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Background Mobile phones in hospital settings have been identified as an important source of cross-contamination because of the low frequency with which mobile phones are cleaned by health workers and cyclical contamination of the hands and face. The aim of this study was to investigate whether the mobile phones of the anesthesia team at a teaching hospital are potential reservoirs of nosocomial bacteria. In addition, differences in device sanitization and hand hygiene habits between attending and resident anesthesiologists were correlated with mobile phone colonization. Methods A prevalence study was conducted over a 6-month period from 2017 to 2018 that involved the collection of samples from the mobile phones of the anesthesiology team and culturing for surveillance. A questionnaire was administered to assess the mobile phone sanitization and hand washing routines of the anesthesia team in specific situations. Results Bacterial contamination was detected for 86 of the 128 mobile phones examined (67.2%). A greater presence of Micrococcus spp. on devices was correlated with a higher frequency of mobile phone use (p = 0.003) and a lower frequency of sanitization (p = 0.003). The presence of bacteria was increased on the mobile phones of professionals who did not perform handwashing after tracheal intubation (p = 0.003). Conclusion Hand hygiene and device sanitization habits were more important than the use behavior, as a higher presence of bacteria correlated with poorer hygiene habits. Furthermore, handwashing is the best approach to prevent serious colonization of mobile devices and the possible transmission of pathogens to patients under the care of anesthesiologists.

Purpose: Top surgery, or masculinization of the chest, is often the first and sometimes only procedure in gender-affirming surgery for transgender- and gender-diverse persons assigned female at bir...

Technological advancement has decreased network latencies while simultaneously increasing local latencies. This may impact exergames-video games that incorporate exercise-the most since exergames tend to have complicated platforms to capture player actions. This article presents a study using a custom desktop-based exergame that controls for local latency and measures player performance and quality of experience (QoE). Analysis of the results from a 37-person user study shows that while player performance and QoE degrade with latency, exergame actions are fairly tolerant of even hundreds of milliseconds of latency. Our data point toward a crucial tipping point at latency values of approximately 400 ms.

Preoperative meningioma consistency prediction is highly beneficial for surgical planning and prognostication. We aimed to use magnetic resonance fingerprinting (MRF)-derived T1 and T2 values to preoperatively predict meningioma consistency.A total of 51 patients with meningiomas were enrolled in this study. MRF, T1-weighted imaging, T2-weighted imaging, and diffusion-weighted imaging were performed in all patients before surgery using a 3T MRI scanner. MRF-derived T1 and T2 values, T1-weightd and T2-weighted signal intensities, as well as apparent diffusion coefficient value yield from diffusion-weighted imaging were compared between the soft, moderate and hard meningiomas. Receiver operating characteristic curve analyses were used to determine the diagnostic performance of T1, T2 value, and a combination of T1 and T2 values.After Bonferroni corrections, quantitative T1 and T2 values yielded from MRF were significantly different between the soft, moderate and hard meningiomas (all p0.05). T2 signal intensity was significantly different between the soft and hard, soft and moderate meningiomas (both p0.05), whereas was not significantly different between the moderate and hard meningiomas. However, T1 signal intensity and apparent diffusion coefficient value had no significant differences between the soft, moderate and hard meningiomas (all p0.05). The combination of T1 and T2 values had greater areas under receiver operating characteristic curve curves compared to individual T1 or T2 value.MRF may help to preoperatively differentiate between the soft, moderate and hard meningiomas and may be useful in guiding the surgical planning.

Retrospective performance evaluation of a computer-aided detection (CAD) system on standard posteroanterior (PA) chest radiographs (PA-CXR) in detection of pulmonary nodules, infectious consolidation, pneumothorax, pleural effusion, aortic calcification, cardiomegaly and rib fractures compared to radiologists analyzing PA-CXR including dual-energy subtraction radiography (further termed as DESR).PA-CXR/DESR images of 197 patients were included. All patients underwent chest CT (gold standard) within a short interval (mean 28 hours). All images were evaluated by three blinded readers for the presence of pulmonary nodules, infectious consolidation, pneumothorax, pleural effusion, aortic calcification, cardiomegaly, and rib fractures. Meanwhile PA-CXR were analyzed by a CAD software. CAD results were compared to the majority result of the three readers. Sensitivity and specificity were calculated. McNemar's test was applied to test for significant differences. Interobserver agreement was defined using Cohen's kappa (κ).Sensitivity of the CAD software was significantly higher (p0.05) for detection of infectious consolidation and pulmonary nodules (67.9% vs 26.8% and 54% vs 35.6%, respectively; p0.001) compared to radiologists analyzing DESR images. For the residual evaluated pathologies no statistical significant differences could be found. Overall, mean inter observer agreement between the three radiologists was moderate (k = 0.534). The best interobserver agreement could be reached for pneumothorax (k = 0.708) and pleural effusion (k = 0.699), while the worst was obtained for rib fractures (k = 0.412).The CAD system has the potential to improve the detection of infectious consolidation and pulmonary nodules on CXR images.

Head-mounted loupes can increase the user's visual acuity to observe the details of an object. On the other hand, optical see-through head-mounted displays (OST-HMD) are able to provide virtual augmentations registered with real objects. In this article, we propose AR-Loupe, combining the advantages of loupes and OST-HMDs, to offer augmented reality in the user's magnified field-of-vision. Specifically, AR-Loupe integrates a commercial OST-HMD, Magic Leap One, and binocular Galilean magnifying loupes, with customized 3D-printed attachments. We model the combination of user's eye, screen of OST-HMD, and the optical loupe as a pinhole camera. The calibration of AR-Loupe involves interactive view segmentation and an adapted version of stereo single point active alignment method (Stereo-SPAAM). We conducted a two-phase multi-user study to evaluate AR-Loupe. The users were able to achieve sub-millimeter accuracy ( 0.82 mm) on average, which is significantly ( ) smaller compared to normal AR guidance ( 1.49 mm). The mean calibration time was 268.46 s. With the increased size of real objects through optical magnification and the registered augmentation, AR-Loupe can aid users in high-precision tasks with better visual acuity and higher accuracy.

Deep latent generative models have attracted increasing attention due to the capacity of combining the strengths of deep learning and probabilistic models in an elegant way. The data representations learned with the models are often continuous and dense. However in many applications, sparse representations are expected, such as learning sparse high dimensional embedding of data in an unsupervised setting, and learning multi-labels from thousands of candidate tags in a supervised setting. In some scenarios, there could be further restriction on degree of sparsity: the number of non-zero features of a representation cannot be larger than a pre-defined threshold $L_{0}$ . In this paper we propose a sparse deep latent generative model SDLGM to explicitly model degree of sparsity and thus enable to learn the sparse structure of the data with the quantified sparsity constraint. The resulting sparsity of a representation is not fixed, but fits to the observation itself under the pre-defined restriction. In particular, we introduce to each observation $i$ an auxiliary random variable $L_{i}$ , which models the sparsity of its representation. The sparse representations are then generated with a two-step sampling process via two Gumbel-Softmax distributions. For inference and learning, we develop an amortized variational method based on MC gradient estimator. The resulting sparse representations are differentiable with backpropagation. The experimental evaluation on multiple datasets for unsupervised and supervised learning problems shows the benefits of the proposed method.

