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Background There is emerging evidence for abnormal beta oscillations in psychosis. Beta oscillations are likely to play a key role in the coordination of sensorimotor information that is crucial to healthy mental function. Growing evidence suggests that beta oscillations typically manifest as transient beta bursts that increase in probability following a motor response, observable as post-movement beta rebound. Evidence indicates that post-movement beta rebound is attenuated in psychosis, with greater attenuation associated with greater symptom severity and impairment. Delineating the functional role of beta bursts therefore may be key to understanding the mechanisms underlying persistent psychotic illness. Methods We used concurrent electroencephalography and functional magnetic resonance imaging to identify blood oxygen level–dependent correlates of beta bursts during the n-back working memory task and intervening rest periods in healthy participants (n = 30) and patients with psychosis (n = 48). Results During both task blocks and intervening rest periods, beta bursts phasically activated regions implicated in task-relevant content while suppressing currently tonically active regions. Patients showed attenuated post-movement beta rebound that was associated with persisting disorganization symptoms as well as impairments in cognition and role function. Patients also showed greater task-related reductions in overall beta burst rate and showed greater, more extensive, beta burst–related blood oxygen level–dependent activation. Conclusions Our evidence supports a model in which beta bursts reactivate latently maintained sensorimotor information and are dysregulated and inefficient in psychosis. We propose that abnormalities in the mechanisms by which beta bursts coordinate reactivation of contextually appropriate content can manifest as disorganization, working memory deficits, and inaccurate forward models and may underlie a core deficit associated with persisting symptoms and impairment.

BACKGROUND Little is known about patient characteristics predicting postdischarge pleural space complications (PDPSCs) after thoracic trauma. We sought to analyze the patient population who required unplanned hospital readmission for PDPSC. METHODS Retrospective review of adult patients admitted to a Level I Trauma Center with a chest Abbreviated Injury Scale (AIS) score of 2 or greater between January 2015 and August 2020. Those readmitted within 30 days of index hospitalization discharge for PDPSC were compared with those not readmitted. Demographics, injury characteristics, surgical procedures, imaging, and readmission data were retrieved. RESULTS Out of 17,192 trauma evaluations, 3,412 (19.8%) suffered a chest AIS score of 2 or greater injury and 155 experienced an unplanned 30-day hospital readmission. Of those, 49 (1.4%) were readmitted for the management of PDPSC (readmit PDPSC) and were compared with patients who were not readmitted (no readmit, n = 3,257). The readmit PDPSC group was significantly older age, heavier, comprised of fewer men, and suffered a higher mean chest AIS score. The readmit PDPSC group had a significantly higher incidence of rib fractures, flail chest, pneumothorax, hemothorax, scapula fractures, and a higher rate of tube thoracostomy placement during index admission. The discharge chest X-ray in the readmit PDPSC group demonstrated a pleural space abnormality in 36 (73%) of patients. Mean time to readmission was 10.2 (7.2) days, and hospital length of stay on readmission was 5.8 (3.7) days. Pleural effusion was the most common readmission diagnosis (44 [90%]), and 42 (86%) required tube thoracostomy. CONCLUSION We describe the subset of chest wall injury patients who require hospital readmission for PDPSC. Characteristics from index hospitalization associated with PDPSC include older age, female sex, heavier weight, presence of rib fractures, pleural space abnormality, scapular fracture, and chest tube placement. Further studies are needed to characterize this at-risk chest wall injury population, and to determine what interventions can facilitate outpatient management of postdischarge pleural space complications and mitigate readmission risk. LEVEL OF EVIDENCE Prognostic and epidemiologic, Level IV; Care management, Level V.

Background : Publications investigating the efficacy of surgical stabilization of rib fractures (SSRF) have increased exponentially. However, there is currently no standardized reporting structure for these studies, rendering both comparisons and extrapolation problematic. Methods : A subject matter expert group was formed by the Chest Wall Injury Society. This group conducted a review of the SSRF investigational literature and identified variable reporting within several general categories of relevant parameters. A compliment of guidelines was then generated. Results : The reporting guidelines consist of 26 recommendations in the categories of: (1) study type, (2) patient and injury characteristics, (3) patient treatments, (4) outcomes, and (5) statistical considerations. Conclusion : Our review identified inconsistencies in reporting within the investigational SSRF literature. In response to these inconsistencies, we propose a set of recommendations to standardize reporting of original investigations into the efficacy of SSRF.

BACKGROUND Prospective studies of surgical stabilization of rib fractures (SSRF) have excluded elderly patients, and no study has exclusively addressed the ≥80-year-old subgroup. We hypothesized that SSRF is associated with decreased mortality in trauma patients 80 years or older. METHODS Multicenter retrospective cohort study involving eight centers. Patients who underwent SSRF from 2015 to 2020 were matched to controls by study center, age, injury severity score, and presence of intracranial hemorrhage. Patients with chest Abbreviated Injury Scale score less than 3, head Abbreviated Injury Scale score greater than 2, death within 24 hours, and desire for no escalation of care were excluded. A subgroup analysis compared early (0-2 days postinjury) to late (3-7 days postinjury) SSRF. Poisson regression accounting for clustered data by center calculated the relative risk (RR) of the primary outcome of mortality for SSRF versus nonoperative management. RESULTS Of 360 patients, 133 (36.9%) underwent SSRF. Compared with nonoperative patients, SSRF patients were more severely injured and more likely to receive locoregional analgesia. There were 31 hospital deaths among the entire sample (8.6%). Multivariable regression demonstrated a decreased risk of mortality for the SSRF group, as compared with the nonoperative group (RR, 0.41; 95% confidence interval, 0.24-0.69; p < 0.01). However, SSRF patients were more likely to develop pneumonia, and had an increased duration of both mechanical ventilation and intensive care unit stay. There were no differences in discharge destination, although the SSRF group was less likely to be discharged on narcotics (RR, 0.66; 95% confidence interval, 0.48-0.90; p = 0.01). There was no difference in adjusted mortality between the early and late SSRF subgroups. CONCLUSION Patients selected for SSRF were substantially more injured versus those managed nonoperatively. Despite this, SSRF was independently associated with decreased mortality. With careful patient selection, SSRF may be considered a viable treatment option in octogenarian/nonagenarians. LEVEL OF EVIDENCE Therapeutic, Level IV.

