Most ankle sprain research is either false or clinically unimportant: A 30-year audit of Randomized Controlled Trials

Background: Lateral ankle sprain is the most common musculoskeletal injury. Although clinical research in this field is growing, there is a broader concern that clinical trial outcomes are often false and fail to translate into patient benefits. Methods: We audited 30 years of experimental research related to lateral ankle sprain management (n = 74 randomized controlled trials) to determine if reports of treatment effectiveness could be validated beyond statistical certainty. Results: A total of 77% of trials reported positive treatment effects, but there was a high risk of false discovery. Most trials were unregistered and relied solely on statistical significance, or lack of statistical significance, rather than on interpreting key measures of minimum clinical importance (e.g., minimal detectable change, minimal clinically important difference). Conclusion: Future clinical trials must adopt higher standards of reporting and data interpretation. This includes consideration of the ethical responsibility to preregister their research and interpretation of clinical outcomes beyond statistical significance

Summer-Long Grazing of High vs. Low Endophyte (\u3cem\u3eNeotyphodium coenophialum\u3c/em\u3e)-Infected Tall Fescue by Growing Beef Steers Results in Distinct Temporal Blood Analyte Response Patterns, with Poor Correlation to Serum Prolactin Levels

Previously, we reported the effects of fescue toxicosis on developing Angus-cross steer growth, carcass, hepatic mRNA, and protein expression profiles of selected serum proteins, and blood clinical and chemical profiles, after summer-long grazing (85 days) of high endophyte (HE)- vs. low endophyte (LE)-infected fescue pastures. We now report the temporal development of acute, intermediate, and chronic responses of biochemical and clinical blood analytes determined at specified time intervals (period 1, day 0–36; period 2, day 37–58; and period 3, day 59–85). Throughout the trial, the alkaloid concentrations of the HE forage was consistently 19–25 times greater (P ≤ 0.002) than the concentration in the LE forage, and HE vs. LE steers had continuously lower (P ≤ 0.049) serum prolactin (85%), cholesterol (27%), and albumin (5%), but greater red blood cells (7%). The HE steers had decreased (P = 0.003) ADG only during period 1 (−0.05 vs. 0.4 kg/day). For period 1, HE steers had reduced (P ≤ 0.090) numbers of eosinophils (55%) and lymphocytes (18%), serum triglyceride (27%), and an albumin/globulin ratio (9%), but an increased bilirubin concentration (20%). During period 2, serum LDH activities were 18% lower (P = 0.022) for HE vs. LE steers. During period 3, serum levels of ALP (32%), ALT (16%), AST (15%), creatine kinase (35%), glucose (10%), and LDH (23%) were lower (P ≤ 0.040) for HE steers. Correlation analysis of serum prolactin and other blood analytes revealed that triglycerides (P = 0.042) and creatinine (P = 0.021) were moderately correlated (r ≤ 0.433) with HE serum prolactin. In conclusion, three HE-induced blood analyte response patterns were identified: continually altered, initially altered, and subsequently “recovered,” or altered only after long-term exposure. Blood analytes affected by length of grazing HE vs. LE forages were either not or poorly correlated with serum prolactin. These data reveal important, temporal, data about how young cattle respond to the challenge of consuming HE pasture

Spectral Functions of the Uniform Electron Gas via Coupled-Cluster Theory and Comparison to the GWGW and Related Approximations

We use, for the first time, ab initio coupled-cluster theory to compute the spectral function of the uniform electron gas at a Wigner-Seitz radius of $r_\mathrm{s}=4$. The coupled-cluster approximations we employ go significantly beyond the diagrammatic content of state-of-the-art $GW$ theory. We compare our calculations extensively to $GW$ and $GW$-plus-cumulant theory, illustrating the strengths and weaknesses of these methods in capturing the quasiparticle and satellite features of the electron gas. Our accurate calculations further allow us to address the long-standing debate over the occupied bandwidth of metallic sodium. Our findings indicate that the future application of coupled-cluster theory to condensed phase material spectra is highly promising.Comment: 6 pages, 2 figure

Nutritional and Physiological Constraints Contributing to Limitations in Small Intestinal Starch Digestion and Glucose Absorption in Ruminants

