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Background: Detailed characterization of on-field helmet impacts in football through video analysis has mostly been limited to professional games due to the availability of high quality, multi-view video (e.g., broadcast footage). Few studies have assessed youth football helmet impacts using video-based methods, often with only a single-camera view. Objective: A multi-camera approach was used in this observation-based study to describe the mechanisms and situational factors of in-game helmet impacts experienced by youth football players. Methods: A descriptive video analysis was performed in which video of three games from two old divisions (game A: 9–12 years; games B and C: 13–14 years) was reviewed and parameters related to all cases of observed helmet impact were documented. Results: Overall, 95 helmet impact cases were identified (single helmet contact: 81.1%; multiple helmet contacts: 18.9%), with 115 helmet contacts. Helmet-to-ground contacts were most common (59.1%), followed by helmet-to-helmet (24.3%) and helmet-to-body (16.5%). Helmet impact cases generally occurred during a rush play (67.4%) and were concentrated in the mid-field (81%). Helmet contact locations were predominantly distributed between the rear (upper) (28.7%) and side (upper) (27.8%) helmet regions. Tackling was the most frequent activity leading to helmet impact (41.1%). Conclusion: These findings offer detailed on-field helmet impact characteristics at the youth level that can help inform athlete safety improvement efforts.

Purpose of Review Given the rapid development of diagnostic approaches to test for and diagnose infection with SARS-CoV-2, many options are available to assess infection. Multiple established diagnostic companies are now providing testing platforms whereas initially, testing was being performed with simple PCR-based tests using standard laboratory reagents. Recent Findings. Additional testing platforms continue to be developed but challenges with testing, including obtaining testing reagents and other related supplies, are frequently encountered. With time, the testing supply chain will improve and more companies will be providing materials to support these testing efforts. In the USA, the need for rapid assay development and subsequent approval through attainment of emergency use authorization (EUA) has superseded the traditional arduous diagnostic testing approval workflow mandated by the FDA. It is anticipated that the USA will be able to continue to significantly increase its testing capabilities to address this pandemic; however, challenges remain due to the diversity of the performance characteristics of tests being utilized. Summary This review provides an overview of the current diagnostic testing landscape, with pertinent information related to SARS-CoV-2 virology and antibody responses, that is available to diagnose infection.

The design of completely synthetic proteins from first principles—de novo protein design—is challenging. This is because, despite recent advances in computational protein-structure prediction and design, we do not understand fully the sequence-to-structure relationships for protein folding, assembly, and stabilization. Antiparallel 4-helix bundles are amongst the most studied scaffolds for de novo protein design. We set out to re-examine this target, and to determine clear sequence-to-structure relationships, or design rules, for the structure. Our aim was to determine a common and robust sequence background for designing multiple de novo 4-helix bundles, which, in turn, could be used in chemical and synthetic biology to direct protein-protein interactions and as scaffolds for functional protein design. Our approach starts by analyzing known antiparallel 4-helix coiled-coil structures to deduce design rules. In terms of the heptad repeat, abcdefg—i.e., the sequence signature of many helical bundles—the key features that we identify are: a = Leu, d = Ile, e = Ala, g = Gln, and the use of complementary charged residues at b and c. Next, we implement these rules in the rational design of synthetic peptides to form antiparallel homo- and heterotetramers. Finally, we use the sequence of the homotetramer to derive a single-chain 4-helix-bundle protein for recombinant production in E. coli. All of the assembled designs are confirmed in aqueous solution using biophysical methods, and ultimately by determining high-resolution X-ray crystal structures. Our route from peptides to proteins provides an understanding of the role of each residue in each design.

