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We use textual analysis of high-dimensional data from patent documents to create new indicators of technological innovation. We identify important patents based on textual similarity of a given patent to previous and subsequent work: these patents are distinct from previous work but related to subsequent innovations. Our importance indicators correlate with existing measures of patent quality but also provide complementary information. We identify breakthrough innovations as the most important patents—those in the right tail of our measure—and construct time series indices of technological change at the aggregate and sectoral levels. Our technology indices capture the evolution of technological waves over a long time span (1840 to the present) and cover innovation by private and public firms as well as nonprofit organizations and the US government. Advances in electricity and transportation drive the index in the 1880s, chemicals and electricity in the 1920s and 1930s, and computers and communication in the post-1980s. (JEL C43, N71, N72, O31, O33, O34)

PURPOSE OF REVIEW: Despite the growth in chronic kidney disease (CKD) epidemics, evidence-based lifestyle recommendations for primary prevention of CKD are limited by reliance on observational studies and predominantly pilot clinical trials. RECENT FINDINGS: Emerging data have shown lifestyle modification strategies for primary CKD prevention with the most evidence favoring a healthy dietary pattern (rich in fruit, vegetables, potassium and have a higher plant-based to animal protein ratio), and diet low in sodium, being physically active, avoiding tobacco smoking, moderating alcohol consumption and maintaining a healthy body weight. The way these behavioral interventions can be implemented in practice should consider their synergistic benefit as well as mechanisms to facilitate long-term behavior change. Sustaining long-term behavior change remains a challenge in practice, particularly due to a lack of healthcare resources and behavior relapse. Some suggestions to mitigate this include ensuring adequate time is spent in intervention codesign and planning, utilizing adaptive trial/intervention designs with regular intervention tailoring for intervention dose, intensity, duration, and modality. SUMMARY: A number of modifiable lifestyle behaviors consistently associate with developing CKD in the community. The current evidence base, despite its inherent limitations, may inform both public health recommendations and clinical practice.

A data-driven approach to predict dynamic responses of mistuned cyclic dynamic structures is presented. Nominally cyclic structures such as turbomachinery bladed disks, or blisks, contain deviation...

Objectives To describe the quantity and cost of in-person and telehealth exercise physiology (EP) reimbursed under the Medicare Benefits Schedule (MBS) in Australia before and during the coronavirus disease 2019 (COVID-19) pandemic. Methods This study uses publicly available MBS data to describe EP services (in-person and telehealth) reimbursed by Medicare between January 2020 and December 2021. Data were extracted at state and national levels. Results Despite a reduction in quantity and cost in quartile (Q) 2 2020 (41% reduction), MBS-reimbursed EP services have remained relatively constant at a national level through the 2-year observation period. Service claims averaged 88 555 per quarter in 2020 and 95 015 in 2021. The proportion of telehealth consultations relative to total quarterly claims for EP was

Understanding intraspecific variation in habitat use, particularly of long-lived fishes across multiple life history stages, is core to improved conservation management. Here, we present results from a synthesis of acoustic telemetry data for sub-adult and adult white sturgeon (Acipenser transmontanus) from 2010 to 2017 in the San Francisco Estuary and Sacramento River ecosystems. We focused primarily on uncovering spatial patterns of inferred habitat occupancy across life stages, and on linking habitat use to extant anthropogenic threats. We found substantial differences in habitat use across individuals and over time that was related to fish size classes defined relative to the slot limit (102-152 cm) used to regulate recreational fishing. However, differences in habitat use were not explained by fish sex or water year flow conditions. We also estimated indices of overall exposure for two major threats: capture by anglers and habitat modification. Fish of harvestable size were detected less often than others in areas where many are caught. Future monitoring and management of white sturgeon might benefit from examining multiple phases of white sturgeon life history. For example, additional tracking studies could improve our understanding of juvenile habitat use, adult survival rates, patterns of anadromy, and cross-basin habitat utilization.

