Molecular Diagnosis of Invasive Fungal Disease

BACKGROUND: Invasive fungal infections (IFI) are opportunistic infections caused by yeast or filamentous fungi, typically presenting in immunocompromised patients (haemato-oncology, intensive care, HIV, solid organ transplant settings). This research aims to comprehensively evaluate molecular diagnostics to address the current shortfall in IFI diagnosis and, where appropriate, embed molecular methods into routine clinical service. METHODS: Molecular methodologies, including PCR, MALDI-TOF MS and PNA-FISH, were evaluated on clinical sample cohorts from the Royal Free Hospital NHS Foundation Trust. Each method was critically appraised for: statistical performance, clinical utility and suitability for service adoption. RESULTS: MALDI-TOF MS improved yeast agar culture identification, demonstrating 97.4% (185/190) concordance with ITS rRNA sequencing, and time to identification was significantly reduced (p<0.01, 24 hrs. v’s 15 mins). Lower identification rates of 66% (33/50) were observed when applying MALDI-TOF MS directly to blood culture for yeast identification. In contrast PNA-FISH identified 98.5% (93/96, CI: 91.2, 98.9) of yeasts direct from blood culture within 30 minutes. Using PCP PCR a 60% (3/5) increase in the detection of PCP from BAL in non-HIV patients was demonstrated compared with GMS staining. Overall sensitivity was 100% (95% CI: 56.6, 100) and specificity was 97.9% (95% CI: 88.9, 99.6) for the diagnosis of PCP. Aspergillus PCR demonstrated a sensitivity of 100% (95% CI: 34.2, 100) and specificity of 93.8% (95% CI: 86.4, 97.3) for the diagnosis of IA but a low PPV of 28.6% (95% CI: 8.2, 64.1). CONCLUSIONS: Molecular diagnostic assays can improve the diagnosis of IFI through improved accuracy of identification and increased detection of fungal pathogens from specimens. Results must be interpreted alongside clinical presentation, as false positivity occurs utilising highly sensitive molecular assays. Dual biomarker strategies may improve the performance of molecular diagnostics but the associated impact on healthcare economics must also be considered

Sensitivity of the Norwegian and Barents Sea Atlantis end-to-end ecosystem model to parameter perturbations of key species

Using end-to-end models for ecosystem-based management requires knowledge of the structure, uncertainty and sensitivity of the model. The Norwegian and Barents Seas (NoBa) Atlantis model was implemented for use in ‘what if’ scenarios, combining fisheries management strategies with the influences of climate change and climate variability. Before being used for this purpose, we wanted to evaluate and identify sensitive parameters and whether the species position in the foodweb influenced their sensitivity to parameter perturbation. Perturbing recruitment, mortality, prey consumption and growth by +/- 25% for nine biomass-dominating key species in the Barents Sea, while keeping the physical climate constant, proved the growth rate to be the most sensitive parameter in the model. Their trophic position in the ecosystem (lower trophic level, mid trophic level, top predators) influenced their responses to the perturbations. Top-predators, being generalists, responded mostly to perturbations on their individual life-history parameters. Mid-level species were the most vulnerable to perturbations, not only to their own individual life-history parameters, but also to perturbations on other trophic levels (higher or lower). Perturbations on the lower trophic levels had by far the strongest impact on the system, resulting in biomass changes for nearly all components in the system. Combined perturbations often resulted in non-additive model responses, including both dampened effects and increased impact of combined perturbations. Identifying sensitive parameters and species in end-to-end models will not only provide insights about the structure and functioning of the ecosystem in the model, but also highlight areas where more information and research would be useful—both for model parameterization, but also for constraining or quantifying model uncertainty.publishedVersio

Promising findings on preschoolers’ emergent literacy and school readiness in arts-integrated early childhood settings

Abstract An approach to early childhood education that integrates visual and performing arts throughout the preschool curriculum-Art as a Way of Learning-was implemented in a program (Promoting and Supporting Early Literacy through the Arts) designed to improve the emergent literacy and school readiness of at-risk young children in community-based preschool settings. A quasiexperimental pre-post treatment-only design was used to explore this program&apos;s potential effects in a real-world setting. Preliminary results revealed improvements in young children&apos;s emergent literacy on a number of targeted and standardized measures after participation in the program. This arts-integrated approach to the teaching of and learning in young children shows considerable promise and warrants a rigorous test of its effects

Optimising the reproducibility of measurements of the post-IR IRSL signal from single-grains of K-feldspar for dating.

