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Consistently engaging with client distress can negatively impact mental health workers (MHWs). This has been described by the concept of empathy-based stress (EBS) (which encompasses burnout; secondary traumatic stress; compassion fatigue and vicarious trauma). Previous reviews of interventions to reduce EBS have not addressed MHWs as a distinct group, despite evidence suggesting they are particularly vulnerable to it. In the context of rising demand for mental health services, it is especially important to understand how to mitigate the impact of EBS on MHWS. This scoping review therefore aimed to identify and describe available interventions to reduce or prevent EBS in MHWs. A systematic scoping review of the literature between 1970 and 2022 was undertaken using five electronic databases. A total of 51 studies were included, which varied significantly with regards to: interventions used; study methodology and theoretical underpinnings. Studies were grouped according to the level at which they aimed to intervene, namely: individual; team or organisational. The review concluded that most studies intervened at the level of the individual, despite the proposed causes of EBS being predominantly organisational. Furthermore, theoretical links to the origins of EBS were largely unclear. This suggests a lack of empirical evidence from which organisations employing MHWs can draw, to meaningfully prevent or reduce EBS in their staff. A dedicated research agenda is outlined to address this, and, other pertinent issues in the field and signifies a call for more theoretically grounded research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 May et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

PROTAC® (proteolysis-targeting chimera) molecules induce proximity between an E3 ligase and protein-of-interest (POI) to target the POI for ubiquitin-mediated degradation. Cooperative E3-PROTAC-POI complexes have potential to achieve neo-substrate selectivity beyond that established by POI binding to the ligand alone. Here, we extend the collection of ubiquitin ligases employable for cooperative ternary complex formation to include the C-degron E3 KLHDC2. Ligands were identified that engage the C-degron binding site in KLHDC2, subjected to structure-based improvement, and linked to JQ1 for BET-family neo-substrate recruitment. Consideration of the exit vector emanating from the ligand engaged in KLHDC2's U-shaped degron-binding pocket enabled generation of SJ46421, which drives formation of a remarkably cooperative, paralog-selective ternary complex with BRD3 BD2 . Meanwhile, screening pro-drug variants enabled surmounting cell permeability limitations imposed by acidic moieties resembling the KLHDC2-binding C-degron. Selectivity for BRD3 compared to other BET-family members is further manifested in ubiquitylation in vitro, and prodrug version SJ46420-mediated degradation in cells. Selectivity is also achieved for the ubiquitin ligase, overcoming E3 auto-inhibition to engage KLHDC2, but not the related KLHDC1, KLHDC3, or KLHDC10 E3s. In sum, our study establishes neo-substrate-specific targeted protein degradation via KLHDC2, and provides a framework for developing selective PROTAC protein degraders employing C-degron E3 ligases., (© 2024. The Author(s).)

Background: People with severe mental illness who experience co-occurring substance use experience poor outcome including suicide, violence, relapses and use of crisis services. They struggle to access care and treatment due to a lack of an integrated and co-ordinated approach which means that some people can fall between services. Despite these concerns, there is limited evidence as to what works for this population., Objectives: To undertake a realist evaluation of service models in order to identify and refine programme theories of what works under what contexts for this population., Design: Realist synthesis and evaluation using published literature and case study data., Setting: Mental health, substance use and related services that had some form of service provision in six locations in the United Kingdom (five in England and one in Northern Ireland)., Participants: People with lived experience of severe mental illness and co-occurring substance use, carers and staff who work in the specialist roles as well as staff in mental health and substance use services., Results: Eleven initial programme theories were generated by the evidence synthesis and in conjunction with stakeholders. These theories were refined through focus groups and interviews with 58 staff, 25 service users and 12 carers across the 6 case study areas. We identified three forms of service provision (network, consultancy and lead and link worker); however, all offered broadly similar interventions. Evidence was identified to support most of the 11 programme theories. Theories clustered around effective leadership, workforce development and collaborative integrated care pathways. Outcomes that are meaningful for service users and staff were identified, including the importance of engagement., Limitations: The requirement for online data collection (due to the COVID-19 pandemic) worked well for staff data but worked less well for service users and carers. Consequently, this may have reduced the involvement of those without access to information technology equipment., Conclusion: The realist evaluation co-occurring study provides details on how and in what circumstances integrated care can work better for people with co-occurring severe mental health and alcohol/drug conditions. This requires joined-up policy at government level and local integration of services. We have also identified the value of expert clinicians who can support the workforce in sustaining this programme of work. People with co-occurring severe mental health and alcohol/drug conditions have complex and multifaceted needs which require a comprehensive and long-term integrated approach. The shift to integrated health and social care is promising but will require local support (local expert leaders, network opportunities and clarity of roles)., Future Work: Further work should evaluate the effectiveness and cost-effectiveness of service models for this group., Study Registration: This study is registered as PROSPERO CRD42020168667., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128128) and is published in full in Health Technology Assessment ; Vol. 28, No. 67. See the NIHR Funding and Awards website for further award information.

Introduction: Frailty is a well-defined clinical syndrome in humans caused by accumulation of impairments which result in loss of reserve capacity and increased vulnerability to disability, dependence, and death. Dogs are of particular interest in studies of frailty due to the similarities they share with people in their environment, lifestyles, and age-related diseases., Materials and Methods: The aim of this study was to develop a frailty phenotype screening tool, based on previously validated measures in dogs, which could be easily applied in the clinical setting, and which was predictive of all-cause, short term (6-month) mortality. The study was conducted in two phases. In phase 1, a retrospective cohort of 51 dogs was used to identify and evaluate potential measures for the five domains of frailty. This information was then used to develop a simple frailty phenotype based on examination findings and owner directed questions. In phase 2 of the study, this phenotype was evaluated in a prospective cohort of 198 dogs aged 9 years or older from multiple different specialty and primary care services to determine how the phenotype performed across a diverse canine population., Results: The developed frailty phenotype was predictive of all-cause, short-term mortality independent of age, sex, or weight (hazard ratio = 4.71; 95% CI, 2.66-8.8). Of the covariates evaluated only breed was significant, with purebred dogs having 1.85 times higher mortality than mixed breed dogs (95% CI, 1.04-3.31). The frailty phenotype performed similarly across all hospital services from which patients were enrolled., Conclusion: Based on these findings, the defined frailty phenotype represents a valuable screening tool for early risk identification and intervention, and can aid in clinical decision making for owners and veterinarians. Additionally, it will promote further research into the understanding and treatment of frailty in dogs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Russell, Mondino, Fefer, Griffith, Saker, Gruen and Olby.)

We present genome sequences of 29 species of ducks from 8 genera. Illumina sequencing was performed on tissue from wild-collected museum specimens. The reads were assembled using a de novo method followed by a finishing step. The raw and assembled data are publicly available via Genbank.

