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Computing systems are becoming increasingly data-intensive because of the explosion of data and the needs for processing the data, and subsequently storage management is critical to application performance in such data-intensive computing systems. However, if existing resource management frameworks in these systems lack the support for storage management, this would cause unpredictable performance degradation when applications are under input/output (I/O) contention. Storage management of data-intensive systems is a challenge. Big Data plays a most major role in storage systems for data-intensive computing. This article deals with these difficulties along with discussion of High Performance Computing (HPC) systems, background for storage systems for data-intensive applications, storage patterns and storage mechanisms for Big Data, the Top 10 Cloud Storage Systems for data-intensive computing in today's world, and the interface between Big Data Intensive Storage and Cloud/Fog Computing. Big Data storage and its server statistics and usage distributions for the Top 500 Supercomputers in the world are also presented graphically and discussed as data-intensive storage components that can be interfaced with Fog-to-cloud interactions and enabling protocols.

Up to a third of children undergoing partial hepatectomy for primary hepatic malignancies experience at least one perioperative complication, with a presumed deleterious effect on both short- and long-term outcomes. We implemented a multidisciplinary treatment protocol in the management of these patients in order to improve complication rates following partial hepatectomy.A retrospective chart review was completed for all patients 18 years of age who underwent liver resection at our institution between 2002 and 2019 for primary hepatic cancer. Demographic, intraoperative, postoperative, pathologic, and outcome data were analyzed for perioperative complications using the CLASSIC and Clavien-Dindo (CD) scales, event-free survival (EFS) and overall survival (OS).A total of 73 patients were included in the analysis with 33 prior-to and 40 after dedicated provider protocol implementation. Perioperative complication rates decreased from 52% to 20% (p = 0.005) with major complications going from 18% to 10% (p = 0.31). On multivariable logistic regression, protocol implementation was associated with a reduction in any (OR 0.29 [95% CI 0.09 - 0.89]) but not major complications. On multivariate cox models, post protocol implementation was associated with improved event free survival (EFS) (HR 0.19 (0.036 - 0.195). Among patients with a diagnosis of hepatoblastoma (n = 62), the occurrence of a major perioperative complication was associated with a worse EFS (HR=5.45, p = 0.03) on multivariate analysis, however this did not translate into an impact on overall survival.Our results demonstrate that, for children with primary liver malignancies, a dedication of patients to high-volume surgeons can improve rates of complications of liver resections and may improve the oncological outcome of hepatoblastoma.

The initial description of robotic tracheobronchoplasty for the treatment of tracheobronchomalacia demonstrated feasibility, safety, and short-term symptomatic and functional improvement. The purpose of the current study was to demonstrate intermediate outcomes in postoperative pulmonary function and quality of life after robotic tracheobronchoplasty.We retrospectively reviewed prospectively collected clinical data from 42 patients who underwent robotic tracheobronchoplasty from May 2016 to December 2017. The Institutional Review Board or equivalent ethics committee of the Northwell Health approved the study protocol and publication of data. Patient written consent for the publication of the study data was waived by the Institutional Review Board.A total of 42 patients underwent robotic tracheobronchoplasty during the study period. Median total follow-up is 40 months. There was 1 death since surgery from an unrelated disease. Significant decreases in St George's Respiratory Questionnaire total score (preoperative mean: 64.01, postoperative mean: 38.91, P = .002), St George's Respiratory Questionnaire symptom score (preoperative median: 82.6, postoperative median: 43.99, P .001), and St George's Respiratory Questionnaire impact score (preoperative median: 55.78, postoperative median: 25.95, P .001) were apparent at a median follow-up of 13 months. Comparison of preoperative and postoperative pulmonary function tests revealed a significant increase in percent predicted forced expiratory volume in 1 second (preoperative median: 74% vs postoperative median: 82%, P = .001), forced vital capacity (preoperative median: 68.5% vs postoperative median: 80.63%, P .001), and peak expiratory flow (preoperative median: 61.5% vs postoperative median: 75%, P = .02) measured at a median follow-up of 29 months.Robotic tracheobronchoplasty is associated with low intermediate-term mortality. Robotic tracheobronchoplasty results in significant improvement in quality of life and postoperative pulmonary function. Longer-term follow-up is necessary to continue to elucidate the effect of robotic tracheobronchoplasty on halting pathologic progression of tracheobronchomalacia and to determine the long-term impact of tracheobronchoplasty on symptomatic and functional improvement.

Background Recent analyses of the volume-outcome relationship for percutaneous coronary intervention (PCI) have suggested a less robust association than previously reported. It is unknown if novel factors such as lifetime operator experience influence this relationship. Objectives To assess the relationship between annual volumes and outcomes for PCI and determine whether lifetime operator experience modulates the association. Methods Annual PCI volumes for facilities and operators within the Veterans Affairs Healthcare System and their relationship with 30-day mortality following PCI were described. The influence of operator lifetime experience on the volume-outcome relationship was assessed. Hierarchical logistic regression was used to adjust for patient and procedural factors. Results 57,608 PCIs performed from 2013 to 2018 by 382 operators and 63 institutions were analyzed. Operator annualized PCI volume averaged 47.6 (standard deviation [SD] 49.1) and site annualized volume averaged 189.2 (SD 105.2). Median operator experience was 9.0 years (interquartile range [IQR] 4.0–15.0). There was no independent relationship between operator annual volume, institutional volume, or operator lifetime experience with 30-day mortality (p > 0.10). However, the interaction between operator volume and lifetime experience was associated with a marginal decrease in mortality (odds ratio [OR] 0.9998, 95% CI 0.9996–0.9999). Conclusions There were no significant associations between facility or operator-level procedural volume and 30-day mortality following PCI in a nationally integrated healthcare system. There was a marginal association between the interaction of operator lifetime experience, operator annual volume, and 30-day mortality that is unlikely to be clinically relevant, though does suggest an opportunity to explore novel factors that may influence the volume-outcome relationship.

