Teaching Medical Students Optimal Consulting Skills: The Challenge of Generating Better Referring Physicians.

Rationale and objectives We sought to incorporate a new teaching module into the traditional medical student radiology clerkship, to improve the necessary skills for future referring physicians. Materials and methods A new required and graded module was introduced in 2014 into the radiology clerkship in year three of medical school: the Mystery Case. Each student was provided a unique and undifferentiated case from a dedicated teaching file containing de-identified images and requisition data. Students were expected to complete three serial tasks over one week: 1) prepare a voice recognition-derived, structured radiological report utilizing appropriate and relevant vocabulary; 2) discuss pertinent additional clinical information; and 3) discuss appropriate follow-up imaging, in addition to information on how to best prepare patients for these potential patient exams (e.g., with or without contrast, bowel preparation, and length of study). Students were provided written examples and dedicated class instruction with interactive discussions covering specific cases and associated related cases through random pairing with radiology resident and attending mentors. At the close of the week, students gave brief oral presentations of their cases and submitted the tasks for a written evaluation. Upon completion of the clerkship, the students completed a Likert-type six-item survey to evaluate the perceived improvement in select skills. Results The survey was completed by 82% (54/66) of the enrolled students, with 85% finding the Mystery Case an effective use of time. Medical students perceived an improved awareness of the patient care process (77%), awareness of the medical imaging resources available (89%), ability to understand a radiology report (74%), and ability to advise patients (69%). Conclusion Introduction of the Mystery Case as a graded exercise in the medical school radiology clerkship was perceived by students as effective use of time, with an improvement in the skills essential for future referring physicians

Comparative Analysis of Illicit Supply Network Structure and Operations: Cocaine, Wildlife, and Sand

Illicit supply networks (ISNs) are composed of coordinated human actors that source, transit, and distribute illicitly traded goods to consumers, while also creating widespread social and environmental harms. Despite growing documentation of ISNs and their impacts, efforts to understand and disrupt ISNs remain insufficient due to the persistent lack of knowledge con-necting a given ISN’s modus operandi and its patterns of activity in space and time. The core challenge is that the data and knowledge needed to integrate it remain fragmented and/or compartmentalized across disciplines, research groups, and agencies tasked with understanding or monitoring one or a few specific ISNs. One path forward is to conduct comparative analyses of multiple diverse ISNs. We present and apply a conceptual framework for linking ISN modus operandi to spatial-temporal dynamics and patterns of activity. We demonstrate this through a comparative analysis of three ISNs – cocaine, illegally traded wildlife, and illegally mined sand – which range from well-established to emergent, global to domestic in geographic scope, and fully illicit to de facto legal. The proposed framework revealed consistent traits related to geographic price structure, value capture at different supply chain stages, and key differ-ences among ISN structure and operation related to commodity characteristics and their relative illicitness. Despite the diversity of commodities and ISN attributes compared, social and environmental harms inflicted by the illicit activity consistently become more widespread with increasing law enforcement disruption. Drawing on these lessons from diverse ISNs, which varied in their histories and current sophistication, possible changes in the structure and function of nascent and/or low salience ISNs may be anticipated if future conditions or law enforcement pressure change

A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum

A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20ka, 15ka, 10ka and 5ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse 1a. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorit. © 2014 The Authors

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Recombination processes in quantum dot lasers.

The drive for low threshold and temperature-stable semiconductor lasers for telecommunication applications has led to a significant interest in quantum dot (QD) lasers emitting in the 1.3 mum and 1.5 mum wavelength range. The literature shows that although low threshold current densities can be achieved, this is usually at the expense of a poor temperature stability. Low-temperature and high-pressure measurements of the threshold current and its radiative component are performed on undoped and p-doped 1.3 mum InAs/GaAs and 1.5 mum InAs/InP (311)B QD lasers. The results show that despite a fairly temperature-stable radiative current around room temperature, undoped QD lasers suffer from a poor temperature stability of their threshold current. This is because there is a large contribution (70% and 90% of the threshold current at room temperature in 1.3 and 1.5 mum lasers, respectively) from a strongly temperature sensitive non-radiative Auger recombination process. Several pieces of evidence are found to explain the observed decrease of the radiative current, explained by an improvement of the carrier distribution with increasing temperature. We find that in p-doped devices the temperature dependence of the radiative component of the threshold current can be modified by the doping. In these devices the radiative current can decrease with increasing temperature around room temperature while the non-radiative current increases. This results in a small range of temperatures over which the threshold current is constant (from ~ 270 to 300 K). This effect is very sensitive to the doping concentration. If the doping concentration is carefully chosen, this can result in high T0 devices but with larger threshold currents than in comparable undoped lasers. Gain measurements reveal that the differential gain of p-doped lasers is less than that of the undoped devices because of the increased non-radiative current and the non-thermal distribution of the carriers induced by the doping. Finally, a new method is demonstrated to measure the band gap dependence of the Auger coefficient, C, using a combination of high hydrostatic pressure measurements coupled with gain calculations

Recombination processes in quantum dot lasers.

The drive for low threshold and temperature-stable semiconductor lasers for telecommunication applications has led to a significant interest in quantum dot (QD) lasers emitting in the 1.3 mum and 1.5 mum wavelength range. The literature shows that although low threshold current densities can be achieved, this is usually at the expense of a poor temperature stability. Low-temperature and high-pressure measurements of the threshold current and its radiative component are performed on undoped and p-doped 1.3 mum InAs/GaAs and 1.5 mum InAs/InP (311)B QD lasers. The results show that despite a fairly temperature-stable radiative current around room temperature, undoped QD lasers suffer from a poor temperature stability of their threshold current. This is because there is a large contribution (70% and 90% of the threshold current at room temperature in 1.3 and 1.5 mum lasers, respectively) from a strongly temperature sensitive non-radiative Auger recombination process. Several pieces of evidence are found to explain the observed decrease of the radiative current, explained by an improvement of the carrier distribution with increasing temperature. We find that in p-doped devices the temperature dependence of the radiative component of the threshold current can be modified by the doping. In these devices the radiative current can decrease with increasing temperature around room temperature while the non-radiative current increases. This results in a small range of temperatures over which the threshold current is constant (from ~ 270 to 300 K). This effect is very sensitive to the doping concentration. If the doping concentration is carefully chosen, this can result in high T0 devices but with larger threshold currents than in comparable undoped lasers. Gain measurements reveal that the differential gain of p-doped lasers is less than that of the undoped devices because of the increased non-radiative current and the non-thermal distribution of the carriers induced by the doping. Finally, a new method is demonstrated to measure the band gap dependence of the Auger coefficient, C, using a combination of high hydrostatic pressure measurements coupled with gain calculations