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Background context : Low back pain is a major cause of morbidity and disability worldwide and is responsible for vast societal impact. Rates of surgical intervention for lumbar spine disorders continue to rise but poor outcomes remain common. Understanding how the social determinants of health (SDH) influence spinal surgical outcomes stands to inform appropriately tailored care practices and lead to better patient outcomes. Purpose : To determine the relationships between the SDH and pain, opioid use, disability and work absenteeism following lumbar spine surgery. Study design : Systematic review and narrative synthesis. Methods : We searched Embase, the Cochrane Library, Medline, and Web of Science from inception to 21/4/2020. Studies eligible for inclusion involved participants receiving lumbar spine surgery and investigated the relationship between at least one SDH and post-surgical pain, opioid use, disability or work absenteeism. We evaluated the risk of bias of included studies and used the PROGRESS-Plus framework to organise a narrative synthesis of findings. Results : Relevant data was extracted from twenty-three studies involving 30,987 adults from 12 countries. 107 relationships between the SDH and post-surgical outcomes were evaluated, 67 in multivariate analyses. Education was investigated in 23 analyses (14 studies): 70% revealed significant independent relationships between lower education and poorer outcomes. Socioeconomic status was investigated in nine analyses (four studies): 67% revealed independent relationships between lower socioeconomic status and poorer outcomes. Gender was investigated in 40 analyses (22 studies): indications that male versus female sex was associated with poorer outcomes were equivocal. Place of residence, race/ethnicity, and social capital were infrequently investigated. Conclusions : Low educational attainment and low income status are clear independent contributors to poorer outcomes following lumbar spine surgery. Occupational factors and work context are likely to be influential. Further research is critical to guide best-practice spinal surgery through a health equity lens. Study registration : PROSPERO registration number CRD42015015778

Purpose Infected orthopaedic metalwork is challenging to treat. Negative pressure wound therapy (NPWT) with irrigation is an emerging therapy for infected wounds as an adjunct to antibiotic therapy. The senior author had devised a modified technique to augment its efficacy, utilising high-flow rate irrigation and skin closure over the standard NPWT dressing. This novel technique was originally evaluated in a different centre and produced 100% success in metalwork retention. The present study is a reproducibility test of the same technique. Methods A retrospective review was performed on 24 patients with infected orthopaedic metalwork, including 3 upper limb and 21 lower limb cases, for outcomes relating to implant retention and infection resolution. Patients underwent a modified NPWT technique as an adjunct to antibiotic therapy and surgical debridement. Detailed medical and microbiology information were obtained from the patient records. Results 23 of 24 (96%) patients had successful metalwork retainment with healed wounds and resolution of infection, allowing fracture union. 27 infective organisms were identified in this cohort, and the antibiotic regimens for each patient are provided. The average follow-up was 663 days. No adverse effects were observed. Conclusion This series supports the modified NPWT technique as a safe, reliable and effective adjunct therapy to resolve metalwork infection. The same results have been reproduced as the previous cohort in a different centre.

This paper reports perceptions of over 1,000 accounting faculty regarding 12 accounting journals, specifically in how open they are to: (1) diverse topic areas, (2) diverse research methodologies, how effectively they produce new and useful knowledge for (3) non-academic stakeholders, and (4) academics. We find that the traditional Top 6 journals do not lead the academy along these four dimensions; in fact, some are viewed as the worst performers in these areas. Furthermore, we find that academics have a relatively poor understanding of the actual diversity of several journals. We also report how the academy perceives each journal's current value and how each journal should be valued when evaluating faculty on research productivity. We find that respondents believe the traditional Top 6 journals are and should continue to be weighted highly in faculty evaluation, but that the other journals should receive greater weighting.

OBJECTIVE To synthesize and critically appraise literature exploring patient perceptions regarding the therapeutic use of noninvasive brain stimulation. MATERIAL AND METHODS A systematic search of CINHAL, PUBMED, Web of Science, and Medline was performed. Reference lists of relevant articles were also screened. Studies exploring participant perceptions regarding the therapeutic use of noninvasive brain stimulation were eligible for inclusion. Perceptions were divided into three domains: knowledge, experience, and attitudes. Noninvasive brain stimulation was defined as any neuromodulation technique that alters brain activity but does not require invasive methods such as surgery. No restrictions were placed upon study design or participant population. Two reviewers performed data extraction and risk of bias assessment. Data relating to methodological characteristics, participant demographics, type of noninvasive brain stimulation, and nature of perceptions (knowledge, experience, or attitudes) were extracted. RESULTS Four studies comprising data from 163 participants met the inclusion criteria. All studies investigated perceptions of repetitive transcranial magnetic stimulation (rTMS) in psychiatric populations. Most participants perceived rTMS to be safe and beneficial, demonstrated low-levels of fear, and were willing to recommend the intervention to others. No studies were found investigating patient perception of transcranial direct current stimulation (tDCS). CONCLUSION The findings from this review suggest that rTMS is well accepted as a therapeutic treatment among psychiatric populations, providing support for its clinical utility. Future work is needed to determine if similar findings exist for other conditions (e.g., chronic pain) and for other therapeutic forms of brain stimulation (e.g., tDCS).

