High dose multiple micronutrient supplementation improves villous morphology in environmental enteropathy without HIV enteropathy: results from a double-blind randomised placebo controlled trial in Zambian adults

PMCID: PMC3897937This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Direct Imaging Confirmation and Characterization of a Dust-Enshrouded Candidate Exoplanet Orbiting Fomalhaut

We present Subaru/IRCS J band data for Fomalhaut and a (re)reduction of archival 2004--2006 HST/ACS data first presented by Kalas et al. (2008). We confirm the existence of a candidate exoplanet, Fomalhaut b, in both the 2004 and 2006 F606W data sets at a high signal-to-noise. Additionally, we confirm the detection at F814W and present a new detection in F435W. Fomalhaut b's space motion may be consistent with it being in an apsidally-aligned, non debris ring-crossing orbit, although new astrometry is required for firmer conclusions. We cannot confirm that Fomalhaut b exhibits 0.7-0.8 mag variability cited as evidence for planet accretion or a semi-transient dust cloud. The new, combined optical SED and IR upper limits confirm that emission identifying Fomalhaut b originates from starlight scattered by small dust, but this dust is most likely associated with a massive body. The Subaru and IRAC/4.5 micron upper limits imply M < 2 Mj, still consistent with the range of Fomalhaut b masses needed to sculpt the disk. Fomalhaut b is very plausibly "a planet identified from direct imaging" even if current images of it do not, strictly speaking, show thermal emission from a directly imaged planet.Comment: 13 pages, 3 figures; ApJ Letters in press. Fixed one outdated reference and a few typo

Dimension reduction and shrinkage methods for high dimensional disease risk scores in historical data

Abstract Background Multivariable confounder adjustment in comparative studies of newly marketed drugs can be limited by small numbers of exposed patients and even fewer outcomes. Disease risk scores (DRSs) developed in historical comparator drug users before the new drug entered the market may improve adjustment. However, in a high dimensional data setting, empirical selection of hundreds of potential confounders and modeling of DRS even in the historical cohort can lead to over-fitting and reduced predictive performance in the study cohort. We propose the use of combinations of dimension reduction and shrinkage methods to overcome this problem, and compared the performances of these modeling strategies for implementing high dimensional (hd) DRSs from historical data in two empirical study examples of newly marketed drugs versus comparator drugs after the new drugs’ market entry—dabigatran versus warfarin for the outcome of major hemorrhagic events and cyclooxygenase-2 inhibitor (coxibs) versus nonselective non-steroidal anti-inflammatory drugs (nsNSAIDs) for gastrointestinal bleeds. Results Historical hdDRSs that included predefined and empirical outcome predictors with dimension reduction (principal component analysis; PCA) and shrinkage (lasso and ridge regression) approaches had higher c-statistics (0.66 for the PCA model, 0.64 for the PCA + ridge and 0.65 for the PCA + lasso models in the warfarin users) than an unreduced model (c-statistic, 0.54) in the dabigatran example. The odds ratio (OR) from PCA + lasso hdDRS-stratification [OR, 0.64; 95 % confidence interval (CI) 0.46–0.90] was closer to the benchmark estimate (0.93) from a randomized trial than the model without empirical predictors (OR, 0.58; 95 % CI 0.41–0.81). In the coxibs example, c-statistics of the hdDRSs in the nsNSAID initiators were 0.66 for the PCA model, 0.67 for the PCA + ridge model, and 0.67 for the PCA + lasso model; these were higher than for the unreduced model (c-statistic, 0.45), and comparable to the demographics + risk score model (c-statistic, 0.67). Conclusions hdDRSs using historical data with dimension reduction and shrinkage was feasible, and improved confounding adjustment in two studies of newly marketed medications

The Origin of Jovian Planets in Protostellar Disks: The Role of Dead Zones

The final masses of Jovian planets are attained when the tidal torques that they exert on their surrounding protostellar disks are sufficient to open gaps in the face of disk viscosity, thereby shutting off any further accretion. In sufficiently well-ionized disks, the predominant form of disk viscosity originates from the Magneto-Rotational Instability (MRI) that drives hydromagnetic disk turbulence. In the region of sufficiently low ionization rate -- the so-called dead zone -- turbulence is damped and we show that lower mass planets will be formed. We considered three ionization sources (X-rays, cosmic rays, and radioactive elements) and determined the size of a dead zone for the total ionization rate by using a radiative, hydrostatic equilibrium disk model developed by Chiang et al. (2001). We studied a range of surface mass density (Sigma_{0}=10^3 - 10^5 g cm^{-2}) and X-ray energy (kT_{x}=1 - 10 keV). We also compared the ionization rate of such a disk by X-rays with cosmic rays and find that the latter dominate X-rays in ionizing protostellar disks unless the X-ray energy is very high (5 - 10 keV). Among our major conclusions are that for typical conditions, dead zones encompass a region extending out to several AU -- the region in which terrestrial planets are found in our solar system. Our results suggest that the division between low and high mass planets in exosolar planetary systems is a consequence of the presence of a dead zone in their natal protoplanetary disks. We also find that the extent of a dead zone is mainly dependent on the disk's surface mass density. Our results provide further support for the idea that Jovian planets in exosolar systems must have migrated substantially inwards from their points of origin.Comment: 28 pages, 10 figures, accepted by Ap