We consider a simple long short-term memory (LSTM) neural network extension of the Poisson Lee-Carter model, with a particular focus on different procedures for how to use training data efficiently, combined with ensembling to stabilise the predictive performance. We compare the standard approach of withholding the last fraction of observations for validation, with two other approaches: sampling a fraction of observations randomly in time; and splitting the population into two parts by sampling individual life histories. We provide empirical and theoretical support for using these alternative approaches. Furthermore, to improve the stability of long-term predictions, we consider boosted versions of the Poisson Lee-Carter LSTM. In the numerical illustrations it is seen that even in situations where mortality rates are essentially log-linear as a function of calendar time, the boosted model does not perform significantly worse than a simple random walk with drift, and when non-linearities are present the predictive performance is improved. Moreover, boosting allows us to obtain reasonable model calibrations based on as few data points as 20 years.

Specialty palliative care (PC) clinicians are frequently asked to discuss prognosis with patients and their families. When conveying information about prognosis, PC clinicians need also to discuss the likelihood of prolonged hospitalization, cognitive and functional disabilities, and death. As PC moves further and further upstream, it is crucial that PC providers have a broad understanding of curative and palliative treatments for serious diseases and can collaborate in prognostication with specialists. In this article, we present 10 tips for PC clinicians to consider when caring and discussing prognosis for the seriously ill patients along with their caregivers and care teams. This is the second in a three-part series around prognostication in adult and pediatric PC.

Background Dynamic myocardial CT perfusion (CTP) has emerged as a potential strategy to combine anatomical and functional evaluation in a single modality. However, this method results in a high radiation dose. Methods Dynamic CTP was performed in 56 patients with suspected or known ischemic heart disease of whom 48 had complete CT-data. Datasets with reduced sampling rate of 2- and 3 RR-intervals (2RR and 3RR) were constructed post hoc. Myocardial blood flow (MBF) estimates from the 2RR and 3RR datasets were compared with estimates based on the full dataset (1RR) using the two one-sided test of equivalence for paired samples. Results Significant equivalence was found for rest MBFLV (p ​ Conclusion MBF can be quantitated with dynamic CTP using a sampling strategy of one volume for every second heartbeat. This strategy could lead to a significant reduction in radiation dose.

Many drugs interact with ion channels in the cells of the heart and trigger heart rhythm disorders with potentially fatal consequences. Computational modeling can provide mechanistic insight into the onset and propagation of drug-induced arrhythmias, but the effect of drugs on the mechanical behavior of the heart remains poorly understood. Here we establish a multiphysics framework that integrates the biochemical, electrical, and mechanical effects of drugs from single cardiac cells to the overall response of the whole heart. For the example of the drug dofetilide, we show that drug concentrations of 3.0x and 4.8x increase the heart rate to 122 and 114 beats per minute, increase the myofiber stretches up to 10%, and decrease tissue relaxation by 6%. Strikingly, the drug-induced interventricular and atrial-ventricular dyssynchrony results in a 2.5% decreased and 7% increased cardiac output, respectively. Our results demonstrate the potential for multiphysics, multiscale modeling towards understanding the mechanical implications of drug-induced arrhythmias. Knowing how differing drug concentrations affect the performance of the heart has important clinical implications in drug safety evaluation and personalized medicine.

Summery Background Breast augmentation is one of the most frequently performed cosmetic surgeries worldwide. Some of the most severe short-term complications after breast augmentation are hematoma and deep surgical site infection. However, these complications are relatively rare; therefore, large patient populations are required to perform statistical analyses. In this study, we provide a detailed analysis of the complications after primary breast augmentation with an emphasis on deep surgical site infection and hematoma. Method We retrospectively reviewed the medical records of women who underwent primary breast augmentation performed without the use of pocket irrigation between 2012 and 2019 in a single private clinic. A cumulative hazard function and a multivariate analysis on the risk of hematoma were performed. Results We included 1128 patients in the study. Thirty patients (2.7%) developed postoperative hematoma after a median time of 14 hours (IQR 5 hours-9 days). Six patients (0.5%) contracted a deep surgical site infection after a median time of 14 days (range 4-41 days). Neither age, BMI, implant volume or implant placement were significantly associated with hematoma. Conclusion Our findings support that the risk of hematoma after primary breast augmentation is highest within the first 24 hours after the surgery. This time period should be considered when planning postoperative care for these patients. We did not find an increased rate of deep surgical site infection compared with studies of breast augmentations with pocket irrigation. Further studies and meta-analyses are needed to explore the effect of pocket irrigation and other risk factors.

Numerous new emerging therapies, including oral targeted chemotherapies, have recently entered the therapeutic arsenal against acute myeloid leukemia (AML). The significant shift toward the use of these novel therapeutics, administered either alone or in combination with intensive or low-intensity chemotherapy, changes the prospects for the control of this disease, especially for elderly patients. Glasdegib, an oral Hedgehog pathway inhibitor, showed satisfactory response rates associated with moderate toxicity and less early mortality than standard induction regimens in this population. It was approved in November 2018 by the FDA and in June 2020 by the EMA for use in combination with low-dose cytarabine as a treatment of newly-diagnosed AML in patients aged ≥ 75 and/or unfit for intensive induction chemotherapy. The current paper proposes an extensive, up-to-date review of the preclinical and clinical development of glasdegib. Elements of its routine clinical use and the landscape of ongoing clinical trials are also stated.

Objective To evaluate the nationwide implementation of the “Living well with COPD” program by the Swiss Lung Association in various cantons in Switzerland. Methods For the process evaluation, we used qualitative (interview, focus group) and quantitative (questionnaires, documentation analysis) methods to assess the implementation outcomes reach, dose, fidelity and acceptability. For the effectiveness, we performed a pre-post analysis of patient data collected at baseline and program end (after 14 months). Results Seven Cantonal Lung Associations implemented the program into their services according to plan, conducted it 13 times and included 122 COPD patients. Patients’ attendance rate was 81% and coaches’ fidelity to protocol 94%. Acceptance and satisfaction of all involved persons was high. Integration of the coaches’ additional workload, uncertainties regarding roles and responsibilities and sustainable reimbursement were major challenges. Patients significantly improved in COPD specific quality of life and increased exercise capacity with on average 3.2 more repetitions in the 1-minute sit-to-stand test. Conclusion The program was successfully implemented throughout Switzerland with high acceptability and positive association with patients’ quality of life. Practice implications Our findings support the broader multiplication throughout Switzerland and serves the international community since it is one of the first nationwide implementations beyond study settings.

