A superconducting nanowire single-photon camera with 400,000 pixels.

For the past 50 years, superconducting detectors have offered exceptional sensitivity and speed for detecting faint electromagnetic signals in a wide range of applications. These detectors operate at very low temperatures and generate a minimum of excess noise, making them ideal for testing the non-local nature of reality1,2, investigating dark matter3,4, mapping the early universe5-7 and performing quantum computation8-10 and communication11-14. Despite their appealing properties, however, there are at present no large-scale superconducting cameras-even the largest demonstrations have never exceeded 20,000 pixels15. This is especially true for superconducting nanowire single-photon detectors (SNSPDs)16-18. These detectors have been demonstrated with system detection efficiencies of 98.0% (ref. 19), sub-3-ps timing jitter20, sensitivity from the ultraviolet21 to the mid-infrared22 and microhertz dark-count rates3, but have never achieved an array size larger than a kilopixel23,24. Here we report on the development of a 400,000-pixel SNSPD camera, a factor of 400 improvement over the state of the art. The array spanned an area of 4 × 2.5 mm with 5 × 5-µm resolution, reached unity quantum efficiency at wavelengths of 370 nm and 635 nm, counted at a rate of 1.1 × 105 counts per second (cps) and had a dark-count rate of 1.0 × 10-4 cps per detector (corresponding to 0.13 cps over the whole array). The imaging area contains no ancillary circuitry and the architecture is scalable well beyond the present demonstration, paving the way for large-format superconducting cameras with near-unity detection efficiencies across a wide range of the electromagnetic spectrum.

Socio-economic disadvantage and utilisation of labour epidural analgesia in Scotland: a population-based study†.

Socio-economic deprivation is associated with adverse maternal and childhood outcomes. Epidural analgesia, the gold standard for labour analgesia, may improve maternal well-being. We assessed the association of socio-economic status with utilisation of epidural analgesia and whether this differed when epidural analgesia was advisable for maternal safety. This was a population-based study of NHS data for all women in labour in Scotland between 1 January 2007 and 23 October 2020, excluding elective caesarean sections. Socio-economic status deciles were defined using the Scottish Index of Multiple Deprivation. Medical conditions for which epidural analgesia is advisable for maternal safety (medical indications) and contraindications were defined according to national guidelines. Of 593,230 patients in labour, 131,521 (22.2%) received epidural analgesia. Those from the most deprived areas were 16% less likely to receive epidural analgesia than the most affluent (relative risk 0.84 [95%CI 0.82-0.85]), with the inter-decile mean change in receiving epidural analgesia estimated at -2% ([95%CI -2.2% to -1.7%]). Among the 21,219 deliveries with a documented medical indication for epidural analgesia, the socio-economic gradient persisted (relative risk 0.79 [95%CI 0.75-0.84], inter-decile mean change in receiving epidural analgesia -2.5% [95%CI -3.1% to -2.0%]). Women in the most deprived areas with a medical indication for epidural analgesia were still less likely (absolute risk 0.23 [95%CI 0.22-0.24]) to receive epidural analgesia than women from the most advantaged decile without a medical indication (absolute risk 0.25 [95%CI 0.24-0.25]). Socio-economic deprivation is associated with lower utilisation of epidural analgesia, even when epidural analgesia is advisable for maternal safety. Ensuring equitable access to an intervention that alleviates pain and potentially reduces adverse outcomes is crucial.

Association between inflammation and post-intensive care syndrome: a systematic review.

