Learning a Factor Model via Regularized PCA

We consider the problem of learning a linear factor model. We propose a regularized form of principal component analysis (PCA) and demonstrate through experiments with synthetic and real data the superiority of resulting estimates to those produced by pre-existing factor analysis approaches. We also establish theoretical results that explain how our algorithm corrects the biases induced by conventional approaches. An important feature of our algorithm is that its computational requirements are similar to those of PCA, which enjoys wide use in large part due to its efficiency

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

A multilevel intervention to increase physical activity and improve healthy eating and physical literacy among young children (ages 3-5) attending early childcare centres: the Healthy Start-Départ Santé cluster randomised controlled trial study protocol

Abstract: Background: Childhood obesity is a growing concern for public health. Given a majority of children in many countries spend approximately 30 h per week in early childcare centers, this environment represents a promising setting for implementing strategies to foster healthy behaviours for preventing and controlling childhood obesity. Healthy Start-Départ Santé was designed to promote physical activity, physical literacy, and healthy eating among preschoolers. The objectives of this study are to assess the effectiveness of the Healthy Start-Départ Santé intervention in improving physical activity levels, physical literacy, and healthy eating among preschoolers attending early childcare centers. Methods/Design: This study follows a cluster randomized controlled trial design in which the childcare centers are randomly assigned to receive the intervention or serve as usual care controls. The Healthy Start-Départ Santé intervention is comprised of interlinked components aiming to enable families and educators to integrate physical activity and healthy eating in the daily lives of young children by influencing factors at the intrapersonal, interpersonal, organizational, community, physical environment and policy levels. The intervention period, spanning 6-8 months, is preceded and followed by data collections. Participants are recruited from 61 childcare centers in two Canadian provinces, New Brunswick and Saskatchewan. Centers eligible for this study have to prepare and provide meals for lunch and have at least 20 children between the ages of 3 and 5. Centers are excluded if they have previously received a physical activity or nutrition promoting intervention. Eligible centers are stratified by province, geographical location (urban or rural) and language (English or French), then recruited and randomized using a one to one protocol for each stratum. Data collection is ongoing. The primary study outcomes are assessed using accelerometers (physical activity levels), the Test of Gross Motor Development-II (physical literacy), and digital photography-assisted weighted plate waste (food intake). Discussion: The multifaceted approach of Healthy Start-Départ Santé positions it well to improve the physical literacy and both dietary and physical activity behaviors of children attending early childcare centers. The results of this study will be of relevance given the overwhelming prevalence of overweight and obesity in children worldwide. Trial registration: NCT02375490 (ClinicalTrials.gov registry)

Genome-wide association study for renal traits in the Framingham Heart and Atherosclerosis Risk in Communities Studies

Background: The Framingham Heart Study (FHS) recently obtained initial results from the first genome-wide association scan for renal traits. The study of 70,987 single nucleotide polymorphisms (SNPs) in 1,010 FHS participants provides a list of SNPs showing the strongest associations with renal traits which need to be verified in independent study samples. Methods: Sixteen SNPs were selected for replication based on the most promising associations with chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and serum cystatin C in FHS. These SNPs were genotyped in 15,747 participants of the Atherosclerosis in Communities (ARIC) Study and evaluated for association using multivariable adjusted regression analyses. Primary outcomes in ARIC were CKD and eGFR. Secondary prospective analyses were conducted for association with kidney disease progression using multivariable adjusted Cox proportional hazards regression. The definition of the outcomes, all covariates, and the use of an additive genetic model was consistent with the original analyses in FHS. Results: The intronic SNP rs6495446 in the gene MTHFS was significantly associated with CKD among white ARIC participants at visit 4: the odds ratio per each C allele was 1.24 (95% CI 1.09–1.41, p = 0.001). Borderline significant associations of rs6495446 were observed with CKD at study visit 1 (p = 0.024), eGFR at study visits 1 (p = 0.073) and 4 (lower mean eGFR per C allele by 0.6 ml/min/1.73 $\text{m}^2$, p = 0.043) and kidney disease progression (hazard ratio 1.13 per each C allele, 95% CI 1.00–1.26, p = 0.041). Another SNP, rs3779748 in EYA1, was significantly associated with CKD at ARIC visit 1 (odds ratio per each T allele 1.22, p = 0.01), but only with eGFR and cystatin C in FHS. Conclusion: This genome-wide association study provides unbiased information implicating MTHFS as a candidate gene for kidney disease. Our findings highlight the importance of replication to identify common SNPs associated with renal traits

Can cognitive insight predict symptom remission in a first episode psychosis cohort?