Kidney international 101(2), 256-273 (2022). doi:10.1016/j.kint.2021.10.025, Published by Elsevier, New York, NY

Background & Aims Porto-sinusoidal vascular disease (PSVD) was recently proposed as novel clinical entity characterized by typical histological changes with or without portal hypertension (PH) in the absence of cirrhosis. Thus, we aimed to describe clinical characteristics and the outcome of PSVD patients and to compare these to patients meeting traditional idiopathic non-cirrhotic portal hypertension (INCPH) criteria. Methods Patients undergoing liver biopsy (baseline) ±hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 2000-2019 were screened for PSVD and INCPH criteria. Results 91 patients were diagnosed with PSVD of which 28 (30.8%) also fulfilled INCPH criteria (INCPH+/PSVD+). Specific histological and specific clinical PH signs were found in 72 (79.1%) and 54 (59.3%) patients, respectively. INCPH+/PSVD+ showed higher Child-Pugh-scores (7±2 vs 6±1 points; P = .002) and a higher prevalence of decompensation (57.1% vs 28.6%; P = .009) than INCPH-/PSVD+ patients. Importantly, hepatic decompensation after three years (3Y) occurred in 11.2% of PSVD patients with specific clinical signs of PH, while no decompensation occurred in patients with only specific histological or with unspecific clinical/histological signs (P = .002). When categorizing by INCPH definition, 3Y decompensation was 13.4% in INCPH+/PSVD+ and 3.8% in INCPH-/PSVD+ (P = .120). While overall mortality was similar in INCPH+/PSVD+ (n = 6; 21.4%) and INCPH-/PSVD+ (n = 10; 15.9%) patients (P = .558), liver-related mortality tended to be higher in INCPH+/PSVD+ (6.9%) than in INCPH-/PSVD+ (0%; P = .078). Conclusion Novel PSVD criteria facilitate diagnosis. Compared to INCPH, clinical course of PSVD patients is more favorable. Importantly, specific signs of PH including varices and collaterals are associated with hepatic decompensation and mortality.

Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Contains fulltext : 248871.pdf (Publisher’s version ) (Open Access) BACKGROUND: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson's disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. OBJECTIVE: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. METHODS: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). RESULTS: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60-0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. CONCLUSION: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.

Despite recent breakthroughs in deep learning for materials informatics, there exists a disparity between their popularity in academic research and their limited adoption in the industry. A significant contributor to this “interpretability-adoption gap” is the prevalence of black-box models and the lack of built-in methods for model interpretation. While established methods for evaluating model performance exist, an intuitive understanding of the modeling and decision-making processes in models is nonetheless desired in many cases. In this work, we demonstrate several ways of incorporating model interpretability to the structure-agnostic Compositionally Restricted Attention-Based network, CrabNet. We show that CrabNet learns meaningful, material property-specific element representations based solely on the data with no additional supervision. These element representations can then be used to explore element identity, similarity, behavior, and interactions within different chemical environments. Chemical compounds can also be uniquely represented and examined to reveal clear structures and trends within the chemical space. Additionally, visualizations of the attention mechanism can be used in conjunction to further understand the modeling process, identify potential modeling or dataset errors, and hint at further chemical insights leading to a better understanding of the phenomena governing material properties. We feel confident that the interpretability methods introduced in this work for CrabNet will be of keen interest to materials informatics researchers as well as industrial practitioners alike.

Biallelic mutations of the CEBPA gene (CEBPAbi) define a distinct entity associated with favorable prognosis; however, the role of monoallelic mutations (CEBPAsm) is poorly understood. We retrospectively analyzed 4708 adults with acute myeloid leukemia (AML) who had been recruited into the Study Alliance Leukemia trials, to investigate the prognostic impact of CEBPAsm. CEBPA mutations were identified in 240 patients (5.1%): 131 CEBPAbi and 109 CEBPAsm (60 affecting the N-terminal transactivation domains [CEBPAsmTAD] and 49 the C-terminal DNA-binding or basic leucine zipper region [CEBPAsmbZIP]). Interestingly, patients carrying CEBPAbi or CEBPAsmbZIP shared several clinical factors: they were significantly younger (median, 46 and 50 years, respectively) and had higher white blood cell (WBC) counts at diagnosis (median, 23.7 × 109/L and 35.7 × 109/L) than patients with CEBPAsmTAD (median age, 63 years, median WBC 13.1 × 109/L; P < .001). Co-mutations were similar in both groups: GATA2 mutations (35.1% CEBPAbi; 36.7% CEBPAsmbZIP vs 6.7% CEBPAsmTAD; P < .001) or NPM1 mutations (3.1% CEBPAbi; 8.2% CEBPAsmbZIP vs 38.3% CEBPAsmTAD; P < .001). CEBPAbi and CEBPAsmbZIP, but not CEBPAsmTAD were associated with significantly improved overall (OS; median 103 and 63 vs 13 months) and event-free survival (EFS; median, 20.7 and 17.1 months vs 5.7 months), in univariate and multivariable analyses. Additional analyses revealed that the clinical and molecular features as well as the favorable survival were confined to patients with in-frame mutations in bZIP (CEBPAbZIP-inf). When patients were classified according to CEBPAbZIP-inf and CEBPAother (including CEBPAsmTAD and non-CEBPAbZIP-inf), only patients bearing CEBPAbZIP-inf showed superior complete remission rates and the longest median OS and EFS, arguing for a previously undefined prognostic role of this type of mutation.

This study compared the therapeutic potential of the chemotherapy using meglumine antimoniate encapsulated in a mixture of conventional and PEGylated liposomes (Nano Sbv) and immunotherapy with anti-canine IL-10 receptor-blocking monoclonal antibody (Anti IL-10R) on canine visceral leishmaniasis (CVL). Twenty mongrel dogs naturally infected by L. infantum, displaying clinical signs of visceral leishmaniasis were randomly divided in two groups. In the first one, nine dogs received six intravenous doses of a mixture of conventional and PEGylated liposomes containing meglumine antimoniate at 6.5 mg Sb/kg/dose. In the second one, eleven dogs received two intramuscular doses of 4 mg of anti-canine IL-10 receptor-blocking monoclonal antibody. The animals were evaluated before (T0) and 30, 90, and 180 days after treatments. Our major results demonstrated that both treatments were able to maintain hematological and biochemical parameters, increase circulating T lymphocytes subpopulations, increase the IFN-γ producing T-CD4 lymphocytes, restore the lymphoproliferative capacity and improve the clinical status. However, although these improvements were observed in the initial post-treatment times, they did not maintain until the end of the experimental follow-up. We believe that the use of booster doses or the association of chemotherapy and immunotherapy (immunochemotherapy) is promising to improve the effectiveness of treating CVL for improving the clinical signs and possibly reducing the parasite burden in dogs infected with Leishmania infantum.

