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As the coronavirus disease 2019 (COVID-19) pandemic progresses to an endemic phase, a greater number of patients with a history of COVID-19 will undergo surgery. Major adverse cardiovascular and cerebrovascular events (MACE) are the primary contributors to postoperative morbidity and mortality; however, studies assessing the relationship between a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and postoperative MACE outcomes are limited. Here, we analyzed retrospective data from 457,804 patients within the N3C Data Enclave, the largest national, multi-institutional data set on COVID-19 in the United States. However, 7.4% of patients had a history of COVID-19 before surgery. When comorbidities, age, race, and risk of surgery were controlled, patients with preoperative COVID-19 had an increased risk for 30-day postoperative MACE. MACE risk was influenced by an interplay between COVID-19 disease severity and time between surgery and infection; in those with mild disease, MACE risk was not increased even among those undergoing surgery within 4 wk following infection. In those with moderate disease, risk for postoperative MACE was mitigated 8 wk after infection, whereas patients with severe disease continued to have elevated postoperative MACE risk even after waiting for 8 wk. Being fully vaccinated decreased the risk for postoperative MACE in both patients with no history of COVID-19 and in those with breakthrough COVID-19 infection. Together, our results suggest that a thorough assessment of the severity, vaccination status, and timing of SARS-CoV-2 infection must be a mandatory part of perioperative stratification. NEW & NOTEWORTHY With an increasing proportion of patients undergoing surgery with a prior history of COVID-19, it is crucial to understand the impact of SARS-CoV-2 infection on postoperative cardiovascular/cerebrovascular risk. Our work assesses a large, national, multi-institutional cohort of patients to highlight that COVID-19 infection increases risk for postoperative major adverse cardiovascular and cerebrovascular events (MACE). MACE risk is influenced by an interplay between disease severity and time between infection and surgery, and full vaccination reduces the risk for 30-day postoperative MACE. These results highlight the importance of stratifying time-to-surgery guidelines based on disease severity. [ABSTRACT FROM AUTHOR]

Reducing the duration of refueling outage is possible by optimizing the core design and the shuffling sequence. For both options software tools have been developed that have been applied to the three most recent cycles of the Borssele plant in the Netherlands. Applicability of the shuffling sequence optimization to boiling water reactors has been demonstrated by a comparison to a recent shuffle plan used in the Hatch plant located in the United States. Their uses have shown that both core design and shuffling sequence optimization can be exploited to reduce the time needed for reloading a core with an in-core shuffling scheme. Ex-core shuffling schemes for pressurized water reactors can still have substantial benefit from a core design using a minimized number of insert shuffles. [ABSTRACT FROM AUTHOR]

The long convergence time required to achieve high-precision position solutions with integer ambiguity resolution-enabled precise point positioning (PPP-RTK) is driven by the presence of ionospheric delays. When precise real-time ionospheric information is available and properly applied, it can strengthen the underlying model and substantially reduce the time required to achieve centimeter-level accuracy. In this study, we present and analyze the real-time PPP-RTK user performance using ionospheric corrections from multi-scale regional networks during a day with medium ionospheric disturbance. It is the goal of this contribution to measure the impact the network dimension has on the ambiguity-resolved user position through the predicted ionospheric corrections. The user-specific undifferenced ionospheric corrections are computed at the network side, along with the satellite phase biases needed for single-receiver ambiguity resolution, using the best linear unbiased predictor. Such corrections necessitate the parameterization of an estimable user receiver code bias, on which emphasis is given in this study. To this end, we process GPS dual-frequency data from four four-station evenly distributed CORS networks in the United States with varying station spacings in order to evaluate if and to what extent the ionospheric corrections from multi-scale networks can improve the user convergence times. Based on a large number of samples, our experimental results showed that sub-10 cm horizontal accuracy can be achieved almost instantaneously in the ionosphere-weighted partially-ambiguity-fixed kinematic PPP-RTK solutions based on corrections from a network with 68 km spacing. Most of the solutions (90%) were shown to require less than 6.0 min, compared to the ionosphere-float PPP solutions that needed 68.5 min. In case of sparser networks with 115, 174 and 237 km spacing, 50% of the horizontal positioning errors are shown to become less than one decimeter after 1.5, 4.0 and 7.0 min, respectively, while 90% of them require 10.5, 16.5 and 20.0 min. We also numerically demonstrated that the user's convergence times bear a linear relationship with the network density and get shorter as the density increases, for both full and partial ambiguity resolution. [ABSTRACT FROM AUTHOR]

