Engaging Emergency Department Patients in the Creation of a Shared Decision-­Making Tool Regarding CT Scanning in Kidney Stones: Challenges to Traditional Stakeholder Engagement

Background: Every year approximately 2 million patients are seen in US EDs for suspected renal colic, and the majority receive CT scans. The objective of our study was to develop a stakeholder-informed conversation aid to help clinicians use SDM regarding CT scanning in patients with suspected renal colic. Methods: Using a published decision aid development framework, and under the direction of a multi-disciplinary Steering Committee, we engaged a diverse set of stakeholders via qualitative methods. EM clinicians, urologists, radiologists, researchers, and emergency department patients participated in focus groups and semi-structured interviews. All groups were recorded, transcribed, and analyzed in an iterative process by a four-person coding team. Emergent themes were identified and used to develop a decision aid which was iteratively refined. Results: A total of 8 interviews and 7 focus groups were conducted with 36 stakeholders (including local ED patients) The following three themes emerged: 1. Patient participants reported a desire to be involved in this decision and wanted more information regarding risks and benefits of CT scans. 2. Clinicians were comfortable diagnosing kidney stones without a CT scan, however, some felt that clinical uncertainty was a barrier to SDM. 3. All stakeholders identified strategies to facilitate this conversation such as check-lists and visual aids. Conclusion: Using stakeholder input, we developed a communication tool to facilitate an SDM conversation around the use of CT in suspected renal colic. Further testing will assess whether this tool can safely improve patient engagement and decrease low yield CT usage

Event trees and epistemic uncertainty in long‐term volcanic hazard assessment of Rift Volcanoes: the example of Aluto (Central Ethiopia)

Aluto is a peralkaline rhyolitic caldera located in a highly populated area in central Ethiopia. Its postcaldera eruptive activity has mainly consisted of self‐similar, pumice‐cone‐building eruptions of varying size and vent location. These eruptions are explosive, generating hazardous phenomena that could impact proximal to distal areas from the vent. Volcanic hazard assessments in Ethiopia and the East African Rift are still limited in number. In this study, we develop an event tree model for Aluto volcano. The event tree is doubly useful: It facilitates the design of a conceptual model for the volcano and provides a framework to quantify volcanic hazard. We combine volcanological data from past and recent research at Aluto, and from a tool to objectively derive analog volcanoes (VOLCANS), to parameterize the event tree, including estimates of the substantial epistemic uncertainty. Results indicate that the probability of a silicic eruption in the next 50 years is highly uncertain, ranging from 2% to 35%. This epistemic uncertainty has a critical influence on event‐tree estimates for other volcanic events, like the probability of occurrence of pyroclastic density currents (PDCs) in the next 50 years. The 90% credible interval for the latter is 5–16%, considering only the epistemic uncertainty in conditional eruption size and PDC occurrence, but 2–23% when adding the epistemic uncertainty in the probability of eruption in 50 years. Despite some anticipated challenges, we envisage that our event tree could be translated to other rift volcanoes, making it an important tool to quantify volcanic hazard in Ethiopia and elsewhere

First radial velocity results from the MINiature Exoplanet Radial Velocity Array (MINERVA)

The MINiature Exoplanet Radial Velocity Array (MINERVA) is a dedicated observatory of four 0.7m robotic telescopes fiber-fed to a KiwiSpec spectrograph. The MINERVA mission is to discover super-Earths in the habitable zones of nearby stars. This can be accomplished with MINERVA's unique combination of high precision and high cadence over long time periods. In this work, we detail changes to the MINERVA facility that have occurred since our previous paper. We then describe MINERVA's robotic control software, the process by which we perform 1D spectral extraction, and our forward modeling Doppler pipeline. In the process of improving our forward modeling procedure, we found that our spectrograph's intrinsic instrumental profile is stable for at least nine months. Because of that, we characterized our instrumental profile with a time-independent, cubic spline function based on the profile in the cross dispersion direction, with which we achieved a radial velocity precision similar to using a conventional "sum-of-Gaussians" instrumental profile: 1.8 m s$^{-1}$ over 1.5 months on the RV standard star HD 122064. Therefore, we conclude that the instrumental profile need not be perfectly accurate as long as it is stable. In addition, we observed 51 Peg and our results are consistent with the literature, confirming our spectrograph and Doppler pipeline are producing accurate and precise radial velocities.Comment: 22 pages, 9 figures, submitted to PASP, Peer-Reviewed and Accepte

