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Here we present the development of the Mentoring in Undergraduate Research Survey (MURS) as a measure of a range of mentoring experienced by undergraduate science researchers. We drafted items based on qualitative research and refined the items through cognitive interviews and expert sorting. We used one national dataset to evaluate the internal structure of the measure and a second national dataset to examine how responses on the MURS related to theoretically relevant constructs and student characteristics. Our factor analytic results indicate seven lower order forms of mentoring experiences: abusive supervision, accessibility, technical support, psychosocial support, interpersonal mismatch, sexual harassment, and unfair treatment. These forms of mentoring mapped onto two higher-order factors: supportive and destructive mentoring experiences. Although most undergraduates reported experiencing supportive mentoring, some reported experiencing absence of supportive as well as destructive experiences. Undergraduates who experienced less supportive and more destructive mentoring also experienced lower scientific integration and a dampening of their beliefs about the value of research. The MURS should be useful for investigating the effects of mentoring experienced by undergraduate researchers and for testing interventions aimed at fostering supportive experiences and reducing or preventing destructive experiences and their impacts.

Abstract Symptoms of the Post-COVID-19 Condition are often non-specific making it a challenge to distinguish them from symptoms due to other medical conditions. In this study, we compare the proportion of emergency department patients who developed symptoms consistent with the World Health Organization’s Post-COVID-19 Condition clinical case definition between those who tested positive for Severe Acute Respiratory Syndrome Coronavirus-2 infection and time-matched patients who tested negative. Our results show that over one-third of emergency department patients with a proven acute infection meet Post-COVID-19 Condition criteria 3 months post-index visit. However, one in five test-negative patients who claim never having been infected also report symptoms consistent with Post-COVID-19 Condition highlighting the lack of specificity of the clinical case definition. Testing for SARS-CoV-2 during the acute phase of a suspected infection should continue until specific biomarkers of Post-COVID-19 Condition become available for diagnosis and treatment.

Although music education researchers often utilize music major status as a single-item proxy variable for musician status--and with this designation presume musical competencies or abilities of research participants--there is a lack of research demonstrating links between status as a music major and those assumed competencies. In this study, we compared undergraduate music majors and non-music majors (N = 237) at the group and individual levels using Goldsmiths Musical Sophistication Index (Gold-MSI), a well-established measure of multiple ways in which people report engaging with music. Comparing group means, we found that music majors scored higher than non-music majors on each Gold-MSI subscale. Moderate distribution overlap suggested that these results should be considered cautiously. A logistic regression analysis further suggested the complexity of using music major status as a single-item measure, given that music major status was only strongly predicted by the musical training subscale. Measures such as Gold-MSI may provide a viable and psychometrically sound way of determining musical sophistication that will allow more granular and refined analyses of studies relating to musical competencies.

This study aimed to evaluate the effectiveness of an automated tail movement sensor device (Moocall; Bluebell, Dublin, Ireland) to predict time of calving in dairy cows. At a commercial dairy farm in southern Ontario, Moocall (MC) devices were attached with the device's strap, and an additional elastic wrap, to the tail of cows approximately 3 d before their expected calving date. The MC has 2 types of alarm, a high activity alarm in the previous hour (1HA), and a high activity alarm in the previous 2 h (2HA); these alarms were sent and registered to the MC software. The calving and close-up pens were video monitored to determine the exact time of the onset of stage II of calving (amniotic sac visible at the vulva) and the end of stage II of calving (total expulsion of the calf). A total of 49 cows were enrolled, but we excluded 13 animals from the analysis as they had 3 or more MC drops from the tail (n = 6), a swollen tail (n = 3), or the MC device was lost (n = 4); this left 36 cows. In total, the device dropped off 21 (42%) cows. The average number of alarms (1HA and 2HA) per cow before stage II of calving was 2.7 ± 2.3 (± standard error). The first alarm after fitting the device on the tail was used to determine the device's sensitivity and specificity. Depending on the interval before the onset of parturition (i.e., 2, 4, 8, 12 h) in which the alarm was triggered, sensitivity varied from 5% to 72% and specificity from 50% to 93%. The false positive rate varied between 6% and 50% depending on the interval from the alarm to the onset of parturition. The high false positive and device drop rates (despite the addition of the elastic wrap) may compromise the applicability of this sensor device in a commercial setting.

Abstract The African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest quality de novo genome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided little support for the currently described four subspecies. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.