Achieving good environmental status in the Baltic Sea region requires decision support tools which are based on scientific knowledge across multiple disciplines. Such tools should integrate the complexity of the ecosystem and enable exploration of different natural and anthropogenic pressures such as climate change, eutrophication and fishing pressures in order to compare alternative management strategies. We present a new framework, with a Baltic implementation of the spatially-explicit end-to-end Atlantis ecosystem model linked to two external models, to explore the different pressures on the marine ecosystem. The HBM-ERGOM initializes the Atlantis model with high-resolution physical-chemical-biological and hydrodynamic information while the FISHRENT model analyses the fisheries economics of the output of commercial fish biomass for the Atlantis terminal projection year. The Baltic Atlantis model composes 29 sub-areas, 9 vertical layers and 30 biological functional groups. The balanced calibration provides realistic levels of biomass for, among others, known stock sizes of top predators and of key fish species. Furthermore, it gives realistic levels of phytoplankton biomass and shows reasonable diet compositions and geographical distribution patterns for the functional groups. By simulating several scenarios of nutrient load reductions on the ecosystem and testing sensitivity to different fishing pressures, we show that the model is sensitive to those changes and capable of evaluating the impacts on different trophic levels, fish stocks, and fisheries associated with changed benthic oxygen conditions. We conclude that the Baltic Atlantis forms an initial basis for strategic management evaluation suited for conducting medium to long term ecosystem assessments which are of importance for a number of pan-Baltic stakeholders in relation to anthropogenic pressures such as eutrophication, climate change and fishing pressure, as well as changed biological interactions between functional groups

Assessing the Impact of Stakeholder Engagement in Management Strategy Evaluation

After completing a large, regional, multi-use Management Strategy Evaluation, we attempt to assess the impact of stakeholder engagement on the project. We do so by comparing the original project plan to the actual project development and highlight the changes which can be more directly related to stakeholder engagement aided by the application of a logic model for program evaluation. The impact can be summarised into four broad classes: a) change in the actual project development; b) a measurable change in the network of interactions both stakeholders (which includes researchers); c) changes in how the computer model was developed and run; and d) changes in attitudes among stakeholders (including researchers). We discuss these changes, the way they have been detected and some lessons we learnt which may benefit future Management Strategy Evaluation projects

Suicide rates amongst individuals from ethnic minority backgrounds: A systematic review and meta-analysis.

From Europe PMC via Jisc Publications RouterHistory: epub 2022-04-28, ppub 2022-05-01Publication status: PublishedBackgroundExisting evidence suggests that some individuals from ethnic minority backgrounds are at increased risk of suicide compared to their majority ethnic counterparts, whereas others are at decreased risk. We aimed to estimate the absolute and relative risk of suicide in individuals from ethnic minority backgrounds globally.MethodsDatabases (Medline, Embase, and PsycInfo) were searched for epidemiological studies between 01/01/2000 and 3/07/2020, which provided data on absolute and relative rates of suicide amongst ethnic minority groups. Studies reporting on clinical or specific populations were excluded. Pairs of reviewers independently screened titles, abstracts, and full texts. We used random effects meta-analysis to estimate overall, sex, location, migrant status, and ancestral origin, stratified pooled estimates for absolute and rate ratios. PROSPERO registration: CRD42020197940.FindingsA total of 128 studies were included with 6,026,103 suicide deaths in individuals from an ethnic minority background across 31 countries. Using data from 42 moderate-high quality studies, we estimated a pooled suicide rate of 12·1 per 100,000 (95% CIs 8·4-17·6) in people from ethnic minority backgrounds with a broad range of estimates (1·2-139·7 per 100,000). There was weak statistical evidence from 51 moderate-high quality studies that individuals from ethnic minority groups were more likely to die by suicide (RR 1·3 95% CIs 0·9-1·7) with again a broad range amongst studies (RR 0·2-18·5). In our sub-group analysis we only found evidence of elevated risk for indigenous populations (RR: 2·8 95% CIs 1·9-4·0; pooled rate: 23·2 per 100,000 95% CIs 14·7-36·6). There was very substantial heterogeneity (I2  > 98%) between studies for all pooled estimates.InterpretationThe homogeneous grouping of individuals from ethnic minority backgrounds is inappropriate. To support suicide prevention in marginalised groups, further exploration of important contextual differences in risk is required. It is possible that some ethnic minority groups (for example those from indigenous backgrounds) have higher rates of suicide than majority populations.FundingNo specific funding was provided to conduct this research. DK is funded by Wellcome Trust and Elizabeth Blackwell Institute Bristol. Matthew Spittal is a recipient of an Australian Research Council Future Fellowship (project number FT180100075) funded by the Australian Government. Rebecca Musgrove is funded by the NIHR Greater Manchester Patient Safety Translational Research Centre (PSTRC-2016-003)

