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Molecular blood biomarkers are lacking for high‐grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA‐based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1‐2 but has not been studied in HG GEP‐NEN. Patients with advanced HG GEP‐NEN were prospectively included in an observational study. A blood sample was collected before the start of chemotherapy and pseudonymised before NETest was performed. NETest results are expressed as an activity index (NETest score) from 0 to 100. The normal score cut‐off is 20. Histological sections were pseudonymised before centralized pathological re‐evaluation. Samples from 60 patients were evaluable with the NETest. Main primary tumor sites were colon (14), rectum (12), pancreas (11) and esophagus (7). Re‐classification: 30 NEC, 12 NET G3, 3 HG‐NEN ambiguous morphology, 8 MiNEN, 3 adenocarcinomas with neuroendocrine differentiation (ADNE), 3 adenocarcinomas and 1 NET G2. Elevated NETest (>20) was seen in 38/45 (84%) HG GEP‐NEN, all 17 large‐cell NEC (100%), 11/13 (85%) small‐cell NEC, all ambiguous cases and 7/12 (64%) NET G3. NETest was elevated in 5/8 (63%) MiNEN, 2/3 ADNE, however not in 3 adenocarcinomas. Median survival was 10.2 months (9.6–10.8 95%CI) for evaluable HG GEP‐NEN treated with palliative chemotherapy (n = 39), and survival was significantly shorter in patients with NETest >60 with an OS of only 6.5 months. This is the first study to evaluate use of the NETest in advanced HG GEP‐NEN. The NETest was almost always elevated in GEP‐NEC and in all large‐cell NEC. The NETest was also frequently elevated in NET G3 and MiNEN, however cases were limited. Baseline NETest was not predictive for benefit of chemotherapy, however a NETest >60 was prognostic with a shorter survival for patients receiving chemotherapy. [ABSTRACT FROM AUTHOR]

BackgroundThe Discovery Critical Care Research Network Program for Resilience and Emergency Preparedness (Discovery PREP) partnered with a third-party technology vendor to design and implement an electronic data capture tool that addressed multisite data collection challenges during public health emergencies (PHE) in the United States. The basis of the work was to design an electronic data capture tool and to prospectively gather data on usability from bedside clinicians during national health system stress queries and influenza observational studies. ObjectiveThe aim of this paper is to describe the lessons learned in the design and implementation of a novel electronic data capture tool with the goal of significantly increasing the nation’s capability to manage real-time data collection and analysis during PHE. MethodsA multiyear and multiphase design approach was taken to create an electronic data capture tool, which was used to pilot rapid data capture during a simulated PHE. Following the pilot, the study team retrospectively assessed the feasibility of automating the data captured by the electronic data capture tool directly from the electronic health record. In addition to user feedback during semistructured interviews, the System Usability Scale (SUS) questionnaire was used as a basis to evaluate the usability and performance of the electronic data capture tool. ResultsParticipants included Discovery PREP physicians, their local administrators, and data collectors from tertiary-level academic medical centers at 5 different institutions. User feedback indicated that the designed system had an intuitive user interface and could be used to automate study communication tasks making for more efficient management of multisite studies. SUS questionnaire results classified the system as highly usable (SUS score 82.5/100). Automation of 17 (61%) of the 28 variables in the influenza observational study was deemed feasible during the exploration of automated versus manual data abstraction. The creation and use of the Project Meridian electronic data capture tool identified 6 key design requirements for multisite data collection, including the need for the following: (1) scalability irrespective of the type of participant; (2) a common data set across sites; (3) automated back end administrative capability (eg, reminders and a self-service status board); (4) multimedia communication pathways (eg, email and SMS text messaging); (5) interoperability and integration with local site information technology infrastructure; and (6) natural language processing to extract nondiscrete data elements. ConclusionsThe use of the electronic data capture tool in multiple multisite Discovery PREP clinical studies proved the feasibility of using the novel, cloud-based platform in practice. The lessons learned from this effort can be used to inform the improvement of ongoing global multisite data collection efforts during the COVID-19 pandemic and transform current manual data abstraction approaches into reliable, real time, and automated information exchange. Future research is needed to expand the ability to perform automated multisite data extraction during a PHE and beyond.