Polymer passivation layers can improve the open-circuit voltage of perovskite solar cells when inserted at the perovskite-charge transport layer interfaces. Unfortunately, many such layers are poor conductors, leading to a trade-off between passivation quality (voltage) and series resistance (fill factor, FF). Here, we introduce a nanopatterned electron transport layer that overcomes this trade-off by modifying the spatial distribution of the passivation layer to form nanoscale localized charge transport pathways through an otherwise passivated interface, thereby providing both effective passivation and excellent charge extraction. By combining the nanopatterned electron transport layer with a dopant-free hole transport layer, we achieved a certified power conversion efficiency of 21.6% for a 1-square-centimeter cell with FF of 0.839, and demonstrate an encapsulated cell that retains ~91.7% of its initial efficiency after 1000 hours of damp heat exposure.

We acknowledge the support of the Australian Renewable Energy Agency (ARENA), the Australian Centre for Advanced Photovoltaics (ACAP), and the ANFF ACT Node in carrying out this research. H.T.N. acknowledges the fellowship support of the Australian Centre for Advanced Photovoltaics. T.P.W. is the recipient of an Australian Research Council Future Fellowship (Project No. FT180100302) funded by the Australian Government.

Communication requires both the encoding of information and its effective transmission and reception. The latter need is most acute in ‘noisy’ environments which set limits on the salience of signals, but little is known about the features of displays that work primarily in the service of efficacy. Here we examined the elaborate courtships of the muscid fly Lispe cana, a cursorial species that lives and mates in heterogeneous foreshores. In a field-based assay we quantified the broad structure of male colour signals, display behaviours, and signalling environments, and tested the prediction that males should seek to enhance signal salience — and consequent fitness — through the flexible choice of display locations. We show that courting males gain direct access to the field of view of females by straddling them and holding their wings closed, before presenting their structurally coloured faces in ritualised dances. During these displays males preferentially present their UV-white facial signals against darker visual backgrounds, and the magnitude of signal/background contrast predicts the duration of displays, which in turn predicts mating success. The indirect influence of signal contrast on mating success suggests it captures female attention which, combined with the motion and retinal sweep of the display, serves to enhance signal salience. Our results demonstrate a striking interplay between the physical and attentional manipulation of receivers during sexual communication, and reveal innovative routes to the enhancement of signal efficacy in noisy environments.

Aims/hypothesis It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). Methods We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. Results The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. Conclusions/interpretation These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.

Introduction The optimal time to initiate venous thromboembolism (VTE) chemoprophylaxis in blunt solid organ injury (BSOI) patients is debated. We hypothesize that 1) BSOI patients are hypercoagulable within 12 h of injury and 2) hypercoagulability dominates in patients who develop clot complications (CC). Material and methods This is a prospective study of BSOI patients admitted to two Level-1 Trauma Centers’ trauma intensive care units (ICU). Serial kaolin thrombelastography (TEG) and tissue plasminogen activator (tPA)-challenge TEGs were performed. CC included VTE and cerebrovascular accidents. Results On ICU admission, all patients (n = 95) were hypercoagulable, 58% were in fibrinolysis shutdown, and 50% of patients were tPA-resistant. Twelve patients (13%) developed CC. Compared to those without CC, they demonstrated decreased fibrinolysis at 12 h and higher clot strength at 48 h Conclusions BSOI patients are universally hypercoagulable upon ICU admission. VTE chemoprophylaxis should be started immediately in BSOI patients with hypercoagulability on TEG.

Testing has been central to our response to the COVID-19 pandemic. However, the accuracy of testing relies on standards, including reference materials, proficiency testing schemes, and information and reporting guidelines. The use of standards is a simple, inexpensive, and effective method to ensure reliable test results that inform clinical and public health decisions. Here we describe the central role of standards during the COVID-19 pandemic, where they have enabled population-scale screening, genomic surveillance and measures of immune protection measures. Given these benefits, the Coronavirus Standards Working Group (CSWG) was formed to coordinate standards in SARS-CoV-2 testing. This network of scientists has developed best-practices, reference materials, and conducted proficiency studies to harmonize laboratory performance. We propose that this coordinated development of standards should be prioritized as a key early step in the public health response to future pandemics that is necessary for reliable, large-scale testing for infectious disease.

X-ray phase-contrast imaging of micron-scale objects and features requires high spatial coherence. These highly spatially coherent x-rays can be generated at fourth generation light sources or by passing laser-produced x-rays through a narrow slit. By coupling these sources to an isochoric heating platform, we can measure the dynamic changes in density gradients at the interface between two warm dense matter (WDM) samples with micron-scale spatial resolution. The high spatial coherence gives rise to refractive and diffractive features at the interface 1 , 2 , 3 , allowing for precise measurement of dynamic processes in WDM, including transport properties and measuring the equation of state. We will present an overview of successful experiments at both the Omega Laser Facility and the European XFEL that demonstrate our platform's high efficacy and spatial resolution for characterizing density gradients in dynamically evolving WDM systems.

We present an overview of the development of our Fresnel Refractive Diffractive Radiography (FDR) platform for the Extreme Light Laboratory (ELL) at the University of Nebraska–Lincoln. This platform couples isochorically heated buried wires with dynamic X-ray phase-contrast imaging of the warm dense matter (WDM) samples 1 . By utilizing novel 1 µm-wide slits, we obtain a highly spatially coherent x-ray source that gives rise to significant refractive and diffractive features from micron-scale density gradients at the interface 2 . Measurement of the evolution of this density profile, driven primarily by the equation of state and thermal conductivity, opens the door for direct measurements of transport properties in WDM 3 . By utilizing a copper tape drive and novel wire extruder we create replenishing solid targets that allow for significantly higher repetition rates than previously demonstrated.

Funder: MAVA Foundation; Id: http://dx.doi.org/10.13039/100013324, The crisis generated by the emergence and pandemic spread of COVID‐19 has thrown into the global spotlight the dangers associated with novel diseases, as well as the key role of animals, especially wild animals, as potential sources of pathogens to humans. There is a widespread demand for a new relationship with wild and domestic animals, including suggested bans on hunting, wildlife trade, wet markets or consumption of wild animals. However, such policies risk ignoring essential elements of the problem as well as alienating and increasing hardship for local communities across the world, and might be unachievable at scale. There is thus a need for a more complex package of policy and practical responses. We undertook a solution scan to identify and collate 161 possible options for reducing the risks of further epidemic disease transmission from animals to humans, including potential further SARS‐CoV‐2 transmission (original or variants). We include all categories of animals in our responses (i.e. wildlife, captive, unmanaged/feral and domestic livestock and pets) and focus on pathogens (especially viruses) that, once transmitted from animals to humans, could acquire epidemic potential through high rates of human‐to‐human transmission. This excludes measures to prevent well‐known zoonotic diseases, such as rabies, that cannot readily transmit between humans. We focused solutions on societal measures, excluding the development of vaccines and other preventive therapeutic medicine and veterinary medicine options that are discussed elsewhere. We derived our solutions through reading the scientific literature, NGO position papers, and industry guidelines, collating our own experiences, and consulting experts in different fields. Herein, we review the major zoonotic transmission pathways and present an extensive list of options. The potential solutions are organised according to the key stages of the trade chain and encompass solutions that can be applied at the local, regional and international scales. This is a set of options targeted at practitioners and policy makers to encourage careful examination of possible courses of action, validating their impact and documenting outcomes.

