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Introduction: Despite high vulnerability to infection, hand disinfection compliance in emergencies is low. This is regularly justified as the disinfection procedure delays life support, and instead, wearing disposable gloves is preferred. Simulation studies showed higher achievable compliance than detected in real-life situations. This study aimed to explore healthcare providers’ attitudes toward hand disinfection and using gloves in emergencies. Methods: We conducted an anonymous online survey in Germany on the attitude and subjective behavior in the five moments of hand hygiene in a closed environment and an open convenience sampling survey. Statistics included paired student's t-tests corrected for multiple testing. For qualitative analysis, we employed a single-coder approach. Results: In 400 participants, we detected low priority of WHO-1 (before touching a patient) and WHO-2 (before clean/aseptic procedure) hand hygiene moments, despite knowing the risks of omission of hand disinfection. For all moments, self-assessment exceeded the assessment of colleagues (p < 0.001). For WHO-3, we detected a lower disinfection priority for wearing gloves compared to contaminated bare hands. Qualitative analyses revealed five themes: basic conditions, didactic implementations, cognitive load, and uncertainty about feasibility and efficacy. Discussion: Considering bias, the study's subjective nature, the unknown role of emergency-related infections contributing to hospital-acquired infections, and different experiences of healthcare providers, we conclude that hand disinfection before emergencies is de-prioritized and justified by the emergency situation regardless of the objective feasibility. Conclusion: This study reveals subjective and objective barriers to implementation of WHO-1 and WHO-2 moments of hand disinfection to be further evaluated and addressed in educational programs.

BackgroundOlder nursing home (NH) residents with glycemic overtreatment are at significant risk of hypoglycemia and other harms and may benefit from deintensification. However, little is known about deintensification practices in this setting.MethodsWe conducted a cohort study from January 1, 2013 to December 31, 2019 among Veterans Affairs (VA) NH residents. Participants were VA NH residents age ≥65 with type 2 diabetes with a NH length of stay (LOS) ≥ 30 days and an HbA1c result during their NH stay. We defined overtreatment as HbA1c

While the game design and game studies communities have analyzed combat both in specific games and game genres, and while combat is clearly central to many types of games, there is no general account of combat that is portable across diverse games. We provide such an account in the form of criteria which are satisfied by games that players inter- pret as “having combat.” These requirements are eventually fulfilled via operational logics, which tie the game’s observ- able behavior (including its instantial assets) to play expe- riences and cultural knowledge, creating what we refer to as a “combat model.” In addition to establishing a com- prehensive model of combat, making it possible to discuss combat across game genres, this work is the first to describe how complex playable models are constructed from composi- tions of operational logics working in concert; we also define two families of logics which are novel in the literature. This broad model of combat has already proved useful in practice, yielding insights in the analysis of the art game Unmanned; it also promises exciting computational applications in areas such as game design support tools and general game playing.

Dynamic contrast-enhanced (DCE) perfusion imaging has shown great potential to non-invasively assess cancer development and its treatment by their characteristic tissue signatures. Different tracer kinetics models are being applied to estimate tissue and tumor perfusion parameters from DCE perfusion imaging. The goal of this work is to provide an in silico model-based pipeline to evaluate how these DCE imaging parameters may relate to the true tissue parameters. As histology data provides detailed microstructural but not functional parameters, this work can also help to better interpret such data. To this aim in silico vasculatures are constructed and the spread of contrast agent in the tissue is simulated. As a proof of principle we show the evaluation procedure of two tracer kinetic models from in silico contrast-agent perfusion data after a bolus injection. Representative microvascular arterial and venous trees are constructed in silico. Blood flow is computed in the different vessels. Contrast-agent input in the feeding artery, intra-vascular transport, intra-extravascular exchange and diffusion within the interstitial space are modeled. From this spatiotemporal model, intensity maps are computed leading to in silico dynamic perfusion images. Various tumor vascularizations (architecture and function) are studied and show spatiotemporal contrast imaging dynamics characteristic of in vivo tumor morphotypes. The Brix II also called 2CXM, and extended Tofts tracer-kinetics models common in DCE imaging are then applied to recover perfusion parameters that are compared with the ground truth parameters of the in silico spatiotemporal models. The results show that tumor features can be well identified for a certain permeability range. The simulation results in this work indicate that taking into account space explicitly to estimate perfusion parameters may lead to significant improvements in the perfusion interpretation of the current tracer-kinetics models.