Background: Epidermolysis bullosa (EB), characterized by skin fragility and blistering, often requires hospitalization. Training for inpatient management of EB is limited, with no unified recommendations available in North America., Objective: To develop consensus-derived best practices for hands-on inpatient management of EB in both the neonatal and postneonatal period., Methods: A modified Delphi method (expert-based input via 2 surveys and a final review) was implemented. Available guidelines from EB Clinical Research Consortium centers were analyzed to determine areas of focus and formulate statements to be voted on by EB Clinical Research Consortium members, experienced EB nurses, and select family members. Study participants evaluated statements using a Likert scale: statements with at least 70% agreement were accepted; statements with 30% or more disagreement were rejected., Results: Ten areas of focus were identified. Delphi participants included 15 dermatologists, 8 nurses, and 6 nonhealth care caregivers. Consensus was established on 103/119 neonatal statements and 105/122 postneonatal statements; no statements were rejected. Most recommendations applied to both age groups., Limitations: Recommendations may require adjustment based on individual patient's clinical context., Conclusion: Using the Delphi method, a consensus-derived resource for hospital-based health care professionals who manage patients with EB has been developed to improve the quality of inpatient care., Competing Interests: Conflicts of interest Dr Garcia-Romero has received the EBCRC grant and has been a speaker for Cerave Latinamerica and Carnot Mexico Laboratories. Dr Price’s’ conflicts of interest are Aegle (PI clinical trial), Rheacell (PI clinical trial) Krystal Biotech (consultant). Dr Perman has served as a consultant for Abeona. Dr Lucky has served as investigator for Krystal Pharma and Phoenicis. Dr McCuaig’s conflicts of interest are AbbVie, Bausch, Boehringer, Galderma, Incyte, J&J, Eli Lilly, Leo, Novartis, Oreal Pfizer, Sanofi, and Sun. Dr Gorell has served as a consultant for Krystal Biotech, Abeona Therapeutics, and Amryt Pharma. Dr Levy’s conflicts of interest are Abeona, Castle Creek, Krystal, and Rheacell. Dr Bruckner’s conflicts of interest are Abeona (consultant), Amryt (consultant and investigator), Castle Creek (consultant and investigator), Krystal Biotech (consultant), Phoenix Tissue Repair (investigator), Phoenicis (investigator), Rheacell (investigator), and TWi Bio (consultant). Dr Paller has been an investigator for AbbVie, Applied Pharma Research, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, Regeneron, and UCB; a consultant for Aegerion Pharma, Azitra, BioCryst, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Johnson & Johnson, Krystal, LEO Pharma, Novartis, Primus, Regeneron, Sanofi/Genzyme, Seanergy, TWI Biotechnology, and UCB; and on the data safety monitoring board for AbbVie, Abeona, Catawba, Galderma, and InMed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: People who present to the emergency department with self-harm and co-occurring substance use problems often have difficulty accessing effective care. Aims: To develop a brief psychosocial intervention for this population, which would be suitable for testing in a future randomized controlled trial. Methods: A modified Delphi method was used. A 34-item, 3-round, online Delphi survey was informed by a literature review and stakeholder telephone discussions ( n = 17). Two panels consisting of people with lived experience (PWLE: n = 15) and people with occupational experience (PWOE: n = 21) participated in the survey. The threshold for consensus was a pooled agreement rate across the two panels of 80% or more. Results: Expert consensus was achieved for 22 items. The new intervention consists of weekly follow-up phone calls for up to 1 month, delivered by Liaison Psychiatry practitioners, in which both self-harm and substance use problems are explored and addressed, and patients are supported in accessing community services. Limitations: Some stakeholder ideas regarding intervention components could not be included as survey options due to anticipated difficulties with implementation. Conclusions: The key elements of a brief psychosocial intervention for self-harm and co-occurring substance use problems have been agreed. Feasibility testing is currently underway.

Age-related decline in mobility and cognition are associated with cellular senescence and NAD + depletion in dogs and people. A combination of a novel NAD + precursor and senolytic, LY-D6/2, was examined in this randomized controlled trial. Seventy dogs with mild to moderate cognitive impairment were enrolled and allocated into placebo, low or full dose groups. Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors. Fifty-nine dogs completed evaluations at the 3-month primary endpoint, and 51 reached the 6-month secondary endpoint. There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group. No difference was detected between groups using in house cognitive testing. There were no significant differences between groups in changes in measured activity. The proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups, however this difference was not significant. Adverse events occurred equally across groups. All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation. We conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period and may have broader, but more subtle effects on frailty, activity and happiness as reported by owners., (© 2024. The Author(s).)

Context: Clinical clerkships provide osteopathic medical students the opportunity to participate in the diagnosis and treatment of commonly encountered medical conditions. Appropriate management of these conditions may include pharmacotherapy and/or nonpharmacologic interventions, such as osteopathic manipulative treatment (OMT). Opportunities may exist to expand the utilization of OMT in the management of common conditions, particularly for geriatric patients, who are at increased risk for adverse outcomes from pharmacologic treatments., Objectives: This study aimed to assess the most common diagnoses and corresponding treatments logged by osteopathic medical students within an ambulatory geriatric population., Methods: Patient encounters logged electronically by osteopathic medical students were retrospectively reviewed to determine the most commonly reported diagnostic codes and their treatments. Logged interventions were filtered to include patients over the age of 65 years who were seen on family medicine rotations within an ambulatory setting. The top 10 diagnoses were sorted and assessed to determine the associated treatments, including medications, procedures, and OMT., Results: Between January 2018 and June 2020, a total of 11,185 primary diagnoses were logged pertaining to the defined patient population. The most frequently documented diagnoses were essential hypertension (n=1,420; 12.7 %), encounter for well examination (n=1,144; 10.2 %), type 2 diabetes mellitus (n=837; 7.5 %), hyperlipidemia (n=346; 3.1 %), chronic obstructive pulmonary disease (COPD; n=278; 2.5 %), osteoarthritis (OA; n=221; 2.0 %), low back pain (LBP; n=202; 1.8 %), pain in joint (n=187; 1.7 %), hypothyroidism (n=164; 1.5 %), and urinary tract infections (n=160; 1.4 %). Three of the top 10 logged diagnoses were musculoskeletal in nature (OA, LBP, and pain in joint). Pharmacotherapy was reported as the predominant treatment for musculoskeletal conditions, with OMT being logged as a treatment for 10.9 % (n=50) of those cases. The most commonly logged medication class in the management of patients with those musculoskeletal conditions was nonsteroidal anti-inflammatory drugs (NSAIDs; n=128; 27.9 %), while opioids were the second most frequently documented class of medications (n=65; 14.2 %)., Conclusions: Musculoskeletal complaints were commonly logged by osteopathic medical students within the studied population. Opioids were documented as a treatment for musculoskeletal conditions more frequently than OMT. As such, opportunities exist to expand the utilization of OMT during clinical clerkships and to decrease the frequency of prescribed medications for pain management., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Competing Interests: Declaration of Competing Interest None.

The hip capsule has been recognized as a vital structure in the stability and proper function of the hip. Preserving its integrity during arthroscopic surgery is one of the utmost important principles in hip preservation surgery. When capsular deficiency is present, capsular reconstruction may be indicated to restore stability and proper hip mechanics. In this technical note, we introduce a simple and reproducible shuttle method technique for hip capsular reconstruction using a dermal allograft., (© 2023 The Authors.)

Approximately 30-50% of people with serious mental illness have co-existing drug or alcohol problems (COSMHAD), associated with adverse health and social care outcomes. UK guidelines advocate both co-occurring needs being met within mental health services, but uncertainty remains about how to operationalise this to improve outcomes. Various unevaluated service configurations exist in the UK. A realist synthesis was done to identify, test, and refine programme theories of how context shapes the mechanisms through which UK service models for COSMHAD work, for whom, and in what circumstances. Structured and iterative realist searches of seven databases identified 5099 records. A two-stage screening process identified 132 papers. Three broad contextual factors shaped COSMHAD services across 11 programme theories: committed leadership, clear expectations regarding COSMHAD from mental health and substance use workforces, and clear care-coordination processes. These contextual factors led to increased staff empathy, confidence, legitimisation, and multidisciplinary ethos, which improved care coordination and increased the motivation of people with COSMHAD to work towards their goals. Our synthesis highlights that integrating COSMHAD care is complex, and both individual and cultural behavioural shifts in leadership, workforce, and service delivery are essential to ensure people with COSMHAD receive compassionate, trauma-informed care that meets their needs., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Cognitive-behavioural therapy (CBT) has been shown to be an effective treatment for depression and anxiety. However, most research has focused on the sum scores of symptoms. Relatively little is known about how individual symptoms respond., Methods: Longitudinal models were used to explore how depression and generalised anxiety symptoms behave over the course of CBT in a retrospective, observational cohort of patients from primary care settings ( n = 5306). Logistic mixed models were used to examine the probability of being symptom-free across CBT appointments, using the 9-item Patient Health Questionnaire and the 7-item Generalised Anxiety Disorder scale as measures., Results: All symptoms improve across CBT treatment. The results suggest that low mood/hopelessness and guilt/worthlessness improved quickest relative to other depressive symptoms, with sleeping problems, appetite changes, and psychomotor retardation/agitation improving relatively slower. Uncontrollable worry and too much worry were the anxiety symptoms that improved fastest; irritability and restlessness improved the slowest., Conclusions: This research suggests there is a benefit to examining symptoms rather than sum scores alone. Investigations of symptoms provide the potential for precision psychiatry and may explain some of the heterogeneity observed in clinical outcomes when only sum scores are considered.