Modeled source attribution information from the Community Multiscale Air Quality model was coupled with ambient data from the 2011 Deriving Information on Surface conditions from Column and Vertically Resolved Observations Relevant to Air Quality Baltimore field study. We assess source contributions and evaluate the utility of using aircraft measured CO and NO

Shellfish growing areas in rural catchments are occasionally affected by elevated faecal contamination from diffuse sources and may be subject to frequent harvest closures/classification downgrades. We combined traditional risk management methods based on sanitary surveys and monitoring of Escherichia coli in seawater and shellfish with faecal source tracking, bacterial source apportionment, and hydrometeorological modelling to determine the causes of elevated E. coli concentrations contributing to harvest closures in Papanui Inlet (Aotearoa New Zealand). These multiple lines of evidence were used to inform a weight of evidence assessment of bacterial contamination in the inlet. Ruminant livestock was estimated to contribute 80% of the faecal coliform loading. Concentrations of E. coli in seawater were low (≤ 87 MPN 100 ml− 1) while those in tuaki (Austrovenus stutchburyi) occasionally exceeded the “Approved” classification limit (230 MPN 100 g− 1). The most frequent positive genetic markers in seawater were the seagull (Catellicoccus marimammalium) (54% of seawater samples), and in shellfish, the bovine and seagull markers (both 12.5% of shellfish samples). Solar radiation was negatively correlated with E. coli in tuaki. We found that the growing area is affected by faecal inputs from animal and, to a lesser extent, human (septic tank discharges) sources which elevate contamination to levels detectable in tuaki but not in seawater, particularly in the summer months. The innovative approach can enhance the management of shellfish growing areas affected by intermittent contamination and enables more targeted action to reduce pollution to improve shellfish water quality.

We investigate the use of reduced precision arithmetic to solve the linear equation for the Newton step. If one neglects the backward error in the linear solve, then well-known convergence theory implies that using single precision in the linear solve has very little negative effect on the nonlinear convergence rate. However, if one considers the effects of backward error, then the usual textbook estimates are very pessimistic and even the state-of-the-art estimates using probabilistic rounding analysis do not fully conform to experiments. We report on experiments with a specific example. We store and factor Jacobians in double, single, and half precision. In the single precision case we observe that the convergence rates for the nonlinear iteration do not degrade as the dimension increases and that the nonlinear iteration statistics are essentially identical to the double precision computation. In half precision we see that the nonlinear convergence rates, while poor, do not degrade as the dimension increases. This work was supported by theCenter for Exascale Monte-Carlo Neutron Transport (CEMeNT)a PSAAP-III project funded by the Department of Energy, grant number: DE-NA003967.

Current trends toward naturally occurring compounds of therapeutic interest have contributed to an increasing number of studies on olive oil phenolics in the treatment of diseases with oxidative and inflammatory origins. Recent focus has been on olive oil wastewater, which is richer in phenolic compounds than olive oil itself. In this review, we present findings demonstrating the potential use of olive mill wastewater in dermatology. Particular attention is given to compounds with proven benefits in topical pharmacology: caffeic and ferulic acids, tyrosol and hydroxytyrosol, verbascoside, and oleuropein. The review is divided into different sections: inflammatory skin diseases, microbial effects, wound healing in addition to the antimelanoma properties of olive mill waste phenolics, and their potential in sun protection agents. There is strong evidence to support further studies into the valorization of this abundant and sustainable source of phenolic compounds for use in dermatology and dermo-cosmetic preparations.

Background Hip arthroscopy is associated with moderate to severe postoperative pain. This prospective, randomized, double-blinded study investigates the clinically analgesic effect of anterior quadratus lumborum block with multimodal analgesia compared to multimodal analgesia alone. The authors hypothesized that an anterior quadratus lumborum block with multimodal analgesia would be superior for pain control. Methods Ninety-six adult patients undergoing ambulatory hip arthroscopy were enrolled. Patients were randomized to either a single-shot anterior quadratus lumborum block (30 ml bupivacaine 0.5% with 2 mg preservative-free dexamethasone) or no block. All patients received neuraxial anesthesia, IV sedation, and multimodal analgesia (IV acetaminophen and ketorolac). The primary outcome was numerical rating scale pain scores at rest and movement at 30 min and 1, 2, 3, and 24 h. Results Ninety-six patients were enrolled and included in the analysis. Anterior quadratus lumborum block with multimodal analgesia (overall treatment effect, marginal mean [standard error]: 4.4 [0.3]) was not superior to multimodal analgesia alone (overall treatment effect, marginal mean [standard error]: 3.7 [0.3]) in pain scores over the study period (treatment differences between no block and anterior quadratus lumborum block, 0.7 [95% CI, –0.1 to 1.5]; P = 0.059). Postanesthesia care unit antiemetic use, patient satisfaction, and opioid consumption for 0 to 24 h were not significantly different. There was no difference in quadriceps strength on the operative side between groups (differences in means, 1.9 [95% CI, –1.5 to 5.3]; P = 0.268). Conclusions Anterior quadratus lumborum block may not add to the benefits provided by multimodal analgesia alone after hip arthroscopy. Anterior quadratus lumborum block did not cause a motor deficit. The lack of treatment effect in this study demonstrates a surgical procedure without benefit from this novel block. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

