Attitudes of UK pathologists and judicial officers towards medicolegal view and grant examinations: a cross-sectional mixed-methods study.

AIMS: Despite the 1988 'Dundee Initiative', which maximised the use of view and grant examinations to reduce the invasive forensic autopsy rate in Tayside, the view and grant itself remains controversial. This is the first study to measure attitudes towards view and grants, applying the Theory of Planned Behaviour to investigate what attitudes are held, the reasons behind them and their association with deciding the scope of postmortem examinations. METHODS: A mixed-methods cross-sectional study examined 62 UK pathologists, coroners and procurators fiscal using an online questionnaire. Participants were asked their demographics and attitudes towards view and grants before allocating five fictitious reportable deaths to either view and grant or invasive forensic autopsy (both in ideal and real world conditions), explaining their decisions using free-text. RESULTS: Participants held both positive and negative attitudes towards view and grants, and most were relatively strong and ambivalent. Attitudes predicted respondents' decisions to favour view and grant or invasive forensic autopsy in all ideal world scenarios, but no real world scenarios. There were significant differences in attitudes and decisions when comparing pathologists and judicial officers, and respondents working in Coroner and Fiscal systems. Thematic analysis was conducted on free-text responses. CONCLUSIONS: Discrepancies between attitudes, and ideal and real world choices suggest that what respondents wanted to do did not necessarily translate to what they would actually do in the scenarios tested. Applying concepts of attitudes, norms and perceived control can help to understand decision-making by death investigators, and why some jurisdictions favour more invasive procedures.

Definitive coverage of distal vein graft in a case of early skin necrosis following popliteal to dorsalis pedis bypass.

Inframalleolar bypass is an effective intervention for chronic limb threatening ischemia. A successful outcome can be compromised by early pedal wound disruption with secondary bypass exposure. We describe the case of a 74-year-old man with a WIfI (wound, ischemia, foot infection) clinical stage 4 foot who underwent popliteal-dorsalis pedis bypass, complicated by early skin necrosis overlying the pedal anastomosis. This necessitated a multidisciplinary approach to obtain tissue coverage over the anastomosis. The wound healed within 28 days, and at 2 years, the patient was mobilizing independently. We outline the approach taken and discuss the management of this challenging limb salvage problem.

MedNeRF: Medical Neural Radiance Fields for Reconstructing 3D-aware CT-Projections from a Single X-ray.

Computed tomography (CT) is an effective med-ical imaging modality, widely used in the field of clinical medicine for the diagnosis of various pathologies. Advances in Multidetector CT imaging technology have enabled additional functionalities, including generation of thin slice multi planar cross-sectional body imaging and 3D reconstructions. However, this involves patients being exposed to a considerable dose of ionising radiation. Excessive ionising radiation can lead to deterministic and harmful effects on the body. This paper proposes a Deep Learning model that learns to reconstruct CT projections from a few or even a single-view X-ray. This is based on a novel architecture that builds from neural radiance fields, which learns a continuous representation of CT scans by disentangling the shape and volumetric depth of surface and internal anatomical structures from 2D images. Our model is trained on chest and knee datasets, and we demonstrate qual-itative and quantitative high-fidelity renderings and compare our approach to other recent radiance field-based methods. Our code and link to our datasets are available at https://qithub.com/abrilcf/mednerf Clinical relevance- Our model is able to infer the anatomical 3D structure from a few or a single-view X-ray showing future potential for reduced ionising radiation exposure during the imaging process.

Deep Generative Modelling: A Comparative Review of VAEs, GANs, Normalizing Flows, Energy-Based and Autoregressive Models.

Deep generative models are a class of techniques that train deep neural networks to model the distribution of training samples. Research has fragmented into various interconnected approaches, each of which make trade-offs including run-time, diversity, and architectural restrictions. In particular, this compendium covers energy-based models, variational autoencoders, generative adversarial networks, autoregressive models, normalizing flows, in addition to numerous hybrid approaches. These techniques are compared and contrasted, explaining the premises behind each and how they are interrelated, while reviewing current state-of-the-art advances and implementations.