We aimed to describe elderly engagement in recreational activities, their injury patterns, preinjury risks and outcomes.A 16-year retrospective trauma registry review. All trauma patients ≥65 years admitted after injury sustained during sport were evaluated, and compared to a non-sport cohort of elderly trauma patients.During the study period, 9697 admissions age ≥65 were identified. 526 (5%) were sport-related. Compared to the non-sport group, the sport cohort was younger, had fewer medical comorbidities, and was more severely injured. The common sport mechanisms were skiing, offroad vehicle use and bicycling, and common sport injuries involved lower extremity, chest, and head. Sport patients were more often discharged home than non-sport patients (73% vs 36%, p 0.001). There was no difference in ICU or hospital LOS between groups. The hospital mortality rate was 3% in sport and 5% in non-sport patients (p = 0.06).Over time, the number of elderly sport-related trauma patients increased. Our data suggest that being active may improve outcomes after trauma in older adults.

Carbon-based perovskite solar cells show great potential owing to their low-cost production and superior stability in air, compared to their counterparts using metal contacts. The photovoltaic performance of carbon-based PSCs, however, has been progressing slowly in spite of an impressive efficiency when they were first reported. One of the major obstacles is that the hole transport materials developed for state-of-the-art Au-based PSCs are not suitable for carbon-based PSCs. Here, we develop a low-temperature, solution-processed Poly(3-hexylthiophene-2,5-diyl) (P3HT)/graphene composite hole transport layer (HTL), that is compatible with paintable carbon-electrodes to produce state-of-the-art perovskite devices. Space-charge-limited-current measurements reveal that the as-prepared P3HT/graphene composite exhibits outstanding charge mobility and thermal tolerance, with hole mobility increasing from 8.3 × 10−3 cm2 V-1 s-1 (as-deposited) to 1.2 × 10-2 cm2 V-1 s-1 (after annealing at 100 °C) - two orders of magnitude larger than pure P3HT. The improved charge transport and extraction provided by the composite HTL provides a significant efficiency improvement compared to cells with a pure P3HT HTL. As a result, we report carbon-based solar cells with a record efficiency of 17.8% (certified by Newport); and the first perovskite cells to be certified under the stabilized testing protocol. The outstanding device stability is demonstrated by only 3% drop after storage in ambient conditions (humidity: ca. 50%) for 1680 h (non-encapsulated), and retention of ca. 89% of their original output under continuous 1-Sun illumination at room-temperature for 600 h (encapsulated) in a nitrogen environment.

BackgroundAssociations between driving and physical-activity (PA) intensities are unclear, particularly among older adults. We estimated prospective associations of travel modes with total PA, sedentary time (ST), light-intensity PA (LPA), and moderate-to-vigorous intensity PA (MVPA) among adults aged 39–70 years.MethodsWe studied 90 810 UK Biobank participants (56.1 ± 7.8 years). Driving status, specific travel modes (non-work travel; commuting to/from work) and covariates were assessed by questionnaire (2006–10). PA was assessed over 7 days by wrist-worn accelerometers (2013–15). We estimated associations using overall and age-stratified multivariable linear-regression models.ResultsDrivers accumulated 1.4% more total PA (95% confidence interval: 0.9, 1.9), 11.2 min/day less ST (–12.9, –9.5), 12.2 min/day more LPA (11.0, 13.3) and 0.9 min/day less MVPA (–1.6, –0.2) than non-drivers. Compared with car/motor-vehicle users, cyclists and walkers had the most optimal activity profiles followed by mixed-mode users (e.g. for non-work travel, cyclists: 10.7% more total PA, 9.0, 12.4; 20.5 min/day less ST, –26.0, –15.0; 14.5 min/day more MVPA, 12.0, 17.2; walkers: 4.2% more total PA, 3.5, 5.0; 7.5 min/day less ST –10.2, –4.9; 10.1 min/day more MVPA, 8.9, 11.3; mixed-mode users: 2.3% more total PA, 1.9, 2.7; 3.4 min/day less ST –4.8, –2.1; 4.9 min/day more MVPA, 4.3, 5.5). Some associations varied by age (p interaction ConclusionsAssessing specific travel modes rather than driving status alone may better capture variations in activity. Walking, cycling and, to a lesser degree, mixed-mode use are associated with more optimal activity profiles in adults of all ages.

BackgroundMany large studies have implemented wrist or thigh accelerometry to capture physical activity, but the accuracy of these measurements to infer Activity Energy Expenditure (AEE) and consequently Total Energy Expenditure (TEE) has not been demonstrated. The purpose of this study was to assess the validity of acceleration intensity at wrist and thigh sites as estimates of AEE and TEE under free-living conditions using a gold-standard criterion.MethodsMeasurements for 193 UK adults (105 men, 88 women, aged 40-66 years, BMI 20.4-36.6 kg·m-2) were collected with triaxial accelerometers worn on the dominant wrist, non-dominant wrist and thigh in free-living conditions for 9-14 days. In a subsample (50 men, 50 women) TEE was simultaneously assessed with doubly labelled water (DLW). AEE was estimated from non-dominant wrist using an established estimation model, and novel models were derived for dominant wrist and thigh in the non-DLW subsample. Agreement with both AEE and TEE from DLW was evaluated by mean bias, Root Mean Squared Error (RMSE) and Pearson correlation.ResultsMean TEE and AEE derived from DLW was 11.6 (2.3) MJ·day-1 and 49.8 (16.3) kJ·day-1·kg-1. Dominant and non-dominant wrist acceleration were highly correlated in free-living (r=0.93), but less so with thigh (r=0.73 and 0.66, respectively). Estimates of AEE were 48.6 (11.8) kJ·day-1·kg-1 from dominant wrist, 48.6 (12.3) from non-dominant wrist, and 46.0 (10.1) from thigh; these agreed strongly with AEE (RMSE ~12.2 kJ·day-1·kg-1, r ~0.71) with small mean biases at the population level (~6%). Only the thigh estimate bias was statistically significantly different from the criterion. When combining these AEE estimates with estimated REE, agreement was stronger with the criterion (RMSE ~1.0 MJ·day-1, r ~0.90). Conclusions: In UK adults, acceleration measured at either wrist or thigh can be used to estimate population levels of AEE and TEE in free-living conditions with high precision.

