A global map of species at risk of extinction due to natural hazards.

An often-overlooked question of the biodiversity crisis is how natural hazards contribute to species extinction risk. To address this issue, we explored how four natural hazards, earthquakes, hurricanes, tsunamis, and volcanoes, overlapped with the distribution ranges of amphibians, birds, mammals, and reptiles that have either narrow distributions or populations with few mature individuals. To assess which species are at risk from these natural hazards, we combined the frequency and magnitude of each natural hazard to estimate their impact. We considered species at risk if they overlapped with regions where any of the four natural hazards historically occurred (n = 3,722). Those species with at least a quarter of their range subjected to a high relative impact were considered at high risk (n = 2,001) of extinction due to natural hazards. In total, 834 reptiles, 617 amphibians, 302 birds, and 248 mammals were at high risk and they were mainly distributed on islands and in the tropics. Hurricanes (n = 983) and earthquakes (n = 868) affected most species, while tsunamis (n = 272), and volcanoes (n = 171) affected considerably fewer. The region with the highest number of species at high risk was the Pacific Ring of Fire, especially due to volcanoes, earthquakes, and tsunamis, while hurricane-related high-risk species were concentrated in the Caribbean Sea, Gulf of Mexico, and northwestern Pacific Ocean. Our study provides important information regarding the species at risk due to natural hazards and can help guide conservation attention and efforts to safeguard their survival.

The reorganization of predator-prey networks over 20 million years explains extinction patterns of mammalian carnivores.

Linking the species interactions occurring at the scale of local communities to their potential impact at evolutionary timescales is challenging. Here, we used the high-resolution fossil record of mammals from the Iberian Peninsula to reconstruct a timeseries of trophic networks spanning more than 20 million years and asked whether predator-prey interactions affected regional extinction patterns. We found that, despite small changes in species richness, trophic networks showed long-term trends, gradually losing interactions and becoming sparser towards the present. This restructuring of the ecological networks was driven by the loss of medium-sized herbivores, which reduced prey availability for predators. The decrease in prey availability was associated with predator longevity, such that predators with less available prey had greater extinction risk. These results not only reveal long-term trends in network structure but suggest that prey species richness in ecological communities may shape large scale patterns of extinction and persistence among predators.

Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening.

BACKGROUND AND AIMS: Implementation of screening modalities have reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy. METHODS: In this prospective multi-center study, eight blood-based biomarkers (CEA, Ferritin, hsCRP, HE4, Cyfra21-1, Hepsin, IL-8 and OPG) were investigated in 1,977 FIT positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on ARCHITECT i2000®, ARCHITECT c8000® or Luminex xMAP® machines. FIT analyses and blood-based biomarker data were combined with clinical data (i.e., age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity. RESULTS: The cohort included individuals with CRC (n = 240), adenomas (n = 938) or no neoplastic lesions (n = 799). The cross-validated algorithm combining the eight biomarkers, quantitative FIT result and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (AUC 0.77 versus 0.67, p < 0.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the AUCs were 0.68 versus 0.64 for the algorithm and FIT model, respectively. CONCLUSIONS: The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenomas detection rates or vice versa.

Simulation-based assessment of upper abdominal ultrasound skills.

BACKGROUND: Ultrasound is a safe and effective diagnostic tool used within several specialties. However, the quality of ultrasound scans relies on sufficiently skilled clinician operators. The aim of this study was to explore the validity of automated assessments of upper abdominal ultrasound skills using an ultrasound simulator. METHODS: Twenty five novices and five experts were recruited, all of whom completed an assessment program for the evaluation of upper abdominal ultrasound skills on a virtual reality simulator. The program included five modules that assessed different organ systems using automated simulator metrics. We used Messick's framework to explore the validity evidence of these simulator metrics to determine the contents of a final simulator test. We used the contrasting groups method to establish a pass/fail level for the final simulator test. RESULTS: Thirty seven out of 60 metrics were able to discriminate between novices and experts (p < 0.05). The median simulator score of the final simulator test including the metrics with validity evidence was 26.68% (range: 8.1-40.5%) for novices and 85.1% (range: 56.8-91.9%) for experts. The internal structure was assessed by Cronbach alpha (0.93) and intraclass correlation coefficient (0.89). The pass/fail level was determined to be 50.9%. This pass/fail criterion found no passing novices or failing experts. CONCLUSIONS: This study collected validity evidence for simulation-based assessment of upper abdominal ultrasound examinations, which is the first step toward competency-based training. Future studies may examine how competency-based training in the simulated setting translates into improvements in clinical performances.

