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Introduction Brain tumors cause morbidity and mortality in part through peritumoral brain edema. The current main treatment for peritumoral brain edema are corticosteroids. Due to the increased recognition of their side-effect profile, there is growing interest in finding alternatives to steroids but there is little formal study of animal models of peritumoral brain edema. This study aims to summarize the available literature. Methods A systematic search was undertaken of 5 literature databases (Medline, Embase, CINAHL, PubMed and the Cochrane Library). The generic strategy was to search for various terms associated with “brain tumors”, “brain edema” and “animal models”. Results We identified 603 reports, of which 112 were identified as relevant for full text analysis that studied 114 peritumoral brain edema animal models. We found significant heterogeneity in the species and strain of tumor-bearing animals, tumor implantation method and edema assessment. Most models did not produce appreciable brain edema and did not test for observable manifestations thereof. Conclusion No animal model currently exists that enable the investigation of novel candidates for the treatment of peritumoral brain edema. With current interest in alternative treatments for peritumoral brain edema, there is an unmet need for clinically relevant animal models.

Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases1,2. However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs, a phenomenon termed microsatellite instability; however, larger repeat expansions have not been systematically analysed in cancer3–8. Here we identified TR expansions in 2,622 cancer genomes spanning 29 cancer types. In seven cancer types, we found 160 recurrent repeat expansions (rREs), most of which (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with enrichment near candidate cis-regulatory elements, suggesting a potential role in gene regulation. One rRE, a GAAA-repeat expansion, located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, in preliminary experiments, treating cells that harbour this rRE with a GAAA-targeting molecule led to a dose-dependent decrease in cell proliferation. Overall, our results suggest that rREs may be an important but unexplored source of genetic variation in human cancer, and we provide a comprehensive catalogue for further study.

The advent of Industry 4.0 has led to a rapid increase in cyber attacks on industrial systems and processes, particularly on Industrial Control Systems (ICS). These systems are increasingly becoming prime targets for cyber criminals and nation-states looking to extort large ransoms or cause disruptions due to their ability to cause devastating impact whenever they cease working or malfunction. Although myriads of cyber attack detection systems have been proposed and developed, these detection systems still face many challenges that are typically not found in traditional detection systems. Motivated by the need to better understand these challenges to improve current approaches, this paper aims to (1) understand the current vulnerability landscape in ICS, (2) survey current advancements of Machine Learning (ML) based methods with respect to the usage of ML base classifiers (3) provide insights to benefits and limitations of recent advancement with respect to two performance vectors; detection accuracy and attack variety. Based on our findings, we present key open challenges which will represent exciting research opportunities for the research community.

Background Surgical mortality indicators should be risk-adjusted when evaluating the performance of organisations. This study evaluated the performance of risk-adjustment models that used English hospital administrative data for 30-day mortality after neurosurgery. Methods This retrospective cohort study used Hospital Episode Statistics (HES) data from 1 April 2013 to 31 March 2018. Organisational-level 30-day mortality was calculated for selected subspecialties (neuro-oncology, neurovascular and trauma neurosurgery) and the overall cohort. Risk adjustment models were developed using multivariable logistic regression and incorporated various patient variables: age, sex, admission method, social deprivation, comorbidity and frailty indices. Performance was assessed in terms of discrimination and calibration. Results The cohort included 49,044 patients. Overall, 30-day mortality rate was 4.9%, with unadjusted organisational rates ranging from 3.2 to 9.3%. The variables in the best performing models varied for the subspecialties; for trauma neurosurgery, a model that included deprivation and frailty had the best calibration, while for neuro-oncology a model with these variables plus comorbidity performed best. For neurovascular surgery, a simple model of age, sex and admission method performed best. Levels of discrimination varied for the subspecialties (range: 0.583 for trauma and 0.740 for neurovascular). The models were generally well calibrated. Application of the models to the organisation figures produced an average (median) absolute change in mortality of 0.33% (interquartile range (IQR) 0.15–0.72) for the overall cohort model. Median changes for the subspecialty models were 0.29% (neuro-oncology, IQR 0.15–0.42), 0.40% (neurovascular, IQR 0.24–0.78) and 0.49% (trauma neurosurgery, IQR 0.23–1.68). Conclusions Reasonable risk-adjustment models for 30-day mortality after neurosurgery procedures were possible using variables from HES, although the models for trauma neurosurgery performed less well. Including a measure of frailty often improved model performance.