The curious case of Mars' formation

Dynamical models of planet formation coupled with cosmochemical data from martian meteorites show that Mars' isotopic composition is distinct from that of Earth. Reconciliation of formation models with meteorite data require that Mars grew further from the Sun than its present position. Here, we evaluate this compositional difference in more detail by comparing output from two $N$-body planet formation models. The first of these planet formation models simulates what is termed the "Classical" case wherein Jupiter and Saturn are kept in their current orbits. We compare these results with another model based on the "Grand Tack", in which Jupiter and Saturn migrate through the primordial asteroid belt. Our estimate of the average fraction of chondrite assembled into Earth and Mars assumes that the initial solid disk consists of only sources of enstatite chondrite composition in the inner region, and ordinary chondrite in the outer region. Results of these analyses show that both models tend to yield Earth and Mars analogues whose accretion zones overlap. The Classical case fares better in forming Mars with its documented composition (29% to 68% enstatite chondrite plus 32% to 67% ordinary chondrite) though the Mars analogues are generally too massive. However, if we include the restriction of mass on the Mars analogues, the Classical model does not work better. We also further calculate the isotopic composition of $^{17} \rm O$, $^{50} \rm Ti$, $^{54} \rm Cr$, $^{142} \rm Nd$, $^{64} \rm Ni$, and $^{92} \rm Mo$ in the martian mantle from the Grand Tack simulations. We find that it is possible to match the calculated isotopic composition of all the above elements in Mars' mantle with their measured values, but the resulting uncertainties are too large to place good restriction on the early dynamical evolution and birth place of Mars.Comment: 14 pages, 8 figures, presented in the 2017 DPS meeting, 2018 Solar system symposium in Sapporo and 2018 AOGS annual meeting, Accepted for publishing in A&

Deep Thermal Infrared Imaging of HR 8799 bcde: New Atmospheric Constraints and Limits on a Fifth Planet

We present new $L^\prime$ (3.8 $\mu m$) and Br-$\alpha$ (4.05 $\mu m$) data and reprocessed archival $L^\prime$ data for the young, planet-hosting star HR 8799 obtained with Keck/NIRC2, VLT/NaCo and Subaru/IRCS. We detect all four HR 8799 planets in each dataset at a moderate to high signal-to-noise (SNR $\gtrsim$ 6-15). We fail to identify a fifth planet, "HR 8799 f", at $r$ $<$ 15 $AU$ at a 5-$\sigma$ confidence level: one suggestive, marginally significant residual at 0.2" is most likely a PSF artifact. Assuming companion ages of 30 $Myr$ and the Baraffe (Spiegel \& Burrows) planet cooling models, we rule out an HR 8799 f with mass of 5 $M_{J}$ (7 $M_{J}$), 7 $M_{J}$ (10 $M_{J}$), and 12 $M_{J}$ (13 $M_{J}$) at $r_{proj}$ $\sim$ 12 $AU$, 9 $AU$, and 5 $AU$, respectively. All four HR 8799 planets have red early T dwarf-like $L^\prime$ - [4.05] colors, suggesting that their SEDs peak in between the $L^\prime$ and $M^\prime$ broadband filters. We find no statistically significant difference in HR 8799 cde's colors. Atmosphere models assuming thick, patchy clouds appear to better match HR 8799 bcde's photometry than models assuming a uniform cloud layer. While non-equilibrium carbon chemistry is required to explain HR 8799 bc's photometry/spectra, evidence for it from HR 8799 de's photometry is weaker. Future, deep IR spectroscopy/spectrophotometry with the Gemini Planet Imager, SCExAO/CHARIS, and other facilities may clarify whether the planets are chemically similar or heterogeneous.Comment: 18 pages, 6 Tables, and 9 Figures. Fig. 1a is the key figure. Accepted for publication in Ap

Lifestyle Changes in Relation to Initiation of Antihypertensive and Lipid-Lowering Medication : A Cohort Study

