Age-related decrease of the chorda tympani nerve terminal field in the nucleus of the solitary tract is prevented by dietary sodium restriction during development

Institution of a low-NaCl diet beginning at embryonic day 3 and continued throughout pre- and postnatal development has widespread effects on the neuroanatomical organization of the first gustatory relay in the nucleus of the solitary tract. To determine when these effects are expressed postnatally, the terminal field of the chorda tympani nerve was compared between sodium-restricted and sodium-replete rats at postnatal days 15–17, postnatal days 25–27, postnatal days 35–37, and adults. Total terminal fields were significantly larger in postnatal days 35–37 and adult sodium-restricted rats compared with aged-matched controls. The group-related differences appear related more to a remodeling of the terminal field in the dorsal zone of the terminal field in controls. Specifically, the terminal field volume in the dorsal zone in controls decreased dramatically from postnatal days 25–27 to postnatal days 35–37 and then again from postnatal days 35–37 to adulthood. In contrast, the fields did not change during development in sodium-restricted rats. These findings suggest that remodeling of the chorda tympani field occurs in controls at about the developmental period of taste response maturation. The lack of remodeling in sodium-restricted rats may be explained by a corresponding lack of functional response development to sodium salts. These results also illustrate the specificity and extent of how early dietary manipulations shape the developing brainstem

Cost-effectiveness thresholds : pros and cons

Cost-effectiveness analysis is used to compare the costs and outcomes of alternative policy options. Each resulting cost-effectiveness ratio represents the magnitude of additional health gained per additional unit of resources spent. Cost-effectiveness thresholds allow cost-effectiveness ratios that represent good or very good value for money to be identified. In 2001, the World Health Organization’s Commission on Macroeconomics in Health suggested cost-effectiveness thresholds based on multiples of a country’s per-capita gross domestic product (GDP). In some contexts, in choosing which health interventions to fund and which not to fund, these thresholds have been used as decision rules. However, experience with the use of such GDP-based thresholds in decision-making processes at country level shows them to lack country specificity and this-in addition to uncertainty in the modelled cost-effectiveness ratios-can lead to the wrong decision on how to spend health-care resources. Cost-effectiveness information should be used alongside other considerations-e.g. budget impact and feasibility considerations-in a transparent decision-making process, rather than in isolation based on a single threshold value. Although cost-effectiveness ratios are undoubtedly informative in assessing value for money, countries should be encouraged to develop a context-specific process for decision-making that is supported by legislation, has stakeholder buy-in, for example the involvement of civil society organizations and patient groups, and is transparent, consistent and fair

Priority Medicines for Maternal and Child Health: A Global Survey of National Essential Medicines Lists

BACKGROUND: In April 2011, the World Health Organization (WHO) published a list of "priority medicines" for maternal and child health based on 1) the global burden of disease and 2) evidence of efficacy and safety. The objective of this study was to examine the occurrence of these priority medicines on national essential medicines lists. METHODS AND FINDINGS: All essential medicines lists published since 1999 were selected from the WHO website collection. The most-up-to date list for each country was then selected, resulting in 89 unique country lists. Each list was evaluated for inclusion of medicines (chemical entity, concentration, and dosage form) on the Priority Medicines List. There was global variation in the listing of the Priority Medicines. The most frequently listed medicine was paracetamol, on 94% (84/89) of lists. Sodium chloride, gentamicin and oral rehydration solution were on 93% (83/89) of lists. The least frequently listed medicine was the children's antimalarial rectal artesunate, on 8% of lists (7/89); artesunate injection was on 16% (14/89) of lists. Pediatric artemisinin combination therapy, as dispersible tablets or flexible oral solid dosage form, appeared on 36% (32/89) of lists. Procaine benzylpenicillin, for treatment of pediatric pneumonia and neonatal sepsis, was on 50% (45/89) of the lists. Zinc, for treatment of diarrhoea in children, was included on only 15% (13/89) of lists. For prevention and treatment of postpartum hemorrhage in women, oxytocin was more prevalent on the lists than misoprostol; they were included on 55 (62%) and 31 (35%) of lists, respectively. Cefixime, for treatment of uncomplicated anogenital gonococcal infection in woman was on 26% (23/89) of lists. Magnesium sulfate injection for treatment of severe pre-eclampsia and eclampsia was on 50% (45/89) of the lists. CONCLUSIONS: The findings suggest that countries need to urgently amend their lists to provide all priority medicines as part of the efforts to improve maternal and child health