Purpose To determine the prevalence of physician burnout among ophthalmologists in the United States and identify associated risks. Design Cross-sectional study. Setting All practice types within the United States. Methods A survey was distributed via email list-serves to several national ophthalmology societies. Participants completed a modified Mini Z Burnout Survey, a 10-item questionnaire measured in 5-point Likert scales followed by demographic questions. The Mini Z Burnout survey assessed 3 main outcomes: stress, burnout, and work satisfaction. The percentage of subgroups experiencing burnout are presented and comparisons were made with odds ratios from logistic regression modeling. Results Of the 592 ophthalmologists responding to the survey, 37.8% (224) self-reported symptoms of burnout with a low of 30.8% (12/39) for vitreo-retinal specialists to a high of 45.4% (30/66) for uveitis specialists. A majority of those reporting burnout were categorized as mild (65.2%, 146/224), followed by moderate (29.5%, 66/224), and severe (5.4%, 12/224). Females had almost twice the odds of reporting burnout (OR = 1.9 (95% CI: 1.3-2.7); p=0.0005). Physicians employed in academic (OR = 2.0 (95% CI: 1.2-3.2); p=0.007) and hospital facilities (OR = 2.4 (95% CI: 1.3-4.6); p=0.008) reported higher rates of burnout compared to those in large private groups. Burnout was associated with self-reported low work control, insufficient time for documentation, and misalignment with departmental leaders (p Conclusion Ophthalmologists exhibit a high degree of self-reported burnout in the United States. This study highlights gender, employment autonomy, and practice type as major factors associated with burnout.

Made available in DSpace on 2022-04-28T19:46:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-09 Background and ObjectivesPeople with multiple sclerosis MS are a vulnerable group for severe coronavirus disease 2019 COVID-19, particularly those taking immunosuppressive disease-modifying therapies DMTs. We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data sources in 28 countries were aggregated sources could include patients from 1-12 countries. Demographic age, sex, clinical MS phenotype, disability, and DMT untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit ICU admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale EDSS score.ResultsSix hundred fifty-seven 28.1% with suspected and 1,683 61.9% with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02 and ICU admission aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89, although only rituximab was associated with higher risk of artificial ventilation aOR 4.00, 95% CI 1.54-10.39. Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07 and ICU admission aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23, but only rituximab was associated with artificial ventilation aOR 6.15, 95% CI 3.09-12.27. Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92 and ICU admission aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91, but only rituximab was associated with ventilation aOR 5.52, 95% CI 1.71-17.84. Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.DiscussionUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19. CORe Department of Medicine and Neuroepidemiology Unit Melbourne School of Population and Global Health Menzies Institute for Medical Research University of Tasmania ESAT-STADIUS KU Leuven Department of Neurology Melbourne MS Centre Royal Melbourne Hospital MS International Federation Department of Clinical Neuroscience Swedish MS Registry Department of Neurology CHU Pontchaillou Karolinska Institutet Biomedical Research Institute-Data Science Institute Hasselt University Department of Medical Informatics University Medical Center Department of Computer Science and AI KU Leuven QMENTA Medpace Reference Laboratories Molecular Unit IConquerMS People-Powered Research Network Accelerated Cure Project for MS NeuroTransData Study Group NeuroTransData German MS-Register by the National MS Society MS Forschungs- und Projektentwicklungs-gGmbH MS Register Swansea University COViMS Division of Biostatistics Washington University in St. Louis Mellen Center for Multiple Sclerosis Cleveland Clinic Department of Neuroscience Central Clinical School Monash University Al-Amiri Hospital Kuwait City Dokuz Eylul University Neurology Department Hospital Universitario de CEMIC RELACOEM Australian MS Longitudinal Study Menzies Institute for Medical Research University of Tasmania Bulgarian SmartMS COVID-19 Dataset ABEM-Brazilian MS Patients Association Danish Multiple Sclerosis Registry Department of Neurology University Hospital Rigshospitalet Universidade Estadual Paulista Unesp Faculdade de Medicina REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders Irmandade da Santa Casa de Misericórdia de São Paulo Multiple Sclerosis University Center Ramos Mejia Hospital-EMA Imperial College Swansea University Mental Health Area MS and Demyelinating Diseases Hospital Británico de Buenos Aires EMA Servei de Neurologia-Neuroimmunologia Centre d'Esclerosi Múltiple de Catalunya Cemcat Vall d'Hebron Institut de Recerca Vall d'Hebron Hospital Universitari Universitat Autònoma de Barcelona Institute of Experimental Neurology Ospedale San Raffaele Universidade Estadual Paulista Unesp Faculdade de Medicina

