Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

Gestational Exposure to Endocrine-Disrupting Chemicals and Reciprocal Social, Repetitive, and Stereotypic Behaviors in 4- and 5-Year-Old Children: The HOME Study

Background: Endocrine-disrupting chemicals (EDCs) may be involved in the etiology of autism spectrum disorders, but identifying relevant chemicals within mixtures of EDCs is difficult. Objective: Our goal was to identify gestational EDC exposures associated with autistic behaviors. Methods: We measured the concentrations of 8 phthalate metabolites, bisphenol A, 25 polychlorinated biphenyls (PCBs), 6 organochlorine pesticides, 8 brominated flame retardants, and 4 perfluoroalkyl substances in blood or urine samples from 175 pregnant women in the HOME (Health Outcomes and Measures of the Environment) Study (Cincinnati, OH). When children were 4 and 5 years old, mothers completed the Social Responsiveness Scale (SRS), a measure of autistic behaviors. We examined confounder-adjusted associations between 52 EDCs and SRS scores using a two-stage hierarchical analysis to account for repeated measures and confounding by correlated EDCs. Results: Most of the EDCs were associated with negligible absolute differences in SRS scores (≤ 1.5). Each 2-SD increase in serum concentrations of polybrominated diphenyl ether-28 (PBDE-28) (β = 2.5; 95% CI: –0.6, 5.6) or trans-nonachlor (β = 4.1; 95% CI: 0.8–7.3) was associated with more autistic behaviors. In contrast, fewer autistic behaviors were observed among children born to women with detectable versus nondetectable concentrations of PCB-178 (β = –3.0; 95% CI: –6.3, 0.2), β-hexachlorocyclohexane (β = –3.3; 95% CI: –6.1, –0.5), or PBDE-85 (β = –3.2; 95% CI: –5.9, –0.5). Increasing perfluorooctanoate (PFOA) concentrations were also associated with fewer autistic behaviors (β = –2.0; 95% CI: –4.4, 0.4). Conclusions: Some EDCs were associated with autistic behaviors in this cohort, but our modest sample size precludes us from dismissing chemicals with null associations. PFOA, β-hexachlorocyclohexane, PCB-178, PBDE-28, PBDE-85, and trans-nonachlor deserve additional scrutiny as factors that may be associated with childhood autistic behaviors. Citation: Braun JM, Kalkbrenner AE, Just AC, Yolton K, Calafat AM, Sjödin A, Hauser R, Webster GM, Chen A, Lanphear BP. 2014. Gestational exposure to endocrine-disrupting chemicals and reciprocal social, repetitive, and stereotypic behaviors in 4- and 5-year-old children: the HOME Study. Environ Health Perspect 122:513–520; http://dx.doi.org/10.1289/ehp.130726

Diurnal and Seasonal Variations in Chlorophyll Fluorescence Associated with Photosynthesis at Leaf and Canopy Scales

There is a critical need for sensitive remote sensing approaches to monitor the parameters governing photosynthesis, at the temporal scales relevant to their natural dynamics. The photochemical reflectance index (PRI) and chlorophyll fluorescence (F) offer a strong potential for monitoring photosynthesis at local, regional, and global scales, however the relationships between photosynthesis and solar induced F (SIF) on diurnal and seasonal scales are not fully understood. This study examines how the fine spatial and temporal scale SIF observations relate to leaf level chlorophyll fluorescence metrics (i.e., PSII yield, YII and electron transport rate, ETR), canopy gross primary productivity (GPP), and PRI. The results contribute to enhancing the understanding of how SIF can be used to monitor canopy photosynthesis. This effort captured the seasonal and diurnal variation in GPP, reflectance, F, and SIF in the O2A (SIFA) and O2B (SIFB) atmospheric bands for corn (Zea mays L.) at a study site in Greenbelt, MD. Positive linear relationships of SIF to canopy GPP and to leaf ETR were documented, corroborating published reports. Our findings demonstrate that canopy SIF metrics are able to capture the dynamics in photosynthesis at both leaf and canopy levels, and show that the relationship between GPP and SIF metrics differs depending on the light conditions (i.e., above or below saturation level for photosynthesis). The sum of SIFA and SIFB (SIFA+B), as well as the SIFA+B yield, captured the dynamics in GPP and light use efficiency, suggesting the importance of including SIFB in monitoring photosynthetic function. Further efforts are required to determine if these findings will scale successfully to airborne and satellite levels, and to document the effects of data uncertainties on the scaling

The Orphan Adhesion-GPCR GPR126 Is Required for Embryonic Development in the Mouse

Adhesion-GPCRs provide essential cell-cell and cell-matrix interactions in development, and have been implicated in inherited human diseases like Usher Syndrome and bilateral frontoparietal polymicrogyria. They are the second largest subfamily of seven-transmembrane spanning proteins in vertebrates, but the function of most of these receptors is still not understood. The orphan Adhesion-GPCR GPR126 has recently been shown to play an essential role in the myelination of peripheral nerves in zebrafish. In parallel, whole-genome association studies have implicated variation at the GPR126 locus as a determinant of body height in the human population. The physiological function of GPR126 in mammals is still unknown. We describe a targeted mutation of GPR126 in the mouse, and show that GPR126 is required for embryonic viability and cardiovascular development

SN 2010j1: Optical to Hard X-Ray Observations Reveal an Explosion Embedded in a Ten Solar Mass Cocoon