Post-intensive care syndrome describes the physical, cognitive and emotional symptoms which persist following critical illness. At present there is limited understanding of the pathological mechanisms contributing to the development of post-intensive care syndrome. The aim of this systematic review was to synthesise current evidence exploring the association between inflammation and features of post-intensive care syndrome in survivors of critical illness. Relevant databases were systematically searched for studies of human participants exposed to critical illness. We sought studies that reported results for biomarkers with an identified role in the pathophysiology of inflammation obtained at any time-point in the patient journey and an outcome measure of any feature of post-intensive care syndrome at any point following hospital discharge. We included 32 studies, with 23 in the primary analysis and nine in a brain injury subgroup analysis. In the primary analysis, 47 different biomarkers were sampled and 44 different outcome measures were employed. Of the biomarkers which were sampled in five or more studies, interleukin-8, C-reactive protein and interleukin-10 most frequently showed associations with post-intensive care syndrome outcomes in 71%, 62% and 60% of studies, respectively. There was variability in terms of which biomarkers were sampled, time-points of sampling and outcome measures reported. Overall, there was mixed evidence of a potential association between an inflammatory process and long-term patient outcomes following critical illness. Further high-quality research is required to develop a longitudinal inflammatory profile of survivors of critical illness over the recovery period and evaluate the association with outcomes.

Predicting time to asystole following withdrawal of life-sustaining treatment: a systematic review.

The planned withdrawal of life-sustaining treatment is a common practice in the intensive care unit for patients where ongoing organ support is recognised to be futile. Predicting the time to asystole following withdrawal of life-sustaining treatment is crucial for setting expectations, resource utilisation and identifying patients suitable for organ donation after circulatory death. This systematic review evaluates the literature for variables associated with, and predictive models for, time to asystole in patients managed on intensive care units. We conducted a comprehensive structured search of the MEDLINE and Embase databases. Studies evaluating patients managed on adult intensive care units undergoing withdrawal of life-sustaining treatment with recorded time to asystole were included. Data extraction and PROBAST quality assessment were performed and a narrative summary of the literature was provided. Twenty-three studies (7387 patients) met the inclusion criteria. Variables associated with imminent asystole (<60 min) included: deteriorating oxygenation; absence of corneal reflexes; absence of a cough reflex; blood pressure; use of vasopressors; and use of comfort medications. We identified a total of 20 unique predictive models using a wide range of variables and techniques. Many of these models also underwent secondary validation in further studies or were adapted to develop new models. This review identifies variables associated with time to asystole following withdrawal of life-sustaining treatment and summarises existing predictive models. Although several predictive models have been developed, their generalisability and performance varied. Further research and validation are needed to improve the accuracy and widespread adoption of predictive models for patients managed in intensive care units who may be eligible to donate organs following their diagnosis of death by circulatory criteria.

People have shaped most of terrestrial nature for at least 12,000 years.

Archaeological and paleoecological evidence shows that by 10,000 BCE, all human societies employed varying degrees of ecologically transformative land use practices, including burning, hunting, species propagation, domestication, cultivation, and others that have left long-term legacies across the terrestrial biosphere. Yet, a lingering paradigm among natural scientists, conservationists, and policymakers is that human transformation of terrestrial nature is mostly recent and inherently destructive. Here, we use the most up-to-date, spatially explicit global reconstruction of historical human populations and land use to show that this paradigm is likely wrong. Even 12,000 y ago, nearly three quarters of Earth's land was inhabited and therefore shaped by human societies, including more than 95% of temperate and 90% of tropical woodlands. Lands now characterized as "natural," "intact," and "wild" generally exhibit long histories of use, as do protected areas and Indigenous lands, and current global patterns of vertebrate species richness and key biodiversity areas are more strongly associated with past patterns of land use than with present ones in regional landscapes now characterized as natural. The current biodiversity crisis can seldom be explained by the loss of uninhabited wildlands, resulting instead from the appropriation, colonization, and intensifying use of the biodiverse cultural landscapes long shaped and sustained by prior societies. Recognizing this deep cultural connection with biodiversity will therefore be essential to resolve the crisis.

COVID-19 Infection Enhances Susceptibility to Oxidative Stress-Induced Parkinsonism.