Background Sustained high levels of astronaut cognitive performance are a prerequisite for mission success. A neuropsychological battery of 10 brief cognitive tests (Cognition) covering a range of cognitive domains was specifically developed for high performing astronauts to objectively assess cognitive performance. Extended mission durations require repeated cognitive testing and thus high acceptability of the Cognition software to the astronaut population. The aim of this qualitative study was to evaluate acceptability of Cognition to astronauts and astronaut surrogate populations. Methods Cognition was administered repeatedly to N = 87 subjects (mean age ± SD 35.1 ± 8.7 years, 52.8% male) on a laptop or iPad across five individual studies on the International Space Station or in space analog environments on Earth. Following completion of each study, participants were interviewed regarding their experience using Cognition in a semi-structured debrief. Participant comments were analyzed using a qualitative conventional content analysis approach. Results The majority of participants’ comments (86.1%) were coded as positive or neutral in valence, with most positive comments relating to software usability, engagement, and overall design. Among the 10 Cognition tests, subjects liked the Visual Object Learning Test most (28 likes, 32.2% of participants), while the Emotion Recognition Test was liked least (44 dislikes, 50.6% of participants). Some subjects (36.8%) were frustrated with the level of difficulty of some of the 10 Cognition tests, especially during early administrations, which was by design to avoid ceiling effects in repeated administrations of high-performers. Technical difficulties were rare (20.7% of participants), and most often observed in environments with restricted internet access. Most participants (82.3% of those who commented) liked the feedback provided by Cognition after each test, which includes a graph showing performance history. Conclusion Cognition was found to be acceptable to astronaut and astronaut-surrogate populations across a variety of settings and mission durations. Participant feedback provided was used to further improve Cognition and increase its acceptability during sustained space missions.

Background A sterilizing cure of HIV-1 infection has been reported in 2 persons living with HIV-1 who underwent allogeneic hematopoietic stem cell transplantations from donors who were homozygous for the CCR5Δ32 gene polymorphism. However, this has been considered elusive during natural infection. Objective To evaluate persistent HIV-1 reservoir cells in an elite controller with undetectable HIV-1 viremia for more than 8 years in the absence of antiretroviral therapy. Design Detailed investigation of virologic and immunologic characteristics. Setting Tertiary care centers in Buenos Aires, Argentina, and Boston, Massachusetts. Patient A patient with HIV-1 infection and durable drug-free suppression of HIV-1 replication. Measurements Analysis of genome-intact and replication-competent HIV-1 using near-full-length individual proviral sequencing and viral outgrowth assays, respectively; analysis of HIV-1 plasma RNA by ultrasensitive HIV-1 viral load testing. Results No genome-intact HIV-1 proviruses were detected in analysis of a total of 1.188 billion peripheral blood mononuclear cells and 503 million mononuclear cells from placental tissues. Seven defective proviruses, some of them derived from clonally expanded cells, were detected. A viral outgrowth assay failed to retrieve replication-competent HIV-1 from 150 million resting CD4+ T cells. No HIV-1 RNA was detected in 4.5 mL of plasma. Limitations Absence of evidence for intact HIV-1 proviruses in large numbers of cells is not evidence of absence of intact HIV-1 proviruses. A sterilizing cure of HIV-1 can never be empirically proved. Conclusion Genome-intact and replication-competent HIV-1 were not detected in an elite controller despite analysis of massive numbers of cells from blood and tissues, suggesting that this patient may have naturally achieved a sterilizing cure of HIV-1 infection. These observations raise the possibility that a sterilizing cure may be an extremely rare but possible outcome of HIV-1 infection. Primary funding source National Institutes of Health and Bill & Melinda Gates Foundation.

Zusammenfassung. Hintergrund: Eine Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im Kindesalter stellt einen Risikofaktor für Substanzmissbrauch und Störungen durch Substanzgebrauch (Substance Use Disorder, SUD) in der Pubertät und dem (frühen) Erwachsenenalter dar. ADHS und SUD treten auch häufig bei therapiesuchenden Jugendlichen auf, was die Diagnosestellung und Therapie erschwert sowie mit schlechten Behandlungsergebnissen verbunden ist. Forschungsergebnisse über die Wirkung der Behandlung von ADHS im Kindesalter auf die Prävention von SUD im Jugendalter sind nicht eindeutig und Studien über die Diagnose und Behandlung von Jugendlichen mit ADHS und SUD sind selten. Daher reicht die verfügbare Evidenz allgemein nicht aus, um starke Behandlungsempfehlungen zu rechtfertigen. Fragestellung: Ziel dieser Arbeit war es, eine Konsenserklärung auf der Grundlage von wissenschaftlichen Daten und klinischen Erfahrungen zu erhalten. Methodik: Es wurde eine modifizierte Delphi-Studie durchgeführt, um basierend auf der Kombination von wissenschaftlichen Daten und klinischer Erfahrung mit einer multidisziplinären Gruppe von 55 Expert_innen aus 17 Ländern einen Konsens zu erzielen. Die Expert_innen wurden gebeten, eine Reihe von Aussagen über die Wirkung der Behandlung von ADHS im Kindesalter auf die SUD bei Jugendlichen sowie über das Screening, die Diagnostik und die Behandlung von Jugendlichen mit komorbidem ADHS und SUD zu bewerten. Ergebnisse: Nach drei iterativen Bewertungsrunden und der Anpassung von 37 Aussagen wurde ein Konsens über 36 dieser Aussagen erzielt, die sechs Bereiche repräsentieren: allgemein ( n = 4), Risiko der Entwicklung einer SUD ( n = 3), Screening und Diagnostik ( n = 7), psychosoziale Behandlung ( n = 5), pharmakologische Behandlung ( n = 11) und komplementäre Behandlungen ( n = 7). Der Einsatz von Routinescreenings auf ADHS wird bei adoleszenten Patient_innen in einer Suchtbehandlung ebenso wie Routinescreenings auf SUD bei jugendlichen Patient_innen mit ADHS in allgemeinpsychiatrischen Therapiesettings empfohlen. Langwirksame Stimulanzien werden als Behandlung der ersten Wahl von ADHS bei Jugendlichen mit gleichzeitiger ADHS und SUD empfohlen. Die Pharmakotherapie sollte vorzugsweise in psychosoziale Behandlung eingebettet werden. Die einzige nichtkonsentierte Aussage betraf die Notwendigkeit von Abstinenz vor Beginn einer pharmakologischen Behandlung bei Jugendlichen mit ADHS und gleichzeitigem SUD. Im Gegensatz zur Mehrheit verlangten einige Expert_innen eine vollständige Abstinenz vor Beginn einer pharmakologischen Behandlung, einige waren gegen die Verwendung von Stimulanzien bei der Behandlung dieser Patient_innen (unabhängig von Abstinenz), während einige sich gegen die alternative Anwendung von Bupropion aussprachen. Schlussfolgerungen: Diese internationale Konsenserklärung kann von Kliniker_innen und Patient_innen zusammen in einem gemeinsamen Entscheidungsprozess genutzt werden, um die besten Interventionen auszuwählen und die bestmöglichen Ergebnisse bei adoleszenten Patient_innen mit gleichzeitiger ADHS und SUD zu erzielen.