The use of digital technology is increasing rapidly across surgical specialities, yet there is no consensus for the term ‘digital surgery’. This is critical as digital health technologies present technical, governance, and legal challenges which are unique to the surgeon and surgical patient. We aim to define the term digital surgery and the ethical issues surrounding its clinical application, and to identify barriers and research goals for future practice. 38 international experts, across the fields of surgery, AI, industry, law, ethics and policy, participated in a four-round Delphi exercise. Issues were generated by an expert panel and public panel through a scoping questionnaire around key themes identified from the literature and voted upon in two subsequent questionnaire rounds. Consensus was defined if >70% of the panel deemed the statement important and

Delayed cerebral ischaemia (DCI) is a significant complication of aneurysmal subarachnoid haemorrhage (aSAH) and is strongly associated with poorer outcome. The Alberta Stroke Program Early Computer Tomography (ASPECT) score is an established scoring tool, used in acute ischaemic stroke, to quantify early ischaemic changes on CT head scans. We aim to identify if ASPECT scoring correlates with functional outcome in DCI following aSAH. Retrospective case–control study. Inclusion criteria: admission to the Department of Neurosurgery at Leeds Teaching Hospitals NHS Trust (a tertiary neurosurgical centre in the United Kingdom) between 2014 and 2018, with a diagnosis of anterior circulation aneurysmal subarachnoid haemorrhage; as confirmed by initial CT scan and subsequent CT angiography or catheter digital subtraction angiography. Cases were those who developed DCI (n = 43) and controls were randomly selected from those who did not develop DCI (n = 46) but otherwise met the same inclusion criteria. The primary outcome measure was Glasgow Outcome Score (GOS): assessed at discharge and 3 months. ASPECT scores were calculated from non-contrast CT head scans by three researchers blinded to each other and clinical outcome. Spearman’s rank correlation was used to calculate correlation between ASPECT scores and GOS. ASPECT score positively correlated with GOS in the cases both at discharge (Spearman rho 0.436, p = 0.003) and at 3 months (Spearman rho 0.431, p = 0.004). When corrected for Fisher grading, the adjusted odds ratio of having a high GOS with a low ASPECT score at discharge was OR 0.74 (95% CI 0.61–0.94, p = 0.003), and 3 months OR 0.73 (95% CI 0.59–0.91, p = 0.005). ASPECT score significantly correlates with clinical outcome in DCI post aSAH, even after correcting for Fisher grade. ASPECT scoring may identify patients at risk of poor outcome following DCI and represents a quick and reliable tool that aids in clinical decision-making and prognostication.

Using time-driven activity-based costing (TDABC), we examined resource allocation and costs for HIV services throughout Tanzania at patient and facility levels. This national, cross-sectional analysis of 22 health facilities quantified costs and resources associated with 886 patients receiving care for five HIV services: antiretroviral therapy, prevention of mother-to-child transmission, HIV testing and counseling, voluntary medical male circumcision, and pre-exposure prophylaxis. We also documented total provider-patient interaction time, the cost of services with and without inclusion of consumables, and conducted fixed-effects multivariable regression analyses to examine patient- and facility-level correlates of costs and provider-patient time. Findings showed that resources and costs for HIV care varied significantly throughout Tanzania, including as a function of patient- and facility-level characteristics. While some variation may be preferable (e.g., needier patients received more resources), other areas suggested a lack of equity (e.g., wealthier patients received more provider time) and presented opportunities to optimize care delivery protocols.

Background Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. Methods We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. Results A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. Conclusions In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

Estimates suggest that over 15,000 people are buried at East End Cemetery, a historic African American cemetery in Richmond, Virginia, that until recently received no public funding for upkeep. Here, we present a case study analysis and potentially replicable methodology for counting and locating unmarked burial depressions in non-forested areas using a low-cost sUAV (drone) and simple, hydrology-based geographic information systems analyses. Upon visual inspection of 12% of our final 8,000 burial site dataset, we find our dataset is a plausible representation (75% accuracy) of potential grave locations. We hope that the methods presented below can be implemented to assist in reclaiming historically underfunded Black cemeteries across the American South.