BACKGROUND: Viral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic. Given the similarities in the systemic responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with those observed after pandemic influenza, there is a question whether a similar syndrome of postencephalic parkinsonism could follow coronavirus disease 2019 infection. OBJECTIVE: The goal of this study was to determine whether prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. METHODS: K18-hACE2 mice were infected with SARS-CoV-2 to induce mild-to-moderate disease. After 38 days of recovery, mice were administered a non-lesion-inducing dose of the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and euthanized 7 days later. Subsequent neuroinflammation and substantia nigra pars compacta (SNpc) dopaminergic (DA) neuron loss were determined and compared with SARS-CoV-2 or MPTP alone. RESULTS: K18-hACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss after MPTP. In mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc DA neurons than SARS-CoV-2 or MPTP, respectively (P < 0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in both the SNpc and striatum of the SARS-CoV-2 + MPTP group compared with SARS-CoV-2 or MPTP alone. CONCLUSIONS: Our observations have important implications for long-term public health, given the number of people who have survived SARS-CoV-2 infection, as well as for future public policy regarding infection mitigation. However, it will be critical to determine whether other agents known to increase risk for PD also have synergistic effects with SARS-CoV-2 and are abrogated by vaccination. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cellular miR-150-5p may have a crucial role to play in the biology of SARS-CoV-2 infection by regulating nsp10 gene.

The role for circulating miRNAs as biomarkers of the COVID-19 disease remains uncertain. We analysed the circulating miRNA profile in twelve COVID-19 patients with moderate-severe disease. This analysis was conducted by performing next generation sequencing (NGS) followed by real-time polymerase chain reaction (RT-qPCR). Compared with healthy controls, we detected significant changes in the circulating miRNA profile of COVID-19 patients. The miRNAs that were significantly altered in all the COVID-19 patients were miR-150-5p, miR-375, miR-122-5p, miR-494-3p, miR-3197, miR-4690-5p, miR-1915-3p, and miR-3652. Infection assays performed using miRNA mimics in HEK-293 T cells determined miR-150-5p to have a crucial role in SARS-CoV-2 infection and this was based on the following data: (i) miR-150-5p mimic lowered in vitro SARS-CoV-2 infection; (ii) miR-150-5p inhibitor reversed the effects of miR-150-5p mimic on SARS-CoV-2 infection of cells; and (iii) a novel miRNA recognition element (MRE) was identified in the coding strand of SARS-CoV-2 nsp10, the expression of which could be inhibited by miR-150-5p mimic. Our findings identified crucial miRNA footprints in COVID-19 patients with moderate-severe disease. A combination of co-transfection and Western blotting experiments also determined the ability of miR-150-5p to inhibit SARS-CoV-2 infection via directly interacting with MRE in the coding strand of nsp10. Our investigation showed that a sharp decline in the miR-150-5p plasma levels in COVID-19 patients may support enhanced SARS-CoV-2 infection. Furthermore, this study provides insight into one possible mechanism by which COVID-19-induced changes to miR-150-5p levels may promote SARS-CoV-2 infection via modulating nsp10 expression.

Comparison of ultra-low, low and high concentration local anaesthetic for labour epidural analgesia: a systematic review and network meta-analysis.