We propose a new latent factor conditional asset pricing model. Like Kelly, Pruitt, and Su (KPS, 2019), our model allows for latent factors and factor exposures that depend on covariates such as asset characteristics. But, unlike the linearity assumption of KPS, we model factor exposures as a flexible nonlinear function of covariates. Our model retrofits the workhorse unsupervised dimension reduction device from the machine learning literature – autoencoder neural networks – to incorporate information from covariates along with returns themselves. This delivers estimates of nonlinear conditional exposures and the associated latent factors. Furthermore, our machine learning framework imposes the economic restriction of no-arbitrage. Our autoencoder asset pricing model delivers out-of-sample pricing errors that are far smaller (and generally insignificant) compared to other leading factor models.

This brief editorial describes an emerging area of machine learning technology called large language models (LLMs). LLMs, such as ChatGPT, are the technological disruptor of this decade. They are going to be integrated into search engines (Bing and Google) and into Microsoft products in the coming months. They will therefore fundamentally change the way patients and clinicians access and receive information. It is essential that telehealth clinicians are aware of LLMs and appreciate their capabilities and limitations.

Practice guidelines for non-alcoholic fatty liver disease (NAFLD) recommend promoting the Mediterranean dietary pattern (MDP) which is cardioprotective and may improve hepatic steatosis. This study aimed to explore multidisciplinary clinicians’ perspectives on whether the MDP is recommended in routine management of NAFLD and barriers and facilitators to its implementation in a multi-ethnic setting. Semi-structured individual interviews were conducted with fourteen clinicians (seven doctors, three nurses, three dietitians and one exercise physiologist) routinely managing patients with NAFLD in metropolitan hospital outpatient clinics in Australia. Interviews were audio-recorded, transcribed and analysed using thematic content analysis. Clinicians described that lifestyle modification was their primary treatment for NAFLD and promoting diet was recognised as everyone’s role, whereby doctors and nurses raise awareness and dietitians provide individualisation. The MDP was regarded as the most evidence-based diet choice currently and was frequently recommended in routine care. Facilitators to MDP implementation in practice were: improvement in diet quality as a parallel goal to weight loss; in-depth knowledge of the dietary pattern; access to patient education and monitoring resources and; service culture, including an interdisciplinary clinic goal, and knowledge sharing from expert dietitians. Barriers included perceived challenges for patients from diverse cultural and socio-economic backgrounds and limited clinician training, time and resourcing to support behaviour change. Integration of MDP in routine management of NAFLD in specialist clinics was facilitated by a focus on diet quality, knowledge sharing, belief in evidence and an interdisciplinary team. Innovations to service delivery could better support and empower patients to change dietary behaviour long-term.

Objective: Suicide in Canadian men is high and rising. Research consistently indicates increased suicide risk in male subgroups including sexual minority, Indigenous, middle-aged, and military men. The current scoping review addresses the research question: Among male subgroups featured in Canadian suicide research, what are the key findings to inform suicide prevention efforts?. Method: A scoping review was undertaken in accord with PRISMA-ScR guidelines. Structured searches were conducted in CIHAHL, Medline, PsychInfo, and Web of Science to identify studies reporting suicidality (suicidal ideation, plans and/or attempts) and suicide among men in Canada. Inclusion criteria comprised primary empirical studies featuring Canadian male subgroups published in English from 2009 to 2020 inclusive. Results: Sixty-eight articles met the inclusion criteria, highlighting significant rates of male suicidality and/or suicide in 3 categories: (1) health inequities ( n = 29); (2) age-specific ( n = 30); and (3) occupation ( n = 9). The health inequities category included sexual minority men, Indigenous, and other marginalized males (i.e., homeless, immigrant men, and men who use opiates). Age-specific men focused on adolescents and youth, and middle-aged and older males. Active military, veterans, and first responders featured in the occupation category. Studies compared at risk male subgroups to females, general male populations, and/or other marginalized groups in emphasizing mental health disparities and increased suicide risk. Some men’s suboptimal connections to existing mental health care services were also highlighted. Conclusion: While male subgroups who are vulnerable to suicidality and suicide were consistently described, these insights have not translated to tailored upstream suicide prevention services for Canadian boys and men. There may be some important gains through integrating social and mental health care services for marginalized men, implementing school-based masculinity programs for adolescent males, orientating clinicians to the potential for men’s mid-life suicide risks (i.e., separation, bereavement, retirement) and lobbying employers to norm help-seeking among activate military, veterans, and first responder males.

