59 research outputs found

    Long-term survival after primary intracerebral hemorrhage : A population-based case-control study spanning a quarter of a century

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    Background and purpose The aim of this study was to determine the differences in life expectancy and causes of death after primary intracerebral hemorrhage (ICH) relative to general population controls. Methods In a population-based setting, 963 patients from Northern Ostrobothnia who had their first-ever ICH between 1993 and 2008 were compared with a cohort of 2884 sex- and age-matched controls in terms of dates and causes of death as extracted from the Causes of Death Register kept by Statistics Finland and valid up to the end of 2017. Results Of our 963 patients, 781 died during the follow-up time (mortality 81.1%). Cerebrovascular disease was the most common cause of death for these patients, 37.3% compared with 8.2% amongst the controls. The most common reasons for cerebrovascular mortality in the ICH patients were late sequelae of ICH in 12.8% (controls 0%) and new bleeding in 10.6% (controls 1.0%). The long-term survivors had a smaller ICH volume (median 12 ml) than those patients who died within 3 months (median 39 ml). The mortality rate of ICH patients during a follow-up between 12 and 24 years was still higher than that of their controls (hazard ratio 2.08, 95% confidence interval 1.58-2.74, p < 0.001). Conclusions Very long-term ICH survivors have a constant excess mortality relative to controls even 10 years after the index event. A significantly larger proportion of patients died of cerebrovascular causes and fewer because of cancer relative to the controls.Peer reviewe

    A novel approach to assessing the ecosystem-wide impacts of reintroductions

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    Reintroducing a species to an ecosystem can have significant impacts on the recipient ecological community. Although reintroductions can have striking and positive outcomes, they also carry risks; many well intentioned conservation actions have had surprising and unsatisfactory outcomes. A range of network-based mathematical methods have been developed to make quantitative predictions of how communities will respond to management interventions. These methods are based on the limited knowledge of which species interact with each other and in what way. However, expert knowledge isn’t perfect and can only take models so far. Fortunately, other types of data, such as abundance time-series, is often available, but, to date, no quantitative method exists to integrate these various data types into these models, allowing more precise ecosystem-wide predictions. In this paper, we develop mathematical methods that combine time-series data of multiple species with knowledge of species interactions and we apply it to proposed reintroductions at Booderee National Park in Australia. There have been large fluctuations in species abundances at Booderee National Park in recent history, following intense feral fox (Vulpes vulpes) control – including the local extinction of the greater glider (Petauroides volans). These fluctuations can provide information about the system isn’t readily obtained from a stable system, and we use them to inform models that we then use to predict potential outcomes of eastern quoll (Dasyurus viverrinus) and long-nosed potoroo (Potorous tridactylus) reintroductions. One of the key species of conservation concern in the park is the eastern bristlebird (Dasyornis brachypterus), and we find that long-nosed potoroo introduction would have very little impact on the eastern bristlebird population, while the eastern quoll introduction increased the likelihood of eastern bristlebird decline, although that depends on the strength and form of any possible interaction.We thank the ARC Centre of Excellence for Environmental Decisions, The National Environmental Research Project Decisions Hub and an ARC Linkage Project (LP160100496) for funding. CB is the recipient of a John Stocker Postdoctoral Fellowship from the Science and Industry Endowment Fund. MB is supported by an ARC Future Fellowship (FT170100274). EMM is a current ARC Future Fellowship (FT170100140) and was supported by an ARC DECRA Fellowship for the majority of this work