Increased efficiency of nutrient utilization can potentially be gained with increased starch digestion in the small intestine in ruminants. However, ruminants have quantitative limits in the extent of starch disappearance in the small intestine. The objective is to explore the nutritional and physiological constraints that contribute to limitations of carbohydrate assimilation in the ruminant small intestine. Altered digesta composition and passage rate in the small intestine, insufficient pancreatic α-amylase and/or small intestinal carbohydrase activity, and reduced glucose absorption could all be potentially limiting factors of intestinal starch assimilation. The absence of intestinal sucrase activity in ruminants may be related to quantitative limits in small intestinal starch hydrolysis. Multiple sequence alignment of the sucrase-isomaltase complex gives insight into potential molecular mechanisms that may be associated with the absence of intestinal sucrase activity, reduced capacity for intestinal starch digestion, and limitations in the efficiency of feed utilization in cattle and sheep. Future research efforts in these areas will aid in our understanding of small intestinal starch digestion and glucose absorption to optimize feeding strategies for increased meat and milk production efficiency

Pituitary Genomic Expression Profiles of Steers Are Altered by Grazing of High vs. Low Endophyte-Infected Tall Fescue Forages

Consumption of ergot alkaloid-containing tall fescue grass impairs several metabolic, vascular, growth, and reproductive processes in cattle, collectively producing a clinical condition known as “fescue toxicosis.” Despite the apparent association between pituitary function and these physiological parameters, including depressed serum prolactin; no reports describe the effect of fescue toxicosis on pituitary genomic expression profiles. To identify candidate regulatory mechanisms, we compared the global and selected targeted mRNA expression patterns of pituitaries collected from beef steers that had been randomly assigned to undergo summer-long grazing (89 to 105 d) of a high-toxic endophyte-infected tall fescue pasture (HE; 0.746 μg/g ergot alkaloids; 5.7 ha; n = 10; BW = 267 ± 14.5 kg) or a low-toxic endophyte tall fescue–mixed pasture (LE; 0.023 μg/g ergot alkaloids; 5.7 ha; n = 9; BW = 266 ± 10.9 kg). As previously reported, in the HE steers, serum prolactin and body weights decreased and a potential for hepatic gluconeogenesis from amino acid-derived carbons increased. In this manuscript, we report that the pituitaries of HE steers had 542 differentially expressed genes (P \u3c 0.001, false discovery rate ≤ 4.8%), and the pattern of altered gene expression was dependent (P \u3c 0.001) on treatment. Integrated Pathway Analysis revealed that canonical pathways central to prolactin production, secretion, or signaling were affected, in addition to those related to corticotropin-releasing hormone signaling, melanocyte development, and pigmentation signaling. Targeted RT-PCR analysis corroborated these findings, including decreased (P \u3c 0.05) expression of DRD2, PRL, POU1F1, GAL, and VIP and that of POMC and PCSK1, respectively. Canonical pathway analysis identified HE-dependent alteration in signaling of additional pituitary-derived hormones, including growth hormone and GnRH. We conclude that consumption of endophyte-infected tall fescue alters the pituitary transcriptome profiles of steers in a manner consistent with their negatively affected physiological parameters

ALMA Observations of the Orion Proplyds

We present ALMA observations of protoplanetary disks ("proplyds") in the Orion Nebula Cluster. We imaged 5 individual fields at 856um containing 22 HST-identified proplyds and detected 21 of them. Eight of those disks were detected for the first time at submillimeter wavelengths, including the most prominent, well-known proplyd in the entire Orion Nebula, 114-426. Thermal dust emission in excess of any free-free component was measured in all but one of the detected disks, and ranged between 1-163 mJy, with resulting disk masses of 0.3-79 Mjup. An additional 26 stars with no prior evidence of associated disks in HST observations were also imaged within the 5 fields, but only 2 were detected. The disk mass upper limits for the undetected targets, which include OB stars, theta1Ori C and theta1Ori F, range from 0.1-0.6 Mjup. Combining these ALMA data with previous SMA observations, we find a lack of massive (>3 Mjup) disks in the extreme-UV dominated region of Orion, within 0.03 pc of O-star theta1Ori C. At larger separations from theta1Ori C, in the far-UV dominated region, there is a wide range of disk masses, similar to what is found in low-mass star forming regions. Taken together, these results suggest that a rapid dissipation of disk masses likely inhibits potential planet formation in the extreme-UV dominated regions of OB associations, but leaves disks in the far-UV dominated regions relatively unaffected.Comment: ApJ, in pres

