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.

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.

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.

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'.

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.

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.

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.

Performance of SARS-CoV-2 nucleic acid amplification testing in Austria as measured by external quality assessment schemes during 3 years of the COVID-19 pandemic: an observational retrospective study.

BACKGROUND: The aim of external quality assessment (EQA) schemes is to evaluate the analytical performance of laboratories and test systems in a near-to-real-life setting. This monitoring service provides feedback to participant laboratories and serves as a control measure for the epidemiological assessment of the regional incidence of a pathogen, particularly during epidemics. Using data from EQA schemes implemented as a result of the intensive effort to monitor SARS-CoV-2 infections in Austria, we aimed to identify factors that explained the variation in laboratory performance for SARS-CoV-2 detection over the course of the COVID-19 pandemic. METHODS: For this observational study, we retrospectively analysed 6308 reverse transcriptase quantitative PCR (RT-qPCR) test results reported by 191 laboratories on 71 samples during 14 rounds of three SARS-CoV-2 pathogen detection EQA schemes in Austria between May 18, 2020, and Feb 20, 2023. We calculated the overall rates of false and true-negative, false and true-positive, and inconclusive results. We then assessed laboratory performance by estimating the sensitivity by testing whether significant variation in the odds of obtaining a true-positive result could be explained by virus concentration, laboratory type, or assay format. We also assessed whether laboratory performance changed over time. FINDINGS: 4371 (93·7%) of 4663 qPCR test results were true-positive, 241 (5·2%) were false-negative, and 51 (1·1%) were inconclusive. The mean per-sample sensitivity was 99·7% in samples with high virus concentrations (1383 [99·4%] true-positive, three [0·2%] false-negative, and five [0·4%] inconclusive results for 1391 tests in which the sample cycle threshold was ≤32), whereas detection rates were lower in samples with low virus concentrations (mean per-sample sensitivity 92·5%; 2988 [91·3%] true-positive, 238 [7·3%] false-negative, and 46 [1·4%] inconclusive results for 3272 tests in which the cycle threshold was >32). Of the 1645 results expected to be negative, 1561 (94·9%) were correctly reported as negative, 10 (0·6%) were incorrectly reported as positive, and 74 (4·5%) were reported as inconclusive. Notably, the overall performance of the tests did not change significantly over time. The odds of reporting a correct result were 2·94 (95% CI 1·75-4·96) times higher for a medical laboratory than for a non-medical laboratory, and 4·60 (2·91-7·41) times greater for automated test systems than for manual test systems. Automated test systems within medical laboratories had the highest sensitivity when compared with systems requiring manual intervention in both medical and non-medical laboratories. INTERPRETATION: High rates of false-negativity in all PCR analyses evaluated in comprehensive, multiple, and repeated EQA schemes outline a clear path for improvement in the future. The performance of some laboratories (eg, non-medical laboratories or those using non-automated test systems) should receive additional scrutiny-for example, by requiring additional EQA schemes for certification or accreditation-if the aggregated data from EQA rounds suggest lower sensitivity than that recorded by others. This strategy will provide assurances that epidemiological data as a whole are reliable when testing on such a large scale. Although performance did not improve over time, we cannot exclude extenuating circumstances-such as shortages and weakened supply chains-that could have prevented laboratories from seeking alternative methods to improve performance. FUNDING: None.

Climate change should drive mammal defaunation in tropical dry forests.

Human-induced climate change has intensified negative impacts on socioeconomic factors, the environment, and biodiversity, including changes in rainfall patterns and an increase in global average temperatures. Drylands are particularly at risk, with projections suggesting they will become hotter, drier, and less suitable for a significant portion of their species, potentially leading to mammal defaunation. We use ecological niche modelling and community ecology biodiversity metrics to examine potential geographical range shifts of non-volant mammal species in the largest Neotropical dryland, the Caatinga, and evaluate impacts of climate change on mammal assemblages. According to projections, 85% of the mammal species will lose suitable habitats, with one quarter of species projected to completely lose suitable habitats by 2060. This will result in a decrease in species richness for more than 90% of assemblages and an increase in compositional similarity to nearby assemblages (i.e., reduction in spatial beta diversity) for 70% of the assemblages. Small-sized mammals will be the most impacted and lose most of their suitable habitats, especially in highlands. The scenario is even worse in the eastern half of Caatinga where habitat destruction already prevails, compounding the threats faced by species there. While species-specific responses can vary with respect to dispersal, behavior, and energy requirements, our findings indicate that climate change can drive mammal assemblages to biotic homogenization and species loss, with drastic changes in assemblage trophic structure. For successful long-term socioenvironmental policy and conservation planning, it is critical that findings from biodiversity forecasts are considered.