The geographic ranges in which species live is a function of many factors underlying ecological and evolutionary contingencies. Observing the geographic range of an individual species provides valuable information about these historical contingencies for a lineage, determining the distribution of many distantly related species in tandem provides information about large-scale constraints on evolutionary and ecological processes generally. We present a linear regression method that allows for the discrimination of various hypothetical biogeographical models for determining which landscape distributional pattern best matches data from the fossil record. The linear regression models used in the discrimination rely on geodesic distances between sampling sites (typically geologic formations) as the independent variable and three possible dependent variables: Dice/Sorensen similarity; Euclidean distance; and phylogenetic community dissimilarity. Both the similarity and distance measures are useful for full-community analyses without evolutionary information, whereas the phylogenetic community dissimilarity requires phylogenetic data. Importantly, the discrimination method uses linear regression residual error to provide relative measures of support for each biogeographical model tested, not absolute answers or p-values. When applied to a recently published dataset of Campanian pollen, we find evidence that supports two plant communities separated by a transitional zone of unknown size. A similar case study of ceratopsid dinosaurs using phylogenetic community dissimilarity provided no evidence of a biogeographical pattern, but this case study suffers from a lack of data to accurately discriminate and/or too much temporal mixing. Future research aiming to reconstruct the distribution of organisms across a landscape has a statistical-based method for determining what biogeographic distributional model best matches the available data., (© 2022 The Authors. The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Background: Various effective psychotherapies exist for the treatment of depression; however, only approximately half of patients recover after treatment. In efforts to improve clinical outcomes, research has focused on personalised psychotherapy - an attempt to match patients to treatments they are most likely to respond to., Aim: The present research aimed to evaluate the benefit of a data-driven model to support clinical decision-making in differential treatment allocation to cognitive-behavioural therapy versus counselling for depression., Method: The present analysis used electronic healthcare records from primary care psychological therapy services for patients receiving cognitive-behavioural therapy ( n = 14 544) and counselling for depression ( n = 4725). A linear regression with baseline sociodemographic and clinical characteristics was used to differentially predict post-treatment Patient Health Questionnaire (PHQ-9) scores between the two treatments. The benefit of differential prescription was evaluated in a held-out validation sample., Results: On average, patients who received their model-indicated optimal treatment saw a greater improvement (by 1.78 PHQ-9 points). This translated into 4-10% more patients achieving clinically meaningful changes. However, for individual patients, the estimated differences in benefits of treatments were small and rarely met the threshold for minimal clinically important differences., Conclusion: Precision prescription of psychotherapy based on sociodemographic and clinical characteristics is unlikely to produce large benefits for individual patients. However, the benefits may be meaningful from an aggregate public health perspective when applied at scale.

Kaposi sarcoma (KS) of the gastrointestinal (GI) tract in a patient with acquired immunodeficiency syndrome (AIDS) has not been reported in an adolescent outside of Africa. We present a 16-year homosexual old male with AIDS, cutaneous KS, pulmonary KS, and gastrointestinal KS (GI-KS) lesions. Eighty percent of patients with GI-KS are asymptomatic, but our patient presented with a month-long history of dysphagia, abdominal pain, and hematochezia. Endoscopy with biopsies revealed multiple KS lesions within the stomach and lower GI tract. This novel case demonstrates the importance of considering early endoscopic screening in immunocompromised adolescents with cutaneous KS to improve morbidity and mortality., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Distributed virtual environments (DVEs) are challenging to create as the goals of consistency and responsiveness become contradictory under increasing latency. DVEs have been considered as both distributed transactional databases and force-reflection systems. Both are good approaches, but they do have drawbacks. Transactional systems do not support Level 3 (L3) collaboration: manipulating the same degree-of-freedom at the same time. Force-reflection requires a client-server architecture and stabilisation techniques. With Consensus Based Networking (CBN), we suggest DVEs be considered as a distributed data-fusion problem. Many simulations run in parallel and exchange their states, with remote states integrated with continous authority. Over time the exchanges average out local differences, performing a distribued-average of a consistent, shared state. CBN aims to build simulations that are highly responsive, but consistent enough for use cases such as the piano-movers problem. CBN's support for heterogeneous nodes can transparently couple different input methods, avoid the requirement of determinism, and provide more options for personal control over the shared experience. Our work is early, however we demonstrate many successes, including L3 collaboration in room-scale VR, 1000's of interacting objects, complex configurations such as stacking, and transparent coupling of haptic devices. These have been shown before, but each with a different technique; CBN supports them all within a single, unified system.

Electrophysiological oscillations in the brain have been shown to occur as multicycle events, with onset and offset dependent on behavioral and cognitive state. To provide a baseline for state-related and task-related events, we quantified oscillation features in resting-state recordings. We developed an open-source wavelet-based tool to detect and characterize such oscillation events (OEvents) and exemplify the use of this tool in both simulations and two invasively-recorded electrophysiology datasets: one from human, and one from nonhuman primate (NHP) auditory system. After removing incidentally occurring event-related potentials (ERPs), we used OEvents to quantify oscillation features. We identified ∼2 million oscillation events, classified within traditional frequency bands: δ, θ, α, β, low γ, γ, and high γ. Oscillation events of 1-44 cycles could be identified in at least one frequency band 90% of the time in human and NHP recordings. Individual oscillation events were characterized by nonconstant frequency and amplitude. This result necessarily contrasts with prior studies which assumed frequency constancy, but is consistent with evidence from event-associated oscillations. We measured oscillation event duration, frequency span, and waveform shape. Oscillations tended to exhibit multiple cycles per event, verifiable by comparing filtered to unfiltered waveforms. In addition to the clear intraevent rhythmicity, there was also evidence of interevent rhythmicity within bands, demonstrated by finding that coefficient of variation of interval distributions and Fano factor (FF) measures differed significantly from a Poisson distribution assumption. Overall, our study provides an easy-to-use tool to study oscillation events at the single-trial level or in ongoing recordings, and demonstrates that rhythmic, multicycle oscillation events dominate auditory cortical dynamics., (Copyright © 2022 Neymotin et al.)

Aging is associated with impairment in postural control in humans. While dogs are a powerful model for the study of aging, the associations between age and postural control in this species have not yet been elucidated. The aims of this work were to establish a reliable protocol to measure center of pressure excursions in standing dogs and to determine age-related changes in postural sway. Data were obtained from 40 healthy adult dogs (Group A) and 28 senior dogs (Group B) during seven trials (within one session of data collection) of quiet standing on a pressure sensitive walkway system. Velocity, acceleration, root mean square, 95% ellipse area, range and frequency revolve were recorded as measures of postural sway. In Group A, reliability was assessed with intraclass correlation, and the effect of morphometric variables was evaluated using linear regression. By means of stepwise linear regression we determined that root mean square overall and acceleration in the craniocaudal direction were the best variables able to discriminate between Group A and Group B. The relationship between these two center-of-pressure (COP) measures and the dogs' fractional lifespan was examined in both groups and the role of pain and proprioceptive deficits was evaluated in Group B. All measures except for frequency revolve showed good to excellent reliability. Weight, height and length were correlated with most of the measures. Fractional lifespan impacted postural control in Group B but not Group A. Joint pain and its interaction with proprioceptive deficits influence postural sway especially in the acceleration in the craniocaudal direction, while fractional lifespan was most important in the overall COP displacement. In conclusion, our study found that pressure sensitive walkway systems are a reliable tool to evaluate postural sway in dogs; and that postural sway is affected by morphometric parameters and increases with age and joint pain., Competing Interests: The authors have declared that no competing interests exist.

