Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial.

BACKGROUND: In areas co-endemic for Plasmodium vivax and Plasmodium falciparum there is an increased risk of P vivax parasitaemia following P falciparum malaria. Radical cure is currently only recommended for patients presenting with P vivax malaria. Expanding the indication for radical cure to patients presenting with P falciparum malaria could reduce their risk of subsequent P vivax parasitaemia. METHODS: We did a multicentre, open-label, superiority randomised controlled trial in five health clinics in Bangladesh, Indonesia, and Ethiopia. In Bangladesh and Indonesia, patients were excluded if they were younger than 1 year, whereas in Ethiopia patients were excluded if they were younger than 18 years. Patients with uncomplicated P falciparum monoinfection who had fever or a history of fever in the 48 h preceding clinic visit were eligible for enrolment and were required to have a glucose-6-dehydrogenase (G6PD) activity of 70% or greater. Patients received blood schizontocidal treatment (artemether-lumefantrine in Ethiopia and Bangladesh and dihydroartemisinin-piperaquine in Indonesia) and were randomly assigned (1:1) to receive either high-dose short-course oral primaquine (intervention arm; total dose 7 mg/kg over 7 days) or standard care (standard care arm; single dose oral primaquine of 0·25 mg/kg). Random assignment was done by an independent statistician in blocks of eight by use of sealed envelopes. All randomly assigned and eligible patients were included in the primary and safety analyses. The per-protocol analysis excluded those who did not complete treatment or had substantial protocol violations. The primary endpoint was the incidence risk of P vivax parasitaemia on day 63. This trial is registered at ClinicalTrials.gov, NCT03916003. FINDINGS: Between Aug 18, 2019, and March 14, 2022, a total of 500 patients were enrolled and randomly assigned, and 495 eligible patients were included in the intention-to-treat analysis (246 intervention and 249 control). The incidence risk of P vivax parasitaemia at day 63 was 11·0% (95% CI 7·5-15·9) in the standard care arm compared with 2·5% (1·0-5·9) in the intervention arm (hazard ratio 0·20, 95% CI 0·08-0·51; p=0·0009). The effect size differed with blood schizontocidal treatment and site. Routine symptom reporting on day 2 and day 7 were similar between groups. In the first 42 days, there were a total of four primaquine-related adverse events reported in the standard care arm and 26 in the intervention arm; 132 (92%) of all 143 adverse events were mild. There were two serious adverse events in the intervention arm, which were considered unrelated to the study drug. None of the patients developed severe anaemia (defined as haemoglobin <5 g/dL). INTERPRETATION: In patients with a G6PD activity of 70% or greater, high-dose short-course primaquine was safe and relatively well tolerated and reduced the risk of subsequent P vivax parasitaemia within 63 days by five fold. Universal radical cure therefore potentially offers substantial clinical, public health, and operational benefits, but these benefits will vary with endemic setting. FUNDING: Australian Academy of Science Regional Collaborations Program, Bill & Melinda Gates Foundation, and National Health and Medical Research Council.

Adapting international clinical trials during COVID-19 and beyond.

BACKGROUND: The COVID-19 pandemic and resulting restrictions, particularly travel restrictions, have had significant impact on the conduct of global clinical trials. Our clinical trials programme, which relied on in-person visits for training, monitoring and capacity building across nine low- and middle-income countries, had to adapt to those unprecedented operational challenges. We report the adaptation of our working model with a focus on the operational areas of training, monitoring and cross-site collaboration. THE NEW WORKING MODEL: Adaptations include changing training strategies from in-person site visits with three or four team members to a multi-pronged virtual approach, with generic online training for good clinical practice, the development of a library of study-specific training videos, and interactive virtual training sessions, including practical laboratory-focused training sessions. We also report changes from in-person monitoring to remote monitoring as well as the development of a more localized network of clinical trial monitors to support hybrid models with in-person and remote monitoring depending on identified risks at each site. We established a virtual network across different trial and study sites with the objective to further build capacity for good clinical practice-compliant antimalarial trials and foster cross-country and cross-study site collaboration. CONCLUSION: The forced adaptation of these new strategies has come with advantages that we did not envisage initially. This includes improved, more frequent engagement through the established network with opportunities for increased south-to-south support and a substantially reduced carbon footprint and budget savings. Our new approach is challenging for study sites with limited prior experience but this can be overcome with hybrid models. Capacity building for laboratory-based work remains difficult using a virtual environment. The changes to our working model are likely to last, even after the end of the pandemic, providing a more sustainable and equitable approach to our research.

