Measurement uncertainty interval in case of a known relationship between precision and mean [version 1; peer review: 2 approved, 1 approved with reservations]

Background: Measurement uncertainty is typically expressed in terms of a symmetric interval y±U, where y denotes the measurement result and U the expanded uncertainty. However, in the case of heteroscedasticity, symmetric uncertainty intervals can be misleading. In this paper, a different approach for the calculation of uncertainty intervals is introduced. Methods: This approach is applicable when a validation study has been conducted with samples with known concentrations. In a first step, test results are obtained at the different known concentration levels. Then, on the basis of precision estimates, a prediction range is calculated. The measurement uncertainty for a given test result can then be obtained by projecting the intersection of the test result with the limits of the prediction range back onto the axis of the known values, now interpreted as representing the measurand. Results: It will be shown how, under certain circumstances, asymmetric uncertainty intervals arise quite naturally and lead to more reliable uncertainty intervals. Conclusions:  This article establishes a conceptual framework in which measurement uncertainty can be derived from precision whenever the relationship between the latter and concentration has been characterized. This approach is applicable for different types of distributions. Closed expressions for the limits of the uncertainty interval are provided for the simple case of normally distributed test results and constant relative standard deviation

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

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

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

JUDGES: a descriptive group decision support system for the ranking of items

A set of tools for group decision support are presented. Decision problems involving several decision makers, here-after called judges, that have to rank several alternatives, are considered. The toolbox is called JUDGES. It includes the four following procedures: &x02022; - a hierarchical representation of the judges allows to display the existing conflicts between groups of judges, &x02022; - enhanced box-plots representations of the alternatives are generated in order to detect those that are responsible for the major conflicts, &x02022; - specific advice is issued to each judge in order to reach more easily a consensus, &x02022; - a general framework for a pairwise group preference structure is proposed, and can be used to finalise the decision. These procedures are embedded in an interactive software, implemented on micro-computer, which currently simulates the use on a network. Actual network implementation is foreseen in the near future. Several applications are presented and future developments are discussed. © 1994.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Recreational value of regional forests: the case of Belgium’s Walloon Region

peer reviewedThe Walloon forest, which is geographically close to densely populated areas of Atlantic Europe, fulfils an important recreational function. Two surveys were set up, among which a large-scale statistical survey in 40 woodlands, distributed throughout the Walloon forest and resulting in over 4,000 questionnaires collected. These give information about the recreational activities carried out in the forest, which helps determine the unit value of visits. The regional value is based on the estimated number of visits annually for the total woodlands. Contingent valuation is used to estimate recreational values for this data set comprising the whole regional level with heterogeneous visits and comparisons with other methods and other hypotheses are undertaken. Although the valuation varies depending on the method and the application modalities selected, it is very large and confirms the importance of this non-benefit service and the weight it could carry in terms of regional forest policy

Une malformation nasale congénitale non retrouvée dans la littérature : à propos de 5 cas

International audienc

Cost Analysis of Aprotinin Reintroduction in French Cardiac Surgery Centres: A Real-World Data-Based Analysis

International audienceIntroduction: The European Medicines Agency restored aprotinin (APR) use for preventing blood loss in patients undergoing isolated coronary artery bypass graft (iCABG) in 2016 but requested the collection of patient and surgery data in a registry (NAPaR). The aim of this analysis was to evaluate the impact of APR reintroduction in France on the main hospital costs (operating room, transfusion and intensive unit stay) compared to the current use of tranexamic acid (TXA), which was the only antifibrinolytic available before APR reinstatement.Methods: A multicenter before-after post-hoc analysis to compare APR and TXA was carried out in four French university hospitals. APR use followed the ARCOTHOVA (French Association of Cardiothoracic and Vascular Anesthetists) protocol, which had framed three main indications in 2018. Data from 236 APR patients were retrieved from the NAPaR (N = 874); 223 TXA patients were retrospectively retrieved from each center database and matched to APR patients upon indication classes. Budget impact was evaluated using both direct costs associated with antifibrinolytics and transfusion products (within the first 48 h) and other costs such as surgery duration and ICU stay.Results: The 459 collected patients were distributed as: 17% on-label; 83% off-label. Mean cost per patient until ICU discharge tended to be lower in the APR group versus the TXA group, which resulted in an estimated gross saving of €3136 per patient. These savings concerned operating room and transfusion costs but were mainly driven by reduced ICU stays. When extrapolated to the whole French NAPaR population, the total savings of the therapeutic switch was estimated at around €3 million.Conclusion: The budget impact projected that using APR according to ARCOTHOVA protocol resulted in decreased requirement for transfusion and complications related to surgery. Both were associated with substantial cost savings from the hospital’s perspective compared with exclusive use of TXA