Di Domenico et al., provide a comprehensive assessment of DNA methylation in a large cohort of pancreatic neuroendocrine tumors. This work provides new insights into the epigenetic heterogeneity of the disease and cellular basis.

En las dos últimas décadas, la historia económica argentina ha experimentado un auténtico boom. Dejó de ser la hermana menor de la nueva historia política y la historia social, buques insignia de la renovación historiográfica de la inmediata postdictadura, para convertirse en un campo académico de auténtica envergadura. La multiplicación de revistas especializadas, la relevancia que adquirieron las Jornadas Argentinas de Historia Económica en el calendario científico nacional y el creciente número de tesis sobre la materia son algunos de los síntomas de una especialidad que fue tomando distancia de sus humildes orígenes. Una multitud de trabajos abrió fronteras que resultaban inimaginables tan solo algunas décadas atrás, desde una caracterización más ajustada de los actores que dieron vida a la campaña hasta los siempre complejos tempos de la industrialización. Este rico corpus fue la base sobre la cual se sostuvieron los primeros esfuerzos de síntesis. El libro reseñado debe inscribirse en esa tradición, bastante reciente, por cierto, inaugurada por obras del calibre de autores como Rapoport (2003), Gelman (2006), Míguez (2008), Hora (2010) y Belini y Korol (2012).

BACKGROUND: Patient blood management (PBM) promotes the routine detection and treatment of anaemia before surgery, optimising the management of bleeding disorders, thus minimising iatrogenic blood loss and pre-empting allogeneic blood utilisation. PBM programmes have expanded from the elective surgical setting to nonsurgical patients, including those in intensive care units (ICUs), but their dissemination in a whole country is unknown. METHODS: We performed a cross-sectional, anonymous survey (10 October 2018 to 13 March 2019) of all ordinary medical members of the Swiss Society of Intensive Care Medicine and the registered ICU nurses from the 77 certified adult Swiss ICUs. We analysed PBM-related interventions adopted in Swiss ICUs and related them to the spread of PBM in Swiss hospitals. We explored blood test ordering policies, blood-sparing strategies and red blood cell-related transfusion practices in ICUs. RESULTS: A total of 115 medical doctors and 624 nurses (response rates 27% and 30%, respectively) completed the surveys. Hospitals had implemented a PBM programme according to 42% of physicians, more commonly in Switzerland’s German-speaking regions (Odds Ratio [OR] 3.39, 95% confidence interval [CI] 1.23–9.35; p = 0.018) and in hospitals with more than 500 beds (OR 3.91, 95% CI 1.48–10.4; p = 0.006). The PBM programmes targeted the detection and correction of anaemia before surgery (79%), minimising perioperative blood loss (94%) and optimising anaemia tolerance (98%). Laboratory tests were ordered in 70.4% by the intensivist during morning rounds; the nurses performed arterial blood gas analyses autonomously in 48.4%. Blood-sparing techniques were used by only 42.1% of nurses (263 of 624, missing: 6) and 47.0% of physicians (54 of 115). Approximately 60% of respondents used an ICU-specific transfusion guideline. The reported haemoglobin threshold for the nonbleeding ICU population was 70 g/l and, therefore, was at the lower limit of current guidelines. CONCLUSIONS: Based on this survey, the estimated proportion of the intensivists working in hospitals with a PBM initiative is 42%, with significant variability between regions and hospitals of various sizes. The risk of iatrogenic anaemia is relevant due to liberal blood sample collection practices and the underuse of blood-sparing techniques. The reported transfusion threshold suggests excellent adherence to current international ICU-specific transfusion guidelines.