Background: Information sampling is the cognitive process of accumulating information before committing to a decision. Patients across numerous disorders show decreased information sampling relative to controls. Aims: Here, we used the Beads and the Best Choice Tasks to study the role of dopamine signaling in information sampling. Methods: Participants were given placebo, amisulpride, or ropinirole in each session, in a double-blind cross-over design. Results: We found that ropinirole (agonist) increased the number of beads drawn in the Beads Task specifically when participants faced a loss, and decreased the rank of the chosen option in the Best Choice Task. Conclusions: These effects are likely driven by a combination of effects at presynaptic D2 receptors, which affect dopamine release, and post-synaptic D2 receptors. Increased D2 relative to D1 receptor activation in the striatum leads to increased sampling in the loss condition in the Beads Task. It also leads to choice of a poorer ranked option in the Best Choice Task. Decreased D2 relative to D1 receptor activation leads to decreased sampling in the Beads Task in the loss condition.

In the USA, Species Conservation Banking is a prominent example of compensatory biodiversity impact mitigation, with an annual market value estimated at US$354.2 million. Species Conservation Banking represents a useful case study of a well‐established program that can provide empirical insights into the practicalities of implementing quantitative compensatory biodiversity mitigation on‐the‐ground. Using semi‐structured key‐informant interviews structured around well‐established technical challenges to compensatory mitigation, this study aimed to understand (i) how and why these challenges are or are not addressed in practice; and (ii) how these challenges relate to practical challenges faced by conservation banking stakeholders on‐the‐ground. Challenges identified included: (i) defining trading currencies and equivalence, (ii) regulatory and political uncertainty, (iii) regulatory agency capacity, will and knowledge, (iv) lack of policies, standards, and competition with other mitigation mechanisms, (v) long‐term uncertainty/longevity, and (vi) lack of species knowledge and data transparency. These challenges are numerous, diverse, interlinked and transdisciplinary, and collectively inhibit the ability of practitioners to resolve underlying technical challenges—a finding likely applicable to related biodiversity offset programs. To help address challenges and navigate this complexity, we formulate several recommendations for conservation banking stakeholders to improve the chances of beneficial biodiversity outcomes being achieved.

Evidence-based decision making is most effective with comprehensive access to scientific studies. If studies face delays or barriers to being published, the useful information they contain may not reach decision-makers in a timely manner. This represents a potential problem for mission-oriented disciplines where access to the latest data is paramount to ensure effective actions are deployed. We sought to analyse the severity of publication delay in conservation science — a field that requires urgent action to prevent the loss of biodiversity. We used the Conservation Evidence database to assess the length of publication delay (time from finishing data collection to publication) in the literature that tests the effectiveness of conservation interventions. From 7,415 peer-reviewed and non-peer-reviewed studies of conservation interventions published over eleven decades, we find that the mean publication delay (time from completing data collection to publication) was 3.6 years and varied by conservation subject — a smaller delay was observed for studies focussed on the management of captive animals. Publication delay was significantly smaller for studies in the non-journal literature (typically non-peer-reviewed) compared to studies published in scientific journals. Although we found publication delay has marginally increased over time (1912-2020), this change was weak post-1980s. Publication delay also varied inconsistently between studies on species with different IUCN Red List statuses and there was little evidence that studies on more threatened species were subject to a smaller delay. We discuss the possible drivers of publication delay and present suggestions for scientists, funders, publishers, and practitioners to reduce the time taken to publish studies. Although our recommendations are aimed at conservation science, they are highly relevant to other mission-driven disciplines where the rapid dissemination of scientific findings is important.

The development of new medicines through the clinical trials process offers countless opportunities for the application of approaches such as those offered by artificial intelligence and machine learning. Broadly speaking, the application of these techniques is usually aimed at doing one of the following: 1. Increasing the speed and therefore reducing the time to develop a medicine and get it to patients who need it. 2. Becoming more accurate at picking the winners—those potential new medicines that will go on to succeed, rather than produce negative clinical trial results. 3. Generating productivity or efficiency gains to offset the large costs of running clinical trial programs. These are all difficult problems to solve. However, the good news is that the clinical trials process tends to generate large volumes of data, some of which are of good quality—because it is required to be according to regulatory standards. These data are vital for using AI and machine learning techniques to achieve gains in one of the three opportunity areas outlined above. In addition, new data streams are maturing all the time—such as patient data from sensors and wearable devices, genomic testing, and real-world evidence.

We present on the design, use, and alignment procedure of novel 1 µm-wide slits for use in x-ray diffractive radiography of warm dense matter at the Omega Laser Facility at the Laboratory for Laser Energetics.

Review of scientific instruments 92(1), 013101 (2021). doi:10.1063/5.0022886, We introduce a setup to measure high-resolution inelastic x-ray scattering at the High Energy Density scientific instrument at the European X-Ray Free-Electron Laser (XFEL). The setup uses the Si (533) reflection in a channel-cut monochromator and three spherical diced analyzer crystals in near-backscattering geometry to reach a high spectral resolution. An energy resolution of 44 meV is demonstrated for the experimental setup, close to the theoretically achievable minimum resolution. The analyzer crystals and detector are mounted on a curved-rail system, allowing quick and reliable changes in scattering angle without breaking vacuum. The entire setup is designed for operation at 10 Hz, the same repetition rate as the high-power lasers available at the instrument and the fundamental repetition rate of the European XFEL. Among other measurements, it is envisioned that this setup will allow studies of the dynamics of highly transient laser generated states of matter., Published by American Institute of Physics, [S.l.]

AimsTo identify the BOLD (blood oxygenation level dependent) correlates of bursts of beta frequency band electrophysiological activity, and to compare BOLD responses between healthy controls and patients with psychotic illness.The post movement beta rebound (PMBR) is a transient increase in power in the beta frequency band (13-30 Hz), recorded with methods such as electroencephalography (EEG), following the completion of a movement. PMBR size is reduced in patients with schizophrenia and inversely correlated with severity of illness. PMBR size is inversely correlated with measures of schizotypy in non-clinical groups. Therefore, beta-band activity may reflect a fundamental neural process whose disruption plays an important role in the pathophysiology of schizophrenia. Recent work has found that changes in beta power reflect changes in the probability-of-occurrence of transient bursts of beta-frequency activity. Understanding the generators of beta bursts could help unravel the pathophysiology of psychotic illness and thus identify novel treatment targets.MethodEEG data were recorded simultaneously with BOLD data measured with 3T functional magnetic resonance imaging (fMRI), whilst participants performed an n-back working memory task. We included seventy-eight participants – 32 patients with schizophrenia, 16 with bipolar disorder and 30 healthy controls. Beta bursts were identified in the EEG data using a thresholding method and burst timings were used as markers in an event-related fMRI design convolved with a conventional haemodynamic response function. A region of interest analysis compared beta-event-related BOLD activity between patients and controls.ResultBeta bursts phasically activated brain regions implicated in coding task-relevant content (specifically, regions involved in the phonological representation of letter stimuli, as well as areas representing motor responses). Further, bursts were associated with suppression of tonically-active regions. In the EEG, PMBR was greater in controls than patients, and, in patients, PMBR size was positively correlated with Global Assessment of Functioning scores, and negatively correlated with persisting symptoms of disorganisation and performance on a digit symbol substition test. Despite this, patients showed greater, more extensive, burst-related BOLD activation than controls.ConclusionOur findings are consistent with a recent model in which beta bursts serve to reactivate latently-maintained, task-relevant, sensorimotor information. The increased BOLD response associated with bursts in patients, despite reduced PMBR, could reflect inefficiency of burst-mediated cortical synchrony, or it may suggest that the sensorimotor information reactivated by beta bursts is less precisely specified in psychosis. We propose that dysfunction of the mechanisms by which beta bursts reactivate task-relevant content can manifest as disorganisation and working memory deficits, and may contribute to persisting symptoms and impairment in psychosis.

It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435).We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively.The TC and TC-PA models showed better fit than null models (TC: χThese analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.

Background Estrogen may inhibit cell senescence that contributes to age‐related disorders. This study determined the effects of menopausal hormone treatments on circulating levels of markers of cell senescence. Methods Growth differentiation factor 15 (GDF15), tumor necrosis factor receptor 1 (TNFR1), FAS, and macrophage inflammatory protein 1α (MIP1α) were measured in serum using multiplexed bead‐based assays and compared among menopausal women participating in the Kronos Early Estrogen Prevention Study randomized to either placebo (n = 38), oral conjugated equine estrogen (oCEE, n = 37), or transdermal 17β‐estradiol (tE2, n = 34). Serum levels of the senescent markers for each treatment were compared to placebo 36 months after randomization using the Wilcoxon rank sum test. Results Serum levels of GDF15, TNFR1, and FAS, but not MIP1α, were lower in both the oCEE and tE2 groups compared to placebo. The difference in levels between treatment and placebo for GDF15, TNFR1, and FAS were greater for oCEE [−108 pg/mL (p = .008), −234 pg/mL (p = .0006), and −1374 pg/mL (p, Hormonal treatments reduced the levels of selected markers of aging in the blood of recently menopausal women.

INTRODUCTION: The COVID-19 pandemic has resulted in cancellation of medical peer meetings. The Chest Wall Injury Society Annual Summit was scheduled for April 2020. Due to safety concerns, the Society altered the meeting to an online format. The purpose of this paper is to describe how this was accomplished and also to highlight its outcomes. METHODS: An online survey of participants was carried out to assess their views on the educational yield and technical difficulties encountered as compared to in-person meetings. RESULTS: Sixty two of 275 (23%) registered participants filled out the survey. Eighty four percent felt that the educational quality was excellent/good. Seventy five percent and 95% felt in-person meetings are better for education and for networking, respectively. Eighty seven percent preferred in-person meetings in the future but would attend a virtual meeting again. Thirteen percent had technical difficulties accessing the meeting. CONCLUSION: Online meetings are feasible but in-person meetings have more educational and networking value.

Background Numerous currently incurable human diseases have been causally linked to mutations in connexin (Cx) genes. In several instances, pathological mutations generate abnormally active Cx hemichannels, referred to also as “leaky” hemichannels. The goal of this study was to assay the in vivo efficacy of a potent antagonist antibody targeting Cx hemichannels. Methods We employed the antibody to treat Cx30A88V/A88V adult mutant mice, the only available animal model of Clouston syndrome, a rare orphan disease caused by Cx30 p.A88V leaky hemichannels. To gain mechanistic insight into antibody action, we also performed patch clamp recordings, Ca2+ imaging and ATP release assay in vitro. Findings Two weeks of antibody treatment sufficed to repress cell hyperproliferation in skin and reduce hypertrophic sebaceous glands (SGs) to wild type (wt) levels. These effects were obtained whether mutant mice were treated topically, by application of an antibody cream formulation, or systemically, by intraperitoneal antibody injection. Experiments with mouse primary keratinocytes and HaCaT cells revealed the antibody blocked Ca2+ influx and diminished ATP release through leaky Cx30 p.A88V hemichannels. Interpretation Our results show anti-Cx antibody treatment was effective in vivo and sufficient to counteract the effects of pathological connexin expression in Cx30A88V/A88V mice. In vitro experiments suggest antibodies gained control over leaky hemichannels and contributed to restoring epidermal homeostasis. Therefore, regulating cell physiology by antibodies targeting the extracellular domain of Cxs may enforce an entirely new therapeutic strategy. These findings support the further development of antibodies as drugs to address unmet medical needs for Cx-related diseases. Fund Fondazione Telethon, GGP19148; University of Padova, SID/BIRD187130; Consiglio Nazionale delle Ricerche, DSB.AD008.370.003\TERABIO-IBCN; National Science Foundation of China, 31770776; Science and Technology Commission of Shanghai Municipality, 16DZ1910200.

Produced by senescent cells, the senescence-associated secretory phenotype (SASP) is a potential driver of age-related dysfunction. We tested whether circulating concentrations of SASP proteins reflect age and medical risk in humans. We first screened senescent endothelial cells, fibroblasts, preadipocytes, epithelial cells, and myoblasts to identify candidates for human profiling. We then tested associations between circulating SASP proteins and clinical data from individuals throughout the life span and older adults undergoing surgery for prevalent but distinct age-related diseases. A community-based sample of people aged 20–90 years (retrospective cross-sectional) was studied to test associations between circulating SASP factors and chronological age. A subset of this cohort aged 60–90 years and separate cohorts of older adults undergoing surgery for severe aortic stenosis (prospective longitudinal) or ovarian cancer (prospective case-control) were studied to assess relationships between circulating concentrations of SASP proteins and biological age (determined by the accumulation of age-related health deficits) and/or postsurgical outcomes. We showed that SASP proteins were positively associated with age, frailty, and adverse postsurgery outcomes. A panel of 7 SASP factors composed of growth differentiation factor 15 (GDF15), TNF receptor superfamily member 6 (FAS), osteopontin (OPN), TNF receptor 1 (TNFR1), ACTIVIN A, chemokine (C-C motif) ligand 3 (CCL3), and IL-15 predicted adverse events markedly better than a single SASP protein or age. Our findings suggest that the circulating SASP may serve as a clinically useful candidate biomarker of age-related health and a powerful tool for interventional human studies.

