Molecular epidemiology of carriage and disease associated strains of serogroup C Neisseria meningitidis, in the Irish Republic following the introduction of the meningococcal conjugate vaccine.

In the Irish Republic during the 1990s incidence meningococcal disease caused by serogroup C increased dramatically. During the 1999-2000 epidemiological year Ireland had the highest reported incidence of meningococcal disease in Europe (www.hpsc.ie). The national menC vaccination programme was introduced into the infant schedule in October 2000 and also offered to all persons under 23 years. At the same time, as part of a period of enhanced surveillance following the vaccine introduction, the National Meningococcal Carriage Survey was launched and continued each winter for the next 4 epidemiological years. The results of the vaccine campaign were impressive; a decrease in both carriage and incidence of serogroup C meningococci were observed. There were 29, 24, 13, 8 and 3 serogroup C organisms (n=77) recovered fromthe survey during the 2000 - 2001 - 2004 - 2005 epidemiological years respectively, which were available for this study. To gain a better understanding of the relationships between these organisms they were serotyped and serosubtyped using a conventional panel of antisera. They were also typed using Multi Locus Sequence Typing (MLST) and Multi Locus Restriction Typing (MLRT), a less expensive and more rapid alternative to MLST. BURST (Based Upon Related Sequence Type), is a grouping algorithm which uses the halotype data generated from MLSTIMLRT to form a visual depiction of the organisms inter-relatedness. BURST and other tools can be found in the START package (Sequence Type and Recombination Tests). In addition PAUP (Phylogenetic Analysis Using Parsimony) was applied to further elucidate these organisms relatedness. PAUP uses parsimony and concatenated MLST sequence data to generate relationships. Surveillance of the disease associated meningococcal population is hampered by the fact that only approximately 30% of the time is an organism recovered from the blood or CSF. The remaining 70% are usually assigned a capsule type by PCR with other relevant epidemiological typing data absent. MLST by nested PCR can help identify the genetic background of these organisms, but because most of the cases are infants and young children (\u3c 4 years) it is often the case that insufficient clinical DNA extract is available. To address this problem a nested multiplex PCR to generate an MLST result from a minimal clinical sample was designed and applied to 60 clinical samples (blood1CSF DNA extracts) fi-om the 1997-1998 - 2006-2007 epidemiological years, resulting in 40 complete MLST profiles. In addition to these 40 extracts, a total of 42 disease associated serogroup C organisms were recovered during the same period. This allowed a phenotypic and genotypic comparison of pre and post vaccine era. ST-I 1 meningococci still exist in the disease associated Irish meningococcal population, but at greatly decreased numbers. In addition to this work it was noticed at the time, that a large number of organisms recovered from the first year of the carriage survey did not give a group by PCR. A representative collection of these were also analysed by MLST/..MLRT/PAUP. Further, several possible \u27capsule switch\u27 phenotypes from the first year of the survey were investigated by MLST to find if they shared a similar genetic background

Four millennia of dairy surplus and deposition revealed through compound-specific stable isotope analysis and radiocarbon dating of Irish bog butters

Bog butters are large white or yellow waxy deposits regularly discovered within the peat bogs of Ireland and Scotland. They represent an extraordinary survival of prehistoric and later agricultural products, comprising the largest deposits of fat found anywhere in nature. Often found in wooden containers or wrapped in animal bladders, they are considered to have been buried intentionally by past farming communities. While previous analysis has determined that Irish bog butters derive from animal fat, their precise characterisation could not be achieved due to diagenetic compositional alterations during burial. Via compound-specific stable isotope analysis, we provide the first conclusive evidence of a dairy fat origin for the Irish bog butter tradition, which differs from bog butter traditions observed elsewhere. Our research also reveals a remarkably long-lived tradition of deposition and possible curation spanning at least 3500 years, from the Early Bronze Age (c. 1700 BC) to the 17th century AD. This is conclusively established via an extensive suite of both bulk and compound-specific radiocarbon dates

A Map of the Nanoworld: Sizing up the Science, Politics, and Business of the Infinitesimal

Mapping out the eight main nodes of nanotechnology discourse that have emerged in the past decade, we explore how various scientific, social, and ethical islands of discussion have developed, been recognized, and are being continually renegotiated. We do so by (1) identifying the ways in which scientists, policy makers, entrepreneurs, educators, and environmental groups have drawn boundaries on issues relating to nanotechnology; (2) describing concisely the perspectives from which these boundaries are drawn; and (3) exploring how boundaries on nanotechnology are marked and negotiated by various nodes of nanotechnology discourse.Comment: 25 page

Cost-effectiveness analysis of 3-D computerized tomography colonography versus optical colonoscopy for imaging symptomatic gastroenterology patients.