Lumbar epidural is the gold standard for labour analgesia. Low concentrations of local anaesthetic are recommended. This network meta-analysis investigated whether further reducing the concentration of local anaesthetic can improve maternal and neonatal outcomes without compromising analgesia. We conducted a systematic search of relevant databases for randomised controlled trials comparing high (>0.1%), low (>0.08% to ≤0.1%) or ultra-low (≤0.08%) concentration local anaesthetic (bupivacaine or equivalent) for labour epidural. Outcomes included mode of delivery, duration of labour and maternal/neonatal outcomes. Bayesian network meta-analysis with random-effects modelling was used to calculate odds ratios or weighted mean differences and 95% credible intervals. A total of 32 studies met inclusion criteria (3665 women). The total dose of local anaesthetic received increased as the concentration increased; ultra-low compared with low (weighted mean difference -14.96 mg, 95% credible interval [-28.38 to -1.00]) and low compared with high groups (weighted mean difference -14.99 [-28.79 to -2.04]), though there was no difference in the number of rescue top-ups administered between the groups. Compared with high concentration, ultra-low concentration local anaesthetic was associated with increased likelihood of spontaneous vaginal delivery (OR 1.46 [1.18 to 1.86]), reduced motor block (Bromage score >0; OR 0.32 [0.18 to 0.54]) and reduced duration of second stage of labour (weighted mean difference -13.02 min [-21.54 to -4.77]). Compared with low, ultra-low concentration local anaesthetic had similar estimates for duration of second stage of labour (weighted mean difference -1.92 min [-14.35 to 10.20]); spontaneous vaginal delivery (OR 1.07 [0.75 to 1.56]; assisted vaginal delivery (OR 1.35 [0.75 to 2.26]); caesarean section (OR 0.76 [0.49 to 1.22]); pain (scale 1-100, weighted mean difference -5.44 [-16.75 to 5.93]); and maternal satisfaction. Although a lower risk of an Apgar score < 7 at 1 min (OR 0.43 [0.15 to 0.79]) was reported for ultra-low compared with low concentration, this was not sustained at 5 min (OR 0.12 [0.00 to 2.10]). Ultra-low concentration local anaesthetic for labour epidural achieves similar or better maternal and neonatal outcomes as low and high concentration, but with reduced local anaesthetic consumption.

Hospital re-admission after critical care survival: a systematic review and meta-analysis.

Survivors of critical illness frequently require increased healthcare resources after hospital discharge. We undertook a systematic review and meta-analysis to assess hospital re-admission rates following critical care admission and to explore potential re-admission risk factors. We searched the MEDLINE, Embase and CINAHL databases on 05 March 2020. Our search strategy incorporated controlled vocabulary and text words for hospital re-admission and critical illness, limited to the English language. Two reviewers independently applied eligibility criteria and assessed quality using the Newcastle Ottawa Score checklist and extracted data. The primary outcome was acute hospital re-admission in the year after critical care discharge. Of the 8851 studies screened, 87 met inclusion criteria and 41 were used within the meta-analysis. The analysis incorporated data from 3,897,597 patients and 741,664 re-admission episodes. Pooled estimates for hospital re-admission after critical illness were 16.9% (95%CI: 13.3-21.2%) at 30 days; 31.0% (95%CI: 24.3-38.6%) at 90 days; 29.6% (95%CI: 24.5-35.2%) at six months; and 53.3% (95%CI: 44.4-62.0%) at 12 months. Significant heterogeneity was observed across included studies. Three risk factors were associated with excess acute care rehospitalisation one year after discharge: the presence of comorbidities; events during initial hospitalisation (e.g. the presence of delirium and duration of mechanical ventilation); and subsequent infection after hospital discharge. Hospital re-admission is common in survivors of critical illness. Careful attention to the management of pre-existing comorbidities during transitions of care may help reduce healthcare utilisation after critical care discharge. Future research should determine if targeted interventions for at-risk critical care survivors can reduce the risk of subsequent rehospitalisation.

Improving Medical Student Attitudes Toward Suicide Prevention Through a Patient Safety Planning Clerkship Initiative.

OBJECTIVE: This project aimed to understand medical students' attitudes toward suicide prevention and their experiences in an innovative clerkship training program that engaged students in patient safety planning. METHODS: Medical students were invited to complete the Attitudes to Suicide Prevention (ASP) scale to explore student perceptions of suicide prevention and risk assessment. Seventy-five psychiatry clerkship students also completed a new safety planning training program with at-risk patients on psychiatry inpatient units. Each student observed a patient safety plan being completed, discussed this process with the resident or attending, completed a safety plan with another patient, and then debriefed with the observing physician. Participants completed the ASP before and after the rotation. RESULTS: The cross-sectional data (n=490) showed that student perceptions of suicide prevention were generally positive (M=27.8, SD=6.1) with variation among classes, but many students did not fully recognize the potential effectiveness of suicide risk reduction strategies. After the clerkship intervention, students were significantly more likely to report that working with suicidal patients was rewarding (p=0.035) and less likely to report discomfort assessing patients for suicide risk (p=0.001). CONCLUSIONS: Medical educators can reinforce the process and efficacy of suicide interventions by modeling the described initiative. Psychiatry clerkship training that intentionally engages students in safety planning with patients is generalizable, and these skills could be extended to the student burnout crisis. Longitudinal studies will help determine how individual perceptions change through medical school and whether students apply safety planning skills in psychiatry and other specialties to care for suicidal patients.