Background: Calibrated CT fat fraction (FFCT) measurements derived from non-enhanced abdominal CT reliably reflect liver fat content, allowing largescale population-level investigations of steatosis prevalence and associations. Objective: To compare prevalence of hepatic steatosis, assessed by calibrated CT measurements, between population-based Chinese and U.S. cohorts, and to investigate in these populations the relationship of steatosis with age, sex, and body mass index (BMI). Methods: This retrospective study included 3176 adults (1985 women, 1191 men) from seven Chinese provinces and 8748 adults (4834 women, 3914 men) from a single U.S. medical center, drawn from earlier studies. All participants were at least 40 years old and underwent unenhanced abdominal CT for the earlier studies. Liver fat content measurements on CT were cross-calibrated to MRI proton density fat fraction measurements using phantoms and expressed as adjusted FFCT. Mild, moderate, and severe steatosis were defined as adjusted FFCT of 5.0%-14.9%, 15.0%-24.9%, and ≥25.0%, respectively. The two cohorts were compared. Results: Median adjusted FFCT was for women 4.7% and 4.8%, and for men 5.8% and 6.2%, in the Chinese and U.S. cohorts, respectively. Steatosis prevalence was for women 46.3% and 48.7%, and for men 58.9% and 61.9%, in the Chinese and U.S. cohorts, respectively. Severe steatosis prevalence was for women 0.9% and 1.8%, and for men, 0.2% and 2.6%, in the Chinese and U.S. cohorts, respectively. Adjusted FFCT did not vary across age decades in women or men in the Chinese cohort, though increased across age decades in women and men in the U.S. cohort. Adjusted FFCT and BMI exhibited weak correlation (r=0.312-0.431). Among participants with normal BMI, 36.8% and 38.5% of those in the Chinese and U.S. cohorts had mild steatosis, and 3.0% and 1.5% had moderate or severe steatosis, respectively. Among U.S. participants with BMI ≥40.0, 17.7% had normal liver content. Conclusion: Steatosis and severe steatosis had higher prevalence in the U.S. than Chinese cohort in both women and men. BMI did not reliably predict steatosis. Clinical Impact: The findings provide new information on the dependence of hepatic steatosis on age, sex, and BMI.

Background Disability is common following critical illness, impacting the quality of life of survivors, and is difficult to measure. ‘Participation’ can be quantified as involvement in life outside of their home requiring movement from their home to other locations. Participation restriction is a key element of disability, and following critical illness, participation may be diminished. It may be possible to quantify this change using pre-existing smartphone data. Objectives The feasibility of extracting location data from smartphones of survivors of intensive care unit (ICU) admission and assessing participation, using location-based outcomes, during recovery from critical illness was evaluated. Methods Fifty consecutively admitted, consenting adult survivors of non-elective admission to ICU of greater than 48-h duration were recruited to a prospective observational cohort study where they were followed up at 3 and 6 months following discharge. The feasibility of extracting location data from survivors' smartphones and creating location-derived outcomes assessing participation was investigated over three 28-d study periods: pre-ICU admission and at 3 and 6 months following discharge. The following were calculated: time spent at home; the number of destinations visited; linear distance travelled; and two ‘activity spaces’, a minimum convex polygon and standard deviation ellipse. Results Results are median [interquartile range] or n (%). The number of successful extractions was 9/50 (18%), 12/39 (31%), and 13/33 (39%); the percentage of time spent at home was 61 [56–68]%, 77 [66–87]%, and 67 [58–77]% (P = 0.16); the number of destinations visited was 34 [18–64], 38 [22–63], and 65 [46–88] (P = 0.02); linear distance travelled was 367 [56–788], 251 [114–323], and 747 [326–933] km over 28 d (P = 0.02), pre-ICU admission and at 3 and 6 months following ICU discharge, respectively. Activity spaces were successfully created. Conclusion Limited smartphone ownership, missing data, and time-consuming data extraction limit current implementation of mass extraction of location data from patients’ smartphones to aid prognostication or measure outcomes. The number of journeys taken and the linear distance travelled increased between 3 and 6 months, suggesting participation may improve over time.

In terms of natural hazard events, resilience characterizations provide a means of identifying risk profiles, degrees of preparedness, and the ability of communities to respond and recover. While nationally consistent measures of community resilience to natural hazards are needed to address widespread socio-ecological impacts from a broad policy perspective, geographically specific resilience characterizations are needed to target local resources to increase community resilience. The Climate Resilience index (CRSI) was developed to characterize the resilience of socio-ecological systems in the context of governance and risk to natural hazard events for all U.S. counties for the years 2000–2015. Those resilience characterizations were based on the full range of nationwide county domain scores. This paper presents a re-scaled application of CRSI, where county domain scores are limited to the range of scores within a specific set of U.S. coastal and shoreline counties within each of eight coastal regions. The re-scaled CRSI values for selected counties/parishes in the Gulf of Mexico (GOM) region are also presented in conjunction with calculated Location Quotients (LQ) values >1.0, which represent a high employment dependence on ocean economy sectors. Using a combination of re-scaled CRSI and LQ values provides a more holistic picture of vulnerability and resilience in these U.S. coastal shoreline counties. The relative resilience assessments presented for coastal regions are useful in identifying potential strengths and weaknesses in resilience aspects given similar hazard profiles, a signature otherwise diluted in nation-wide county-level assessments. The unique approach of combining CRSI and LQ for characterizing natural hazard resilience described could be transferred to other specific geographies as defined by population groups, hazard profiles and economic dependence.