"The Stars and Stripes: The American Soldiers' Newspaper of World War I, 1918-1919" collection at the Library of Congress provides access to the newspaper distributed to military personnel during World War I. The news articles reveal what members of the American Expeditionary Force actually read about military battles and campaigns in the last year of "The Great War." This newspaper, written by servicemen for servicemen, was created to improve morale and generate unity within the American forces. It included news from the homefront, sports coverage, cartoons, and poetry. Poetry was part of "The Stars and Stripes" from its first issue. Through their poetry, soldiers commented on life in the trenches, homesickness, patriotism, and the camaraderie essential for wartime success. Reading their work more than a century later can help students understand the interests and concerns of American soldiers during wartime, and offer insights into activities that occupied soldiers' time abroad and how they responded to news from the homefront. In this article, the authors discuss how reading and analyzing poetry by World War I American soldiers can reveal a great deal about the life and observations of servicemen.

Inositol 1,4,5-trisphosphate (IP3) receptor type 1 (ITPR1), 2 (ITPR2), and 3 (ITPR3) encode the IP3 receptor (IP3R), a key player in intracellular calcium release. In four unrelated patients, we report that an identical ITPR3 de novo variant--NM_002224.3:c.7570C>T, p.Arg2524Cys--causes, through a dominant-negative effect, a complex multisystemic disorder with immunodeficiency. This leads to defective calcium homeostasis, mitochondrial malfunction, CD4+ lymphopenia, a quasi-absence of naïve CD4+ and CD8+ cells, an increase in memory cells, and a distinct TCR repertoire. The calcium defect was recapitulated in Jurkat knock-in. Site-directed mutagenesis displayed the exquisite sensitivity of Arg2524 to any amino acid change. Despite the fact that all patients had severe immunodeficiency, they also displayed variable multisystemic involvements, including ectodermal dysplasia, Charcot-Marie-Tooth disease, short stature, and bone marrow failure. In conclusion, unlike previously reported ITPR1-3 deficiencies leading to narrow, mainly neurological phenotypes, a recurrent dominant ITPR3 variant leads to a multisystemic disease, defining a unique role for IP3R3 in the tetrameric IP3R complex. [ABSTRACT FROM AUTHOR]

Moderate alcohol consumption has been associated with a lower risk of coronary artery disease (CAD) in the general population but has not been well studied in US veterans. We obtained self-reported alcohol consumption from Million Veteran Program participants. Using electronic health records, CAD events were defined as 1 inpatient or 2 outpatient diagnosis codes for CAD, or 1 code for a coronary procedure. We excluded participants with prevalent CAD (n = 69,995) or incomplete alcohol information (n = 8,449). We used a Cox proportional hazards model to estimate hazard ratios and 95% confidence intervals for CAD, adjusting for age, gender, body mass index, race, smoking, education, and exercise. Among 156,728 participants, the mean age was 65.3 years (standard deviation = 12.1) and 91% were men. There were 6,153 CAD events during a mean follow-up of 2.9 years. Adjusted hazard ratios (95% confidence intervals) for CAD were 1.00 (reference), 1.02 (0.92 to 1.13), 0.83 (0.74 to 0.93), 0.77 (0.67 to 0.87), 0.71 (0.62 to 0.81), 0.62 (0.51 to 0.76), 0.58 (0.46 to 0.74), and 0.95 (0.85 to 1.06) for categories of never drinker; former drinker; current drinkers of ≤0.5 drink/day, >0.5 to 1 drink/day, >1 to 2 drinks/day, >2 to 3 drinks/day, and >3 to 4 drinks/day; and heavy drinkers (>4 drinks/day) or alcohol use disorder, respectively. For a fixed amount of ethanol, intake at ≥3 days/week was associated with lower CAD risk compared with ≤1 day/week. Beverage preference (beer, wine, or liquor) did not influence the alcohol-CAD relation. Our data show a lower risk of CAD with light-to-moderate alcohol consumption among US veterans, and drinking frequency may provide a further reduction in risk.