Difficult diagnosis and management of a complicated Nellix graft infection.

An 81-year-old man, with a complex vascular surgical history, presents with sepsis from an infected Nellix stent-graft. He required an urgent laparotomy, explantation of the graft, and extra-anatomical repair. Although now widely used for this indication, the preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography was nondiagnostic for his stent-graft infection. We describe our management of a complicated Nellix graft infection and discuss the utility of positron emission tomography/computed tomography for stent-graft infections.

Prevalence and correlates of stress and burnout among U.S. healthcare workers during the COVID-19 pandemic: A national cross-sectional survey study.

BACKGROUND: COVID-19 has put extraordinary stress on healthcare workers. Few studies have evaluated stress by worker role, or focused on experiences of women and people of color. METHODS: The "Coping with COVID" survey assessed US healthcare worker stress. A stress summary score (SSS) incorporated stress, fear of exposure, anxiety/depression and workload (Omega 0.78). Differences from mean were expressed as Cohen's d Effect Sizes (ESs). Regression analyses tested associations with stress and burnout. FINDINGS: Between May 28 and October 1, 2020, 20,947 healthcare workers responded from 42 organizations (median response rate 20%, Interquartile range 7% to 35%). Sixty one percent reported fear of exposure or transmission, 38% reported anxiety/depression, 43% suffered work overload, and 49% had burnout. Stress scores were highest among nursing assistants, medical assistants, and social workers (small to moderate ESs, p < 0.001), inpatient vs outpatient workers (small ES, p < 0.001), women vs men (small ES, p < 0.001), and in Black and Latinx workers vs Whites (small ESs, p < 0.001). Fear of exposure was prevalent among nursing assistants and Black and Latinx workers, while housekeepers and Black and Latinx workers most often experienced enhanced meaning and purpose. In multilevel models, odds of burnout were 40% lower in those feeling valued by their organizations (odds ratio 0.60, 95% CIs [0.58, 0.63], p< 0.001). INTERPRETATION: Stress is higher among nursing assistants, medical assistants, social workers, inpatient workers, women and persons of color, is related to workload and mental health, and is lower when feeling valued.

Preliminary Report: US Physician Stress During the Early Days of the COVID-19 Pandemic.

OBJECTIVE: To assess the impact of the COVID-19 crisis on physician stress and mental health. METHODS: The 10-item Coping With COVID survey assessed stress among 2373 physicians from April 4 to May 27, 2020. A stress summary score with 4 items (a single-item [overall] stress measure, fear of exposure, perceived anxiety/depression due to COVID, and work overload, each scored 1-4) ranged from 4 to 16. Hypothesized stress mitigators included enhanced purpose and feeling valued by one's organization. Multilevel linear regression tested associations of variables with overall stress and stress summary scores. RESULTS: In 2373 physicians in 17 organizations (median response rate of 32%), mean stress summary score was 9.1 (SD 2.6). Stress was highest among women (stress summary score, 9.4 [SD 2.5] vs 8.7 [SD 2.6] in men; P <.001), inpatient physicians (stress summary score, 9.4 [SD 2.8] vs 8.9 [SD 2.5] in outpatient physicians; P <.001), early- and mid-career physicians (stress summary score, 9.5 [SD 2.6] vs 8.6 [SD 2.5] in late-career physicians; P <.001), and physicians in critical care (stress summary score, 10.8), emergency departments (10.2), and hospital medicine (10.1). Increases in perceived anxiety/depression (regression coefficient, 0.30), workload (0.28), and fear (0.14) were associated with higher overall stress (P values <.001). Increases in feeling valued were associated with lower stress summary scores (regression coefficient, -0.67; P <.001) and explained 11% of stress summary score variance at the physician level and 31% of variance at the organizational level. CONCLUSION: Mental health support, modulation of workload, and noting physicians' organizational value should be explored as means to reduce COVID-related stress.

Prehospital clinical signs are a poor predictor of raised intracranial pressure following traumatic brain injury.