Background Encapsulating Peritoneal Sclerosis (EPS) is a rare phenomenon in paediatric patients with kidney failure treated with peritoneal dialysis (PD). This study highlights clinical challenges in the management of EPS, with particular emphasis on peri-operative considerations and surgical technique. Methods Retrospective analysis of all paediatric patients with EPS treated at the Manchester Centre for Transplantation. Results Four patients were included with a median duration of 78 months on PD. All patients had recurrent peritonitis (> 3 episodes), and all had symptoms within three months of a change of dialysis modality from PD to haemodialysis or transplant. In Manchester, care was delivered by a multi-disciplinary team, including surgeons delivering the adult EPS surgical service with a particular focus on nutritional optimisation, sepsis control, and wound management. The surgery involved laparotomy, lavage, and enterolysis of the small bowel + / − stoma formation, depending on intra-abdominal contamination. Two patients had a formal stoma, which were reversed at three and six months, respectively. Two patients underwent primary closure of the abdomen, whereas two patients had re-look procedures at 48 h with secondary closure. One patient had a post-operative wound infection, which was managed medically. One patient’s stoma became detached, leading to an intra-abdominal collection requiring re-laparotomy. The median length of stay was 25 days, and patients were discharged once enteral feeding was established. All patients remained free of recurrence with normal gut function and currently two out of four have functioning transplants. Conclusions This series demonstrates 100% survival and parenteral feed independence following EPS surgery. Post-operative morbidity was common; however, with individualised experience-based decision-making and relevant additional interventions, patients made full recoveries. Health and development post-surgery continued, allowing the potential for transplantation. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

In the context of workplace safety, activated carbon in the fiber form (i.e., activated carbon fiber, ACF) represents an alternative adsorbent to granular activated carbon (GAC) for use in organic vapor respiratory protection devices. ACFs are high surface area carbonaceous materials that are often available in a self-supporting non-woven form. The physical form of ACF suggests the potential for a filtration medium that is capable of supporting both organic vapor adsorption and particulate filtration.To study the application of these materials in respiratory protection devices, ACFs (ACFF 1200 m2/g, ACFF 1800 m2/g, and ACFF 2000 m2/g) were challenged with representative organic vapors (toluene, hexane, and methyl ethyl ketone (MEK)) at an occupationally relevant concentration (200 ppm). Breakthrough curves were generated for at least three different bed weights of adsorbent. Pressure drop (i.e., the resistance across the filtration media) was also measured to determine maximum ACF bed depths for use in respiratory protection devices.Breakthrough experiments indicate that ACFF 2000 has the highest adsorption capacity for toluene (381 mg/g), followed by ACFF 1800 and ACFF 1200 (344 mg/g and 239 mg/g, respectively). A similar trend was observed for hexane: 221 mg/g, 196 mg/g, and 146 mg/g for ACFF 2000, ACFF 1800, and ACFF 1200, respectively. ACFF 1200 showed the highest adsorption capacity for the polar adsorbate MEK (168 mg/g), followed by ACFF 1800 and ACFF 2000 (166 mg/g and 147 mg/g, respectively). Based on the constraints of pressure drop, it seems unlikely the exclusive use of ACF in a filtering facepiece respirator can provide an adsorbent mass sufficient for full shift protection against organic vapor contaminants at or above the legally enforceable permissible exposure level (PEL). Nevertheless, the incorporation of ACF into a facepiece respirator appears promising for "nuisance odor" applications; i.e., the further reduction of organic vapor concentrations when workplace exposures are already below PEL concentrations. Implication StatementThis research brings innovation to the field of occupational health and air pollution control technology by investigating the adsorption performance of activated carbon fiber (ACF) media in the context of worker respiratory protection. ACF properties such as high specific surface area (m2/g), high permeability to airflow, and rapid adsorption kinetics make it ideal for use in thin, N95-style respirators for organic vapors. Respiratory protection is an exciting and relevant application for ACF media. A lightweight adsorbent such as ACF, if incorporated into an N95-style respirator, could potentially provide nuisance-level VOC protection in a physical form that is accessible to workers and consistent with OSHA's voluntary use provisions for facepiece respirators. The research presented in this manuscript represents one of several steps planned in the characterization of ACF media for this particular application.

Almost 1 in 10 individuals can suffer from one of many rare diseases (RDs). The average time to diagnosis for an RD patient is as high as 7 years. Artificial intelligence (AI)-based positron emission tomography (PET), if implemented appropriately, has tremendous potential to advance the diagnosis of RDs. Patient advocacy groups must be active stakeholders in the AI ecosystem if we are to avoid potential issues related to the implementation of AI into health care. AI medical devices must not only be RD-aware at each stage of their conceptualization and life cycle but also should be trained on diverse and augmented datasets representative of the end-user population including RDs. Inability to do so leads to potential harm and unsustainable deployment of AI-based medical devices (AIMDs) into clinical practice.

