The Dementias Platform UK (DPUK) Data Portal Bauermeister, Sarah; Orton, Christopher; Thompson, Simon ...
European journal of epidemiology,
06/2020, Letnik:
35, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a ...secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
Osteogenesis imperfecta (OI), or brittle bone disease, is most often caused by dominant mutations in the collagen I genes COL1A1/COL1A2, whereas rarer recessive OI is often caused by mutations in ...genes encoding collagen I-interacting proteins. Recently, mutations in the gene for the proteinase bone morphogenetic 1 (BMP1) were reported in two recessive OI families. BMP1 and the closely related proteinase mammalian tolloid-like 1 (mTLL1) are co-expressed in various tissues, including bone, and have overlapping activities that include biosynthetic processing of procollagen precursors into mature collagen monomers. However, early lethality of Bmp1- and Tll1-null mice has precluded use of such models for careful study of in vivo roles of their protein products. Here we employ novel mouse strains with floxed Bmp1 and Tll1 alleles to induce postnatal, simultaneous ablation of the two genes, thus avoiding barriers of Bmp1(-/-) and Tll1(-/-) lethality and issues of functional redundancy. Bones of the conditionally null mice are dramatically weakened and brittle, with spontaneous fractures-defining features of OI. Additional skeletal features include osteomalacia, thinned/porous cortical bone, reduced processing of procollagen and dentin matrix protein 1, remarkably high bone turnover and defective osteocyte maturation that is accompanied by decreased expression of the osteocyte marker and Wnt-signaling inhibitor sclerostin, and by marked induction of canonical Wnt signaling. The novel animal model presented here provides new opportunities for in-depth analyses of in vivo roles of BMP1-like proteinases in bone and other tissues, and for their roles, and for possible therapeutic interventions, in OI.
Summary Background Health workers' malaria case-management practices often differ from national guidelines. We assessed whether text-message reminders sent to health workers' mobile phones could ...improve and maintain their adherence to treatment guidelines for outpatient paediatric malaria in Kenya. Methods From March 6, 2009, to May 31, 2010, we did a cluster-randomised controlled trial at 107 rural health facilities in 11 districts in coastal and western Kenya. With a computer-generated sequence, health facilities were randomly allocated to either the intervention group, in which all health workers received text messages on their personal mobile phones on malaria case-management for 6 months, or the control group, in which health workers did not receive any text messages. Health workers were not masked to the intervention, although patients were unaware of whether they were in an intervention or control facility. The primary outcome was correct management with artemether-lumefantrine, defined as a dichotomous composite indicator of treatment, dispensing, and counselling tasks concordant with Kenyan national guidelines. The primary analysis was by intention to treat. The trial is registered with Current Controlled Trials, ISRCTN72328636. Findings 119 health workers received the intervention. Case-management practices were assessed for 2269 children who needed treatment (1157 in the intervention group and 1112 in the control group). Intention-to-treat analysis showed that correct artemether-lumefantrine management improved by 23·7 percentage-points (95% CI 7·6–40·0; p=0·004) immediately after intervention and by 24·5 percentage-points (8·1–41·0; p=0·003) 6 months later. Interpretation In resource-limited settings, malaria control programmes should consider use of text messaging to improve health workers' case-management practices. Funding The Wellcome Trust.