Triclosan induces apoptosis in Burkitt lymphoma-derived BJAB cells through caspase and JNK/MAPK pathways.

Burkitt's lymphoma (BL) is the fastest growing human tumor. Current treatment consists of a multiagent regimen of cytotoxic drugs with serious side effjects including tumor lysis, cardiotoxicity, hepatic impairment, neuropathy, myelosuppression, increased susceptibility to malignancy, and death. Furthermore, therapeutic interventions in areas of BL prevalence are not as feasible as in high-income countries. Therefore, there exists an urgent need to identify new therapies with a safer profile and improved accessibility. Triclosan (TCS), an antimicrobial used in personal care products and surgical scrubs, has gained considerable interest as an antitumor agent due to its interference with fatty acid synthesis. Here, we investigate the antitumor properties and associated molecular mechanisms of TCS in BL-derived BJAB cells. Dose-dependent cell death was observed following treatment with 10-100 µM TCS for 24 h, which was associated with membrane phospholipid scrambling, compromised permeability, and cell shrinkage. TCS-induced cell death was accompanied by elevated intracellular calcium, perturbed redox balance, chromatin condensation, and DNA fragmentation. TCS upregulated Bad expression and downregulated that of Bcl2. Moreover, caspase and JNK MAPK signaling were required for the full apoptotic activity of TCS. In conclusion, this report identifies TCS as an antitumor agent and provides new insights into the molecular mechanisms governing TCS-induced apoptosis in BL cells.

Two different begomovirus species are associated with yellow vein mosaic disease of okra in Sri Lanka.

Yellow vein mosaic disease is the major biotic constraint of okra cultivation in Sri Lanka. Identification and detailed molecular characterization of associated pathogen is needed for effective disease management. The genome of the begomovirus and betasatellite were amplified in symptomatic plant samples using specific degenerate primers. DNA-A genome of twelve isolates representing different locations in Sri Lanka were cloned, sequenced and deposited in GenBank database (Accession No- KX698087- KX698092 and MH455207- MH455212). Size of the complete nucleotide sequences ranged from 2735 to 2786 bp. The genome organization showed characteristics of begomoviruses. The pairwise sequence identity revealed the association of two different begomovirus species. Five of the isolates showed > 91% of sequences identity with Bhendi yellow vein mosaic virus, and the rest of the seven isolates were around 92% of identity with Okra enation leaf curl virus. This is further supported by phylogenetic analysis where both of these group of isolates were in different cluster. Recombination analysis showed the presence of recombinant fragments in the virus isolates associated with okra yellow vein mosaic disease (OYVMD) in Sri Lanka. Attempts to amplify DNA- B were failed in any of the samples tested. However, both type of the begomovirus species associated with betasatellite species, Bhendi yellow vein mosaic betasatellite. The present study has revealed the association of two distinct monopartite begomovirus species, Bhendi yellow vein mosaic virus or Okra enation leaf curl virus, with OYVMD in Sri Lanka.

Airway events in obese vs. non-obese elective surgical patients: a cross-sectional observational study.