Background The most common cause of preventable death after injury is haemorrhage. Resuscitative endovascular balloon occlusion of the aorta is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis. Objective To compare standard care plus resuscitative endovascular balloon occlusion of the aorta versus standard care in patients with exsanguinating haemorrhage in the emergency department. Design Pragmatic, multicentre, Bayesian, group-sequential, registry-enabled, open-label, parallel-group randomised controlled trial to determine the clinical and cost-effectiveness of standard care plus resuscitative endovascular balloon occlusion of the aorta, compared to standard care alone. Setting United Kingdom Major Trauma Centres. Participants Trauma patients aged 16 years or older with confirmed or suspected life-threatening torso haemorrhage deemed amenable to adjunctive treatment with resuscitative endovascular balloon occlusion of the aorta. Interventions Participants were randomly assigned 1 : 1 to: standard care, as expected in a major trauma centre standard care plus resuscitative endovascular balloon occlusion of the aorta. Main outcome measures Primary: Mortality at 90 days. Secondary: Mortality at 6 months, while in hospital, and within 24, 6 and 3 hours; need for haemorrhage control procedures, time to commencement of haemorrhage procedure, complications, length of stay (hospital and intensive care unit-free days), blood product use. Health economic: Expected United Kingdom National Health Service perspective costs, life-years and quality-adjusted life-years, modelled over a lifetime horizon. Data sources Case report forms, Trauma Audit and Research Network registry, NHS Digital (Hospital Episode Statistics and Office of National Statistics data). Results Ninety patients were enrolled: 46 were randomised to standard care plus resuscitative endovascular balloon occlusion of the aorta and 44 to standard care. Mortality at 90 days was higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group (54%) compared to the standard care group (42%). The odds ratio was 1.58 (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (indicating increased odds of death with resuscitative endovascular balloon occlusion of the aorta) was 86.9%. The overall effect did not change when an enthusiastic prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3, 6 and 24 hours mortality), the posterior probability that standard care plus resuscitative endovascular balloon occlusion of the aorta was harmful was higher than for the primary outcome. Additional analyses to account for intercurrent events did not change the direction of the estimate for mortality at any time point. Death due to haemorrhage was more common in the standard care plus resuscitative endovascular balloon occlusion of the aorta group than in the standard care group. There were no serious adverse device effects. Resuscitative endovascular balloon occlusion of the aorta is less costly (probability 99%), due to the competing mortality risk but also substantially less effective in terms of lifetime quality-adjusted life-years (probability 91%). Limitations The size of the study reflects the relative infrequency of exsanguinating traumatic haemorrhage in the United Kingdom. There were some baseline imbalances between groups, but adjusted analyses had little effect on the estimates. Conclusions This is the first randomised trial of the addition of resuscitative endovascular balloon occlusion of the aorta to standard care in the management of exsanguinating haemorrhage. All the analyses suggest that a strategy of standard care plus resuscitative endovascular balloon occlusion of the aorta is potentially harmful. Future work The role (if any) of resuscitative endovascular balloon occlusion of the aorta in the pre-hospital setting remains unclear. Further research to clarify its potential (or not) may be required. Trial registration This trial is registered as ISRCTN16184981. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/199/09) and is published in full in Health Technology Assessment; Vol. 28, No. 54. See the NIHR Funding and Awards website for further award information. Plain language summary Trauma (physical injury) is a major cause of death and disability. The most common cause of preventable death after injury is uncontrolled bleeding. Resuscitative endovascular balloon occlusion of the aorta is a technique whereby a small balloon is inflated in the aorta (main blood vessel) which aims to limit blood loss until an operation can be done to stop the bleeding. In this study, which is the first randomised trial in the world of this technique, we investigated whether adding resuscitative endovascular balloon occlusion of the aorta to the standard care received in a major trauma centre reduced the risk of death in trauma patients who had life-threatening uncontrolled bleeding. The study took place in 16 major trauma centres in the United Kingdom. Ninety adult trauma patients with confirmed or suspected uncontrolled bleeding took part and were randomly divided into two groups: (1) those who received standard care and (2) those who received standard care plus resuscitative endovascular balloon occlusion of the aorta. We followed participants for 6 months using routinely collected data from the National Health Service and from the Trauma Audit Research Network registry. We also contacted surviving patients at 6 months to ask about their quality of life. In the standard care group, 42% of participants died within 90 days of their injury compared to 54% of participants in the standard care plus resuscitative endovascular balloon occlusion of the aorta group. Risk of death was also higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group at all other time points (3, 6 and 24 hours, in hospital and at 6 months). Overall, the study showed that the use of resuscitative endovascular balloon occlusion of the aorta in hospital increased the risk of death. Scientific summary Background Trauma is a major cause of death and disability. Trauma (physical injury) disproportionately affects the young, killing those who might otherwise have lived long and productive lives. The most common cause of preventable death after injury is haemorrhage. The addition of resuscitative endovascular balloon occlusion of the aorta (REBOA) to current standard care is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite, for definitive haemostasis. Objectives The UK-REBOA trial was a pragmatic, multicentre, Bayesian, open-label, group-sequential, parallel-group randomised controlled trial comparing standard care plus REBOA versus standard care in patients with exsanguinating haemorrhage in the emergency room. The study included an elicitation exercise, an embedded mixed-methods process evaluation and a health economic evaluation. The primary clinical outcome was 90-day mortality (defined as death within 90 days of injury, before or after discharge from hospital). Secondary clinical outcomes included 3-, 6- and 24-hour mortality, in-hospital mortality, 6-month mortality, length of stay (in hospital and intensive care unit), 24-hour blood product use, need for haemorrhage control procedures (operation or angioembolisation), time to commencement of haemorrhage control procedure, complications/safety data and functional outcome [measured using the extended Glasgow Outcome Scale (GOS-E)] at discharge. Economic outcomes were 6-month (within trial) and lifetime (modelled) UK NHS perspective costs, life-years and quality-adjusted life-years (QALYs) [calculated using EuroQol Group’s 5-dimension health status 5-level questionnaire (EQ-5D-5L)], 6-month quality of life (measured using EQ-5D-5L). Methods Trauma patients were recruited in 16 UK major trauma centres. Trauma patients aged (or believed to be aged) 16 years or older, with confirmed or suspected life-threatening torso haemorrhage thought to be amenable to adjunctive treatment with REBOA were eligible. Women known (or thought to be) pregnant and those with injuries deemed unsurvivable were excluded. The trauma team leader assessed the patients for eligibility. Patients who were eligible for inclusion in the trial were incapacitated and unable to give consent at the time of eligibility assessment and randomisation. There was also not sufficient time to consult a surrogate decision-maker, or even an independent medical practitioner, for advice about including the patient. Enrolment therefore took place without prior consent following Research Ethics Committee approval for this approach. Consent for continuing participation (i.e. data collection) was sought by a member of the UK-REBOA trial team once patients were no longer in a critical condition (defined as being cared for in a ward area rather than an intensive care unit or high-dependency unit) or from a personal (or nominated professional) consultee. The trauma team leader enrolled the participant using a dedicated, secure website, available on a handheld device (smartphone, tablet) or desktop computer which is linked directly to the 24-hour randomisation system at the Centre for Healthcare Randomised Trials, based in the Health Services Research Unit, University of Aberdeen. Patients were randomised into one of the two intervention arms, in a 1 : 1 allocation ratio, in randomly generated blocks of two or four. Standard care: Patients allocated to the control group received ‘standard care’, as expected in a specialist major trauma centre. Such treatment typically included intubation, blood transfusion including blood products in a 1 : 1 : 1 ratio, interventions such as tourniquet application, and early operative or endovascular haemorrhage control. Treatment could also have included open aortic occlusion of the thoracic or abdominal aorta. Standard care plus REBOA: Patients allocated to this arm of the trial additionally received the technique of endovascular aortic occlusion, for the purpose of resuscitation, as part of an overall treatment strategy. The addition of REBOA to current standard care was intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis. The trial sought to evaluate the technique of REBOA rather than a specific brand of device, and therefore permitted the use of any licensed occlusion balloon, and did not prescribe or mandate a particular product. The trial had an integrated training programme to ensure familiarity with the REBOA procedure. In patients who had been randomised to the standard care plus REBOA arm of the trial, clinicians could decide not to insert the balloon occlusion device if: the patient’s haemodynamic status improved (as a result of other resuscitative measures), if they were deemed to no longer have life-threatening torso haemorrhage requiring adjunctive treatment with REBOA; they deteriorated (to the point of imminent death); or there was technical difficulty in obtaining arterial access, and it was felt that operative control of haemorrhage could be obtained more quickly. The data collection strategy for the UK-REBOA trial was designed to minimise the burden on participants and clinicians, and for the avoidance of duplication. The randomisation system collected balloon inflation/deflation times. The trial drew on routinely collected data, primarily from the Trauma Audit and Research Network (TARN) registry which includes demographic, injury, treatment and outcome data (including the GOS-E and EQ-5D-5L). Mortality and hospital resource use data were also sought from NHS Digital. The main analysis was based on the intention-to-treat principle. There were two planned interim analyses of survival and a final analysis of all outcomes after follow-up was complete. Baseline and follow-up data were summarised using descriptive statistics and graphical summaries. Treatment effects are presented with 95% credible intervals for the primary and secondary outcomes. Elicitation exercise An elicitation exercise involving 20 subject matter experts (12 emergency medicine physicians, 3 pre-hospital care doctors, 4 surgeons and 1 intensivist) was undertaken to derive prior probability distributions to help contextualise the interpretation for the primary and secondary outcomes of the trial. Subject matter experts, on average, estimated in-hospital and 90-day mortality in this patient group, without the use of REBOA, to be in excess of 50%. Mortality at earlier time points (6 and 24 hours) was estimated to be closer to 25%. The elicited data, and the resulting prior probability distributions, indicate that the experts, on average, had a favourable opinion of REBOA, that is they expect the addition of REBOA to standard care to improve mortality at all time points. Clinical results Sixteen recruitment sites were opened in a staggered manner. Recruitment commenced in October 2017, was halted in March 2020 due to COVID-19, and restarted in July 2020. The second interim analysis (including 80 participants) triggered one of the pre-specified stopping rules, and recruitment closed in March 2022, by which time 90 participants had been recruited. Forty-four participants were randomised to standard care (2 of whom did receive REBOA) and 46 were randomised to standard care plus REBOA (19 of whom had the catheter inserted and balloon inserted and the remaining 27 progressed to different time points along this pathway). The groups were well-matched in terms of age, gender, comorbidities, mechanism of injury and injury severity. In the standard care arm, the median age was 39 years (interquartile range 30–56 years) and 77% were male. In the standard care plus REBOA arm, the median age was 46 years (interquartile range 33–62) and 61% were male. The median Injury Severity Score in both arms was 41 (interquartile range 29–50), with the majority classed as having very severe injury. Of the 46 patients allocated to standard care plus REBOA treatment, 25 (54%) died within 90 days. Of the 43 standard care patients for whom primary outcome data are available, 18 (42%) died within 90 days. Using the minimally informative prior, the odds of 90-day mortality were 1.58 for patients allocated to the standard care plus REBOA arm (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (i.e. that REBOA was harmful) was 86.9%. The direction of the estimate did not change when an enthusiastic (the elicited) prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3-, 6- and 24-hour mortality), the posterior probability that REBOA was harmful was higher than for the primary outcome. Additional analyses to account for intercurrent events did not change the direction of the estimate for mortality at 3, 6 and 24 hours, at 90 days or 6 months, or in-hospital mortality. Death due to haemorrhage was more common in the standard care plus REBOA group than in the standard care group. The mean number of days spent in intensive care and in hospital were lower in the standard care plus REBOA group compared to the standard care group, partly because of the higher number of earlier deaths in the standard care plus REBOA arm. There were no serious adverse device effects. Health economics We costed individual components of resources and summed these to generate a total cost for the whole initial hospitalisation admission period. Total NHS resource use for the index hospitalisation was obtained from patient-level data in TARN and the key resource use variables for costing included time of arrival, time of emergency department departure, time of first operation, time of death/discharge, number and type of operative procedures and volume of blood transfusions that were required. Secondary care contacts and episodes of care that were commenced between the date of discharge from the index hospitalisation through 6 months post randomisation were sourced, where available, through linkage of patient records to the Hospital Episode Statistics database. All costs are reported from a UK NHS perspective in Great British pounds (GBP) (year 2020-1). Quality of life was measured using the EQ-5D-5L prior to patient’s discharge from their index hospitalisation and at 6 months post admission. EQ-5D-5L asks respondents to report any problems on a given day across five dimensions of mobility, self-care, usual activities, anxiety/depression and pain. The data were available from TARN and supplemented with data collected by the local trial teams. EQ-5D-5L data were cross-walked to the 3L version and valued using UK general population preference tariffs. Baseline utility was set equal to the unconscious state (−0.402) and utility following death was set to 0. QALYs were calculated using an area under the curve approach assuming linear extrapolation between time points. From the within-trial health economic analysis, participants in the standard care plus REBOA arm of the study incurred lower costs {index hospital admission: mean cost £57,384 [standard deviation (SD) £62,863]} compared to those in standard care [mean cost £116,064 (SD £128,957)]. Lower costs in the standard care plus REBOA arm of the study were mainly due to lower use of hospital resources (length of stay, etc.) due to the competing risk of death (i.e. a higher number of deaths in the REBOA plus standard care group). Similarly, life-years accrued and QALYs over 6 months post randomisation were also lower in standard care plus REBOA compared to standard care due to a greater proportion of trial participants dying, with mortality also occurring earlier in the follow-up period for the REBOA arm. The mean life-years gained in the standard care plus REBOA arm was 0.232 (SD 0.247) compared to 0.305 (SD 0.236) in the standard care arm. When modelled over a full lifetime horizon, standard care plus REBOA is less costly (probability 99%), due to the competing risk of mortality but is also substantially less effective in terms of QALYs accrued over a lifetime horizon (probability 91%). The findings are robust to a range of scenario analyses undertaken, with the probability of standard care being the optimal treatment strategy ranging from 66% to 81% at a threshold value of a QALY = £50,000. Process evaluation The process evaluation was conducted in two phases; both phases involved interviews with clinical and research staff based at recruitment sites. Phase 1 was designed to identify barriers during trial initial and set-up; Phase 2 focused on exploring barriers and facilitators of recruitment into the trial and intervention delivery. A behavioural framework was used in Phase 2 to direct analysis and generate solutions designed to enhance trial practices, which included regular online meetings between the principal investigators from each site, updates to training materials and delivery, and e-mail/Twitter feedback on recruitment activity. Conclusions This is the first randomised trial ever to be conducted examining the potential clinical effectiveness of REBOA for the management of exsanguinating haemorrhage. All the analyses conducted suggest with high probability that a strategy of standard care plus REBOA is harmful. Implications for health care: The continuing use of REBOA, at least in the UK in-hospital setting, should be re-evaluated. Implications for research: The role (if any) of REBOA in the pre-hospital setting remains unclear. Further research to clarify its potential (or not) may be required. Trial registration This trial is registered as ISRCTN16184981. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/199/09) and will be published in full in Health Technology Assessment; Vol. 28, No. 54. See the NIHR Funding and Awards website for further award information.