Purpose: To investigate the relationship between dry eye disease (DED) and vision-related quality of life (VR-QoL) at population level.Methods: DED and VR-QoL were assessed in 89,022 participants (18–96 years, 59% female) from the Dutch population-based Lifelines cohort using the Women's Health study (WHS) and Visual function 25 (VFQ25) questionnaires. The relationship between DED and compromised VR-QoL was assessed with logistic regression, corrected for age, sex, BMI, income, education, smoking, and 55 comorbidities.Results: 9.1% of participants had DED. The participants with DED had higher risk of compromised average of ten domains of VR-QoL (OR 3.12 (95% CI 2.98–3.27) corrected for age, sex, BMI, income, smoking, and 55 comorbidities). Increasing symptom frequency was highly associated with decreasing VR-QoL (P < 0.0005). In all VR-QoL domains, including measures of daily visual function and emotional well-being, DED was clearly associated with compromised VR-QoL. Compared to macular degeneration, glaucoma, retinal detachment, and allergic conjunctivitis, DED presented similar or higher risks for compromised score on all VR-QoL domains. The population-attributable fraction of DED for compromised general vision exceeded that of other eye diseases investigated, especially in the younger age groups.Conclusion: DED is associated with reductions in all domains of VR-QoL, also after correction for associated comorbidities. We found that DED imposes an extensive population burden regarding compromised VR-QoL due to its high prevalence and substantial impact on VR-QoL, higher than that for other common vision-affecting eye disorders. Our results emphasize the importance of recognizing DED as a serious disorder from both patient and public health perspectives.

High mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD).Plasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator.Mannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness 65 μm (odds ratio = 1.32 per each 10 μmol/L mannose change [95% confidence interval, 1.05-1.65]) and was an independent predictor of death (hazard ratio for mannose≥vs 84.6 μmol/L: 4.0(95%CI, 1.4-11.3), p = 0.006).The current data add novel evidence that high mannose is a signature of CAD with a vulnerable plaque phenotype, consistently across measures of severity of vessel involvement and independent of the traditional correlates of CVD, and that it is an independent predictor of incident adverse outcomes.

A methodological debate within social pharmacy is ongoing regarding how to apply a qualitative approach. This paper emanates from a workshop at the Nordic Social Pharmacy Conference in 2019, named ‘How do we know it's good? A workshop on quality criteria in qualitative social and clinical pharmacy research’, that addressed this debate. The aim of this paper is twofold (1) to present the main key points raised during the workshop and (2) based on these inputs to contribute to the ongoing discussion on qualitative methodology within social pharmacy research. This paper starts with what was discussed at the workshop and further elaborated are some of the challenges with conducting qualitative research within social pharmacy. These include methodological and disciplinary competence and insecurity, reflections on the consequences of that many social pharmacy researchers come from a natural science background and how this (possibly) shapes the practice of qualitative research within the field. For example, how concepts like transparency and saturation, together with checklists and quality criteria are understood and used. Finally, we make suggestions for the next step for qualitative research in social pharmacy.

Background: Echocardiography is the diagnostic modality for assessing cardiac systolic and diastolic function to diagnose and manage heart failure. However, manual interpretation of echocardiograms can be time consuming and subject to human error. Therefore, we developed a fully automated deep learning workflow to classify, segment, and annotate two-dimensional (2D) videos and Doppler modalities in echocardiograms. Methods: We developed the workflow using a training dataset of 1145 echocardiograms and an internal test set of 406 echocardiograms from the prospective heart failure research platform (Asian Network for Translational Research and Cardiovascular Trials; ATTRaCT) in Asia, with previous manual tracings by expert sonographers. We validated the workflow against manual measurements in a curated dataset from Canada (Alberta Heart Failure Etiology and Analysis Research Team; HEART; n=1029 echocardiograms), a real-world dataset from Taiwan (n=31 241), the US-based EchoNet-Dynamic dataset (n=10 030), and in an independent prospective assessment of the Asian (ATTRaCT) and Canadian (Alberta HEART) datasets (n=142) with repeated independent measurements by two expert sonographers. Findings: In the ATTRaCT test set, the automated workflow classified 2D videos and Doppler modalities with accuracies (number of correct predictions divided by the total number of predictions) ranging from 0·91 to 0·99. Segmentations of the left ventricle and left atrium were accurate, with a mean Dice similarity coefficient greater than 93% for all. In the external datasets (n=1029 to 10 030 echocardiograms used as input), automated measurements showed good agreement with locally measured values, with a mean absolute error range of 9–25 mL for left ventricular volumes, 6–10% for left ventricular ejection fraction (LVEF), and 1·8–2·2 for the ratio of the mitral inflow E wave to the tissue Doppler e' wave (E/e' ratio); and reliably classified systolic dysfunction (LVEF

BACKGROUND: Bystander-initiated basic life support (BLS) plays an important role in improving survival after out-of-hospital cardiac arrest. In 2009, laws mandating BLS course participation when acquiring a driver's licence were implemented in Denmark. The aim of this study was to characterise Danish BLS course participants.METHODS: This study is a Danish, registry-based, follow-up study that examined all Danish BLS course participants from 2016 to 2019. Data concerning BLS course participation were supplied by the major Danish BLS course providers. Socio-economic and healthcare data on all Danish inhabitants were assessed using national registers from Statistics Denmark.RESULTS: Between January 1, 2016, and January 1, 2020, 3.6% of the entire adult population of Denmark attended certified BLS courses annually. Since the implementation of a law mandating BLS course participation when acquiring a driver licence in 2009, approximately 44% of the adult population has participated in a BLS course. BLS course participants were commonly younger and healthier than the general population (mean 31.3 years old vs. 51.3 years old, P < 0.001). Furthermore, law-mandated BLS course participants had a lower disposable income (adjusted OR: 0.23; 95% CI: 0.23-0.23; P < 0.001) and were more likely to live in rural areas (adjusted OR: 0.57; 95% CI: 0.57-0.58; P < 0.001).CONCLUSION: In Denmark, 3.6% of the entire adult population attend certified courses annually. BLS participants are commonly male, younger, healthier, less likely to have small children in the household, and more likely to live in rural areas. Law-mandated BLS course participation prior to acquiring a driver's licence has been successful in reaching segments of the society that are known to have limited participation.