Background Transcranial focused ultrasound (tFUS) is a noninvasive brain stimulation method that may modulate deep brain structures. This study investigates whether sonication of the right anterior thalamus would modulate thermal pain thresholds in healthy individuals. Methods We enrolled 19 healthy individuals in this three-visit, double-blind, sham-controlled, crossover trial. Participants first underwent a structural MRI scan used solely for tFUS targeting. They then attended two identical experimental tFUS visits (counterbalanced by condition) at least one week apart. Within the MRI scanner, participants received two, 10-min sessions of either active or sham tFUS spread 10 min apart targeting the right anterior thalamus [fundamental frequency: 650 kHz, Pulse repetition frequency: 10 Hz, Pulse Width: 5 ms, Duty Cycle: 5%, Sonication Duration: 30s, Inter-Sonication Interval: 30 s, Number of Sonications: 10, ISPTA.0 995 mW/cm2, ISPTA.3 719 mW/cm2, Peak rarefactional pressure 0.72 MPa]. The primary outcome measure was quantitative sensory thresholding (QST), measuring sensory, pain, and tolerance thresholds to a thermal stimulus applied to the left forearm before and after right anterior thalamic tFUS. Results The right anterior thalamus was accurately sonicated in 17 of the 19 subjects. Thermal pain sensitivity was significantly attenuated after active tFUS. The pre-post x active-sham interaction was significant (F(1,245.95) = 4.03, p = .046). This interaction indicates that in the sham stimulation condition, thermal pain thresholds decreased 1.08 °C (SE = 0.28) pre-post session, but only decreased .51 °C (SE = 0.30) pre-post session in the active stimulation group. Conclusions Two 10-min sessions of anterior thalamic tFUS induces antinociceptive effects in healthy individuals. Future studies should optimize the parameter space, dose and duration of this effect which may lead to multi-session tFUS interventions for pain disorders.

Malignant lymphomas are a family of heterogenous disorders caused by clonal proliferation of lymphocytes. 18F-FDG-PET has proven to provide essential information for accurate quantification of disease burden, treatment response evaluation, and prognostication. However, manual delineation of hypermetabolic lesions is often a time-consuming and impractical task. Applications of artificial intelligence (AI) may provide solutions to overcome this challenge. Beyond segmentation and detection of lesions, AI could enhance tumor characterization and heterogeneity quantification, as well as treatment response prediction and recurrence risk stratification. In this scoping review, we have systematically mapped and discussed the current applications of AI (such as detection, classification, segmentation as well as the prediction and prognostication) in lymphoma PET.

BACKGROUND. Sarcopenia is associated with adverse clinical outcomes. CT-based skeletal muscle measurements for sarcopenia assessment are most commonly performed at the L3 vertebral level. OBJECTIVE. The purpose of this article is to compare the utility of fully automated deep learning CT-based muscle quantitation at the L1 versus L3 level for predicting future hip fractures and death. METHODS. This retrospective study included 9223 asymptomatic adults (mean age, 57 ± 8 [SD] years; 4071 men, 5152 women) who underwent unenhanced low-dose abdominal CT. A previously validated fully automated deep learning tool was used to assess muscle for myosteatosis (by mean attenuation) and myopenia (by cross-sectional area) at the L1 and L3 levels. Performance for predicting hip fractures and death was compared between L1 and L3 measures. Performance for predicting hip fractures and death was also evaluated using the established clinical risk scores from the fracture risk assessment tool (FRAX) and Framingham risk score (FRS), respectively. RESULTS. Median clinical follow-up interval after CT was 8.8 years (interquartile range, 5.1–11.6 years), yielding hip fractures and death in 219 (2.4%) and 549 (6.0%) patients, respectively. L1-level and L3-level muscle attenuation measurements were not different in 2-, 5-, or 10-year AUC for hip fracture (p = .18–.98) or death (p = .19–.95). For hip fracture, 5-year AUCs for L1-level muscle attenuation, L3-level muscle attenuation, and FRAX score were 0.717, 0.709, and 0.708, respectively. For death, 5-year AUCs for L1-level muscle attenuation, L3-level muscle attenuation, and FRS were 0.737, 0.721, and 0.688, respectively. Lowest quartile hazard ratios (HRs) for hip fracture were 2.20 (L1 attenuation), 2.45 (L3 attenuation), and 2.53 (FRAX score), and for death were 3.25 (L1 attenuation), 3.58 (L3 attenuation), and 2.82 (FRS). CT-based muscle cross-sectional area measurements at L1 and L3 were less predictive for hip fracture and death (5-year AUC ≤ 0.571; HR ≤ 1.56). CONCLUSION. Automated CT-based measurements of muscle attenuation for myosteatosis at the L1 level compare favorably with previously established L3-level measurements and clinical risk scores for predicting hip fracture and death. Assessment for myopenia was less predictive of outcomes at both levels. CLINICAL IMPACT. Alternative use of the L1 rather than L3 level for CT-based muscle measurements allows sarcopenia assessment using both chest and abdominal CT scans, greatly increasing the potential yield of opportunistic CT screening.

Trust in artificial intelligence (AI) by society and the development of trustworthy AI systems and ecosystems are critical for the progress and implementation of AI technology in medicine. With the growing use of AI in a variety of medical and imaging applications, it is more vital than ever to make these systems dependable and trustworthy. Fourteen core principles are considered in this article aiming to move the needle more closely to systems that are accurate, resilient, fair, explainable, safe, and transparent: toward trustworthy AI.

This review discusses the current state of artificial intelligence (AI) in 18F-NaF-PET/CT imaging and the potential applications to come in diagnosis, prognostication, and improvement of care in patients with bone diseases, with emphasis on the role of AI algorithms in CT bone segmentation, relying on their prevalence in medical imaging and utility in the extraction of spatial information in combined PET/CT studies.