Precision Epoch of Reionization studies with next-generation CMB experiments

Future arcminute resolution polarization data from ground-based Cosmic Microwave Background (CMB) observations can be used to estimate the contribution to the temperature power spectrum from the primary anisotropies and to uncover the signature of reionization near $\ell=1500$ in the small angular-scale temperature measurements. Our projections are based on combining expected small-scale E-mode polarization measurements from Advanced ACTPol in the range $300<\ell<3000$ with simulated temperature data from the full Planck mission in the low and intermediate $\ell$ region, $2<\ell<2000$. We show that the six basic cosmological parameters determined from this combination of data will predict the underlying primordial temperature spectrum at high multipoles to better than $1\%$ accuracy. Assuming an efficient cleaning from multi-frequency channels of most foregrounds in the temperature data, we investigate the sensitivity to the only residual secondary component, the kinematic Sunyaev-Zel'dovich (kSZ) term. The CMB polarization is used to break degeneracies between primordial and secondary terms present in temperature and, in effect, to remove from the temperature data all but the residual kSZ term. We estimate a $15 \sigma$ detection of the diffuse homogeneous kSZ signal from expected AdvACT temperature data at $\ell>1500$, leading to a measurement of the amplitude of matter density fluctuations, $\sigma_8$, at $1\%$ precision. Alternatively, by exploring the reionization signal encoded in the patchy kSZ measurements, we bound the time and duration of the reionization with $\sigma(z_{\rm re})=1.1$ and $\sigma(\Delta z_{\rm re})=0.2$. We find that these constraints degrade rapidly with large beam sizes, which highlights the importance of arcminute-scale resolution for future CMB surveys.Comment: 10 pages, 10 figure

The Atacama Cosmology Telescope: A Measurement of the Thermal Sunyaev-Zel'dovich Effect Using the Skewness of the CMB Temperature Distribution

We present a detection of the unnormalized skewness induced by the thermal Sunyaev-Zel'dovich (tSZ) effect in filtered Atacama Cosmology Telescope (ACT) 148 GHz cosmic microwave background temperature maps. Contamination due to infrared and radio sources is minimized by template subtraction of resolved sources and by constructing a mask using outlying values in the 218 GHz (tSZ-null) ACT maps. We measure = -31 +- 6 \mu K^3 (measurement error only) or +- 14 \mu K^3 (including cosmic variance error) in the filtered ACT data, a 5-sigma detection. We show that the skewness is a sensitive probe of sigma_8, and use analytic calculations and tSZ simulations to obtain cosmological constraints from this measurement. From this signal alone we infer a value of sigma_8= 0.79 +0.03 -0.03 (68 % C.L.) +0.06 -0.06 (95 % C.L.). Our results demonstrate that measurements of non-Gaussianity can be a useful method for characterizing the tSZ effect and extracting the underlying cosmological information.Comment: 9 pages, 5 figures. Replaced with version accepted by Phys. Rev. D, with improvements to the likelihood function and the IR source treatment; only minor changes in the result

Challenges in Developing Evidence-Based Recommendations Using the GRADE Approach: The Case of Mental, Neurological, and Substance Use Disorders

Corrado Barbui and colleagues describe their use and adaptation of the GRADE approach in developing the guidelines for the WHO mental health Gap Action Programme (mhGAP)

Combination adherence strategy to support HIV antiretroviral therapy and pre-exposure prophylaxis adherence during pregnancy and breastfeeding: protocol for a pair of pilot randomised trials.