Background--Lifestyle modification is a key component of cardiovascular disease prevention before and concurrently with pharmacologic interventions. We evaluated whether lifestyle factors change in relation to the initiation of antihypertensive or lipidlowering medication (statins). Methods and Results--The study population comprised 41 225 participants of the FPS (Finnish Public Sector) study aged =40 years who were free of cardiovascular disease at baseline and responded to =2 consecutive surveys administered in 4-year intervals in 2000-2013. Medication use was ascertained through pharmacy-claims data. Using a series of pre-post data sets, we compared changes in body mass index, physical activity, alcohol consumption, and smoking between 8837 initiators and 46 021 noninitiators of antihypertensive medications or statins. In participants who initiated medication use, body mass index increased more (difference in change 0.19; 95% CI, 0.16-0.22) and physical activity declined (-0.09 metabolic equivalent of task hour/day; 95% CI, -0.16 to -0.02) compared with noninitiators. The likelihood of becoming obese (odds ratio: 1.82; 95% CI, 1.63-2.03) and physically inactive (odds ratio: 1.08; 95% CI, 1.01-1.17) was higher in initiators. However, medication initiation was associated with greater decline in average alcohol consumption (-1.85 g/week; 95% CI, -3.67 to -0.14) and higher odds of quitting smoking (odds ratio for current smoking in the second survey: 0.74; 95% CI, 0.64-0.85). Conclusions--These findings suggest that initiation of antihypertensive and statin medication is associated with lifestyle changes, some favorable and others unfavorable. Weight management and physical activity should be encouraged in individuals prescribed these medications.Peer reviewe

Impact of Baseline Heart Failure Burden on Post-Implantable Cardioverter-Defibrillator Mortality Among Medicare Beneficiaries

ObjectivesThis study sought to assess the impact of baseline heart failure (HF) burden on survival with primary implantable cardioverter-defibrillator (ICD) among Medicare recipients.BackgroundSurvival after primary ICD implantation may differ between trial and Medicare populations.MethodsLinking data from the CMS (Centers for Medicare and Medicaid Services) ICD registry and the Medicare files (2005 to 2009), we identified primary ICD recipients age ≥66 years with ejection fraction ≤35%. Number of previous HF hospitalizations (prev-HF-hosp) and length of hospitalization prior to implantation were used to define HF burden. Crude all-cause mortality was estimated. Adjusted hazard ratios (HR) were derived from Cox models.ResultsOf 66,974 ICD recipients (73% men, 88% white, mean age 75 years), 11,876 died (average follow-up = 1.4 years), with 3-year mortality of 31%. Among patients with no prev-HF-hosp, 3-year mortality was 27% compared with 63% in those with ≥3 prev-HF-hosp (adjusted HR: 1.8). Among patients with same-day implantation, 3-year mortality was 25% compared with 53% in those with >1-week hospitalization days prior to implantation (adjusted HR: 1.9). Mortality at 3-year follow-up among the 31,685 ICD recipients with no prev-HF-hosp and same-day implantation (low HF burden) was similar to that in trials (22%).ConclusionsNearly one-third of Medicare ICD recipients died within 3 years, reflecting a population with more advanced age and disease than seen in trial populations for primary prevention ICD. Nearly one-half of Medicare recipients had a low HF burden and had a survival similar to trial ICD recipients. Future research is warranted to understand the effectiveness of primary ICD implantation among Medicare beneficiaries with heavy HF burdens

Modelling climate change impact on the spatial distribution of fresh water snails hosting trematodes in Zimbabwe

BACKGROUND: Freshwater snails are intermediate hosts for a number of trematodes of which some are of medical and veterinary importance. The trematodes rely on specific species of snails to complete their life cycle; hence the ecology of the snails is a key element in transmission of the parasites. More than 200 million people are infected with schistosomes of which 95% live in sub-Saharan Africa and many more are living in areas where transmission is on-going. Human infection with the Fasciola parasite, usually considered more of veterinary concern, has recently been recognised as a human health problem. Many countries have implemented health programmes to reduce morbidity and prevalence of schistosomiasis, and control programmes to mitigate food-borne fascioliasis. As these programmes are resource demanding, baseline information on disease prevalence and distribution becomes of great importance. Such information can be made available and put into practice through maps depicting spatial distribution of the intermediate snail hosts. METHODS: A biology driven model for the freshwater snails Bulinus globosus, Biomphalaria pfeifferi and Lymnaea natalensis was used to make predictions of snail habitat suitability by including potential underlying environmental and climatic drivers. The snail observation data originated from a nationwide survey in Zimbabwe and the prediction model was parameterised with a high resolution Regional Climate Model. Georeferenced prevalence data on urinary and intestinal schistosomiasis and fascioliasis was used to calibrate the snail habitat suitability predictions to produce binary maps of snail presence and absence. RESULTS: Predicted snail habitat suitability across Zimbabwe, as well as the spatial distribution of snails, is reported for three time slices representative for present (1980-1999) and future climate (2046-2065 and 2080-2099). CONCLUSIONS: It is shown from the current study that snail habitat suitability is highly variable in Zimbabwe, with distinct high- and low- suitability areas and that temperature may be the main driving factor. It is concluded that future climate change in Zimbabwe may cause a reduced spatial distribution of suitable habitat of host snails with a probable exception of Bi. pfeifferi, the intermediate host for intestinal schistosomiasis that may increase around 2055 before declining towards 2100. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-014-0536-0) contains supplementary material, which is available to authorized users