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There are research questions whose answers require record linkage of multiple databases that may be characterized by limited options for full data sharing. For this purpose, the Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI) consortium has supported the development of the ODISSEI Secure Supercomputer (OSSC) platform that allows researchers to link cohort data to data from Statistics Netherlands and run large-scale analyses in a high-performance computing (HPC) environment. Here, we report a successful record linkage genomewide association (GWA) study on expenditure for total health, mental health, primary and hospital care, and medication. Record linkage for genotype data from 16,726 participants from the Netherlands Twin Register (NTR) with data from Statistics Netherlands was accomplished in the secure OSSC platform, followed by gene-based tests and estimation of total and single nucleotide polymorphism (SNP)-based heritability. The total heritability of expenditure ranged between 29.4% (SE 0.8) and 37.5% (SE 0.8), but GWA analyses did not identify SNPs or genes that were genomewide significantly associated with health care expenditure. SNP-based heritability was between 0.0% (SE 3.5) and 5.4% (SE 4.0) and was different from zero for mental health care and primary care expenditure. We conclude that successfully linking genotype data to administrative health care expenditure data from Statistics Netherlands is feasible and demonstrates a series of analyses on health care expenditure. The OSSC platform offers secure possibilities for analyzing linked data in large scale and realizing sample sizes required for GWA studies, providing invaluable opportunities to answer many new research questions.
Flaviviruses include many viruses causing encephalitis, including West Nile encephalitis, St. Louis encephalitis, tick-borne encephalitis and Japanese encephalitis. Human pegivirus genotype-1 (HPgV-1) is a lesser known member of the Flaviviridae family and has been identified in human serum, cerebrospinal fluid and brain tissue. Here, we describe two adult patients with fatal HPgV-1-associated encephalitis. Neuroimaging revealed multifocal lesions, initially present in the periventricular and brain stem white matter, then one year later throughout the corona radiata bilaterally with marked involvement of the brainstem and cervical spinal cord. Phylogenetic analyses of HPgV-1 showed clustering of brain-derived sequences from both patients with other human pegiviruses. In both patients, a novel 87-nucleotide deletion in the viral NS2 gene was detected. The presence of positive and negative strand HPgV-1 RNA and viral antigens in both patients indicated viral persistence and replication in the CNS. Autopsy showed lymphocyte infiltration and gliosis predominantly in white matter of the brain and brain stem but, to a lesser extent, also in grey matter. Immunofluorescence revealed HPgV-1 NS5A antigen in lymphocytes as well as in astrocytes and oligodendrocytes. Thus, we hypothesize that the novel deletion in the NS2 coding region may have caused HPgV-1 neuroadaptation or might represent a yet unrecognized genotype of human pegivirus.
This presentation will enable the learner to:
1. Describe the clinical and neuropathological features of fatal human pegivirus-associated encephalitis
2. Recognize the importance of molecular analysis in encephalitis cases with unknown etiology
Adult schistosomes live in the blood vessels and cannot easily be sampled from humans, so archived miracidia larvae hatched from eggs expelled in feces or urine are commonly used for population genetic studies. Large collections of archived miracidia on FTA cards are now available through the Schistosomiasis Collection at the Natural History Museum (SCAN). Here we describe protocols for whole genome amplification of Schistosoma mansoni and Schistosome haematobium miracidia from these cards, as well as real time PCR quantification of amplified schistosome DNA. We used microgram quantities of DNA obtained for exome capture and sequencing of single miracidia, generating dense polymorphism data across the exome. These methods will facilitate the transition from population genetics, using limited numbers of markers to population genomics using genome-wide marker information, maximising the value of collections such as SCAN.
In 1964 (Solar Cycle 20; SC 20), Patrick McIntosh began creating hand-drawn synoptic maps of solar magnetic features, based on Hα images. These synoptic maps were unique in that they traced magnetic polarity inversion lines, and connected widely separated filaments, fibril patterns, and plage corridors to reveal the large-scale organization of the solar magnetic field. Coronal hole boundaries were later added to the maps, which were produced, more or less continuously, into 2009 (i.e., the start of SC 24). The result was a record of ~45 years (~570 Carrington rotations), or nearly four complete solar cycles of synoptic maps. We are currently scanning, digitizing and archiving these maps, with the final, searchable versions publicly available at NOAA's National Centers for Environmental Information. In this paper we present preliminary scientific studies using the archived maps from SC 23. We show the global evolution of closed magnetic structures (e.g., sunspots, plage, and filaments) in relation to open magnetic structures (e.g., coronal holes), and examine how both relate to the shifting patterns of large-scale positive and negative polarity regions.