Background: Chronic mesenteric ischemia (CMI) is the result of insufficient blood supply to the gastrointestinal tract and is caused by atherosclerotic stenosis of one or more mesenteric arteries in > 90% of cases. Revascularization therapy is indicated in patients with a diagnosis of atherosclerotic CMI to relieve symptoms and to prevent acute-on-chronic mesenteric ischemia, which is associated with high morbidity and mortality. Endovascular therapy has rapidly evolved and has replaced surgery as the first choice of treatment in CMI. Bare-metal stents (BMS) are standard care currently, although retrospective studies suggested significantly higher patency rates for covered stents (CS). The Covered stents versus Bare-metal stents in chronic atherosclerotic Gastrointestinal Ischemia (CoBaGI) trial is designed to prospectively assess the patency of CS versus BMS in patients with atherosclerotic CMI.Methods/design: The CoBaGI trial is a randomized controlled, parallel-group, patient- and investigator-blinded, superiority, multicenter trial conducted in six centers of the Dutch Mesenteric Ischemia Study group (DMIS). Eighty-four patients with a consensus diagnosis of atherosclerotic CMI are 1:1 randomized to either a balloon-expandable BMS (Palmaz Blue with rapid-exchange delivery system, Cordis Corporation, Bridgewater, NJ, USA) or a balloon-expandable CS (Advanta V12 over-the-wire, Atrium Maquet Getinge Group, Hudson, NH, USA). The primary endpoint is the primary stent-patency rate at 24 months assessed with CT angiography. Secondary endpoints are primary stent patency at 6 and 12 months and secondary patency rates, freedom from restenosis, freedom from symptom recurrence, freedom from re-intervention, quality of life according the EQ-5D-5 L and SF-36 and cost-effectiveness at 6, 12 and 24 months.Discussion: The CoBaGI trial is designed to assess the patency rates of CS versus BMS in patients treated for CMI caused by atherosclerotic mesenteric stenosis. Furthermore, the CoBaGI trial should provide insights in the quality of life of these patients before and after stenting and its cost-effectiveness. The CoBaGI trial is the first randomized controlled trial performed in CMI caused by atherosclerotic mesenteric artery stenosis.Trial Registration: ClinicalTrials.gov, ID: NCT02428582 . Registered on 29 April 2015. [ABSTRACT FROM AUTHOR]

Presents an abstract on characterization of the hydrogenase from the hyperthermophilic bacterium Thermotoga maritima from the Art of Anaerobes Conference last August 15-16, 1996 held in Athens, Georgia. Molecular mass of soluble Iron-only hydrogenase from Thermotoga maritima; How hydrogen oxidation activity was found during purification of the hydrogenase from T. maritima.

Harmonized European NSCLC incidence, treatment approach, and survival based on national tumor registries are unclear. Surgery has the potential to cure NSCLC and significantly prolong survival. This large-scale international study aimed to investigate treatment variations in Europe and the USA, as well as the determinants for its utilization. The retrospective cohort study analyzed data from six European national population-based cancer registries (Belgium, Denmark, Estonia, Germany, the Netherlands, and Slovenia) and the US SEER database from 2010–2015. The study computed cancer incidence, survival, and age-standardized proportions of the use of various therapies. Multivariable logistic regression models were used to assess associations between resection and demographic and clinical parameters. A total of 428,107 records were analyzed. Among all countries, Estonia had the highest surgical resection rate (79.3 %) and the lowest radiation rate (7.3 %) for stage I patients. The Netherlands had the highest rate of radiotherapy across all years of investigation and the lowest surgery rate between 2012 and 2015. The primary treatment for early-stage NSCLC showed significant international variation, with the USA having a decrease in surgical rates from 67.6 % to 59.5 %. Resection was less frequently performed as tumor stage increased, patients aged, other lung cancer besides adenocarcinoma was present, and when the tumor site overlapped multiple lobes. Resection rates have declined in some studied European countries and the USA and resection rates vary substantially among countries. Interpretation of current scientific lung cancer evidence and international guidelines results in wide variations in patient treatment. • Primary treatment of early stage NSCLC varies widely in Europe and the USA. • The Netherlands had the relatively highest SBRT rates and the lowest resection rates for stage I NSCLC. • The USA experienced a significant decreasing trend in Stage I surgical resections. • Higher Age/Stage and unknown histology are strongly associated with lower surgery rates. [ABSTRACT FROM AUTHOR]