BACKGROUND: When symptomatic gastroenterology patients have an indication for colonic imaging, clinicians have a choice between optical colonoscopy (OC) and computerized tomography colonography with three-dimensional reconstruction (3-D CTC). 3-D CTC provides a minimally invasive and rapid evaluation of the entire colon, and it can be an efficient modality for diagnosing symptoms. It allows for a more targeted use of OC, which is associated with a higher risk of major adverse events and higher procedural costs. A case can be made for 3-D CTC as a primary test for colonic imaging followed if necessary by targeted therapeutic OC; however, the relative long-term costs and benefits of introducing 3-D CTC as a first-line investigation are unknown. AIM: The aim of this study was to assess the cost effectiveness of 3-D CTC versus OC for colonic imaging of symptomatic gastroenterology patients in the UK NHS. METHODS: We used a Markov model to follow a cohort of 100,000 symptomatic gastroenterology patients, aged 50 years or older, and estimate the expected lifetime outcomes, life years (LYs) and quality-adjusted life years (QALYs), and costs (£, 2010-2011) associated with 3-D CTC and OC. Sensitivity analyses were performed to assess the robustness of the base-case cost-effectiveness results to variation in input parameters and methodological assumptions. RESULTS: 3D-CTC provided a similar number of LYs (7.737 vs 7.739) and QALYs (7.013 vs 7.018) per individual compared with OC, and it was associated with substantially lower mean costs per patient (£467 vs £583), leading to a positive incremental net benefit. After accounting for the overall uncertainty, the probability of 3-D CTC being cost effective was around 60 %, at typical willingness-to-pay values of £20,000-£30,000 per QALY gained. CONCLUSION: 3-D CTC is a cost-saving and cost-effective option for colonic imaging of symptomatic gastroenterology patients compared with OC

What factors are associated with adolescents\u27 school break time physical activity and sedentary time?

Purpose Adolescents\u27 physical activity levels during school break time are low and understanding correlates of physical activity and sedentary time in this context is important. This study investigated cross-sectional and longitudinal associations between a range of individual, behavioural, social and policy/organisational correlates and objectively measured school break time physical activity and sedentary time.Methods In 2006, 146 adolescents (50% males; mean age = 14.1&plusmn;0.6 years) completed a questionnaire and wore an accelerometer for &ge;3 school days. Time spent engaged in sedentary, light (LPA) and moderate-to-vigorous physical activity (MVPA) during school break times (recess and lunchtime) were calculated using existing cut-points. Measures were repeated in 2008 among 111 adolescents. Multilevel models examined cross-sectional and longitudinal associations.Results Bringing in equipment was cross-sectionally associated with 3.2% more MVPA during break times. Females engaged in 5.1% more sedentary time than males, whilst older adolescents engaged in less MVPA than younger adolescents. Few longitudinal associations were observed. Adolescents who brought sports equipment to school engaged in 7.2% less LPA during break times two years later compared to those who did not bring equipment to school.Conclusion These data suggest that providing equipment and reducing restrictions on bringing in sports equipment to school may promote physical activity during school recess. Strategies targeting females\u27 and older adolescents\u27, in particular, are warranted.<br /

Genomic analysis of the Meningococcal ST-4821 complex – western clade, potential sexual transmission and predicted antibiotic susceptibility and vaccine coverage

Introduction: The ST-4821 complex (cc4821) is a leading cause of serogroup C and serogroup B invasive meningococcal disease in China where diverse strains in two phylogenetic groups (groups 1 and 2) have acquired fluoroquinolone resistance. cc4821 was recently prevalent among carriage isolates in men who have sex with men in New York City (USA). Genome-level population studies have thus far been limited to Chinese isolates. The aim of the present study was to build upon these with an extended panel of international cc4821 isolates. Methods: Genomes of isolates from Asia (1972 to 2017), Europe (2011 to 2018), North America (2007), and South America (2014) were sequenced or obtained from the PubMLST Neisseria database. Core genome comparisons were performed in PubMLST. Results: Four lineages were identified. Western isolates formed a distinct, mainly serogroup B sublineage with alleles associated with fluoroquinolone susceptibility (MIC &lt;0.03 mg/L) and reduced penicillin susceptibility (MIC 0.094 to 1 mg/L). A third of these were from anogenital sites in men who have sex with men and had unique denitrification gene alleles. Generally 4CMenB vaccine strain coverage was reliant on strain-specific NHBA peptides. Discussion: The previously identified cc4821 group 2 was resolved into three separate lineages. Clustering of western isolates was surprising given the overall diversity of cc4821. Possible association of this cluster with the anogenital niche is worthy of monitoring given concerns surrounding antibiotic resistance and potential subcapsular vaccine escape

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization

Component based evolution

This project focused on developing a methodology to support the semi-automatic evolution of a database application. As a case study, we implemented an Enterprise JavaBeans (EJB) application that persisted its data to a MySQL database. Changes were then made to the database structure and we applied our methodology to evolve the application. We determined that entity beans with container-managed persistence were most friendly to schema evolution; as a result, we recommend that most business logic be placed inside session beans

The upcoming energy crisis

Even according to the most optimistic projections, the supply of oil and natural gas will be exhausted during the 21st century. Humanity must start to look for alternative and possibly cleaner energy sources that will be in place before we hit the actual crisis. In this project we shall examine the accuracy of these predictions, identify alternative energy sources and develop recommendations for the preparation of their use. The impact of these policies on our health, economy and politics will be considered

PCR-Based Assay for Detection of Neisseria meningitidis Capsular Serogroups 29E, X, and Z

PCR-based assays for the identification of Neisseria meningitidis serogroups 29E, X, and Z by detection of specific regions of the ctrA gene are described. The specificities of these assays were confirmed using serogroups A, B, C, 29E, H, W135, X, Y, and Z and nongroupable meningococcal isolates