ISSUE ADDRESSED: Health outcomes linked to men's relationships have the potential to both promote and risk the well-being of males and their families. The current scoping review provides a synthesis of men's relationship programs (excluding criminal court mandated services) in Australia, Canada and the United Kingdom to distil predominant program designs, access points, delivery modes and evaluative strategies. METHODS: Databases CINAHL, Medline, PsycInfo and Web of Science were searched for eligible articles published January 2010 and June 2020. The inclusion criteria consisted of empirical studies focussed on relationship programs for men. RESULTS: The review identified 21 articles comprising eight focussed on Fathering Identities as the Catalyst for Relationship Building and 13 targeting Men's Behaviour Change in Partner Relationships. Findings highlight the prevalence of group-based, in-person programs which men accessed via third party or self-referrals. Fathering programs highlighted the impact of men's violence on their children in appealing to attendees to strategise behavioural adjustments. Men's partner relationship programs emphasised self-control amid building strategies for proactively dealing with distress and conflict. Program evaluations consistently reported attendee feedback to gauge the acceptability and usefulness of services. CONCLUSIONS: That most men attending fathering and partner relationship programs were referred as a result of domestic violence and/or intimate partner violence underscores men's reticence for proactively seeking help as well as the absence of upstream relationship programs. There are likely enormous gains to be made by norming boys and men's relationship programs to prevent rather than correct violent and/or abusive behaviours.

To determine interobserver and intraobserver reliabilities of the combination of classification systems, including the Beck and acetabular labral articular disruption (ALAD) systems for transition zone cartilage, the Outerbridge system for acetabular and femoral head cartilage, and the Beck system for labral tears. Additionally, we sought to determine interobserver and intraobserver agreements in the location of injury to labrum and cartilage. Three fellowship trained surgeons reviewed 30 standardized videos of the central compartment with one surgeon re-evaluating the videos. Labral pathology, transition zone cartilage and acetabular cartilage were classified using the Beck, Beck and ALAD systems, and Outerbridge system, respectively. The location of labral tears and transition zone cartilage injury was assessed using a clock face system, and acetabular cartilage injury using a five-zone system. Intra- and interobserver reliabilities are reported as Gwet’s agreement coefficients. Interobserver and intraobserver agreement on the location of acetabular cartilage lesions was highest in superior and anterior zones (0.814–0.914). Outerbridge interobserver and intraobserver agreement was >0.90 in most zones of the acetabular cartilage. Interobserver and intraobserver agreement on location of transition zone lesions was 0.844–0.944. The Beck and ALAD classifications showed similar interobserver and intraobserver agreement for transition zone cartilage injury. The Beck classification of labral tears was 0.745 and 0.562 for interobserver and intraobserver agreements, respectively. The Outerbridge classification had almost perfect interobserver and intraobserver agreement in classifying chondral injury of the true acetabular cartilage and femoral head. The Beck and ALAD classifications both showed moderate to substantial interobserver and intraobserver reliabilities for transition zone cartilage injury. The Beck system for classification of labral tears showed substantial agreement among observers and moderate intraobserver agreement. Interobserver agreement on location of labral tears was highest in the region where most tears occur and became lower at the anterior and posterior extents of this region. The available classification systems can be used for documentation regarding intra-articular pathology. However, continued development of a concise and highly reproducible classification system would improve communication.

Real-time flight data from the Automatic Dependent Surveillance–Broadcast (ADS-B) has been integrated, through a data interface, with a flight performance computer program to predict aviation emissions at altitude. The ADS-B, along with data from Mode-S, are then used to ‘fly’ selected long-range aircraft models (Airbus A380-841, A330-343 and A350-900) and one turboprop (ATR72). Over 2,500 flight trajectories have been processed to demonstrate the integration between databases and software systems. Emissions are calculated for altitudes greater than 3,000 feet (609m) and exclude landing and take-off cycles. This proof of concept fills a gap in the aviation emissions inventories, since it uses real-time flights and produces estimates at a very granular level. It can be used to analyse emissions of gases such as carbon dioxide ($\mathrm{CO}_2$), carbon monoxide (CO), nitrogen oxides ($\mathrm{NO}_x$) and water vapour on a specific route (city pair), for a specific aircraft, for an entire fleet, or on a seasonal basis. It is shown how$\mathrm{NO}_x$and water vapour emissions concentrate around tropospheric altitudes only for long-range flights, and that the cruise range is the biggest discriminator in the absolute value of these and other exhaust emissions.