BACKGROUND: For the prehospital diagnosis of raised intracranial pressure (ICP), clinicians are reliant on clinical signs such as the Glasgow Coma Score (GCS), pupillary response and/or Cushing's triad (hypertension, bradycardia and an irregular breathing pattern). This study aimed to explore the diagnostic accuracy of these signs as indicators of a raised ICP. METHODS: We performed a retrospective cohort study of adult patients attended by a Helicopter Emergency Medical Service (Air Ambulance Kent, Surrey Sussex), who had sustained a traumatic brain injury (TBI), requiring prehospital anaesthesia between 1 January 2016 and 1 January 2018. We established optimal cut-off values for clinical signs to identify patients with a raised ICP and investigated diagnostic accuracy for combinations of these values. RESULTS: Outcome data for 249 patients with TBI were available, of which 87 (35%) had a raised ICP. Optimal cut-off points for systolic blood pressure (SBP), heart rate (HR) and pupil diameter to discriminate patients with a raised ICP were, respectively, >160 mm Hg,<60 bpm and >5 mm. Cushing criteria (SBP >160 mm Hg and HR <60 bpm) and pupillary response and size were complimentary in their ability to detect patients with a raised ICP. The presence of a fixed blown pupil or a Cushing's response had a specificity of 93.2 (88.2-96.6)%, and a positive likelihood ratio (LR+) of 5.4 (2.9-10.2), whereas sensitivity and LR- were only 36.8 (26.7-47.8)% and 0.7 (0.6-0.8), respectively, (Area Under the Curve (AUC) 0.65 (0.57-0.73)). Sensitivity analysis revealed that optimal cut-off values and resultant accuracy were dependent on injury pattern. CONCLUSION: Traditional clinical signs of raised ICP may under triage patients to prehospital treatment with hyperosmolar drugs. Further research should identify more accurate clinical signs or alternative non-invasive diagnostic aids in the prehospital environment.

Association between Obstructive Sleep Apnea and Exfoliation Syndrome: The Utah Project on Exfoliation Syndrome.

PURPOSE: Exfoliation syndrome (XFS), the most common recognizable cause of open-angle glaucoma worldwide, is a systemic disorder with genetic predisposition due to variations in lysyl oxidase-like 1 (LOXL1) function, leading to altered elastin matrices in ocular and systemic tissues. Obstructive sleep apnea (OSA) is a highly prevalent disorder also involving elastic tissue dysfunction and is associated with glaucoma. Because of the similarities between the disorders, we sought to uncover any relationship in the prevalence of these diagnoses. DESIGN: Case-control, retrospective cohort study. PARTICIPANTS: A cohort of 81 735 patients diagnosed with OSA at ages 50 to 90 years was identified from medical records from 1996 to 2017 in the Utah Population Database. Case subjects were matched to random controls on sex and birth year in a 4:1 ratio. METHODS: International Classification of Diseases, Ninth Revision (ICD-9) codes or their Tenth Revision equivalent were used to define a diagnosis of OSA (ICD-9 327.23) and a diagnosis of XFS (ICD-9 365.52 and 366.11). Conditional logistic regression odds ratios (ORs) accounting for individual matching on sex and birth year were used to estimate the risk of XFS in patients with OSA. Models included adjustment for race, obesity, tobacco use, hypertension (HTN), atrial fibrillation (AF), and chronic obstructive pulmonary disease (COPD). MAIN OUTCOME MEASURE: Whether patients with OSA have an increased risk of diagnosis of XFS compared with controls without OSA. RESULTS: There was an increased risk of an XFS diagnosis in patients with OSA compared with non-OSA controls (OR, 1.27; 95% confidence interval [CI], 1.02-1.59; P = 0.03). In a stratification of patients by HTN diagnosis history, patients with OSA and HTN exhibited an increased risk of XFS compared with non-OSA controls with HTN (OR, 2.67; 95% CI, 2.06-3.46; P < 0.0001). CONCLUSIONS: Patients with OSA may be at an increased risk of XFS compared with patients without OSA, particularly in patients with a history of HTN.

High-fructose corn syrup enhances intestinal tumor growth in mice.