Fibrinogen replacement therapy is a treatment mainstay for patients with afibrinogenemia and significant bleeding. A male infant with congenital afibrinogenemia and several spontaneous hemarthroses commenced cryoprecipitate prophylaxis but developed severe urticarial reactions. He transitioned to a human fibrinogen concentrate (HFC) (RiaSTAP®, CSL Behring; 70 mg/kg biweekly) but continued experiencing hemarthroses (estimated annualized bleeding rate [ABR]: 5‐6) and severe anaphylactic reactions, despite pre‐ and postinfusion medications. Following switching to a new HFC (Fibryga®, Octapharma; 50 mg/kg biweekly), ABR was 0‐1 with no further infusion reactions. Aged 9 years, because of limited quality of life, development of obesity and fatty liver disease, he underwent orthotopic liver transplant (OLT) under HFC coverage. Pharmacokinetic analysis guided presurgical fibrinogen levels > 150 mg/dL. No intraoperative HFC infusions were required. Coagulation profile and fibrinogen levels remained within normal limits during and posttransplant. To our knowledge, this is the first pediatric report of afibrinogenemia successfully treated with OLT.

Background: Regression equations using anthropometric measurements to predict soft (fat mass [FM], lean mass [LM], wobbling mass [WM]) and rigid (bone mineral content [BMC]) tissue masses of the extremities and core body segments have been developed for younger adults (16-35 years), but not older adults (36-65 years). Tissue mass estimates such as these would facilitate biomechanical modeling and analyses of older adults following fall or collision-related impacts that might occur during sport and recreational activities. Purpose: The purpose of this study was to expand on the previously established tissue mass prediction equations of the head, neck, trunk, and pelvis for healthy, younger adults by generating a comparable set of equations for an older adult population. Methods: A generation sample (38 males, 38 females) was used to create head, neck, trunk, and pelvis tissue mass prediction equations via multiple linear stepwise regression. A validation sample (13 males, 12 females) was used to assess equation accuracy; actual tissue masses were acquired from manually segmented full body Dual-Energy X-ray Absorptiometry scans. Results: Adjusted R2 values for the prediction equations ranged from 0.326 to 0.949, where BMC equations showed the lowest explained variances overall. Mean relative errors between actual and predicted masses ranged from –2.6% to 6.1% for trunk LM and FM, respectively. All actual tissue masses except head BMC (R2 = 0.092) were significantly correlated to those predicted from the equations (R2 = 0.403 to 0.963). Conclusion: This research provides a simple and effective method for predicting head, neck, trunk, and pelvis tissue masses in older adults that can be incorporated into biomechanical models for analyzing sport and recreational activities. Future work with this population should aim to improve core segment BMC predictions and develop equations for the extremities.

Soft tissues overlying the hip play a critical role in protecting against fractures during fall-related hip impacts. Consequently, the development of an efficient and cost-effective method for estimating hip soft tissue thicknesses in living people may prove to be valuable for assessing an individual’s injury risk and need to adopt preventative measures. The present study used multiple linear stepwise regression to generate prediction equations from participant characteristics (i.e., height, sex) and anthropometric measurements of the pelvis, trunk, and thigh to estimate soft tissue thickness at the iliac crests (IC) and greater trochanters (GT) in younger (16–35 years of age: 37 males, 37 females) and older (36–65 years of age: 38 males, 38 females) adults. Equations were validated against soft tissue thicknesses measured from full body Dual-energy X-ray Absorptiometry scans of independent samples (younger: 13 males, 13 females; older: 13 males, 12 females). Younger adult prediction equations exhibited adjusted R2 values ranging from 0.704 to 0.791, with more explained variance for soft tissue thicknesses at the GT than the IC; corresponding values for the older adult equations were higher overall and ranged from 0.819 to 0.852. Predicted and actual soft tissue thicknesses were significantly correlated for both the younger (R2 = 0.466 to 0.738) and older (R2 = 0.842 to 0.848) adults, averaging ≤ 0.75cm of error. This research demonstrates that soft tissue thicknesses overlying the GT and IC can be accurately predicted from equations using anthropometric measurements. These equations can be used by clinicians to identify individuals at higher risk of hip fractures who may benefit from the use of preventative measures.