A basin-scale hydrologic-energy balance model that integrates modern climatological, hydrological, and hypsographic observations was developed for the modern Lake Titicaca watershed (northern ...Altiplano, South America) and operated under variable conditions to understand controls on post-glacial changes in lake level. The model simulates changes in five environmental variables (air temperature, cloud fraction, precipitation, relative humidity, and land surface albedo). Relatively small changes in three meteorological variables (mean annual precipitation, temperature, and/or cloud fraction) explain the large mid-Holocene lake-level decrease (85 m) inferred from seismic reflection profiling and supported by sediment-based paleoproxies from lake sediments. Climatic controls that shape the present-day Altiplano and the sediment-based record of Holocene lake-level change are combined to interpret model-derived lake-level simulations in terms of changes in the mean state of ENSO and its impact on moisture transport to the Altiplano.PUBLICATION ABSTRACT
Our analysis of lipid molecular fossils from a Lake Titicaca (16° S, 69° W) sediment core reveals distinct changes in the ecology of the lake over an ∼25,000-yr period spanning latest Pleistocene to ...late Holocene time. Previous investigations have shown that over this time period Lake Titicaca was subject to large changes in lake level in response to regional climatic variability. Our results indicate that lake algal populations were greatly affected by the changing physical and chemical conditions in Lake Titicaca. Hydrocarbons are characterized by a combination of odd-numbered, mid- to long-chain (C
21–C
31) normal alkanes and alkenes. During periods when lake level was higher (latest Pleistocene, early Holocene, and late Holocene), the C
21
n-alkane, and the C
25 and C
27 alkenes dominate hydrocarbon distributions and indicate contribution from an algal source, potentially the freshwater alga
Botryococcus braunii. The C
30 4 α-methyl sterol (dinosterol) increases sharply during the mid-Holocene, suggesting a greatly increased dinoflagellate presence at that time. Long-chain alkenones (LCAs) become significant during the early Holocene and are highly abundant in mid-Holocene samples. There are relatively few published records of LCA detection in lake sediments but their occurrence is geographically widespread (Antarctica, Asia, Europe, North America). Lake Titicaca represents the first South American lake and the first low-latitude lake in which LCAs have been reported. LCA abundance and distribution may be related to the temperature-dependent response of an unidentified algal precursor. Although the LCA unsaturation indices cannot be used to determine absolute Lake Titicaca temperatures, we suspect that the published LCA
U
37
K
unsaturation calibrations can be applied to infer relative temperatures for early to mid-Holocene time when LCA concentrations are high. Using these criteria, the
U
37
K
unsaturation indices suggest relatively warmer temperatures in the mid-Holocene. In contrast to previous speculation, lipid analysis provides little evidence of a greatly increased presence of aquatic plants during the mid-Holocene. Instead, it appears that a few algal species were dominant in the lake. Based on the dramatic rise in abundances of LCAs and dinosterol during the early to mid-Holocene, we suspect that the algal producers of these compounds rose in response to a combination of physical and chemical changes in the lake. These include temperature, salinity, and alkalinity changes that occurred as lake level dropped sharply during a multi-millennial drought affecting the Central Andean Altiplano.
This study examines perceived stress and its relationship to depressive symptoms, life changes and functional capacity in a large sample of individuals who are positive for the Huntington disease ...(HD) gene expansion but not yet diagnosed. Participants were classified by estimated proximity to HD diagnosis (far, mid, near) and compared with a non-gene-expanded comparison group. Persons in the mid group had the highest stress scores. A significant interaction between age and time since HD genetic testing was also found. Secondary analyses using data from a different data collection point and including a diagnosed group showed the highest stress scores in the diagnosed group. Possible explanations and implications are discussed.
Abstract Background Patients with frequent asthma exacerbations resulting in emergency department (ED) visits are at increased risk for future exacerbations. We examined the ability of 1 dose of ...benralizumab, an investigational antiinterleukin 5 receptor α monoclonal antibody, to reduce recurrence after acute asthma exacerbations. Methods In this randomized, double-blind, placebo-controlled study, eligible subjects presented to the ED with an asthma exacerbation, had partial response to treatment, and greater than or equal to 1 additional exacerbation within the previous year. Subjects received 1 intravenous infusion of placebo (n = 38) or benralizumab (0.3 mg/kg, n = 36 or 1.0 mg/kg, n = 36) added to outpatient management. The primary outcome was the proportion of subjects with greater than or equal to 1 exacerbation at 12 weeks in placebo vs the combined benralizumab groups. Other outcomes included the time-weighted rate of exacerbations at week 12, adverse events, blood eosinophil counts, asthma symptom changes, and health care resource utilization. Results The proportion of subjects with greater than or equal to 1 asthma exacerbation at 12 weeks was not different between placebo and the combined benralizumab groups (38.9% vs 33.3%; P = .67). However, compared with placebo, benralizumab reduced asthma exacerbation rates by 49% (3.59 vs 1.82; P = .01) and exacerbations resulting in hospitalization by 60% (1.62 vs 0.65; P = .02) in the combined groups. Benralizumab reduced blood eosinophil counts but did not affect other outcomes, while demonstrating an acceptable safety profile. Conclusions When added to usual care, 1 dose of benralizumab reduced the rate and severity of exacerbations experienced over 12 weeks by subjects who presented to the ED with acute asthma.