Some supernovae (SNe) may be powered by the interaction of the SN ejecta with a large amount of circumstellar matter (CSM). However, quantitative estimates of the CSM mass around such SNe are missing when the CSM material is optically thick. Specifically, current estimators are sensitive to uncertainties regarding the CSM density profile and the ejecta velocity. Here we outline a method to measure the mass of the optically thick CSM around such SNe. We present new visible-light and X-ray observations of SN 2010jl (PTF 10aaxf), including the first detection of an SN in the hard X-ray band using NuSTAR. The total radiated luminosity of SN 2010jl is extreme atleast 9 1050 erg. By modeling the visible-light data, we robustly show that the mass of the circumstellar material within 1016 cm of the progenitor of SN 2010jl was in excess of 10M_. This mass was likely ejected tens of years prior to the SN explosion. Our modeling suggests that the shock velocity during shock breakout was 6000 km s1, decelerating to 2600 km s1 about 2 yr after maximum light. Furthermore, our late-time NuSTAR and XMM spectra of the SN presumably provide the first direct measurement of SN shock velocity 2 yr after the SN maximum light measured to be in the range of 2000-4500 km s1 if the ions and electrons are in equilibrium, and_2000 km s1 if they are not in equilibrium. This measurement is in agreement with the shock velocity predicted by our modeling of the visible-light data. Our observations also show that the average radial density distribution of the CSM roughly follows an r2 law. A possible explanation for the _10M_ of CSM and the wind-like profile is that they are the result of multiple pulsational pair instability events prior to the SN explosion, separated from each other by years

Correlated Mutations: A Hallmark of Phenotypic Amino Acid Substitutions

Point mutations resulting in the substitution of a single amino acid can cause severe functional consequences, but can also be completely harmless. Understanding what determines the phenotypical impact is important both for planning targeted mutation experiments in the laboratory and for analyzing naturally occurring mutations found in patients. Common wisdom suggests using the extent of evolutionary conservation of a residue or a sequence motif as an indicator of its functional importance and thus vulnerability in case of mutation. In this work, we put forward the hypothesis that in addition to conservation, co-evolution of residues in a protein influences the likelihood of a residue to be functionally important and thus associated with disease. While the basic idea of a relation between co-evolution and functional sites has been explored before, we have conducted the first systematic and comprehensive analysis of point mutations causing disease in humans with respect to correlated mutations. We included 14,211 distinct positions with known disease-causing point mutations in 1,153 human proteins in our analysis. Our data show that (1) correlated positions are significantly more likely to be disease-associated than expected by chance, and that (2) this signal cannot be explained by conservation patterns of individual sequence positions. Although correlated residues have primarily been used to predict contact sites, our data are in agreement with previous observations that (3) many such correlations do not relate to physical contacts between amino acid residues. Access to our analysis results are provided at http://webclu.bio.wzw.tum.de/~pagel/supplements/correlated-positions/

SN 2010jl: Optical to Hard X-ray Observations Reveal an Explosion Embedded In a Ten Solar Mass Cocoon

Some supernovae (SNe) may be powered by the interaction of the SN ejecta with a large amount of circumstellar matter (CSM). However, quantitative estimates of the CSM mass around such SNe are missing when the CSM material is optically thick. Specifically, current estimators are sensitive to uncertainties regarding the CSM density profile and the ejecta velocity. Here we outline a method to measure the mass of the optically thick CSM around such SNe. We present new visible-light and X-ray observations of SN 2010jl (PTF 10aaxf), including the first detection of an SN in the hard X-ray band using NuSTAR. The total radiated luminosity of SN 2010jl is extreme—at least 9 × 1050 erg. By modeling the visible-light data, we robustly show that the mass of the circumstellar material within ~1016 cm of the progenitor of SN 2010jl was in excess of 10 M☉. This mass was likely ejected tens of years prior to the SN explosion. Our modeling suggests that the shock velocity during shock breakout was ~6000 km s–1, decelerating to ~2600 km s–1 about 2 yr after maximum light. Furthermore, our late-time NuSTAR and XMM spectra of the SN presumably provide the first direct measurement of SN shock velocity 2 yr after the SN maximum light—measured to be in the range of 2000-4500 km s–1 if the ions and electrons are in equilibrium, and ≳2000 km s–1 if they are not in equilibrium. This measurement is in agreement with the shock velocity predicted by our modeling of the visible-light data. Our observations also show that the average radial density distribution of the CSM roughly follows an r–2 law. A possible explanation for the ≳10 M☉ of CSM and the wind-like profile is that they are the result of multiple pulsational pair instability events prior to the SN explosion, separated from each other by years

Measurement of the prompt J/psi and psi(2S) polarizations in pp collisions at sqrt(s) = 7 TeV

The polarizations of prompt J/psi and psi(2S) mesons are measured in proton-proton collisions at sqrt(s) = 7 TeV, using a dimuon data sample collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 4.9 inverse femtobarns. The prompt J/psi and psi(2S) polarization parameters lambda[theta], lambda[phi], and lambda[theta, phi], as well as the frame-invariant quantity lambda(tilde), are measured from the dimuon decay angular distributions in three different polarization frames. The J/psi results are obtained in the transverse momentum range 14 < pt < 70 GeV, in the rapidity intervals abs(y) < 0.6 and 0.6 < abs(y) < 1.2. The corresponding psi(2S) results cover 14 < pt < 50 GeV and include a third rapidity bin, 1.2 < abs(y) < 1.5. No evidence of large transverse or longitudinal polarizations is seen in these kinematic regions, which extend much beyond those previously explored