Obesity is an increasingly prevalent comorbidity within the UK population. The aim of this study was to determine the proportion of obese patients in an elective surgical population. The second aim was to determine the choice of airway equipment and incidence of airway events in obese vs. non-obese patients. We conducted a cross-sectional observational study over two 24-h periods in March 2018 across 39 hospitals in the greater London area. Data were collected regarding 1874 patients. The incidence of obesity was 32% in the study population compared with 26% in the general UK population (p < 0.0001). Minor airway events were defined as: desaturation to Sp O2 < 90%; failed mask ventilation; supraglottic airway device problem; aspiration; airway trauma and difficult intubation; or recognised oesophageal intubation. Major airway events were defined as: unrecognised oesophageal intubation; a 'cannot intubate cannot oxygenate' emergency; the need for unplanned front-of-neck airway; cardiac arrest; or unplanned intensive care unit admission due to an airway event. In total, 89 minor and two major airway events were recorded. Obese patients were more likely to experience a minor airway event (RR 2.39, 95%CI 1.60-3.57), the most common being desaturation (Sp O2 < 90%). The use of a supraglottic airway device in obese vs. non-obese patients was associated with increased airway events (RR 3.46 [1.88-6.40]). Tracheal intubation vs. supraglottic airway device use increased with obesity class but was not associated with a decrease in airway events (RR 0.90 [0.53-1.55]). Our data suggest that obesity is more common in the elective surgical vs. general population and minor airway events are more common in obese vs. non-obese elective patients.

Anaemia in cardiac surgery - a retrospective review of a centre's experience with a pre-operative intravenous iron clinic.

Pre-operative anaemia is associated with higher rates of transfusion and worse outcomes, including prolonged hospital stay, morbidity and mortality. Iron deficiency is associated with significantly lower haemoglobin levels throughout the peri-operative period and more frequent blood transfusion. Correction of iron stores before surgery forms part of the first pillar of patient blood management. We established a pre-operative anaemia clinic to aid identification and treatment of patients with iron deficiency anaemia scheduled for elective cardiac surgery. We present a retrospective observational review of our experience from January 2017 to December 2019. One-hundred and ninety patients received treatment with intravenous iron, a median of 21 days before cardiac surgery. Of these, 179 had a formal laboratory haemoglobin level measured before surgery, demonstrating a median rise in haemoglobin of 8.0 g.l-1 . Patients treated with i.v. iron demonstrated a significantly higher incidence of transfusion (60%) compared with the non-anaemic cohort (22%) during the same time period, p < 0.001. Significantly higher rates of new requirement for renal replacement therapy (6.7% vs. 0.6%, p < 0.001) and of stroke (3.7% vs. 1.2%, p = 0.010) were also seen in this group compared with those without anaemia, although there was no significant difference in in-hospital mortality (1.6% vs. 0.8%, p = 0.230). In patients where the presenting haemoglobin was less than 130 g.l-1 , but there was no intervention or treatment, there was no difference in rates of transfusion or of complications compared with the anaemic group treated with iron. In patients with proven iron deficiency anaemia, supplementation with intravenous iron showed only a modest effect on haemoglobin and this group still had a significantly higher transfusion requirement than the non-anaemic cohort. Supplementation with intravenous iron did not improve outcomes compared with patients with anaemia who did not receive intravenous iron and did not reduce peri-operative risk to non-anaemic levels. Questions remain regarding identification of patients who will receive most benefit, the use of concomitant treatment with other agents, and the optimum time frames for treatment in order to produce benefit in the real-world setting.

Perspectives of Transgender and Genderqueer Standardized Patients.

