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Cariolou, M.

Publications and source records attributed to Cariolou, M..

3 recordsLinked to original sources

The ReAct project: Analysis of data from 23 differentlaboratories to characterise DNA recovery given twosets of activity level propositions

The ReAct (Recovery, Activity) project is an ENFSI (European Network of Forensic Science Institutes) supported initiative comprising a large consortium of laboratories. Here, the results from more than 23 laboratories are presented. The primary purpose was to design experiments simulating typical casework circumstances; collect data and to implement Bayesian networks to assess the value (i.e., likelihood ratio) of DNA results given activity level propositions. Two different experimental designs were used to simulate a robbery, where a screwdriver was used to force a door or window. Propositions and case information were chosen following laboratory feedback listing typical casework circumstances (included in the paper). Whereas the proposition representing prosecutions view is applicable to many cases: the defendant forced the door/window with his screwdriver; the proposition representing defences view are more variable depending on what is alleged to have happened. In a direct transfer experiment, the defendant owned and used the screwdriver, but he did not force the door/window in question. An unknown person used the defendants stolen screwdriver. In an indirect transfer experiment, the defendant neither owned, saw, nor used the screwdriver, nor did they force the door or window. Instead, an unknown individual--someone with whom the defendant had interacted (e.g., by shaking hands or touching the same objects)--used the recovered tool to force entry. In the first experiment, if the defendant forced the door/window, then s/he is the last handler of the screw driver, whereas if the tool was stolen and used by an unknown person, the defendant is the first handler. For the second experiment, given the defence view, the defendant never held the screwdriver. We envisaged the situation where an object manipulated by the defendant (or the defendant himself/herself) would be touched by the unknown offender who would then force the window. The time delay between the touching of the object and the forcing of the window was 0, 1h, and 2h. This was accomplished by handshaking experiments, where the person forcing the door would shake a persons hand, and then use the screwdriver either immediately after hand-shake or after 1, 2 hours. It was found for the direct transfer experiment that unless a single contributor profile aligning with the known persons of interest profile was retrieved, the results did not allow to discriminate propositions. On the other hand, for the indirect transfer experiment, both single and major contributor profiles that aligned with the person of interest (POI) supported the proposition that the person used the tool rather than an unknown person who had touched an object, when indeed the former was true. There was considerable variation in median recoveries of DNA between laboratories (between 200pg - 5ng) for a given experiment if quantities are taken into account. These differences affect the likelihood ratios given activity level propositions. More than 2,700 samples were analysed in the course of this study. Two different Bayesian Networks are made available via an open source application written in Shiny R: Shiny_React(). For comparison, all datasets were analysed using a qualitative method categorised into absent, single, balanced or major given contributors. The need for standardisation of methods is highlighted, along with the need for new methods to assess probability of laboratory dependent DNA recovery. Open access databases that are made freely available are important adjuncts

genetics↗

Importance of vitamin D in critically ill children with subgroup analyses of sepsis and respiratory tract infections: a systematic review and meta-analysis

BackgroundCritical care and sepsis remain high priority concerns in children. Observational studies report high prevalence of vitamin D deficiency and present mixed results regarding the correlation between vitamin D status and adverse outcomes. Associations between deficiency and mortality, particularly in children with sepsis, remain unclear. We performed a systematic review and meta-analysis to address this uncertainty.\n\nMethodsPubMed, OVID and Google Scholar were searched for observational studies in critically ill children. We obtained pooled prevalence estimates for vitamin D deficiency and odds ratios for the association of mortality in critically ill children treated in intensive care units, with subgroup analysis for children with sepsis. Meta-regression and sensitivity analyses were used to investigate heterogeneity.\n\nFindingsForty-eight studies were included. The total sample size was 7,199, with 1,679 (23%) children acting as controls in case-control studies. Of 5,520 critically ill children, 2,664 (48%) were vitamin D deficient (< 50 nmol/L). Results of the random effects model demonstrated a pooled prevalence of vitamin D deficiency of 54.9% (95% CI 48.0-61.6, I2=95.0%, 95% CI 94.0-95.8, p < 0.0001). In subgroup analysis of children with sepsis (16 studies, 788 total individuals) we observed higher prevalence of deficiency (63.8%, 95% CI 49.9-75.7, I2=90.5%, 95% CI 86.2-93.5%, p < 0.0001). In patients admitted to intensive care for respiratory tract infections (24 studies, 1,683 total individuals), prevalence was 49.9% (95% CI 37.6-62.2; I2 = 93.9%, 95% CI 92.1-95.3, p < 0.0001). Only one identified study assessed vitamin D levels in sepsis and mortality. The meta-regression model with all available variables (year of publication, total study sample size, quality score, study design, country group and clinical setting) explained 37.52% of I2 (F = 5.1119, p = 0.0005) with clinical setting and country groups being significant predictors for prevalence.\n\nOur meta-analysis (18 studies, 2,463 total individuals) showed an increased risk of death in vitamin D deficient critically ill children both with the random (OR 1.81, 95% CI 1.24-2.64, p-value = 0.002) and fixed effects (OR 1.72, 95% CI 1.27-2.33, p= 0.0005) models with low heterogeneity (I2 = 25.7%, 95% CI 0.0-58.0, p = 0.153) and low evidence of publication bias (p = 0.084, Eggers test).\n\nInterpretationCirculating vitamin D deficiency is common amongst critically ill children, particularly in those with sepsis. Our results suggest that vitamin D deficiency in critically ill children is associated with increased mortality. Clinical trials, studies with larger sample sizes and standardized approaches are needed to further assess associations between circulating levels of vitamin D and mortality or other outcomes in the pediatric population.\n\nFundingNone\n\nRegistrationPROSPERO (CRD42016050638)\n\nCopyrightOpen access article under terms of CC BY