Biological sources of carbon sequestration such as revegetation have been highlighted as important avenues to combat climate change and meet global targets by the global community including the Paris Climate Agreement. However, current and projected carbon prices present a considerable barrier to broad‐scale adoption of tree planting as a key mitigation strategy. One avenue to provide additional economic and environmental incentives to encourage wider adoption of revegetation is the bundling or stacking of additional co‐beneficial ecosystem services that can be realized from tree planting. Using the World's largest land‐based carbon credit trading scheme, the Australian Emissions Reduction Scheme (ERF), we examine the potential for three pairs of ecosystem services, where the carbon sequestration value of land use change is paired with an additional co‐benefit with strong prospects for local tangible benefits to land owners/providers. Two cases consider agricultural provisioning values that can be realized by the landowners in higher returns: increased pollination services and reduced lamb mortality. The third case examined payments for tree plantings along riparian buffers, with payments to farmers by a water utility who realizes the benefit from reduced treatment cost due to water quality improvements. Economic incentives from these co‐benefit case studies were found to be mixed, with avoided treatment costs from water quality paired with carbon payments the most promising, while pollination and reduced lamb mortality paired with carbon payments were unable to bridge the economic gap except under the most optimistic assumptions. We conclude that the economics case for significant land use change are likely to be geographically dispersed and only viable in relatively niche landscape positions in high establishment, high opportunity cost areas even when carbon payments are augmented with the value of co‐benefits classified as providing direct and local benefits. Refereed/Peer-reviewed

Objectives: Hamstring injuries in athletes can lead to significant time away from competition as a result of persistent posterior thigh pain. These cases are often difficult to treat as the state of the tissues alone cannot explain symptoms. In non-athletic populations with persistent pain, disruptions to tactile, proprioceptive, and spatial cortical representations exist, which has led to promising brain-based treatments.Here, we explored whether athletes with persistent posterior thigh pain also display impairments in these cortical representations.Design: Cross-sectional study.Methods: Fourteen male professional athletes with persistent posterior thigh pain (‘Patients’) and 14pain-free age, sport, body mass index and level-matched controls (‘Controls’) participated. The tactile cortical representation was assessed using two-point discrimination (TPD) threshold and accuracy of tactile localisation; the proprioceptive cortical representation was assessed using a left/right judgement task; spatial processing was assessed using an auditory detection task. Results: TPD thresholds were similar for Patients and Controls (p = 0.70). Patients were less accurate at localising tactile stimuli delivered to their affected leg, slower to make left/right judgements when the lower limb image corresponded to the side of their affected leg, and less accurate at detecting auditory stimuli delivered near their affected leg, when compared to their healthy leg or to the leg of Controls(p < 0.01 for all). Conclusions: Leg-specific tactile, proprioceptive, and spatial processing deficits exist in athletes with persistent posterior thigh pain. That these processing deficits exist despite rehabilitation and normal tissue healing time suggests they may play a role in the persistence of posterior thigh pain. Refereed/Peer-reviewed

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

How did Britons view China in 2020, at the height of the Covid-19 pandemic? This paper presents new, detailed evidence of the negative and worsening perceptions of China in the UK across three domains: public opinion (based on survey data collected in autumn 2020), political elites in parliament, and the media. The worsening of perceptions of China emerged in the context of a changing and more contested China policy from the UK government and a greater level of public debate about China, partly a consequence of the onset of the Covid-19 pandemic. The paper places analysis of these perceptions in the context of the development of relations between the UK and China. Together with deteriorating Chinese views of the UK's China policy and controversy over a number of developments in China, widespread negative views about China among the British public and in political circles will constrain UK-China relations from developing in a more positive direction.

Ectopic lipids play a key role in numerous pathologies, including heart disease, stroke, and diabetes. Of all the lipids studied, perhaps the most well understood is cholesterol, a widely used clinical biomarker of cardiovascular disease and a target of pharmacological interventions (e.g., statins). Thousands of studies have interrogated the regulation and action of this disease-causing sterol. As a growing body of literature indicates, a new class of lipid-based therapies may be on the horizon. Ceramides are cholesterol-independent biomarkers of heart disease and diabetes in humans. Studies in rodents suggest that they are causative agents of disease, as lowering ceramides through genetic or pharmacological interventions prevents cardiovascular disease and diabetes. Herein, we discuss the evidence supporting the potential of therapeutics targeting ceramides to treat cardiometabolic disease, contrasting it with the robust datasets that drove the creation of cholesterol-lowering pharmaceuticals.

BACKGROUND: While genome-wide association studies (GWAS) have identified germline variants influencing the risk of developing colorectal cancer (CRC), there has been limited examination of the possible role of inherited variation as a determinant of patient outcome. PATIENTS AND METHODS: We performed a GWAS for overall survival (OS) in 1926 patients with advanced CRC from the COIN and COIN-B clinical trials. For single nucleotide polymorphisms (SNPs) showing an association with OS (P < 1.0 × 10(−5)), we conducted sensitivity analyses based on the time from diagnosis to death and sought independent replications in 5675 patients from the Study of Colorectal Cancer in Scotland (SOCCS) and 16,964 patients from the International Survival Analysis in Colorectal cancer Consortium (ISACC). We analysed the Human Protein Atlas to determine if ERBB4 expression was associated with survival in 438 patients with colon adenocarcinomas. RESULTS: The most significant SNP associated with OS was rs79612564 in ERBB4 (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 1.16–1.32, P = 1.9 × 10(−7)). SNPs at 17 loci had suggestive associations for OS and all had similar effects on the time from diagnosis to death. No lead SNPs were independently replicated in the meta-analysis of all patients from SOCCS and ISACC. However, rs79612564 was significant in stage-IV patients from SOCCS (P = 2.1 × 10(−2)) but not ISACC (P = 0.89) and SOCCS combined with COIN and COIN-B attained genome-wide significance (P = 1.7 × 10(−8)). Patients with high ERBB4 expression in their colon adenocarcinomas had worse survival (HR = 1.50, 95% CI = 1.1–1.9, P = 4.6 × 10(−2)). CONCLUSIONS: Genetic and expression data support a potential role for rs79612564 in the receptor tyrosine kinase ERBB4 as a predictive biomarker of survival.