Background Bariatric surgery can influence the presentation, diagnosis, and management of gastrointestinal cancers. Oesophago-Gastric (OG) malignancies in patients who have had a prior bariatric procedure have not been fully characterised. Objective To characterise OG malignancies after bariatric procedures. Setting University Hospital, United Kingdom. Methods We performed a retrospective, multi-centre observational study of patients with OG malignancies after bariatric surgery to characterise this condition. Results This study includes 170 patients from 75 centres in 25 countries who underwent bariatric procedures between 1985 and 2020. At the time of the bariatric procedure, the mean age was 50.2 ± 10 years and the mean weight 128.8 ± 28.9 kg. Females comprised 57.3% (n=98) of the population. Most (n=64) patients underwent a Roux-en-Y Gastric Bypass (RYGB) followed by Adjustable Gastric Band (AGB) (n = 46) and Sleeve Gastrectomy (SG) (n = 43). Time to cancer diagnosis after bariatric surgery was 9.5 ± 7.4 years and mean weight at diagnosis was 87.4 ± 21.9 kg. The time lag was 5.9 ± 4.1 years after SG compared to 9.4 ± 7.1 years after RYGB and 10.5 ± 5.7 years after AGB. One-third of patients presented with metastatic disease. The majority of tumours were adenocarcinoma (82.9%). Approximately 1 in 5 patients underwent palliative treatment from the outset. Time from diagnosis to mortality was under one year for most patients who died over the intervening period. Conclusions The OGMOS (Oesophago-Gastric Malignancies after Obesity/ Bariatric Surgery) study presents the largest series to date of patients developing OG malignancies after bariatric surgery and attempts to characterise this condition.

Objective To determine if there is an association between patient race and physician time spent with the patient during outpatient urology consultations. Methods We identified all adult urology new outpatient visits in the National Ambulatory Medical Care Survey dataset for 2012-2016. Patient race was dichotomized as White or non-White. Our primary outcome was time spent during the visit between the patient and urologist. Using population-level weighting, we compared differences in mean time spent during visits with White and non-White patients. Mixed-effects linear regression was used to adjust for confounding factors and to account for clustering among individual physicians. Secondary outcomes included number of services provided and if ancillary providers were seen. Results Over the 5 year period, 1668 raw visits met criteria and were used to estimate 21million new outpatient urology visits nationwide. 80% of all visits were with White patients. Mean physician time spent among visits with white patients was 23.9 minutes and 24.4 minutes for non-White patients. There was no difference in number of services provided but visits with non-white patients were less likely to include an ancillary provider. After adjustment, there was no significant difference in mean time spent with the urologist among visits with White and non-White patients (difference 0.9 minutes, 95% CI: -0.6-2.4). There were also no differences in adjusted mean time spent among return visits or new visits for hematuria, urologic cancers, or BPH. Conclusion We found no statistically significant difference in time spent with a urologist during outpatient office consultations between White and non-White patients.

Purpose Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the most common primary malignant tumors of childhood. Intraoperative indocyanine green (ICG) administration with near-infrared imaging (NIR) has emerged as a surgical technology that can be used to assist with localization of pulmonary metastases secondary to HB; however, there has been limited application as an adjunct for resection of the primary liver tumor and assessment of extrahepatic disease. Methods We present 14 patients treated for HB, HCC, and malignant rhabdoid tumor at our institution with the use of intraoperative NIR-ICG guidance. All patients were treated with 0.2–0.75 mg/kg IV ICG, 48–96 h prior to surgery. Intraoperative NIR-ICG guided imaging was performed with several commercial devices. Results Intraoperative NIR-ICG guidance allowed pulmonary metastasectomy in five patients using thoracoscopy or thoracotomy allowing for visualization of multiple nodules not seen on preoperative imaging most of which were positive for malignancy. NIR-ICG guidance allowed for assessment of extrahepatic extension in three patients; an HCC patient with extrahepatic lymph node extension of disease, an HB patient with extrapulmonary thoracic recurrence in the diaphragm and chest wall, and a patient with tumor rupture at diagnosis with peritoneal nodules at the time of surgery. This technique was used to guide partial hepatectomy in 11 patients for which the technique enabled successful identification of tumor and tumor margins. Three patients had nonspecific staining of the liver secondary to decreased timing from ICG injection to surgery or biliary obstruction. NIR-ICG enabled resection of satellite HB lesions in three multifocal patients and confirmed a benign satellite lesion in two additional patients. Conclusions Intraoperative use of NIR-ICG imaging during partial hepatectomy enabled enhanced identification and guidance for surgical resection of extrahepatic disease and multifocal liver tumors for the treatment of children with primary liver cancer.