Coevolutionary hotspots favour dispersal and fuel biodiversity in mutualistic landscapes under environmental changes.

Mutualistic interactions are key to sustaining Earth's biodiversity. Yet, we are only beginning to understand how coevolution in mutualistic assemblages can shape the distribution and persistence of species across landscapes. Here, we combine the geographic mosaic theory of coevolution with metacommunity dynamics to understand how geographically structured selection can shape patterns of richness, dispersal, extinction and persistence of mutualistic species. In this model, species may experience strong or weak reciprocal selection imposed by mutualisms within each patch (i.e. hotspots and coldspots, respectively). Using numerical simulations, we show that mutualistic coevolution leads to a concentration of species richness at hotspots. Such an effect occurs because hotspots sustain higher rates of colonization and lower rates of extinction than coldspots, whether the environment changes or not. Importantly, under environmental changes, coldspots fail to sustain a positive colonization-to-extinction balance. Rather, species persistence within coldspots relies on hotspots acting as biodiversity sources and enhancing population dispersal across the landscape. In fact, even a few hotspots in the landscape can fuel the spatial network of dispersal of populations in the metacommunity. Our study highlights that coevolutionary hotspots can act as biodiversity sources, favouring colonization and allowing species to expand their distribution across landscapes even in changing environments. This article is part of the theme issue 'Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics'.

Treatment Strategies for Filamentous Fungi Keratitis.

INTRODUCTION: This research aims to describe clinical findings, epidemiology and treatment outcomes in patients with filamentous fungi keratitis of a tertiary centre in Germany over a 7-year period and to compare the efficacy of different antifungal treatments and the effect of additive topical steroids. METHODS: This retrospective study included 25 eyes of 23 patients from October 2013 to December 2020 with cultural isolates of filamentous fungi and corresponding keratitis. Best-corrected visual acuity (BCVA), clinical signs, symptoms, risk factors and outcome were extracted from medical records. RESULTS: Improvement of BVCA was noted in 68% of eyes. Mean BCVA of the study population increased from 0.75 logMAR [median 0.40, standard deviation (SD) 0.82, range 0-2.3] to 0.48 logMAR (median 0.10, SD 0.88, range - 0.1 to 3). The most commonly used antifungal topical treatment was a combination of natamycin 5% and voriconazole 2% (44% of eyes), followed by voriconazole 2% in 36% of cases. An antiinflammatory topical steroid was applied in 52%. In 16% of the eyes, penetrating keratoplasty (pKP) was performed. CONCLUSION: Diagnosis of filamentous fungi keratitis is often difficult or delayed. Outcomes can be poor even with intensive treatment because of high resistance to common antifungals. Access to natamycin 5% seems to lead to favourable outcomes in filamentous fungi keratitis.

External quality assessments for SARS-CoV-2 genome detection in Austria : A comparison of the first postpandemic round with results from the pandemic era.

BACKGROUND: External quality assessment (EQA) schemes provide objective feedback to participating laboratories about the performance of their analytical systems and information about overall regional analytical performance. The EQAs are particularly important during pandemics as they also assess the reliability of individual test results and show opportunities to improve test strategies. With the end of the COVID-19 pandemic, the testing frequency significantly decreased in Austria. Here, we analyzed whether this decrease had an effect on participation and/or performance in SARS-CoV­2 virus detection EQAs, as compared to the pandemic era. MATERIAL AND METHODS: Identical samples were sent to all participating laboratories, and the EQA provider evaluated the agreement of the reported results with defined targets. The EQA was operated under two schemes with identical samples and therefore we analyzed it as a single EQA round. The performance of testing was reported as true positive ratios, comparing the post-pandemic data to previous rounds. Furthermore, subgroups of participants were analyzed stratified by laboratory type (medical or nonmedical) and the test system format (fully automated or requiring manual steps). RESULTS: While the frequency of false negative results per sample did not change during the 3 years of the pandemic (5.7%, 95% confidence interval [CI] 3.1-8.4%), an average per sample false negative ratio of 4.3% was observed in the first post-pandemic EQA (0%, 1.8%, and 11% for the 3 positive samples included in the test panel, n = 109 test results per sample). In this first post-pandemic EQA medical laboratories (average 0.4% false negative across 3 samples, n = 90) and automated test systems (average 1.2% false negative, n = 261) had lower false negative ratios than nonmedical laboratories (22.8%, n = 19) and manual test systems (16.7%, n = 22). These lower average ratios were due to a low concentration sample, where nonmedical laboratories reported 36.8% and manual test systems 54.5% true positive results. CONCLUSION: Overall ratios of true positive results were below the mean of all results during the pandemic but were similar to the first round of the pandemic. A lower post-pandemic true positive ratio was associated with specific laboratory types and assay formats, particularly for samples with low concentration. The EQAs will continue to monitor the laboratory performance to ensure the same quality of epidemiological data after the pandemic, even if vigilance has decreased.