Compartment Syndrome after Crotalid Envenomation in the United States: A Review of the North American Snakebite Registry from 2013 to 2021 on Behalf of the ToxIC Snakebite Study Group.

INTRODUCTION: Compartment syndrome (CS) is a rare but serious complication after crotalid envenomation in the United States. Few data are available regarding the epidemiology and management of these cases. Significant controversy and misunderstanding over best practices, including measurement of compartment pressures and use of fasciotomy, exist for this syndrome. This study aims to describe presentation and management of suspected CS cases after native snakebite reported to the North American Snakebite Registry (NASBR). METHODS: This is an analysis of snakebite cases reported to the Toxicology Investigators Consortium NASBR between January 1, 2013 and December 31, 2021. Cases of native snakebite with documented concern for CS were included. RESULTS: Over an 8-y period, 22 cases of suspected CS were identified, representing 1% of all cases reported to the NASBR. Fasciotomies were performed in 41% (n=9) of these cases, most commonly to the upper extremity (67%, n=6). In cases of suspected CS, intracompartmental pressures (ICPs) were rarely measured (23%, n=5) and fasciotomies were performed without measurement of ICPs frequently (56%, n=5). In 1 case, ICPs were measured and found to be low (8 mm Hg) and fasciotomy was avoided. CONCLUSIONS: Measurement of compartment pressures in cases of suspected CS was uncommon in cases reported to the NASBR. Fasciotomy was commonly performed without measurement of compartment pressures.

Molecular basis of the association between transcription regulators nuclear respiratory factor 1 and inhibitor of DNA binding protein 3 and the development of microvascular lesions.

The prognosis of patients with microvascular lesions remains poor because vascular remodeling eventually obliterates the lumen. Here we have focused our efforts on vessel dysfunction in two different organs, the lung and brain. Despite tremendous progress in understanding the importance of blood vessel integrity, gaps remain in our knowledge of the underlying molecular factors contributing to vessel injury, including microvascular lesions. Most of the ongoing research on these lesions have focused on oxidative stress but have not found major molecular targets for the discovery of new treatment or early diagnosis. Herein, we have focused on elucidating the molecular mechanism(s) based on two new emerging molecules NRF1 and ID3, and how they may contribute to microvascular lesions in the lung and brain. Redox sensitive transcriptional activation of target genes depends on not only NRF1, but the recruitment of co-activators such as ID3 to the target gene promoter. Our review highlights the fact that targeting NRF1 and ID3 could be a promising therapeutic approach as they are major players in influencing cell growth, cell repair, senescence, and apoptotic cell death which contribute to vascular lesions. Knowledge about the molecular biology of these processes will be relevant for future therapeutic approaches to not only PAH but cerebral angiopathy and other vascular disorders. Therapies targeting transcription regulators NRF1 or ID3 have the potential for vascular disease-modification because they will address the root causes such as genomic instability and epigenetic changes in vascular lesions. We hope that our findings will serve as a stimulus for further research towards an effective treatment of microvascular lesions.

A Psychological Resilience Briefing Intervention for Helicopter Emergency Medical Service Observers.