Introduction: Individual and institutional disparities in CT imaging rates for patients with head injuries have long been recognized, leading to the development of well-validated clinical decision rules designed to standardize clinical practice. To assess their impact on current practice, we sought to evaluate variation in CT imaging by emergency physicians for patients presenting with head injury across the province of Alberta. Methods: A unique data warehouse merging administrative, clinical, and imaging platforms for 11 Alberta emergency departments (EDs) was created. Unique identifiers were obtained for all emergency physicians who were included in this analysis if they evaluated in excess of ten ED patients presenting with a chief complaint of “head injury”. Patients with high triage acuity (CTAS 1) were excluded, as were patients who were admitted to hospital. Descriptive statistics were employed to describe variation between physicians and sites for a 24 month period from 2013-2015. Results: 311 emergency physicians treating 20,797 patient encounters for head injury were included. Overall a total of 8,245 head injury patients (40%) received one or more CT scans. Physician variation across the 11 sites ranged from 4% -100% of head injury patients receiving a CT. Within sites CT ordering between physicians varied from 9-fold (4% - 36%) at the lowest variation site, to more than 20-fold (4% - 90%) at the highest variation site. After removing the 5% lowest and highest ordering physicians, variation in ordering continued to range from 10% - 72%. No trends were observed across the two years examined. Conclusion: This is the largest study to date examining physician level variation in CT ordering practices for ED head injury patients. We have identified marked persistent practice variation despite the presence of well-validated clinical decision rules and a relatively low risk medicolegal environment. Variable risk tolerance and limited use of validated clinical decision rules are likely contributors making this area an ideal focus for targeted interventions to improve imaging appropriateness and reduce practice variation.
The University of Tasmania balloon-borne large area X-ray telescope was flown from Alice Springs on 20 November 1978. A number of known X-ray sources were observed and a transient increase believed to be a gamma ray burst was detected.
Most of the recent advances in X-ray astronomy have resulted from satellite observations in the low energy (< 20 keV) range. The Einstein X-ray Observatory in particular has been responsible for a dramatic increase in our knowledge of the X-ray sky, in that all major classes of astronomical objects have been detected.
The binary X-ray source GX 1 + 4 was observed during a balloon flight in 1986, November. The source was in a relatively high intensity state. Time analysis of the data shows that the pulsation period was 111.8 ± 1.0 s indicating that one or more episodes of spin-down occurred between 1980 and 1986. Folded pulse profiles are very broad with an indication of a notch at the peak. Evidence has been found for a correlation between hard X-ray intensity and phase of the proposed 304 day orbital period. The time averaged intensity since 1980 is an order of magnitude lower than during the 1970’s. A survey of the post 1980 data shows that several reversals of the period derivative have occurred. Spin-up at the rates typical of the 1970’s has been followed by a dramatic spin-down episode with dP/dt>2.4 × 10−7 s/s.
In August 2011, one of the earliest cases of influenza A(H3N2) variant [A(H3N2)v] virus infection was hospitalized with severe illness. To investigate the potential for healthcare-associated transmission of influenza A(H3N2)v, we evaluated both healthcare providers and patient contacts of the case. We found that healthcare-associated transmission was unlikely.
Biochar, a carbon-rich product formed by the incomplete combustion of biomass, has been shown to improve soil quality and increase crop growth but has not been evaluated in prairie ecosystems. We assessed the response of a native perennial grass, big bluestem, and an invasive herbaceous perennial, sericea, to biochar amendments in two greenhouse experiments in 2010 and 2011. In the first experiment, big bluestem and sericea were grown in monoculture; the main treatments were soil type (silt, sand), percent biochar (0%, 1%, 2%, and 4%) and nitrogen (0 and 10 g N m−2). Big bluestem growth was increased by the addition of biochar, particularly in the sand soil. In contrast, sericea growth was either not affected or decreased when biochar was added to the soil, particularly at the higher biochar rates. Adding N to the soil appeared to increase sericea growth in the presence of biochar and the silt soil, which suggests that biochar may have reduced N availability. A replacement series was used in the second experiment to evaluate the effect of biochar on competition between the two species. Main treatments were biochar rates (0% and 2%), nitrogen rates (0 and 10 g N m−2) and the following big bluestem to sericea ratios: 6 : 0, 4 : 2, 3 : 3, 2 : 4, and 0 : 6. After 180 d, big bluestem height and biomass were significantly greater in biochar-amended soils than in unamended soils. However, sericea height and biomass were unaffected by biochar amendments and the addition of biochar did not alter competitive outcomes. Competition between big bluestem and sericea was asymmetrical; sericea reduced the growth of big bluestem but big bluestem had relatively little effect on the growth of sericea. Our research suggests that biochar has the potential to increase the growth of big bluestem and may be a useful tool for prairie restoration.