The optics of the ocular lens are determined by its geometry (shape and volume) and its inherent gradient of refractive index (water to protein ratio), which are in turn maintained by unique cellular physiology known as the lens internal microcirculation system. Previously, magnetic resonance imaging (MRI) has been used on ex vivo organ cultured bovine lenses to show that pharmacological perturbations to this microcirculation system disrupt ionic and fluid homeostasis and overall lens optics. In this study, we have optimised in vivo MRI protocols for use on wild-type and transgenic mouse models so that the effects of genetically perturbing the lens microcirculation system on lens properties can be studied. In vivo MRI protocols and post-analysis methods for studying the mouse lens were optimised and used to measure the lens geometry, diffusion, T1 and T2, as well as the refractive index (n) calculated from T2, in wild-type mice and the genetically modified Cx50KI46 mouse. In this animal line, gap junctional coupling in the lens is increased by knocking in the gap junction protein Cx46 into the Cx50 locus. Relative to wild-type mice, Cx50KI46 mice showed significantly reduced lens size and radius of curvature, increased T1 and T2 values, and decreased n in the lens nucleus, which was consistent with the developmental and functional changes characterised previously in this lens model. These proof of principle experiments show that in vivo MRI can be applied to transgenic mouse models to gain mechanistic insights into the relationship between lens physiology and optics, and in the future suggest that longitudinal studies can be performed to determine how this relationship is altered by age in mouse models of cataract.

Epsilon-near-zero (ENZ) materials offer unique properties for applications including optical clocking, nonlinear optics, and telecommunication. To date, the fabrication of ENZ materials at visible wavelengths relies mostly on the use of periodic structures, providing some manufacturing and material challenges. Here, we present the engineering of nonperiodic sodium tungsten bronzes (Na

Current decision algorithms involving surgical stabilization of rib fractures (SSRF) do not consider either specific fracture locations or other chest wall bony injuries. Our objective was to characterize the impact of scapula fractures on morbidity among patients who underwent fixation of sub-scapular rib fractures. We hypothesized that an ipsilateral scapula fracture was associated with poor acute and long-term outcomes. Retrospective review of two institutions’ prospectively maintained SSRF databases (October 2010 to January 2019). Patients who underwent repair of ≥ 1 sub-scapular rib fracture were included. Patients were grouped by the presence of an ipsilateral scapula fracture. Outcomes were acute SSRF complications, long-term rib implant removal, and quality of life via phone survey. A total of 144 patients were analyzed; 53 (36.8%) had an ipsilateral scapula fracture. Patients with a scapula fracture had a higher injury severity score (p = 0.02), degree of pulmonary contusion (p

The silks of certain orb weaving spiders are emerging as high-quality optical materials. This motivates study of the optical properties of such silk and particularly the comparative optical properties of the silks of different species. Any differences in optical properties may impart biological advantage for a spider species and make the silks interesting for biomimetic prospecting as optical materials. A prior study of the reflectance of spider silks from 18 species reported results for three species of modern orb weaving spiders ( Nephila clavipes, Argiope argentata and Micrathena Schreibersi ) as having reduced reflectance in the UV range. (Modern in the context used here means more recently derived.) The reduced UV reflectance was interpreted as an adaptive advantage in making the silks less visible to insects. Herein, a standard, experimental technique for measuring the reflectance spectrum of diffuse surfaces, using commercially available equipment, has been applied to samples of the silks of four modern species of orb weaving spiders: Phonognatha graeffei , Eriophora transmarina , Nephila plumipes and Argiope keyserlingi . This is a different technique than used in the previous study. Three of the four silks measured have a reduced signal in the UV. By taking the form of the silks as optical elements into account, it is shown that this is attributable to a combination of wavelength-dependent absorption and scattering by the silks rather than differences in reflectance for the different silks. Phonognatha graeffei dragline silk emerges as a very interesting spider silk with a flat ‘reflectance'/scattering spectrum which may indicate it is a low UV absorbing dielectric micro-fibre. Overall the measurement emerges as having the potential to compare the large numbers of silks from different species to prospect for those which have desirable optical properties.

Acta crystallographica / A Foundations and advances Section A 76(2), 1-11 (2020). doi:10.1107/S2053273319015559, A crystallographic indexing algorithm, pinkIndexer, is presented for the analysis of snapshot diffraction patterns. It can be used in a variety of contexts including measurements made with a monochromatic radiation source, a polychromatic source or with radiation of very short wavelength. As such, the algorithm is particularly suited to automated data processing for two emerging measurement techniques for macromolecular structure determination: serial pink-beam X-ray crystallography and serial electron crystallography, which until now lacked reliable programs for analyzing many individual diffraction patterns from crystals of uncorrelated orientation. The algorithm requires approximate knowledge of the unit-cell parameters of the crystal, but not the wavelengths associated with each Bragg spot. The use of pinkIndexer is demonstrated by obtaining 1005 lattices from a published pink-beam serial crystallography data set that had previously yielded 140 indexed lattices. Additionally, in tests on experimental serial crystallography diffraction data recorded with quasi-monochromatic X-rays and with electrons the algorithm indexed more patterns than other programs tested., Published by Blackwell, Oxford [u.a.]