Herein we report the use of Chaperonin-Containing TCP-1 (CCT or TRiC) as a marker to detect circulating tumor cells (CTCs) that are shed from tumors during oncogenesis. Most detection methods used in liquid biopsy approaches for enumeration of CTCs from blood, employ epithelial markers like cytokeratin (CK). However, such markers provide little information on the potential of these shed tumor cells, which are normally short-lived, to seed metastatic sites. To identify a marker that could go beyond enumeration and provide actionable data on CTCs, we evaluated CCT. CCT is a protein-folding complex composed of eight subunits. Previously, we found that expression of the second subunit (CCT2 or CCTβ) inversely correlated with cancer patient survival and was essential for tumorigenesis in mice, driving tumor-promoting processes like proliferation and anchorage-independent growth. In this study, we examined CCT2 expression in cancer compared to normal tissues and found statistically significant increases in tumors. Because not all blood samples from cancer patients contain detectable CTCs, we used the approach of spiking a known number of cancer cells into blood from healthy donors to test a liquid biopsy approach using CCT2 to distinguish rare cancer cells from the large number of non-cancer cells in blood. Using a clinically validated method for capturing CTCs, we evaluated detection of intracellular CCT2 staining for visualization of breast cancer and small cell lung (SCLC) cancer cells. We demonstrated that CCT2 staining could be incorporated into a CTC capture and staining protocol, providing biologically relevant information to improve detection of cancer cells shed in blood. These results were confirmed with a pilot study of blood from SCLC patients. Our studies demonstrate that detection of CCT2 could identify rare cancer cells in blood and has application in liquid biopsy approaches to enhance the use of minimally invasive methods for cancer diagnosis., Competing Interests: We have read the journal’s policy and one of the authors of this manuscript (Dr. Annette Khaled) has the following competing interests: [shareholder in Seva Therapeutics, Inc.] This commercial entity holds a license to use intellectual property developed by the inventor (Dr. Khaled) and provided no funding and had no role in the design, preparation, or submission of this manuscript and did not employ any of the authors. This competing interest does not alter our adherence to PLOS ONE policies on sharing data and materials.

Excessive barking is a major source of noise pollution in dog kennels and negatively impacts welfare. Because resources are often limited, minimizing barking in the simplest and most easily implementable way is imperative. This pilot study implemented a Quiet Kennel Exercise (QKE) that utilized classical counterconditioning to change the dogs' negative emotional state (which can lead to barking) to a more positive emotional state. Therefore, barking motivation is reduced, so barking should decrease. This study aims to show proof of concept that decreasing barking through classical counterconditioning is effective. It was conducted in one ward of day-time boarding kennels at North Carolina State University College of Veterinary Medicine. Data was collected three times per day and included decibel readings, number of dogs present, and number of dogs barking during a 5-day initial baseline and 10-day intervention period. During baseline, people passing through the ward acted as they normally would. During intervention, passersby were asked to simply toss each dog a treat regardless of the dogs' behaviors in the kennel. Descriptive results show improvement in maximum level of barking after QKE, fewer dogs barking over time, dogs barking less each time, and the most improvement noted in the afternoon.

Substantial molecular and morphological character differences lead us to the description of a new species of the genus Pristimantis from the cloud forest of Cerro Chucantí, Maje Mountains, Darien Province, as well as from several other mountain ranges in eastern and central Panama. Pristimantisgretathunbergae sp. nov. is a sister species to the allopatric P.erythropleura-penelopus group from northern Colombia with a mtDNA sequence divergence of > 4.4% at 16S and > 14.6% at COI. Its closest congener in sympatry is P.cruentus that differs by a large sequence divergence of > 9.6% in 16S mtDNA and 19.0% at COI, and from which it differs also by ventral and groin coloration, unusually prominent black eyes, a contrasting light upper lip, commonly a single conical to spine-like tubercle on the upper eyelid, and a larger head. While the habitat continuity at most sites in eastern Panama is moderate, habitats in central Panama are severely fragmented. Cerro Chucantí and the surrounding Maje Mountains are highly threatened by rapid deforestation and replaced by plantations and cattle pastures. Thus, investigations on the ecology of the new species and its population status, especially at the type locality, are highly recommended. As a flagship species, this new frog can help to preserve the Chucantí cloud forest including several recently described species known only from this isolated area in eastern Panama., (Konrad Mebert, Macario González-Pinzón, Madian Miranda, Edgardo Griffith, Milan Vesely, P. Lennart Schmid, Abel Batista.)

Background: This implementation feasibility study was conducted to determine whether an evidence-based parent-implemented distance-learning intervention model for young children at high likelihood of having ASD could be implemented at fidelity by Part C community providers and by parents in low-resource communities., Methods: The study used a community-academic partnership model to adapt an evidence-based intervention tested in the current pilot trial involving randomization by agency in four states and enrollment of 35 coaches and 34 parent-family dyads. After baseline data were gathered, providers in the experimental group received 12-15 h of training while control providers received six webinars on early development. Providers delivered 6 months of intervention with children-families, concluding with data collection. Regression analyses were used to model outcomes of the coach behaviors, the parent fidelity ratings, and child outcomes., Results: A block design model-building approach was used to test the null model followed by the inclusion of group as a predictor, and finally the inclusion of the planned covariates. Model fit was examined using changes in R 2 and F-statistic. As hypothesized, results demonstrated significant gains in (1) experimental provider fidelity of coaching implementation compared to the control group; and (2) experimental parent fidelity of implementation compared to the control group. There were no significant differences between groups on child developmental scores., Conclusions: Even though the experimental parent group averaged less than 30 min of intervention weekly with providers in the 6 months, both providers and parents demonstrated statistically significant gains on the fidelity of implementation scores with moderate effect sizes compared to control groups. Since child changes in parent-mediated models are dependent upon the parents' ability to deliver the intervention, and since parent delivery is dependent upon providers who are coaching the parents, these results demonstrated that two of these three links of the chain were positively affected by the experimental implementation model. However, a lack of significant differences in child group gains suggests that further work is needed on this model. Factors to consider include the amount of contact with the provider, the amount of practice children experience, the amount of contact both providers and parents spend on training materials, and motivational strategies for parents, among others., Trial Registration: Registry of Efficacy and Effectiveness Studies: #4360, registered 1xx, October, 2020 - Retrospectively registered, https://sreereg.icpsr.umich.edu/sreereg/., (© 2022. The Author(s).)

