Engineered Human Skin Substitutes Undergo Large-Scale Genomic Reprogramming and Normal Skin-Like Maturation after Transplantation to Athymic Mice

Bioengineered skin substitutes can facilitate wound closure in severely burned patients, but deficiencies limit their outcomes compared with native skin autografts. To identify gene programs associated with their in vivo capabilities and limitations, we extended previous gene expression profile analyses to now compare engineered skin after in vivo grafting with both in vitro maturation and normal human skin. Cultured skin substitutes were grafted on full-thickness wounds in athymic mice, and biopsy samples for microarray analyses were collected at multiple in vitro and in vivo time points. Over 10,000 transcripts exhibited large-scale expression pattern differences during in vitro and in vivo maturation. Using hierarchical clustering, 11 different expression profile clusters were partitioned on the basis of differential sample type and temporal stage-specific activation or repression. Analyses show that the wound environment exerts a massive influence on gene expression in skin substitutes. For example, in vivo–healed skin substitutes gained the expression of many native skin-expressed genes, including those associated with epidermal barrier and multiple categories of cell–cell and cell–basement membrane adhesion. In contrast, immunological, trichogenic, and endothelial gene programs were largely lacking. These analyses suggest important areas for guiding further improvement of engineered skin for both increased homology with native skin and enhanced wound healing

A Review of Target Mass Corrections

With recent advances in the precision of inclusive lepton--nuclear scattering experiments, it has become apparent that comparable improvements are needed in the accuracy of the theoretical analysis tools. In particular, when extracting parton distribution functions in the large-x region, it is crucial to correct the data for effects associated with the nonzero mass of the target. We present here a comprehensive review of these target mass corrections (TMC) to structure functions data, summarizing the relevant formulas for TMCs in electromagnetic and weak processes. We include a full analysis of both hadronic and partonic masses, and trace how these effects appear in the operator product expansion and the factorized parton model formalism, as well as their limitations when applied to data in the x->1 limit. We evaluate the numerical effects of TMCs on various structure functions, and compare fits to data with and without these corrections.Comment: 41 pages, 13 figures; minor updates to match published versio

National Athletic Trainers\u27 Association Position Statement: Evaluation, Management, and Outcomes of and Return-to-Play Criteria for Overhead Athletes With Superior Labral Anterior-Posterior Injuries

Objective: To present recommendations for the diagnosis, management, outcomes, and return to play of athletes with superior labral anterior-posterior (SLAP) injuries. Background: In overhead athletes, SLAP tears are common as either acute or chronic injuries. The clinical guidelines presented here were developed based on a systematic review of the current evidence and the consensus of the writing panel. Clinicians can use these guidelines to inform decision making regarding the diagnosis, acute and long-term conservative and surgical treatment, and expected outcomes of and return-to-play guidelines for athletes with SLAP injuries. Recommendations: Physical examination tests may aid diagnosis; 6 tests are recommended for confirming and 1 test is recommended for ruling out a SLAP lesion. Combinations of tests may be helpful to diagnose SLAP lesions. Clinical trials directly comparing outcomes between surgical and nonoperative management are absent; however, in cohort trials, the reports of function and return-to-sport outcomes are similar for each management approach. Nonoperative management that includes rehabilitation, nonsteroidal anti-inflammatory drugs, and corticosteroid injections is recommended as the first line of treatment. Rehabilitation should address deficits in shoulder internal rotation, total arc of motion, and horizontal-adduction motion, as well as periscapular and glenohumeral muscle strength, endurance, and neuromuscular control. Most researchers have examined the outcomes of surgical management and found high levels of satisfaction and return of shoulder function, but the ability to return to sport varied widely, with 20% to 94% of patients returning to their sport after surgical or nonoperative management. On average, 55% of athletes returned to full participation in prior sports, but overhead athletes had a lower average return of 45%. Additional work is needed to define the criteria for diagnosing and guiding clinical decision making to optimize outcomes and return to play

Broadening Participation in Biology Education Research: Engaging Community College Students and Faculty

Nearly half of all undergraduates are enrolled at community colleges (CCs), including the majority of U.S. students who represent groups underserved in the sciences. Yet only a small minority of studies published in discipline-based education research journals address CC biology students, faculty, courses, or authors. This marked underrepresentation of CC biology education research (BER) limits the availability of evidence that could be used to increase CC student success in biology programs. To address this issue, a diverse group of stakeholders convened at the Building Capacity for Biology Education Research at Community Colleges meeting to discuss how to increase the prevalence of CC BER and foster participation of CC faculty as BER collaborators and authors. The group identified characteristics of CCs that make them excellent environments for studying biology teaching and learning, including student diversity and institutional cultures that prioritize teaching, learning, and assessment. The group also identified constraints likely to impede BER at CCs: limited time, resources, support, and incentives, as well as misalignment between doing research and CC faculty identities as teachers. The meeting culminated with proposing strategies for faculty, administrators, journal editors, scientific societies, and funding agencies to better support CC BER

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease

Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. Results: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. Conclusions: These data do not justify use of CoQ as a treatment to slow functional decline in HD

A Probabilistic, Distributed, Recursive Mechanism for Decision-making in the Brain

Decision formation recruits many brain regions, but the procedure they jointly execute is unknown. Here we characterize its essential composition, using as a framework a novel recursive Bayesian algorithm that makes decisions based on spike-trains with the statistics of those in sensory cortex (MT). Using it to simulate the random-dot-motion task, we demonstrate it quantitatively replicates the choice behaviour of monkeys, whilst predicting losses of otherwise usable information from MT. Its architecture maps to the recurrent cortico-basal-ganglia-thalamo-cortical loops, whose components are all implicated in decision-making. We show that the dynamics of its mapped computations match those of neural activity in the sensorimotor cortex and striatum during decisions, and forecast those of basal ganglia output and thalamus. This also predicts which aspects of neural dynamics are and are not part of inference. Our single-equation algorithm is probabilistic, distributed, recursive, and parallel. Its success at capturing anatomy, behaviour, and electrophysiology suggests that the mechanism implemented by the brain has these same characteristics