Cognitive and behavioral improvement in adults with fragile X syndrome treated with metformin-two cases.

BackgroundThe majority of individuals with fragile X syndrome (FXS) have intellectual disability, behavioral problems, autism, and language deficits. IQ typically declines with age in boys with the full mutation. The results of preclinical studies demonstrated that metformin, a biguanide used to treat type 2 diabetes, rescues multiple phenotypes of FXS in both Drosophila and mouse models. Preliminary studies of patients with FXS demonstrated improvements in behavior.MethodsHere, we present two cases of individuals who have been treated with metformin clinically for one year.ResultsBoth patients demonstrated significant cognitive and behavioral improvements. They also improved eating habits and normalization of their weight percentiles.ConclusionMetformin may be a candidate drug for treatment of several types of symptoms in individuals with FXS

Alternative causal inference methods in population health research: Evaluating tradeoffs and triangulating evidence.

Population health researchers from different fields often address similar substantive questions but rely on different study designs, reflecting their home disciplines. This is especially true in studies involving causal inference, for which semantic and substantive differences inhibit interdisciplinary dialogue and collaboration. In this paper, we group nonrandomized study designs into two categories: those that use confounder-control (such as regression adjustment or propensity score matching) and those that rely on an instrument (such as instrumental variables, regression discontinuity, or differences-in-differences approaches). Using the Shadish, Cook, and Campbell framework for evaluating threats to validity, we contrast the assumptions, strengths, and limitations of these two approaches and illustrate differences with examples from the literature on education and health. Across disciplines, all methods to test a hypothesized causal relationship involve unverifiable assumptions, and rarely is there clear justification for exclusive reliance on one method. Each method entails trade-offs between statistical power, internal validity, measurement quality, and generalizability. The choice between confounder-control and instrument-based methods should be guided by these tradeoffs and consideration of the most important limitations of previous work in the area. Our goals are to foster common understanding of the methods available for causal inference in population health research and the tradeoffs between them; to encourage researchers to objectively evaluate what can be learned from methods outside one's home discipline; and to facilitate the selection of methods that best answer the investigator's scientific questions

Dynamics of a Massive Binary at Birth

Almost all massive stars have bound stellar companions, existing in binaries or higher-order multiples. While binarity is theorized to be an essential feature of how massive stars form, essentially all information about such properties is derived from observations of already formed stars, whose orbital properties may have evolved since birth. Little is known about binarity during formation stages. Here we report high angular resolution observations of 1.3 mm continuum and H30alpha recombination line emission, which reveal a massive protobinary with apparent separation of 180 au at the center of the massive star-forming region IRAS07299-1651. From the line-of-sight velocity difference of 9.5 km/s of the two protostars, the binary is estimated to have a minimum total mass of 18 solar masses, consistent with several other metrics, and maximum period of 570 years, assuming a circular orbit. The H30alpha line from the primary protostar shows kinematics consistent with rotation along a ring of radius of 12 au. The observations indicate that disk fragmentation at several hundred au may have formed the binary, and much smaller disks are feeding the individual protostars.Comment: Published in Nature Astronomy. This is author's version. Full article is available here (https://rdcu.be/brENk). 47 pages, 10 figures, including methods and supplementary informatio

The SOFIA Massive (SOMA) Star Formation Survey. I. Overview and First Results

We present an overview and first results of the Stratospheric Observatory For Infrared Astronomy Massive (SOMA) Star Formation Survey, which is using the FORCAST instrument to image massive protostars from $\sim10$--$40\:\rm{\mu}\rm{m}$. These wavelengths trace thermal emission from warm dust, which in Core Accretion models mainly emerges from the inner regions of protostellar outflow cavities. Dust in dense core envelopes also imprints characteristic extinction patterns at these wavelengths, causing intensity peaks to shift along the outflow axis and profiles to become more symmetric at longer wavelengths. We present observational results for the first eight protostars in the survey, i.e., multiwavelength images, including some ancillary ground-based MIR observations and archival {\it{Spitzer}} and {\it{Herschel}} data. These images generally show extended MIR/FIR emission along directions consistent with those of known outflows and with shorter wavelength peak flux positions displaced from the protostar along the blueshifted, near-facing sides, thus confirming qualitative predictions of Core Accretion models. We then compile spectral energy distributions and use these to derive protostellar properties by fitting theoretical radiative transfer models. Zhang and Tan models, based on the Turbulent Core Model of McKee and Tan, imply the sources have protostellar masses $m_*\sim10$--50$\:M_\odot$ accreting at $\sim10^{-4}$--$10^{-3}\:M_\odot\:{\rm{yr}}^{-1}$ inside cores of initial masses $M_c\sim30$--500$\:M_\odot$ embedded in clumps with mass surface densities $\Sigma_{\rm{cl}}\sim0.1$--3$\:{\rm{g\:cm}^{-2}}$. Fitting Robitaille et al. models typically leads to slightly higher protostellar masses, but with disk accretion rates $\sim100\times$ smaller. We discuss reasons for these differences and overall implications of these first survey results for massive star formation theories.Comment: Accepted to ApJ, 32 page