Early to Middle Miocene sea-level oscillations of approximately 40-60 m estimated from far-field records 1-3 are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth 2 . This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene 4,5 . Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes. Here we provide the earliest geological evidence proving large WAIS expansions occurred during the Early Miocene (~17.72-17.40 Ma). Geochemical and petrographic data show glacimarine sediments recovered at International Ocean Discovery Program (IODP) Site U1521 in the central Ross Sea derive from West Antarctica, requiring the presence of a WAIS covering most of the Ross Sea continental shelf. Seismic, lithological and palynological data reveal the intermittent proximity of grounded ice to Site U1521. The erosion rate calculated from this sediment package greatly exceeds the long-term mean, implying rapid erosion of West Antarctica. This interval therefore captures a key step in the genesis of a marine-based WAIS and a tipping point in Antarctic ice-sheet evolution., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: Fear of relapse (FOR) after experiencing psychosis has been found to predict actual relapse; however, potential mechanisms underlying this relationship have not been investigated. Negative appraisals of 'prodromal symptoms' are believed to play an important role in both psychosis and mental health anxiety (MHA). This study aimed to explore whether people in recovery from psychosis or anxiety disorders show an enduring tendency to negatively interpret ambiguous experiences both related and less related to their previous mental health difficulty relative to controls., Design: Cross-sectional between-groups questionnaire design., Methods: Participants self-reported as in recovery from psychosis (n = 33) or anxiety (n = 77) or without previous experience of mental health problems (n = 61) were recruited online or via NHS services. Interpretations of psychosis-like, anxiety-like, and external-control experiences were measured using the newly developed Experiences Interpretation Questionnaire (EIQ). MHA and FOR were measured using self-report questionnaires., Results: People in recovery from psychosis interpreted psychosis-like experiences significantly more negatively than the other groups. Negative interpretations of anxiety-like experiences were greater than controls but comparable between mental health groups. Contrary to predictions, FOR was not significantly different between the mental health groups. MHA and FOR did not significantly predict negative interpretations of psychosis-like items in the psychosis group, however, MHA predicted negative interpretations of anxiety-like items in the anxiety group. The EIQ subscales demonstrated good test-retest reliability., Conclusions: People in self-defined recovery from psychosis or anxiety are more likely to negatively interpret ambiguous experiences relating to their previous mental health difficulties. Clinical and future research implications are outlined., Practitioner Points: People in recovery from psychosis or anxiety appraise possible symptoms of their previous difficulties negatively/catastrophically (as indicating relapse) relative to those without prior MH problems. Clinicians should consider attending to how people in recovery appraise possible symptoms when encouraging early signs monitoring as part of relapse prevention. This may be important to ensure that self-monitoring leads to helpful responses rather than being counterproductive, with catastrophic interpretations leading to anxiety and thus increasing the risk of relapse. Interventions drawing on CBT principles to address catastrophic interpretations of possible symptoms may potentially be a useful addition to relapse prevention work; in psychosis this may also include symptoms of anxiety., (© 2021 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Objective: To compare hemostatic variables performed on blood samples obtained from indwelling jugular catheters or direct venipuncture over a 72-hour period., Design: Prospective experimental study., Setting: University research laboratory., Animals: Five healthy neutered male purpose-bred Beagle dogs., Interventions: Each dog was sedated to facilitate placement of a long-stay 20-Ga polyurethane IV catheter into the jugular vein. Blood samples were obtained from the preplaced catheters at 4 time points corresponding to 0, 24, 48, and 72 hours relative to placement. Blood samples were also obtained by direct venipuncture of a peripheral vein using a 21-Ga butterfly catheter and evacuated blood tubes at the same time points. Platelet count, platelet closure time, prothrombin time, activated partial thromboplastin time, fibrinogen, and kaolin-activated thromboelastography were performed on these paired samples at each time point. The patency of the indwelling catheters was maintained by flushing every 6 hours with heparinized saline., Measurements and Main Results: No significant differences were identified in any of the hemostatic variables obtained by either blood collection technique at any time point during the study (P > 0.05). There was also no significant day-to-day variation in any catheter-derived hemostatic variable obtained from individual dogs identified over the course of the study., Conclusions: These data suggest that accurate hemostatic variables may be obtained using blood collected from indwelling jugular catheters, maintained with heparinized saline for at least 72 hours, in healthy dogs., (© Veterinary Emergency and Critical Care Society 2021.)

Objective: Previous research on the minimal clinically important difference (MCID) for depression and anxiety is based on population averages. The present study aimed to identify the MCID across the spectrum of baseline severity., Study Design and Settings: The present analysis used secondary data from 2 randomized controlled trials for depression (n = 1,122) to calibrate the Global Rating of Change with the PHQ-9 and GAD-7. The MCID was defined as a change in scores corresponding to a 50% probability of patients "feeling better", given their baseline severity, referred to as Effective Dose 50 (ED50)., Results: MCID estimates depended on baseline severity and ranged from no change for very mild up to 14 points (52%) on the PHQ-9 and up to 10 points (48%) on the GAD-7 for very high severity. The average MCID estimates were 3.7 points (23%) and 3.3 (28%) for the PHQ-9 and GAD-7 respectively., Conclusion: The ED50 method generates MCID estimates across the spectrum of baseline severity, offering greater precision but at the cost of greater complexity relative to population average estimates. This has important implications for evaluations of treatments and clinical practice where users can use these results to tailor the MCID to specific populations according to baseline severities., (Copyright © 2021. Published by Elsevier Inc.)

Background: There are growing concerns about the impact of the COVID-19 pandemic on mental health. With government-imposed restrictions as well as a general burden on healthcare systems, the pandemic has the potential to disrupt the access to, and delivery of, mental healthcare., Methods: Electronic healthcare records from primary care psychological therapy services (Improving Access to Psychological Therapy) in England were used to examine changes in access to mental health services and service delivery during early stages of the COVID-19 pandemic. A descriptive time series was conducted using data from five NHS trusts to examine patterns in referrals to services (1st January 2019 to 24th May 2020) and appointments (1st January 2020 to 24th May 2020) taking place., Findings: The number of patients accessing mental health services dropped by an average of 55% in the early weeks after the March 2020 lockdown was announced, reaching a maximum reduction of 74% in the initial 3 weeks after lockdown in the UK, which gradually recovered to a 28% reduction by May. We found some evidence suggesting changes in the sociodemographic and clinical characteristics of referrals. Despite a reduction in access, the impact on appointments appeared limited with service providers shifting to remote delivery of care., Interpretation: Services appeared to adapt to provide continuity of care in mental healthcare. However, patients accessing services reduced, potentially placing a future burden on service. Despite the observational nature of the data, the present study can inform the planning of service provision and policy., Funding: AD and TS were funded by Innovate UK (KTP #11,105)., Competing Interests: CBS, JF, KB, TS, AD, DB, WW, CE report no conflicts of interest. EG reports grants from the British Psychological Society outside the submitted work and is a member of the British Psychological Society, Division of Clinical Psychology, Digital Healthcare., (© 2021 The Author(s).)

Mobile HMDs must sacrifice compute performance to achieve ergonomic and power requirements for extended use. Consequently, applications must either reduce rendering and simulation complexity - along with the richness of the experience - or offload complexity to a server. Within the context of edge-computing, a popular way to do this is through render streaming. Render streaming has been demonstrated for desktops and consoles. It has also been explored for HMDs. However, the latency requirements of head tracking make this application much more challenging. While mobile GPUs are not yet as capable as their desktop counterparts, we note that they are becoming more powerful and efficient. With the hard requirements of VR, it is worth continuing to investigate what schemes could optimally balance load, latency and quality. We propose an alternative we call edge-physics: streaming at the scene-graph level from a simulation running on edge-resources, analogous to cluster rendering. Scene streaming is not only straightforward, but compute and bandwidth efficient. The most demanding loops run locally. Jobs that hit the power-wall of mobile CPUs are off-loaded, while improving GPUs are leveraged, maximising compute utilisation. In this paper we create a prototypical implementation and evaluate its potential in terms of fidelity, bandwidth and performance. We show that an effective system which maintains high consistencies on typical edge-links can be easily built, but that some traditional concepts are not applicable, and a better understanding of the perception of motion is required to evaluate such a system comprehensively.