Study objective Recent-onset atrial fibrillation and flutter are the most common arrhythmias managed in the emergency department (ED). We evaluate the management and 30-day outcomes for recent-onset ...atrial fibrillation and flutter patients in Canadian EDs, where cardioversion is commonly practiced. Methods We conducted a prospective cohort study in 6 academic hospital EDs and enrolled patients who had atrial fibrillation and flutter onset within 48 hours. Patients were followed for 30 days by health records review and telephone. Adverse events included death, stroke, acute coronary syndrome, heart failure, subsequent admission, or ED electrocardioversion. Results We enrolled 1,091 patients with mean age 63.9 years, atrial fibrillation 84.7%, atrial flutter 15.3%, hospital admission 9.0%, and converted to sinus rhythm 80.1%. Although 10.5% of recent-onset atrial fibrillation and flutter patients had adverse events within 30 days, there were no related deaths and 1 stroke (0.1%). Adjusted odds ratios for factors associated with adverse event were hours from onset (1.03/hour; 95% confidence interval CI 1.01 to 1.05), history of stroke or transient ischemic attack (2.09; 95% CI 1.01 to 4.36), and pulmonary congestion on chest radiograph (7.37; 95% CI 2.40 to 22.64). Patients who left the ED in sinus rhythm were much less likely to experience an adverse event ( P <.001). Conclusion Although most recent-onset atrial fibrillation and flutter patients were treated aggressively in the ED, there were few 30-day serious outcomes. Physicians underprescribed oral anticoagulants. Potential risk factors for adverse events include longer duration from arrhythmia onset, previous stroke or transient ischemic attack, pulmonary congestion on chest radiograph, and not being in sinus rhythm at discharge. An ED strategy of sinus rhythm restoration and discharge in most patients is effective and safe.
Background Differentiating asthma from other causes of chronic airflow limitation, such as chronic obstructive pulmonary disease (COPD), can be difficult in a typical outpatient setting. The ...inflammation of asthma typically is different than that of COPD, and the degree of inflammation and cellular damage varies with asthma severity. Metabolomics is the study of molecules created by cellular metabolic pathways. Objectives We hypothesized that the metabolic activity of adults with asthma would differ from that of adults with COPD. Furthermore, we hypothesized that nuclear magnetic resonance spectroscopy (NMR) would measure such differences in urine samples. Methods Clinical and urine-based NMR data were collected on adults meeting the criteria of asthma and COPD before and after an exacerbation (n = 133 and 38, respectively) and from patients with stable asthma or COPD (n = 54 and 23, respectively). Partial least-squares discriminant analysis was performed on the NMR data to create models of separation (86 metabolites were measured per urine sample). Some subjects' metabolomic data were withheld from modeling to be run blindly to determine diagnostic accuracy. Results Partial least-squares discriminant analysis of the urine NMR data found unique differences in select metabolites between patients with asthma and those with COPD seen in the emergency department and even in follow-up after exacerbation. By using these select metabolomic profiles, the model could correctly diagnose blinded asthma and COPD with greater than 90% accuracy. Conclusion This is the first report showing that metabolomic analysis of human urine samples could become a useful clinical tool to differentiate asthma from COPD.
Sediment cores from Lake Titicaca contain proxy records of past lake level and hydrologic change on the South American Altiplano. Large downcore shifts in the isotopic composition of organic carbon, ...C/N, wt. %Corg, %CaCO3, and % biogenic silica illustrate the dynamic changes in lake level that occurred during the past 20,000 years.
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