OBJECTIVES:. Describe the effects of data literacy training and continuous performance reports on ICU staff compliance with the 6-element ICU quality bundle approach known as the ABCDEF (A–F) bundle and patient outcomes. DESIGN:. Stepped-wedge cluster randomized trial conducted during an institutional A–F bundle implementation program. SETTING:. Single-center study conducted in eight adult ICUs. PATIENTS:. Adult patients admitted for at least 24 hours, not undergoing active withdrawal of life support or palliative care. INTERVENTIONS:. Four ICUs in the intervention group received bundle-related staff education, data literacy training, and weekly bundle performance reports during the 12-month study period. The four ICUs in the nonintervention group received none of these interventions. Bundle compliance and patient outcomes were tracked, including ICU and hospital mortality, transfer and discharge, discharge disposition, mechanical ventilation, and ICU delirium. MEASUREMENT AND RESULTS:. In the intervention group, staff education alone increased bundle compliance from 9% to 16% (p < 0.0001); data literacy training further increased compliance from 16% to 21% (p = 0.03). This improvement was sustained throughout the study period including the onset of the COVID-19 pandemic and was greater than improvement in the nonintervention group (p < 0.001). Full A–F bundle compliance was associated with a lower likelihood of next-day ICU and hospital mortality, discharge to a facility other than home, and was associated with a higher likelihood of next-day extubation in patients. Next-day ICU and hospital discharge likelihood decreased, and delirium frequency was not affected. CONCLUSIONS:. This is the first study demonstrating that the combination of staff education, data literacy training, and access to performance data improves A–F bundle compliance, sustains performance, and improves ICU patient outcomes (ICU and hospital mortality, mechanical ventilation duration, and home discharge rates). In contrast to previous studies, increased bundle compliance did not hasten ICU or hospital discharges or reduce delirium frequency in patients.

BackgroundAcute kidney injury (AKI) is one of the most common and significant problems in patients with Coronavirus Disease 2019 (COVID-19). However, little is known about the incidence and impact of AKI occurring in the community or early in the hospital admission. The traditional Kidney Disease Improving Global Outcomes (KDIGO) definition can fail to identify patients for whom hospitalisation coincides with recovery of AKI as manifested by a decrease in serum creatinine (sCr). We hypothesised that an extended KDIGO (eKDIGO) definition, adapted from the International Society of Nephrology (ISN) 0by25 studies, would identify more cases of AKI in patients with COVID-19 and that these may correspond to community-acquired AKI (CA-AKI) with similarly poor outcomes as previously reported in this population.Methods and findingsAll individuals recruited using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)-World Health Organization (WHO) Clinical Characterisation Protocol (CCP) and admitted to 1,609 hospitals in 54 countries with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection from February 15, 2020 to February 1, 2021 were included in the study. Data were collected and analysed for the duration of a patient's admission. Incidence, staging, and timing of AKI were evaluated using a traditional and eKDIGO definition, which incorporated a commensurate decrease in sCr. Patients within eKDIGO diagnosed with AKI by a decrease in sCr were labelled as deKDIGO. Clinical characteristics and outcomes-intensive care unit (ICU) admission, invasive mechanical ventilation, and in-hospital death-were compared for all 3 groups of patients. The relationship between eKDIGO AKI and in-hospital death was assessed using survival curves and logistic regression, adjusting for disease severity and AKI susceptibility. A total of 75,670 patients were included in the final analysis cohort. Median length of admission was 12 days (interquartile range [IQR] 7, 20). There were twice as many patients with AKI identified by eKDIGO than KDIGO (31.7% versus 16.8%). Those in the eKDIGO group had a greater proportion of stage 1 AKI (58% versus 36% in KDIGO patients). Peak AKI occurred early in the admission more frequently among eKDIGO than KDIGO patients. Compared to those without AKI, patients in the eKDIGO group had worse renal function on admission, more in-hospital complications, higher rates of ICU admission (54% versus 23%) invasive ventilation (45% versus 15%), and increased mortality (38% versus 19%). Patients in the eKDIGO group had a higher risk of in-hospital death than those without AKI (adjusted odds ratio: 1.78, 95% confidence interval: 1.71 to 1.80, p-value < 0.001). Mortality and rate of ICU admission were lower among deKDIGO than KDIGO patients (25% versus 50% death and 35% versus 70% ICU admission) but significantly higher when compared to patients with no AKI (25% versus 19% death and 35% versus 23% ICU admission) (all p-values ConclusionsAn extended KDIGO definition of AKI resulted in a significantly higher detection rate in this population. These additional cases of AKI occurred early in the hospital admission and were associated with worse outcomes compared to patients without AKI.

