The incidence of all stroke and stroke subtype in the United Kingdom, 1985 to 2008: a systematic review

<p>Abstract</p> <p>Background</p> <p>There is considerable geographic variation in stroke mortality around the United Kingdom (UK). Whether this is due to geographical differences in incidence or case-fatality is unclear. We conducted a systematic review of high-quality studies documenting the incidence of any stroke and stroke subtypes, between 1985 and 2008 in the UK. We aimed to study geographic and temporal trends in relation to equivalent mortality trends.</p> <p>Methods</p> <p>MEDLINE and EMBASE were searched, reference lists inspected and authors of included papers were contacted. All rates were standardised to the European Standard Population for those over 45, and between 45 and 74 years. Stroke mortality rates for the included areas were then calculated to produce rate ratios of stroke mortality to incidence for each location.</p> <p>Results</p> <p>Five papers were included in this review. Geographic variation was narrow but incidence appeared to largely mirror mortality rates for all stroke. For men over 45, incidence (and confidence intervals) per 100,000 ranged from 124 (109-141) in South London, to 185 (164-208) in Scotland. For men, premature (45-74 years) stroke incidence per 100,000 ranged from 79 (67-94) in the North West, to 112 (95-132) in Scotland. Stroke subtype data was more geographically restricted, but did suggest there is no sizeable variation in incidence by subtype around the country. Only one paper, based in South London, had data on temporal trends. This showed that there has been a decline in stroke incidence since the mid 1990 s. This could not be compared to any other locations in this review.</p> <p>Conclusions</p> <p>Geographic variations in stroke incidence appear to mirror variations in mortality rates. This suggests policies to reduce inequalities in stroke mortality should be directed at risk factor profiles rather than treatment after a first incident event. More high quality stroke incidence data from around the UK are needed before this can be confirmed.</p

B →Vℓ+ℓ− in the Standard Model from light-cone sum rules

We present $B_q\to\rho$, $B_q\to\omega$, $B_q\to K^*$, $B_s\to K^*$ and $B_s\to \phi$ form factors from light-cone sum rules (LCSR) at $\mathcal{O}(\alpha_s)$ for twist-2 and 3 and $\mathcal{O}(\alpha_s^0)$ for twist-4 with updated hadronic input parameters. Three asymptotic light-cone distribution amplitudes of twist-$4$ (and $5$) are determined, necessary for the form factors to obey the equations of motion. It is argued that the latter constrain the uncertainty of tensor-to-vector form factor ratios thereby improving the prediction of zeros of helicity amplitudes of major importance for $B\to K^*\ell\ell$ angular observables. We provide easy-to-use fits to the LCSR results, including the full error correlation matrix, in all modes at low $q^2$ as well as combined fits to LCSR and lattice results covering the entire kinematic range for $B_q\to K^*$, $B_s\to K^*$ and $B_s\to \phi$. The error correlation matrix avoids the problem of overestimating the uncertainty in phenomenological applications. Using the new form factors and recent computations of non-factorisable contributions we provide Standard Model predictions for $B\to K^*\gamma$ as well as $B\to K^*\ell^+\ell^-$ and $B_s\to\phi\mu^+\mu^-$ at low dilepton invariant mass. Employing our $B \to (\rho,\omega)$ form factor results we extract the CKM element $|V_\mathrm{ub}|$ from the semileptonic decays $B\to(\rho,\omega) \ell\nu$ and find good agreement with other exclusive determinations.Comment: 64 pages, 7 figures, 15 tables. v3: Minor clarifications, numerics unchanged. Matches version published in JHE

Mercury in Nelson's Sparrow Subspecies at Breeding Sites

Background: Mercury is a persistent, biomagnifying contaminant that can cause negative effects on ecosystems. Marshes are often areas of relatively high mercury methylation and bioaccumulation. Nelson’s Sparrows (Ammodramus nelsoni) use marsh habitats year-round and have been documented to exhibit tissue mercury concentrations that exceed negative effects thresholds. We sought to further characterize the potential risk of Nelson’s Sparrows to mercury exposure by sampling individuals from sites within the range of each of its subspecies

A Novel Mouse Fgfr2 Mutant, Hobbyhorse (hob), Exhibits Complete XY Gonadal Sex Reversal

