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Segurado, Ricardo
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Segurado, Ricardo
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Segurado, Ricardo
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- PublicationContact tracing during the COVID-19 outbreak: a protocol for enabling rapid learning from experiences and exploring the psychological impact on contact tracersBackground: Given the unprecedented nature of the COVID-19 pandemic, the Irish health system required the redeployment of public sector staff and the recruitment of dedicated contact tracing staff in the effort to contain the spread of the virus. Contact tracing is crucial for effective disease control and is normally a role carried out by public health teams. Contact tracing staff are provided with rapid intensive training but are operating in a dynamic environment where processes and advice are adapting continuously. Real-time data is essential to inform strategy, coordinate interconnected processes, and respond to needs. Given that many contact tracers have been newly recruited or redeployed, they may not have significant experience in healthcare and may experience difficulties in managing the anxieties and emotional distress of members of the public. Aim: This research aims to: (i) identify emerging needs and issues and feed this information back to the Health Service Executive for updates to the COVID-19 Contact Management Programme (CMP); (ii) understand the psychological impact on contact tracers and inform the development of appropriate supports. Methods: We will use a mixed-methods approach. A brief online survey will be administered at up to three time points during 2021 to measure emotional exhaustion, anxiety, general health, and stress of contact tracing staff, identify tracing systems or processes issues, as well as issues of concern and confusion among the public. Interviews will also be conducted with a subset of participants to achieve a more in-depth understanding of these experiences. Observations may be conducted in contact tracing centres to document processes, practices, and explore any local contextual issues. Impact: Regular briefs arising from this research with data, analysis, and recommendations will aim to support the work of the CMP to identify problems and implement solutions. We will deliver regular feedback on systems issues; challenges; and the psychological well-being of contact tracing staff.
280 - PublicationReference ranges for fetal volumes in the late first trimester, obtained using 9-degree rotational steps(2019-10-16)
; ; ; ; ; Objectives: In the course of another study, we calculated fetal volume centile values for each week of gestation from 11 to 14 weeks using nine-degree rotation steps.24 - PublicationLarge-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis(BioMed Central, 2007-12-18)
; ; ; ; ; Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates.449 - PublicationAnalyses of single marker and pairwise effects of candidate loci for rheumatoid arthritis using logistic regression and random forests(BioMed Central, 2007-12-18)
; ; ; ; ; ; Using parametric and nonparametric techniques, our study investigated the presence of single locus and pairwise effects between 20 markers of the Genetic Analysis Workshop 15 (GAW15) North American Rheumatoid Arthritis Consortium (NARAC) candidate gene data set (Problem 2), analyzing 463 independent patients and 855 controls. Specifically, our work examined the correspondence between logistic regression (LR) analysis of single-locus and pairwise interaction effects, and random forest (RF) single and joint importance measures. For this comparison, we selected small but stable RFs (500 trees), which showed strong correlations (r~0.98) between their importance measures and those by RFs grown on 5000 trees. Both RF importance measures captured most of the LR single-locus and pairwise interaction effects, while joint importance measures also corresponded to full LR models containing main and interaction effects. We furthermore showed that RF measures were particularly sensitive to data imputation. The most consistent pairwise effect on rheumatoid arthritis was found between two markers within MAP3K7IP2/SUMO4 on 6q25.1, although LR and RFs assigned different significance levels.Within a hypothetical two-stage design, pairwise LR analysis of all markers with significant RF single importance would have reduced the number of possible combinations in our small data set by 61%, whereas joint importance measures would have been less efficient for marker pair reduction. This suggests that RF single importance measures, which are able to detect a wide range of interaction effects and are computationally very efficient, might be exploited as pre-screening tool for larger association studies. Follow-up analysis, such as by LR, is required since RFs do not indicate high-risk genotype combinations.236 - PublicationCombining linkage data sets for meta-analysis and mega-analysis: the GAW15 rheumatoid arthritis data set(BioMed Central, 2007-12-18)
; ; ; ; ; We have used the genome-wide marker genotypes from Genetic Analysis Workshop 15 Problem 2 to explore joint evidence for genetic linkage to rheumatoid arthritis across several samples. The data consisted of four high-density genome scans on samples selected for rheumatoid arthritis. We cleaned the data, removed intermarker linkage disequilibrium, and assembled the samples onto a common genetic map using genome sequence positions as a reference for map interpolation. The individual studies were combined first at the genotype level (mega-analysis) prior to a multipoint linkage analysis on the combined sample, and second using the genome scan meta-analysis method after linkage analysis of each sample. The two approaches were compared, and give strong support to the HLA locus on chromosome 6 as a susceptibility locus. Other regions of interest include loci on chromosomes 11, 2, and 12.240 - PublicationCommunity first responders for out-of-hospital cardiac arrest in adults and children(Wiley, 2019-07-19)
; ; ; ; ; ; ; Background: Mobilization of community first responders (CFRs) to the scene of an out-of-hospital cardiac arrest (OHCA) event has been proposed as a means of shortening the interval from occurrence of cardiac arrest to performance of cardiopulmonary resuscitation (CPR) and defibrillation, thereby increasing patient survival. Objectives: To assess the effect of mobilizing community first responders (CFRs) to out-of-hospital cardiac arrest events in adults and children older than four weeks of age, in terms of survival and neurological function. Search methods We searched the following databases for relevant trials in January 2019: CENTRAL, MEDLINE (Ovid SP), Embase (Ovid SP), and Web of Science. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov, and we scanned the abstracts of conference proceedings of the American Heart Association and the European Resuscitation Council. Selection criteria We included randomized and quasi-randomized trials (RCTs and q-RCTs) that compared routine emergency medical services (EMS) care versus EMS care plus mobilization of CFRs in instances of OHCA.Trials with randomization by cluster were eligible for inclusion, including cluster-design studies with intervention cross-over. In some communities, the statutory ambulance service/EMS is routinely provided by the local fire service. For the purposes of this review, this group represents the statutory ambulance service/EMS, as distinct from CFRs, and was not included as an eligible intervention. We did not include studies primarily focused on opportunistic bystanders. Individuals who were present at the scene of an OHCA event and who performed CPR according to telephone instruction provided by EMS call takers were not considered to be CFRs. Studies primarily assessing the impact of specific additional interventions such as administration of naloxone in narcotic overdose or adrenaline in anaphylaxis were also excluded. We included adults and children older than four weeks of age who had experienced an OHCA. Data collection and analysis Two review authors independently reviewed all titles and abstracts received to assess potential eligibility, using set inclusion criteria. We obtained and examined in detail full-text copies of all papers considered potentially eligible, and we approached authors of trials for additional information when necessary. We summarized the process of study selection in a PRISMA flowchart. Three review authors independently extracted relevant data using a standard data extraction form and assessed the validity of each included trial using the Cochrane ’Risk of bias’ tool. We resolved disagreements by discussion and consensus. We synthesized findings in narrative fashion due to the heterogeneity of the included studies. We used the principles of the GRADE system to assess the certainty of the body of evidence associated with specific outcomes and to construct a ’Summary of findings’ table. Main results: We found two completed studies involving a total of 1136 participants that ultimately met our inclusion criteria. We also found one ongoing study and one planned study. We noted significant heterogeneity in the characteristics of interventions and outcomes measured or reported across these studies, thus we could not pool study results. One completed study considered the dispatch of police and fire service CFRs equipped with automatic external defibrillators (AEDs) in an EMS system in Amsterdam and surrounding areas. This study was an RCT with allocation made by cluster according to non-overlapping geographical regions. It was conducted between 5 January 2000 and 5 January 2002. All participants were 18 years of age or older and had experienced witnessed OHCA. The study found no difference in survival at hospital discharge (odds ratio (OR) 1.3, 95% confidence interval (CI) 0.8 to 2.2; 1 RCT; 469 participants; low-certainty evidence), despite the observation that all 72 incidences of defibrillation performed before EMS arrival occurred in the intervention group (OR and 95% CI-not applicable; 1 RCT; 469 participants; moderate-certainty evidence). This study reported increased survival to hospital admission in the intervention group (OR 1.5, 95% CI 1.1 to 2.0; 1 RCT; 469 participants; moderate-certainty evidence). The second completed study considered the dispatch of nearby lay volunteers in Stockholm, Sweden, who were trained to perform cardiopulmonary resuscitation (CPR). This represented a supplementary CFR intervention in an EMS system where police and fire services were already routinely dispatched to OHCA in addition to EMS ambulances. This study, an RCT, included both witnessed and unwitnessed OHCA and was conducted between 1 April 2012 and 1 December 2013. Participants included adults and children eight years of age and older. Researchers found no difference in 30-day survival (OR 1.34, 95% CI 0.79 to 2.29; 1 RCT; 612 participants; low-certainty evidence), despite a significant increase in CPR performed before EMS arrival (OR 1.49, 95% CI 1.09 to 2.03; 1 RCT; 665 participants; moderate-certainty evidence). Neither of the included completed studies considered neurological function at hospital discharge or at 30 days, measured by cerebral performance category or by any other means. Neither of the included completed studies considered health-related quality of life. The overall certainty of evidence for the outcomes of included studies was low to moderate. Authors’ conclusions Moderate-certainty evidence shows that context-specific CFR interventions result in increased rates of CPR or defibrillation performed before EMS arrival. It remains uncertain whether this can translate to significantly increased rates of overall patient survival. When possible, further high-quality RCTs that are adequately powered to measure changes in survival should be conducted. The included studies did not consider survival with good neurological function. This outcome is likely to be important to patients and should be included routinely wherever survival is measured. We identified one ongoing study and one planned trial whose results once available may change the results of this review. As this review was limited to randomized and quasi-randomized trials, we may have missed some important data from other study types.191Scopus© Citations 2 - PublicationThe impact of introducing nurse-led analgesia and sedation guidelines in ventilated infants following cardiac surgery(Elsevier, 2020-10)
; ; ; ; Introduction: Enhanced clinical outcomes in the Paediatric Intensive Care Unit following standardisation of analgesia and sedation practice are reported. Little is known about the impact of standardisation of analgesia and sedation practice including incorporation of a validated distress assessment instrument on infants post cardiac surgery, a subset of whom have Trisomy 21. This study investigated whether the parallel introduction of nurse-led analgesia and sedation guidelines including regular distress assessment would impact on morphine administered to infants post cardiac surgery, and whether any differences observed would be amplified within the Trisomy 21 population. Methodology: A retrospective single centre before/after study design was used. Patients aged between 44 weeks postconceptual age and one year old who had open cardiothoracic surgery were included. Results: 61 patients before and 64 patients after the intervention were included. After the intervention, a reduction in the amount of morphine administered was not evident, while greater use of adjuvant sedatives and analgesics was observed. Patients with Trisomy 21 had a shorter duration of mechanical ventilation after the change in practice. Conclusion: The findings from this study affirm the importance of the nurses’ role in managing prescribed analgesia and sedation supported by best available evidence. A continued education and awareness focus on analgesia and sedation management in the pursuit of best patient care is imperative.81Scopus© Citations 1 - PublicationGenetic classification of populations using supervised learning(Public Library of Science, 2011-05-12)
; ; ; ; ; ; ; There are many instances in genetics in which we wish to determine whether two candidate populations are distinguishable on the basis of their genetic structure. Examples include populations which are geographically separated, case-control studies and quality control (when participants in a study have been genotyped at different laboratories). This latter application is of particular importance in the era of large scale genome wide association studies, when collections of individuals genotyped at different locations are being merged to provide increased power. The traditional method for detecting structure within a population is some form of exploratory technique such as principal components analysis. Such methods, which do not utilise our prior knowledge of the membership of the candidate populations. are termed unsupervised. Supervised methods, on the other hand are able to utilise this prior knowledge when it is available.In this paper we demonstrate that in such cases modern supervised approaches are a more appropriate tool for detecting genetic differences between populations. We apply two such methods, (neural networks and support vector machines) to the classification of three populations (two from Scotland and one from Bulgaria). The sensitivity exhibited by both these methods is considerably higher than that attained by principal components analysis and in fact comfortably exceeds a recently conjectured theoretical limit on the sensitivity of unsupervised methods. In particular, our methods can distinguish between the two Scottish populations, where principal components analysis cannot. We suggest, on the basis of our results that a supervised learning approach should be the method of choice when classifying individuals into pre-defined populations, particularly in quality control for large scale genome wide association studies.236Scopus© Citations 15 - PublicationGenome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms(Nature Publishing Group, 2011-07-19)
; ; ; ; Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing.275Scopus© Citations 24 - PublicationA genome-wide scan for common alleles affecting risk for autism(Oxford University Press, 2010-07-27)
; ; ; ; ; ; ; ; Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.947Scopus© Citations 453