Phenomenon: Disparities in health and healthcare for gender minorities (GMs) such as transgender people are significant, and medical educators have a responsibility to ensure trainees master the clinical skills required to provide them with quality care. We implemented a standardized patient (SP) scenario designed to measure students' ability to provide gender-affirming care and sought to understand the experiences and perceptions of the GMs who served as SPs in this case. Our key research question was: how do GM SPs describe the experience of serving as an SP on a gender-affirming care clinical case? Approach: Semi-structured focus groups were conducted with GM SPs (n = 10) to understand their experiences and gauge their perceptions of portraying a patient seeking gender-affirming care. The patient they portrayed matched their own gender identity. Focus groups were transcribed verbatim and analyzed using inductive thematic analysis. Findings: We developed three primary themes in our analysis: personal connection, gap identification, and insight into medical education. The SPs reported a personal connection to this case, enabling them to give nuanced feedback, confront bias they encountered, and foster connection to their broader community. They were able to identify specific gaps related to communication skills, assumptions, and knowledge about gender identity and gender-affirming care. They gained valuable insight into medical education such as the complexity of learning clinical skills and roadblocks to inclusive simulation. Insights: By sharing the perspectives of GMs in patient simulation, this study demonstrates that GMs can also benefit from engagement with medical education, as the SPs in our study described hope, empowerment, and engagement as positive aspects of participation. This study also shows that GMs' lived experiences seeking medical care were instrumental in their ability to note gaps, which provides valuable insight for other institutions attempting to improve students' GM clinical skills. Further, GM SPs' perspectives are valuable to provide a rationale and guidance to other schools implementing gender-affirming education. Efforts to create and implement gender-affirming care curriculum should include GMs in order to build partnerships and prioritize the voices and agency of GMs.

Association between Characteristics of Impostor Phenomenon in Medical Students and Step 1 Performance.

THEORY: Impostor phenomenon (IP) is a widely recognized experience in which highly performing individuals do not internalize success. Self-doubt toward one's ability or intelligence is unexpectedly common. Prior research has associated IP with medical student perceptions, burnout, and demographic characteristics. However, understanding how student IP experiences are related to actual academic achievement could help medical schools better support student performance and resilience. Hypotheses: The purpose of this research was to examine whether there is a relationship between medical students' USMLE Step 1 scores and experiences of IP. Because medical students receive frequent, objective feedback on exam performance, we hypothesized that students with lower Step 1 scores would experience higher levels of IP. Methods: In 2019, all M1-M4 students at the University of Louisville were invited to complete Clance's (1985) Impostor Phenomenon Scale (CIPS), a previously validated, 20-item, Likert-style scoring instrument designed to reflect respondents' IP experience. We categorized subjects into one of four levels based on CIPS scoring guidelines. For students who had completed Step 1 at the time of the survey, we conducted a Welch's ANOVA test to identify relationships between a student's level of experienced IP and Step 1 scores. We also completed an item analysis comparing individual CIPS item responses with Step 1 performance. Results: Per the CIPS scoring guidelines, we categorized the 233 respondents as experiencing few (10.3%), moderate (47.6%), frequent (31.8%), or intense (10.3%) characteristics of IP. Nearly 90% of our sample experienced at least moderate levels of IP, with over 40% experiencing frequent or intense IP. There were no statistically significant differences among CIPS groups and mean Step 1 scores [F (3, 59.8) = 1.81, p = 0.155], and total/inter-quartile Step 1 score ranges broadly overlapped among all four IP experience levels. Within-item response patterns among high and low-scoring students also varied across individual CIPS items. Conclusions: The association between IP experience and Step 1 performance was nonlinear in our cross-sectional sample: the group having the most intense IP experiences did not have the lowest score rank on Step 1, nor did the group with the fewest IP characteristics make up our highest performing group. This, along with the broad dispersion of scores within each of the four IP levels, suggests that students' internalization of achievement and feelings of IP are not consistently aligned with their actual performance on this assessment. Response variation on individual CIPS items suggest that underlying factors may drive variation in IP and performance. These results highlight the need for additional work to identify the constructs of IP that influence medical students specifically so that medical education stakeholders may better understand IP's impact on other facets of medical school and implement the resources necessary to support individuals who experience IP.

High burden of viral respiratory co-infections in a cohort of children with suspected pulmonary tuberculosis.