We assessed the usefulness of environmental DNA (eDNA) for monitoring the introduced pest fish Gambusia affinis by filtering water samples from streams in the Nelson and Tasman regions, South Islan...

We report on the combination of nanodroplet sample preparation, ultra-low-flow nanoLC, high-field asymmetric ion mobility spectrometry (FAIMS), and the latest-generation Orbitrap Eclipse Tribrid mass spectrometer for greatly improved single-cell proteome profiling. FAIMS effectively filtered out singly charged ions for more effective MS analysis of multiply charged peptides, resulting in an average of 1056 protein groups identified from single HeLa cells without MS1-level feature matching. This is 2.3 times more identifications than without FAIMS and a far greater level of proteome coverage for single mammalian cells than has been previously reported for a label-free study. Differential analysis of single microdissected motor neurons and interneurons from human spinal tissue indicated a similar level of proteome coverage, and the two subpopulations of cells were readily differentiated based on single-cell label-free quantification., The combination of nanodroplet sample preparation, ultra-low-flow nanoLC, high-field asymmetric ion mobility spectrometry (FAIMS) and latest-generation mass spectrometry instrumentation provides dramatically improved single-cell proteome profiling.

The Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 assesses generic-related quality of life, but has not been well studied in the orthopaedic literature. The purpose was to compare PROMIS Global-10 and legacy hip-specific patient-reported outcome measures (PROMs) in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). This study included patients who underwent primary hip arthroscopy with complete preoperative and 6-month post-operative follow-up. PROMIS Global-10 Physical (PROMIS-P) and Mental (PROMIS-M) components, as well as the modified Harris hip score (mHHS) and International Hip Outcome Tool-33 (iHOT-33) were assessed. PROM analysis included: post-operative changes, correlations, floor and ceiling effects and responsiveness. Final analysis included 112 patients. Average age and body mass index were 36.1±11.7 years and 24.8±3.9 kg/m2, respectively. All 6-month PROMs, except PROMIS-M, were significantly improved compared to preoperative level (P

This article reports a study of the effects of temperature on chaotropic anion (CA)-induced star-globule shape transitions in acidic water of three-arm star bottlebrushes composed of heterografted poly(ethylene oxide) (PEO) and either poly(2-(N,N-dimethylamino)ethyl methacrylate) (PDMAEMA) or poly(2-(N,N-diethylamino)ethyl methacrylate) (PDEAEMA) (the brushes denoted as SMB-11 and -22, respectively). The brush polymers were synthesized by grafting alkyne-end-functionalized PEO and PDMAEMA or PDEAEMA onto an azide-bearing three-arm star backbone polymer using the copper(I)-catalyzed alkyne-azide cycloaddition reaction. Six anions were studied for their effects on the conformations of SMB-11 and -22 in acidic water: super CAs [Fe(CN)6]3− and [Fe(CN)6]4−, moderate CAs PF6− and ClO4−, weak CA I−, and for comparison, kosmotropic anion SO42−. At 25 °C, the addition of super and moderate CAs induced shape transitions of SMB-11 and -22 in pH 4.50 water from a starlike to a collapsed globular state stabilized by PEO side chains, which was driven by the ion pairing of protonated tertiary amine groups with CAs and the chaotropic effect. The shape changes occurred at much lower salt concentrations for super CAs than moderate CAs. Upon heating from near room temperature to 70 °C, the super CA-collapsed brushes remained in the globular state, whereas the moderate CA-collapsed brushes underwent reversible globule-to-star shape transitions. The transition temperature increased with increasing salt concentration and was found to be higher for SMB-22 at the same salt concentration, presumably caused by the chaotropic effect. In contrast, I− and SO42− had small effects on the conformations of SMB-11 and -22 at 25 °C in the studied salt concentration range, and only small and gradual size variations were observed upon heating to 70 °C. The results reported here may have potential uses in the design of stimuli-responsive systems for substance encapsulation and release.

Fire can promote biodiversity but changing patterns of fire threaten species worldwide. While scientific literature often describes ‘inappropriate fire regimes’ as a significant threat to biodiversity, less attention has been paid to the characteristics that make a fire regime inappropriate. We go beyond this generic description and synthesize how inappropriate fire regimes contribute to declines of animal populations, using threatened mammals as a case study. We developed a demographic framework for classifying mechanisms by which fire regimes cause population decline, and applied the framework in a systematic review to identify fire characteristics and interacting threats associated with population declines in Australian threatened land mammals (n=99). Inappropriate fire regimes threaten 88% of Australian threatened land mammals. Our review indicates that intense, large, and frequent fires are the primary cause of fire-related population declines, particularly through their influence on survival rates. However, several species are threatened by a lack of fire and there is considerable uncertainty in the evidence base for fire-related declines. Climate change and predation are documented or predicted to interact with fire to exacerbate mammalian declines. This demographic framework will help target conservation actions globally and would be enhanced by empirical studies of animal survival, dispersal, and reproduction.

Since the COVID-19 pandemic onset, there has been exponential growth in the uptake of telehealth, globally. However, evidence suggests that people living in lower socioeconomic areas, cultural and linguistically diverse communities, people with disabilities, and with low health literacy are less likely to receive telehealth services. These population groups have disproportionately higher health needs and face additional barriers to healthcare access. Barriers that reduce access to telehealth further exacerbate existing gaps in care delivery. To improve equity of access to telehealth, we need to reduce the digital divide through a multi-stakeholder approach. This article proposes practical steps to reduce the digital divide and encourage equitable access to telehealth. Enabling more equitable access to telehealth requires improvements in digital health literacy, workforce training in clinical telehealth, co-design of new telehealth-enabled models of care, change management, advocacy for culturally appropriate services, and sustainable funding models.

Compressor performance prediction is still one of the significant interests in the turbomachinery research field. The two critical parameters for compressor design are adiabatic efficiency and stability margin. The Spalart-Allmaras (SA) turbulence model and modified SA models are widely used in that design process. However, the prediction accuracy is not always satisfactory. In most cases, the SA model predicts larger stall mass flow, and the RC-QCR SA model underestimates efficiency. This study proposes a new combination of the modified SA model (R-H-QCR model). R-H-QCR stands for Rotation-Helicity-Quadratic constitutive relation. The model increases or decreases turbulent viscosity based on flow rotation, energy backscatter, and anisotropy of turbulence flow field. The Bayesian inference framework calibrates the model parameters to predict accurately both efficiency and stability in the 3.5 stage compressor. The R-H-QCR, RC-QCR, and default SA models are evaluated in the multi-stage compressor. For the performance prediction, the R-H-QCR model predicts a better stability margin than the SA model and better efficiency than the RC-QCR model. In addition, the spanwise distribution of normalized total pressure is well captured by the R-H-QCR model, indicating that the R-H-QCR model improves flow field prediction.

Cancer clinical trials have traditionally occurred in-person. However, the COVID-19 pandemic has forced adaptions of all aspects of cancer care (including clinical trials) so they can be delivered remotely. We aimed to quantify and qualify current use of telehealth and how it can be further improved and routinely integrated into cancer clinical trials in Australia.We used a mixed-method study design, involving surveys of 14 multi-site Collaborative Cancer Clinical Trial Groups members across Australia (n = 98) and qualitative interviews with trial administrators and clinicians (n = 21).The results of our study indicated a strong willingness to use telehealth for certain transactions of clinical trials because it was perceived as a way of increasing efficiency and reach of services. Hybrid models (including telehealth and in-person methods), which considered transaction, cancer type, and patient preferences were most favorable. Additionally, telehealth allowed for greater equity to access and reduced trial burden but interestingly had little effect on increased diversity and recruitment. Factors influencing telehealth service implementation and uptake included communication among trial stakeholders, training, and learning from the experience of others in the clinical trials community.Many but not all aspects of clinical trial care are appropriate to be delivered via telehealth. A hybrid approach provides flexibility to trial delivery and may support greater equity of access to trials in the future. Our findings and actionable recommendations support the need for greater planning, training, and guidelines to enable telehealth to be better integrated into clinical trials. Opportunities exist to expand the use of remote patient monitoring to enable more objective data collection from trial participants in the future.

BackgroundUnderstanding movement patterns of anadromous fishes is critical to conservation management of declining wild populations and preservation of habitats. Yet, infrequent observations of individual animals fundamentally constrain accurate descriptions of movement dynamics.MethodsIn this study, we synthesized over a decade (2006–2018) of acoustic telemetry tracking observations of green sturgeon (Acipenser medirostris) in the Sacramento River system to describe major anadromous movement patterns.ResultsWe observed that green sturgeon exhibited a unimodal in-migration during the spring months but had a bimodal distribution of out-migration timing, split between an ‘early’ out-migration (32%) group during May - June, or alternatively, holding in the river until a ‘late’ out-migration (68%), November - January. Focusing on these out-migration groups, we found that river discharge, but not water temperature, may cue the timing of migration, and that fish showed a tendency to maintain out-migration timing between subsequent spawning migration events.ConclusionsWe recommend that life history descriptions of green sturgeon in this region reflect the distinct out-migration periods described here. Furthermore, we encourage the continued use of biotelemetry to describe migration timing and life history variation, not only this population but other green sturgeon populations and other species.