Objectives: Digital practice in psychological services is a rapidly expanding and innovative area which is supporting continuation of clinical provision during the COVID-19 pandemic. Training the workforce to deliver safe and effective online psychological provision is key to service success and relies on accurate mapping of competences and current training needs. This paper discusses the initial stage for developing the first digital mental health competence framework for applied psychology in the UK. It reports on the digital training currently provided nationally and barriers/facilitators to acquiring these competencies., Methods: Eighteen of the thirty UK Clinical Psychology Doctoral training programmes completed a 16-item survey. This mapped current digital health teaching and skills acquisition for trainee Clinical Psychologists throughout their 3-year pre-registration training. Furthermore, potential barriers and facilitators to developing these digital skills for both trainee and qualified Clinical Psychologists were investigated., Results: The quantitative analysis highlighted the majority of respondents viewed developing digital mental health competencies with importance, but were not integrating this into teaching or clinical placements activity. The qualitative, inductive content analysis revealed seven key themes influencing the development of digital mental health skills, with the majority of respondents identifying with two themes; the need for practice guidelines (50% of respondents) and opportunities for digital mental health experience., Conclusions: The findings suggest the need for a greater focus on developing the digital health knowledge, skills, and confidence across trainee and qualified Clinical Psychologists. Strategic analysis indicated the need to develop a framework for digital mental health competences across the curriculum and placement experience. Easily accessible learning packages may support the implementation of training nationally., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objective: Rivaroxaban is a new anticoagulant option for dogs, yet its reported oral bioavailability is as low as 60%. The objective of this study was to examine the influence of feeding and gastroprotectant medications on the bioactivity (anti-Xa activity) of rivaroxaban in healthy dogs., Design: Prospective experimental study., Setting: University research laboratory., Animals: Five healthy neutered male purpose-bred Beagles., Interventions: Dogs were administered a median dose of 1.8 mg/kg rivaroxaban (range, 1.6-1.8 mg/kg) orally once daily for 2 consecutive days with either (1) no food, (2) food, (3) sucralfate 30 minutes before rivaroxaban, or (4) omeprazole at the same time as rivaroxaban. Blood was collected from preplaced jugular catheters immediately before and at 6 time points after rivaroxaban administration (2, 4, 8, 24, 36, and 48 hours). A rivaroxaban calibrated anti-Xa activity assay (RIVA) was used to monitor anticoagulant effect., Measurements and Main Results: Rivaroxaban administration resulted in significant increases in RIVA (P = 0.02), with peak activities occurring 2 to 4 hours after dosingduring each study arm. No feeding was associated with significantly higher RIVA at the 36-hour time point compared to all other treatment arms (P < 0.0001), and feeding resulted in high RIVA at the 48-hour time point compared with sucralfate administration (P = 0.003). No significant changes in RIVA were otherwise identified with respect to feeding or gastroprotectant administration (P = 0.2)., Conclusions and Clinical Importance: Although administration without food demonstrated an apparent increase in RIVA 36 hours after drug administration, clinically relevant differences among treatment groups were not identified in combined analyses of time points. Based on these results, dogs treated with rivaroxaban do not require special modification of feeding practices or gastroprotectant drug administration., (© Veterinary Emergency and Critical Care Society 2020.)

Influenza D virus (IDV), a novel orthomyxovirus, is currently emerging in cattle worldwide. It shares >50% sequence similarity with the human influenza C virus (HICV). Two clades of IDV are currently co-circulating in cattle herds in the U.S. New assays specific for each lineage are needed for accurate surveillance. Also, differential diagnosis between zoonotic human influenza C virus and the two clades of IDV are important to assess the zoonotic potential of IDV. We developed an enzyme-linked immunosorbent assay (ELISA) based on two different epitopes HEF and NP and four peptides, and fluorescent focus neutralization assay to differentiate between IDV bovine and swine clades. Calf sera were obtained, and bovine samples underwent surveillance. Our results highlight the importance of position 215 with 212 in determining the heterogeneity between the two lineages. We needed IFA and FFN for tissue culture-based analysis and a BSL2 facility for analyzing virus interactions. Unfortunately, these are not available in many veterinary centers. Hence, our second aim was to develop an iELISA using specific epitopes to detect two lineages of IDVs simultaneously. Epitope-iELISA accurately detects neutralizing and non-neutralizing antibodies against the IDV in non-BSL2 laboratories and veterinary clinics and is cost-effective and sensitive. To differentiate between IDVs and HICVs, whole antigen blocking, polypeptides, and single-peptide ELISAs were developed. A panel of ferret sera against both viruses was used. Results suggested that both IDV and ICV had a common ancestor, and IDV poses a zoonotic risk to individuals with prior or current exposure to cattle. IDV peptides IANAGVK (286-292 aa), KTDSGR (423-428 aa), and RTLTPAT (448-455 aa) could differentiate between the two viruses, whereas peptide AESSVNPGAKPQV (203-215 aa) detected the presence of IDV in human sera but could not deny that it could be ICV, because the only two conserved influenza C peptides shared 52% sequence similarity with IDV and cross-reacted with IDV. However, blocking ELISAs differentiated between the two viruses. Diagnostic tools and assays to differentiate between ICV and IDV are required for serological and epidemiological analysis to clarify the complexity and evolution and eliminate misdiagnosis between ICV and IDV in human samples., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Okda, Griffith, Sakr, Nelson and Webby.)

Naturally occurring thoracolumbar spinal cord injury (SCI) is common in dogs, and multi-center veterinary clinical studies can serve as translational tools to identify potentially effective therapies for human clinical trials. Assessment of gait is a key outcome, and several scales are used in dogs. The purpose of this study was to determine whether an international group of researchers could score gait reliably, to compare and contrast the performance of gait scales and to describe appropriate data analysis techniques. A training module was developed for a binary scale, modified Frankel Scale (MFS), Texas SCI Scale (TSCIS), and Open Field Scale (OFS). Raters viewed the training module, scored five training video clips to achieve proficiency, then scored 30 video clips from 10 dogs recovering from SCI. Interrater reliability was calculated, and correlation between scales was examined. Ceiling effect was described. Twenty raters with differing experience participated. The training module took 16 min to view. Raters chose identical binary outcomes in 597 of 600 observations. Intraclass correlation for MFS, TSCIS, and OFS was excellent at 0.85, 0.96, and 0.96, respectively, regardless of rater expertise. Ceiling effect occurred in all dogs that recovered ambulation, particularly using MFS and binary outcome. The TSCIS and OFS captured recovery of ambulatory dogs better, and addition of scores on hopping and proprioception mitigated ceiling effect. We conclude that gait in dogs with SCI can be scored reliably after training. A variety of different gait scales can be used in multi-center trials to capture outcome in different ways.

Mitral valve prolapse is prevalent in about 6% of young healthy females yet two to three times as prevalent in patients with hyperthyroidism [1, 8]. Hyperthyroidism is often missed as an underlying diagnosis when mitral valve prolapse is visualized by echocardiogram. There are many cardiac findings reported in the literature associated with hyperthyroidism. However, hyperthyroidism may be difficult to diagnose in the early stages of the disease process without other classic signs and symptoms. We report a case of an adolescent female who presented to our cardiology clinic with palpitations and chest pain diagnosed with hyperthyroidism after subtle findings of mitral valve prolapse and trivial mitral regurgitation. This case report will review the classic cardiac changes which may be observed on echocardiography in patients with hyperthyroidism., Competing Interests: Authors have no conflicts to disclose., (© 2020 Elsevier B.V. All rights reserved.)

