron star of mass $M=1.4M_\odot$, or even lower for a more massive accretor. However, the source spectra exhibit strong relativistic reflection features, indicating the presence of an accretion disk which extends close to the accretor, for which we measure a high spin, $a=0.967\pm0.013$. In addition to a change in flux and spectral shape, we find evidence for other changes between the soft and hard states, including moderate disk truncation with the inner disk radius increasing from $R_\mathrm{in}\approx3\,R_\mathrm{g}$ to $R_\mathrm{in}\approx8\,R_\mathrm{g}$, narrow Fe emission whose centroid decreases from $6.8\pm0.1$ keV to $6.3 \pm 0.1$ keV, and an increase in low-frequency ($10^{-3}$-$10^{-1}$ Hz) variability. Due to the high spin we conclude that the source is likely to be a black hole rather than a neutron star, and we discuss physical interpretations of the low apparent luminosity as well as the narrow Fe emission.Comment: 19 pages, 9 figures, 3 tables. Accepted for publication in Ap

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Familial clustering of Leiomyomatosis peritonealis disseminata: an unknown genetic syndrome?

BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is defined as the occurrence of multiple tumorous intraabdominal lesions, which are myomatous nodules. LPD is a rare disease with only about 100 cases reported. The usual course of LPD is benign with the majority of the patients being premenopausal females. Only two cases involving men have been reported, no syndrome or familial occurrence of LPD has been described. CASE PRESENTATION: We describe a Caucasian-American family in which six members (three men) are diagnosed with Leiomyomatosis peritonealis disseminata (LPD) and three deceased family members most likely had LPD (based on the autopsy reports). Furthermore we describe the association of LPD with Raynaud's syndrome and Prurigo nodularis. CONCLUSION: Familial clustering of Leiomyomatosis peritonealis disseminata (LPD) has not been reported so far. The etiology of LPD is unknown and no mode of inheritance is known. We discuss possible modes of inheritance in the presented case, taking into account the possibility of a genetic syndrome. Given the similarity to other genetic syndromes with leiomyomatosis and skin alterations, we describe possible similar genetic pathomechanisms

Roles of AP-2 in clathrin-mediated endocytosis.

The notion that AP-2 clathrin adaptor is an essential component of an endocytic clathrin coat appears to conflict with recent observations that substantial AP-2 depletion, using RNA interference with synthesis of AP-2 subunits, fails to block uptake of certain ligands known to internalize through a clathrin-based pathway