One challenge for the design and analysis of hybrid electric aircraft configurations is an increased demand in the rejection of excess waste heat. A wing surface heat exchanger concept, which is explored as part of the IMOTHEP project, foresees transferring heat from the propulsive electrical components to the wing surface of the aircraft. Here, heat is mainly dissipated and transported by forced convection. The present study focuses on the analysis of the impact of heat rejection via the wing surface on the wing’s heat transfer and aerodynamic efficiency characteristics. For this purpose, RANS CFD studies of 2D airfoils and a 3D wing propeller geometry of a regional turboprop configuration in representative flight conditions (take off, cruise, and taxi in) are carried out. For each condition, the influence of defining parameters, such as altitude, freestream velocity, angle of attack, surface temperature, and propeller thrust is explored. It is shown that, when increasing the wing surface temperature compared against the freestream temperature, the aerodynamic efficiency of the wing deteriorates for all flight conditions. In reference cruise conditions for example, the lift-to-drag ratio decreases by 4%, while the average heat transfer coefficient is reduced by almost 20% when increasing the surface temperature by 300 K. Furthermore, the propeller slipstream enhances the wing’s heat transfer capacity significantly.

OBJECTIVES:. Demonstrate the feasibility of weekly data collection and analysis of public health emergency (PHE) data. Assess fluctuations in, and challenges of, resource matching and potential effect on patient care for influenza in ICUs. DESIGN:. Multicenter prospective noninterventional study testing effectiveness of leveraging the Discovery Critical Care Research Network Program for Resilience and Emergency Preparedness (Discovery-PREP) in performing PHE research. A 20-question internet survey was developed to prospectively assess ICU influenza-related resource stress. An informatics tool was designed to track responses; data were analyzed within 24 hours of weekly survey completion by the team biostatistician for timely reporting. PARTICIPANTS:. Critical care and Emergency Medicine Discovery-PREP network investigators self-selected to participate in the voluntary query. SETTING:. ICUs of 13 hospitals throughout the United States, 12 academic, and one community. INTERVENTIONS:. ICU physicians were electronically surveyed weekly over 17 weeks during the influenza season (January 2018–April 2018). Responses were collected for 48 hours after each email query. MEASUREMENTS AND MAIN RESULTS:. The average weekly response among the sites was 79% (range, 65–100%). Significant stress, defined as alterations in ICU staffing and/or resource allocation, occurred in up to 41% of sites during the national peak of influenza activity. These alterations included changes in staffing, not accepting external patient transfers, and canceling elective surgery. During this same period, up to 17% of the sites indicated that these changes might not have been sufficient to prevent potentially avoidable patient harm. CONCLUSIONS:. This novel approach to querying ICU operational stress indicated that almost half of participating sites experienced critical care resource limitations during peak influenza season and required process and/or staffing changes to better balance resources with patient care demands. This weekly national reporting infrastructure could be adapted and expanded to better inform providers, hospital emergency management teams, and government leaders during PHEs.

The Milky Way Bulge extra-tidal star survey is a spectroscopic survey with the goal of identifying stripped globular cluster stars from inner Galaxy clusters. In this way, an indication of the fraction of metal-poor bulge stars that originated from globular clusters can be determined. We observed and analyzed stars in and around BH 261, an understudied globular cluster in the bulge. From seven giants within the tidal radius of the cluster, we measured an average heliocentric radial velocity of 〈RV〉 = −61 ± 2.6 km s ^−1 with a radial velocity dispersion of 〈 σ 〉 = 6.1 ± 1.9 km s ^−1 . The large velocity dispersion may have arisen from tidal heating in the cluster’s orbit about the Galactic center, or because BH 261 has a high dynamical mass as well as a high mass-to-light ratio. From spectra of five giants, we measure an average metallicity of 〈[Fe/H]〉 = −1.1 ± 0.2 dex. We also spectroscopically confirm an RR Lyrae star in BH 261, which yields a distance to the cluster of 7.1 ± 0.4 kpc. Stars with 3D velocities and metallicities consistent with BH 261 reaching to ∼0.°5 from the cluster are identified. A handful of these stars are also consistent with the spatial distribution of potential debris from models focusing on the most recent disruption of the cluster.