Objectives: It is well known that mental health problems can recur even after effective treatment, leading to an understandable fear of illness recurrence (FIR) and mental health anxiety (MHA). These may themselves contribute to the process of relapse. This study aims to examine whether people recovering from psychosis have greater FIR than those recovering from common mental health problems or healthy controls. The study also hypothesized that there will be a relationship between FIR and MHA and that both these constructs will be associated with maladaptive coping behaviours. Finally, the relationship between mental defeat with FIR and psychological distress (anxiety and depression) will be examined., Method: A cross-sectional questionnaire design was employed. Thirty-nine participants in recovery from psychosis, eighty-two in recovery from other mental health difficulties, and sixty-one healthy controls aged 18-73 were recruited from NHS services and via social media. Self-report questionnaires measured mental defeat, mental health anxiety, fear of illness recurrence, maladaptive coping behaviours, and psychological distress., Results: Those recovering from psychosis were found to more negatively evaluate the likely consequences of relapse than those recovering from common mental health problems or healthy controls. However, the levels of FIR in common mental health problems were also significantly elevated when compared to healthy controls. There were no other differences between these groups (in terms of mental defeat, anxiety, depression, social functioning, and maladaptive coping behaviours). The hypothesized relationship between FIR and MHA was also found, and both were associated with maladaptive coping behaviours. Mental defeat was associated with FIR and psychological distress (anxiety and depression)., Conclusions: This study found that those with psychosis experienced higher FIR than those with common mental health problems. Furthermore, people defining themselves as in recovery are worried about relapse and the extent of this is linked to mental health anxiety. Given that such responses may contribute to actual relapse, it is important that these issues are better understood and interventions developed to ameliorate them., Practitioner Points: Following recovery, fear of relapse may be particularly high in those with experience of psychosis; it is also present in those with common mental health problems The importance of this observation lies in the issue that anxiety about relapse may initiate a self-fulfilling process, with increased anxiety worsening symptoms and vice versa. Cognitive-behavioural therapy for health anxiety may be beneficial to those experiencing high levels of mental health anxiety. Cognitions related to relapse need to be explored and addressed both in further research and, when clearly identified, may be a target during relapse-prevention planning., (© 2020 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Objective: Maintaining adequate muscle tissue oxygenation is of paramount importance during equine general anesthesia. The objectives of this study were to assess the feasibility, reliability and repeatability of near-infrared spectroscopy (NIRS) muscle oximetry using the Inspectra m650 in conscious healthy adult horses., Study Design: Prospective, observational study., Animals: A group of 30 healthy client-owned adult horses admitted to the equine hospital between July 2017 and July 2018., Methods: The probe of an Inspectra m650 NIRS tissue oximeter was placed on the hairless surface of five muscle sites (omotransversarius, triceps long head, extensor carpi ulnaris, vastus lateralis and lateral digital extensor) on the left side of the body of each standing, unsedated horse. Each site had muscle oxygenation (StO 2 ) recordings measured in triplicate and statistical modeling used to assess the reading reliability and repeatability within and between muscle sites., Results: The readings acquired at the vastus lateralis and extensor carpi ulnaris muscle sites had highly repeatable values [mean (90% confidence interval): StO 2 , 95% (93.8%, 96.5%) and 93% (91.6%, 93.9%), respectively; intraclass correlation coefficients, 0.92 and 0.80, respectively]. These two sites also had high reliability (represented by the percentage of successful readings; 70% and 86%, respectively)., Conclusions and Clinical Relevance: The use of NIRS muscle oxygenation technology is a clinically feasible means to assess tissue oxygenation in horses. The vastus lateralis and extensor carpi ulnaris muscle sites provided the most reliable and repeatable readings when using the Inspectra m650 machine in horses., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

The natural product colletoic acid (CA) is a selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which primarily converts cortisone to the active glucocorticoid (GC) cortisol. Here, CA's mode of action and its potential as a chemical tool to study intracellular GC signaling in adipogenesis are disclosed. 11β-HSD1 biochemical studies of CA indicated that its functional groups at C-1, C-4, and C-9 were important for enzymatic activity; an X-ray crystal structure of 11β-HSD1 bound to CA at 2.6 Å resolution revealed the nature of those interactions, namely, a close-fitting and favorable interactions between the constrained CA spirocycle and the catalytic triad of 11β-HSD1. Structure-activity relationship studies culminated in the development of a superior CA analogue with improved target engagement. Furthermore, we demonstrate that CA selectively inhibits preadipocyte differentiation through 11β-HSD1 inhibition, suppressing other relevant key drivers of adipogenesis (i.e., PPARγ, PGC-1α), presumably by negatively modulating the glucocorticoid signaling pathway. The combined findings provide an in-depth evaluation of the mode of action of CA and its potential as a tool compound to study adipose tissue and its implications in metabolic syndrome.

The International Consensus Definition for Sepsis and Septic Shock Task Force has recently developed new methods to determine whether a patient is at risk for end organ failure after he has been suspected to have sepsis. One of the newest measures developed is a quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA), and it is used to identify patients who are at risk of sepsis outside the intensive care unit. The systemic inflammatory response syndrome (SIRS) score has previously been the standard for determining a patient's sepsis risk and prognosis for future mortality. With the development of these new tools, it is imperative to compare qSOFA to SIRS in order to determine which method is best and under which circumstances. We conclude that according to evidence currently available, qSOFA has limited use for patients in the intensive care unit at the time of evaluation for predicting mortality and organ dysfunction. Furthermore, qSOFA outranks SIRS for patients in the emergency department except for SIRS delivering positive results more quickly., Competing Interests: The authors have declared that no competing interests exist.

Background It is not uncommon for emergencies to present at primary care offices. As such, it is necessary for those offices to be prepared to handle, at a minimum, the most common types of emergencies. Objective To evaluate the effectiveness of in-situ simulation training in improving emergency preparedness within pediatric primary care settings. Methods Simulation training was provided at 20 primary care offices in Central Florida. The participants were asked to complete a pre-simulation survey that utilized a five-point Likert-type scale to evaluate office preparedness and the confidence of staff members in managing emergency presentations within their settings. Subsequent to the simulation, participants were asked to complete a post-survey to evaluate the effectiveness of the simulation training. Results Primary care office staff members reported an enhanced preparedness in managing emergencies post-simulation training (pre-simulation 2.95 vs. post-simulation 4.02; p-value<0.05). They also reported higher levels of comfort in managing emergency situations after the simulation training (pre-simulation 3.22 vs. post-simulation 4.53; p-value<0.05). Overall, 100% of participants found the simulation to be effective or extremely effective. Conclusions Our data suggests that the simulation training has improved office preparedness in managing emergencies in a pediatric primary care setting. The simulation training has also been shown to improve the comfort level of pediatric primary care office staff in handling emergency situations. This study was limited to pediatric primary care settings in the Central Florida region, and it is unclear if the findings of this study are generalizable to all primary care practices. Further studies are required to explore whether such training can result in practice change and improve outcomes for more patients., Competing Interests: The authors have declared that no competing interests exist.

Spinal cord injury (SCI) attributed to acute intervertebral disc extrusions (IVDEs) is common in dogs and is treated by surgical decompression. Dogs with sensorimotor complete injuries have an incomplete recovery. Pulsed electromagnetic fields (PEMFs) reduce post-operative pain through anti-inflammatory effects and there is growing evidence for neuroprotective effects. This randomized, controlled clinical trial evaluated the effect of PEMF on post-operative pain and neurological recovery in dogs with surgically treated sensorimotor complete SCI attributed to acute IVDE. Sixteen dogs with surgically treated complete thoracolumbar SCI were randomized to receive PEMF (15 min every 2 h for 2 weeks then twice-daily for 4 weeks) or placebo starting immediately after diagnosis. The primary outcome was gait score at 2 weeks. Secondary measures of gait, pain perception, and proprioceptive function were evaluated at 2 and 6 weeks. Plasma glial fibrillary acidic protein (GFAP) concentration was measured as an SCI biomarker. Post-operative pain was quantified by measuring mechanical sensory thresholds (MSTs) at control and surgical sites. There was no significant difference in demographics or GFAP concentration between the two groups at trial entry. There was no difference in primary outcome or in secondary measures of gait, but proprioceptive placing was significantly better at 6 weeks and GFAP concentrations were significantly lower at 2 weeks in the PEMF group. MSTs were significantly higher in the PEMF-treated group. We conclude that PEMF reduced incision-associated pain in dogs post-surgery for IVDE and may reduce extent of SCI and enhance proprioceptive placing. Larger clinical trials are warranted.