The Coronavirus Disease 2019 (COVID-19) pandemic, caused by SARS Coronavirus 2 (SARS-CoV-2), continues to cause significant mortality in human populations worldwide. SARS-CoV-2 has high sequence similarity to SARS-CoV and other related coronaviruses circulating in bats. It is still unclear whether transmission occurred directly from bats to humans, or through an intermediate host, bringing into question the broader host range of SARS-CoV-2. Using a combination of low biocontainment entry assays as well as live virus, we explored the receptor usage of SARS-CoV-2 using angiotensin-converting enzyme 2 (ACE2) receptors from 22 different species. We demonstrated that in addition to human ACE2, the Spike of SARS-CoV-2 has broad tropism for other mammalian ACE2s, including dog, cat and cattle. However, comparison of SARS-CoV-2 receptor usage to the related SARS-CoV and bat coronavirus, RaTG13, identified distinct patterns of receptor usage, with the two human viruses being more closely aligned. Finally, using bioinformatics, structure analysis and targeted mutagenesis, we identified key residues at the Spike-ACE2 interface which may have played a pivotal role in the emergence of SARS-CoV-2 in humans, some of which are also mutated in newly circulating variants of the virus. To summarise, the broad tropism of SARS-CoV-2 at the point of viral entry identifies the potential risk of infection of a wide range of companion animals, livestock and wildlife.

The purpose of this study was to validate time frames for postoperative care following stoma surgery and to determine participants' current practice with convex pouching systems during the postoperative period.A Cross-sectional survey.The sample comprised 332 ostomy care specialists practicing in the United States. Most (n = 220; 66%) had more than 10 years' experience caring for patients with ostomies, 82% (n = 272) were certified WOC or ostomy care nurses (CWOCN and COCN), and 7% (n = 23) were board-certified colorectal surgeons.A 23-item online questionnaire was created for purposes of the study. Items in the questionnaire queried professional background and experience caring for patients with an ostomy. A single item was used to identify postoperative care periods following ostomy surgery. Additional items queried current practice patterns related to use of convex pouching systems and the timing of their use. Data were collected from January 18 to February 8, 2021.Most respondents (n = 270; 90%) agreed with the following postoperative periods after ostomy surgery: immediate postoperative period (days 0-8); postoperative period (days 9-30); and transition phase (days 31-180). Most respondents (n = 274; 95%) indicated they would use a convex pouching system when clinically appropriate during the first 30 days following ostomy surgery and 79% (n = 228) indicated using a convex pouching system regardless of when the surgery was performed. Less than 1% (n = 2) indicated never using convexity within the first 30 days following stoma surgery, and only 3% (n = 8) indicated avoidance of convexity pouching systems in the immediate postoperative period.Findings indicate that use of convexity during the postoperative period is prevalent to provide a secure seal and predictable wear time.

Gas phase hydrogen chloride (HCl) was measured at Pasadena and San Joaquin Valley (SJV) ground sites in California during May and June 2010 as part of the CalNex study. Observed mixing ratios were on average 0.83 ppbv at Pasadena, ranging from below detection limit (0.055 ppbv) to 5.95 ppbv, and were on average 0.084 ppbv at SJV with a maximum value of 0.776 ppbv. At both sites, HCl levels were highest during midday and shared similar diurnal variations with HNO(3). Coupled phase partitioning behavior was found between HCl/Cl(−) and HNO(3)/NO(3)(−) using thermodynamic modelling and observations. Regional modeling of Cl(−) and HCl using CMAQ captures some of the observed relationships but underestimates measurements by a factor of 5 or more. Chloride in the 2.5-10 μm size range in Pasadena was sometimes higher than sea salt abundances, based on co-measured Na(+), implying that sources other than sea salt are important. The acid-displacement of HCl/Cl(−) by HNO(3)/NO(3)(−) (phase partitioning of semi-volatile acids) observed at the SJV site can only be explained by aqueous phase reaction despite low RH conditions and suggests the temperature dependence of HCl phase partitioning behavior was strongly impacted by the activity coefficient changes under relevant aerosol conditions (e.g., high ionic strength). Despite the influence from activity coefficients, the gas-particle system was found to be well constrained by other stronger buffers and charge balance so that HCl and Cl(−) concentrations were reproduced well by thermodynamic models.