Excessive consumption of beverages sweetened with high-fructose corn syrup (HFCS) is associated with obesity and with an increased risk of colorectal cancer. Whether HFCS contributes directly to tumorigenesis is unclear. We investigated the effects of daily oral administration of HFCS in adenomatous polyposis coli (APC) mutant mice, which are predisposed to develop intestinal tumors. The HFCS-treated mice showed a substantial increase in tumor size and tumor grade in the absence of obesity and metabolic syndrome. HFCS increased the concentrations of fructose and glucose in the intestinal lumen and serum, respectively, and the tumors transported both sugars. Within the tumors, fructose was converted to fructose-1-phosphate, leading to activation of glycolysis and increased synthesis of fatty acids that support tumor growth. These mouse studies support the hypothesis that the combination of dietary glucose and fructose, even at a moderate dose, can enhance tumorigenesis.

Open retrieval of an inferior vena cava filter penetrating into a horseshoe kidney.

Retrievable inferior vena cava filters carry a risk of penetrating into adjacent structures, which may necessitate open retrieval. We report a unique case of a retrievable inferior vena cava filter penetrating into an overlying horseshoe kidney, leading to clinical hematuria. After repeated failed endovascular retrieval, an open approach with associated access challenges was required.

Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption.

BRCA2 encodes a protein with a fundamental role in homologous recombination that is essential for normal development. Carrier status of mutations in BRCA2 is associated with familial breast and ovarian cancer, while bi-allelic BRCA2 mutations can cause Fanconi anemia (FA), a cancer predisposition syndrome with cellular cross-linker hypersensitivity. Cancers associated with BRCA2 mutations can acquire chemo-resistance on relapse. We modeled acquired cross-linker resistance with an FA-derived BRCA2-mutated acute myeloid leukemia (AML) platform. Associated with acquired cross-linker resistance was the expression of a functional BRCA2 protein variant lacking exon 5 and exon 7 (BRCA2ΔE5+7), implying a role for BRCA2 splicing for acquired chemo-resistance. Integrated network analysis of transcriptomic and proteomic differences for phenotyping of BRCA2 disruption infers impact on transcription and chromatin remodeling in addition to the DNA damage response. The striking overlap with transcriptional profiles of FA patient hematopoiesis and BRCA mutation associated ovarian cancer helps define and explicate the 'BRCAness' profile.

Next-Generation Sequencing Analysis and Algorithms for PDX and CDX Models.

Patient-derived xenograft (PDX) and circulating tumor cell-derived explant (CDX) models are powerful methods for the study of human disease. In cancer research, these methods have been applied to multiple questions, including the study of metastatic progression, genetic evolution, and therapeutic drug responses. As PDX and CDX models can recapitulate the highly heterogeneous characteristics of a patient tumor, as well as their response to chemotherapy, there is considerable interest in combining them with next-generation sequencing to monitor the genomic, transcriptional, and epigenetic changes that accompany oncogenesis. When used for this purpose, their reliability is highly dependent on being able to accurately distinguish between sequencing reads that originate from the host, and those that arise from the xenograft itself. Here, we demonstrate that failure to correctly identify contaminating host reads when analyzing DNA- and RNA-sequencing (DNA-Seq and RNA-Seq) data from PDX and CDX models is a major confounding factor that can lead to incorrect mutation calls and a failure to identify canonical mutation signatures associated with tumorigenicity. In addition, a highly sensitive algorithm and open source software tool for identifying and removing contaminating host sequences is described. Importantly, when applied to PDX and CDX models of melanoma, these data demonstrate its utility as a sensitive and selective tool for the correction of PDX- and CDX-derived whole-exome and RNA-Seq data.Implications: This study describes a sensitive method to identify contaminating host reads in xenograft and explant DNA- and RNA-Seq data and is applicable to other forms of deep sequencing. Mol Cancer Res; 15(8); 1012-6. ©2017 AACR.

Emergency EVAR for ruptured abdominal aortic aneurysms: New Zealand experience.