The authors reflect on the issues and problems regarding injuries in the pediatric athlete in the U.S. They argue that injuries in pediatric athletes are the results of improper technique, poorly fitting protective equipment, training errors, muscle weakness and growth imbalance. They suggest that in order to reduce the risk of sports and recreation-related injuries, one must have personal countermeasures, behavioral interventions, and environmental modifications.

Abstract: Context: The first therapeutic cancer vaccine demonstrating effectiveness in a phase 3 study was approved by the US Food and Drug Administration on 29 April 2010. The pivotal trial demonstrated overall survival (OS) benefit in patients treated with antigen-loaded leukapheresis cells compared with a control infusion. Results of other prostate cancer (PCa) vaccination strategies are awaited, as this approach may herald a new era in the care for patients with advanced PCa. Objective: Consider effectiveness and safety of vaccination strategies in the treatment of PCa. Evidence acquisition: We searched three bibliographic databases (January 1995 through October 2010) for randomised phase 2 and 3 studies of vaccination strategies for PCa based on predetermined relevant Medical Subject Heading terms and free text terms. Evidence synthesis: Data from 3 randomised phase 3 and 10 randomised phase 2 vaccination trials are discussed with respect to clinical outcome in terms of progression-free survival and OS, toxicity, prostate-specific antigen (PSA) response, and immunologic response. Three phase 3 trials (D9901, D9902A, and D9902B) that enrolled a total of 737 patients, all controlled and double-blinded, tested the efficacy of sipuleucel-T. The largest of these three trials, called Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT), has demonstrated safety and effectiveness of sipuleucel-T (now marketed as Provenge) as measured by prolonged survival of 512 asymptomatic patients with metastatic castration-resistant PCa (mCRPC). The study showed a 4.1-mo median survival benefit in the sipuleucel-T vaccine-treated group compared with the control group (25.8 vs 21.7 mo; hazard ratio [HR]: 0.78; 95% confidence interval [CI], 0.62–0.98; p =0.032) and extended 3-yr survival (31.7% vs 23.0%). In contrast, two phase 3 vaccination trials with a whole-tumour-cell mixture of two PCa cell lines (GVAX) and testing GVAX either alone or in combination with chemotherapy versus chemotherapy alone (VITAL1 and 2) were terminated prematurely based on futility and increased deaths. Other phase 2 vaccination trials testing different types of vaccines in castration-resistant PCa patients have been reported with variable outcomes. Notably, a controlled, double-blind, randomised phase 2 vaccine trial of PROSTVAC-VF, a recombinant viral vector containing complementary DNA encoding PSA, in 125 patients with chemotherapy-naïve, minimally symptomatic mCRPC also demonstrated safety but no significant effect on the time to disease progression. In comparison with controls (n =40), PROSTVAC-VF-treated patients (n =82) experienced longer median survival of 8.5 mo (25.1 vs 16.6 mo; HR: 0.56; 95% CI, 0.37–0.85; p =0.0061) and extended 3-yr survival (30% vs 17%). In general, PCa vaccines are perceived to have less toxicity compared with current cytotoxic or targeted therapies. Evaluation of clinical efficacy of different vaccination strategies (eg, protein-, peptide- and DNA-based vaccines) in the context of properly designed and controlled phase 3 studies is warranted. Conclusions: Cancer vaccines represent a new paradigm in the treatment of PCa. The IMPACT trial showed improved survival but no difference in time to disease progression in mCRPC patients with minimal tumour burden. Observations in phase 2 and 3 trials pave the way for other vaccination approaches for this disease, raise questions regarding the most appropriate clinical trial designs, and underscore the importance of identifying biomarkers for antitumour effect to better implement such therapies. [Copyright &y& Elsevier]