Abstract We estimated the operating characteristics of ICD-10 code U07.1, introduced by the World Health Organization in 2020, to identify lab-confirmed SARS-CoV-2. CCEDRRN is a national research registry of adults (March 2020–August 2021) with suspected/confirmed SARS-CoV-2 identified in Canadian emergency departments (EDs) using chart review (symptoms, clinical information, and lab test results including SARS-CoV-2 polymerase chain reaction, PCR results). CCEDRRN data were linked to administrative hospitalization discharge and ED ICD-10 diagnostic codes (accessed centrally via the Canadian Institute for Health Information). We identified ICD-10 diagnostic codes in CCEDRRN participants. We defined lab-confirmed SARS-CoV-2 based on at least one positive PCR in the 0–14 days before the ED presentation and/or during hospitalization (in those admitted from ED). We performed separate analyses for CCEDRRN participants discharged from ED and those hospitalized from the ED. Additional analyses were stratified by province, sex, age, and (for hospitalized patients) timing of the first PCR test. The sensitivity of ICD-10 code U07.1 for a positive SARS-CoV-2 test was 93.6% (95% CI 93.0–94.1%) in those hospitalized from ED and 83.0% (95% CI 82.1–83.9%) in those discharged from the ED. Sensitivity was similar across provinces and demographics, but in each stratified analysis, values were higher in those hospitalized versus those discharged from ED. The ICD-10 diagnostic code for U07.1 within administrative data identified most lab-confirmed SARS-CoV-2 within persons hospitalized from ED, although a significant number of cases discharged from ED were missed. This should be considered when using administrative data for research and public health planning.

BackgroundTsetse flies (Glossina sp.) are vectors of Trypanosoma brucei subspecies that cause human African trypanosomiasis (HAT). Capturing and screening tsetse is critical for HAT surveillance. Classically, tsetse have been microscopically analysed to identify trypanosomes, but this is increasingly replaced with molecular xenomonitoring. Nonetheless, sensitive T. brucei-detection assays, such as TBR-PCR, are vulnerable to DNA cross-contamination. This may occur at capture, when often multiple live tsetse are retained temporarily in the cage of a trap. This study set out to determine whether infected tsetse can contaminate naïve tsetse with T. brucei DNA via faeces when co-housed.Methodology/principle findingsInsectary-reared teneral G. morsitans morsitans were fed an infectious T. b. brucei-spiked bloodmeal. At 19 days post-infection, infected and naïve tsetse were caged together in the following ratios: (T1) 9:3, (T2) 6:6 (T3) 1:11 and a control (C0) 0:12 in triplicate. Following 24-hour incubation, DNA was extracted from each fly and screened for parasite DNA presence using PCR and qPCR. All insectary-reared infected flies were positive for T. brucei DNA using TBR-qPCR. However, naïve tsetse also tested positive. Even at a ratio of 1 infected to 11 naïve flies, 91% of naïve tsetse gave positive TBR-qPCR results. Furthermore, the quantity of T. brucei DNA detected in naïve tsetse was significantly correlated with cage infection ratio. With evidence of cross-contamination, field-caught tsetse from Tanzania were then assessed using the same screening protocol. End-point TBR-PCR predicted a sample population prevalence of 24.8%. Using qPCR and Cq cut-offs optimised on insectary-reared flies, we estimated that prevalence was 0.5% (95% confidence interval [0.36, 0.73]).Conclusions/significanceOur results show that infected tsetse can contaminate naïve flies with T. brucei DNA when co-caged, and that the level of contamination can be extensive. Whilst simple PCR may overestimate infection prevalence, quantitative PCR offers a means of eliminating false positives.

Abstract. Introduction:. Chronic pain affects a wide range of physical and psychological aspects of life for those impacted. Psychosocial treatment approaches may be of support, but outreach is still limited. Objectives:. To evaluate the efficacy of EPIO, an evidence-informed, user-centered digital self-management intervention for people with chronic pain, in a 12-month randomized controlled trial. Methods:. People living with chronic pain (N = 266) were randomized to the EPIO intervention (n = 132) or a usual-care control group (n = 134). The intervention was delivered in a simple blended care model, and outcome measures collected at baseline, 6 months, and 12 months. Generalized linear models for repeated measures were fitted to compare groups over time. Results:. Participants were primarily female (81%), median age 49 years (range 22–78), with heterogeneous pain conditions, and had lived with pain >5 years (77.6%). A mixed linear model with all timepoints included revealed no statistically significant group differences for the primary outcome of pain interference. Significant psychological benefits in favor of the intervention group were however detected for depression (P = 0.022), self-regulatory fatigue (P = 0.024), vitality (P = 0.016), and mental health (P = 0.047). Baseline to 12-month changes showed additional favorable effects for anxiety (between-group mean differences [MDs] = 0.79, P = 0.047), depression (MD = 1.08, P = 0.004), self-regulatory fatigue (MD = 2.42, P = 0.021), pain catastrophizing (MD = 2.62, P = 0.009), and health-related quality of life. Conclusions:. The EPIO program aims to improve outreach of evidence-based pain self-management interventions. Findings demonstrate how using EPIO can lead to sustainable psychological change, enhancing mental health and health-related quality of life for people suffering from pain, providing a chance to live well with the pain.

The phase space of a noncanonical Hamiltonian system is partially inaccessible due to dynamical constraints (Casimir invariants) arising from the kernel of the Poisson tensor. When an ensemble of noncanonical Hamiltonian systems is allowed to interact, dissipative processes eventually break the phase space constraints, resulting in a thermodynamic equilibrium described by a Maxwell–Boltzmann distribution. However, the time scale required to reach Maxwell–Boltzmann statistics is often much longer than the time scale over which a given system achieves a state of thermal equilibrium. Examples include diffusion in rigid mechanical systems, as well as collisionless relaxation in magnetized plasmas and stellar systems, where the interval between binary Coulomb or gravitational collisions can be longer than the time scale over which stable structures are self-organized. Here, we focus on self-organizing phenomena over spacetime scales such that particle interactions respect the noncanonical Hamiltonian structure, but yet act to create a state of thermodynamic equilibrium. We derive a collision operator for general noncanonical Hamiltonian systems, applicable to fast, localized interactions. This collision operator depends on the interaction exchanged by colliding particles and on the Poisson tensor encoding the noncanonical phase space structure, is consistent with entropy growth and conservation of particle number and energy, preserves the interior Casimir invariants, reduces to the Landau collision operator in the limit of grazing binary Coulomb collisions in canonical phase space, and exhibits a metriplectic structure. We further show how thermodynamic equilibria depart from Maxwell–Boltzmann statistics due to the noncanonical phase space structure, and how self-organization and collisionless relaxation in magnetized plasmas and stellar systems can be described through the derived collision operator.

Abstract Animal African trypanosomiasis (AAT) is a significant food security and economic burden in sub-Saharan Africa. Current AAT empirical and immunodiagnostic surveillance tools suffer from poor sensitivity and specificity, with blood sampling requiring animal restraint and trained personnel. Faecal sampling could increase sampling accessibility, scale, and species range. Therefore, this study assessed feasibility of detecting Trypanosoma DNA in the faeces of experimentally-infected cattle. Holstein–Friesian calves were inoculated with Trypanosoma brucei brucei AnTat 1.1 (n = 5) or T. congolense Savannah IL3000 (n = 6) in separate studies. Faecal and blood samples were collected concurrently over 10 weeks and screened using species-specific PCR and qPCR assays. T. brucei DNA was detected in 85% of post-inoculation (PI) faecal samples (n = 114/134) by qPCR and 50% by PCR between 4 and 66 days PI. However, T. congolense DNA was detected in just 3.4% (n = 5/145) of PI faecal samples by qPCR, and none by PCR. These results confirm the ability to consistently detect T. brucei DNA, but not T. congolense DNA, in infected cattle faeces. This disparity may derive from the differences in Trypanosoma species tissue distribution and/or extravasation. Therefore, whilst faeces are a promising substrate to screen for T. brucei infection, blood sampling is required to detect T. congolense in cattle.