Phosphatidyl inositol (4,5)-bisphosphate (PI(4,5)P

Though much literature describes the value of experiential and place-based learning experiences for participants, we have found little comparable literature regarding the facilitator experience. This paper provides current and future facilitators of workshops, especially those that take place outdoors, our reflections and ideas as facilitators, including tips for success. Our findings reinforce the conclusion that experiential learning can be as beneficial and transformative for facilitators as for participants, and that what we encounter during workshops parallels what students may go through in our classrooms as they learn. We identify five clear themes from facilitator reflections and encourage readers to consider leading an outdoor experiential learning sessions. Keywords: reflection, facilitators; outdoor education; place-based learning; conference pedagogy; educational development S’il existe beaucoup d’études décrivant la valeur des expériences d’apprentissage expérientiel axé sur la dimension locale, notre examen a révélé peu d’études du genre portant sur l’animateur. Notre article présente des idées, des réflexions et des conseils à l’intention des personnes qui animent ou animeront des ateliers, tout particulièrement des ateliers en plein air, en vue de la réussite de ces activités. Nos conclusions indiquent, premièrement, que l’apprentissage expérientiel peut être bénéfique et peut induire des changements chez l’animateur aussi bien que chez le participant et, deuxièmement, que notre expérience en tant qu’animateurs au cours des ateliers recoupe l’expérience d’apprentissage des étudiants en classe. Nous cernons cinq thèmes issus des réflexions des animateurs et nous encourageons les lecteurs de l’article à envisager la possibilité d’animer des sessions d’apprentissage expérientiel en plein air. Mots clés : réflexion, animateurs; enseignement en plein air; apprentissage axé sur la dimension locale; pédagogie de conférence; perfectionnement de l’enseignement

Background: Muscle activations (MA) during maximum voluntary contractions (MVC) are commonly utilized to normalize muscle contributions. Isometric MVC protocols may not activate muscles to the same extent as during dynamic activities, such as falls on outstretched hands (FOOSH), that can occur during sport or recreational activities. Objective: The purpose of this study was to compare the peak MA of upper extremity muscles during isometric and dynamic MVC protocols. Methods: Twenty-four (12 M, 12 F) university-aged participants executed wrist and elbow flexion and extension actions during five-second MVC protocols targeting six upper extremity muscles (three flexors and three extensors). Each protocol [isometric (ISO); dynamic (eccentric (ECC), concentric (CON), elastic band (ELAS), un-resisted (UNRES)] consisted of three contractions (with one-minute rest periods between) during two sessions separated by one week. Muscle activation levels were collected using standard electromyography (EMG) preparations, electrode placements and equipment reported previously. Results: Overall, the ECC and CON dynamic protocols consistently elicited higher peak muscle activation levels than the ISO protocol for both males and females during both sessions. Over 95% of the CON trials resulted in mean and peak muscle activation ratios greater than ISO, with 56.3% being significantly greater than ISO (p < 0.05). Conclusion: Higher activation levels can be elicited in upper extremity muscles when resistance is applied dynamically through a full range of motion during MVC protocols.

The scholarship of teaching and learning (SoTL) as a field invites researchers to examine their teaching practice with the goal of understanding its impact and effect on student learning (Hutchings & Shulman, 1999). Though inclusive by nature – belonging to no discipline yet informing practice in all – SoTL does have its own discourse, assumptions, and literature that may intimidate disciplinary scholars. This paper uses the human body as a metaphor to explain how researchers from diverse disciplines can use familiar entry points to ease their transition into SoTL. We identify and analyze parts and systems of the human and research body, revealing connections between particular disciplinary research bodies and the SoTL research body – connections that we hope provide disciplinary scholars with the confidence they need to navigate and engage in SoTL.

Protein–protein interactions (PPIs) are central to biological mechanisms, and can serve as compelling targets for drug discovery. Yet, the discovery of small molecule inhibitors of PPIs remains challenging given the large and typically shallow topography of the interacting protein surfaces. Here, we describe a general approach to the discovery of orthosteric PPI inhibitors that mimic specific secondary protein structures. Initially, hot residues at protein–protein interfaces are identified in silico or from experimental data, and incorporated into secondary structure-based queries. Virtual libraries of small molecules are then shape-matched against the queries, and promising ligands docked to target proteins. The approach is exemplified experimentally using two unrelated PPIs that are mediated by an α-helix (p53/hDM2) and a β-strand (GKAP/SHANK1-PDZ). In each case, selective PPI inhibitors are discovered with low μM activity as determined by a combination of fluorescence anisotropy and 1H–15N HSQC experiments. In addition, hit expansion yields a series of PPI inhibitors with defined structure–activity relationships. It is envisaged that the generality of the approach will enable discovery of inhibitors of a wide range of unrelated secondary structure-mediated PPIs., Small-molecule protein–protein interaction inhibitors were prioritised on the basis of shape similarity to secondary structure-based queries incorporating hot-spot residues.

We describe a case of SARS-CoV-2 post-infectious inflammatory syndrome in an adult who presented with multiorgan failure two months following his initial diagnosis of SARS-CoV-2 infection. This case highlights clinician's early recognition of this devastating sequela and challenges in appropriate management of this patient.

Herein we measured CD4+ T-cell responses against common cold coronaviruses (CCC) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC-reactive T cells in SARS-CoV-2–seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 T-cell reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC T-cell reactivity was decreased in SARS-CoV-2–infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego. CD4+ T-cell responses against common cold coronaviruses (CCC) are elevated in SARS-CoV-2 seronegative high-risk health care workers (HCW) compared to COVID-19 convalescent HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses and/or cross-reactivity associated with a protective effect.

We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS), current Version 1.0, is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.

The synthetic cadaver is a high-fidelity model intended to replace or supplement other anatomy learning modalities. Academic attainment and student perceptions were examined in an undergraduate human anatomy course using a combination of plastic models and synthetic cadavers to learn lower body anatomy ("Experimental group"), compared to a Historical group who used only plastic models. Grades on an upper body test, for which both groups used only plastic models, were compared to ensure that no academic differences existed between groups (P = 0.7653). Students in the Experimental group performed better on the lower body test for which they used both plastic models and synthetic cadavers (median = 73.8% (95% CI: 72.0%-75.0%) compared to the Historical group (70.1% (95% CI: 68.3%-70.7%), P < 0.0001); however, less than half of students (49%) attributed this to the synthetic cadavers. Students' perception of laboratory resources (P < 0.0001) and learning experience (P < 0.0001) both improved with the addition of synthetic cadavers compared to using only plastic models, and 60% of students in the Experimental group agreed that the synthetic cadavers would be a key reason that they would choose that institution for undergraduate studies. This investigation showed improved student grades when plastic models and synthetic cadavers were combined, in addition to improved student perceptions of the learning experience. Results of the student questionnaires also suggested that although synthetic cadavers carry a notable up-front cost, they may be a useful recruitment tool for institutions.

Severe acute respiratory syndrome coronavirus 2 is associated with severe disease in patients with hematologic malignancy. We report a series of patients with underlying hematologic malignancy and coronavirus disease of 2019 with discrepancy between radiographic findings and molecular testing. Initial chest x-ray findings should raise suspicion in immunosuppressed patients with typical clinical presentation even with negative initial testing.

When South Florida became a hotspot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists and administrators, who rapidly built a multi-platform, PCR- and serology-based detection program, established drive-thru facilities and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and to multiple diagnostic laboratory companies and government officials enabled us to implement both FDA authorized and laboratory developed testing (LDT)-based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers, to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity, to testing hundreds of healthcare workers and patients daily, within three weeks. We believe our experience can inform the efforts of others, when faced with a crisis situation.