Summary: Background: In an open-label phase 1 trial, gene delivery of the trophic factor neurturin via an adeno-associated type-2 vector (AAV2) was well tolerated and seemed to improve motor function in patients with advanced Parkinson''s disease. We aimed to assess the safety and efficacy of AAV2-neurturin in a double-blind, phase 2 randomised trial. Methods: We did a multicentre, double-blind, sham-surgery controlled trial in patients with advanced Parkinson''s disease. Patients were randomly assigned (2:1) by a central, computer generated, randomisation code to receive either AAV2-neurturin (5·4×1011 vector genomes) injected bilaterally into the putamen or sham surgery. All patients and study personnel with the exception of the neurosurgical team were masked to treatment assignment. The primary endpoint was change from baseline to 12 months in the motor subscore of the unified Parkinson''s disease rating scale in the practically-defined off state. All randomly assigned patients who had at least one assessment after baseline were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT00400634. Results: Between December, 2006, and November, 2008, 58 patients from nine sites in the USA participated in the trial. There was no significant difference in the primary endpoint in patients treated with AAV2-neurturin compared with control individuals (difference −0·31 [SE 2·63], 95% CI −5·58 to 4·97; p=0·91). Serious adverse events occurred in 13 of 38 patients treated with AAV2-neurturin and four of 20 control individuals. Three patients in the AAV2-neurturin group and two in the sham surgery group developed tumours. Interpretation: Intraputaminal AAV2-neurturin is not superior to sham surgery when assessed using the UPDRS motor score at 12 months. However, the possibility of a benefit with additional targeting of the substantia nigra and longer term follow-up should be investigated in further studies. Funding: Ceregene and Michael J Fox Foundation for Parkinson''s Research. [Copyright &y& Elsevier]

What is the best way to care for a child with severe neurologic impairment who seems to be dying and is in intractable pain? Can we give sedation as we remove life support? Is it ethically permissible to hasten death? In the United States, 5 states have legalized assisted suicide (although only for competent adults). In Belgium and the Netherlands, euthanasia is legal for children under some circumstances. We present a case in which parents and doctors face difficult decisions about palliative care. Experts from Belgium, the Netherlands, and the United States then discuss how they would respond to such a case., (Copyright © 2016 by the American Academy of Pediatrics.)

Objective: To clarify the process of end-of-life decision-making in culturally different neonatal intensive care units (NICUs)., Study Design: Review of medical files of newborns >22 weeks gestation who died in the delivery room (DR) or the NICU during 12 months in 4 NICUs (Chicago, Milwaukee, Montreal, and Groningen). We categorized deaths using a 2-by-2 matrix and determined whether mechanical ventilation was withdrawn/withheld and whether the child was dying despite ventilation or physiologically stable but extubated for neurological prognosis., Results: Most unstable patients in all units died in their parents' arms after mechanical ventilation was withdrawn. In Milwaukee, Montreal, and Groningen, 4% to 12% of patients died while receiving cardiopulmonary resuscitation. This proportion was higher in Chicago (31%). Elective extubation for quality-of-life reasons never occurred in Chicago and occurred in 19% to 35% of deaths in the other units. The proportion of DR deaths in Milwaukee, Montreal, and Groningen was 16% to 22%. No DR deaths occurred in Chicago., Conclusions: Death in the NICU occurred differently within and between countries. Distinctive end-of-life decisions can be categorized separately by using a model with uniform definitions of withholding/withdrawing mechanical ventilation correlated with the patient's physiological condition. Cross-cultural comparison of end-of-life practice is feasible and important when comparing NICU outcomes.