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018–2020) and post-AC (2020–2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96–74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15–0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

Children with vesicoureteral reflux (VUR) are at an increased risk of recurrent urinary tract infections (UTIs) and renal scarring. Gut microbiota are associated with disease phenotypes, but there has been no study that associates urinary microbiota (uMB) and metabolic profiles with VUR pathology. To identify dominant uMB genera and metabolites associated with UTIs in VUR, urine samples collected under sterile conditions underwent 16S ribosomal RNA sequencing (n = 49) and metabolomic analysis by mass spectrometry (n = 96). Alterations in uMB and metabolomic profiles in VUR patients suggest remodeling of urinary bacterial communities after UTIs: Dorea- and Escherichia-dominant uMB profiles were more frequently identified in participants with VUR. Prevotella- and Lactobacillus-dominant uMB profiles were more prevalent in controls (p 0.001). Microbial composition varied based on recurrent febrile UTI status (p = 0.001). A total of 243 urinary metabolites involved in energy, amino acid, nucleotide, and lipid metabolism were altered in VUR patients with UTIs (p 0.05). Importantly, VUR specimens revealed changes in the bacteria-associated metabolic pathways such as glutamate degradation, methyl-citrate cycle, and bile acid metabolism. PATIENT SUMMARY: Differences in urinary commensal bacteria and metabolites exist between children with and without vesicoureteral reflux (VUR). These changes may be utilized to identify patients at risk of VUR-associated kidney damage.

Changes in the gravitational vector by postural changes or weightlessness induce fluid shifts impacting ocular hemodynamics and regional pressures. This investigation explores the impact of changes in direction of the gravitational vector on intraocular pressure (IOP), mean arterial pressure at eyelevel (MAPeye), and ocular perfusion pressure (OPP), which is critical for ocular health. Thirteen subjects underwent 360° of tilt (including both prone and supine positions) at 15o increments. At each angle, steady-state IOP and MAPeye were measured and OPP calculated as MAPeye-IOP. Experimental data were compared to a 6-compartment lumped parameter model of the eye. Mean IOP, MAPeye, and OPP significantly increased from 0o supine to 90o head down tilt (HDT) by 20.7±1.7 mmHg (ᵅD; < 0.001), 38.5±4.1 mmHg (ᵅD; < 0.001), and 17.4±3.2 mmHg (ᵅD

Background Over the last decade, preoperative anemia has become recognized as a clinical condition in need of management. Although the etiology of preoperative anemia can be multifactorial, two-thirds of anemic elective surgical patients have iron deficiency anemia. At the same time, one-third of non-anemic elective surgical patients are also iron deficient. Methods Modified-RAND Delphi methodology was employed to identify areas of consensus among an expert panel regarding the management of iron deficiency in patients undergoing cardiac surgery. A list of statements was sent to panel members to respond to using a five-point Likert Scale. All panel members subsequently attended a face-to-face meeting. The initial survey was presented and discussed, and panel members responded to each statement on the Likert scale again. Based on the second survey, the panel came to a consensus on recommendations. Results The panel recommended all patients undergoing cardiac surgery be evaluated for iron deficiency, whether or not anemia is present. Evaluation should include iron studies and reticulocyte hemoglobin content. If iron deficiency is present, with or without anemia, patients should receive parenteral iron. Erythropoietin stimulating agents may be appropriate for some patients. Conclusions Consensus of an expert panel resulted in a standardized approach to diagnosing and managing iron deficiency in patients undergoing cardiac surgery.

Scapulothoracic dissociation is a rare and devastating injury that is considered an orthopedic emergency. It is critical to recognize this injury early based on mechanism, physical examination, and radiographic parameters. Initial management should be focused on resuscitation and evaluation for potential limb-threatening ischemia.

Background Recent suggestions of therapeutic inequivalence of brand and generic sertraline have raised concerns about disproportionately higher adverse events among generic users. Objective To assess the impact of confounding in a comparison of the risks of worsening depression and intentional self-harm (ISH) between users of brand name sertraline and its pharmaceutically equivalent authorized generic (AG). Methods Using a retrospective new-user cohort design, we identified patients with a diagnosis code for depression aged ≥12 years who were continuously enrolled in a Sentinel Data Partner health plan for ≥180 days before their first sertraline dispensing between June 30, 2006 and September 30, 2015. New use was defined as no evidence of sertraline dispensing in the 180 days before index date. We matched each brand name user to up to 10 AG users using propensity scores (PS) and conducted case-centered logistic regression to assess the risks of hospitalized depression and ISH. Results Before PS matching, brand name users were significantly less likely to be hospitalized for depression [Hazard Ratio (HR) = 0.70 (95% confidence interval (CI): 0.53-0.94)]. However, in the matched analysis, we observed no statistical difference between brand and AG users [HR = 0.84 (95% CI: 0.59-1.21)]. The risk of ISH did not significantly differ between the exposure groups in unmatched (HR = 0.99 (95% CI: 0.60-1.62) and matched analyses [HR = 0.91 (95% CI: 0.49-1.70). Conclusion In depressed patients receiving brand versus AG sertraline, patient characteristics confounded the association with hospitalization. Baseline differences were ameliorated by PS matching resulting in no statistical difference between brand and AG sertraline users.