The SOFIA Massive (SOMA) Star Formation Survey. II. High Luminosity Protostars

We present multi-wavelength images observed with SOFIA-FORCAST from $\sim$10 to 40 $\mu$m of seven high luminosity massive protostars, as part of the SOFIA Massive (SOMA) Star Formation Survey. Source morphologies at these wavelengths appear to be influenced by outflow cavities and extinction from dense gas surrounding the protostars. Using these images, we build spectral energy distributions (SEDs) of the protostars, also including archival data from Spitzer, Herschel and other facilities. Radiative transfer (RT) models of Zhang & Tan (2018), based on Turbulent Core Accretion theory, are then fit to the SEDs to estimate key properties of the protostars. Considering the best five models fit to each source, the protostars have masses $m_{*} \sim 12-64 \: M_{\odot}$ accreting at rates of $\dot{m}_{*} \sim 10^{-4}-10^{-3} \: M_{\odot} \: \rm yr^{-1}$ inside cores of initial masses $M_{c} \sim 100-500 \: M_{\odot}$ embedded in clumps with mass surface densities $\Sigma_{\rm cl} \sim 0.1-3 \: \rm g \: cm^{-2}$ and span a luminosity range of $10^{4} -10^{6} \: L_{\odot}$. Compared with the first eight protostars in Paper I, the sources analyzed here are more luminous, and thus likely to be more massive protostars. They are often in a clustered environment or have a companion protostar relatively nearby. From the range of parameter space of the models, we do not see any evidence that $\Sigma_{\rm cl}$ needs to be high to form these massive stars. For most sources the RT models provide reasonable fits to the SEDs, though the cold clump material often influences the long wavelength fitting. However, for sources in very clustered environments, the model SEDs may not be such a good description of the data, indicating potential limitations of the models for these regions.Comment: 30 pages, 19 figures, Accepted for publication in Ap

Evaluation of the Efficacy and Safety of a Marine-Derived Bacillus Strain for Use as an In-Feed Probiotic for Newly Weaned Pigs

peer-reviewedForty eight individual pigs (8.7±0.26 kg) weaned at 28±1 d of age were used in a 22-d study to evaluate the effect of oral administration of a Bacillus pumilus spore suspension on growth performance and health indicators. Treatments (n = 16) were: (1) non-medicated diet; (2) medicated diet with apramycin (200 mg/kg) and pharmacological levels of zinc oxide (2,500 mg zinc/kg) and (3) B. pumilus diet (non-medicated diet + 1010 spores/day B. pumilus). Final body weight and average daily gain tended to be lower (P = 0.07) and feed conversion ratio was worsened (P<0.05) for the medicated treatment compared to the B. pumilus treatment. Ileal E. coli counts were lower for the B. pumilus and medicated treatments compared to the non-medicated treatment (P<0.05), perhaps as a result of increased ileal propionic acid concentrations (P<0.001). However, the medicated treatment reduced fecal (P<0.001) and cecal (P<0.05) Lactobacillus counts and tended to reduce the total cecal short chain fatty acid (SCFA) concentration (P = 0.10). Liver weights were lighter and concentrations of liver enzymes higher (P<0.05) in pigs on the medicated treatment compared to those on the non-medicated or B. pumilus treatments. Pigs on the B. pumilus treatment had lower overall lymphocyte and higher granulocyte percentages (P<0.001) and higher numbers of jejunal goblet cells (P<0.01) than pigs on either of the other two treatments or the non-medicated treatment, respectively. However, histopathological examination of the small intestine, kidneys and liver revealed no abnormalities. Overall, the B. pumilus treatment decreased ileal E. coli counts in a manner similar to the medicated treatment but without the adverse effects on growth performance, Lactobacillus counts, cecal SCFA concentration and possible liver toxicity experienced with the medicated treatment.The study was funded by the Higher Education Authority/Institutes of Technology Ireland Technological Sector Research Strand III Programme