OBJECTIVE: Helicopter emergency medical services (HEMS) observers may be at risk of negative psychological effects associated with exposure to traumatic events during shifts. This article describes a quality improvement project for HEMS observers at Essex & Herts Air Ambulance. METHODS: A psychological resilience briefing intervention (PRBi) was developed and delivered during induction training with 60 HEMS observers. The PRBi aimed to raise awareness of traumatic events that observers may experience and provided basic education on 5 domains, including likely forms of trauma exposure, possible psychological reactions, advice on coping strategies and supporting colleagues, and resources that they could use if required. The intervention was intended to bolster resilience and reduce posttraumatic stress disorder symptoms, and to encourage adaptive coping styles in observers. RESULTS: Observers learned from and valued the PRBi; statistically significant increases were observed in awareness of the 5 domains from pre- to post-delivery, and free-text responses cited a variety of benefits to the observers. There was no indication that the PRBi caused harm. CONCLUSION: The PRBi has now been included in the routine induction of observers at Essex & Herts Air Ambulance and has the potential to be repurposed for use in other settings, including medical schools.

Emergency scalpel cricothyroidotomy use in a prehospital trauma service: a 20-year review.

BACKGROUND: This study aimed to determine the rate of scalpel cricothyroidotomy conducted by a physician-paramedic prehospital trauma service over 20 years and to identify indications for, and factors associated with the intervention. METHODS: A retrospective observational study was conducted from 1 January 2000 to 31 December 2019 using clinical database records. This study was conducted in a physician-paramedic prehospital trauma service, serving a predominantly urban population of approximately 10 million in an area of approximately 2500 km2. RESULTS: Over 20 years, 37 725 patients were attended by the service, and 72 patients received a scalpel cricothyroidotomy. An immediate 'primary' cricothyroidotomy was performed in 17 patients (23.6%), and 'rescue' cricothyroidotomies were performed in 55 patients (76.4%). Forty-one patients (56.9%) were already in traumatic cardiac arrest during cricothyroidotomy. Thirty-two patients (44.4%) died on scene, and 32 (44.4%) subsequently died in hospital. Five patients (6.9%) survived to hospital discharge, and three patients (4.2%) were lost to follow-up. The most common indication for primary cricothyroidotomy was mechanical entrapment of patients (n=5, 29.4%). Difficult laryngoscopy, predominantly due to airway soiling with blood (n=15, 27.3%) was the most common indication for rescue cricothyroidotomy. The procedure was successful in 97% of cases. During the study period, 6570 prehospital emergency anaesthetics were conducted, of which 30 underwent rescue cricothyroidotomy after failed tracheal intubation (0.46%, 95% CI 0.31% to 0.65%). CONCLUSIONS: This study identifies a number of indications leading to scalpel cricothyroidotomy both as a primary procedure or after failed intubation. The main indication for scalpel cricothyroidotomy in our service was as a rescue airway for failed laryngoscopy due to a large volume of blood in the airway. Despite high levels of procedural success, 56.9% of patients were already in traumatic cardiac arrest during cricothyroidotomy, and overall mortality in patients with trauma receiving this procedure was 88.9% in our service.

Scoping the Demand for Night Operation of Essex & Herts Air Ambulance: A Prospective Observational Study.

OBJECTIVE: Helicopter emergency medical services play an important role in the prehospital care of critically ill and injured patients, providing enhanced interventions and direct transfer to specialist centers. Essex & Herts Air Ambulance (EHAAT) delivers prehospital critical care to patients in Essex, Hertfordshire, and the surrounding areas. Historically, EHAAT's resources have not operated during the night. This study aimed to ascertain demand for prehospital critical care in Essex and Hertfordshire during night hours. METHODS: A prospective observational design was used. Data were collected by 11 critical care paramedics during night shifts on a critical care desk using an online survey. Details were recorded for incidents in Essex and Hertfordshire between 21:00 and 07:00 deemed appropriate for a prehospital critical care response. RESULTS: A total of 108 incidents were recorded across 52 nights, equating to an average of 2.08 incidents per night. For 52 incidents, there was no critical care resource available to attend. The majority of incidents fell in closer proximity to EHAAT's North Weald base than its Earls Colne base. CONCLUSION: The findings suggest a potential need for prehospital critical care during night hours in Essex and Hertfordshire and support the operation of a resource from EHAAT's North Weald base.

Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival.

OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world's healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. "First come, first served" is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.

Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients.

A global health emergency has been declared by the World Health Organization as the 2019-nCoV outbreak spreads across the world, with confirmed patients in Canada. Patients infected with 2019-nCoV are at risk for developing respiratory failure and requiring admission to critical care units. While providing optimal treatment for these patients, careful execution of infection control measures is necessary to prevent nosocomial transmission to other patients and to healthcare workers providing care. Although the exact mechanisms of transmission are currently unclear, human-to-human transmission can occur, and the risk of airborne spread during aerosol-generating medical procedures remains a concern in specific circumstances. This paper summarizes important considerations regarding patient screening, environmental controls, personal protective equipment, resuscitation measures (including intubation), and critical care unit operations planning as we prepare for the possibility of new imported cases or local outbreaks of 2019-nCoV. Although understanding of the 2019-nCoV virus is evolving, lessons learned from prior infectious disease challenges such as Severe Acute Respiratory Syndrome will hopefully improve our state of readiness regardless of the number of cases we eventually manage in Canada.

RéSUMé: Une urgence sanitaire mondiale a été déclarée par l'Organisation mondiale de la Santé alors que l'épidémie de 2019-nCoV se répand dans le monde et que des cas ont été confirmés au Canada. Les patients infectés par le 2019-nCoV sont à risque d'insuffisance respiratoire et peuvent nécessiter une admission à l'unité de soins intensifs. Lors d'une prise en charge optimale de ces patients, il est indispensable de prendre soin d'exécuter rigoureusement les mesures de contrôle des infections afin de prévenir la transmission nosocomiale aux autres patients et aux travailleurs de la santé prodiguant les soins. Bien que les mécanismes précis de transmission ne soient pas encore connus, la transmission d'humain à humain peut survenir, et le risque de dissémination aérienne pendant les interventions médicales générant des aérosols est préoccupant dans certaines circonstances spécifiques. Cet article résume des considérations importantes en ce qui touche au dépistage des patients, aux contrôles environnementaux, au matériel de protection personnelle, aux mesures de réanimation (y compris l'intubation), et à la planification des activités à l'unité de soins intensifs alors que nous nous préparons à la possibilité de nouveaux cas importés ou d'éclosions locales du 2019-nCoV. Bien que la compréhension du virus 2019-nCoV continue d'évoluer, nous espérons que les leçons retenues des éclosions précédentes de maladies infectieuses telles que le syndrome respiratoire aigu sévère nous permettront d'améliorer notre degré de préparation, indépendamment du nombre de cas que nous traiterons au Canada.

The safety of double- and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, open-label, cluster-randomized study.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings. METHODS AND FINDINGS: Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 µg/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were ≥5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites. CONCLUSIONS: In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA. TRIAL REGISTRATION: Clinicaltrials.gov registration number: NCT02899936.

Juvenile-onset systemic lupus erythematosus: Update on clinical presentation, pathophysiology and treatment options.

Juvenile-onset systemic lupus erythematosus (jSLE) accounts for up to 20% of all SLE patients. Key differences between juvenile- and adult-onset (aSLE) disease include higher disease activity, earlier development of damage, and increased use of immunosuppressive treatment in jSLE suggesting (at least partial) infectivity secondary to variable pathomechanisms. While the exact pathophysiology of jSLE remains unclear, genetic factors, immune complex deposition, complement activation, hormonal factors and immune cell dysregulation are involved to variable extents, promising future patient stratification based on immune phenotypes. Though less effective and potentially toxic, jSLE patients are treated based upon evidence from studies in aSLE cohorts. Here, age-specific clinical features of jSLE, underlying pathomechanisms, treatment options and disease outcomes will be addressed. Future directions to improve the care of jSLE patients, including implementation of the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) recommendations, biomarkers, treat to target and personalized medicine approaches are discussed.