A growing number of studies are providing evidence that a suite of anthropogenic stressors — habitat loss and fragmentation, pollution, invasive species, climate change and overharvesting — are seriously reducing insect and other invertebrate abundance, diversity and biomass across the biosphere. These declines affect all functional groups: herbivores, detritivores, parasitoids, predators and pollinators. Insects are vitally important in a wide range of ecosystem services of which some are vitally important for food production and security (for example, pollination and pest control). […]. info:eu-repo/semantics/publishedVersion

In the compelling race of finding alternative plasmonic material, metallic sodium tungsten bronzes, NaxWO3 with x

Objectives: To determine the role of physical activity intensity and bout-duration in modulating associations between physical activity and cardiometabolic risk markers.Methods: A cross-sectional study using the International Children’s Accelerometry Database (ICAD) including 38,306 observations (in 29,734 individuals aged 4–18 years). Accelerometry data was summarized as time accumulated in 16 combinations of intensity thresholds (≥500 to ≥3000 counts/min) and bout-durations (≥1 to ≥10 min). Outcomes were body mass index (BMI, kg/m2), waist circumference, biochemical markers, blood pressure, and a composite score of these metabolic markers. A second composite score excluded the adiposity component. Linear mixed models were applied to elucidate the associations and expressed per 10 min difference in daily activity above the intensity/bout-duration combination. Estimates (and variance) from each of the 16 combinations of intensity and bout-duration examined in the linear mixed models were analyzed in meta-regression to investigate trends in the association.Results: Each 10 min positive difference in physical activity was significantly and inversely associated with the risk factors irrespective of the combination of intensity and bout-duration. In meta-regression, each 1000 counts/min increase in intensity threshold was associated with a −0.027 (95% CI: −0.039 to −0.014) standard deviations lower composite risk score, and a −0.064 (95% CI: −0.09 to −0.038) kg/m2 lower BMI. Conversely, meta-regression suggested bout-duration was not significantly associated with effect-sizes (per 1 min increase in bout-duration: −0.002 (95% CI: −0.005 to 0.0005) standard deviations for the composite risk score, and −0.005 (95% CI: −0.012 to 0.002) kg/m2 for BMI).Conclusions: Time spent at higher intensity physical activity was the main determinant of variation in cardiometabolic risk factors, not bout-duration. Greater magnitude of associations was consistently observed with higher intensities. These results suggest that, in children and adolescents, physical activity, preferably at higher intensities, of any bout-duration should be promoted.

Background Venous thromboembolism is a cause of morbidity and mortality in trauma patients. Chemoprophylaxis with low-molecular-weight heparin at a standardized dose is recommended. Conventional chemoprophylaxis may be inadequate. We hypothesized that a weight-adjusted enoxaparin prophylaxis regimen would reduce the frequency of venous thromboembolism in hospitalized trauma patients and at 90-day follow-up. Methods This prospective, randomized pilot study enrolled adult patients admitted to a level 1 trauma center between July 2013 and January 2015. Subjects were randomized to receive either standard (30 mg subcutaneously every 12 hours) or weight-based (0.5mg/kg subcutaneously every 12 hours) enoxaparin. Surveillance duplex ultrasound for lower extremity deep vein thrombosis was performed on hospital days 1, 3, and 7, and weekly thereafter. The primary outcome was deep vein thrombosis during hospitalization. Secondary outcomes included venous thromboembolism at 90 days and significant bleeding events. Results Two hundred thirty-four (124 standard, 110 weight-based) subjects were enrolled. There was no difference between standard and weight-based regarding age, body mass index, percentage female gender, injury severity score, or percentage that had surgery. There was a trend toward less in-hospital deep vein thrombosis in weight-based (12 [9.7%] standard vs 4 [3.6%] weight-based, P = .075). At 90 days, there was no difference in venous thromboembolism (12 [9.7%] standard vs 6 [5.5%] weight-based, P =.34). There was 1 bleeding event, which occurred in a standard subject. Conclusion Weight-based enoxaparin dosing for venous thromboembolism chemoprophylaxis in trauma patients may provide better protection against venous thromboembolism than standard. A definitive study is necessary to determine whether weight-based dosing is superior to standard.

An outstanding challenge for the study of color traits is how best to use “colour spaces†to represent their visual perception, particularly when asking questions of color difference (e.g. the (dis)similarity of males and females, mimics and models, or sister species, to a given viewer). We use simulations to show that existing methods fail to statistically and biologically estimate the separation of groups in color space, and we suggest a flexible, robust, alternative that avoids those pitfalls.

Blunt trauma to the chest wall and rib fractures are remarkably frequent and are the basis of considerable morbidity and possible mortality. Surgical remedies for highly displaced rib fractures, especially in cases of flail chest, have been undertaken intermittently for more than 50 years. Rib-specific plating systems have started to be used in the last 10 years. These have ushered in the modern era of rib repair with chest wall stabilization (CWS) techniques that are safer, easier to perform, and more efficient. Recent consensus statements have sought to define the indications and contraindications, as well as the when, the how, and the technical details of CWS. Repair should be considered for patients who have three or more displaced rib fractures or a flail chest, whether or not mechanical ventilation is required. Additional candidates include patients who fail non-operative management irrespective of fracture pattern and those with rib fractures who need thoracic procedures for other reasons. Traditionally, unstable spine fracture and severe traumatic brain injury are definite contraindications. Pulmonary contusion's role in the decision to perform CWS remains controversial. A range of rib-specific plating systems are now commercially available.

GaN/Al0.20Ga0.80N/GaN heterostructures were grown by molecular beam epitaxy and fabricated into micro-Hall effect sensors for the purpose of simultaneous current and temperature detection. The devices were characterized over a temperature range of −183 °C to 252 °C and were determined to be linearly dependent on magnetic field and temperature throughout. The high room temperature mobility of 2000 cm2/Vs allowed for a very high magnetic field sensitivity of 113 VA−1T−1, which only decreased to 80 VA−1T−1 at 252 °C. The ability to measure temperature while at the same time measure the magnitude of the B-field, and thus current in a nearby line is demonstrated. A method of decoupling temperature and current signatures is also shown together with a simple method of offset voltage understanding and removal.

A perovskite/CIGS tandem configuration is an attractive and viable approach to achieve an ultra-high efficiency and cost-effective all-thin-film solar cell. In this work, we developed a semi-transparent perovskite solar cell (PSC) with a maximum efficiency of 18.1% at a bandgap of ∼1.62 eV. Combining this cell in a mechanically stacked tandem configuration with a 16.5% CIGS cell results in a tandem efficiency of 23.9%. We also present a semi-transparent high bandgap (∼1.75 eV) PSC with a champion efficiency of 16.0% that enables a tandem efficiency of 23.4%. Optical simulation predicts that a perovskite/CIGS tandem efficiency of over 30% is feasible with a high bandgap perovskite top cell. The multiple-cation perovskite absorbers enabling high tandem efficiencies in this work are found to be remarkably less sensitive towards oxygen exposure compared to the widely used CH3NH3PbI3 (MAPbI3). By combining systematic compositional tuning of perovskite materials and the simultaneous probe of terminal open-circuit voltage (Voc) and Photoluminence (PL) of PSCs, it is deduced that an interaction between methylamonnium (MA) cations and oxygen molecules results in an increased surface recombination rate, and this is the main driver for oxygen-induced degradation. The extraordinary device performance and stability reported in this work pave the way for ultimately realizing the commercialization of all-thin-film photovoltaic technology.