Abstract Background Altered Airway Anatomy (AAA), including tracheostomies and laryngectomies, may represent an area of unease for non-Otolaryngology trainees, due to a lack of exposure, structured education, or dedicated training in altered airway management. Inability to effectively stabilize an altered airway is associated with significant risk of patient morbidity and mortality. This study aims to assess the efficacy of a concise curriculum using three-dimensional (3D) printed airway models for skill training in improving Anesthesiology trainees’ competency in AAA management. Methods A prospective cohort of 42 anesthesiology residents at a tertiary care institution were guided through a 75-min curriculum on AAA, including case discussion, surgical video, and hands-on practice with tracheostomy and laryngectomy skills trainers. Pre- and post- course surveys assessing provider confidence (Likert scale) and knowledge (multiple choice questions) were administered. Additionally, an observed skills competency assessment was performed. Results Self-perceived confidence improved from a summative score across all domains of 23.65/40 pre-course to 36.39/40 post-course (n = 31, p

East Coast Fever (ECF) is a disease affecting cattle in sub-Saharan Africa, caused by the tick-borne Apicomplexan pathogen Theileria parva. The disease is a major problem for cattle farmers in affected regions and there are few methods of control, including a complex infection and treatment vaccine, expensive chemotherapy, and the more widespread tick control through acaricides. New intervention strategies are, therefore, sorely needed. Benzoxaboroles are a versatile class of boron-heterocyclic compounds with demonstrable pharmacological activity against a diverse group of pathogens, including those related to T. parva. In this study, the in vitro efficacy of three benzoxaboroles against the intracellular schizont stage of T. parva was investigated using a flow cytometry approach. Of the benzoxaboroles tested, only one showed any potency, albeit only at high concentrations, even though there is high protein sequence similarity in the CPSF3 protein target compared to other protozoan pathogen species. This finding suggests that benzoxaboroles currently of interest for the treatment of African animal trypanosomiasis, toxoplasmosis, cryptosporidiosis and malaria may not be suitable for the treatment of ECF. We conclude that testing of further benzoxaborole compounds is needed to fully determine whether any lead compounds can be identified to target T. parva.

Introduction Emergency psychiatric care, unplanned hospital admissions, and inpatient health care are the costliest forms of mental health care. According to Statistics Canada (2018), almost 18% (5.3 million) of Canadians reported needing mental health support. However, just above half of this figure (56.2%) have reported their needs were fully met. To further expand capacity and access to mental health care in the province, Nova Scotia Health has launched a novel mental health initiative, the Rapid Access, and Stabilization Program (RASP). Objectives This study evaluates the effectiveness and impact of the RASP on high-cost health services utilization (e.g. ED visits, mobile crisis visits, and inpatient treatments) and related costs. It also assesses healthcare partners’ (e.g. healthcare providers, policymakers, community leaders) perceptions and patient experiences and satisfaction with the program and identifies sociodemographic characteristics, psychological conditions, recovery, well-being, and risk measures in the assisted population. Methods This is a hypothesis-driven program evaluation study that employs a mixed methods approach. A within-subject comparison will examine health services utilization data from patients attending RASP, one year before and one year after their psychiatry assessment at the program. A controlled between-subject comparison will use historical data from a control population will examine whether possible changes in high-cost health services utilization are associated with the intervention (RASP). The primary analysis involves extracting secondary data from provincial information systems, electronic medical records, and regular self-reported clinical assessments. Additionally, a qualitative sub-study will examine patient experience and satisfaction, and examine health care partners’ impressions. Results The results for the primary, secondary, and qualitative outcome measures to be available within 6 months of study completion. We expect that RASP evaluation findings will demonstrate a minimum 10% reduction in high-cost health services utilization and corresponding 10% cost savings, and also a reduction in the wait times for patient consultations with psychiatrists to less than 30 calendar days. In addition, we anticipate that patients, healthcare providers, and healthcare partners would express high levels of satisfaction with the new service. Conclusions This study will demonstrate the results of the Mental Health and Addictions Program (MHAP) efforts to provide stepped-care, particularly community-based support, to individuals with mental illnesses. Results will provide new insights into a novel community-based approach to mental health service delivery and contribute to knowledge on how to implement mental health programs across varying contexts. Disclosure of Interest None Declared

Objectives This study investigates the effectiveness of a virtual format of an advanced communication skills observed structured clinical examination (OSCE) for senior medical students in comparison to an in-person format. The study also examines the emotional support students experience in the virtual setting. Our analysis was based on quantitative data collected through objective checklists and post-OSCE survey results. Methods The virtual OSCE was a revision of an earlier in-person formative advanced communication skills OSCE for fourth-year medical students. Student performances were assessed by self and peers using objective checklists—the modified Master Interview Rating Scale (mMIRS) and Communication Behavior Checklist (CBC). The mMIRS measured interview process such as avoiding jargon and demonstrating empathy. The CBC examined interview content which included tasks specific to the content of the case. The OSCE was followed by a faculty-led debrief and quantitative survey. The virtual OSCE was conducted in 2021, and the results of the checklists and survey were compared with those collected from two earlier in-person OSCEs. Results Eighty-three students participated in the virtual OSCE. There was no difference in mMIRS scores between the virtual and in-person OSCE. Overall CBC scores were lower in the virtual OSCE compared to in-person ( p

Understanding the soil bacterial communities involved in carbon (C) and nitrogen (N) cycling can inform beneficial tillage and crop rotation practices for sustainability and crop production. This study evaluated soil bacterial diversity, compositional structure, and functions associated with C-N cycling at two soil depths (0–15 cm and 15–30 cm) under long-term tillage (conventional tillage [CT] and no-till [NT]) and crop rotation (monocultures of corn, soybean, and wheat and corn–soybean–wheat rotation) systems. The soil microbial communities were characterized by metabarcoding the 16S rRNA gene V4–V5 regions using Illumina MiSeq. The results showed that long-term NT reduced the soil bacterial diversity at 15–30 cm compared to CT, while no significant differences were found at 0–15 cm. The bacterial communities differed significantly at the two soil depths under NT but not under CT. Notably, over 70% of the tillage-responding KEGG orthologs (KOs) associated with C fixation (primarily in the reductive citric acid cycle) were more abundant under NT than under CT at both depths. The tillage practices significantly affected bacteria involved in biological nitrogen (N2) fixation at the 0–15 cm soil depth, as well as bacteria involved in denitrification at both soil depths. The crop type and rotation regimes had limited effects on bacterial diversity and structure but significantly affected specific C-N-cycling genes. For instance, three KOs associated with the Calvin–Benson cycle for C fixation and four KOs related to various N-cycling processes were more abundant in the soil of wheat than in that of corn or soybean. These findings indicate that the long-term tillage practices had a greater influence than crop rotation on the soil bacterial communities, particularly in the C- and N-cycling processes. Integrated management practices that consider the combined effects of tillage, crop rotation, and crop types on soil bacterial functional groups are essential for sustainable agriculture.

● An expert survey highlighted the most effective strategies for GHG and ammonia mitigation. ● Interventions considered to have the highest mitigation potential are discussed. ● Experts agreed that no single mitigation measure can uniquely deliver GHG and ammonia mitigation. ● Experts noted a need for further investment in research, knowledge exchange, education and to develop implementation pathways. ● There is a need for more data to better quantify mitigation potentials and implement effective management strategies. Agriculture is essential for providing food and maintaining food security while concurrently delivering multiple other ecosystem services. However, agricultural systems are generally a net source of greenhouse gases and ammonia. They, therefore, need to substantively contribute to climate change mitigation and net zero ambitions. It is widely acknowledged that there is a need to further reduce and mitigate emissions across sectors, including agriculture to address the climate emergency and emissions gap. This discussion paper outlines a collation of opinions from a range of experts within agricultural research and advisory roles following a greenhouse gas and ammonia emission mitigation workshop held in the UK in March 2022. The meeting identified the top mitigation priorities within the UK’s agricultural sector to achieve reductions in greenhouse gases and ammonia that are compatible with policy targets. In addition, experts provided an overview of what they believe are the key knowledge gaps, future opportunities and co-benefits to mitigation practices as well as indicating the potential barriers to uptake for mitigation scenarios discussed.

Abstract Background Obesity is associated with an increased risk of multiple conditions, ranging from heart disease to cancer. However, there are few predictive models for these outcomes that have been developed specifically for people with overweight/obesity. Objective To develop predictive models for obesity‐related complications in patients with overweight and obesity. Methods Electronic health record data of adults with body mass index 25–80 kg/m2 treated in primary care practices between 2000 and 2019 were utilized to develop and evaluate predictive models for nine long‐term clinical outcomes using a) Lasso‐Cox models and b) a machine‐learning method random survival forests (RSF). Models were trained on a training dataset and evaluated on a test dataset over 100 replicates. Parsimonious models of

Abstract Objective To review new drugs and devices relevant to otolaryngology approved by the Food and Drug Administration (FDA) in 2022. Data Sources Publicly available FDA data on drugs and devices approved in 2022. Review Methods A preliminary screen was conducted to identify drugs and devices relevant to otolaryngology. A secondary screen by members of the American Academy of Otolaryngology–Head and Neck Surgery's (AAO‐HNS) Medical Devices and Drugs Committee differentiated between minor updates and new approvals. The final list of drugs and devices was sent to members of each subspecialty for review and analysis. Conclusion A total of 1251 devices and 37 drugs were identified on preliminary screening. Of these, 329 devices and 5 drugs were sent to subspecialists for further review, from which 37 devices and 2 novel drugs were selected for further analysis. The newly approved devices spanned all subspecialties within otolaryngology. Many of the newly approved devices aimed to enhance patient experience, including over‐the‐counter hearing aids, sleep monitoring devices, and refined CPAP devices. Other advances aimed to improve surgical access, convenience, or comfort in the operating room and clinic. Implications for Practice Many new devices and drugs are approved each year to improve patient care and care delivery. By staying up to date with these advances, otolaryngologists can leverage new innovations to improve the safety and quality of care. Given the recent approval of these devices, further studies are needed to assess long‐term impact within the field of otolaryngology.

