1,117 research outputs found
Applications of Multi-Body Dynamical Environments: The ARTEMIS Transfer Trajectory Design
The application of forces in multi-body dynamical environments to pennit the transfer of spacecraft from Earth orbit to Sun-Earth weak stability regions and then return to the Earth-Moon libration (L1 and L2) orbits has been successfully accomplished for the first time. This demonstrated transfer is a positive step in the realization of a design process that can be used to transfer spacecraft with minimal Delta-V expenditures. Initialized using gravity assists to overcome fuel constraints; the ARTEMIS trajectory design has successfully placed two spacecraft into EarthMoon libration orbits by means of these applications
Type 1 diabetes incidence in Scotland between 2006 and 2019
Aims: To describe type 1 diabetes incidence in Scotland between 2006 and 2019. Methods: Repeated annual crossâsectional studies of type 1 diabetes incidence were conducted. Incident cases were identified from the Scottish Care InformationâDiabetes Collaboration (SCIâDC), a populationâbased register of people with diagnosed diabetes derived from primary and secondary care data. Midâyear population estimates for Scotland were used as the denominator to calculate annual incidence with stratification by age and sex. Joinpoint regression was used to investigate whether incidence changed during the study period. Age and sexâspecific type 1 diabetes incidence over the whole time period was estimated by quintile of the Scottish Index of Multiple Deprivation (SIMD), an areaâbased measure, in which Q1 and Q5 denote the most and least deprived fifths of the population, respectively, with quasiâPoisson regression used to compare incidence for Q5 compared to Q1. Results: The median (IQR) age of the study population of 14,564 individuals with incident type 1 diabetes was 24.1 (12.3â42.4) years, 56% were men, 23% were in Q1 and 16% were in Q5. Incidence of T1DM was higher in men than women overall (at around 22 and 17 per 100,000, respectively) and in under 15 year olds (approximately 40 per 100,000 in both sexes) than other age groups and was similar across the study period in all strata. There was an inverse association between socioâeconomic status and type 1 diabetes incidence for 15â29, 30â49 and 50+ year olds [incidence rate ratio (IRR) for Q5 compared to Q1; IRR (95% CI) 0.52 (0.47â0.58), 0.68 (0.61â0.76) and 0.53(0.46â0.61), respectively] but not for under 15 year olds [1.02 (0.92â1.12)]. Conclusion: Incidence of type 1 diabetes varies by age, sex and socioâeconomic status and has remained approximately stable from 2006 to 2019 in Scotland
Recommendations for patient screening in ultra-rare inherited metabolic diseases: what have we learned from Niemann-Pick disease type C?
Rare and ultra-rare diseases (URDs) are often chronic and life-threatening conditions that have a profound impact on sufferers and their families, but many are notoriously difficult to detect. Niemann-Pick disease type C (NP-C) serves to illustrate the challenges, benefits and pitfalls associated with screening for ultra-rare inborn errors of metabolism (IEMs). A comprehensive, non-systematic review of published information from NP-C screening studies was conducted, focusing on diagnostic methods and study designs that have been employed to date. As a key part of this analysis, data from both successful studies (where cases were positively identified) and unsuccessful studies (where the chosen approach failed to identify any cases) were included alongside information from our own experiences gained from the planning and execution of screening for NP-C. On this basis, best-practice recommendations for ultra-rare IEM screening are provided. Twenty-six published screening studies were identified and categorised according to study design into four groups: 1) prospective patient cohort and family-based secondary screenings (18 studies);2) analyses of archived 'biobank' materials (one study);3) medical chart review and bioinformatics data mining (five studies);and 4) newborn screening (two studies). NPC1/NPC2 sequencing was the most common primary screening method (Sanger sequencing in eight studies and next-generation sequencing [gene panel or exome sequencing] in five studies), followed by biomarker analyses (usually oxysterols) and clinical surveillance. Historically, screening for NP-C has been based on single-patient studies, small case series, and targeted cohorts, but the emergence of new diagnostic methods over the last 5-10 years has provided opportunities to screen for NP-C on a larger scale. Combining clinical, biomarker and genetic diagnostic methods represents the most effective way to identify NP-C cases, while reducing the likelihood of misdiagnosis. Our recommendations are intended as a guide for planning screening protocols for ultra-rare IEMs in general
Serum Fatty Acid Binding Protein 4 (FABP4) Predicts Pre-eclampsia in Women with Type 1 Diabetes
OBJECTIVE
To examine the association between fatty acid binding protein 4 (FABP4) and pre-eclampsia risk in women with type 1 diabetes.
RESEARCH DESIGN AND METHODS
Serum FABP4 was measured in 710 women from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT) in early pregnancy and in the second trimester (median 14 and 26 weeksâ gestation, respectively).
RESULTS
FABP4 was significantly elevated in early pregnancy (geometric mean 15.8 ng/mL [interquartile range 11.6â21.4] vs. 12.7 ng/mL [interquartile range 9.6â17]; P < 0.001) and the second trimester (18.8 ng/mL [interquartile range 13.6â25.8] vs. 14.6 ng/mL [interquartile range 10.8â19.7]; P < 0.001) in women in whom pre-eclampsia later developed. Elevated second-trimester FABP4 level was independently associated with pre-eclampsia (odds ratio 2.87 [95% CI 1.24â6.68], P = 0.03). The addition of FABP4 to established risk factors significantly improved net reclassification improvement at both time points and integrated discrimination improvement in the second trimester.
CONCLUSIONS
Increased second-trimester FABP4 independently predicted pre-eclampsia and significantly improved reclassification and discrimination. FABP4 shows potential as a novel biomarker for pre-eclampsia prediction in women with type 1 diabetes.
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Human severe sepsis cytokine mixture increases ÎČ2-integrin-dependent polymorphonuclear leukocyte adhesion to cerebral microvascular endothelial cells in vitro.
INTRODUCTION: Sepsis-associated encephalopathy (SAE) is a state of acute brain dysfunction in response to a systemic infection. We propose that systemic inflammation during sepsis causes increased adhesion of leukocytes to the brain microvasculature, resulting in blood-brain barrier dysfunction. Thus, our objectives were to measure inflammatory analytes in plasma of severe sepsis patients to create an experimental cytokine mixture (CM), and to use this CM to investigate the activation and interactions of polymorphonuclear leukocytes (PMN) and human cerebrovascular endothelial cells (hCMEC/D3) in vitro.
METHODS: The concentrations of 41 inflammatory analytes were quantified in plasma obtained from 20 severe sepsis patients and 20 age- and sex-matched healthy controls employing an antibody microarray. Two CMs were prepared to mimic severe sepsis (SSCM) and control (CCM), and these CMs were then used for PMN and hCMEC/D3 stimulation in vitro. PMN adhesion to hCMEC/D3 was assessed under conditions of flow (shear stress 0.7 dyn/cm(2)).
RESULTS: Eight inflammatory analytes elevated in plasma obtained from severe sepsis patients were used to prepare SSCM and CCM. Stimulation of PMN with SSCM led to a marked increase in PMN adhesion to hCMEC/D3, as compared to CCM. PMN adhesion was abolished with neutralizing antibodies to either ÎČ2 (CD18), αL/ÎČ2 (CD11α/CD18; LFA-1) or αM/ÎČ2 (CD11ÎČ/CD18; Mac-1) integrins. In addition, immune-neutralization of the endothelial (hCMEC/D3) cell adhesion molecule, ICAM-1 (CD54) also suppressed PMN adhesion.
CONCLUSIONS: Human SSCM up-regulates PMN pro-adhesive phenotype and promotes PMN adhesion to cerebrovascular endothelial cells through a ÎČ2-integrin-ICAM-1-dependent mechanism. PMN adhesion to the brain microvasculature may contribute to SAE
Human severe sepsis cytokine mixture increases beta 2-integrin-dependent polymorphonuclear leukocyte adhesion to cerebral microvascular endothelial cells in vitro
Introduction: Sepsis-associated encephalopathy (SAE) is a state of acute brain dysfunction in response to a systemic infection. We propose that systemic inflammation during sepsis causes increased adhesion of leukocytes to the brain microvasculature, resulting in blood-brain barrier dysfunction. Thus, our objectives were to measure inflammatory analytes in plasma of severe sepsis patients to create an experimental cytokine mixture (CM), and to use this CM to investigate the activation and interactions of polymorphonuclear leukocytes (PMN) and human cerebrovascular endothelial cells (hCMEC/D3) in vitro. Methods: The concentrations of 41 inflammatory analytes were quantified in plasma obtained from 20 severe sepsis patients and 20 age- and sex-matched healthy controls employing an antibody microarray. Two CMs were prepared to mimic severe sepsis (SSCM) and control (CCM), and these CMs were then used for PMN and hCMEC/D3 stimulation in vitro. PMN adhesion to hCMEC/D3 was assessed under conditions of flow (shear stress 0.7 dyn/cm(2)). Results: Eight inflammatory analytes elevated in plasma obtained from severe sepsis patients were used to prepare SSCM and CCM. Stimulation of PMN with SSCM led to a marked increase in PMN adhesion to hCMEC/D3, as compared to CCM. PMN adhesion was abolished with neutralizing antibodies to either beta 2 (CD18), alpha(L)/beta(2) (CD11 alpha/CD18; LFA-1) or alpha(M)/beta(2) (CD11 beta/CD18; Mac-1) integrins. In addition, immune-neutralization of the endothelial (hCMEC/D3) cell adhesion molecule, ICAM-1 (CD54) also suppressed PMN adhesion. Conclusions: Human SSCM up-regulates PMN pro-adhesive phenotype and promotes PMN adhesion to cerebrovascular endothelial cells through a beta 2-integrin-ICAM-1-dependent mechanism. PMN adhesion to the brain microvasculature may contribute to SAE
Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK and Ireland and the impact on major congenital malformations
Objectives: After 20 years of data collection, pregnancy registers have informed prescribing practice. Various populations show trends for a reduction in valproate prescribing, which is associated with an increased risk of anatomical teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim was to determine if any shifts in prescribing trends have occurred in the UK and Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been any change in the overall major congenital malformation (MCM) rate over time. Methods: The UK and Ireland Epilepsy and Pregnancy Register, a prospective, observational, registration and follow-up study established in 1996, was used to determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and the MCM rate between 1996 and 2016. Linear regression analysis was used to assess changes in AED utilisation, and Poisson regression was used for the analysis of trends in the MCM rates. Results: Outcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (p<0.003) changes were found in monotherapy prescribing with increases in lamotrigine and levetiracetam and decreases in valproate and carbamazepine use. Between 1996 and 2016, the total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95% CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not statistically significant p=0.08). Conclusion: Significant changes are seen in the prescribing habits in this cohort over 20 years, but a statistically significant change in the MCM rate was not detected. This work should be replicated on a larger scale to determine if significant changes are occurring in the MCM rate, which would allow a robust economic estimate of the benefits of improvements in prescribing practice and the personal effect of such changes
The geography of recent genetic ancestry across Europe
The recent genealogical history of human populations is a complex mosaic
formed by individual migration, large-scale population movements, and other
demographic events. Population genomics datasets can provide a window into this
recent history, as rare traces of recent shared genetic ancestry are detectable
due to long segments of shared genomic material. We make use of genomic data
for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of
recent genealogical ancestry over the past three thousand years at a
continental scale. We detected 1.9 million shared genomic segments, and used
the lengths of these to infer the distribution of shared ancestors across time
and geography. We find that a pair of modern Europeans living in neighboring
populations share around 10-50 genetic common ancestors from the last 1500
years, and upwards of 500 genetic ancestors from the previous 1000 years. These
numbers drop off exponentially with geographic distance, but since genetic
ancestry is rare, individuals from opposite ends of Europe are still expected
to share millions of common genealogical ancestors over the last 1000 years.