The optimal timing of surgical stabilization of rib fractures (SSRF) remains debated. We hypothesized that (1) demographic, radiologic, and clinical variables are associated with time to surgery and (2) shorter time to SSRF improves acute outcomes.Prospectively collected SSRF databases from four trauma centers were merged and analyzed (2006-2016). The independent variable was days from hospital admission to SSRF (early [1 day], mid [1-2 days], and late [3-10 days]). Outcomes included length of operation, number of ribs repaired, prolonged (24 hours) mechanical ventilation, pneumonia, tracheostomy, length of stay, and mortality. Multivariable logistic regression was used to control for significant differences in covariates between groups.Five hundred fifty-one patients were analyzed. The median time to SSRF was 1 day (range, 0-10); 207 (37.6%) patients were in the early group, 168 (30.5%) in the midgroup, and 186 (31.9%) in the late group. There was a significant shift toward earlier SSRF over the study period. Time to SSRF was significantly associated with study center (p0.01), year of surgery (p0.01), age (p = 0.02), mechanism of injury (p = 0.04), and body mass index (p = 0.02). Injury severity was not associated with time to surgery. Despite repairing the same median number of ribs (4; range, 1-13), median length of surgery was 68 minutes longer for the late as compared to the early group (p0.01). After controlling for the aforementioned significant covariates, each additional hospital day before SSRF was independently associated with a 31% increased likelihood of pneumonia (p0.01), a 27% increased likelihood of prolonged mechanical ventilation (p0.01), and a 26% increased likelihood of tracheostomy (p0.01).Surgical stabilization of rib fractures within 1 day of admission is associated with certain demographic and physiologic variables. After controlling for confounding factors, early SSRF was accomplished using less operative time, and was associated with favorable outcomes. When indicated and feasible, SSRF should occur as early as possible.Therapy, level III.

Recognizing the commercial potential of university-based inventions and discoveries, legislators and administrators have called upon academic scientists to become academic entrepreneurs. Yet, appar...

This work was supported by the Australian Renewable Energy Agency (ARENA) through research grants RND017 and 2020/RND001. The authors acknowledge the support from the Australian National Fabrication Facility (ANFF), ACT Node, The Australian National University. H.T.N. acknowledges fellowship support from the Australian Centre for Advanced Photovoltaics (ACAP).

Methods are described for processing XFEL data from individual crystalline fibrils. The methods are applied to data collected at the Linac Coherent Light Source from an amyloid-forming oligopeptide from the adenovirus shaft., Serial diffraction data collected at the Linac Coherent Light Source from crystalline amyloid fibrils delivered in a liquid jet show that the fibrils are well oriented in the jet. At low fibril concentrations, diffraction patterns are recorded from single fibrils; these patterns are weak and contain only a few reflections. Methods are developed for determining the orientation of patterns in reciprocal space and merging them in three dimensions. This allows the individual structure amplitudes to be calculated, thus overcoming the limitations of orientation and cylindrical averaging in conventional fibre diffraction analysis. The advantages of this technique should allow structural studies of fibrous systems in biology that are inaccessible using existing techniques.

Purpose To review recent enforcement actions in which the Securities and Exchange Commission (“SEC”) enforced Rule 21F-17(a) under the Securities Exchange Act, which prohibits actions to impede whistleblower communications with the SEC, and to identify changes that entities subject to SEC regulation (including public companies, broker-dealers and investment managers) may wish to consider in their employee separation agreements and other documents that may include confidentiality provisions. Design/methodology/approach Examines settled cases since 2015, in which the SEC found that contractual provisions in employee separation agreements and other documents impeded employees from communicating with the SEC staff about possible violations of the securities laws, to identify the types of language that the SEC found to be problematic and the types of provisions that the SEC believes are desirable, if not legally mandated, to protect employee whistleblower rights and avoid impeding communications under Rule 21F-17(a). Findings Beginning in 2015, the SEC has actively enforced Rule 21F-17(a), focusing on provisions in separation agreements and other employee-related documents that potentially prevent employees from reporting legal violations to the SEC. The SEC’s efforts have resulted in settled orders involving alleged violations of the rule. The cases generally allege that provisions in employee separation agreements or other documents violated the rule because they prohibited or chilled employee communications with the SEC about possible legal violations. Practical implications Entities subject to SEC regulation (including public companies, broker-dealers and investment managers) should review their confidentiality agreements with employees and consider whether changes are warranted to address the SEC’s concerns as identified in the Rule 21F-17(a) cases. Originality/value Practical guidance regarding important whistleblower developments from experienced securities lawyer.

There are currently no evidence-based indications for surgical stabilization of rib fractures (SSRF) in patients without flail chest. The purpose of this survey was to identify patients for whom there is relative equipoise (operative vs. non-operative) in order to assist in designing a randomized clinical trial. Members of the Chest Wall Injury Society were sent an online survey, in which 18 patient scenarios were presented. The baseline patient had ≥ three displaced, contiguous fractures and had no other contraindications for surgery. This default scenario was then varied based upon patient age, degree of traumatic brain injury (TBI), fracture series location, and number of abnormal pulmonary physiologic variables (oxygen requirement, respiratory rate, incentive spirometry ability, cough, and numeric pain score). Thirty respondents provided a total of 540 answers. Overall, the majority of responses were in favor of SSRF (n = 413, 84.1%). Furthermore, the vast majority of responses indicated that some degree of pulmonary compromise was necessary to recommend SSRF (n = 44, 90.4%), with ≥ two abnormal parameters being the most common threshold (n = 156, 31.8%). Decision to recommend SSRF varied significantly by number of abnormal clinical variables, age, and degree of TBI, but not by fracture series location. Patients aged 85 years old and those with moderate TBI were the least likely to be recommended for SSRF, regardless of abnormal pulmonary physiologic variables. The most appropriate cutoff for equipoise appeared to be a patient aged 21–79 years old, with no or mild TBI, ≥ two abnormal pulmonary parameters, and regardless of fracture location (44.8% consensus for SSRF). SSRF was recommended for most patients with non-flail, displaced rib fractures. However, this recommendation was contingent upon patient age, degree of TBI, and pulmonary clinical status. Results of this survey may be used to inform inclusion criteria for a future randomized, clinical trial.