Widespread distribution of rodenticide resistance-conferring mutations in the Vkorc1 gene among house mouse populations in Portuguese Macaronesian islands and Iberian Atlantic areas.

Growing evidence of widespread resistance to anticoagulant rodenticides (ARs) in house mice pose significant challenges to pest control efforts. First-generation ARs were introduced in the early 1950s but resistance to these emerged later that decade. Second-generation rodenticides were then developed, with resistance being reported in the late 1970s. Research has linked resistance to ARs with mutations in the Vkorc1 gene, leading to the use of more toxic and environmentally harmful compounds. In this study, 243 tail tips of house mice from mainland Portugal and Southern Spain, the Azores and Madeira archipelagos were analysed for all 3 exons of the Vkorc1 gene. Mutations L128S, Y139C, along with the so-called spretus genotype Vkorc1spr are considered responsible for reduced susceptibility of house mice to ARs. All these sequence variants were broadly detected throughout the sampling regions. Vkorc1spr was the most often recorded among mainland populations, whereas Y139C was nearly ubiquitous among the insular populations. In contrast, L128S was only detected in mainland Portugal and four islands of the Azores archipelago. All first generation ARs such as warfarin and coumatetralyl are deemed ineffective against all Vkorc1 variants identified in this study. Second-generation bromadiolone and difenacoum should also be discarded to control populations carrying Vkorc1spr, Y139C or L128S mutations. Inadequate use of ARs in regions where resistant animals have been found in large proportions will result in the spreading of rodenticide resistance among rodent populations through the positive selection of non-susceptible individuals. Consequently, ineffectiveness of rodent control will increase and potentiate environmental contamination, hazarding non-target wildlife through secondary poisoning. We highlight the need for Vkorc1 screening as a crucial tool in rodent management, aiding in the selection of the most appropriate control/eradication method in order to prevent misuse of these toxic biocides and the spread of rodenticide resistance among house mouse populations.

Indirect effects shape species fitness in coevolved mutualistic networks.

Ecological interactions are one of the main forces that sustain Earth's biodiversity. A major challenge for studies of ecology and evolution is to determine how these interactions affect the fitness of species when we expand from studying isolated, pairwise interactions to include networks of interacting species1-4. In networks, chains of effects caused by a range of species have an indirect effect on other species they do not interact with directly, potentially affecting the fitness outcomes of a variety of ecological interactions (such as mutualism)5-7. Here we apply analytical techniques and numerical simulations to 186 empirical mutualistic networks and show how both direct and indirect effects alter the fitness of species coevolving in these networks. Although the fitness of species usually increased with the number of mutualistic partners, most of the fitness variation across species was driven by indirect effects. We found that these indirect effects prevent coevolving species from adapting to their mutualistic partners and to other sources of selection pressure in the environment, thereby decreasing their fitness. Such decreases are distributed in a predictable way within networks: peripheral species receive more indirect effects and experience higher reductions in fitness than central species. This topological effect was also evident when we analysed an empirical study of an invasion of pollination networks by honeybees. As honeybees became integrated as a central species within networks, they increased the contribution of indirect effects on several other species, reducing their fitness. Our study shows how and why indirect effects can govern the adaptive landscape of species-rich mutualistic assemblages.

Design of external quality assessment schemes and definition of the roles of their providers in future epidemics.

