748 research outputs found
Harnessing real-world data to inform decision-making: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS)
Multiple metal contamination from house paints: consequences of power sanding and paint scraping in New Orleans.
Power sanding exterior paint is a common practice during repainting of old houses in New Orleans, Louisiana, that triggers lead poisoning and releases more than Pb. In this study we quantified the Pb, zinc, cadmium, manganese, nickel, copper, cobalt, chromium, and vanadium in exterior paint samples collected from New Orleans homes (n = 31). We used interior dust wipes to compare two exterior house-painting projects. House 1 was measured in response to the plight of a family after a paint contractor power sanded all exterior paint from the weatherboards. The Pb content (approximately 130,000 microg Pb/g) was first realized when the family pet died; the children were hospitalized, the family was displaced, and cleanup costs were high. To determine the quantity of dust generated by power sanding and the benefits of reducing Pb-contaminated dust, we tested a case study house (house 2) for Pb (approximately 90,000 microg/g) before the project was started; the house was then dry scraped and the paint chips were collected. Although the hazards of Pb-based paints are well known, there are other problems as well, because other toxic metals exist in old paints. If house 2 had been power sanded to bare wood like house 1, the repainting project would have released as dust about 7.4 kg Pb, 3.5 kg Zn, 9.7 g Cd, 14.8 g Cu, 8.8 g Mn, 1.5 g Ni, 5.4 g Co, 2.4 g Cr, and 0.3 g V. The total tolerable daily intake (TTDI) for a child under 6 years of age is 6 microg Pb from all sources. Converting 7.4 kg Pb to this scale is vexing--more than 1 billion (10(9)) times the TTDI. Also for perspective, the one-time release of 7.4 x 10(9) microg of Pb dust from sanding compares to 50 x 10(9) microg of Pb dust emitted annually per 0.1 mile (0.16 km) from street traffic during the peak use of leaded gasoline. In this paper, we broaden the discussion to include an array of metals in paint and underscore the need and possibilities for curtailing the release of metal dust
Perspectives and experiences with COVID-19 vaccines in people with MS
Background: People with MS may have unique perspectives on COVID-19 vaccines due to their condition and/or medications.
Objective: Assess perspectives and experiences with COVID-19 vaccination, and quantify variables impacting COVID-19 vaccine willingness in people with MS.
Methods: A survey captured demographics, MS characteristics, and COVID-19 infection and exposures data; opinions on COVID-19 vaccine safety, side effects, and efficacy; and experiences following vaccination. Chi-square tests and a logistic regression model were used to denote between-group differences and variables predicting vaccine willingness, respectively.
Results: Most (87.8%) of the 237 participants were willing to receive the vaccine. Fifteen percent held or delayed a DMT dose for vaccination. MS symptoms worsened in a minority (7.6% first/only dose; 14.7% second dose), and most side effects were mild (80.0%; 55.3%). Those not planning to receive the vaccine were primarily concerned with long-term safety (70.4%). Medical comorbidities (adjusted odds ratio [aOR]=5.222; p=0.04) and following infection prevention precautions (aOR=6.330; p=0.008) were associated with vaccine willingness.
Conclusion: Most individuals with MS surveyed plan to receive the COVID-19 vaccine. People with MS experience similar side effects to the general population, and few experience transient MS symptom worsening. These results can inform conversations on vaccination between providers and people with MS
Just-In-Time Locality and Percolation for Optimizing Irregular Applications on a Manycore Architecture
Genetic influences on cost-efficient organization of human cortical functional networks
The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09–0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization
Benefits of early treatment with natalizumab: A real-world study
BACKGROUND: The impact of early versus later high-efficacy disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) is uncertain. This study reported the association of early versus later natalizumab treatment with real-world clinical outcomes in MS patients.
METHODS: The study included 661 participants diagnosed with MS in 1994 or later from 7 US centers participating in the MS Partners Advancing Technology for Health Solutions (MS PATHS) network. Time to natalizumab treatment between diagnosis and first infusion (TTNT) was determined from the Tysabri Outreach: Unified Commitment to Health (TOUCH) registry. Clinical outcomes were defined using neuroperformance tests included in the Multiple Sclerosis Performance Test. Associations were tested using TTNT as a categorical and continuous variable. Linear mixed models addressed within-subject and within-site clustering.
RESULTS: TTNT varied from 0.1 to 19.8 years (median [interquartile range] 4.2 [1.8, 9.0] years). A significant association between later natalizumab use and worse outcomes was demonstrated for walking speed (p \u3c 0.001), processing speed (p \u3c 0.001), manual dexterity (p \u3c 0.001), brain atrophy (p = 0.001), and T2 lesion volume (p = 0.02). Covariate-adjusted modelling of a sensitivity population diagnosed with MS in 2006 or later (n = 424) demonstrated significant associations between longer TTNT and worse walking speed (p \u3c 0.05), processing speed (p \u3c 0.001), and manual dexterity (p \u3c 0.001).
CONCLUSION: Later initiation of natalizumab was associated with worse clinical and radiologic imaging outcomes. Thus, high-efficacy DMT may have greater benefit when started earlier in MS patients. These results provide a rationale for randomized controlled trials to further assess the impact of early highly-effective DMT use versus later escalation of therapy
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Real-time monitoring of volatile organic compounds using chemical ionization mass spectroscopy: Final report
Volatile organic compound (VOC) emission to the atmosphere is of great concern to semiconductor manufacturing industries, research laboratories, the public, and regulatory agencies. Some industries are seeking ways to reduce emissions by reducing VOCs at the point of use (or generation). This paper discusses the requirements, design, calibration, and use of a sampling inlet/quadrupole mass spectrometer system for monitoring VOCs in a semiconductor manufacturing production line. The system uses chemical ionization to monitor compounds typically found in the lithography processes used to manufacture semiconductor devices (e.g., acetone, photoresist). The system was designed to be transportable from tool to tool in the production line and to give the operator real-time feedback so the process(es) can be adjusted to minimize VOC emissions. Detection limits ranging from the high ppb range for acetone to the low ppm range fore other lithography chemicals were achieved using chemical ionization mass spectroscopy at a data acquisition rate of approximately 1 mass spectral scan (30 to 200 daltons) per second. A demonstration of exhaust VOC monitoring was performed at a working semiconductor fabrication facility during actual wafer processing
Advances in multiple sclerosis research in 2009
The following review summarizes the progress in multiple sclerosis research published in the Journal of Neurology in 2009
Interaction testing and polygenic risk scoring to estimate the association of common genetic variants with treatment resistance in schizophrenia
Importance About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts.
Objective To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples.
Design, Setting, and Participants Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n=10 501) and individuals with non-TRS (n=20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]).
Main Outcomes and Measures GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition.
Results The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r² = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r² = 1.09%; P = .04).
Conclusions and Relevance In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance.Funding/Support: This work was supported by Medical Research Council Centre grant MR/ L010305/1, Medical Research Council Program grant MR/P005748/1, and Medical Research Council Project grants MR/L011794/1 and MC_PC_17212 to Cardiff University and by the National Centre for Mental Health, funded by the Welsh Government through Health and Care Research Wales. This work acknowledges the support of the Supercomputing Wales project, which is partially funded by the European Regional Development Fund via the Welsh Government. Dr Pardiñas was supported by an Academy of Medical Sciences Springboard Award (SBF005\1083). Dr Andreassen was supported by the Research Council of Norway (grants 283798, 262656, 248980, 273291, 248828, 248778, and 223273); KG Jebsen Stiftelsen, South-East Norway Health Authority, and the European Union’s Horizon 2020 Research and Innovation Programme (grant 847776). Dr Ajnakina was supported by an National Institute for Health Research postdoctoral fellowship (PDF-2018-11-ST2-020). Dr Joyce was supported by the University College London Hospitals/UCL University College London Biomedical Research Centre. Dr Kowalec received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement (793530) from the government of Canada Banting postdoctoral fellowship programme and the University of Manitoba. Dr Sullivan was supported by the Swedish Research Council (Vetenskapsrådet, D0886501), the European Union’s Horizon 2020 programme (COSYN, 610307) and the US National Institute of Mental Health (U01 MH109528 and R01 MH077139). The Psychiatric Genomics Consortium was partly supported by the National Institute Of Mental Health (grants R01MH124873). The Sweden Schizophrenia Study was supported by the National Institute Of Mental Health (grant R01MH077139). The STRATA consortium was supported by a Stratified Medicine Programme grant to Dr MacCabe from the Medical Research Council (grant