INTRODUCTION To realise the expected gains from prevention of mother-to-child HIV transmission initiatives, adherence to preventative and therapeutic antiretroviral regimens is critical and interventions deployable in busy programmatic settings with a high HIV burden are needed. Based on formative research, we developed an approach that integrates patient-centred counselling and engagement of an adherence supporter for pregnant and breastfeeding women initiating HIV treatment (ie, antiretroviral therapy (ART)) or biomedical HIV prevention (ie, pre-exposure prophylaxis (PrEP)). METHODS Tonse Pamodzi 2 is a pilot study designed to provide acceptability, fidelity and clinical outcomes data on a set of behavioural interventions for adherence support. The study comprises two parallel randomised trials, enrolling HIV-positive pregnant women initiating ART (Trial 1, n=100) and HIV-negative pregnant women with risk of HIV acquisition and willing to initiate PrEP (Trial 2, n=200). Within each trial, participants are randomised 1:1 to either the intervention or control group. The Tonse Pamodzi adherence intervention comprises patient-centred counselling (adapted Integrated Next Step Counseling(iNSC)) and external adherence support tailored to the clinical context (ie, for ART or PrEP). Participants randomly assigned to the control group receive standard counselling based on local HIV guidelines. Participants are followed for 6 months. To assess intervention acceptability, we will employ a mixed method approach to describe participant engagement, satisfaction, and discussion content. We will audit and score recorded counselling sessions to evaluate the implementation fidelity of iNSC sessions. We will also assess clinical outcomes at 3 and 6 months for both Trial 1 (retention in care and viral suppression of HIV) and Trial 2 (retention in care, and plasma and intracellular tenofovir drug concentrations). ETHICS AND DISSEMINATION The study protocol was approved by the Malawi National Health Science Research Committee (19/05/2334) and the University of North Carolina at Chapel Hill Institutional Review Board (19-1060). TRIAL REGISTRATION NUMBER NCT04330989

Detection of the pairwise kinematic Sunyaev-Zel'dovich effect with BOSS DR11 and the Atacama Cosmology Telescope

We present a new measurement of the kinematic Sunyaev-Zeldovich effect using data from the Atacama Cosmology Telescope (ACT) and the Baryon Oscillation Spectroscopic Survey (BOSS). Using 600 square degrees of overlapping sky area, we evaluate the mean pairwise baryon momentum associated with the positions of 50,000 bright galaxies in the BOSS DR11 Large Scale Structure catalog. A non-zero signal arises from the large-scale motions of halos containing the sample galaxies. The data fits an analytical signal model well, with the optical depth to microwave photon scattering as a free parameter determining the overall signal amplitude. We estimate the covariance matrix of the mean pairwise momentum as a function of galaxy separation, using microwave sky simulations, jackknife evaluation, and bootstrap estimates. The most conservative simulation-based errors give signal-to-noise estimates between 3.6 and 4.1 for varying galaxy luminosity cuts. We discuss how the other error determinations can lead to higher signal-to-noise values, and consider the impact of several possible systematic errors. Estimates of the optical depth from the average thermal Sunyaev-Zeldovich signal at the sample galaxy positions are broadly consistent with those obtained from the mean pairwise momentum signal.Comment: 15 pages, 8 figures, 2 table

Centromere Protein B Null Mice are Mitotically and Meiotically Normal but Have Lower Body and Testis Weights

CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented

L Dwarfs Found in Sloan Digital Sky Survey Commissioning Data II. Hobby-Eberly Telescope Observations

Low dispersion optical spectra have been obtained with the Hobby-Eberly Telescope of 22 very red objects found in early imaging data from the Sloan Digital Sky Survey. The objects are assigned spectral types on the 2MASS system (Kirkpatrick et al. 1999) and are found to range from late M to late L. The red- and near-infrared colors from SDSS and 2MASS correlate closely with each other, and most of the colors are closely related to spectral type in this range; the exception is the (i^* - z^*) color, which appears to be independent of spectral type between about M7 and L4. The spectra suggest that this independence is due to the disappearance of the TiO and VO absorption in the i-band for later spectral types; to the presence of strong Na I and K I absorption in the i-band; and to the gradual disappearance of the 8400 Angstrom absorption of TiO and FeH in the z-band.Comment: 20 pages, 7 figures, accepted by AJ, a version with higher resolution figures can be found at ftp://ftp.astro.psu.edu/pub/dps/hetld.p