BACKGROUND: The presentation of pulmonary tuberculosis (PTB) in young children is often clinically indistinguishable from other common respiratory illnesses, which are frequently infections of viral aetiology. As little is known about the role of viruses in children with PTB, we investigated the prevalence of respiratory viruses in children with suspected PTB at presentation and follow-up. METHODS: In an observational cohort study, children < 13 years were routinely investigated for suspected PTB in Cape Town, South Africa between December 2015 and September 2017 and followed up for 24 weeks. Nasopharyngeal aspirates (NPAs) were tested for respiratory viruses using multiplex PCR at enrolment, week 4 and 8. RESULTS: Seventy-three children were enrolled [median age 22.0 months; (interquartile range 10.0-48.0); 56.2% male and 17.8% HIV-infected. Anti-tuberculosis treatment was initiated in 54.8%; of these 50.0% had bacteriologically confirmed TB. At enrolment, ≥1 virus were detected in 95.9% (70/73) children; most commonly human rhinovirus (HRV) (74.0%). HRV was more frequently detected in TB cases (85%) compared to ill controls (60.6%) (p = 0.02). Multiple viruses were detected in 71.2% of all children; 80% of TB cases and 60.6% of ill controls (p = 0.07). At follow-up, ≥1 respiratory virus was detected in 92.2% (47/51) at week 4, and 94.2% (49/52) at week 8. CONCLUSIONS: We found a high prevalence of viral respiratory co-infections in children investigated for PTB, irrespective of final PTB diagnosis, which remained high during follow up. Future work should include investigating the whole respiratory ecosystem in combination with pathogen- specific immune responses.

A prospective cohort study characterising patients declined emergency laparotomy: survival in the 'NoLap' population.

Patients eligible for emergency laparotomy who do not proceed to surgery are not as well characterised as patients who do proceed to surgery. We studied patients eligible for laparotomy, as defined by National Emergency Laparotomy Audit criteria, from August 2015 to October 2016. We analysed the association of individual variables with survival and two composite scores: P-POSSUM and a general survival model. Out of 314 patients, 214 (68%) underwent laparotomy and 100 (32%) did not. Median (IQR [range]) follow-up was 1.3 (0.1-1.8 [0.0-2.5]) years for the cohort, 1.5 (1.1-2.0 [0.0-2.6]) years after laparotomy and 0.0 (0.0-1.1 [0.0-2.2]) years without laparotomy. There were 126/314 (40%) deaths in the follow-up period, 52/214 (24%) deaths after laparotomy and 74/100 (74%) deaths without surgery. Ninety out of 126 deaths (71%) were within one month of hospital admission. Patient variables were different for the two groups, which when combined in the general survival model generated background median (IQR [range]) life expectancies of 12 (6-21 [0-49]) and 4 (2-6 [0-36]) years, respectively, p < 0.0001. 'Poor fitness' precluded laparotomy in 74/100 (74%) patients. The decision to not operate involved a consultant less often than the decision to operate: 66/100 (66%) vs. 178/214 (83%), p = 0.001. Our study supports the contention that survival beyond 30 postoperative days could be predicted reasonably accurately. Survival in patients who did not have laparotomy was shorter than expected. Emergency laparotomy might have prolonged survival in some patients.

De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.

Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive-compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4's function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family.

The impact of type 2 diabetes and body mass index on cerebral structure is modulated by brain reserve.

BACKGROUND AND PURPOSE: Body mass index (BMI), hyperglycaemia and type 2 diabetes and their interactive effects are associated with brain volume atrophy in ageing. It remains to be established if these risk factors are particularly concerning in individuals with high or low brain volumes. METHODS: Demographics, venous blood and magnetic resonance imaging data were collected for 494 healthy community-living adults aged 53-78 (mean 65) years, as part of the Personality and Total Health Through Life study. Associations between BMI, blood glucose, diabetes status and brain volume (whole brain, grey matter, white matter and subcortical structures) were investigated using quantile regression. RESULTS: Quantile regression revealed vulnerability to BMI × glucose interactions particularly in lower volumes and significant main effects for type 2 diabetes particularly in higher volumes. Diabetes was most strongly associated with brain volumes. The association between BMI, blood glucose and diabetes was not consistent across the full range of brain volumes. CONCLUSION: Explicit investigation of the upper and lower boundaries of brain volume distributions was valuable. We found evidence of protective reserve from higher brain volumes and that a combination of high BMI and higher blood glucose was particularly concerning for individuals with lower brain volumes.