    Heterozygous TLR3 Mutation in Patients with Hantavirus Encephalitis

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    Puumala hantavirus (PUUV) hemorrhagic fever with renal syndrome (HFRS) is common in Northern Europe; this infection is usually self-limited and severe complications are uncommon. PUUV and other hantaviruses, however, can rarely cause encephalitis. The pathogenesis of these rare and severe events is unknown. In this study, we explored the possibility that genetic defects in innate anti-viral immunity, as analogous to Toll-like receptor 3 (TLR3) mutations seen in HSV-1 encephalitis, may explain PUUV encephalitis. We completed exome sequencing of seven adult patients with encephalitis or encephalomyelitis during acute PUUV infection. We found heterozygosity for the TLR3 p.L742F novel variant in two of the seven unrelated patients (29%,p = 0.0195). TLR3-deficient P2.1 fibrosarcoma cell line and SV40-immortalized fibroblasts (SV40-fibroblasts) from patient skin expressing mutant or wild-type TLR3 were tested functionally. The TLR3 p.L742F allele displayed low poly(I:C)-stimulated cytokine induction when expressed in P2.1 cells. SV40-fibroblasts from three healthy controls produced increasing levels of IFN-lambda and IL-6 after 24 h of stimulation with increasing concentrations of poly(I:C), whereas the production of the cytokines was impaired in TLR3 L742F/WT patient SV40-fibroblasts. Heterozygous TLR3 mutation may underlie not only HSV-1 encephalitis but also PUUV hantavirus encephalitis. Such possibility should be further explored in encephalitis caused by these and other hantaviruses.Peer reviewe

    Effective detection of proteins following electrophoresis using extracts of locally available food species

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    Procedures in life sciences research laboratories often require chemicals and plasticware that are costly, toxic or pose a risk to the environment. Therefore, sustainable alternatives would be of interest, provided that they generate suitable data quality. Coomassie blue and silver staining are the most widely used methods for detecting proteins following electrophoresis in the laboratory. However, their use presents challenges in terms of safety and waste management. In the current study, aqueous extracts were prepared from a series of common food species and evaluated as alternative stains for protein detection. Beets, blueberries, purple cabbage, raspberries and strawberries were employed to stain identical proteins separated under the same conditions in electrophoresis gels. Extracts of the first two species resulted in protein bands that were detectable through visible light transillumination, whereas extracts from all five species generated specific protein bands under ultraviolet light. The raspberry-derived extract was selected for further study based on the brightness of the fluorescent protein bands and minimal background staining. For both bovine serum albumin and lysozyme at 2.5 μg and 0.5 μg protein per band, the mean signal intensities obtained with raspberry extract staining were just below half of those obtained with Coomassie blue. Furthermore, the mean intensities using raspberry extract were equivalent to those obtained using Coomassie blue in the detection of 0.1 μg protein. Therefore, raspberry could be used to produce an effective stain for the routine laboratory analysis of proteins

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Heterozygous TLR3 Mutation in Patients with Hantavirus Encephalitis

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    Puumala hantavirus (PUUV) hemorrhagic fever with renal syndrome (HFRS) is common in Northern Europe; this infection is usually self-limited and severe complications are uncommon. PUUV and other hantaviruses, however, can rarely cause encephalitis. The pathogenesis of these rare and severe events is unknown. In this study, we explored the possibility that genetic defects in innate anti-viral immunity, as analogous to Toll-like receptor 3 (TLR3) mutations seen in HSV-1 encephalitis, may explain PUUV encephalitis. We completed exome sequencing of seven adult patients with encephalitis or encephalomyelitis during acute PUUV infection. We found heterozygosity for the TLR3 p.L742F novel variant in two of the seven unrelated patients (29%,p = 0.0195). TLR3-deficient P2.1 fibrosarcoma cell line and SV40-immortalized fibroblasts (SV40-fibroblasts) from patient skin expressing mutant or wild-type TLR3 were tested functionally. The TLR3 p.L742F allele displayed low poly(I:C)-stimulated cytokine induction when expressed in P2.1 cells. SV40-fibroblasts from three healthy controls produced increasing levels of IFN-lambda and IL-6 after 24 h of stimulation with increasing concentrations of poly(I:C), whereas the production of the cytokines was impaired in TLR3 L742F/WT patient SV40-fibroblasts. Heterozygous TLR3 mutation may underlie not only HSV-1 encephalitis but also PUUV hantavirus encephalitis. Such possibility should be further explored in encephalitis caused by these and other hantaviruses

    Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

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    Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication
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