Pressure-volume (PV) loop analysis is a sophisticated invasive approach to quantifying load-dependent and independent measures of cardiac function. Biventricular (BV) PV loops allow left and right ventricular function to be quantified simultaneously and independently, which is important for conditions and certain physiologic states, such as ventricular decoupling or acute physiologic changes. BV PV loops can be performed in an entirely endovascular, percutaneous, and closed-chest setting. This technique is helpful in a survival animal model, as a percutaneous monitoring system during endovascular device experiments, or in cases where chest wall compliance is being tested or may be a confounder. In this article, we describe the end-to-end implementation of a completely endovascular, totally percutaneous, and closed-chest large animal model to obtain contemporaneous BV PV loops in 40 to 70 kg swine. We describe the associated surgical and technical challenges and our solutions to obtaining endovascular BV PV loops, closed-chest cardiac output, and stroke volume (including validation of the correction factor necessary for thermodilution), as well as how to perform endovascular inferior vena cava occlusion in this swine model. We also include techniques for data acquisition and analysis that are required for this method. : Clinical Relevance: This article describes the end-to-end implementation of a completely endovascular, percutaneous, and closed-chest large animal model for obtaining biventricular pressure-volume loops in swine. This will allow researchers to obtain contemporaneous, continuous left and right ventricular physiology through a minimally invasive procedure that animals can survive and does not alter chest wall compliance. This model may be used to better quantify the physiology during clinical scenarios of ventricular decoupling, during procedures such as transcatheter aortic valve repair or those that alter left ventricular (LV) function, or during the initiation of resuscitative endovascular balloon occlusion of the aorta or extracorporeal cardiopulmonary resuscitation when LV and right ventricular filling become misaligned.

Summary: Nonoptimal synonymous codons repress gene expression, but the underlying mechanisms are poorly understood. We and others have previously shown that nonoptimal codons slow translation elongation speeds and thereby trigger messenger RNA (mRNA) degradation. Nevertheless, transcript levels are often insufficient to explain protein levels, suggesting additional mechanisms by which codon usage regulates gene expression. Using reporters in human and Drosophila cells, we find that transcript levels account for less than half of the variation in protein abundance due to codon usage. This discrepancy is explained by translational differences whereby nonoptimal codons repress translation initiation. Nonoptimal transcripts are also less bound by the translation initiation factors eIF4E and eIF4G1, providing a mechanistic explanation for their reduced initiation rates. Importantly, translational repression can occur without mRNA decay and deadenylation, and it does not depend on the known nonoptimality sensor, CNOT3. Our results reveal a potent mechanism of regulation by codon usage where nonoptimal codons repress further rounds of translation.

ABSTRACT African trypanosomes are vector-borne protozoa, which cause significant human and animal disease across sub-Saharan Africa, and animal disease across Asia and South America. In humans, infection is caused by variants of Trypanosoma brucei, and is characterized by varying rate of progression to neurological disease, caused by parasites exiting the vasculature and entering the brain. Animal disease is caused by multiple species of trypanosome, primarily T. congolense, T. vivax, and T. brucei. These trypanosomes also infect multiple species of mammalian host, and this complexity of trypanosome and host diversity is reflected in the spectrum of severity of disease in animal trypanosomiasis, ranging from hyperacute infections associated with mortality to long-term chronic infections, and is also a main reason why designing interventions for animal trypanosomiasis is so challenging. In this review, we will provide an overview of the current understanding of trypanosome determinants of infection progression and severity, covering laboratory models of disease, as well as human and livestock disease. We will also highlight gaps in knowledge and capabilities, which represent opportunities to both further our fundamental understanding of how trypanosomes cause disease, as well as facilitating the development of the novel interventions that are so badly needed to reduce the burden of disease caused by these important pathogens.

Abstract Background Understanding the variation between well and poorly adapted cattle breeds to local environments and pathogens is essential for breeding cattle with improved climate and disease-resistant phenotypes. Although considerable progress has been made towards identifying genetic differences between breeds, variation at the epigenetic and chromatin levels remains poorly characterized. Here, we generate, sequence and analyse over 150 libraries at base-pair resolution to explore the dynamics of DNA methylation and chromatin accessibility of the bovine immune system across three distinct cattle lineages. Results We find extensive epigenetic divergence between the taurine and indicine cattle breeds across immune cell types, which is linked to the levels of local DNA sequence divergence between the two cattle sub-species. The unique cell type profiles enable the deconvolution of complex cellular mixtures using digital cytometry approaches. Finally, we show distinct sub-categories of CpG islands based on their chromatin and methylation profiles that discriminate between classes of distal and gene proximal islands linked to discrete transcriptional states. Conclusions Our study provides a comprehensive resource of DNA methylation, chromatin accessibility and RNA expression profiles of three diverse cattle populations. The findings have important implications, from understanding how genetic editing across breeds, and consequently regulatory backgrounds, may have distinct impacts to designing effective cattle epigenome-wide association studies in non-European breeds.

Abstract Many health authorities differentiate hospitalizations in patients infected with SARS-CoV-2 as being “for COVID-19” (due to direct manifestations of SARS-CoV-2 infection) versus being an “incidental” finding in someone admitted for an unrelated condition. We conducted a retrospective cohort study of all SARS-CoV-2 infected patients hospitalized via 47 Canadian emergency departments, March 2020-July 2022 to determine whether hospitalizations with “incidental” SARS-CoV-2 infection are less of a burden to patients and the healthcare system. Using a priori standardized definitions applied to hospital discharge diagnoses in 14,290 patients, we characterized COVID-19 as (i) the “Direct” cause for the hospitalization (70%), (ii) a potential “Contributing” factor for the hospitalization (4%), or (iii) an “Incidental” finding that did not influence the need for admission (26%). The proportion of incidental SARS-CoV-2 infections rose from 10% in Wave 1 to 41% during the Omicron wave. Patients with COVID-19 as the direct cause of hospitalization exhibited significantly longer LOS (mean 13.8 versus 12.1 days), were more likely to require critical care (22% versus 11%), receive COVID-19-specific therapies (55% versus 19%), and die (17% versus 9%) compared to patients with Incidental SARS-CoV-2 infections. However, patients hospitalized with incidental SARS-CoV-2 infection still exhibited substantial morbidity/mortality and hospital resource use.

In this paper we report on the inaugural meetings of the Musical Care International Network held online in 2022. The term “musical care” is defined by Spiro and Sanfilippo (2022) as “the role of music—music listening as well as music-making—in supporting any aspect of people's developmental or health needs” (pp. 2–3). Musical care takes varied forms in different cultural contexts and involves people from different disciplines and areas of expertise. Therefore, the Musical Care International Network takes an interdisciplinary and international approach and aims to better reflect the disciplinary, geographic, and cultural diversity relevant to musical care. Forty-two delegates participated in 5 inaugural meetings over 2 days, representing 24 countries and numerous disciplines and areas of practice. Based on the meetings, the aims of this paper are to (1) better understand the diverse practices, applications, contexts, and impacts of musical care around the globe and (2) introduce the Musical Care International Network. Transcriptions of the recordings, alongside notes taken by the hosts, were used to summarise the conversations. The discussions developed ideas in three areas: (a) musical care as context-dependent and social, (b) musical care's position within the broader research and practice context, and (c) debates about the impact of and evidence for musical care. We can conclude that musical care refers to context-dependent and social phenomena. The term musical care was seen as useful in talking across boundaries while not minimizing individual disciplinary and professional expertise. The use of the term was seen to help balance the importance and place of multiple disciplines, with a role to play in the development of a collective identity. This collective identity was seen as important in advocacy and in helping to shape policy. The paper closes with proposed future directions for the network and its emerging mission statement.

Introduction: Over 400,000 out-of-hospital cardiac arrest (OHCA) occur each year in Canada and the United States with less than 10% survival to hospital discharge. Cardiac arrest is a heterogenous condition and patient outcomes are impacted by a multitude of factors. Prognostication is recommended at 72 hours after return of spontaneous circulation (ROSC), however there may be other factors that could predict patient outcome earlier in the post-arrest period. The objective of our study was to develop and internally validate a novel clinical prediction rule to risk stratify patients early in the post-cardiac arrest period. Methods: We performed a retrospective cohort study of adult (≥18 years) post-cardiac arrest patients between 2010 and 2015 from the Epistry Cardiac Arrest database in Toronto. Our primary analysis used ordinal logistic regression to examine neurologic outcome at discharge using the modified Rankin Scale (mRS). Our secondary analysis used logistic regression for neurologic outcome and survival to hospital discharge. Models were internally validated using bootstrap validation. Results: A total of 3432 patients met our inclusion criteria. Our clinical prediction model was able to predict neurologic outcome on an ordinal scale using our predefined variables with an AUC of 0.89 after internal validation. The predictive performance was maintained when examining neurologic outcome as a binary variable and survival to hospital discharge. Conclusion: We were able to develop a model to accurately risk stratify adult cardiac arrest patients early in the post-cardiac arrest period. Future steps are needed to externally validate this model in other healthcare settings.

Background: Incidental identification of peritoneal nodules during laparoscopy may present a diagnostic dilemma. The differential diagnosis includes a variety of benign and malignant entities such as peritoneal carcinomatosis. Case: A 44-year-old G2P2 woman presented with recurrent menorrhagia and pelvic pain was found to have large uterine fibroids on imaging studies. Bilateral uterine artery embolization was performed with complete devascularization of the fibroid. Seven years later, she presented with similar symptoms. Imaging studies demonstrated a vascular uterine lesion. A total laparoscopic hysterectomy with bilateral salpingectomy was performed with no complications. During surgery, vesicular peritoneal implants were incidentally identified posterior to the uterus between the uterosacral ligaments. Biopsy and pathologic analysis of these nodules confirmed that they contained foreign material consistent with embolization beads. Pathologic analysis of the uterus demonstrated an intramural uterine fibroid, and presence of embolization beads in cervix, myometrium and bilateral peritubal regions. Conclusion: Non-target peritoneal implantation of embolic beads after uterine artery embolization is a rare entity that can result in vesicular appearing nodules.