When South Florida became a hot spot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists, and administrators who rapidly built a multiplatform, polymerase chain reaction- and serology-based detection program, established drive-through facilities, and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and multiple diagnostic laboratory companies, and government officials enabled us to implement both Food and Drug Administration authorized and laboratory-developed testing-based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity to testing hundreds of health care workers and patients daily, within 3 weeks. We believe our experience can inform the efforts of others when faced with a crisis situation.

Background No reports describe falsepositive reverse transcriptase polymerase chain reaction (RT‐PCR) for novel coronavirus in preoperative screening. Methods Preoperative patients had one or two nasopharyngeal swabs, depending on low or high risk of viral transmission. Positive tests were repeated. Results Forty‐three of 52 patients required two or more preoperative tests. Four (9.3%) had discrepant results (positive/negative). One of these left the coronavirus disease (COVID) unit against medical advice despite an orbital abscess, with unknown true disease status. The remaining 3 of 42 (7.1%) had negative repeat RT‐PCR. Although ultimately considered falsepositives, one was sent to a COVID unit postoperatively and two had urgent surgery delayed. Assuming negative repeat RT‐PCR, clear chest imaging, and lack of subsequent symptoms represent the “gold standard,” RT‐PCR specificity was 0.97. Conclusions If false positives are suspected, we recommend computed tomography (CT) of the chest and repeat RT‐PCR. Validated serum immunoglobulin testing may ultimately prove useful.

Background: Investigating soft tissue motion related to impact events is important for understanding how the body mitigates potentially injurious forces through shock attenuation. Objectives: The aims of this study were to: 1) quantify displacement and velocity of the forearm soft tissues following forward fall impacts; and 2) compare two massless skin marker designs (single layer, uniform (SLU) design; stacked, non-uniform (SNU) design) in terms of how well they could be tracked over varying skin pigmentations using automated motion capture software. Methods: Two participant groups (skin pigmentation: light – 9F, 8M; dark – 9F, 6M) underwent simulated forward fall hand impacts for each marker design using a torso-release apparatus. Marker positions associated with planar motion of forearm soft tissues during impact were automatically tracked (ProAnalyst®) in the proximal-distal and anterior-posterior axes from high speed recordings (5000 f/s). Mean peak displacements and velocities for eight forearm regions were then calculated (LabVIEW®). Results: Overall, soft tissue displacement and velocity increased from distal to proximal forearm regions. The greatest displacement (1.47 cm) and velocity (112.8 cm/s) occurred distally toward the wrist. Soft tissue impact responses between sexes did not differ, on average (p > 0.05). The SLU and SNU markers produced different kinematic values (p < 0.05); however, the magnitudes of, and consequently meaningfulness of these statistical differences for automatically tracking soft tissue motion, were negligible (displacement: ≤ 0.05 cm; velocity: ≤ 2.5 cm/s). Conclusions: Forearm soft tissue motion was successfully quantified for forward fall hand impacts; both marker designs were deemed functionally equivalent.

A multi-disciplinary academic unit at a Canadian university completed an evaluation of course syllabi used in its undergraduate programmes over the previous five years. This paper examines the reasons for the evaluation, the processes employed to collect and analyse the data, and how the results will be incorporated into the next steps of the overall curricula reform planned within the unit. The evaluation focused on the unit’s adherence to departmental and university policies, course reading materials, experiential learning opportunities, forms of assessments (e.g. types and weighting of assignments), learning outcomes and instructor-specific policies (e.g. group work expectations, late assignments). While a summary of the results of the evaluation are provided herein, these are meant to highlight the administrative and curricular benefits and uses of the data, rather than an analysis and discussion of the results themselves.

