Our understanding of the etiology, pathophysiology, phenotypic diversity, and progression of Parkinson's disease has stagnated. Consequently, patients do not receive the best care, leading to ...unnecessary disability, and to mounting costs for society. The Personalized Parkinson Project (PPP) proposes an unbiased approach to biomarker development with multiple biomarkers measured longitudinally. Our main aims are: (a) to perform a set of hypothesis-driven analyses on the comprehensive dataset, correlating established and novel biomarkers to the rate of disease progression and to treatment response; and (b) to create a widely accessible dataset for discovery of novel biomarkers and new targets for therapeutic interventions in Parkinson's disease.
This is a prospective, longitudinal, single-center cohort study. The cohort will comprise 650 persons with Parkinson's disease. The inclusion criteria are purposely broad: age ≥ 18 years; and disease duration ≤5 years. Participants are followed for 2 years, with three annual assessments at the study center. Outcomes include a clinical assessment (including motor and neuro-psychological tests), collection of biospecimens (stool, whole blood, and cerebrospinal fluid), magnetic resonance imaging (both structural and functional), and ECG recordings (both 12-lead and Holter). Additionally, collection of physiological and environmental data in daily life over 2 years will be enabled through the Verily Study Watch. All data are stored with polymorphic encryptions and pseudonyms, to guarantee the participants' privacy on the one hand, and to enable data sharing on the other. The data and biospecimens will become available for scientists to address Parkinson's disease-related research questions.
The PPP has several distinguishing elements: all assessments are done in a single center; inclusion of "real life" subjects; deep and repeated multi-dimensional phenotyping; and continuous monitoring with a wearable device for 2 years. Also, the PPP is powered by privacy and security by design, allowing for data sharing with scientists worldwide respecting participants' privacy. The data are expected to open the way for important new insights, including identification of biomarkers to predict differences in prognosis and treatment response between patients. Our long-term aim is to improve existing treatments, develop new therapeutic approaches, and offer Parkinson's disease patients a more personalized disease management approach.
Clinical Trials NCT03364894 . Registered December 6, 2017 (retrospectively registered).
The SUPERFAMILY resource provides protein domain assignments at the structural classification of protein (SCOP) superfamily level for over 1400 completely sequenced genomes, over 120 metagenomes and ...other gene collections such as UniProt. All models and assignments are available to browse and download at http://supfam.org. A new hidden Markov model library based on SCOP 1.75 has been created and a previously ignored class of SCOP, coiled coils, is now included. Our scoring component now uses HMMER3, which is in orders of magnitude faster and produces superior results. A cloud-based pipeline was implemented and is publicly available at Amazon web services elastic computer cloud. The SUPERFAMILY reference tree of life has been improved allowing the user to highlight a chosen superfamily, family or domain architecture on the tree of life. The most significant advance in SUPERFAMILY is that now it contains a domain-based gene ontology (GO) at the superfamily and family levels. A new methodology was developed to ensure a high quality GO annotation. The new methodology is general purpose and has been used to produce domain-based phenotypic ontologies in addition to GO.
In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were ...significantly lower, suggesting alternate causes or the involvement of arboviral cofactors in exacerbating microcephaly rates.
We merged data from multiple national reporting databases in Brazil to estimate exposure to 9 known or hypothesized causes of microcephaly for every pregnancy nationwide since the beginning of the ZIKV outbreak; this generated between 3.6 and 5.4 million cases (depending on analysis) over the time period 1 January 2015-23 May 2017. The association between ZIKV and microcephaly was statistically tested against models with alternative causes or with effect modifiers. We found no evidence for alternative non-ZIKV causes of the 2015-2017 microcephaly outbreak, nor that concurrent exposure to arbovirus infection or vaccination modified risk. We estimate an absolute risk of microcephaly of 40.8 (95% CI 34.2-49.3) per 10,000 births and a relative risk of 16.8 (95% CI 3.2-369.1) given ZIKV infection in the first or second trimester of pregnancy; however, because ZIKV infection rates were highly variable, most pregnant women in Brazil during the ZIKV outbreak will have been subject to lower risk levels. Statistically significant associations of ZIKV with other birth defects were also detected, but at lower relative risks than that of microcephaly (relative risk < 1.5). Our analysis was limited by missing data prior to the establishment of nationwide ZIKV surveillance, and its findings may be affected by unmeasured confounding causes of microcephaly not available in routinely collected surveillance data.