ObjectiveAlcohol misuse is present in over a quarter of trauma patients. Information in the clinical notes of the electronic health record of trauma patients may be used for phenotyping tasks with natural language processing (NLP) and supervised machine learning. The objective of this study is to train and validate an NLP classifier for identifying patients with alcohol misuse.Materials and MethodsAn observational cohort of 1422 adult patients admitted to a trauma center between April 2013 and November 2016. Linguistic processing of clinical notes was performed using the clinical Text Analysis and Knowledge Extraction System. The primary analysis was the binary classification of alcohol misuse. The Alcohol Use Disorders Identification Test served as the reference standard.ResultsThe data corpus comprised 91 045 electronic health record notes and 16 091 features. In the final machine learning classifier, 16 features were selected from the first 24 hours of notes for identifying alcohol misuse. The classifier’s performance in the validation cohort had an area under the receiver-operating characteristic curve of 0.78 (95% confidence interval [CI], 0.72 to 0.85). Sensitivity and specificity were at 56.0% (95% CI, 44.1% to 68.0%) and 88.9% (95% CI, 84.4% to 92.8%). The Hosmer-Lemeshow goodness-of-fit test demonstrates the classifier fits the data well (P = .17). A simpler rule-based keyword approach had a decrease in sensitivity when compared with the NLP classifier from 56.0% to 18.2%.ConclusionsThe NLP classifier has adequate predictive validity for identifying alcohol misuse in trauma centers. External validation is needed before its application to augment screening.

The association between tobacco use and urothelial cancer of the bladder is well known. Given the worsening tobacco epidemic, here we make the case for systematic targeted points of intervention for urologists and other professionals to intervene against bladder cancer. Awareness of contemporary checkpoints where we can intervene for counseling patients may help medical education in a tobacco-pandemic difficult setting.

Aim: Postoperative delirium (POD) is associated with increased morbidity and is poorly understood. The aim of this review was to identify putative mechanisms through re-analysis of randomized trials on treatment or prevention of POD. Materials & methods: A systematic review was performed to identify systematic reviews of treatments for POD. Constituent randomized controlled trials were identified, and interventions were grouped according to hypothesized mechanisms of action. Effects were meta-analyzed by hypothesized mechanism and timing of intervention. Results: A total of 116 randomized controlled trials described 47 individual interventions for POD, with nine mechanisms identified. The largest effects were observed for postoperative inflammation reduction, and preoperative reinforcement of sleep–wake cycle. Conclusion: This approach identifies treatments focused on mechanisms of action that may be front runners for future trials and interventions.

Increased electrification of aircraft power systems has been widely presented as a route toward meeting environmental and emissions targets for aircraft performance, via more-electric aircraft and future hybrid-electric aircraft concepts. In parallel, the superior mechanical performance of carbon fiber reinforced polymer (CFRP) has resulted in its increasing use for aircraft structures. The relatively low electrical conductivity of CFRP compared to traditional aluminum structures and copper conductors limits the use of structural CFRP structures as electrical elements, so separate systems are needed. This adds structural mass and volume to a system, negating some of the benefits of using CFRP. Closer integration of the composite structure and electrical power system (EPS), with an ultimate goal of achieving components with multifunctionality (combined thermal, electrical, and structural functionality), offers a route toward the light-weighting of these systems, thus supporting improvements in aircraft performance. This article presents a roadmap to achieve this multifunctionality, supported by the combination of introducing definitions for different levels of multifunctionality, associated design thresholds, and trades between the EPS and CFRP materials/structures. Existing multifunctional (MF) electrical-thermal-structural CFRP-based solutions are contextualized within this roadmap. This enables the realization of viable routes for developing MF systems for the strategic focus of future research efforts.

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.

The development process of antisense oligonucleotides (ASOs) as therapeutic agents in humans has advanced through the implementation of chemical compound modifications as well as increasingly sophisticated toxicological preclinical screening techniques. The Ionis Integrated Safety Database was utilized to determine if advances in ASO screening and clinical lead identification methods have improved the tolerability profiles of 2′-O-methoxyethyl (2′MOE)-modified ASOs as a class, relative to the first 2′MOE ASO approved for use in humans, mipomersen. Tolerability was assessed by the incidence and percentage of subcutaneous doses leading to adverse events at the injection site or flu-like reactions (FLRs), as well as by the incidence of dose discontinuations due to these events. In randomized placebo-controlled phase 1 and phase 2 trials, the incidence of each measure of tolerability was lower in the test group of 12 ASOs (713 ASO-treated subjects) compared with the reference, mipomersen (266 ASO-treated subjects); with the most marked reduction in the incidence of FLRs (0.6% vs. 9.4%). A similar reduction in the incidence of dose discontinuation due to FLRs was also observed (0.2% vs. 0.9%). When compared with mipomersen, 8 of 12 ASOs showed significant improvements in their respective mean percentage of doses leading to adverse events at the injection site, whereas 7 ASOs showed a significant improvement in mean percentage of doses leading to FLRs. These results support an overall improvement in the tolerability profile in 2′MOE ASOs that entered development after mipomersen, in parallel with advances in the drug discovery screening process as well as the gains in clinical experience during development of each ASO.