New physical characterization of the Fontana Lapilli basaltic Plinian eruption, Nicaragua

The Fontana Lapilli deposit was erupted in the late Pleistocene from a vent, or multiple vents, located near Masaya volcano (Nicaragua) and is the product of one of the largest basaltic Plinian eruptions studied so far. This eruption evolved from an initial sequence of fluctuating fountain-like events and moderately explosive pulses to a sustained Plinian episode depositing fall beds of highly vesicular basaltic-andesite scoria (SiO2 > 53 wt%). Samples show unimodal grain size distribution and a moderate sorting that are uniform in time. The juvenile component predominates (> 96 wt%) and consists of vesicular clasts with both sub-angular and fluidal, elongated shapes. We obtain a maximum plume height of 32 km and an associated mass eruption rate of 1.4 × 108 kg s−1 for the Plinian phase. Estimates of erupted volume are strongly sensitive to the technique used for the calculation and to the distribution of field data. Our best estimate for the erupted volume of the majority of the climactic Plinian phase is between 2.9 and 3.8 km3 and was obtained by applying a power-law fitting technique with different integration limits. The estimated eruption duration varies between 4 and 6 h. Marine-core data confirm that the tephra thinning is better fitted by a power-law than by an exponential trend

The greenhouse gas impacts of converting food production in England and Wales to organic methods

Agriculture is a major contributor to global greenhouse gas (GHG) emissions and must feature in efforts to reduce emissions. Organic farming might contribute to this through decreased use of farm inputs and increased soil carbon sequestration, but it might also exacerbate emissions through greater food production elsewhere to make up for lower organic yields. To date there has been no rigorous assessment of this potential at national scales. Here we assess the consequences for net GHG emissions of a 100% shift to organic food production in England and Wales using life-cycle assessment. We predict major shortfalls in production of most agricultural products against a conventional baseline. Direct GHG emissions are reduced with organic farming, but when increased overseas land use to compensate for shortfalls in domestic supply are factored in, net emissions are greater. Enhanced soil carbon sequestration could offset only a small part of the higher overseas emissions

Transfection of IL-10 expression vectors into endothelial cultures attenuates α4β7-dependent lymphocyte adhesion mediated by MAdCAM-1

BACKGROUND: Enhanced expression of MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is associated with the onset and progression of inflammatory bowel disease. The clinical significance of elevated MAdCAM-1 expression is supported by studies showing that immunoneutralization of MAdCAM-1, or its ligands reduce inflammation and mucosal damage in models of colitis. Interleukin-10 (IL-10) is an endogenous anti-inflammatory and immunomodulatory cytokine that has been shown to prevent inflammation and injury in several animal studies, however clinical IL-10 treatment remains insufficient because of difficulties in the route of IL-10 administration and its biological half-life. Here, we examined the ability of introducing an IL-10 expression vector into endothelial cultures to reduce responses to a proinflammatory cytokine, TNF-α METHODS: A human IL-10 expression vector was transfected into high endothelial venular ('HEV') cells (SVEC4-10); we then examined TNF-α induced lymphocyte adhesion to lymphatic endothelial cells and TNF-α induced expression of MAdCAM-1 and compared these responses to control monolayers. RESULTS: Transfection of the IL-10 vector into endothelial cultures significantly reduced TNF-α induced, MAdCAM-1 dependent lymphocyte adhesion (compared to non-transfected cells). IL-10 transfected endothelial cells expressed less than half (46 ± 6.6%) of the MAdCAM-1 induced by TNF-α (set as 100%) in non-transfected (control) cells. CONCLUSION: Our results suggest that gene therapy of the gut microvasculature with IL-10 vectors may be useful in the clinical treatment of IBD

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome