55 research outputs found
Single board system for fuzzy inference
The very large scale integration (VLSI) implementation of a fuzzy logic inference mechanism allows the use of rule-based control and decision making in demanding real-time applications. Researchers designed a full custom VLSI inference engine. The chip was fabricated using CMOS technology. The chip consists of 688,000 transistors of which 476,000 are used for RAM memory. The fuzzy logic inference engine board system incorporates the custom designed integrated circuit into a standard VMEbus environment. The Fuzzy Logic system uses Transistor-Transistor Logic (TTL) parts to provide the interface between the Fuzzy chip and a standard, double height VMEbus backplane, allowing the chip to perform application process control through the VMEbus host. High level C language functions hide details of the hardware system interface from the applications level programmer. The first version of the board was installed on a robot at Oak Ridge National Laboratory in January of 1990
Analysis of the UK Government's 2011 tourism policy
This review considers the UK Government's 2011 tourism policy document. The policy was produced during a period of public sector restructuring in the UK and also during the global economic crisis, which began in 2008. The policy sets out a number of reforms to the governance of tourism at the national and local levels, which aim to increase the level of private sector involvement in leading and developing the tourism sector and to reduce the sector's dependence on public funding. During a period of economic slowdown in the UK, the tourism industry can make a significant contribution to growth, but it is not yet clear whether these proposed reforms will support or impede the future development of the tourism industry in the UK
Incidence and risk factors for neonatal tetanus in admissions to Kilifi County Hospital, Kenya.
BACKGROUND: Neonatal Tetanus (NT) is a preventable cause of mortality and neurological sequelae that occurs at higher incidence in resource-poor countries, presumably because of low maternal immunisation rates and unhygienic cord care practices. We aimed to determine changes in the incidence of NT, characterize and investigate the associated risk factors and mortality in a prospective cohort study including all admissions over a 15-year period at a County hospital on the Kenyan coast, a region with relatively high historical NT rates within Kenya. METHODS: We assessed all neonatal admissions to Kilifi County Hospital in Kenya (1999-2013) and identified cases of NT (standard clinical case definition) admitted during this time. Poisson regression was used to examine change in incidence of NT using accurate denominator data from an area of active demographic surveillance. Logistic regression was used to investigate the risk factors for NT and factors associated with mortality in NT amongst neonatal admissions. A subset of sera from mothers (n = 61) and neonates (n = 47) were tested for anti-tetanus antibodies. RESULTS: There were 191 NT admissions, of whom 187 (98%) were home deliveries. Incidence of NT declined significantly (Incidence Rate Ratio: 0.85 (95% Confidence interval 0.81-0.89), P<0.001) but the case fatality (62%) did not change over the study period (P = 0.536). Younger infant age at admission (P = 0.001) was the only independent predictor of mortality. Compared to neonatal hospital admittee controls, the proportion of home births was higher among the cases. Sera tested for antitetanus antibodies showed most mothers (50/61, 82%) had undetectable levels of antitetanus antibodies, and most (8/9, 89%) mothers with detectable antibodies had a neonate without protective levels. CONCLUSIONS: Incidence of NT in Kilifi County has significantly reduced, with reductions following immunisation campaigns. Our results suggest immunisation efforts are effective if sustained and efforts should continue to expand coverage
Acute seizures attributable to falciparum malaria in an endemic area on the Kenyan coast
Falciparum malaria is an important cause of acute symptomatic seizures in children admitted to hospitals in sub-Saharan Africa, and these seizures are associated with neurological disabilities and epilepsy. However, it is difficult to determine the proportion of seizures attributable to malaria in endemic areas since a significant proportion of asymptomatic children have malaria parasitaemia. We studied children aged 0–13 years who had been admitted with a history of seizures to a rural Kenyan hospital between 2002 and 2008. We examined the changes in the incidence of seizures with the reduction of malaria. Logistic regression was used to model malaria-attributable fractions for seizures (the proportion of seizures caused by malaria) to determine if the observed decrease in acute symptomatic seizures was a measure of seizures that are attributable to malaria. The overall incidence of acute symptomatic seizures over the period was 651/100 000/year (95% confidence interval 632–670) and it was 400/100 000/year (95% confidence interval 385–415) for acute complex symptomatic seizures (convulsive status epilepticus, repetitive or focal) and 163/100 000/year (95% confidence interval 154–173) for febrile seizures. From 2002 to 2008, the incidence of all acute symptomatic seizures decreased by 809/100 000/year (69.2%) with 93.1% of this decrease in malaria-associated seizures. The decrease in the incidence of acute complex symptomatic seizures during the period was 111/100 000/year (57.2%) for convulsive status epilepticus, 440/100 000/year (73.7%) for repetitive seizures and 153/100 000/year (80.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures with parasitaemia were 92.9% (95% confidence interval 90.4–95.1%) for all acute symptomatic seizures, 92.9% (95% confidence interval 89.4–95.5%) for convulsive status epilepticus, 93.6% (95% confidence interval 90.9–95.9%) for repetitive seizures and 91.8% (95% confidence interval 85.6–95.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures in children above 6 months of age decreased with age. The observed decrease in all acute symptomatic seizures (809/100 000/year) was similar to the predicted decline (794/100 000/year) estimated by malaria-attributable fractions at the beginning of the study. In endemic areas, falciparum malaria is the most common cause of seizures and the risk for seizures in malaria decreases with age. The reduction in malaria has decreased the burden of seizures that are attributable to malaria and this could lead to reduced neurological disabilities and epilepsy in the area
Baby Business: a randomised controlled trial of a universal parenting program that aims to prevent early infant sleep and cry problems and associated parental depression
<p>Abstract</p> <p>Background</p> <p>Infant crying and sleep problems (e.g. frequent night waking, difficulties settling to sleep) each affect up to 30% of infants and often co-exist. They are costly to manage and associated with adverse outcomes including postnatal depression symptoms, early weaning from breast milk, and later child behaviour problems. Preventing such problems could improve these adverse outcomes and reduce costs to families and the health care system. Anticipatory guidance-i.e. providing parents with information about normal infant sleep and cry patterns, ways to encourage self-settling in infants, and ways to develop feeding and settling routines <it>before </it>the onset of problems-could prevent such problems. This paper outlines the protocol for our study which aims to test an anticipatory guidance approach.</p> <p>Methods/Design</p> <p>750 families from four Local Government Areas in Melbourne, Australia have been randomised to receive the <it>Baby Business </it>program (intervention group) or usual care (control group) offered by health services. The <it>Baby Business </it>program provides parents with information about infant sleep and crying via a DVD and booklet (mailed soon after birth), telephone consultation (at infant age 6-8 weeks) and parent group session (at infant age 12 weeks). All English speaking parents of healthy newborn infants born at > 32 weeks gestation and referred by their maternal and child health nurse at their first post partum home visit (day 7-10 postpartum), are eligible. The primary outcome is parent report of infant night time sleep as a problem at four months of age and secondary outcomes include parent report of infant daytime sleep or crying as a problem, mean duration of infant sleep and crying/24 hours, parental depression symptoms, parent sleep quality and quantity and health service use. Data will be collected at two weeks (baseline), four months and six months of age. An economic evaluation using a cost-consequences approach will, from a societal perspective, compare costs and health outcomes between the intervention and control groups.</p> <p>Discussion</p> <p>To our knowledge this is the first randomised controlled trial of a program which aims to prevent both infant sleeping and crying problems and associated postnatal depression symptoms. If effective, it could offer an important public health prevention approach to these common, distressing problems.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN63834603">ISRCTN63834603</a></p
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture
Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
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