Clathrin-mediated endocytosis (CME) is the main mechanism by which mammalian cells control their cell surface proteome. Proper operation of the pivotal CME cargo adaptor AP2 requires membrane-localized Fer/Cip4 homology domain-only proteins (FCHO). Here, live-cell enhanced total internal reflection fluorescence–structured illumination microscopy shows that FCHO marks sites of clathrin-coated pit (CCP) initiation, which mature into uniform-sized CCPs comprising a central patch of AP2 and clathrin corralled by an FCHO/Epidermal growth factor potential receptor substrate number 15 (Eps15) ring. We dissect the network of interactions between the FCHO interdomain linker and AP2, which concentrates, orients, tethers, and partially destabilizes closed AP2 at the plasma membrane. AP2’s subsequent membrane deposition drives its opening, which triggers FCHO displacement through steric competition with phosphatidylinositol 4,5-bisphosphate, clathrin, cargo, and CME accessory factors. FCHO can now relocate toward a CCP’s outer edge to engage and activate further AP2s to drive CCP growth/maturation.

Kobuviruses are an unusual and poorly characterised genus within the picornavirus family, and can cause gastrointestinal enteric disease in humans, livestock and pets. The human Kobuvirus, Aichi virus (AiV) can cause severe gastroenteritis and deaths in children below the age of five years, however this is a very rare occurrence. During the assembly of most picornaviruses (e.g. poliovirus, rhinovirus and foot-and-mouth disease virus), the capsid precursor protein VP0 is cleaved into VP4 and VP2. However, Kobuviruses retain an uncleaved VP0. From studies with other picornaviruses, it is known that VP4 performs the essential function of pore formation in membranes, which facilitates transfer of the viral genome across the endosomal membrane and into the cytoplasm for replication. Here, we employ genome exposure and membrane interaction assays to demonstrate that pH plays a critical role in AiV uncoating and membrane interactions. We demonstrate that incubation at low pH alters the exposure of hydrophobic residues within the capsid, enhances genome exposure and enhances permeabilisation of model membranes. Furthermore, using peptides we demonstrate that the N-terminus of VP0 mediates membrane pore formation in model membranes, indicating that this plays an analogous function to VP4.ImportanceTo initiate infection, viruses must enter a host cell and deliver their genome into the appropriate location. The picornavirus family of small non-enveloped RNA viruses includes significant human and animal pathogens and are also models to understand the process of cell entry. Most picornavirus capsids contain the internal protein VP4, generated from cleavage of a VP0 precursor. During entry, VP4 is released from the capsid. In enteroviruses this forms a membrane pore, which facilitates genome release into the cytoplasm. Due to high levels of sequence similarity, it is expected to play the same role for other picornaviruses. Some picornaviruses, such as Aichi virus, retain an intact VP0, and it is unknown how these viruses re-arrange their capsids and induce membrane permeability in the absence of VP4. Here we have used Aichi virus as a model VP0 virus to test for conservation of function between VP0 and VP4. This could enhance understanding of pore function and lead to development of novel therapeutic agents that block entry.

Single-cell proteomics (SCP) has great potential to advance biomedical research and personalized medicine. The sensitivity of such measurements increases with low-flow separations (

Clathrin-mediated endocytosis (CME) is the main mechanism by which mammalian cells control their cell surface proteome. Proper operation of the pivotal CME cargo-adaptor AP2 requires membrane-localised FCHO. Here, live-cell eTIRF-SIM shows that FCHO marks sites of clathrin- coated pit (CCP) initiation, which mature into uniform sized CCPs comprising a central patch of AP2 and clathrin corralled by an FCHO/Eps15 ring. We dissect the network of interactions between the FCHO interdomain-linker and AP2, which concentrates, orients, tethers and partially destabilizes closed AP2 at the plasma membrane. AP2’s subsequent membrane deposition drives its opening, which triggers FCHO displacement through steric competition with PtdIns4,5P2, clathrin, cargo and CME accessory factors. FCHO can now relocate toward a CCP’s outer edge to engage and activate further AP2s to drive CCP growth/maturation.125 character summaryFCHO primes AP2 for CCV incorporation, a process that triggers FCHO release to enable activation/recruitment of further AP2s