Introduction Patient satisfaction is a quality of care measure and reveals patients’ appreciation of healthcare delivery. We sought to measure patient satisfaction following major gynaecological surgeries in 2 University Teaching Hospitals in Yaounde, Cameroon.Methods Ours was a cross-sectional, prospective study over 9 months (October 1 st 2018, to June 30 th 2018) at the Yaounde Gynaeco-Obstetric and Paediatric Hospital (YGOPH) and the Yaounde Central Hospital (YCH). By administering a modified Surgical Satisfaction Questionnaire (SSQ-8) via phone call 6 months after surgery we appreciated and scored key aspects linked to patient satisfaction, and obtained information on post-operative complications. Data was analysed using Microsoft Excel 18 and SPSS 21 setting significance at p

Aims The aim of this study was to investigate the efficacy and safety of ticagrelor monotherapy in patients undergoing percutaneous coronary intervention (PCI) stratified according to the baseline white blood cell (WBC) count. Methods and results This is a post hoc analysis of the GLOBAL LEADERS trial, a multi-centre, open-label, randomized all-comer trial in patients undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual anti-platelet therapy [DAPT]) with the reference strategy (12-month aspirin monotherapy following 12-month DAPT). Patients were stratified into two WBC groups, either < or ≥median WBC count of 7.8 × 109 cells/L (lower or higher WBC group, respectively). The primary endpoint was a composite of all-cause mortality or new Q-wave myocardial infarction at 2 years. Of 14 576 patients included in the present study, 7212 patients (49.5%) were classified as the lower WBC group, who had a significantly lower risk of both ischaemic and bleeding outcomes at 2 years. At 2 years, the experimental strategy was associated with a significant lower incidence of the primary endpoint compared with the reference strategy in the lower WBC group [2.8% vs. 4.2%; hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.52–0.86] but not in the higher WBC group (4.8% vs. 4.7%; HR: 1.01; 95% CI: 0.82–1.25; Pinteraction=0.013). There were no significant differences in the risks of Bleeding Academic Research Consortium type 3 or 5 bleeding between two anti-platelet strategies regardless of the WBC groups. Conclusion Increased WBC counts, which may reflect degree of inflammation, at the time of index procedure may attenuate the anti-ischaemic benefits of ticagrelor monotherapy observed in patients with lower WBC counts.

Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

AimAssessing the distribution and persistence of species across their range is a crucial component of wildlife conservation. It demands data at adequate spatial scales and over extended periods of time, which may only be obtained through collaborative efforts, and the development of methods that integrate heterogeneous datasets. We aimed to combine existing data on large carnivores to evaluate population dynamics and improve knowledge on their distribution nationwide.LocationBotswana.MethodsBetween 2010 and 2016, we collated data on African wild dog, cheetah, leopard, brown and spotted hyaena and lion gathered with different survey methods by independent researchers across Botswana. We used a multi-species, multi-method dynamic occupancy model to analyse factors influencing occupancy, persistence and colonization, while accounting for imperfect detection. Lastly, we used the gained knowledge to predict the probability of occurrence of each species countrywide.ResultsWildlife areas and communal rangelands had similar occupancy probabilities for most species. Large carnivore occupancy was low in commercial farming areas and where livestock density was high, except for brown hyaena. Lion occupancy was negatively associated with human density; lion and spotted hyaena occupancy was high where rainfall was high, while the opposite applied to brown hyaena. Lion and leopard occupancy remained constant countrywide over the study period. African wild dog and cheetah occupancy declined over time in the south and north, respectively, whereas both hyaena species expanded their ranges. Countrywide predictions identified the highest occupancy for leopards and lowest for the two hyaena species.Main ConclusionsWe highlight the necessity of data sharing and propose a generalizable analytical method that addresses the challenges of heterogeneous data common in ecology. Our approach, which enables a comprehensive multi-species assessment at large spatial and temporal scales, supports the development of data-driven conservation guidelines and the implementation of evidence-based management strategies nationally and internationally. published

Effective public-health measures and vaccination campaigns against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against the ectodomain and the receptor-binding domain of the spike protein as well as the nucleocapsid protein of SARS-CoV-2. We used TRABI for continuous seromonitoring of hospital patients and healthy blood donors (n=72’222) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). Seroprevalence peaked in May 2020 and rose again in November 2020 in both cohorts. Validations of results included antibody diffusional sizing and Western Blotting. Using an extended Susceptible-Exposed-Infectious-Removed model, we found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020 in the population of the canton of Zurich. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19 and up to the timepoint of survey participation. Crucially, we found no evidence for a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2- infected subjects represents a resource for the study of chronic and possibly unexpected sequelae.

©The European Society of Cardiology 2020. Article reuse guidelines : sagepub.com/journals-permissions, Secondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular disease, reducing cardiovascular mortality, morbidity and disability, and to increase quality of life. The delivery of a comprehensive and ‘modern’ cardiac rehabilitation programme is mandatory both in the residential and the out-patient setting to ensure expected outcomes. The present position paper aims to update the practical recommendations on the core components and goals of cardiac rehabilitation intervention in different cardiovascular conditions, in order to assist the whole cardiac rehabilitation staff in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and patients in the recognition of the positive nature of cardiac rehabilitation. Starting from the previous position paper published in 2010, this updated document maintains a disease-oriented approach, presenting both well-established and more controversial aspects. Particularly for implementation of the exercise programme, advances in different training modalities were added and new challenging populations were considered. A general table applicable to all cardiovascular conditions and specific tables for each clinical condition have been created for routine practice.

The risk of recurring coronavirus disease (COVID-19) resurgences that threaten Africa’s health care systems, newly opened communities, schools, and businesses looms as communities abandon precautionary measures, such as mask-wearing, physical distancing, and regular handwashing. In this piece, we unpack the handling of both the first wave and subsequent resurgence in the context of 3 countries that are experiencing such a resurgence at the time of writing (December 2020): Israel, France, and the United Kingdom. While it is difficult to extrapolate on what to expect in South Africa, based on experience in these 3 countries, South Africa’s preparedness for a COVID-19 resurgence should place emphasis on the role of expanded testing and isolation capacity, strengthening enforcement of adherence to non-pharmaceutical interventions, and protection of high-risk populations.

As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and "sporadic" late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.