Purpose : To investigate the use of apparent diffusion coefficient (ADC) values and other MRI features for the prediction of positive surgical margins (PSMs) in patients undergoing radical prostatectomy. Materials and methods : 400 consecutive patients who underwent surgery for prostate cancer between January 2015 and June 2016 were retrospectively identified. ADC values of the index lesion and other preoperative MRI features, including tumor site, laterality and level, Prostate Imaging Reporting and Data System (PI-RADS) category, European Society of Urogenital Radiology (ESUR) extra-capsular extension score (ECE score) and prostate volume, were assessed. Univariate and multivariable logistic regression were performed. Performance in predicting the occurrence of PSMs was measured using the area under the curve (AUC), and AUC differences were evaluated with the DeLong method. The Youden index was calculated to identify the ADC threshold to best discriminate patients with PSMs. Results : A total of 105 out of the 400 patients (26.2%) had PSMs after radical prostatectomy. ADC values, PI-RADS category, ECE score, tumor site and laterality were significantly associated with PSMs (p Conclusions : ADC values and preoperative MRI features can help estimate the risk of PSMs after radical prostatectomy. Micro Abstract : We retrospectively analysed 400 consecutive patients who underwent surgery for prostate cancer to investigate the use of apparent diffusion coefficient (ADC) values and other MRI features for the prediction of positive surgical margins (PSMs). ADC values, PI-RADS category, extra-capsular extension score, site, and laterality were significantly associated with PSMs; ADC performed well in PSM prediction, both in the univariate or multivariable analyses, with lower ADC values being present in patients with PSMs.

X-ray photoelectron spectroscopy (XPS) confirmed that RF magnetron sputtering of h-BN onto unheated substrates produced a-BOxNy films under all of the sputtering conditions studied. The surface roughness improved and pinholes were eliminated as the deposition pressure increased. Analysis of the current density dependence on the electric field of the a-BOxNy films suggests field-enhanced Schottky emission and/or Frenkel-Poole emission transport mechanisms. The highest breakdown strength obtained was 8 MV cm−1. A bandgap of 3.9 eV was confirmed by spectroscopic ellipsometry and UV–Vis spectroscopy. An interface trap concentration (Nit) of 7.3 × 1010 cm−2 and interface state density (Nss) of 7.5 × 1012 eV−1 cm−2 were measured for transparent ITO/a-BOxNy/ZnO metal–insulator-semiconductor (MIS) structures. Approximately, 2 V was required to switch the a-BOxNy/ZnO interface from accumulation to inversion.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool commonly used to drive neural plasticity in the young adult and aged brain. Recent data from mouse models have shown that even at subthreshold intensities (0.12 Tesla), rTMS can drive neuronal and glial plasticity in the motor cortex. However, the physiological mechanisms underlying subthreshold rTMS induced plasticity and whether these are altered with normal ageing are unclear.ObjectiveTo assess the effect of subthreshold rTMS, using the intermittent theta burst stimulation (iTBS) protocol on structural synaptic plasticity in the mouse motor cortex of young and aged mice.MethodsLongitudinal in vivo 2-photon microscopy was used to measure changes to the structural plasticity of pyramidal neuron dendritic spines in the motor cortex following a single train of subthreshold rTMS (in young adult and aged animals) or the same rTMS train administered on 4 consecutive days (in young adult animals only). Data were analysed with Bayesian hierarchical generalized linear regression models and interpreted with the aid of Bayes Factors (BF).ResultsWe found strong evidence (BF>10) that subthreshold rTMS altered the rate of dendritic spine losses and gains, dependent on the number of stimulation sessions and that a single session of subthreshold rTMS was effective in driving structural synaptic plasticity in both young adult and aged mice.ConclusionThese findings provide further evidence that rTMS drives synaptic plasticity in the brain and uncovers structural synaptic plasticity as a key mechanism of subthreshold rTMS induced plasticity.

Cleaning chemistries are detergent-based formulations that are used during the processing of reusable medical devices. Manufacturers are responsible for demonstrating the safety of cleaning formulations when they are used during a device processing cycle, including the risk of device-associated cytotoxicity over the concentration ranges for recommended use and rinsing during cleaning. However, no regulation currently exists requiring manufacturers to demonstrate such safety. Although manufacturers' safety data sheets (SDSs) provide information on the safe use of chemicals for users, this information may not provide sufficient detail to determine the risks of residual chemicals on device surfaces. SDSs are not required to contain a comprehensive list of chemicals used, only those of risk to the user. They should be supplemented with information on the correct concentrations that should be used for cleaning, as well as instructions on the rinsing required to reduce the levels of chemicals to safe (nontoxic) levels prior to further processing. Supporting data, such as toxicity profiles or cytotoxicity data that support the instructions for use, would provide medical device manufacturers and healthcare personnel with the necessary information to make informed decisions about selection and correct use of detergents. In the current work, cytotoxicity profiles for eight commonly used cleaning formulations available internationally were studied. Although all of these products are indicated for use in the cleaning of reusable medical devices, results vary across the serial dilution curves and are not consistent among detergent types. The information presented here can be leveraged by both medical device manufacturers and processing department personnel to properly assess residual detergent risks during processing. This work also serves as a call to cleaning formulation manufacturers to provide this information for all chemistries.