Association of Busulfan Exposure and Outcomes after HCT for Patients with an Inborn Error of Immunity.

Allogeneic HCT is a potentially curative treatment strategy for patients with inborn errors of immunities (IEIs). Objective of this study was to assess the optimal busulfan exposure prior to allogeneic HCT for patients with an IEI who received an intravenous busulfan-based conditioning regimen between 2000 and 2023. Patients from 17 international centers were included. Main outcome of interest was event-free survival (EFS). Patients were categorized into 4 IEI subgroups: combined-immunodeficiency (CID), severe combined immunodeficiency (SCID), neutrophil disorders and hemophagocytic lymphohistiocytosis (HLH)-related disorders. Busulfan exposure was calculated by individual centers (AUCCENTER) and was re-estimated using a validated model (AUCNONMEM). Overall, 562 patients were included: 173 (30.8%) CID, 154 (27.4%) SCID, 101 (18.0%) HLH-related disorders, and 134 (23.8%) neutrophil disorders. Median busulfan AUCNONMEM was 69.0 mg×h/L and correlated poorly with AUCCENTER (r2=0.54). Patients with SCID, HLH-related, and neutrophil disorders were analyzed together (n=389), because CID disease subtype was an effect modifier (p=0.03). Estimated 2-year EFS was 78.5%. In patients with the found optimal busulfan AUCNONMEM of 70-90 mg×h/L, 2-year EFS was superior to <70 mg×h/L (adj-HR 1.97, 95% CI 1.11-3.49, p=0.02), and >90 mg×h/L (adj-HR 5.05, 95% CI 2.43-10.49, p<0.0001). Full donor chimerism increased with higher busulfan AUCNONMEM, plateauing at 90 mg×h/L. For CID patients, optimal AUCNONMEM for donor chimerism was found to be >70 mg×h/L. Improved EFS and higher donor chimerism may be achieved by targeting a cumulative busulfan AUCNONMEM of 80 mg×h/L (range 70-90). Our study stresses the importance to uniformly using a validated population PK-model to estimate the AUCNONMEM.

Population Pharmacokinetic Modeling for Twice-Daily Intravenous Busulfan in a Large Cohort of Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation-A 10-Year Single-Center Experience.

Reaching target exposure of busulfan-based conditioning prior to hematopoietic stem cell transplantation is vital for favorable therapy outcomes. Yet, a wide inter-patient and inter-occasion variability in busulfan exposure has been reported, especially in children. We aimed to identify factors associated with the variability of busulfan pharmacokinetics in 124 consecutive patients transplanted at the University Children's Hospital Zurich between October 2010 and February 2020. Clinical data and busulfan plasma levels after twice-daily intravenous administration were analyzed retrospectively by population pharmacokinetic modeling. The volume of distribution correlated with total body water. The elimination rate constant followed an age-dependent maturation function, as previously suggested, and correlated with the levels of serum albumin. Acute lymphoblastic leukemia reduced busulfan clearance by 20%. Clearance significantly decreased by 17% on average from the start to the third day of busulfan administration, in agreement with other studies. An average reduction of 31% was found in patients with hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease. In conclusion, we demonstrate that in addition to known factors, underlying disease and serum albumin significantly impact busulfan pharmacokinetics in pediatric patients; yet, substantial unexplained variability in some patients remained. Thus, we consider repeated pharmacokinetic assessment essential to achieve the desired target exposure in twice-daily busulfan administration.