Accidental hypothermia (core temperature

Introduction: Beach and patio umbrellas may cause injury. There is limited published information on injuries due to beach and patio umbrellas. This study sought to describe beach and patio umbrella injuries reported to United States emergency departments (EDs). Method: An analysis was performed of beach and patio umbrella injuries using data from the National Electronic Injury Surveillance System during 2000–2019. Results: An estimated 5,512 beach umbrella injuries and 7,379 patio umbrella injuries were identified. The patient was age 40 years or older in 62.1% of the beach umbrella and 65.1% of the patio umbrella injuries. The patient was female in 68.0% of the beach umbrella and 66.9% of the patio umbrella injuries. Wind was reported involved in 50.6% of the beach umbrella and 27.5% of the patio umbrella injuries. The most frequently reported injuries with beach and patio umbrella injuries, respectively, were laceration (44.0% vs 33.0%), contusions or abrasions (19.8% vs 19.0%), and internal organ injury (16.6% vs 17.0%) and most often affected the head/neck (60.2% vs 44.0%) and upper extremity (16.3% vs 30.1%). Conclusions: The majority of patients with beach and patio umbrella injuries treated at EDs were age 40 years or older and most patients were female. For both types of umbrella injury, the most frequently reported injury was laceration followed by contusions or abrasions and internal organ injury, and the body part with the highest proportion of injuries was the head/neck followed by the upper extremity. Practical Applications: Persons should use sturdier models of beach or patio umbrella, use a rocking motion to dig into the sand and secure the beach umbrella with a metal anchor and screws, add weight to the bottom of the umbrella, and tilt the umbrella into the wind. Policy-makers should educate the public about the potential dangers of beach and patio umbrellas.

Background Vasoactive intestinal peptide-secreting tumor (VIPoma) is a very rare, life-threatening, functioning pancreatic neuroendocrine tumor (pNET). The efficacy of antitumor therapies against functioning symptoms and tumor burden have been poorly described in VIPoma. Objective Describe the impact of treatments on the secretory syndrome, tumor burden and survival in patients with VIPoma. Methods We retrospectively reviewed the records of patients with VIPoma treated in seven French expert centers between 1990 and 2016. Diagnostic of VIPoma was reassessed using strict criteria. We evaluated the antisecretory efficacy (>50 % decrease of daily bowel movements), and antitumor efficacy (RECIST 1.1) of all treatments received. Results Twenty-two patients were included. pNETs were mostly metastatic (77 %) and classified as grade 2 (83 %). Median follow-up was 78.2 months. Surgical excision of nonmetastatic VIPoma effectively controlled the secretory syndrome. Although 4/5 patients had metastatic recurrences, all patients were alive after median post-operative follow-up of 171 months. Among the 87 treatments received for metastatic VIPoma, curative-intent surgery (n = 14), somatostatin analogs alone (n = 11), chemotherapy (n = 23), transarterial liver embolization (TALE) (n = 14), everolimus (n = 10) and sunitinib (n = 7) achieved, respectively, 100 %, 67 %, 83 %, 50 %, 20 % and 100 % antisecretory efficacy. The 5-year OS rate was 63.6 %, with pejorative impact of higher Ki-67 index (P = 0.045) and higher plasma VIP concentration (P = 0.025). Conclusions Surgical resection of localized VIPoma is effective but rarely curative. For metastatic VIPoma, curative-intent surgery, chemotherapy and sunitinib are the therapeutic options that best combined antitumor and antisecretory efficacies.

Background Current imaging methods for prediction of complete margin resection (R0) in patients with pancreatic ductal adenocarcinoma (PDAC) are not reliable. Purpose To investigate whether tumor-related and perivascular CT radiomic features improve preoperative assessment of arterial involvement in patients with surgically proven PDAC. Materials and Methods This retrospective study included consecutive patients with PDAC who underwent surgery after preoperative CT between 2012 and 2019. A three-dimensional segmentation of PDAC and perivascular tissue surrounding the superior mesenteric artery (SMA) was performed on preoperative CT images with radiomic features extracted to characterize morphology, intensity, texture, and task-based spatial information. The reference standard was the pathologic SMA margin status of the surgical sample: SMA involved (tumor cells ≤1 mm from margin) versus SMA not involved (tumor cells >1 mm from margin). The preoperative assessment of SMA involvement by a fellowship-trained radiologist in multidisciplinary consensus was the comparison. High reproducibility (intraclass correlation coefficient, 0.7) and the Kolmogorov-Smirnov test were used to select features included in the logistic regression model. Results A total of 194 patients (median age, 66 years; interquartile range, 60-71 years; age range, 36-85 years; 99 men) were evaluated. Aside from surgery, 148 patients underwent neoadjuvant therapy. A total of 141 patients' samples did not involve SMA, whereas 53 involved SMA. A total of 1695 CT radiomic features were extracted. The model with five features (maximum hugging angle, maximum diameter, logarithm robust mean absolute deviation, minimum distance, square gray level co-occurrence matrix correlation) showed a better performance compared with the radiologist assessment (model vs radiologist area under the curve, 0.71 [95% CI: 0.62, 0.79] vs 0.54 [95% CI: 0.50, 0.59]; P < .001). The model showed a sensitivity of 62% (33 of 53 patients) (95% CI: 51, 77) and a specificity of 77% (108 of 141 patients) (95% CI: 60, 84). Conclusion A model based on tumor-related and perivascular CT radiomic features improved the detection of superior mesenteric artery involvement in patients with pancreatic ductal adenocarcinoma. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Do and Kambadakone in this issue.

PURPOSE Patients with cancer are at increased risk for unfavorable outcomes from COVID-19. Knowledge about the outcome determinants of severe acute respiratory syndrome coronavirus 2 infection in this population is essential for risk stratification and definition of appropriate management. Our objective was to evaluate prognostic factors for all-cause mortality in patients diagnosed with both cancer and COVID-19. METHODS All consecutive patients with cancer hospitalized at our institution with COVID-19 were included. Electronic medical records were reviewed for clinical and laboratory characteristics potentially associated with outcomes. RESULTS Five hundred seventy-six consecutive patients with cancer and COVID-19 were included in the present study. An overall in-hospital mortality rate of 49.3% was demonstrated. Clinical factors associated with increased risk of death because of COVID-19 were age over 65 years, Eastern Cooperative Oncology Group performance status > 0 zero, best supportive care, primary lung cancer, and the presence of lung metastases. Laboratory findings associated with a higher risk of unfavorable outcomes were neutrophilia, lymphopenia, and elevated levels of D-dimer, creatinine, C-reactive protein, or AST. CONCLUSION A high mortality rate in patients with cancer who were diagnosed with COVID-19 was demonstrated in the present study, emphasizing the need for close surveillance in this group of patients, especially in those with unfavorable prognostic characteristics.