The profitability of P.G. 600 in well managed sow herd

Adequate results in reproduction are one of the key points for successful pig production. P.G. 600, a combination of pregnant mare serum gonadotropine and human chorionic gonadotropine is used as oestrus promoter on many pig farms. The profitability of P.G. 600 treatment was tested on primiparous sows on well managed farm with 2.500 sows and 14.04 liveborn piglets per litter. The experiment lasted for a period of one year. The experimental group, 502 animals, was treated with P.G. 600 at weaning of the first litter. Control group, 503 animals, was not treated. Data were evaluated according to four seasons: spring, summer, autumn and winter. The costs of feed, sow depreciation, building, labour and P.G. 600 treatment in experimental group were calculated for the period from weaning to successful insemination or fromweaning to culling. In P.G. 600 group production costs were lower in spring (-0.68 EUR per born piglet) and in summer (-0.88 EUR per born piglet), but not in autumn (+0.05 EUR per born piglet) and in winter (+0.46 EUR per born piglet). The calculated total benefit on the farm with yearly production of 65 thousand 30 kg pigs was 3,249 EUR. Calculated benefit for only spring and summer use was 4.937 EUR. The last number represents only 0.15 to 0.19% of estimated turnover of the farm. The use of P.G. 600 on well managed farm will not increase profitability of production.Primerni rezultati reprodukcije so ključnega pomena za uspešno prašičerejsko proizvodnjo. P.G. 600, ki je kombinacija serumskega gonadotopina brejih kobil in človeškega horionskega gonadotropina, se pogosto uporablja kot spodbujevalec estrusa. Gospodarnost uporabe P.G. 600 smo preizkusili na svinjah prvesnicah na dobro vodenem obratu z 2.500 svinjami in 14,04 živorojenimi pujski po gnezdu. Poskus je trajal eno leto. Poskusno skupino, 502 živali, smo tretirali s P.G. 600 ob odstavitvi prvega gnezda. Kontrolne skupine, 503 živali, nismo tretirali. Podatke smo obdelali po štirih letnih sezonah: pomlad, poletje, jesen in zima. Stroške za krmo, amortizacijo svinje in objektov ter opreme, dela in tretiranja s P.G. 600 v poskusni skupini smo ocenili za obdobje od odstavitve do uspešne osemenitve ali do izločitve. Stroški v skupini, tretirani z P.G. 600, so bili nižji spomladi (-0,68 EUR po rojenem pujsku) in poleti (Ž0,88 EUR po rojenem pujsku), ne pa jeseni (+0,05 EUR) in pozimi (+0,46 EUR). Na farmi z letno proizvodnjo 65 tisoč 30 kg težkih pujskov so se stroški znižali za 3.249 EUR. Če bi preparat uporabljali le spomladi in poleti, bi privarčevali 4.973 EUR. To predstavlja le 0,15 do 0,19 % letnega prihodka farme. Uporaba P.G. 600 na dobro vodenem obratu ne bi izboljšala gospodarnosti

Diagnostic Performance of Risk of Ovarian Malignancy Algorithm Against CA125 and HE4 in Connection With Ovarian Cancer: A Meta-analysis

The aim of this study was to determine whether the Risk of Ovarian Malignancy Algorithm (ROMA) is more accurate than the human epididymis 4 (HE4) or carbohydrate antigen 125 (CA125) biomarkers with respect to the differential diagnosis of women with a pelvic mass. The secondary objective is to assess the performance of ROMA in early-stage ovarian cancer (OC) and late-stage OC, as well as premenopausal and postmenopausal patient populations. The PubMed and Google Scholar databases were searched for relevant clinical studies. Eligibility criteria included comparison of ROMA with both HE4 and CA125 levels in OC (unspecified, epithelial, and borderline ovarian tumors), use of only validated ROMA assays, presentation of area under the curve and sensitivity/specificity data, and results from early-stage OC, late-stage OC and premenopausal and postmenopausal women. Area under the curve (AUC), sensitivity/specificity, and the diagnostic odds ratio (DOR) results were summarized. Five studies were selected comprising 1975 patients (premenopausal, n = 1033; postmenopausal, n = 925; benign, n = 1387; early stage, n = 192; and late stage, n = 313). On the basis of the AUC (95% confidence interval) data for all patients, ROMA (0.921 [0.855-0.960]) had a numerically greater diagnostic performance than CA125 (0.883 [0.771-0.950]) and HE4 (0.899 [0.835-0.943]). This was also observed in each of the subgroup populations, in particular, the postmenopausal patients and patients with early OC. The sensitivity and specificity (95% confidence interval) results showed ROMA (sensitivity, 0.873 [0.752-0.940]; specificity, 0.855 [0.719-0.932]) to be numerically superior to CA125 (sensitivity, 0.796 [0.663-0.885]; specificity, 0.825 [0.662-0.919]) and HE4 (sensitivity, 0.817 [0.683-0.902]; specificity, 0.851 [0.716-0.928]) in all patients and for the early- and late-stage OC subgroups. Finally, the ROMA log DOR results were better than HE4 and CA125 log DOR results especially for the early-stage patient group. The results presented support the use of ROMA to improve clinical decision making, most notably in patients with early OC