CASP1 variants influence subcellular caspase-1 localization, pyroptosome formation, pro-inflammatory cell death and macrophage deformability.

CASP1 variants result in reduced enzymatic activity of procaspase-1 and impaired IL-1ß release. Despite this, affected individuals can develop systemic autoinflammatory disease. These seemingly contradictory observations have only partially been explained by increased NF-κB activation through prolonged interaction of variant procaspase-1 with RIP2. To identify further disease underlying pathomechanisms, we established an in vitro model using shRNA-directed knock-down of procaspase-1 followed by viral transduction of human monocytes (THP-1) with plasmids encoding for wild-type procaspase-1, disease-associated CASP1 variants (p.L265S, p.R240Q) or a missense mutation in the active center of procaspase-1 (p.C285A). THP1-derived macrophages carrying CASP1 variants exhibited mutation-specific molecular alterations. We here provide in vitro evidence for abnormal pyroptosome formation (p.C285A, p.240Q, p.L265S), impaired nuclear (pro)caspase-1 localization (p.L265S), reduced pro-inflammatory cell death (p.C285A) and changes in macrophage deformability that may contribute to disease pathophysiology of patients with CASP1 variants. This offers previously unknown molecular pathomechanisms in patients with systemic autoinflammatory disease.

Mechanistic aspects of epigenetic dysregulation in SLE.

Epigenetic events have been linked with disease expression in individuals genetically predisposed to the development of systemic lupus erythematosus (SLE), a severe systemic autoimmune/inflammatory disease. Altered DNA methylation and hydroxymethylation as well as histone modifications mediate changes in chromatin accessibility and gene expression in immune cells from SLE patients. Defective epigenetic control contributes to uncontrolled expression of inflammatory mediators, including cytokines and co-receptors, resulting in systemic inflammation and tissue damage. While the pathophysiological involvement of epigenetic changes in SLE has been accepted for some time, we only recently started to investigate and understand molecular events contributing to epigenetic dysregulation. Here, epigenetic alterations will be discussed with a focus on underling molecular events that may be target of preventative measures or future treatment strategies.

Enzymatically Inactive Procaspase 1 stabilizes the ASC Pyroptosome and Supports Pyroptosome Spreading during Cell Division.

Caspase-1 is a key player during the initiation of pro-inflammatory innate immune responses, activating pro-IL-1ß in so-called inflammasomes. A subset of patients with recurrent febrile episodes and systemic inflammation of unknown origin harbor mutations in CASP1 encoding caspase-1. CASP1 variants result in reduced enzymatic activity of caspase-1 and impaired IL-1ß secretion. The apparent paradox of reduced IL-1ß secretion but systemic inflammation led to the hypothesis that CASP1 mutations may result in variable protein interaction clusters, thus activating alternative signaling pathways. To test this hypothesis, we established and characterized an in vitro system of transduced immortalized murine macrophages expressing either WT or enzymatically inactive (p.C284A) procaspase-1 fusion reporter proteins. Macrophages with variant p.C284A caspase-1 did not secrete IL-1ß and exhibited reduced inflammatory cell death, referred to as pyroptosis. Caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) formed cytosolic macromolecular complexes (so-called pyroptosomes) that were significantly increased in number and size in cells carrying the p.C284A caspase-1 variant compared with WT caspase-1. Furthermore, enzymatically inactive caspase-1 interacted with ASC longer and with increased intensity compared with WT caspase-1. Applying live cell imaging, we documented for the first time that pyroptosomes containing enzymatically inactive variant p.C284A caspase-1 spread during cell division. In conclusion, variant p.C284A caspase-1 stabilizes pyroptosome formation, potentially enhancing inflammation by two IL-1ß-independent mechanisms: pyroptosomes convey an enhanced inflammatory stimulus through the recruitment of additional proteins (such as RIP2, receptor interacting protein kinase 2), which is further amplified through pyroptosome and cell division.

Epigenetics in SLE.