While adherence to healthful dietary patterns has been associated with a lower risk of coronary artery disease (CAD) in the general population, limited data are available among US veterans. We tested the hypothesis that adherence to Dietary Approach to Stop Hypertension (DASH) food pattern is associated with a lower risk of developing CAD among veterans. We analyzed data on 153 802 participants of the Million Veteran Program enrolled between 2011 and 2016. Information on dietary habits was obtained using a food frequency questionnaire at enrollment. We used electronic health records to assess the development of CAD during follow-up. Of the 153 802 veterans who provided information on diet and were free of CAD at baseline, the mean age was 64.0 (SD=11.8) years and 90.4% were men. During a mean follow-up of 2.8 years, 5451 CAD cases occurred. The crude incidence rate of CAD was 14.0, 13.1, 12.6, 12.3, and 11.1 cases per 1000 person-years across consecutive quintiles of Dietary Approach to Stop Hypertension score. Hazard ratios (95% confidence interval) for CAD were 1.0 (ref), 0.91 (0.84-0.99), 0.87 (0.80-0.95), 0.86 (0.79-0.94), and 0.80 (0.73-0.87) from the lowest to highest quintile of Dietary Approach to Stop Hypertension score controlling for age, sex, body mass index, race, smoking, exercise, alcohol intake, and statin use (P linear trend,

Abstract Background Patients with advanced colorectal cancer (CRC) have a poor prognosis. Combinations of immunotherapies and anti-angiogenic agents are currently being evaluated in clinical trials. In this study, the multikinase inhibitor regorafenib (REG) was combined with an anti-programmed cell death protein 1 (aPD1) antibody in syngeneic murine microsatellite-stable (MSS) CT26 and hypermutated MC38 colon cancer models to gain mechanistic insights into potential drug synergism. Methods Growth and progression of orthotopic CT26 and subcutaneous MC38 colon cancers were studied under treatment with varying doses of REG and aPD1 alone or in combination. Sustained effects were studied after treatment discontinuation. Changes in the tumor microenvironment were assessed by dynamic contrast-enhanced MRI, and histological and molecular analyses. Results In both models, REG and aPD1 combination therapy significantly improved anti-tumor activity compared with single agents. However, in the CT26 model, the additive benefit of aPD1 only became apparent after treatment cessation. The combination treatment efficiently prevented tumor regrowth and completely suppressed liver metastasis, whereas the anti-tumorigenic effects of REG alone were abrogated soon after drug discontinuation. During treatment, REG significantly reduced the infiltration of immunosuppressive macrophages and regulatory T (Treg) cells into the tumor microenvironment. aPD1 significantly enhanced intratumoral IFNγ levels. The drugs synergized to induce sustained M1 polarization and durable reduction of Treg cells, which can explain the sustained tumor suppression. Conclusions This study highlights the synergistic immunomodulatory effects of REG and aPD1 combination therapy in mediating a sustained inhibition of colon cancer regrowth, strongly warranting clinical evaluation in CRC, including MSS tumors.

BackgroundThe erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation.MethodsAn individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention.ResultsThe analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization.ConclusionThe early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575.

Acetylsalicylic acid (ASA) is a well-established drug for heart attack and stroke prophylaxis. Furthermore, numerous studies have reported an anti-carcinogenic effect, but its exact mechanism is still unknown. Here, we applied VEGFR-2-targeted molecular ultrasound to explore a potential inhibitory effect of ASA on tumor angiogenesis in vivo. Daily ASA or placebo therapy was performed in a 4T1 tumor mouse model. During therapy, ultrasound scans were performed using nonspecific microbubbles (CEUS) to determine the relative intratumoral blood volume (rBV) and VEGFR-2-targeted microbubbles to assess angiogenesis. Finally, vessel density and VEGFR-2 expression were assessed histologically. CEUS indicated a decreasing rBV in both groups over time. VEGFR-2 expression increased in both groups up to Day 7. Towards Day 11, the binding of VEGFR-2-specific microbubbles further increased in controls, but significantly (p = 0.0015) decreased under ASA therapy (2.24 ± 0.46 au vs. 0.54 ± 0.55 au). Immunofluorescence showed a tendency towards lower vessel density under ASA and confirmed the result of molecular ultrasound. Molecular US demonstrated an inhibitory effect of ASA on VEGFR-2 expression accompanied by a tendency towards lower vessel density. Thus, this study suggests the inhibition of angiogenesis via VEGFR-2 downregulation as one of the anti-tumor effects of ASA.

ObjectivesOur survey aimed to characterize the practice of inducing fetal demise before pregnancy termination among abortion providers, including its technical aspects and why providers have chosen to adopt it.Study designWe conducted a survey of Family Planning Fellowship-trained or Fellowship-affiliated Family Planning (FP) subspecialists about their practice of inducing fetal demise, including questions regarding the circumstances in which they would induce demise, techniques used and rationales for choosing whether to adopt this practice.ResultsOf the 169 FP subspecialists we surveyed, 105 (62%) responded. About half (52%) of respondents indicated that they routinely induced fetal demise before terminations in the second trimester. Providers' practices varied in the gestations at which they started inducing demise as well as the techniques used. Respondents provided legal, technical and psychological reasons for their decisions to induce demise.ConclusionInducing fetal demise before second-trimester abortions is common among US FP specialists for multiple reasons. The absence of professional guidelines or robust data may contribute to the variance in the current practice patterns of inducing demise.ImplicationsOur study documents the widespread practice of inducing fetal demise before second-trimester abortion and further describes wide variation in providers' methods and rationales for inducing demise. It is important for abortion providers as a professional group to come to a formal consensus on the appropriate use of these techniques and to determine whether such practices should be encouraged, tolerated or even permitted.

ObjectiveTo evaluate the association between obesity (body mass index [BMI] 30 or higher) and dilation and evacuation (D&E) complications.MethodsWe conducted a retrospective cohort study of women who underwent D&E abortion from February 2009 to April 2013 at a hospital-based abortion practice in California. We evaluated the association between obesity and risk of complication after D&E using logistic regression. We defined complications a priori as cervical laceration, hemorrhage, uterine atony, anesthesia complications, uterine perforation, disseminated intravascular coagulation, and retained products of conception. We defined major complications as those requiring hospitalization, transfusion, or further surgical intervention.ResultsComplications occurred in 442 of 4,520 D&Es (9.8%), with equal proportions in obese and nonobese women (9.8%). Major complications occurred in 78 (1.7%) patients. After adjustment for age, ethnicity, prior vaginal delivery, prior cesarean delivery, and gestational duration, there was no association between BMI and D&E complications. Any individual complication was associated with each additional week of gestation (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.3-1.4), prior vaginal delivery (OR 1.5, 95% CI 1.2-1.9) and prior cesarean delivery (OR 1.8, 95% CI 1.4-2.3). Major complications were associated with each additional week of gestation (OR 1.3, 95% CI 1.1-1.4) and cesarean delivery (OR 1.8, 95% CI 1.1-3.1).ConclusionWe found no association between obesity and D&E complications. Our findings are consistent with previous studies demonstrating that later gestational duration is associated with an increased risk of complications. Obesity may not warrant referral to a high-risk abortion center, particularly because referral-associated delay might increase the risk of complications.Level of evidenceII.