Hardwood forests in eastern North America are being colonized by multiple nonnative plant and animal species. Colonization rates can be affected by stand structure and distance from edge. We sampled earthworm densities and understory plant species cover in transects located in paired old- and second-growth forests in Indiana. Two 100-m transects were established within each forest stand during late April to early May in each year. One transect was placed parallel to and within 5 m of a south- or west-facing edge. The second transect was placed parallel to the first. but at no less than 100 m from any edge. Nonnative earthworms and plants were found in forest edge and interior regardless of structural stage (second-growth vs. old-growth). The number of native plant species decreased linearly as the densities of adult Lumbricus and Aporrectodea earthworms and the percent cover of multiflora rose (an invasive plant species) increased. Densities of L. terrestris and Aporrectodea earthworms and percent cover of multiflora rose cumulatively explained 39% of the variation in the number of native plant species found in transects across the state. However, multivariate analyses suggested that the species composition of Indiana understory plant communities was affected more by geography than by earthworm densities. Our results suggest that nonnative earthworms and plants are ubiquitous in Indiana hardwood forests and that they may reduce the number of native plant species.
Temperate and boreal forests in Canada and the northeastern United States have been invaded by several exotic species, including European earthworms (family Lumbricidae) and garlic mustard. Earthworms and garlic mustard co-occur and are both known to adversely impact some native plant species. However, relatively little is known about potential interactions between these two invaders. In a series of growth chamber experiments, we determined the palatability of garlic mustard and six native herbaceous forest species (shooting star, columbine, wild geranium, sweet cicely, butterfly milkweed, and yellow jewelweed) to the common nightcrawler. We also assessed the ability of the common nightcrawler to bury and digest garlic mustard and wild geranium. When offered seeds from garlic mustard and a native plant species, the earthworms ingested more garlic mustard seeds than seeds from four of the six native species. In a mesocosm experiment, the common nightcrawlers apparently digested 72 and 27% of garlic mustard and wild geranium seeds, respectively, that were placed on the soil surface. No seeds were observed on the soil surface at the end of the experiment but the majority of recovered seeds for both species were found within the top 10 cm (3.94 in). More seeds were recovered in 0- to 10-cm and 31- to 40-cm sections for wild geranium than for garlic mustard. No difference in seed recovery was detected at the other depths. Garlic mustard seed is readily consumed by common nightcrawlers and appears to be preferred over some native plant species suggesting that common nightcrawlers may reduce the size of the garlic mustard seed bank.
Parasitic nematodes are significant pathogens of humans and other animals. The molecular and genetic basis of animal parasitism is not yet fully understood. Strongyloides spp. are a genus of gastrointestinal nematodes of which species infect approximately 100–200 million people worldwide. S. ratti is a natural parasite of the rat, and a useful and amenable laboratory model. Previous EST and microarray analyses of the S. ratti life cycle have identified genes whose expression was specific, or biased, to the parasitic adult stage, suggesting that they may play a key role in parasitism in this species. Here we have further investigated the expression of these genes (by RT-PCR) throughout the S. ratti life-cycle. We produced recombinant proteins in vitro for a subset of these genes, which were used in Western blot analyses to investigate the distribution of the gene products among different stages of the S. ratti life cycle. We tested the efficacy of these recombinant proteins as anti-S. ratti vaccines. One of the proteins was detected in the excretory/secretory products of the parasitic stages.