Abstract Non-pairwise interactions, or higher-order interactions (HOIs), in microbial communities have been described as significant drivers of emergent features in microbiomes. Yet, the re-organization of microbial interactions between pairwise cultures and larger communities remains largely unexplored from a molecular perspective but is central to our understanding and further manipulation of microbial communities. Here, we used a bottom-up approach to investigate microbial interaction mechanisms from pairwise cultures up to 4-species communities from a simple microbiome (Hafnia alvei, Geotrichum candidum, Pencillium camemberti and Escherichia coli). Specifically, we characterized the interaction landscape for each species combination involving E. coli by identifying E. coli’s interaction-associated mutants using an RB-TnSeq-based interaction assay. We observed a deep reorganization of the interaction-associated mutants, with very few 2-species interactions conserved all the way up to a 4-species community and the emergence of multiple HOIs. We further used a quantitative genetics strategy to decipher how 2-species interactions were quantitatively conserved in higher community compositions. Epistasis-based analysis revealed that, of the interactions that are conserved at all levels of complexity, 82% follow an additive pattern. Altogether, we demonstrate the complex architecture of microbial interactions even within a simple microbiome, and provide a mechanistic and molecular explanation of HOIs.

Abstract Popliteal artery injury following knee dislocation is associated with significant morbidity and high amputation rates. The complex and multi-disciplinary input required to manage this injury effectively can take time to arrange, prolonging the time to revascularization. Furthermore, open surgical bypass or interposition graft can be technically challenging in the acute setting, further prolonging ischemic time. Temporary intravascular shunts can be used to temporarily restore flow but require surgical exposure which takes time. Endovascular techniques can decrease the time to revascularization; however, endovascular popliteal stent-grafting is controversial because the biomechanical forces relating to flexion and extension of the knee may increase the risk of stent thrombosis. An ideal operation would result in rapid revascularization, eventually leading to a definitive and durable surgical solution. We hypothesize that a staged approach combing extracorporeal shunting, temporary endovascular covered stent placement, external fixation of bony injury, and definitive open repair provides for a superior approach to popliteal artery injury than current standard of care. We term this approach lower extremity staged revascularization (LESR) and the aim is to minimize the known factors contributing to poor outcomes after traumatic popliteal artery injury.

Abstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

Abstract Background In cattle, genome-wide association studies (GWAS) have largely focused on European or Asian breeds, using genotyping arrays that were primarily designed for European cattle. Because there is growing interest in performing GWAS in African breeds, we have assessed the performance of 23 commercial bovine genotyping arrays for capturing the diversity across African breeds and performing imputation. We used 409 whole-genome sequences (WGS) spanning global cattle breeds, and a real cohort of 2481 individuals (including African breeds) that were genotyped with the Illumina high-density (HD) array and the GeneSeek bovine 50 k array. Results We found that commercially available arrays were not effective in capturing variants that segregate among African indicine animals. Only 6% of these variants in high linkage disequilibrium (LD) (r2 > 0.8) were on the best performing arrays, which contrasts with the 17% and 25% in African and European taurine cattle, respectively. However, imputation from available HD arrays can successfully capture most variants (accuracies up to 0.93), mainly when using a global, not continent-specific, reference panel, which partially reflects the unusually high levels of admixture on the continent. When considering functional variants, the GGPF250 array performed best for tagging WGS variants and imputation. Finally, we show that imputation from low-density arrays can perform almost as well as HD arrays, if a two-stage imputation approach is adopted, i.e. first imputing to HD and then to WGS, which can potentially reduce the costs of GWAS. Conclusions Our results show that the choice of an array should be based on a balance between the objective of the study and the breed/population considered, with the HD and BOS1 arrays being the best choice for both taurine and indicine breeds when performing GWAS, and the GGPF250 being preferable for fine-mapping studies. Moreover, our results suggest that there is no advantage to using the indicus-specific arrays for indicus breeds, regardless of the objective. Finally, we show that using a reference panel that better represents global bovine diversity improves imputation accuracy, particularly for non-European taurine populations.

BackgroundChronic pain conditions involve numerous physical and psychological challenges, and while psychosocial self-management interventions can be of benefit for people living with chronic pain, such in-person treatment is not always accessible. Digital self-management approaches could improve this disparity, potentially bolstering outreach and providing easy, relatively low-cost access to pain self-management interventions. ObjectiveThis randomized controlled trial aimed to evaluate the short-term efficacy of EPIO (ie, inspired by the Greek goddess for the soothing of pain, Epione), a digital self-management intervention, for people living with chronic pain. MethodsPatients (N=266) were randomly assigned to either the EPIO intervention (n=132) or a care-as-usual control group (n=134). Outcome measures included pain interference (Brief Pain Inventory; primary outcome measure), anxiety and depression (Hospital Anxiety and Depression Scale), self-regulatory fatigue (Self-Regulatory Fatigue 18 scale), health-related quality of life (SF-36 Short Form Health Survey), pain catastrophizing (Pain Catastrophizing Scale), and pain acceptance (Chronic Pain Acceptance Questionnaire). Linear regression models used change scores as the dependent variables. ResultsThe participants were primarily female (210/259, 81.1%), with a median age of 49 (range 22-78) years and a variety of pain conditions. Analyses (n=229) after 3 months revealed no statistically significant changes for the primary outcome of pain interference (P=.84), but significant reductions in the secondary outcomes of depression (mean difference −0.90; P=.03) and self-regulatory fatigue (mean difference −2.76; P=.008) in favor of the intervention group. No other statistically significant changes were observed at 3 months (all P>.05). Participants described EPIO as useful (ie, totally agree or agree; 95/109, 87.2%) and easy to use (101/109, 92.7%), with easily understandable exercises (106/109, 97.2%). ConclusionsEvidence-informed, user-centered digital pain self-management interventions such as EPIO may have the potential to effectively support self-management and improve psychological functioning in the form of reduced symptoms of depression and improved capacity to regulate thoughts, feelings, and behavior for people living with chronic pain. Trial RegistrationClinicalTrials.gov NCT03705104; https://clinicaltrials.gov/ct2/show/NCT03705104

In Canada, the length of the frost-free season necessitates planting crops as early as possible to ensure that the plants have enough time to reach full maturity before they are harvested. Early planting carries inherent risks of cold water imbibition (specifically less than 4°C) affecting seed germination. A marker dataset developed for a previously identified Canadian soybean GWAS panel was leveraged to investigate the effect of cold water imbibition on germination. Seed from a panel of 137 soybean elite cultivars, grown in the field at Ottawa, ON, over three years, were placed on filter paper in petri dishes and allowed to imbibe water for 16 hours at either 4°C or 20°C prior to being transferred to a constant 20°C. Observations on seed germination, defined as the presence of a 1 cm radicle, were done from day two to seven. A three-parameter exponential rise to a maximum equation (3PERM) was fitted to estimate germination, time to the one-half maximum germination, and germination uniformity for each cultivar. Genotype-by-sequencing was used to identify SNPs in 137 soybean lines, and using genome-wide association studies (GWAS - rMVP R package, with GLM, MLM, and FarmCPU as methods), haplotype block analysis, and assumed linkage blocks of ±100 kbp, a threshold for significance was established using the qvalue package in R, and five significant SNPs were identified on chromosomes 1, 3, 4, 6, and 13 for maximum germination after cold water imbibition. Percent of phenotypic variance explained (PVE) and allele substitution effect (ASE) eliminated two of the five candidate SNPs, leaving three QTL regions on chromosomes 3, 6, and 13 (Chr3-3419152, Chr6-5098454, and Chr13-29649544). Based on the gene ontology (GO) enrichment analysis, 14 candidate genes whose function is predicted to include germination and cold tolerance related pathways were identified as candidate genes. The identified QTLs can be used to select future soybean cultivars tolerant to cold water imbibition and mitigate risks associated with early soybean planting.

ABSTRACT The effect of plasma-activated water (PAW) generated with a dielectric barrier discharge diffusor (DBDD) system on microbial load and organoleptic quality of cucamelons was investigated and compared to the established sanitizer, sodium hypochlorite (NaOCl). Pathogenic serotypes of Escherichia coli, Salmonella enterica, and Listeria monocytogenes were inoculated onto the surface of cucamelons (6.5 log CFU g−1) and into the wash water (6 log CFU mL−1). PAW treatment involved 2 min in situ with water activated at 1,500 Hz and 120 V and air as the feed gas; NaOCl treatment was a wash with 100 ppm total chlorine; control treatment was a wash with tap water. PAW treatment produced a 3-log CFU g−1 reduction of pathogens on the cucamelon surface without negatively impacting quality or shelf life. NaOCl treatment reduced the pathogenic bacteria on the cucamelon surface by 3 to 4 log CFU g−1; however, this treatment also reduced fruit shelf life and quality. Both systems reduced 6-log CFU mL−1 pathogens in the wash water to below detectable limits. The critical role of superoxide anion radical (·O2−) in the antimicrobial power of DBDD-PAW was demonstrated through a Tiron scavenger assay, and chemistry modeling confirmed that ·O2− generation readily occurs in DBDD-PAW generated with the employed settings. Modeling of the physical forces produced during plasma treatment showed that bacteria likely experience strong local electric fields and polarization. We hypothesize that these physical effects synergize with reactive chemical species to produce the acute antimicrobial activity seen with the in situ PAW system. IMPORTANCE Plasma-activated water (PAW) is an emerging sanitizer in the fresh food industry, where food safety must be achieved without a thermal kill step. Here, we demonstrate PAW generated in situ to be a competitive sanitizer technology, providing a significant reduction of pathogenic and spoilage microorganisms while maintaining the quality and shelf life of the produce item. Our experimental results are supported by modeling of the plasma chemistry and applied physical forces, which show that the system can generate highly reactive ·O2− and strong electric fields that combine to produce potent antimicrobial power. In situ PAW has promise in industrial applications as it requires only low power (12 W), tap water, and air. Moreover, it does not produce toxic by-products or hazardous effluent waste, making it a sustainable solution for fresh food safety.