Background Although the harm to health from electronic nicotine delivery systems (ENDS) compared to smoked tobacco remains highly uncertain, society and governments still need to know the likely range of the relative harm to inform regulatory policies for ENDS and smoking. Methods We identified biomarkers with specificity of association with different disease groupings e.g., volatile organic compound (VOCs) for chronic obstructive pulmonary disease; and tobacco-specific N´-nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) for all cancers. We conducted a review of recent studies (post January 2017) that compared these biomarkers between people exclusively using ENDS and those exclusively smoking tobacco. The percentage differences in these biomarkers, weighted by study size and adjusted for acrolein from other sources, were used as a proxy for the assumed percentage difference in disease harm between ENDS and smoking. These relative differences were applied to previously modelled estimates of smoking-related health loss (in health-adjusted life-years; HALYs). Results The respective relative biomarker levels (ENDS vs smoking) were: 28% for respiratory diseases (five results, three studies); 42% for cancers (five results, four studies); and 35% for cardiovascular (seven results, four studies). When integrated with the HALY impacts by disease, the overall harm to health from ENDS was estimated to be 33% that of smoking. Conclusions This analysis, suggests that the use of modern ENDS devices (vaping) could be a third as harmful to health as smoking in a high-income country setting. But this estimate is based on a limited number of biomarker studies and is best be considered a likely upper level of ENDS risk given potential biases in our method (i.e., the biomarkers used being correlated with more unaccounted for toxicants in smoking compared to with using ENDS).

Background In the critical care environment, elevated albuminuria values show capacity to reflect illness severity and predict mortality and hence assessing albumin/creatinine ratio (ACR) at the bedside has potential clinical benefit Point-of-care (POC) analysers offer rapid results but may be less accurate then laboratory analysis. Methods Critically ill adult patients with a urinary catheter in situ had albumin, creatinine, and ACR measurements performed via laboratory and POC analysis. Data are presented as mean (standard deviation) or median [interquartile range]. Measurement agreement was assessed by Lin's concordance correlation coefficient, Bland Altman 95% limits of agreement, and classification by Cohen's kappa statistic. Results/Findings Albumin, creatinine, and ACR analysis was performed for 30 patients. Lin's correlation coefficient showed ‘substantial’ agreement for albumin and ACR and ‘almost perfect’ agreement for creatinine for POC vs laboratory analysis. POC vs laboratory analysis also showed poor agreement for identification of normal ACR (>1 mg/mmol) and mild urine ACR (1–3 mg/mmol) and ‘substantial’ agreement for moderately increased urine ACR (3–30 mg/mmol). Conclusions ACR POC values appear to provide an accurate and rapid method that has potential to provide an early indication of injury severity and mortality risk in the critically ill.

Organ segmentation, chest radiograph classification, and lung and liver nodule detections are some of the popular artificial intelligence (AI) tasks in chest and abdominal radiology due to the wide availability of public datasets. AI algorithms have achieved performance comparable to humans in less time for several organ segmentation tasks, and some lesion detection and classification tasks. This article introduces the current published articles of AI applied to chest and abdominal radiology, including organ segmentation, lesion detection, classification, and predicting prognosis.

Context During the COVID-19 pandemic, many clinicians quickly adapted their way of practicing patient care by offering telehealth and virtual office visits while simultaneously having to minimize direct patient care. The shift in direct clinical learning opportunities provided to third- and fourth-year medical students required a shift in the educational curriculum to develop learner skills around the appropriate use of telehealth in patient care. Objectives The aim of this project was to provide exposure to students so they could learn the telemedicine equipment and best practices, and how to identify infectious diseases to improve access to care and meet the needs of the patient. Methods In July and August of 2020, the Indiana Area Health Education Centers Program partnered with Marian University College of Osteopathic Medicine (MUCOM) to support a 1 day telehealth simulation (online curriculum, group lecture, and two standardized patient encounters) into their clerkship curriculum. We utilized a retrospective pretest-posttest to assess changes in learner knowledge around telehealth after the program. At the conclusion of the telehealth training program, students were asked to complete a retrospective pretest-posttest assessing their level of preparedness to utilize telehealth equipment, their preparedness to demonstrate “telehealth best practices” in a manner consistent with protecting patient (and data) privacy, their confidence to utilize telehealth for identification of infectious diseases, and their confidence to utilize telehealth to identify proper treatment plans. Results A total of 96 learners completed the program in 2020. Posttest results demonstrate a statistically significant (p Conclusions Our telehealth curriculum involving a video, interactive learning session, and two standardized patient experiences provided osteopathic medical learners with realistic simulated case scenarios to work through in effort to improve their knowledge and self-efficacy around the utilization of telehealth in practice.