A First Look at the Auriga-California Giant Molecular Cloud With Herschel and the CSO: Census of the Young Stellar Objects and the Dense Gas

We have mapped the Auriga/California molecular cloud with the Herschel PACS and SPIRE cameras and the Bolocam 1.1 mm camera on the Caltech Submillimeter Observatory (CSO) with the eventual goal of quantifying the star formation and cloud structure in this Giant Molecular Cloud (GMC) that is comparable in size and mass to the Orion GMC, but which appears to be forming far fewer stars. We have tabulated 60 compact 70/160um sources that are likely pre-main-sequence objects and correlated those with Spitzer and WISE mid-IR sources. At 1.1 mm we find 18 cold, compact sources and discuss their properties. The most important result from this part of our study is that we find a modest number of additional compact young objects beyond those identified at shorter wavelengths with Spitzer. We also describe the dust column density and temperature structure derived from our photometric maps. The column density peaks at a few x 10^22 cm^-2 (N_H2) and is distributed in a clear filamentary structure along which nearly all the pre-main-sequence objects are found. We compare the YSO surface density to the gas column density and find a strong non-linear correlation between them. The dust temperature in the densest parts of the filaments drops to ~10K from values ~ 14--15K in the low density parts of the cloud. We also derive the cumulative mass fraction and probability density function of material in the cloud which we compare with similar data on other star-forming clouds.Comment: in press Astrophysical Journal, 201

ALMA Observations of Asymmetric Molecular Gas Emission from a Protoplanetary Disk in the Orion Nebula

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations of molecular line emission from d216-0939, one of the largest and most massive protoplanetary disks in the Orion Nebula Cluster (ONC). We model the spectrally resolved HCO$^+$ (4--3), CO (3--2), and HCN (4--3) lines observed at 0\farcs5 resolution to fit the temperature and density structure of the disk. We also weakly detect and spectrally resolve the CS (7--6) line but do not model it. The abundances we derive for CO and HCO$^+$ are generally consistent with expected values from chemical modeling of protoplanetary disks, while the HCN abundance is higher than expected. We dynamically measure the mass of the central star to be $2.17\pm0.07\,M_\odot$ which is inconsistent with the previously determined spectral type of K5. We also report the detection of a spatially unresolved high-velocity blue-shifted excess emission feature with a measurable positional offset from the central star, consistent with a Keplerian orbit at $60\pm20\,\mathrm{au}$. Using the integrated flux of the feature in HCO$^+$ (4--3), we estimate the total H$_2$ gas mass of this feature to be at least $1.8-8\,M_\mathrm{Jupiter}$, depending on the assumed temperature. The feature is due to a local temperature and/or density enhancement consistent with either a hydrodynamic vortex or the expected signature of the envelope of a forming protoplanet within the disk.Comment: 19 pages, 12 figures, accepted for publication in A

The Signature of Primordial Grain Growth in the Polarized Light of the AU Mic Debris Disk

We have used the Hubble Space Telescope/ACS coronagraph to make polarization maps of the AU Mic debris disk. The fractional linear polarization rises monotonically from about 0.05 to 0.4 between 20 and 80 AU. The polarization is perpendicular to the disk, indicating that the scattered light originates from micron sized grains in an optically thin disk. Disk models, which simultaneously fit the surface brightness and polarization, show that the inner disk (< 40-50 AU) is depleted of micron-sized dust by a factor of more than 300, which means that the disk is collision dominated. The grains have high maximum linear polarization and strong forward scattering. Spherical grains composed of conventional materials cannot reproduce these optical properties. A Mie/Maxwell-Garnett analysis implicates highly porous (91-94%) particles. In the inner Solar System, porous particles form in cometary dust, where the sublimation of ices leaves a "bird's nest" of refractory organic and silicate material. In AU Mic, the grain porosity may be primordial, because the dust "birth ring" lies beyond the ice sublimation point. The observed porosities span the range of values implied by laboratory studies of particle coagulation by ballistic cluster-cluster aggregation. To avoid compactification, the upper size limit for the parent bodies is in the decimeter range, in agreement with theoretical predictions based on collisional lifetime arguments. Consequently, AU Mic may exhibit the signature of the primordial agglomeration process whereby interstellar grains first assembled to form macroscopic objects.Comment: 12 pages, 8 figures, ApJ, in pres