Accurate prediction of wobbling mass (WM), fat mass (FM), lean mass (LM), and bone mineral content (BMC) of living people using regression equations developed from anthropometric measures (lengths, circumferences, breadths, skinfolds) has previously been reported, but only for the extremities. Multiple linear stepwise regression was used to generate comparable equations for the head, neck, trunk, and pelvis of young adults (38 males, 38 females). Equations were validated using actual tissue masses from an independent sample of 13 males and 13 females by manually segmenting full-body dual-energy x-ray absorptiometry scans. Prediction equations exhibited adjusted R2 values ranging from .249 to .940, with more explained variance for LM and WM than BMC and FM, especially for the head and neck. Mean relative errors between predicted and actual tissue masses ranged from −11.07% (trunk FM) to 7.61% (neck FM). Actual and predicted tissue masses from all equations were significantly correlated (R2 = .329 to .937), except head BMC (R2 = .046). These results show promise for obtaining in-vivo head, neck, trunk, and pelvis tissue mass estimates in young adults. Further research is needed to improve head and neck FM and BMC predictions and develop tissue mass prediction equations for older populations.

Background: Hip muscle weakness is associated with higher peak knee valgus angles (VA) during drop vertical jumps (DVJ) and linked to ACL injury risk. Objective: To determine if isometric strengthening (IST) of the hip extensor, abductor, and external rotator muscle groups would reduce VA exhibited during a DVJ. Methodology: Fourteen female volleyball players (7 training (TG), 7 control (CG), VA≥9˚ during DVJ) participated. Pre- and post-test gluteal, quadriceps and hamstring strength were measured with a digital force gauge. Three-dimensional kinematics were collected during 15 DVJ trials. TG participated in a 6-week IST program that targeted the hip extensor, abductor, and external rotator muscle groups. Two-way mixed ANOVAs compared mean differences of VA and strength. Single-participant analyses examined if athlete-specific adaptations went undetected in the analyses of aggregated data. Results: TG hip extension, abduction, and knee flexion strength increased, respectively, by 20.5%, 27.5% and 23.5% (P

STUDY OBJECTIVE To compare point-of-care (POC) of international normalized ratio to laboratory-derived values before and after cardiopulmonary bypass, with the primary aim of evaluating for any change in the relationship between the tests. METHODS This is a prospective observational study with 50 patients undergoing cardiac surgery enrolled. The International normalized ratio measured at two time points, precardiopulmonary bypass and after heparin reversal with protamine using both POC i-STAT and standard laboratory analysis for both time points. A difference of 0.2 between tests at either time point was considered clinically significant based on previous literature. A paired t test was used to test for a changing or statistically significant mean difference between tests. At both time points values were categorized into absolute difference of more than 0.2 or less than 0.2, and a Fisher's exact test was used to determine if an association existed between heparin reversal and a difference more than 0.2. Bland-Altman plots were also evaluated for agreement. RESULTS A statistically and clinically significant mean difference [0.09 vs. 0.25, difference -0.163 95% confidence interval (-0.25, -0.08), P = 0.003] was seen between the laboratory and POC tests when pre and postheparin reversal samples were compared. A significantly greater number of patients had a clinically relevant difference between the tests post compared with pre (four patients vs. 18 patients, P = 0.001). Linear regression analysis of the difference compared with the means, showed significant correlation suggesting the presence of a proportional bias (pre r = 0.488, P =

We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS) is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.