This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate leads us to hypothesize that the Northeast region was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason.
We report the results from a search for z > 6.5 quasars using the Dark Energy Survey (DES) Year 3 data set combined with the VISTA Hemisphere Survey (VHS) and WISE All-Sky Survey. Our photometric ...selection method is shown to be highly efficient in identifying clean samples of high-redshift quasars, leading to spectroscopic confirmation of three new quasars – VDES J0244-5008 (z = 6.724), VDES J0020-3653 (z = 6.834), and VDES J0246-5219 (z = 6.90) – which were selected as the highest priority candidates in the survey data without any need for additional follow-up observations. Here, we have obtained spectroscopic observations in the near-infrared for VDES J0244-5008 and VDES J0020-3653 as well as our previously identified quasar, VDES J0224-4711 at z = 6.50 from Reed et al. We use the near-infrared spectra to derive virial black hole masses from the full width at half-maximum of the Mg ii line. These black hole masses are ≃1–2 × 109 M⊙. Combined with the bolometric luminosities of these quasars of Lbol ≃ 1–3 × 1047, these imply that the Eddington ratios are high, ≃0.6–1.1. We consider the C iv emission line properties of the sample and demonstrate that our high-redshift quasars do not have unusual C iv line properties when compared to carefully matched low-redshift samples. Our new DES + VHS z > 6.5 quasars now add to the growing census of luminous, rapidly accreting supermassive black holes seen well into the epoch of reionization.
In this paper we analyze the descriptive statistics of the Google search volume for the terms related to the National Reserve of Copper and Associates (RENCA), a Brazilian mineral reserve in the ...Amazon of 4.6 million hectares, before and after the government signed the decree releasing it for exploration. First, we analyze the volume of searches for expressions related to RENCA in Google Trends using descriptive statistics; second, we assess the cross-correlation coefficient rho.sub.DCCA, which measures the cross-correlation between two nonstationary time series across different time scales. After the government announced the release of the RENCA reserve, there was an increase in the average volume of Google searches for related terms, showing people's concern about the announcement. By using the cross-correlation coefficient rho.sub.DCCA, we identify strong cross-correlations between the different expressions related to RENCA in Google Trends. Our work shows the utility of Google Trends as an indicator of the perception of environmental policies. Additionally, we show that rho.sub.DCCA can be used as a tool to measure the cross-correlation between synonyms extracted from Google Trends for various time scales.
ABSTRACT
We present a blind time-delay cosmographic analysis for the lens system DES J0408−5354. This system is extraordinary for the presence of two sets of multiple images at different redshifts, ...which provide the opportunity to obtain more information at the cost of increased modelling complexity with respect to previously analysed systems. We perform detailed modelling of the mass distribution for this lens system using three band Hubble Space Telescope imaging. We combine the measured time delays, line-of-sight central velocity dispersion of the deflector, and statistically constrained external convergence with our lens models to estimate two cosmological distances. We measure the ‘effective’ time-delay distance corresponding to the redshifts of the deflector and the lensed quasar $D_{\Delta t}^{\rm eff}=$$3382_{-115}^{+146}$ Mpc and the angular diameter distance to the deflector Dd = $1711_{-280}^{+376}$ Mpc, with covariance between the two distances. From these constraints on the cosmological distances, we infer the Hubble constant H0= $74.2_{-3.0}^{+2.7}$ km s−1 Mpc−1 assuming a flat ΛCDM cosmology and a uniform prior for Ωm as $\Omega _{\rm m} \sim \mathcal {U}(0.05, 0.5)$. This measurement gives the most precise constraint on H0 to date from a single lens. Our measurement is consistent with that obtained from the previous sample of six lenses analysed by the H0 Lenses in COSMOGRAIL’s Wellspring (H0LiCOW) collaboration. It is also consistent with measurements of H0 based on the local distance ladder, reinforcing the tension with the inference from early Universe probes, for example, with 2.2σ discrepancy from the cosmic microwave background measurement.
This study aimed to measure the magnitude of education-related inequalities in the use of dental services among older adults (aged 50 y or older) from a sizable multicountry sample of 23 ...upper-middle- and high-income countries. This study used cross-sectional data from nationally representative surveys of people aged 50 y and over. Countries included in the Health and Retirement Study surveys were the following: Brazil, China, South Korea, Mexico, United States, Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, France, Germany, Greece, Italy, Israel, Luxembourg, Poland, Portugal, Slovenia, Spain, Sweden, and Switzerland. The dependent variable was the use of dental services, based on the self-report of having had a dental visit within the previous year, except for the United States and South Korea, which used 2-y recall periods. Educational level was used as the measure of socioeconomic position and was standardized across countries. Multivariate logistic regression modeling was used to evaluate the factors associated with the use of dental services, and the magnitude of education inequalities in the use of dental services was assessed using the slope index of inequality (SII) to measure absolute inequalities and the relative index of inequality for relative inequalities. The pooled prevalence of the use of dental services was 31.7% and ranged from 18.7% in China to 81.2% in Sweden. In the overall sample, the absolute difference in the prevalence of use between the lowest and highest educational groups was 20 percentage points. SII was significant for all countries except Portugal. Relative educational inequalities were significant for all countries and ranged from 3.2 in Poland to 1.2 in Sweden. There were significant education-related inequalities in the use of dental care by older adults in all countries. Monitoring these inequalities is critical to the planning and delivery of dental services.
ABSTRACT
Wide-field imaging surveys such as the Dark Energy Survey (DES) rely on coarse measurements of spectral energy distributions in a few filters to estimate the redshift distribution of source ...galaxies. In this regime, sample variance, shot noise, and selection effects limit the attainable accuracy of redshift calibration and thus of cosmological constraints. We present a new method to combine wide-field, few-filter measurements with catalogues from deep fields with additional filters and sufficiently low photometric noise to break degeneracies in photometric redshifts. The multiband deep field is used as an intermediary between wide-field observations and accurate redshifts, greatly reducing sample variance, shot noise, and selection effects. Our implementation of the method uses self-organizing maps to group galaxies into phenotypes based on their observed fluxes, and is tested using a mock DES catalogue created from N-body simulations. It yields a typical uncertainty on the mean redshift in each of five tomographic bins for an idealized simulation of the DES Year 3 weak-lensing tomographic analysis of σΔz = 0.007, which is a 60 per cent improvement compared to the Year 1 analysis. Although the implementation of the method is tailored to DES, its formalism can be applied to other large photometric surveys with a similar observing strategy.
ABSTRACT
We present and characterize the galaxy shape catalogue from the first 3 yr of Dark Energy Survey (DES) observations, over an effective area of 4143 deg2 of the southern sky. We describe our ...data analysis process and our self-calibrating shear measurement pipeline metacalibration, which builds and improves upon the pipeline used in the DES Year 1 analysis in several aspects. The DES Year 3 weak-lensing shape catalogue consists of 100 204 026 galaxies, measured in the riz bands, resulting in a weighted source number density of neff = 5.59 gal arcmin−2 and corresponding shape noise σe = 0.261. We perform a battery of internal null tests on the catalogue, including tests on systematics related to the point spread function (PSF) modelling, spurious catalogue B-mode signals, catalogue contamination, and galaxy properties.
Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear.
The purpose of this study was to evaluate ...sex-specific associations of CV risk factors and biomarkers with incident HF.
The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio.
Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001).
CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes.
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