BACKGROUND: The outcome of first episode psychosis (FEP) is highly variable and difficult to predict. Cognitive insight measured at illness onset has previously been found to predict psychopathology 12-months later. The aims of this study were to examine whether the prospective relationship between cognitive insight and symptom severity is evident at four-years following FEP and to examine some psychological correlates of cognitive insight. METHODS: FEP participants (n = 90) completed the Beck Cognitive Insight Scale (BCIS) at illness onset, and associations between BCIS scores with symptom severity outcomes (4-years after FEP) were assessed. The BCIS scales (self-reflectiveness and self-certainty) were examined as a composite score, and individually compared to other cognitive measures (IQ and jumping to conclusions (JTC) bias). RESULTS: Regression analyses revealed that the cognitive insight composite did not predict 4-year symptom remission in this study while the self-reflection subscale of the BCIS predicted severity of symptoms at 4-years. Self-certainty items of the BCIS were not associated with symptom severity. Significant correlations between the JTC bias, self-certainty and IQ were found, but self-reflection did not correlate with these other cognitive measures. CONCLUSIONS: Self-reflective capacity is a more relevant and independent cognitive construct than self-certainty for predicting prospective symptom severity in psychosis. Improving self-reflection may be a useful target for early intervention research

Predicting the seasonal evolution of southern African summer precipitation in the DePreSys3 prediction system

We assess the ability of the DePreSys3 prediction system to predict austral summer precipitation (DJF) over southern Africa, defined as the African continent south of 15°S. DePresys3 is a high resolution prediction system (at a horizontal resolution of ~ 60 km in the atmosphere in mid-latitudes and of the quarter degree in the Ocean) and spans the long period 1959–2016. We find skill in predicting interannual precipitation variability, relative to a long-term trend; the anomaly correlation skill score over southern Africa is greater than 0.45 for the first summer (i.e. lead month 2–4), and 0.37 over Mozambique, Zimbabwe and Zambia for the second summer (i.e. lead month 14–16). The skill is related to the successful prediction of the El-Nino Southern Oscillation (ENSO), and the successful simulation of ENSO teleconnections to southern Africa. However, overall skill is sensitive to the inclusion of strong La-Nina events and also appears to change with forecast epoch. For example, the skill in predicting precipitation over Mozambique is significantly larger for the first summer in the 1990–2016 period, compared to the 1959–1985 period. The difference in skill in predicting interannual precipitation variability over southern Africa in different epochs is consistent with a change in the strength of the observed teleconnections of ENSO. After 1990, and consistent with the increased skill, the observed impact of ENSO appears to strengthen over west Mozambique, in association with changes in ENSO related atmospheric convergence anomalies. However, these apparent changes in teleconnections are not captured by the ensemble-mean predictions using DePreSys3. The changes in the ENSO teleconnection are consistent with a warming over the Indian Ocean and modulation of ENSO properties between the different epochs, but may also be associated with unpredictable atmospheric variability

Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND)

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD

First joint observation by the underground gravitational-wave detector KAGRA with GEO 600

We report the results of the first joint observation of the KAGRA detector with GEO 600. KAGRA is a cryogenic and underground gravitational-wave detector consisting of a laser interferometer with 3 km arms, located in Kamioka, Gifu, Japan. GEO 600 is a British-German laser interferometer with 600 m arms, located near Hannover, Germany. GEO 600 and KAGRA performed a joint observing run from April 7 to 20, 2020. We present the results of the joint analysis of the GEO-KAGRA data for transient gravitational-wave signals, including the coalescence of neutron-star binaries and generic unmodeled transients. We also perform dedicated searches for binary coalescence signals and generic transients associated with gamma-ray burst events observed during the joint run. No gravitational-wave events were identified. We evaluate the minimum detectable amplitude for various types of transient signals and the spacetime volume for which the network is sensitive to binary neutron-star coalescences. We also place lower limits on the distances to the gamma-ray bursts analyzed based on the non-detection of an associated gravitational-wave signal for several signal models, including binary coalescences. These analyses demonstrate the feasibility and utility of KAGRA as a member of the global gravitational-wave detector network

All-sky search for continuous gravitational waves from isolated neutron stars using Advanced LIGO and Advanced Virgo O3 data

We present results of an all-sky search for continuous gravitational waves which can be produced by spinning neutron stars with an asymmetry around their rotation axis, using data from the third observing run of the Advanced LIGO and Advanced Virgo detectors. Four different analysis methods are used to search in a gravitational-wave frequency band from 10 to 2048 Hz and a first frequency derivative from $-10^{-8}$ to $10^{-9}$ Hz/s. No statistically-significant periodic gravitational-wave signal is observed by any of the four searches. As a result, upper limits on the gravitational-wave strain amplitude $h_0$ are calculated. The best upper limits are obtained in the frequency range of 100 to 200 Hz and they are ${\sim}1.1\times10^{-25}$ at 95\% confidence-level. The minimum upper limit of $1.10\times10^{-25}$ is achieved at a frequency 111.5 Hz. We also place constraints on the rates and abundances of nearby planetary- and asteroid-mass primordial black holes that could give rise to continuous gravitational-wave signals