End-to-end model of Icelandic waters using the Atlantis framework: Exploring system dynamics and model reliability

Publisher's version (útgefin grein)Icelandic waters are very productive and the fisheries are economically important for the Icelandic nation. The importance of the fisheries has led to progressive fisheries management and extensive monitoring of the ecosystem. However, fisheries management is mainly built on single species stock assessment models, and multi-species or ecological models are essential for building capacity around ecosystem-based fisheries management. This paper describes the first end-to-end model for the Icelandic waters using the Atlantis modeling framework. The modeled area is 1,600,000 km2, and covers the area from Greenland through Icelandic waters to the Faroe Islands. The ocean area was divided into 51 spatial boxes, each with multiple vertical layers. There were 52 functional groups in the model: 20 fish groups (8 at a species level), 5 groups of mammals, 1 seabird group, 16 invertebrates, 5 primary producers, 2 bacteria and 3 detritus groups. The reliability of the model was evaluated using a skill assessment and a sensitivity analysis was conducted to understand the dynamics of the system. The sensitivity study revealed that saithe, redfish and tooth whales had the greatest effect on other groups in the system. The skill assessment showed that the model was able to replicate time-series of biomass and landings for the most important commercial groups and that modeling of the recruitment processes was important for some of the groups. This model now provides a solid basis for evaluating alternative ecosystem and fisheries management scenarios, and should produce reliable results for the most important commercial groups.This study has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 613571 for the project MareFrame and from the European Commission’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 634495 for the project Science, Technology, and Society Initiative to minimize Unwanted Catches in European Fisheries (Minouw). Funding from the Icelandic Research Fund (rannis, No. 152039051) is also acknowledged.Peer Reviewe

Medication Sales and Syndromic Surveillance, France

Real-time over-the-counter drug sales provide an additional tool for disease surveillance

Rapid identification of a Mycobacterium tuberculosis full genetic drug resistance profile through whole genome sequencing directly from sputum.

INTRODUCTION: Resistance to second-line tuberculosis drugs is common, but slow to diagnose with phenotypic drug sensitivity testing. Rapid molecular tests speed up diagnosis, but can only detect limited mutations. Whole genome sequencing (WGS) of culture isolates can generate a complete genetic drug resistance profile, but is delayed by the initial culture step. In the case presented here, successful WGS directly from sputum was achieved using targeted enrichment. CASE REPORT: A 29-year-old Nigerian woman was diagnosed with tuberculosis. Xpert MTB/RIF and Hain line probe assays identified rpoB and inhA mutations consistent with rifampicin and intermediate isoniazid resistance, and a further possible mutation conferring fluoroquinolone resistance. WGS directly from sputum identified a further inhA mutation consistent with high-level isoniazid resistance and confirmed the absence of fluoroquinolone resistance. Isoniazid was stopped, and the patient has completed 18 months of a fluoroquinolone-based regimen without relapse. DISCUSSION: Compared to rapid molecular tests (which can only examine a limited number of mutations) and WGS of culture isolates (which requires a culture step), WGS directly from sputum can quickly generate a complete genetic drug resistance profile. In this case, WGS altered the clinical management of drug-resistant tuberculosis and demonstrated potential for guiding individualized drug treatment where second-line drug resistance is common

Multicentre study on the reproducibility of MALDI-TOF MS for nontuberculous mycobacteria identification

The ability of MALDI-TOF for the identification of nontuberculous mycobacteria (NTM) has improved recently thanks to updated databases and optimized protein extraction procedures. Few multicentre studies on the reproducibility of MALDI-TOF have been performed so far, none on mycobacteria. The aim of this study was to evaluate the reproducibility of MALDI-TOF for the identification of NTM in 15 laboratories in 9 European countries. A total of 98 NTM clinical isolates were grown on Lowenstein-Jensen. Biomass was collected in tubes with water and ethanol, anonymized and sent out to the 15 participating laboratories. Isolates were identified using MALDI Biotyper (Bruker Daltonics). Up to 1330 MALDI-TOF identifications were collected in the study. A score >= 1.6 was obtained for 100% of isolates in 5 laboratories (68.2-98.6% in the other). Species-level identification provided by MALDI-TOF was 100% correct in 8 centres and 100% correct to complex-level in 12 laboratories. In most cases, the misidentifications obtained were associated with closely related species. The variability observed for a few isolates could be due to variations in the protein extraction procedure or to MALDI-TOF system status in each centre. In conclusion, MALDI-TOF showed to be a highly reproducible method and suitable for its implementation for NTM identification