A Massive Protostar Forming by Ordered Collapse of a Dense, Massive Core

We present 30 and 40 micron imaging of the massive protostar G35.20-0.74 with SOFIA-FORCAST. The high surface density of the natal core around the protostar leads to high extinction, even at these relatively long wavelengths, causing the observed flux to be dominated by that emerging from the near-facing outflow cavity. However, emission from the far-facing cavity is still clearly detected. We combine these results with fluxes from the near-infrared to mm to construct a spectral energy distribution (SED). For isotropic emission the bolometric luminosity would be 3.3x10^4 Lsun. We perform radiative transfer modeling of a protostar forming by ordered, symmetric collapse from a massive core bounded by a clump with high mass surface density, Sigma_cl. To fit the SED requires protostellar masses ~20-34 Msun depending on the outflow cavity opening angle (35 - 50 degrees), and Sigma_cl ~ 0.4-1 g cm-2. After accounting for the foreground extinction and the flashlight effect, the true bolometric luminosity is ~ (0.7-2.2)x10^5 Lsun. One of these models also has excellent agreement with the observed intensity profiles along the outflow axis at 10, 18, 31 and 37 microns. Overall our results support a model of massive star formation involving the relatively ordered, symmetric collapse of a massive, dense core and the launching bipolar outflows that clear low density cavities. Thus a unified model may apply for the formation of both low and high mass stars.Comment: 6 pages, 4 figures, 1 table, accepted to Ap

Powering population health research: Considerations for plausible and actionable effect sizes

Evidence for Action (E4A), a signature program of the Robert Wood Johnson Foundation, funds investigator-initiated research on the impacts of social programs and policies on population health and health inequities. Across thousands of letters of intent and full proposals E4A has received since 2015, one of the most common methodological challenges faced by applicants is selecting realistic effect sizes to inform power and sample size calculations. E4A prioritizes health studies that are both (1) adequately powered to detect effect sizes that may reasonably be expected for the given intervention and (2) likely to achieve intervention effects sizes that, if demonstrated, correspond to actionable evidence for population health stakeholders. However, little guidance exists to inform the selection of effect sizes for population health research proposals. We draw on examples of five rigorously evaluated population health interventions. These examples illustrate considerations for selecting realistic and actionable effect sizes as inputs to power and sample size calculations for research proposals to study population health interventions. We show that plausible effects sizes for population health inteventions may be smaller than commonly cited guidelines suggest. Effect sizes achieved with population health interventions depend on the characteristics of the intervention, the target population, and the outcomes studied. Population health impact depends on the proportion of the population receiving the intervention. When adequately powered, even studies of interventions with small effect sizes can offer valuable evidence to inform population health if such interventions can be implemented broadly. Demonstrating the effectiveness of such interventions, however, requires large sample sizes.Comment: 24 pages, 1 figur

Building the evidence on Making Health a Shared Value: Insights and considerations for research.

The Robert Wood Johnson Foundation (RWJF)'s Culture of Health Action Framework guides a movement to improve health and advance health equity across the nation. Action Area One of the Framework, Making Health a Shared Value, highlights the role of individual and community factors in achieving a societal commitment to health and health equity, centered around three drivers: Mindset and Expectations, Sense of Community, and Civic Engagement. To stimulate research about how Action Area One and its drivers may impact health, Evidence for Action (E4A), a signature research funding program of RWJF, developed and released a national Call for Proposals (CFP). The process of formulating the CFP and reviewing proposals surfaced important challenges for research on creating and sustaining shared values to foster and maintain a Culture of Health. In this essay, we describe these considerations and provide examples from funded projects regarding how challenges can be addressed