The secreted molecule fibroblast growth factor 9 (FGF9) plays a critical role in testis determination in the mouse. In embryonic gonadal somatic cells it is required for maintenance of SOX9 expression, a key determinant of Sertoli cell fate. Conditional gene targeting studies have identified FGFR2 as the main gonadal receptor for FGF9 during sex determination. However, such studies can be complicated by inefficient and variable deletion of floxed alleles, depending on the choice of Cre deleter strain. Here, we report a novel, constitutive allele of Fgfr2, hobbyhorse (hob), which was identified in an ENU-based forward genetic screen for novel testis-determining loci. Fgr2hob is caused by a C to T mutation in the invariant exon 7, resulting in a polypeptide with a mis-sense mutation at position 263 (Pro263Ser) in the third extracellular immunoglobulin-like domain of FGFR2. Mutant homozygous embryos show severe limb and lung defects and, when on the sensitised C57BL/6J (B6) genetic background, undergo complete XY gonadal sex reversal associated with failure to maintain expression of Sox9. Genetic crosses employing a null mutant of Fgfr2 suggest that Fgr2hob is a hypomorphic allele, affecting both the FGFR2b and FGFR2c splice isoforms of the receptor. We exploited the consistent phenotype of this constitutive mutant by analysing MAPK signalling at the sex-determining stage of gonad development, but no significant abnormalities in mutant embryos were detected

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Impairment experiences, identity and attitudes towards genetic screening : the views of people with Spinal Muscular Atrophy

Developments in genetics are rapidly changing the capacity and scope of screening practices. However, people with genetic conditions have been under-represented in the literature exploring their implications. This mixed methods study explores the attitudes of people with Spinal Muscular Atrophy (SMA) towards three different population-level genetic screening programmes for SMA: pre-conception, prenatal and newborn. Drawing on qualitative interviews (n= 15) and a survey (n=82), this study demonstrates that more severely affected individuals with early-onset symptoms (Type II SMA), are less likely to support screening and more likely to view SMA positively than those with milder, later onset and/or fluctuating symptoms (Types III/ IV SMA). Indeed, this clinically milder group were more likely to support all forms of screening and view SMA negatively. This paper highlights that screening is a complex issue for people with genetic conditions, and the nature of impairment experiences plays a critical role in shaping attitudes

Bio-Repository of DNA in stroke (BRAINS): A study protocol

<p>Abstract</p> <p>Background</p> <p>Stroke is one of the commonest causes of mortality in the world and anticipated to be an increasing burden to the developing world. Stroke has a genetic basis and identifying those genes may not only help us define the mechanisms that cause stroke but also identify novel therapeutic targets. However, large scale highly phenotyped DNA repositories are required in order for this to be achieved.</p> <p>Methods</p> <p>The proposed Bio-Repository of DNA in Stroke (BRAINS) will recruit all subtypes of stroke as well as controls from two different continents, Europe and Asia. Subjects recruited from the UK will include stroke patients of European ancestry as well as British South Asians. Stroke subjects from South Asia will be recruited from India and Sri Lanka. South Asian cases will also have control subjects recruited.</p> <p>Discussion</p> <p>We describe a study protocol to establish a large and highly characterized stroke biobank in those of European and South Asian descent. With different ethnic populations being recruited, BRAINS has the ability to compare and contrast genetic risk factors between those of differing ancestral descent as well as those who migrate into different environments.</p

Local Adaptation of Aboveground Herbivores towards Plant Phenotypes Induced by Soil Biota

Background: Soil biota may trigger strong physiological responses in plants and consequently induce distinct phenotypes. Plant phenotype, in turn, has a strong impact on herbivore performance. Here, we tested the hypothesis that aboveground herbivores are able to adapt to plant phenotypes induced by soil biota. Methodology and Principal Findings: We bred spider mites for 15 generations on snap beans with three different belowground biotic interactions: (i) no biota (to serve as control), (ii) arbuscular mycorrhizal fungi and (ii) root-feeding nematodes. Subsequently, we conducted a reciprocal selection experiment using these spider mites, which had been kept on the differently treated plants. Belowground treatments induced changes in plant biomass, nutrient composition and water content. No direct chemical defence through cyanogenesis was detected in any of the plant groups. Growth rates of spider mites were higher on the ecotypes on which they were bred for 15 generations, although the statistical significance disappeared for mites from the nematode treatment when corrected for all multiple comparisons. Conclusion/Significance: These results demonstrate that belowground biota may indeed impose selection on the aboveground insect herbivores mediated by the host plant. The observed adaptation was driven by variable quantitativ

Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services