BACKGROUND In agricultural field work many tasks have been cited as high priority risk factors for the development of work-related musculoskeletal disorders (WRMDs). Although video-based biomechanical approaches have been effective in documenting the physical demands and risks associated with various occupational and non-occupational tasks, to date, this method has yet to be used to document jobs such as crop harvesting in a greenhouse environment. OBJECTIVE To document and assess the postural characteristics and 3D peak and cumulative low back and shoulder loads associated with greenhouse pepper harvesting using a video-based posture sampling approach. METHODS Nine male (28.2 (4.1) years) pepper harvesters from a greenhouse in Southwestern Ontario, Canada were videotaped during a normal shift. 3DMatch was used to document working trunk and shoulder postures, from which 3D peak and cumulative forces and moments were quantified. RESULTS On average, workers spent the majority of their time in neutral trunk postures (lateral bend: 99.1%; axial twist: 59.9%; flexion: 89.8%). Consistent results were found for the left and right shoulder, with the arms held in a neutral flexion posture 50% of the time or more. Four participants experienced peak L4/L5 compression forces (between 4116.3 N and 5937.0 N) which exceeded the NIOSH Action Limit (3400 N) during the cart pushing/pulling task, but remained below the threshold during picking. Mean cumulative L4/L5 extension and shoulder flexion moments ranged in magnitude from 18.5 Nm to 28.2 Nm, and between 19.4 Nm and 23.2 Nm, respectively, across all tasks. CONCLUSIONS The postural characteristics and biomechanical loads associated with greenhouse pepper harvesting were quantified with a video-based biomechanical approach. Further investigations of the physical risk factors for low back and shoulder musculoskeletal disorders is warranted in pepper harvesting, given the postures and loads documented in this study.

Transplantation of pancreatic islets is a therapeutic option to preserve or restore β-cell function. Our study was aimed at developing a clinically applicable protocol for extrahepatic transplantation of pancreatic islets. The potency of islets implanted onto the omentum, using an in situ–generated adherent, resorbable plasma-thrombin biologic scaffold, was evaluated in diabetic rat and nonhuman primate (NHP) models. Intraomental islet engraftment in the biologic scaffold was confirmed by achievement of improved metabolic function and preservation of islet cytoarchitecture, with reconstitution of rich intrainsular vascular networks in both species. Long-term nonfasting normoglycemia and adequate glucose clearance (tolerance tests) were achieved in both intrahepatic and intraomental sites in rats. Intraomental graft recipients displayed lower levels of serum biomarkers of islet distress (e.g., acute serum insulin) and inflammation (e.g., leptin and α2-macroglobulin). Importantly, low-purity (30:70% endocrine:exocrine) syngeneic rat islet preparations displayed function equivalent to that of pure (>95% endocrine) preparations after intraomental biologic scaffold implantation. Moreover, the biologic scaffold sustained allogeneic islet engraftment in immunosuppressed recipients. Collectively, our feasibility/efficacy data, along with the simplicity of the procedure and the safety of the biologic scaffold components, represented sufficient preclinical testing to proceed to a pilot phase I/II clinical trial.

The discovery of an orally bioavailable selective estrogen receptor downregulator (SERD) with equivalent potency and preclinical pharmacology to the intramuscular SERD fulvestrant is described. A directed screen identified the 1-aryl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole motif as a novel, druglike ER ligand. Aided by crystal structures of novel ligands bound to an ER construct, medicinal chemistry iterations led to (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid (30b, AZD9496), a clinical candidate with high oral bioavailability across preclinical species that is currently being evaluated in phase I clinical trials for the treatment of advanced estrogen receptor (ER) positive breast cancer.

A growing number of early discovery collaborative agreements are being put in place between large pharma companies and partners in which the rights for assets can reside with a partner, exclusively or jointly. Our corporate screening collection, like many others, was built on the premise that compounds generated in-house and not the subject of paper or patent disclosure were proprietary to the company. Collaborative screening arrangements and medicinal chemistry now make the origin, ownership rights and usage of compounds difficult to determine and manage. The Compound Passport Service is a dynamic database, managed and accessed through a set of reusable services that borrows from social media concepts to allow sample owners to take control of their samples in a much more active way.

Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.