Leçons apprises de la gestion des épidémies de la maladie à virus Ebola en République Démocratique du Congo de 2007 à 2017 / Lessons learned from the management of Ebola outbreaks in the Democratic Republic of Congo from 2007 to 2017

Contexte et objectifs. La RDC a un écosystème favorable à la survenue des maladies d'origine zoonotique à l'interface homme-animal dont la maladie à virus Ebola (MVE). Face à une létalité reconnue être élevée pour cette dernière, cette étude s'est focalisée sur les épidémies survenues à Mweka (2007 et 2008), à Isiro (2012), à Boende (2014) et à Likati (2017) afin de décrire les différents éléments de réponse mis en place lors de chacune de ces épidémies et identifier ceux qui ont une influence significative sur l'ampleur de l'épidémie. Méthodes. Une étude documentaire analytique sur les données secondaires recueillies lors de la gestion de ces cinq épidémies de la MVE survenues en RDC. Les statistiques descriptives ont été réalisées pour caractériser chaque épidémie. Les analyses univariées de chaque élément de réponse ont été menées en rapport avec la létalité. Résultats. Un total de 422 cas a été enregistré avec 282 décès soit 66,8 % de létalité. La grande majorité de cas se trouve dans la tranche d'âge de 15 à 49 ans. Le sexe féminin est le plus représenté. Parmi tous les éléments de la réponse, dans un modèle univarié, le déploiement du laboratoire mobile (p=0,002), la fonctionnalité des commissions (p=0,001), le déploiement d'une équipe multidisciplinaire et le système de surveillance performant (p=0,001) sont associés significativement à la létalité. Conclusion. Le déploiement rapide du laboratoire mobile sur le terrain, le déploiement des équipes multidisciplinaires, la bonne fonctionnalité des commissions et le système de surveillance fonctionnel ont permis de réduire significativement la létalité

Structural vulnerability of hospitals, cemeteries, and crematoriums of the city of São Paulo to COVID-19 / Vulnerabilidade estrutural dos hospitais e cemitérios e crematórios da cidade de São Paulo à COVID-19

This is the first report by the COVID19 Observatory - Group: Contagion Networks analyzing mortality data from the city of São Paulo. In this report, we integrated mortality data for the city of São Paulo between 04/02/2020 and 04/28/2020, with information on the flow of victims between hospitals and cemeteries/crematoriums. We included in our analyzes both confirmed and suspected deaths from COVID-19. The main objectives of this report were: (1) to describe the structure of the flow of victims between locations and (2) to suggest changes in the current flow based on geographical distances in order to avoid a potential overload of the mortuary system. We suggest that the city of São Paulo should plan for a potential overload of the mortuary system (that is, the number of burials), based on the presented results. Thus, our results reinforce the need to adopt specific planning for the management of the extraordinary number of victims of this pandemic. Our predictions are based on the structural analysis of the COVID-19 victim flow network, which shows several hotspots with high vulnerability to system overload. These hotspots concentrate with either the greatest number of deaths (hospital) or of burials (cemetery or crematorium), and therefore have high potential to become overwhelmed by receiving many bodies due to the increase in victims of the pandemic. We recommend special attention to be given to localities on the east side of São Paulo, which has both the most vulnerable hospitals in the city, and also houses cemeteries and crematoriums that have a central role in the network and / or are vulnerable. Based on our optimization analysis, we suggest logistical changes in the current flow of bodies from hospitals to cemeteries/crematoriums so as not to overload the funeral system and minimize transportation costs. In this sense, our results are potentially useful for improving the operational planning of the Municipality of São Paulo, ratifying or rectifying actions underway at the municipal level.

Este é o primeiro relatório do Observatório COVID19 - Grupo: Redes de Contágio analisando os dados de óbitos da cidade de São Paulo. Neste relatório, integramos os dados de óbitos da cidade de São Paulo entre os dias 02/04/2020 e 28/04/2020 com informações sobre o fluxo de vítimas entre os hospitais e os cemitérios e crematórios da cidade de São Paulo. Incluímos em nossas análises óbitos confirmados e óbitos suspeitos de COVID-19. Os principais objetivos deste relatório são: (1) descrever a estrutura do fluxo de vítimas entre localidades e (2) sugerir mudanças no fluxo com base em distâncias geográficas de maneira a evitar uma potencial sobrecarga do sistema funerário. Sugere-se à prefeitura da cidade de São Paulo que seja realizado um planejamento para uma potencial sobrecarga do sistema funerário (isto é, número de sepultamentos) da cidade de São Paulo com base nos resultados apresentados. Desta forma, nossos resultados reforçam a necessidade de ser adotado planejamento específico para a gestão dos casos extraordinários visualizados no contexto da pandemia. Esta previsão está baseada na análise estrutural da rede de fluxos de vítimas da COVID-19, que indica a concentração de vários locais com alta vulnerabilidade à sobrecarga do sistema. Tais locais concentram a maior quantidade de óbitos (hospitais) ou a maior concentração de sepultamentos (cemitérios ou crematórios) e tem portanto alto potencial de tornarem-se sobrecarregados por receberem muitos corpos devido ao aumento de vítimas da pandemia. Recomenda-se especial atenção à localidades da zona leste de São Paulo, que apresenta os hospitais mais vulneráveis da cidade e abriga cemitérios e crematórios que possuem papel central na rede e/ou encontram-se vulneráveis. Com base em nossa análise de otimização, sugerimos mudanças logísticas no atual fluxo de corpos de hospitais para cemitérios/crematórios de modo a não sobrecarregar o sistema funerário e minimizar os custos de transporte. Neste sentido, nossos resultados são potencialmente úteis ao aperfeiçoamento do planejamento operacional da Prefeitura Municipal de São Paulo, ratificando ou retificando ações em curso no âmbito municipal.