epidemiology↗

Neutrophil counts and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies

OBJECTIVETo evaluate the strength and validity of evidence on the association between the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis.\n\nDESIGNUmbrella review of systematic reviews and meta-analyses of observational studies.\n\nDATA SOURCESMedline, EMBASE, and Cochrane Database of Systematic Reviews.\n\nELIGIBILITY CRITERIASystematic reviews or meta-analyses of observational studies evaluating the association between NLR or TAN and specific cancer outcomes related to disease progression or survival.\n\nDATA SYNTHESISThe available evidence was graded as strong, highly suggestive, suggestive, or weak through the application of pre-set grading criteria. For each included meta-analysis, the grading criteria considered the significance of the random effects estimate, the significance of the largest included study, the number of studies and individuals included, the heterogeneity between included studies, the 95% prediction intervals, presence of small study effects, excess significance and credibility ceilings.\n\nRESULTS239 meta-analyses investigating the association between NLR or TAN and cancer outcomes were identified from 57 published studies meeting the eligibility criteria, with 81 meta-analyses from 36 studies meeting the criteria for inclusion. No meta-analyses found a hazard ratio (HR) in the opposite direction of effect (HR<1). When assessed for significance and bias related to heterogeneity and small study effects, only three (4%) associations between NLR and outcomes in gastrointestinal and nasopharyngeal cancers were supported by strong evidence.\n\nCONCLUSIONDespite many publications exploring the association between NLR and cancer prognosis, the evidence is limited by significant heterogeneity and small study effects. There is a lack of evidence on the association between TAN and cancer prognosis, with all nine associations identified arising from the same study. Further research is required to provide strong evidence for associations between both TAN and NLR and poor cancer prognosis.\n\nREGISTRATIONThis umbrella review is registered on PROSPERO (CRD42017069131)\n\nFUNDINGMedical Research Council\n\nCOPYRIGHTOpen access article under terms of CC BY\n\nSHORT TITLENeutrophils and cancer prognosis: an umbrella review\n\nKEY RESULTWhen assessed for significance and bias related to heterogeneity and small study effects, only three (4%) associations between NLR and overall survival and progression-free survival in gastrointestinal and nasopharyngeal cancers were supported by strong evidence.\n\nWHAT THIS PAPER ADDS\n\nWHAT IS ALREADY KNOWN ON THE TOPICO_LINeutrophil counts have been linked to the progression of cancer due to their tumourigenic role in the cancer microenvironment.\nC_LIO_LINumerous meta-analyses and individual studies have explored the association between neutrophil counts and cancer outcomes for a variety of cancer sites, leading to a large body of evidence with variable strength and validity.\nC_LIO_LIUncertainty exists around the association between neutrophils and cancer outcomes, depending on the site, outcome and treatments considered.\nC_LI\n\nWHAT THIS STUDY ADDSO_LIAll meta-analyses included in this review indicated an association between high neutrophil counts and poor cancer prognosis.\nC_LIO_LIThere is strong evidence supporting the association between the neutrophil to lymphocyte ratio and poor cancer prognosis in some respiratory and gastrointestinal cancers.\nC_LIO_LIFurther research is required to strengthen the existing body of evidence, particularly for the association between tumour-associated neutrophils and cancer outcomes.\nC_LI

epidemiology↗