Quantifying soft tissue motion following impact is important in human motion analysis as soft tissues attenuate potentially injurious forces resulting from activities such as running and jumping. This study determined the reliability of leg soft tissue position and velocity following heel impacts. A grid of black dots was applied to the skin of the right leg and foot (n = 20). Dots were automatically detected (ProAnalyst(®)) from high-speed records of pendulum and drop impacts. Three trained measurers selected columns of dots on each participant for analysis; one measurer 6 months later. Between- and within-measurer differences in kinematic variables were all relatively small (0.8 cm for position;3.7 cm/s for velocity) between-measurers and (0.5 cm for position;2.6 cm/s for velocity) within-measurer. Good (coefficients of variation (CV) ≤ 10%) to acceptable (CV 10% and ≤20%) reliability was shown for 95% of the position measures, with mean CVs of 10% and 11% within-measurers and between-measures, respectively. Velocity measures were less reliable; 40% of the measures showed good to marginal (CV 20% and ≤30%) reliability. This study established that leg soft tissue position data from skin markers could be obtained with good to acceptable reliability following heel impacts. Velocity data were less reliable but still acceptable in many cases.

BACKGROUND: A disconnect in manual patient transfer (MPT) training practices for nurses, between what is taught and used in academic and clinical settings, could have implications for injury. OBJECTIVE: This study aimed to determine: 1. what MPTs student and staff nurses use in clinical settings, and 2. if the MPTs used most often were also the ones they perceived that they received training for and had the most confidence performing. METHODS: Survey responses from student nurses (n = 163) (mid-sized university) and staff nurses (n = 33) (local hospital) regarding 19 MPTs were analyzed to determine which transfers were perceived to be used most often, and which ones they had received training for and had the greatest confidence performing. RESULTS: The MPTs nurses perceived using most often were the same transfers they had the greatest confidence performing and for which they perceived receiving training. However, these MPTs were not taught at the university at the time of this investigation. CONCLUSION: Reducing the disconnect between manual patient transfer training obtained in the academic and clinical environments will hopefully reduce the risk of injury for nurses and improve the quality of care for patients.

Forty-three occupational health professionals (observers) and 90 workers were enrolled in this study to perform the cross-cultural adaptation of the Rapid Office Strain Assessment into Brazilian Portuguese (ROSA-Br) and evaluate its psychometric properties. After cross-cultural adaptation, the measurement properties were checked in three stages: study 1 : pre-testing (27 observers rated 15 office worker videos), study 2 : intra- and inter-observer reliability (26 observers rated 15 office worker videos), and study 3 : validity and accuracy of ROSA-Br final scores (90 office workers). For the ROSA scores, acceptable intraclass correlation coefficients were found for 75% and 86% of the intra-observer reliability comparisons for non-trained and trained observers, respectively, and for 100% of the inter-observer reliability comparisons (0.43–0.86). For construct validity, moderate correlations were observed for 70% of the comparisons between ROSA final scores and other ergonomic instruments. Moderate accuracy was observed for a ROSA-Br final score of 6 (AUC [area under the curve] = 0.72, 0.89). Taken together, these results support the use of the ROSA-Br for ergonomic field assessments and research.

The ubiquitin proteasome system is widely postulated to be a new and important field of drug discovery for the future, with the ubiquitin specific proteases (USPs) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the finding that USP28 is required for c-Myc stability suggests that USP28 inhibition may represent a novel approach to targeting this so far undruggable oncogene. Here, we describe the discovery of the first reported inhibitors of USP28, which we demonstrate are able to bind to and inhibit USP28, and while displaying a dual activity against the closest homologue USP25, these inhibitors show a high degree of selectivity over other deubiquitinases (DUBs). The utility of these compounds as valuable probes to investigate and further explore cellular DUB biology is highlighted by the demonstration of target engagement against both USP25 and USP28 in cells. Furthermore, we demonstrate that these inhibitors are able to elicit modulation of both the total levels and the half-life of the c-Myc oncoprotein in cells and also induce apoptosis and loss of cell viability in a range of cancer cell lines. We however observed a narrow therapeutic index compared to a panel of tissue-matched normal cell lines. Thus, it is hoped that these probes and data presented herein will further advance our understanding of the biology and tractability of DUBs as potential future therapeutic targets.