Closures are a language feature supported by many mainstream languages, combining the ability to package up references to code blocks with the possibility of capturing state from the environment of the closure's declaration. Closures are powerful, but complicate understanding and formal reasoning, especially when closure invocations may mutate objects reachable from the captured state or from closure arguments. This paper presents a novel technique for the modular specification and verification of closure-manipulating code in Rust. Our technique combines Rust's type system guarantees and novel specification features to enable formal verification of rich functional properties. It encodes higher-order concerns into a first-order logic, which enables automation via SMT solvers. Our technique is implemented as an extension of the deductive verifier Prusti, with which we have successfully verified many common idioms of closure usage., Proceedings of the ACM on Programming Languages, 5 (OOPSLA), ISSN:2475-1421

Smart contracts are programs that execute in blockchains such as Ethereum to manipulate digital assets. Since bugs in smart contracts may lead to substantial financial losses, there is considerable interest in formally proving their correctness. However, the specification and verification of smart contracts faces challenges that rarely arise in other application domains. Smart contracts frequently interact with unverified, potentially adversarial outside code, which substantially weakens the assumptions that formal analyses can (soundly) make. Moreover, the core functionality of smart contracts is to manipulate and transfer resources; describing this functionality concisely requires dedicated specification support. Current reasoning techniques do not fully address these challenges, being restricted in their scope or expressiveness (in particular, in the presence of re-entrant calls), and offering limited means of expressing the resource transfers a contract performs. In this paper, we present a novel specification methodology tailored to the domain of smart contracts. Our specifications and associated reasoning technique are the first to enable: (1) sound and precise reasoning in the presence of unverified code and arbitrary re-entrancy, (2) modular reasoning about collaborating smart contracts, and (3) domain-specific specifications for resources and resource transfers, expressing a contract's behaviour in intuitive and concise ways and excluding typical errors by default. We have implemented our approach in 2vyper, an SMT-based automated verification tool for Ethereum smart contracts written in Vyper, and demonstrated its effectiveness for verifying strong correctness guarantees for real-world contracts., Proceedings of the ACM on Programming Languages, 5 (OOPSLA), ISSN:2475-1421

Objectives Factors common to socioeconomically disadvantaged neighborhoods, such as low availability of transportation, may limit access to restorative care services for critical illness survivors. Our primary objective was to evaluate whether neighborhood socioeconomic disadvantage was associated with an increased disability burden after critical illness. Our secondary objective was to determine if the effect differed for those discharged to the community compared with those discharged to a facility. Design Longitudinal cohort study with linked Medicare claims data. Setting United States. Patients One hundred ninety-nine older adults, contributing to 239 ICU admissions, who underwent monthly assessments of disability for 12 months following hospital discharge in 13 different functional tasks from 1998 to 2017. Measurements and main results Neighborhood disadvantage was assessed using the area deprivation index, a 1-100 ranking evaluating poverty, housing, and employment metrics. Those living in disadvantaged neighborhoods (top quartile of scores) were less likely to self-identify as non-Hispanic White compared with those in more advantaged neighborhoods. In adjusted models, older adults living in disadvantaged neighborhoods had a 9% higher disability burden over the 12 months following ICU discharge compared with those in more advantaged areas (rate ratio, 1.09; 95% Bayesian credible interval, 1.02-1.16). In the secondary analysis adjusting for discharge destination, neighborhood disadvantage was associated with a 14% increase in disability burden over 12 months of follow-up (rate ratio, 1.14; 95% credible interval, 1.07-1.21). Disability burden was 10% higher for those living in disadvantaged neighborhoods and discharged home as compared with those discharged to a facility, but this difference was not statistically significant (interaction rate ratio, 1.10; 95% credible interval, 0.98-1.25). Conclusions Neighborhood socioeconomic disadvantage is associated with a higher disability burden in the 12 months after a critical illness. Future studies should evaluate barriers to functional recovery for ICU survivors living in disadvantaged neighborhoods.

Background Long-standing health disparities experienced by American Indians (AIs) are associated with increased all-cause mortality rates and shortened life expectancies when compared to other races and ethnicities. Nationally, these disparities have persisted with the COVID-19 pandemic as AIs are more likely than all other races to be infected, hospitalized, or die from SARS-CoV-2. The Mississippi Band of Choctaw Indians, the only federally recognized American Indian tribe in the state, has been one of the hardest hit in the nation. Methods Using de-identified data from the University of Mississippi Medical Center’s COVID-19 Research Registry, a retrospective cohort study was conducted to assess COVID-19 inpatient mortality outcomes among adults (≥ age 18) admitted at the state’s safety net hospital in 2020. Results Exactly 41% (n = 25) of American Indian adults admitted with a deemed diagnosis of COVID-19 died while in hospital, in comparison to 19% (n = 153) of blacks and 23% (n = 65) of whites. Racial disparities persisted even when controlling for those risk factors the CDC reported put adults at greatest risk of severe outcomes from the disease. The adjusted probability of inpatient mortality among American Indians was 46% (p

Therapeutic laser is an increasingly popular tool used in veterinary medicine. Therapeutic laser for veterinary patients aids the body's natural healing process, decreases healing time, alleviates pain and inflammation, and helps to delay progressive diseases. Therapeutic laser can be used immediately following procedures, in postoperative healing, and in a variety of disease processes. Therapeutic lasers are potentially dangerous tools and should be used with caution by trained veterinary nurses. When used properly, the therapeutic laser penetrates the patient's tissues to aid in cell regrowth and reduce pain and inflammation. In order to properly utilise this tool, the veterinary nurse must know what a therapeutic laser is, how it works, and how to handle it properly for each case. Once these concepts are mastered, therapeutic laser can be used by the veterinary nurse, under the supervision of the veterinarian, on a daily basis to help patients with a variety of needs.