There is substantial regional variation in the number of shared genetic
ancestors: especially high numbers of common ancestors between many eastern
populations likely date to the Slavic and/or Hunnic expansions, while much
lower levels of common ancestry in the Italian and Iberian peninsulas may
indicate weaker demographic effects of Germanic expansions into these areas
and/or more stably structured populations. Recent shared ancestry in modern
Europeans is ubiquitous, and clearly shows the impact of both small-scale
migration and large historical events. Population genomic datasets have
considerable power to uncover recent demographic history, and will allow a much
fuller picture of the close genealogical kinship of individuals across the
world.Comment: Full size figures available from
http://www.eve.ucdavis.edu/~plralph/research.html; or html version at
http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm
Effectiveness and cost-effectiveness of a physical activity loyalty scheme for behaviour change maintenance: a cluster randomised controlled trial
Abstract
Background
Increasing physical activity in the workplace can provide employee physical and mental health benefits, and employer economic benefits through reduced absenteeism and increased productivity. The workplace is an opportune setting to encourage habitual activity. However, there is limited evidence on effective behaviour change interventions that lead to maintained physical activity. This study aims to address this gap and help build the necessary evidence base for effective, and cost-effective, workplace interventions.
Methods/design
This cluster randomised control trial will recruit 776 office-based employees from public sector organisations in Belfast and Lisburn city centres, Northern Ireland. Participants will be randomly allocated by cluster to either the Intervention Group or Control Group (waiting list control). The 6-month intervention consists of rewards (retail vouchers, based on similar principles to high street loyalty cards), feedback and other evidence-based behaviour change techniques. Sensors situated in the vicinity of participating workplaces will promote and monitor minutes of physical activity undertaken by participants. Both groups will complete all outcome measures. The primary outcome is steps per day recorded using a pedometer (Yamax Digiwalker CW-701) for 7 consecutive days at baseline, 6, 12 and 18Â months. Secondary outcomes include health, mental wellbeing, quality of life, work absenteeism and presenteeism, and use of healthcare resources. Process measures will assess intervention âdoseâ, website usage, and intervention fidelity. An economic evaluation will be conducted from the National Health Service, employer and retailer perspective using both a cost-utility and cost-effectiveness framework. The inclusion of a discrete choice experiment will further generate values for a cost-benefit analysis. Participant focus groups will explore who the intervention worked for and why, and interviews with retailers will elucidate their views on the sustainability of a public health focused loyalty card scheme.
Discussion
The study is designed to maximise the potential for roll-out in similar settings, by engaging the public sector and business community in designing and delivering the intervention. We have developed a sustainable business model using a âpointsâ based loyalty platform, whereby local businesses âsponsorâ the incentive (retail vouchers) in return for increased footfall to their business.
Trial registration
ISRCTN17975376
(Registered 19/09/2014)
Guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods
There is substantial evidence to link what we eat to the reduction of the risk of major chronic diseases and/or the improvement of functions. Thus, it is important for public health agencies and the food industry to facilitate the consumption of foods with particular health benefits by providing consumer products and messages based on scientific evidence. Although fragmentary advice is available from a range of sources, there is a lack of comprehensive scientific guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods. Such guidelines are needed both to support nutrition science in general, and to facilitate the substantiation of health claims. In the present study, which presents the consensus view of an International Life Sciences Institute Europe Expert Group that included senior scientists from academia and industry, the term âfoods' refers to foods, dietary supplements and food constituents, but not to whole diets. The present study is based on an initial survey of published papers, which identified the range and strengths and weaknesses of current methodologies, and was finalised following exchanges between representatives from industry, academia and regulatory bodies. The major factors involved in the design, conduct and reporting of studies are identified, summarised in a checklist table that is based on the Consolidated Standards of Reporting Trials guidelines, and elaborated and discussed in the tex
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