The recent implementation of mass drug administration (MDA) for control of uro-genital schistosomiasis has identified an urgent need for molecular markers to both directly monitor the impact of MDA, for example to distinguish re-infections from uncleared infections, as well as understand aspects of parasite reproduction and gene flow which might predict evolutionary change, such as the development and spread of drug resistance. We report the development of a novel microsatellite tool-kit allowing, for the first time, robust genetic analysis of individual S. haematobium larvae collected directly from infected human hosts. We genotyped the parasite populations of 47 children from 2 schools in the Ségou region of Mali, the first microsatellite study of this highly neglected parasite. There was only limited evidence of population subdivision between individual children or between the two schools, suggesting that few barriers to gene flow exist in this population. Complex relationships between parasite reproductive success, infection intensity and host age and gender were identified. Older children and boys harboured more diverse infections, as measured by the number of unique adult genotypes present. Individual parasite genotypes had variable reproductive success both across hosts, a pre-requisite for evolutionary selection, and, phenotypically, in hosts of different ages and genders. These data serve as a baseline against which to measure the effect of treatment on parasite population genetics in this region of Mali, and the tools developed are suitable to further investigate this important pathogen, and its close relatives, throughout their range.
Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations.
A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds.
In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20–1.93] and conduct disorder (CD; HR 2.27, CI 1.31–3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00–1.94). Logistic regression analysis suggested that the parental depression–offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63–3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95–6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses.
The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.
In acute ischemic stroke, the volume of threatened but potentially salvageable tissue, i.e. the ischemic penumbra, is critical to the success of all acute therapeutic interventions, most notably thrombolysis. Despite the availability of both CT and MRI based techniques to detect and assess the penumbra, advanced imaging of this type remains under-utilized. Although the optimal selection criteria are still being refined and technical improvements are ongoing, rapid imaging of the penumbra appears to be the most promising approach to expanding the acute thrombolysis population, as well as tailoring treatment based on specific pathophysiological findings. This second article in a two-part series reviews current evidence for penumbral-based treatment selection and discusses the barriers to implementation of these advanced imaging techniques in acute stroke management protocols.
Neuroimaging is essential to stroke diagnosis and management. To date, the non-contrast CT has served as our main diagnostic tool. Although brain parenchymal changes visible on CT do provide valuable prognostic information, they provide limited insight into the potential for tissue salvage in response to reperfusion therapy, such as thrombolysis. Newer advanced CT and MRI based imaging techniques have increased the detection sensitivity for hyperacute and chronic parenchymal changes, including ischemia and hemorrhage, permit visualization of blood vessels and cerebral blood flow. This review outlines the basic principles underlying acquisition and interpretation of these newer imaging modalities in the setting of acute stroke. The utility of advanced brain parenchymal and blood flow imaging in the context of acute stroke patient management is also discussed. Part II in this series is a discussion of how these techniques can be used to rationally select appropriate patients for thrombolysis based on pathophysiological data.
There were two aims of the research with 190 Australian clinical psychologists: (1) to investigate the construct validity of the Therapist Belief Scale (TBS), and (2) to examine the relative contribution of demographics, workplace variables, and individual factors to burnout. Construct validity was examined using exploratory and confirmatory factor analyses and associations between the variables. Multivariate regressions were used to examine the relative contributions to burnout. The TBS showed three factors related to distress, inflexibility, and control, all of which were significantly associated with lower levels of personal accomplishment. Multivariate analyses showed emotional exhaustion to be associated being a woman, working for the government, having less personal resources, and endorsing more therapist beliefs related to control. Higher levels of personal accomplishment were significantly associated with a lower annual income, not having a mixed caseload, having more personal resources, and endorsing lower levels of therapist beliefs related to inflexibility and control.
The effect of prior infection with cytomegalovirus (CMV) on progression of HIV disease in a cohort of 111 men with haemophilia was studied after 13 years followup. The relative hazards associated with CMV positivity on progression to AIDS, death and a CD4 count of 0·05 × 109/1 were 2·28, 2·42 and 2·34, respectively. CMV seropositive patients were significantly older than the seronegative and this was controlled for by using a Cox proportional hazards model. The relative hazards for the three endpoints decreased to 1·89, 1·82 and 1·93 respectively and were marginally non-significant (P = 0·05, 0·08 and 0·08 for the three endpoints respectively). We conclude that this cohort continues to show evidence of a ‘co-factor’ effect associated with prior infection with CMV which is confounded by age but not completely explained by age differences. The potential biological significance of these results is discussed in the context of recent controlled clinical trials which show a survival benefit from long-term high-dose acyclovir, a drug with activity in vivo against CMV and other herpesviruses.