Background The World Trade Center (WTC) general responder cohort (GRC) was exposed to environmental toxins possibly associated with increased risk of developing autoimmune conditions. Objectives Two study designs were used to assess incidence and risks of autoimmune conditions in the GRC. Methods Three clinically trained professionals established the status of possible GRC cases of autoimmune disorders adhering to diagnostic criteria, supplemented, as needed, by specialists' review of consenting responders' medical records. Nested case-control analyses using conditional logistic regression estimated the risk associated with high WTC exposure (being in the 9/11/2001 dust cloud or ≥median days' response worked) compared with low WTC exposure (all other GRC members'). Four controls were matched to each case on age at case diagnosis (±2 years), sex, race/ethnicity, and year of program enrollment. Sex-specific and sensitivity analyses were performed. GRC age- and sex-adjusted standardized incidence ratios (SIRs) were compared with the Rochester Epidemiology Project (REP). Complete REP inpatient and outpatient medical records were reviewed by specialists. Conditions meeting standardized criteria on ≥2 visits were classified as REP confirmed cases. Results Six hundred and twenty-eight responders were diagnosed with autoimmune conditions between 2002 and 2017. In the nested case-control analyses, high WTC exposure was not associated with autoimmune domains and conditions (rheumatologic domain odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.77, 1.37; rheumatoid arthritis OR = 1.12, 95% CI = 0.70, 1.77). GRC members had lower SIR than REP. Women's risks were generally greater than men's. Conclusions The study found no statistically significant increased risk of autoimmune conditions with WTC exposures.

Numerous studies in hepatocellular carcinoma (HCC) have proposed tissue-based gene signatures for individualized prognostic assessments. Here, we develop a novel circulating tumor cell (CTC)–based transcriptomic profiling assay to translate tissue-based messenger RNA (mRNA) signatures into a liquid biopsy setting for noninvasive HCC prognostication. The HCC-CTC mRNA scoring system combines the NanoVelcro CTC Assay for enriching HCC CTCs and the NanoString nCounter platform for quantifying the HCC-CTC Risk Score (RS) panel in enriched HCC CTCs. The prognostic role of the HCC-CTC RS was assessed in The Cancer Genome Atlas (TCGA) HCC cohort (n = 362) and validated in an independent clinical CTC cohort (n = 40). The HCC-CTC RS panel was developed through our integrated data analysis framework of 8 HCC tissue-based gene signatures and identified the top 10 prognostic genes (discoidin domain receptor tyrosine kinase 1 [DDR1], enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase [EHHADH], androgen receptor [AR], lumican [LUM], hydroxysteroid 17-beta dehydrogenase 6[HSD17B6], prostate transmembrane protein, androgen induced 1 [PMEPA1], tsukushi, small leucine rich proteoglycan [TSKU], N-terminal EF-hand calcium binding protein 2 [NECAB2], ladinin 1 [LAD1], solute carrier family 27 member 5 [SLC27A5]) highly expressed in HCC with low expressions in white blood cells. The panel accurately discriminated overall survival in TCGA HCC cohort (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.4-2.9). The combined use of the scoring system and HCC-CTC RS panel successfully distinguished artificial blood samples spiked with an aggressive HCC cell type, SNU-387, from those spiked with PLC/PRF/5 cells (P = 0.02). In the CTC validation cohort (n = 40), HCC-CTC RS remained an independent predictor of survival (HR, 5.7; 95% CI, 1.5-21.3; P = 0.009) after controlling for Model for End-Stage Liver Disease score, Barcelona Clinic Liver Cancer stage, and CTC enumeration count. Our study demonstrates a novel interdisciplinary approach to translate tissue-based gene signatures into a liquid biopsy setting. This noninvasive approach will allow real-time disease profiling and dynamic prognostication of HCC.

In recent years, there have been many high-profile attacks on large, relatively unprotected venues, including entertainment and shopping complexes in the U.S. and around the world. Public and private decision-makers can choose from a wide array of terrorism countermeasures. A question arises as to whether patrons’ complaints about delays, inconvenience and invasion of privacy actually translate into decisions to attend fewer such events. This paper presents the bottom-line economic impacts of terrorism countermeasures on business revenue at three public assembly venues and on their surrounding regional economic activity. These venues include an MLB Stadium, an NBA/NHL Arena, and a Convention Center. The analysis is based primarily on survey responses relating to changes in attendance that stem from public perception of the implementation of four major types of countermeasures. The surveys indicated that the majority of patrons were not affected either way by the presence of the countermeasures, but nearly all of the remainder felt more secure in the presence of the countermeasures to both terrorism and ordinary crime, which resulted in an increased likelihood of attendance. The economic impact estimates yield a small but notable positive impact on business revenues, though this outcome varies significantly across venue types.

Background and ObjectivesTo examine associations between indicators of estrogen exposure from women's reproductive history and brain MRI biomarkers of Alzheimer disease (AD) in midlife.MethodsWe evaluated 99 cognitively normal women 52 ± 6 years of age and 29 men 52 ± 7 years of age with reproductive history data, neuropsychological testing, and volumetric MRI scans. We used multiple regressions to examine associations among reproductive history indicators, voxel-wise gray matter volume (GMV), and memory and global cognition scores, adjusting for demographics and midlife health indicators. Exposure variables were menopause status, age at menarche, age at menopause, reproductive span, hysterectomy status, number of children and pregnancies, and use of menopause hormonal therapy (HT) and hormonal contraceptives (HC).ResultsAll menopausal groups exhibited lower GMV in AD-vulnerable regions compared to men, with perimenopausal and postmenopausal groups also exhibiting lower GMV in temporal cortex compared to the premenopausal group. Reproductive span, number of children and pregnancies, and use of HT and HC were positively associated with GMV, chiefly in temporal cortex, frontal cortex, and precuneus, independent of age, APOE ε4 status, and midlife health indicators. Although reproductive history indicators were not directly associated with cognitive measures, GMV in temporal regions was positively associated with memory and global cognition scores.DiscussionReproductive history events signaling more estrogen exposure such as premenopausal status, longer reproductive span, higher number of children, and use of HT and HC were associated with larger GMV in women in midlife. Further studies are needed to elucidate sex-specific biological pathways through which reproductive history influences cognitive aging and AD risk.