AIM: A ruptured abdominal aortic aneurysm (rAAA) remains a significant threat to life, with a 30-50% in-hospital mortality rate. The recent introduction of emergency endovascular aneurysm repair (rEVAR) in New Zealand presents an alternative to open repair for rAAAs. The aim of this paper is to review the current experience in New Zealand in the repair of rAAAs. METHODS: Data from the Australasian Vascular Audit (AVA) was reviewed, with data pertaining to rAAAs collected for the five-year period from January 2010 to December 2014. RESULTS: Two hundred and eighty-five rAAAs were reported over the five-year period, with an overall mortality rate of 34.0%. There was no significant difference in in-hospital mortality rates alone after rEVAR vs open repair (rOR) (OR 0.39, 95% CI 0.14-1.06, P=0.065). Significant reductions in length of hospital stay (9.710.2 days vs 16.812.9 days, P=0.0125) and the combined in-hospital mortality/post-operative complication rate (35.7% vs 63.6%, OR 0.3, 95% CI 0.1-0.7, P=0.005) were observed after rEVAR vs rOR. CONCLUSION: A primary rEVAR approach is appropriate in selected patients and may represent a paradigm shift in the management of ruptured AAAs in New Zealand.

Modelling the impacts of agricultural management practices on river water quality in Eastern England.

Agricultural diffuse water pollution remains a notable global pressure on water quality, posing risks to aquatic ecosystems, human health and water resources and as a result legislation has been introduced in many parts of the world to protect water bodies. Due to their efficiency and cost-effectiveness, water quality models have been increasingly applied to catchments as Decision Support Tools (DSTs) to identify mitigation options that can be introduced to reduce agricultural diffuse water pollution and improve water quality. In this study, the Soil and Water Assessment Tool (SWAT) was applied to the River Wensum catchment in eastern England with the aim of quantifying the long-term impacts of potential changes to agricultural management practices on river water quality. Calibration and validation were successfully performed at a daily time-step against observations of discharge, nitrate and total phosphorus obtained from high-frequency water quality monitoring within the Blackwater sub-catchment, covering an area of 19.6 km(2). A variety of mitigation options were identified and modelled, both singly and in combination, and their long-term effects on nitrate and total phosphorus losses were quantified together with the 95% uncertainty range of model predictions. Results showed that introducing a red clover cover crop to the crop rotation scheme applied within the catchment reduced nitrate losses by 19.6%. Buffer strips of 2 m and 6 m width represented the most effective options to reduce total phosphorus losses, achieving reductions of 12.2% and 16.9%, respectively. This is one of the first studies to quantify the impacts of agricultural mitigation options on long-term water quality for nitrate and total phosphorus at a daily resolution, in addition to providing an estimate of the uncertainties of those impacts. The results highlighted the need to consider multiple pollutants, the degree of uncertainty associated with model predictions and the risk of unintended pollutant impacts when evaluating the effectiveness of mitigation options, and showed that high-frequency water quality datasets can be applied to robustly calibrate water quality models, creating DSTs that are more effective and reliable.

Duodenal obstruction associated with an abdominal aortic aneurysm.

Aortoduodenal syndrome is a rare clinical entity characterized by an upper gastrointestinal obstruction in association with an abdominal aortic aneurysm. The exact mechanism of obstruction is unknown. We present a case of aortoduodenal syndrome and discuss the interplay of the aneurysm and duodenum in the development of the duodenal obstruction.

Testing the Prey-Trap Hypothesis at Two Wildlife Conservancies in Kenya.

Protecting an endangered and highly poached species can conflict with providing an open and ecologically connected landscape for coexisting species. In Kenya, about half of the black rhino (Diceros bicornis) live in electrically fenced private conservancies. Purpose-built fence-gaps permit some landscape connectivity for elephant while restricting rhino from escaping. We monitored the usage patterns at these gaps by motion-triggered cameras and found high traffic volumes and predictable patterns of prey movement. The prey-trap hypothesis (PTH) proposes that predators exploit this predictable prey movement. We tested the PTH at two semi-porous reserves using two different methods: a spatial analysis and a temporal analysis. Using spatial analysis, we mapped the location of predation events with GPS and looked for concentration of kill sites near the gaps as well as conducting clustering and hot spot analysis to determine areas of statistically significant predation clustering. Using temporal analysis, we examined the time lapse between the passage of prey and predator and searched for evidence of active prey seeking and/or predator avoidance. We found no support for the PTH and conclude that the design of the fence-gaps is well suited to promoting connectivity in these types of conservancies.