Vulnerability of the micro-regions of the South of Brazil to the new coronavirus (SARS-CoV-2) pandemic / Vulnerabilidade das microrregiões da Região Sul do Brasil à pandemia do novo coronavírus (SARS-CoV-2)

This is the first report of the 'Observatório COVID191 - Grupo: Redes de Contágio ­ Laboratório de Estudos de Defesa' for the South region of Brazil. We have combined data of confirmed cases of the new coronavirus (SARS-CoV-2) for the South available up to 17/04/2020, with structural analyses of road networks, from within and between states, to estimate the vulnerability and potential influence of the South micro-regions to propagate the disease.

Este é o primeiro relatório do Observatório COVID19 - Grupo: Redes de Contágio ­ Laboratório de Estudos de Defesa para a região Sul do Brasil. Combinamos dados de casos confirmados do novo coronavírus (SARS-CoV-2) para o Sul, disponíveis até o dia 17/04/2020, com análises estruturais da rede de rotas rodoviárias intra e interestaduais para estimarmos a vulnerabilidade e potencial influência das microrregiões sulinas na propagação da doença.

Local edema and hemorrhage caused by Crotalus durissus terrificus envenoming evaluated by magnetic resonance imaging (MRI)

The objective of this study was to detect the presence of local edema and hemorrhage caused by Crotalus durissus terrificus envenoming using magnetic resonance imaging (MRI). Six patients bitten by Crotalus durissus terrificus snakes were treated at the Emergency Unit and Tropical Diseases Unit of Botucatu School of Medicine, UNESP, Säo Paulo State, Brazil. After receiving specific serotherapy, the patients were submitted to MR of the bite site. Post contrast T1 and T2 spin-echo MRI were obtained revealing the following lesions: edema associated with hemorrhage in subcutaneous and muscular tissue (n=3), edema in subcutaneous tissue (n=2), and perimuscular hemorrhage (n=1). In this study, MR demonstrated a local effect of Crotalus durissus terrificus envenoming in inducing edema and hemorrhage, mainly in muscular tissues and perimuscular areas. These results indicate that Crotalus durissus terrificus venom cause a local muscular tissue damage in human envenoming represented by edema and hemorrhage.

Tissue damage caused by Bothrops sp envenoming evaluated by magnetic resonance imaging (MRI)

The objective of this clinical study was to evaluate local tissue damage caused by Bothrops sp envenoming in relation to lesion type and damaged tissues using magnetic resonance imaging (MRI). Fifteen patients bitten by Bothrops snakes were treated at the Emergency Unit of the Tropical Diseases Unit at the University Hospital, Botucatu School of Medicine, UNESP, Säo Paulo State, Brazil. After receiving specific serotherapy, the patients were submitted to MR of the bite site. T1 spin-echo MRI were obtained revealing the following lesions: edema (n=9), edema associated with hemorrhage (n=5), and hemorrhage (n=1). Perimuscular areas (n=6) and subcutaneous tissues (n=5) were the most affected, followed by muscular tissues (n=4). It is important to mention that MRI did not show myonecrosis of the bite site, a widely reported finding in anatomical and histopathological experimental studies.

Ultrastructural features of the fat body and oenocytes of Rhinocricus padbergi Verhoeff (Diplopoda, Spirobolida).

The fat body of the diplopod Rhinocricus padbergi is located in two preferential areas of its body: a) immediately below the tegument, denominated parietal, and b) filling the body cavity, close to the viscera, mainly the ovaries and alimentary canal, denominated perivisceral. Ultrastructurally, its cells, the adipocytes, presented varied morphology and contained organelles indicating that they are cells that mainly produce and store lipids and proteins. The presence of cells similar to the oenocytes found in insects was observed for the first time in diplopods, associated to the fat body of R. padbergi. Our observations suggest that this tissue probably maintains activity cycles, since the presence of cells undergoing apoptosis was detected.