PURPOSE OF REVIEW: Systemic lupus erythematosus is a severe autoimmune/inflammatory condition of unknown pathophysiology. Though genetic predisposition is essential for disease expression, risk alleles in single genes are usually insufficient to confer disease. Epigenetic dysregulation has been suggested as the missing link between genetic risk and the development of clinically evident disease. RECENT FINDINGS: Over the past decade, epigenetic events moved into the focus of research targeting the molecular pathophysiology of SLE. Epigenetic alteration can be the net result of preceding infections, medication, diet, and/or other environmental influences. While altered DNA methylation and histone modifications had already been established as pathomechanisms, DNA hydroxymethylation was more recently identified as an activating epigenetic mark. Defective epigenetic control contributes to uncontrolled cytokine and co-receptor expression, resulting in immune activation and tissue damage in SLE. Epigenetic alterations promise potential as disease biomarkers and/or future therapeutic targets in SLE and other autoimmune/inflammatory conditions.

Comparison of High-Fidelity Medical Simulation to Short-Answer Written Examination in the Assessment of Emergency Medicine Residents in Medical Toxicology.

We compared high-fidelity medical simulation to short-answer written examination in the assessment of emergency medicine residents (EMR) on a month-long medical toxicology rotation. Knowledge-based assessment tools using cases of an aspirin overdose and a tricyclic antidepressant overdose were used to assess all consecutive rotating EMR (n=53). Assessment by simulation had similar accuracy and precision but higher satisfaction rates when compared to written examination. Incorporating simulation into the ABEM certifying examination warrants further study.

Curved gratings as an integrated photon fluence monitor in x-ray transmission scattering experiments.

A concept to obtain a measure of the photon flux accepted by a solid sample in single-shot transmission experiments with extreme ultraviolet (XUV) or soft x-ray radiation is demonstrated. Shallow, continuously distorted gratings are used to diffract a constant fraction of the incident photons onto an extended area of a CCD detector. The signal can be tailored to fit the dynamic range of the detector, i.e. matching the scattered intensity of the studied structure of interest. Furthermore, composite grating designs that also allow for the measurement of the spatial photon distribution on the sample are demonstrated. The gratings are directly fabricated by focused ion-beam (FIB) lithography into a Si3N4 membrane that supports the actual sample layer. This allows for rapid fabrication of hundreds of samples, making the concept suitable for systematic studies in destructive single-shot measurements at free-electron laser (FEL) sources. We demonstrate relative photon flux measurements in magnetic scattering experiments with synchrotron and FEL radiation at 59.6 eV photon energy.

Sorption and Redox Speciation of Plutonium at the Illite Surface.

The geochemical behavior of Pu strongly depends on its redox speciation. In this study, we investigated Pu sorption onto Na-illite, a relevant component of potential host rocks for high-level nuclear waste repositories, under anaerobic conditions. When contacting Pu (85% Pu(IV), 11% Pu(V), and 4% Pu(III); 8 × 10(-11) < [Pu]tot/M < 10(-8)) with illite in 0.1 M NaCl at pH between 3 and 10, Pu uptake was characterized by log Rd > 4 (Rd: distribution coefficient in L kg(-1)). Small amounts of aqueous Pu(V) were detected in solution on contact with illite after 1 week, which is not expected to be stable at the measured redox potentials (Eh) in our experiments. This observation suggests time-dependent reduction of Pu(V) to Pu(IV). After one year, log Rd values had increased compared to those after 1 week due to the reduction of weakly adsorbing Pu(V). For pH < 5, Pu(IV) and Pu(III) coexisted in solution under our experimental conditions, showing that Pu(IV) reduction to Pu(III) occurred in the illite suspension. Taking (i) surface complexation constants determined for Eu(III)-illite interaction (with redox-insensitive Eu(III) as a chemical analogue to Pu(III)), (ii) the known constant for Pu(III)-Pu(IV) redox transition, and (iii) measured Eh and pH, overall Pu uptake was well-predicted.