Objectives: Perineural invasion (PNI) has not yet gained universal acceptance as an independent predictor of adverse outcomes for prostate cancer treated with external beam radiotherapy (EBRT). We analyzed the prognostic influence of PNI for a large institutional cohort of prostate cancer patients who underwent EBRT with and without androgen deprivation therapy (ADT)., Material and Methods: We, retrospectively, reviewed prostate cancer patients treated with EBRT from 1993 to 2007 at our institution. The primary endpoint was biochemical failure-free survival (BFFS), with secondary endpoints of metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Univariate and multivariable Cox proportional hazards models were constructed for all survival endpoints. Hazard ratios for PNI were analyzed for the entire cohort and for subsets defined by NCCN risk level. Additionally, Kaplan-Meier survival curves were generated for all survival endpoints after stratification by PNI status, with significant differences computed using the log-rank test., Results: Of 888 men included for analysis, PNI was present on biopsy specimens in 187 (21.1%). PNI was associated with clinical stage, pretreatment PSA level, biopsy Gleason score, and use of ADT (all P<0.01). Men with PNI experienced significantly inferior 10-year BFFS (40.0% vs. 57.8%, P = 0.002), 10-year MFS (79.7% vs. 89.0%, P = 0.001), and 10-year PCSS (90.9% vs. 95.9%, P = 0.009), but not 10-year OS (67.5% vs. 77.5%, P = 0.07). On multivariate analysis, PNI was independently associated with inferior BFFS (P<0.001), but not MFS, PCSS, or OS. In subset analysis, PNI was associated with inferior BFFS (P = 0.04) for high-risk patients and with both inferior BFFS (P = 0.01) and PCSS (P = 0.05) for low-risk patients. Biochemical failure occurred in 33% of low-risk men with PNI who did not receive ADT compared to 8% for low-risk men with PNI treated with ADT (P = 0.01)., Conclusion: PNI was an independently significant predictor of adverse survival outcomes in this large institutional cohort, particularly for patients with NCCN low-risk disease. PNI should be carefully considered along with other standard prognostic factors when treating these patients with EBRT. Supplementing EBRT with ADT may be beneficial for select low-risk patients with PNI though independent validation with prospective studies is recommended., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders., Methods: A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities., Results: Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers' compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders., Conclusion: Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature., Competing Interests: BNG receives speaker fees and travel reimbursement, NCMIC Speakers’ Bureau; book royalties, McGraw-Hill; is secretary and chief financial officer of Brighthall Inc and is a stockholder. CDJ is a member of the NCMIC Board of Directors, however she, nor this board, make funding decisions for the NCMIC Foundation; book royalties, McGraw-Hill; is president of Brighthall Inc and is a stockholder. Brighthall, Inc provided funding only for open access publishing fees for PLOS ONE and had no other financial participation in this study. BNG and CDJ received no compensation from Brighthall, Inc for participation in this study, as they were volunteers for the Globa l Spine Care Initiative. SH is president, World Spine Care; Clinical advisory board and stock holder, Palladian Health; advisory board, SpineHealth.com; book royalties, McGraw Hill; travel expense reimbursement, Canadian Memorial Chiropractic College Board. MS is board of directors, North American Spine Society; board of directors, Foundation for PM&R; board of directors, Spine Intervention Society; deputy editor, The Spine Journal; scientific advisor, NuSpine; consultant, State Farm. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. The following authors have no potential conflicts of interest to declare: EG, MBC, EJK, JMC, SR, ELH, KR, HY, MN.

Background: Bone healing and assessment of the state of bone bridging is an important part of clinical orthopedics, whether for fracture healing or for follow up of osteotomy procedures. Tibial tuberosity advancement (TTA) is designed to restore stability in cruciate deficient stifle joints by advancing the tuberosity while creating an osteotomy gap. The current study aims to: 1) compare three different imaging modalities to assess bone healing: ultrasound, radiographs and computed tomography (CT) and, to 2) compare the effect of a gelatinous matrix (GM) versus a demineralized bone matrix mix (DBM mix) on bone healing and bridging of this osteotomy gap in 10 otherwise healthy client-owned dogs with cranial cruciate ligament insufficiency. Osseous union of the osteotomy gap was evaluated with ultrasound, radiographs and CT at one, two, and 3 months postoperatively. Dogs were randomly selected to receive GM or DBM mix to fill the osteotomy gap created during the TTA procedure. Bone healing was assessed subjectively on all modalities as well as scored on radiographs and measured using Hounsfield units (HUs) on CT. Time to heal based on ultrasound, radiographs and CT were statistically compared between groups with significance set at p < 0.05., Results: All osteotomy gaps were bridged with bone within 3 months for all modalities. Bridging bone was diagnosed in 5.6 weeks, 10.4 weeks and 9.6 weeks based on ultrasound, radiographs, and CT, respectively, in dogs treated with DBM mix. In dogs treated with GM osseous union was diagnosed in a mean of 4.0 weeks, 9.6 weeks and 7.2 weeks based on ultrasound, radiographs and CT. Ultrasound diagnosed osseous union significantly faster than both CT and radiographs (p < 0.001). The dimensions of the newly formed bone differed between treatment groups with the central portion of the bone only providing a small bridge in GM cases. Although bridging of the osteotomy gap occurred earlier in the group that received GM, no significant statistical difference was found between the two groups., Conclusions: Radiographs overestimate the time needed for osseous union of the osteotomy gap. All osteotomy sites healed radiographically within 3 months.

OBJECTIVE To evaluate the feasibility of manufacturing gastrojejunostomy tubes from jejunostomy and gastrostomy tubes that would allow for gastric and enteral feeding of and aspiration of gastric contents from small animal patients. DESIGN In vitro study. SAMPLE 9 gastrojejunostomy constructs. PROCEDURES Commercially available gastrostomy and jejunostomy tubes were combined to create 9 constructs. Three investigators tested each construct with 4 solutions (tap water, a commercial enteral diet, and 2 canned food-water mixtures) and 3 syringe sizes for ease of injection through the gastrostomy and jejunostomy tubes and aspiration through the gastrostomy tube. Flow rates were calculated and analyzed to evaluate effects of tube diameter and syringe size for each solution. RESULTS The 20F/8F, 24F/8F, 28F/8F, and 28F/10F (gastrostomy tube/jejunostomy tube) constructs allowed for injection and aspiration of all solutions. The 5F jejunostomy tubes allowed only water to be injected, whereas the 8F jejunostomy tubes did not allow injection of the canned food-water mixtures. The 20F/10F construct did not allow injection or aspiration through the gastrostomy tube, whereas the 18F/8F construct allowed injection but not aspiration through the gastrostomy tube. Faster flow rates through the gastrostomy tube were associated with larger gastrostomy tube diameter, smaller jejunostomy tube diameter, and smaller syringe size. Faster flow rates through the jejunostomy tube were associated with smaller jejunostomy tube diameter. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that homemade gastrojejunostomy constructs would allow for administration of a variety of enteral diets. Limitations to the administration and aspiration of various enteral diets as well as patient needs should be considered before a gastrojejunostomy tube combination is chosen.

Background: Experimental evidence shows benefit of rehabilitation after spinal cord injury (SCI) but there are limited objective data on the effect of rehabilitation on recovery of dogs after surgery for acute thoracolumbar intervertebral disc herniations (TL-IVDH)., Objective: Compare the effect of basic and intensive post-operative rehabilitation programs on recovery of locomotion in dogs with acute TL-IVDH in a randomized, blinded, prospective clinical trial., Animals: Thirty non-ambulatory paraparetic or paraplegic (with pain perception) dogs after decompressive surgery for TL-IVDH., Methods: Blinded, prospective clinical trial. Dogs were randomized (1:1) to a basic or intensive 14-day in-house rehabilitation protocol. Fourteen-day open field gait score (OFS) and coordination (regulatory index, RI) were primary outcomes. Secondary measures of gait, post-operative pain, and weight were compared at 14 and 42 days., Results: Of 50 dogs assessed, 32 met inclusion criteria and 30 completed the protocol. There were no adverse events associated with rehabilitation. Median time to walking was 7.5 (2 - 37) days. Mean change in OFS by day 14 was 6.13 (confidence intervals: 4.88, 7.39, basic) versus 5.73 (4.94, 6.53, intensive) representing a treatment effect of -0.4 (-1.82, 1.02) which was not significant, P=.57. RI on day 14 was 55.13 (36.88, 73.38, basic) versus 51.65 (30.98, 72.33, intensive), a non-significant treatment effect of -3.47 (-29.81, 22.87), P = .79. There were no differences in secondary outcomes between groups., Conclusions: Early postoperative rehabilitation after surgery for TL-IVDH is safe but doesn't improve rate or level of recovery in dogs with incomplete SCI., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)