During an epidemic, individual test results form the basis of epidemiological indicators such as case numbers or incidence. Therefore, the accuracy of measures derived from these indicators depends on the reliability of individual results. In the COVID-19 pandemic, monitoring and evaluating the performance of the unprecedented number of testing facilities in operation, and novel testing systems in use, was urgently needed. External quality assessment (EQA) schemes are unique sources of data reporting on testing performance, and their providers are recognised contacts and support for test facilities (for technical-analytical topics) and health authorities (for planning the monitoring of infection diagnostics). To identify information provided by SARS-CoV-2 genome detection EQA schemes that is relevant for public health microbiology, we reviewed the current literature published in PubMed between January, 2020, and July, 2022. We derived recommendations for EQA providers and their schemes for best practices to monitor pathogen-detection performance in future epidemics. We also showed laboratories, test facilities, and health authorities the information and benefits they can derive from EQA data, and from the non-EQA services of their providers.

Identifying climate change refugia for South American biodiversity.

Refugia-based conservation offers long-term effectiveness and minimize uncertainty on strategies for climate change adaptation. We used distribution modelling to identify climate change refugia for 617 terrestrial mammals and to quantify the role of protected areas (PAs) in providing refugia across South America. To do so, we compared species potential distribution across different scenarios of climate change, highlighting those regions likely to retain suitable climatic conditions by year 2090, and explored the proportion of refugia inside PAs. Moist tropical forests in high-elevation areas with complex topography concentrated the highest local diversity of species refugia, although regionally important refugia centers occurred elsewhere. Andean-Amazon forests contained climate change refugia for more than half of the continental species' pool and for up to 87 species locally (17 × 17 km2 grid cell). The highlands of the southern Atlantic Forest also included megadiverse refugia for up to 76 species per cell. Almost half of the species that may find refugia in the Atlantic Forest will do so in a single region-the Serra do Mar and Serra do Espinhaço. Most of the refugia we identified, however, were not in PAs, which may contain <6% of the total area of climate change refugia, leaving 129-237 species with no refugia inside the territorial limits of PAs of any kind. Our results reveal a dismal scenario for the level of refugia protection in some of the most biodiverse regions of the world. Nonetheless, because refugia tend to be in high-elevation, topographically complex, and remote areas, with lower anthropogenic pressure, formally protecting them may require a comparatively modest investment.

Identificación de refugios para la biodiversidad de Sudamérica ante el cambio climático Resumen Las estrategias de conservación basadas en refugios ofrecen efectividad a largo plazo y minimizan la incertidumbre sobre las estrategias de adaptación al cambio climático. Utilizamos modelos de distribución para identificar los refugios del cambio climático de 617 especies de mamíferos terrestres y cuantificar el papel de las áreas protegidas en la provisión de refugios en Sudamérica. Para esto, comparamos la distribución potencial de las especies en diferentes escenarios de cambio climático, destacando las regiones que probablemente conservarán las condiciones climáticas adecuadas para el año 2090, y exploramos la proporción de refugios dentro de las áreas protegidas. Los bosques tropicales húmedos de zonas de gran altitud y topografía compleja concentraron la mayor diversidad local de refugios de especies, aunque también hubo centros de refugio de importancia regional en otras localidades. Los bosques amazónicos andinos albergaron los refugios ante el cambio climático de más de la mitad del conjunto de especies continentales y para hasta 87 especies a escala local (celda cuadriculada de 17 × 17 km2 ). Las tierras altas del sur del Bosque Atlántico también incluyeron refugios megadiversos para hasta 76 especies por celda. Casi la mitad de las especies que pueden refugiarse en el Bosque Atlántico lo harán en una sola región: la Serra do Mar y la Serra do Espinhaço. Sin embargo, la mayoría de los refugios que identificamos no estaban en áreas protegidas, las cuales pueden contener <6% del área total de refugios del cambio climático, dejando entre 129 y 237 especies sin refugio dentro de los límites territoriales de las áreas protegidas de cualquier tipo. Nuestros resultados revelan un panorama desolador para el nivel de protección de los refugios en algunas de las regiones con mayor biodiversidad del mundo. No obstante, dado que los refugios suelen encontrarse en zonas remotas de gran altitud con topografía compleja y menor presión antropogénica, protegerlos formalmente puede requerir una inversión comparativamente modesta.

Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test, Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden.

BACKGROUND: Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT+) screening population and thereby reduce the colonoscopy burden. MATERIALS AND METHODS: From the Danish National Colorectal Cancer Screening Program, 4048 FIT+ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling. RESULTS: The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs. CONCLUSION: A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.

Decoupled responses of biodiversity facets driven from anuran vulnerability to climate and land-use changes.

Biodiversity loss not only implies the loss of species but also entails losses in other dimensions of biodiversity, such as functional, phylogenetic and interaction diversity. Yet, each of those facets of biodiversity may respond differently to extinctions. Here, we examine how extinction, driven by climate and land-use changes may affect those different facets of diversity by combining empirical data on anuran-prey interaction networks, species distribution modelling and extinction simulations in assemblages representing four Neotropical ecoregions. We found a mismatch in the response of functional, phylogenetic and interaction diversity to extinction. In spite of high network robustness to extinction, the effects on interaction diversity were stronger than those on phylogenetic and functional diversity, declining linearly with species loss. Although it is often assumed that interaction patterns are reflected by functional diversity, assessing species interactions may be necessary to understand how species loss translates into the loss of ecosystem functions.

Three rounds of a national external quality assessment reveal a link between disharmonic anti-SARS-CoV-2 antibody quantifications and the infection stage.

OBJECTIVES: The WHO's standardized measuring unit, "binding antibody units per milliliter (BAU/mL)," should allow the harmonization of quantitative results by different commercial Anti-SARS-CoV-2 immunoassays. However, multiple studies demonstrate inter-assay discrepancies. The antigenic changes of the Omicron variant affect the performance of Spike-specific immunoassays. This study evaluated the variation of quantitative Anti-SARS-CoV-2-Spike antibody measurements among 46, 50, and 44 laboratories in three rounds of a national external quality assessment (EQA) prior to and after the emergence of the Omicron variant in a diagnostic near-to-real-life setting. METHODS: We analyzed results reported by the EQA participant laboratories from single and sequential samples from SARS-CoV-2 convalescent, acutely infected, and vaccinated individuals, including samples obtained after primary and breakthrough infections with the Omicron variant. RESULTS: The three immunoassays most commonly used by the participants displayed a low intra-assay and inter-laboratory variation with excellent reproducibility using identical samples sent to the participants in duplicates. In contrast, the inter-assay variation was very high with all samples. Notably, the ratios of BAU/mL levels quantified by different immunoassays were not equal among all samples but differed between vaccination, past, and acute infection, including primary infection with the Omicron variant. The antibody kinetics measured in vaccinated individuals strongly depended on the applied immunoassay. CONCLUSIONS: Measured BAU/mL levels are only inter-changeable among different laboratories when the same assay was used for their assessment. Highly variable ratios of BAU/mL quantifications among different immunoassays and infection stages argue against the usage of universal inter-assay conversion factors.

Mutualistic coevolution and community diversity favour persistence in metacommunities under environmental changes.

Linking local to regional ecological and evolutionary processes is key to understand the response of Earth's biodiversity to environmental changes. Here we integrate evolution and mutualistic coevolution in a model of metacommunity dynamics and use numerical simulations to understand how coevolution can shape species distribution and persistence in landscapes varying in space and time. Our simulations show that coevolution and species richness can synergistically shape distribution patterns by increasing colonization and reducing extinction of populations in metacommunities. Although conflicting selective pressures emerging from mutualisms may increase mismatches with the local environment and the rate of local extinctions, coevolution increases trait matching among mutualists at the landscape scale, counteracting local maladaptation and favouring colonization and range expansions. Our results show that by facilitating colonization, coevolution can also buffer the effects of environmental changes, preventing species extinctions and the collapse of metacommunities. Our findings reveal the mechanisms whereby coevolution can favour persistence under environmental changes and highlight that these positive effects are greater in more diverse systems that retain landscape connectivity.