Identification of nuclear protein targets for six leukemogenic tyrosine kinases governed by post-translational regulation.

Mutated tyrosine kinases are associated with a number of different haematological malignancies including myeloproliferative disorders, lymphoma and acute myeloid leukaemia. The potential commonalities in the action of six of these leukemogenic proteins on nuclear proteins were investigated using systematic proteomic analysis. The effects on over 3600 nuclear proteins and 1500 phosphopeptide sites were relatively quantified in seven isogenic cell lines. The effects of the kinases were diverse although some commonalities were found. Comparison of the nuclear proteomic data with transcriptome data and cytoplasmic proteomic data indicated that the major changes are due to post-translational mechanisms rather than changes in mRNA or protein distribution. Analysis of the promoter regions of genes whose protein levels changed in response to the kinases showed the most common binding site found was that for NFκB whilst other sites such as those for the glucocorticoid receptor were also found. Glucocorticoid receptor levels and phosphorylation were decreased by all 6 PTKs. Whilst Glucocorticoid receptor action can potentiate NFκB action those proteins where genes have NFκB binding sites were in often regulated post-translationally. However all 6 PTKs showed evidence of NFkB pathway modulation via activation via altered IkB and NFKB levels. Validation of a common change was also undertaken with PMS2, a DNA mismatch repair protein. PMS2 nuclear levels were decreased in response to the expression of all 6 kinases, with no concomitant change in mRNA level or cytosolic protein level. Response to thioguanine, that requires the mismatch repair pathway, was modulated by all 6 oncogenic kinases. In summary common targets for 6 oncogenic PTKs have been found that are regulated by post-translational mechanisms. They represent potential new avenues for therapies but also demonstrate the post-translational regulation is a key target of leukaemogenic kinases.

Synchronized firing among retinal ganglion cells signals motion reversal.

We show that when a moving object suddenly reverses direction, there is a brief, synchronous burst of firing within a population of retinal ganglion cells. This burst can be driven by either the leading or trailing edge of the object. The latency is constant for movement at different speeds, objects of different size, and bright versus dark contrasts. The same ganglion cells that signal a motion reversal also respond to smooth motion. We show that the brain can build a pure reversal detector using only a linear filter that reads out synchrony from a group of ganglion cells. These results indicate that not only can the retina anticipate the location of a smoothly moving object, but that it can also signal violations in its own prediction. We show that the reversal response cannot be explained by models of the classical receptive field and suggest that nonlinear receptive field subunits may be responsible.

Effectiveness of aeration and mixing in the remediation of a saline stratified river.

This study examines the use of an aeration scheme to remediate low oxygen conditions in a saline stratified system. The Tawe estuary was impounded in 1992 and quickly developed saline stratification during the summer months which led to an anoxic hypolimnon. In 1998 trials began in which a suite of aerators was applied to remediate the water quality; the trial was later extended to a full aeration scheme. This study examines pre-aeration conditions in order to delineate conditions under which poor water quality would develop, and would therefore be the conditions when aeration would be necessary. Furthermore, the study compared identical periods within the impoundment during which the following conditions existed: no aeration; and aeration with first 44, then 88, aerators. The study shows that (i) destratification occurred naturally under flows of >10 m3/s, and no low dissolved oxygen conditions were observed at higher flows; (ii) the presence of all levels of aeration had a statistically significant effect upon dissolved oxygen (DO) levels; the effect of increasing the number of aerators was approximately linear; (iii) the average effect of aeration was an increase of up to 3 mg/L DO in the deepest water; (iv) the frequency of low DO conditions decreased from 19% to 3% with the operation of aerators; and (v) aeration is most effective during periods of no tidal incursion and further from the saline water source. This study is the first to demonstrate the effectiveness of aeration in a saline stratified system.