Background Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. We completed an initial feasibility trial of an online self-administered version of the Scleroderma Patient-centered Intervention Network Self-Management (SPIN-SELF) Program using the cohort multiple randomized controlled trial (RCT) design. Due to low intervention offer uptake, we will conduct a new feasibility trial with progression to full-scale trial, using a two-arm parallel, partially nested RCT design. The SPIN-SELF Program has also been revised to include facilitator-led videoconference group sessions in addition to online material. We will test the group-based intervention delivery format, then evaluate the effect of the SPIN-SELF Program on disease management self-efficacy (primary) and patient activation, social appearance anxiety, and functional health outcomes (secondary). Methods This study is a feasibility trial with progression to full-scale RCT, pending meeting pre-defined criteria, of the SPIN-SELF Program. Participants will be recruited from the ongoing SPIN Cohort (http://www.spinsclero.com/en/cohort) and via social media and partner patient organizations. Eligible participants must have SSc and low to moderate disease management self-efficacy (Self-Efficacy for Managing Chronic Disease (SEMCD) Scale score ≤ 7.0). Participants will be randomized (1:1 allocation) to the group-based SPIN-SELF Program or usual care for 3 months. The primary outcome in the full-scale trial will be disease management self-efficacy based on SEMCD Scale scores at 3 months post-randomization. Secondary outcomes include SEMCD scores 6 months post-randomization plus patient activation, social appearance anxiety, and functional health outcomes at 3 and 6 months post-randomization. We will include 40 participants to assess feasibility. At the end of the feasibility portion, stoppage criteria will be used to determine if the trial procedures or SPIN-SELF Program need important modifications, thereby requiring a re-set for the full-scale trial. Otherwise, the full-scale RCT will proceed, and outcome data from the feasibility portion will be utilized in the full-scale trial. In the full-scale RCT, 524 participants will be recruited. Discussion The SPIN-SELF Program may improve disease management self-efficacy, patient activation, social appearance anxiety, and functional health outcomes in people with SSc. SPIN works with partner patient organizations around the world to disseminate its programs free-of-charge. Trial registration ClinicalTrials.govNCT04246528. Registered on 27 January 2020

Three patients developed severe ascending aortic aneurysm requiring surgical resection after heart transplantation. In all 3 cases, the donor aorta of the transplant remained normal in caliber, despite the development of a large aneurysm in the native upper ascending aorta. The aneurysmal disease did not cross the suture line. (Level of Difficulty: Advanced.), Central Illustration

Although much research has examined nursing and physician burnout, the advanced practice provider (APP) population has not yet been studied. The goal of the present study was to survey APPs in neurosurgery to determine whether greater emotional intelligence (EI) is protective against burnout.An 80-item survey was created that incorporated the Maslach Burnout Inventory Human Services Survey for Medical Personnel, the Trait Emotional Intelligence Questionnaire-short form, and original questions developed by us. The collective survey was distributed, administered, and collected using the web-based REDCap (Research Electronic Data Capture) platform. Statistical analyses were completed using a comparison between participants with and without burnout.A total of 106 neurosurgical APPs (26 men, 80 women) completed the survey, of whom, 57 (54%) reported current burnout. High average scores for personal accomplishment and global EI were inversely related to burnout (P = 0.034 and P = 0.003, respectively). In addition, the following factors were associated with burnout: inadequate support staff in the work place (P = 0.008), inadequate time off work (P0.001), inadequate administrative time (P = 0.009), not experiencing support from one's supervisor (P = 0.017), insufficient time for continuing medical education (P0.001), an inability to separate work from personal time (P0.001), and an inability to advance within one's professional field (P = 0.043).For neurosurgical APPs, EI is protective against burnout. Many opportunities exist at the individual and organizational level to alleviate burnout among neurosurgical APPs. Targeted strategies to improve work-life balance, EI, support systems, and opportunities for career development among neurosurgical APPs might enhance employment satisfaction and reduce burnout.

Background Radial head arthroplasty is the preferred surgical management for complex, unreconstructable radial head fractures. There has been increasing use of pyrocarbon prostheses, with potential tribology and modulus advantages over metallic counterparts. This study aims to assess clinical and radiological outcomes for radial head replacement after trauma using a modular, uncemented pyrocarbon prosthesis. Materials and Methods Between September 2009 and March 2020, a consecutive series of 22 trauma cases were available for review. Patients underwent radial head arthroplasty using a pyrocarbon prosthesis (Ascension Modular Radial Head System, Austin, TX). Recorded outcomes included clinical assessment, radiological evaluation, and patient-reported outcome measures specific to elbow function. Results Twenty-two patients (7 male, 15 female) with an average age of 51 years (range 21-64) were analyzed with a minimum 12 months of follow-up. All patients had complex radial head fractures, categorized as a Mason 3 or 4 injury. At follow-up, mean elbow range of motion included flexion 130° (range 100°-150°), extension 19° (0-50°), pronation 73° (30°-90°), and supination 70° (10°-90°). The mean Mayo Elbow Performance Index score was 83 (55-100), and Disabilities of the Arm, Shoulder and Hand score was 22 (2.5-60). Radiological evaluation showed 14 patients with asymptomatic proximal neck resorption and two patients with radiological stem loosening. In total, 3 of 22 implants were revised—2 were excised, and 1 revised to a long stem for traumatic implant fracture. Conclusion Pyrocarbon radial head arthroplasty provided reliable functional results for patients after unreconstructable radial head fracture. The unique potential for fracture of the prosthesis should be considered in long-term follow-up, with appropriate activity advice to patients.