MR/L011794/1), which funded the research and supported Drs Pardiñas, Smart, Kassoumeri, Murray, Walters, and MacCabe. Dr Smart was supported by a Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital National Health Service Foundation Trust. The AESOP (US) cohort was funded by the UK Medical Research Council (grant G0500817). The Belfast (UK) cohort was funded by the Research and Development Office of Northern Ireland. The Bologna (Italy) cohort was funded by the European Community’s Seventh Framework program (HEALTH-F2-2010–241909, project EU-GEI). The Genetics and Psychosis project (London, UK) cohort was funded by the UK National Institute of Health Research Specialist Biomedical Research Centre for Mental Health, South London and the Maudsley National Health Service Mental Health Foundation Trust (SLAM) and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London; Psychiatry Research Trust; Maudsley Charity Research Fund; and the European Community’s Seventh Framework program (HEALTH-F2-2009-241909, project EU-GEI). The Lausanne (Switzerland) cohort was funded by the Swiss National Science Foundation (grants 320030_135736/1, 320030-120686, 324730-144064, 320030-173211, and 171804); the National Center of Competence in Research Synaptic Bases of Mental Diseases from the Swiss National Science Foundation (grant 51AU40_125759); and Fondation Alamaya. The Oslo (Norway) cohort was funded by the Research Council of Norway (grant 223273/F50, under the Centers of Excellence funding scheme, 300309, 283798) and the South-Eastern Norway Regional Health Authority (grants 2006233, 2006258, 2011085, 2014102, 2015088, and 2017-112). The Paris (France) cohort was funded by European Community’s Seventh Framework program (HEALTH-F2-2010–241909, project EU-GEI). The Prague (Czech Republic) cohort was funded by the Ministry of Health of the Czech Republic (grant NU20-04-00393). The Santander (Spain) cohort was funded by the following grants to Dr Crespo-Facorro: Instituto de Salud Carlos III (grants FIS00/3095, PI020499, PI050427, and PI060507), Plan Nacional de Drogas Research (grant 2005-Orden sco/3246/2004), SENY Fundatio Research (grant 2005-0308007), Fundacion Marques de Valdecilla (grant A/02/07, API07/011) and Ministry of Economy and Competitiveness and the European Fund for Regional Development (grants SAF2016-76046-R and SAF2013-46292-R). The West London (UK) cohort was funded by The Wellcome Trust (grants 042025, 052247, and 064607)
Demographic uncertainty and disease risk influence climate-informed management of an alpine species
Climate change is expected to disproportionately affect species occupying ecosystems with relatively hard boundaries, such as alpine ecosystems. Wildlife managers must identify actions to conserve and manage alpine species into the future, while considering other issues and uncertainties. Climate change and respiratory pathogens associated with widespread pneumonia epidemics in bighorn sheep (Ovis canadensis) may negatively affect mountain goat (Oreamnos americanus) populations. Mountain goat demographic and population data are challenging to collect and sparsely available, making population management decisions difficult. We developed predictive models incorporating these uncertainties and analyzed results within a structured decision making framework to make management recommendations and identify priority information needs in Montana, USA. We built resource selection models to forecast occupied mountain goat habitat and account for uncertainty in effects of climate change, and a Leslie matrix projection model to predict population trends while accounting for uncertainty in population demographics and dynamics. We predicted disease risks while accounting for uncertainty about presence of pneumonia pathogens and risk tolerance for mixing populations during translocations. Our analysis predicted that new introductions would produce more area occupied by mountain goats at mid-century, regardless of the effects of climate change. Population augmentations, carnivore management, and harvest management may improve population trends, although this was associated with considerable uncertainty. Tolerance for risk of disease transmission affected optimal management choices because translocations are expected to increase disease risks for mountain goats and sympatric bighorn sheep. Expected value of information analyses revealed that reducing uncertainty related to population dynamics would affect the optimal choice among management strategies to improve mountain goat trends. Reducing uncertainty related to the presence of pneumonia-associated pathogens and consequences of mixing microbial communities should reduce disease risks if translocations are included in future management strategies. We recommend managers determine tolerance for disease risks associated with translocations that they and constituents are willing to accept. From this, an adaptive management program can be constructed wherein a portfolio of management actions are chosen based on risk tolerance in each population range, combined with the amount that uncertainty is reduced when paired with monitoring, to ultimately improve achievement of fundamental objectives
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