AIMS: To study the relationship between subclinical atrial fibrillation (AF) and changes in cognitive function in a large cohort of individuals with stroke risk factors.METHODS: Individuals with no prior AF diagnosis but with risk factors for stroke were recruited to undergo annual cognitive assessment with the Montreal Cognitive Assessment (MoCA) along with implantable loop recorder (ILR) monitoring for AF for 3 years. If AF episodes lasting ≥6 minutes were detected, oral anticoagulation (OAC) treatment was initiated.RESULTS: A total of 1194 participants (55.2 % men, mean age 74.5 (±3.9)) had a combined duration of heart rhythm monitoring of ≈1.3 million days. Among these, 339 participants (28.3%) had adjudicated AF, with a median AF burden of 0.072% (0.02, 0.39), and 324 (96%) initiated OAC. When stratifying the participants into AF burden groups (No AF, AFlow (AF burden 0.25%)), only participants in the AFlow group had a decrease in MoCA score over time (p = 0.03), although this was not significant after adjustment for stroke risk factors. A subgroup analysis of 175 participants (14.6%) with a MoCA CONCLUSIONS: In a high-risk population, subclinical AF detected by continuous monitoring and subsequently treated with OAC was not associated with a significant change in MoCA score over a three-year period.

1 -ABSTRACTDigital light microscopy provides powerful tools for quantitatively probing the real-time dynamics of subcellular structures. While the power of modern microscopy techniques is undeniable, rigorous record-keeping and quality control are required to ensure that imaging data may be properly interpreted (quality), reproduced (reproducibility), and used to extract reliable information and scientific knowledge which can be shared for further analysis (value). Keeping notes on microscopy experiments and quality control procedures ought to be straightforward, as the microscope is a machine whose components are defined and the performance measurable. Nevertheless, to this date, no universally adopted community-driven specifications exist that delineate the required information about the microscope hardware and acquisition settings (i.e., microscopy “data provenance” metadata) and the minimally accepted calibration metrics (i.e., microscopy quality control metadata) that should be automatically recorded by both commercial microscope manufacturers and customized microscope developers. In the absence of agreed guidelines, it is inherently difficult for scientists to create comprehensive records of imaging experiments and ensure the quality of resulting image data or for manufacturers to incorporate standardized reporting and performance metrics. To add to the confusion, microscopy experiments vary greatly in aim and complexity, ranging from purely descriptive work to complex, quantitative and even sub-resolution studies that require more detailed reporting and quality control measures.To solve this problem, the4D Nucleome Initiative (4DN) (1, 2) Imaging Standards Working Group (IWG), working in conjunction with theBioImagingNorthAmerica (BINA) Quality Control and Data Management Working Group (QC-DM-WG) (3), here propose light Microscopy Metadata specifications that scale with experimental intent and with the complexity of the instrumentation and analytical requirements. They consist of a revision of the Core of the Open Microscopy Environment (OME) Data Model, which forms the basis for the widely adopted Bio-Formats library (4–6), accompanied by a suite of three extensions, each with three tiers, allowing the classification of imaging experiments into levels of increasing imaging and analytical complexity (7, 8). Hence these specifications not only provide an OME-based comprehensive set of metadata elements that should be recorded, but they also specify which subset of the full list should be recorded for a given experimental tier. In order to evaluate the extent of community interest, an extensive outreach effort was conducted to present the proposed metadata specifications to members of several core-facilities and international bioimaging initiatives including theEuropeanLightMicroscopyInitiative (ELMI),GlobalBioImaging (GBI), andEuropeanMolecularBiologyLaboratory (EMBL) -EuropeanBioinformaticsInstitute (EBI). Consequently, close ties were established between our endeavour and the undertakings of the recently establishedQUAlity Assessment andREProducibility for Instruments and Images inLightMicroscopy global community initiative (9). As a result this flexible 4DN-BINA-OME (NBO namespace) framework (7, 8) represents a turning point towards achieving community-driven Microscopy Metadata standards that will increase data fidelity, improve repeatability and reproducibility, ease future analysis and facilitate the verifiable comparison of different datasets, experimental setups, and assays, and it demonstrates the method for future extensions. Such universally accepted microscopy standards would serve a similar purpose as the Encode guidelines successfully adopted by the genomic community (10, 11). The intention of this proposal is therefore to encourage participation, critiques and contributions from the entire imaging community and all stakeholders, including research and imaging scientists, facility personnel, instrument manufacturers, software developers, standards organizations, scientific publishers, and funders.

PURPOSE COVID-19 has affected cancer care worldwide. Clinical trials are an important alternative for the treatment of oncologic patients, especially in Latin America, where trials can be the only opportunity for some of them to access novel and, sometimes, standard treatments. METHODS This was a cross-sectional study, in which a 22-question survey regarding the impact of the COVID-19 pandemic on oncology clinical trials was sent to 350 representatives of research programs in selected Latin American institutions, members of the Latin American Cooperative Oncology Group. RESULTS There were 90 research centers participating in the survey, with 70 of them from Brazil. The majority were partly private or fully private (n = 77; 85.6%) and had confirmed COVID-19 cases at the institution (n = 57; 63.3%). Accruals were suspended at least for some studies in 80% (n = 72) of the responses, mostly because of sponsors' decision. Clinical trials' routine was affected by medical visits cancelation, reduction of patients' attendance, reduction of other specialties' availability, and/or alterations on follow-up processes. Formal COVID-19 mitigation policies were adopted in 96.7% of the centers, including remote monitoring and remote site initiation visits, telemedicine visits, reduction of research team workdays or home office, special consent procedures, shipment of oral drugs directly to patients' home, and increase in outpatient diagnostic studies. Importantly, some of these changes were suggested to be part of future oncology clinical trials' routine, particularly the ones regarding remote methods, such as telemedicine. CONCLUSION To our knowledge, this was the first survey to evaluate the impact of COVID-19 on Latin American oncology clinical trials. The results are consistent with surveys from other world regions. These findings may endorse improvements in clinical trials' processes and management in the postpandemic period.

BACKGROUND Patients with cirrhosis are at risk of cirrhotic cardiomyopathy, with resulting cardiac dysfunction and exercise limitations. Six minute walking test (6MWT) assesses functional status and predicts morbidity and mortality in cardiopulmonary diseases. AIM To determine if it associates with mortality by analyzing 6MWT performance in patients with liver cirrhosis. METHODS A cohort of 106 cirrhotic patients was evaluated in the outpatient setting with echocardiogram and 6MWT and follow up for one year to document hepatic decompensation and mortality. The distance in meters was recorded at the end of 6 min (6MWD). RESULTS This cohort had a mean age of 51 years and 56% male; patients were staged as Child A in 21.7%, B 66% and C 12.3%. Walk distance inversely correlated with Child scores, and was significantly reduced as Child stages progresses. Patients who died (10.4%) showed shorter mean 6MWD (P = 0.006). Low 6MWD was an independent predictor of mortality (P = 0.01). CONCLUSION 6MWT is a noninvasive inexpensive test whose result is related to Child scores and mortality. It is useful to identify patients with liver cirrhosis at high risk of mortality for closer monitoring and potential early intervention.