Studies have reported an association between prevalent cardiovascular disease (CVD) and risk of diabetes mellitus (DM). However, factors that may explain the association remain unclear. We examined the association of prevalent CVD with incident DM and assessed whether weight gain and medication use may explain the association.Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visit 1 (2008-2011) and Visit 2 (2014-2017) were used to compare incidence of DM among individuals with and without self-reported CVD at Visit 1. A total of 1899 individuals with self-reported CVD were matched to controls free of self-reported CVD at Visit 1 using 1:1 propensity score matching. Covariates included in the propensity model were sociodemographic characteristics, lifestyle factors, comorbid conditions, and study site. The effect of self-reported CVD on incident DM was examined using a generalized estimating equation. The mediating effects of weight gain and use of cardiovascular medications were evaluated.Covariate distributions were similar among individuals with and without self-reported CVD. The incidence of DM among persons with self-reported CVD was 15.3% vs 12.7% among those without self-reported CVD. Compared to individuals without self-reported CVD, individuals with self-reported CVD had a 24% increased risk for incident DM (odds ratio = 1.24, 95% confidence interval = 1.01, 1.51). The association between self-reported CVD and DM was mediated by the use of beta-blockers (proportion explained = 25.4%), statins (proportion explained = 18%), and diuretics (proportion explained = 8%). We found that weight gain did not explain the observed association.Prevalent cardiovascular disease was associated with a significant increased risk of incident diabetes. The observed association was partially explained by some medications used to manage CVD.背景: 已有研究报道流行的心血管疾病(CVD)与糖尿病(DM)风险之间存在关联。然而, 可能解释这种联系的因素仍不清楚。我们分析了流行的心血管疾病与糖尿病发病的关系, 并评估了体重增加和药物使用是否可以解释这种联系。 方法: 使用西班牙裔社区健康研究/拉丁裔研究(HCHS/SOL) 2008-2011及2014-2017的数据, 比较前者中有和没有自我报告心血管疾病个体的糖尿病发病率。共有1899名自我报告心血管疾病的患者, 采用1:1倾向得分匹配的方法与无自我报告心血管疾病的对照组进行配对。倾向性模型中的协变量包括社会人口学特征, 生活方式因素, 并发症情况和研究地点。使用通用的估计方程来检验自我报告的心血管疾病对糖尿病的影响。评估体重增加和心血管药物使用的中介作用。 结果: 在有和没有自我报告的心血管疾病的个体中, 协变量分布是相似的。自报心血管病患者的糖尿病发病率为15.3%, 非自报心血管病患者的糖尿病发病率为12.7%。与没有自我报告心血管疾病的个体相比, 有自我报告心血管疾病的个体发生糖尿病的风险增加24%(优势比=1.24, 95%可信区间=1.01, 1.51)。自我报告的心血管疾病和糖尿病之间的联系是通过使用β-受体阻滞剂(解释比例=25.4%), 他汀类药物(解释比例=18%)和利尿剂(解释比例=8%)来调节的。我们发现体重增加并不能解释观察到的关联。 结论: 常见的心血管疾病与糖尿病发病风险显著增加相关。一些用于治疗心血管疾病的药物部分解释了观察到的关联。.

Background Dysregulation of histone deacetylases (HDACs) is common in cancer and is critical to the development and progression of the majority of tumors. This first-in-human Phase Ia study assessed the safety, efficacy, and pharmacokinetics (PK) of OBP-801, a cyclic depsipeptide class I HDAC inhibitor. Methods Adult patients with advanced solid tumors were treated in 3 dose cohorts (1.0 mg/m2, 2.0 mg/m2 or 2.8 mg/m2) of OBP-801 that was administered via intravenous infusion weekly. Initially, an accelerated titration design was used that was followed by a 3 + 3 dose escalation strategy. Primary objective was assessment of safety. Secondary objectives included determination of PK and objective response rate. Results Seventeen patients were enrolled, of which 8 patients were evaluable for efficacy. Drug-related ≥ Grade 3 treatment-emergent adverse events included abdominal pain, anemia, fatigue, gamma glutamyl-transferase increase, hypertriglyceridemia and vomiting. No dose-limiting toxicity was observed in the 1.0 mg/m2 cohort. The PK data showed that OBP-801 and its active metabolite OBP-801-SH exposure increased proportionally and more than proportionally, respectively. No accumulation of either agent was noticed after repeat administration. Best response was stable disease (37.5%), with one patient each in the three cohorts. Conclusion Further investigations of the OBP-801 1.0 mg/m2 dose will be needed to better understand the efficacy of the agent, either alone or in combination. Trial registration: NCT02414516 (ClinicalTrials.gov) registered on April 10, 2015.