The control of tick-borne haemoparasites in cattle largely relies on the use of acaricide drugs against the tick vectors, with some vaccination also being used against selected pathogens. These interventions can be difficult in Africa, where accessibility and cost of vaccines can be issues, and the increasing resistance of tick vectors to the widely used acaricides is a complication to disease control. A potential complementary control strategy could be the exploitation of any natural host genetic resistance to the pathogens. However, there are currently very few estimates of the extent of host resistance to tick-borne haemoparasites, and a significant contributing factor to this knowledge gap is likely to be the difficulty of collecting appropriate samples and data in the smallholder systems that predominate livestock production in low- and middle-income countries, particularly at scale. In this study, we have estimated the heritability for the presence/absence of several important haemoparasite species (including Anaplasma marginale, Babesia bigemina, Babesia bovis, and Ehrlichia ruminantium), as well as for relevant traits such as body weight and body condition score (BCS), in 1,694 cattle from four African countries (Burkina Faso, Ghana, Nigeria, and Tanzania). Heritability estimates within countries were mostly not significant, ranging from 0.05 to 0.84 across traits and countries, with standard errors between 0.07 and 0.91. However, the weighted mean of heritability estimates was moderate and significant for body weight and BCS (0.40 and 0.49, respectively), with significant heritabilities also observed for the presence of A. marginale (0.16) and E. ruminantium (0.19). In a meta-analysis of genome-wide association studies (GWAS) for these traits, two peaks were identified as reaching the suggestive significance threshold (p < 1.91 × 10−7 and p < 1.89 × 10−7, respectively): one on chromosome 24 for BCS and one on chromosome 8 for the E. ruminantium infection status. These findings indicate that there is likely to be a genetic basis that contributes to pathogen presence/absence for tick-borne haemoparasite species, which could potentially be exploited to improve cattle resistance in Africa to the economically important diseases caused by these pathogens.

Three geometric formulations of the Hamiltonian structure of the macroscopic Maxwell equations are given: one in terms of the double de Rham complex, one in terms of L2 duality, and one utilizing an abstract notion of duality. The final of these is used to express the geometric and Hamiltonian structure of kinetic theories in general media. The Poisson bracket so stated is explicitly metric free. Finally, as a special case, the Lorentz covariance of such kinetic theories is investigated. We obtain a Lorentz covariant kinetic theory coupled to nonlinear electrodynamics such as Born-Infeld or Euler-Heisenberg electrodynamics.

BackgroundThe accuracy of self-reported vaccination status is important to guide real-world vaccine effectiveness studies and policy making in jurisdictions where access to electronic vaccine registries is restricted. ObjectiveThis study aimed to determine the accuracy of self-reported vaccination status and reliability of the self-reported number of doses, brand, and time of vaccine administration. MethodsThis diagnostic accuracy study was completed by the Canadian COVID-19 Emergency Department Rapid Response Network. We enrolled consecutive patients presenting to 4 emergency departments (EDs) in Québec between March 24, 2020, and December 25, 2021. We included adult patients who were able to consent, could speak English or French, and had a proven COVID-19 infection. We compared the self-reported vaccination status of the patients with their vaccination status in the electronic Québec Vaccination Registry. Our primary outcome was the accuracy of the self-reported vaccination status (index test) ascertained during telephone follow-up compared with the Québec Vaccination Registry (reference standard). The accuracy was calculated by dividing all correctly self-reported vaccinated and unvaccinated participants by the sum of all correctly and incorrectly self-reported vaccinated and unvaccinated participants. We also reported interrater agreement with the reference standard as measured by unweighted Cohen κ for self-reported vaccination status at telephone follow-up and at the time of their index ED visit, number of vaccine doses, and brand. ResultsDuring the study period, we included 1361 participants. At the time of the follow-up interview, 932 participants reported at least 1 dose of a COVID-19 vaccine. The accuracy of the self-reported vaccination status was 96% (95% CI 95%-97%). Cohen κ for self-reported vaccination status at phone follow-up was 0.91 (95% CI 0.89-0.93) and 0.85 (95% CI 0.77-0.92) at the time of their index ED visit. Cohen κ was 0.89 (95% CI 0.87-0.91) for the number of doses, 0.80 (95% CI 0.75-0.84) for the brand of the first dose, 0.76 (95% CI 0.70-0.83) for the brand of the second dose, and 0.59 (95% CI 0.34-0.83) for the brand of the third dose. ConclusionsWe reported a high accuracy of self-reported vaccination status for adult patients without cognitive disorders who can express themselves in English or French. Researchers can use self-reported COVID-19 vaccination data on the number of doses received, vaccine brand name, and timing of vaccination to guide future research with patients who are capable of self-reporting their vaccination data. However, access to official electronic vaccine registries is still needed to determine the vaccination status in certain susceptible populations where self-reported vaccination data remain missing or impossible to obtain. Trial RegistrationClinicaltrials.gov NCT04702945; https://clinicaltrials.gov/ct2/show/NCT04702945

Thoracic endovascular aortic repair (TEVAR) has become the most common strategy for management of traumatic aortic injury. Surgical planning and execution may involve several imaging modalities, including CT, fluoroscopy, and intravascular ultrasound (IVUS). This article describes the technique and successful intraoperative application of transesophageal echocardiogram (TEE) in TEVAR as an adjunct imaging modality to guide stent placement and deployment and evaluate pre- and post-TEVAR flow within an aortic pseudoaneurysm. When coupled with conventional techniques, including IVUS and fluoroscopy, this tool can be an important tool in the vascular surgeon's armamentarium for evaluating intraoperative anatomic questions related to TEVAR with little additional risk, cost, or increased operating time.

Previously described techniques for portomesenteric venous wire access typically require specialized expertise, technical skills, and equipment. The aim of this paper is to describe Portal Endovascular Rendezvous Catheterization (PERC), a simpler approach to access the portal vein for large animal translational research purposes. Using Swine, this technique utilizes a hybrid approach with percutaneous access of the internal jugular vein and open transabdominal access of the portal vein. A through-and-through micropuncture of the portal vein into the inferior vena cava at the level of the hepatic parenchyma allows for the access wire to be snared and access sheath advanced into the portal venous system, which then allows for any indicated sampling or endovascular interventions in the portomesenteric venous circulation. PERC is more manageable than transjugular intrahepatic portosystemic shunt (TIPS) placement for portal venous access, and its use will allow a greater breadth of translational researchers to access the portal vein.

Introduction: Transcarotid artery revascularization (TCAR) with flow reversal has substantially changed the management of carotid artery stenosis, enabling an endovascular approach with a periprocedural stroke rate as low as or lower than that of open carotid surgery. The use of TCAR for blunt carotid artery injury has not yet been described. Methods: A review of the use of TCAR for blunt carotid artery injury was performed at a single center from October 2020 to August 2021. The patient demographics, mechanism of injury, and outcomes were collected and compared. Results: Ten carotid stents were placed via TCAR in eight patients for hemodynamically significant blunt carotid artery injuries. No periprocedural neurologic events occurred, and all stents remained patent during short-term follow-up. Conclusions: TCAR is feasible and safe in the management of significant blunt carotid artery injuries. More data are needed regarding the long-term outcomes and ideal surveillance intervals.

During cell division in Escherichia coli, the highly conserved tubulin homolog FtsZ polymerizes and assembles into a ring-like structure, called the Z-ring, at the site of septation. For recruitment to the membrane surface, FtsZ polymers directly interact with membrane-associated proteins, predominantly FtsA in E. coli. FtsA shares structural homology with actin and, like actin, hydrolyzes ATP. Yeast actin detects nucleotide occupancy through a sensor region adjacent to the nucleotide binding site and adopts distinct conformations in monomeric and filamentous actin. Bacterial actin homologs also display considerable conformational flexibility across different nucleotide-bound states and polymerize. Here, we show that several amino acid residues proximal to the nucleotide binding site in FtsA are critical for function in vitro and in vivo. Each of these residues are important for ATP hydrolysis, phospholipid (PL) binding, ATP-dependent vesicle remodeling, and recruitment to the divisome in vivo, to varying degrees. Notably, we observed that Ser 84 and Glu 14 are essential for ATP-dependent vesicle remodeling and magnesium-dependent membrane release of FtsA from vesicles in vitro, and these defects likely underlie the loss of function by FtsA(E14R) and FtsA(S84L) in vivo. Finally, we demonstrate that FtsA(A188V), which is associated with temperature-sensitive growth in vivo, is defective for rapid ATP hydrolysis and ATP-dependent remodeling of PL vesicles in vitro. Together, our results show that loss of nucleotide-dependent activities by FtsA, such as ATP hydrolysis, membrane binding and release, and, most importantly, ATP-dependent PL remodeling, lead to failed Z-ring assembly and division defects in cells.

BackgroundBiomarkers of oxidation-reduction (redox) homeostasis are commonly measured in human blood to assess whether certain stimuli (e.g., high-glucose ingestion or acute exercise) lead to a state of oxidative distress (detrimental to health) or oxidative eustress (beneficial to health). Emerging research indicates that redox responses are likely to be highly individualized, yet few studies report individual responses. Furthermore, the effects of complex redox stimuli (e.g., high-glucose-ingestion after exercise) on redox homeostasis remains unclear. We investigated the effect of acute exercise (oxidative eustress), high-glucose ingestion (oxidative distress), and high-glucose ingestion after exercise (both oxidative eu/distress), on commonly measured redox biomarkers in serum/plasma.MethodsIn a randomized crossover fashion, eight healthy men (age: 28 ± 4 years; BMI: 24.5 ± 1.5 kg/m2 [mean ± SD]) completed two separate testing conditions; 1) consumption of a high-glucose mixed-nutrient meal (45% carbohydrate [1.1 g glucose.kg-1], 20% protein, and 35% fat) at rest (control trial), and 2) consumption of the same meal 3 h and 24 h after 1 h of moderate-intensity cycling exercise (exercise trial). Plasma and serum were analyzed for an array of commonly studied redox biomarkers.ResultsOxidative stress and antioxidant defense markers (hydrogen peroxide, 8-isoprostanes, catalase, superoxide dismutase, and nitrate levels) increased immediately after exercise (p < 0.05), whereas nitric oxide activity and thiobarbituric acid reactive substances (TBARS) remained similar to baseline (p > 0.118). Nitric oxide activity and nitrate levels decreased at 3 h post-exercise compared to pre-exercise baseline levels. Depending on when the high-glucose mixed nutrient meal was ingested and the postprandial timepoint investigated, oxidative stress and antioxidant defense biomarkers either increased (hydrogen peroxide, TBARS, and superoxide dismutase), decreased (hydrogen peroxide, 8-isoprostanes, superoxide dismutase, nitric oxide activity, nitrate, and nitrite), or remained similar to pre-meal baseline levels (hydrogen peroxide, 8-isoprostanes, TBARS, catalase, superoxide dismutase and nitrite). Redox responses exhibited large inter-individual variability in the magnitude and/or direction of responses.ConclusionFindings highlight the necessity to interpret redox biomarkers in the context of the individual, biomarker measured, and stimuli observed. Individual redox responsiveness may be of physiological relevance and should be explored as a potential means to inform personalized redox intervention.

Future crop varieties must be higher yielding, stress resilient and climate agile to feed a larger population, and overcome the effects of climate change. This will only be achieved by a fusion of plant breeding with multiple “omic” sciences. Field-based, proximal phenomics assesses plant growth and responses to stress and agronomic treatments, in a given environment, over time and requires instruments capable of capturing data, quickly and reliably. We designed the PlotCam following the concepts of cost effective phenomics, being low-cost, light-weight (6.8 kg in total) and portable with rapid and repeatable data collection at high spatial resolution. The platform consisted of a telescoping, square carbon fiber unipod, which allowed for data collection from many heights. A folding arm held the sensor head at the nadir position over the plot, and an accelerometer in the arm ensured the sensor head was level at the time of data acquisition. A computer mounted on the unipod ran custom software for data collection. RGB images were taken with an 18 MP, WiFi controlled camera, infrared thermography data was captured with a 0.3 MP infrared camera, and canopy height measured with a 0.3 MP stereo depth camera. Incoming light and air temperature were logged with every image. New operators were quickly trained to gather reliable and repeatable data and an experienced operator could image up to 300 plots per hour. The PlotCam platform was not limited by field design or topography. Multiple identical PlotCams permitted the study of larger populations generating phenomic information useful in variety improvement. We present examples of data collected with the PlotCam over field soybean experiments to show the effectiveness of the platform.

Introduction: Targeted temperature management plays an important role in the treatment of myriad critical illnesses. Non-invasive, quick-onset options for isolated brain temperature control remain lacking. The goal of this study was to assess the safety and efficacy of a novel intranasal high flow cooled air device using a large animal model. Methods: Yorkshire swine were instrumented with temperature probes in the rectum, brain, ear, and snout, and a novel intranasal cooled air device was applied to half. The primary outcome was effectiveness of brain and snout cooling by the study device. Secondary outcomes included tympanic cooling and absence of rectal cooling, CT, CT perfusion, and histologic evidence of injury in the short- and medium-term. Results: 10 animals (54.7 kgs.+/- 19.4 SD) underwent non-survival evaluation, 3 underwent delayed evaluation (56.1 kgs.+/-6.4). From baseline to cooling period, intranasal (38.1 °C vs. 34.9 °C, p = 0.01), intracranial (38.6 °C vs. 37.2 °C, p = 0.01) and tympanic temperatures (38.3 °C vs. 37.5 °C, p = 0.01) decreased, while rectal temperature remained unchanged.After cooling, nasal temperature (34.9 °C vs. 37.6 °C, p = 0.004) and intracranial temperatures (37.2 °C vs. 37.9 °C, p = 0.01) increased. Rectal temperatures remained unchanged. A mixed effects model showed association between temperature and study period (p

Abstract Background Chronic pain conditions entail significant personal and societal burdens and improved outreach of evidence-based pain self-management programs are needed. Digital cognitive-behavioral self-management interventions have shown promise. However, evidence is still scarce and several challenges with such interventions for chronic pain exist. Exploring patients' experiences and engagement with digital interventions may be an essential step towards developing meaningful digital self-management interventions for those living with chronic pain. Objectives This study aimed to gain insight into the experiences of people with chronic pain when engaging with EPIO, an application (app)-based cognitive-behavioral pain self-management intervention program. Methods Participants (N = 50) living with chronic pain received access to the EPIO intervention in a feasibility pilot-study for 3 months. During this time, all participants received a follow-up phone call at 2–3 weeks, and a subsample (n = 15) also participated in individual semi-structured interviews after 3 months. A qualitative design was used and thematic analysis was employed aiming to capture participants’ experiences when engaging with the EPIO intervention program. Results Findings identifying program-related experiences and engagement were organized into three main topics, each with three sub-themes: (1) Engaging with EPIO; motivation to learn, fostering joy and enthusiasm, and helpful reminders and personalization, (2) Coping with pain in everyday life; awareness, practice and using EPIO in everyday life, and (3) The value of engaging with the EPIO program; EPIO – a friend, making peace with the presence of pain, and fostering communication and social support. Conclusions This qualitative study explored participants’ experiences and engagement with EPIO, a digital self-management intervention program for people living with chronic pain. Findings identified valued aspects related to motivation for engagement, and showed how such a program may be incorporated into daily life, and encourage a sense of acceptance, social support and relatedness. The findings highlight vital components for facilitating digital program engagement and use in support of self-management for people living with chronic pain. Trial registration ClinicalTrials.gov NCT03705104 .

Cattle reference genomes are valuable resources but are currently heavily biased towards European breeds. Here the authors integrate assemblies for African breeds into a more representative cattle graph genome capturing global breed diversity.

Temporary intravascular shunts are used to maintain perfusion in injured vessels, although failure can be unpredictable and lead to significant morbidity. The aim of the present study was to develop a dose- and timing-controlled swine model of intrinsic shunt failure to facilitate the development of a warning system for impending failure. Ten Yorkshire swine (weight, 56.6 ± 4.2 kg) underwent bilateral Argyle shunt (Cardinal Health, Dublin, OH) placement in the external iliac arteries, with proximal cannulation of the circumflex iliac arteries for infusion of thrombin. The thrombin infusion was randomized to the left or right side for 5000 vs 10,000 U/h. The 5000-U/h group required 2.1 times as long as the 10,000-U/h group to reach failure (mean, 21.8 minutes vs 46.4 minutes; P < .0001), as shown by a Kaplan-Meier survival analysis (log-rank P < .0001). However, the 5000-U/h group required the same total amount of thrombin (mean, 3752 ± 856 U; P = .57). Thus, time- and/or thrombin dose-controlled induction of shunt failure is technically feasible. Furthermore, in the final 15 minutes before failure, the flow was similar between the two groups (P > .05), and the slope of the flow curve became more negative the closer the model was to failure. Overall, this model could be used to develop an alert system to predict for impending shunt failure or the need for intervention.

Abstract Objective A group of genes have been reported to be associated with myopathies with tubular aggregates (TAs). Many cases with TAs still lack of genetic clarification. This study aims to explore the genetic background of cases with TAs in order to improve our knowledge of the pathogenesis of these rare pathological structures. Methods Thirty‐three patients including two family members with biopsy confirmed TAs were collected. Whole‐exome sequencing was performed on 31 unrelated index patients and a candidate gene search strategy was conducted. The identified variants were confirmed by Sanger sequencing. The wild‐type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. Results Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. Among them, the c.764A>T (p.Glu255Val) in STIM1 and the c.1333G>C (p.Val445Leu) in SCN4A were novel. Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. The ALG14 variants might be associated with TAs in patients with complex multisystem disorders. Interpretation This study expands the phenotypic and genotypic spectrums of myopathies with TAs. Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N‐linked glycosylation pathway are the main genetic causes of myopathies with TAs.