Protostellar accretion traced with chemistry. High resolution C18O and continuum observations towards deeply embedded protostars in Perseus

Context: Understanding how accretion proceeds is a key question of star formation, with important implications for both the physical and chemical evolution of young stellar objects. In particular, very little is known about the accretion variability in the earliest stages of star formation. Aims: To characterise protostellar accretion histories towards individual sources by utilising sublimation and freeze-out chemistry of CO. Methods: A sample of 24 embedded protostars are observed with the Submillimeter Array (SMA) in context of the large program "Mass Assembly of Stellar Systems and their Evolution with the SMA" (MASSES). The size of the C$^{18}$O emitting region, where CO has sublimated into the gas-phase, is measured towards each source and compared to the expected size of the region given the current luminosity. The SMA observations also include 1.3 mm continuum data, which are used to investigate whether a link can be established between accretion bursts and massive circumstellar disks. Results: Depending on the adopted sublimation temperature of the CO ice, between 20% and 50% of the sources in the sample show extended C$^{18}$O emission indicating that the gas was warm enough in the past that CO sublimated and is currently in the process of refreezing; something which we attribute to a recent accretion burst. Given the fraction of sources with extended C$^{18}$O emission, we estimate an average interval between bursts of 20000-50000 yr, which is consistent with previous estimates. No clear link can be established between the presence of circumstellar disks and accretion bursts, however the three closest known binaries in the sample (projected separations <20 AU) all show evidence of a past accretion burst, indicating that close binary interactions may also play a role in inducing accretion variability.Comment: Accepted for publication in A&A, 21 pages, 13 figure

Mass Assembly of Stellar Systems and Their Evolution with the SMA (MASSES)-Full Data Release

We present and release the full dataset for the Mass Assembly of Stellar Systems and their Evolution with the SMA (MASSES) survey. This survey used the Submillimeter Array (SMA) to image the 74 known protostars within the Perseus molecular cloud. The SMA was used in two array configurations to capture outflows for scales $>$30$^{\prime\prime}$ ($>$9000 au) and to probe scales down to $\sim$1$^{\prime\prime}$ ($\sim$300 au). The protostars were observed with the 1.3 mm and 850 $\mu$m receivers simultaneously to detect continuum at both wavelengths and molecular line emission from CO(2-1), $^{13}$CO(2-1), C$^{18}$O(2-1), N$_2$D$^+$(3-2), CO(3-2), HCO$^+$(4-3), and H$^{13}$CO$^+$(4-3). Some of the observations also used the SMA's recently upgraded correlator, SWARM, whose broader bandwidth allowed for several more spectral lines to be observed (e.g., SO, H$_2$CO, DCO$^+$, DCN, CS, CN). Of the main continuum and spectral tracers observed, 84% of the images and cubes had emission detected. The median C$^{18}$O(2-1) linewidth is $\sim$1.0 km s$^{-1}$, which is slightly higher than those measured with single-dish telescopes at scales of 3000-20000 au. Of the 74 targets, six are suggested to be first hydrostatic core candidates, and we suggest that L1451-mm is the best candidate. We question a previous continuum detection toward L1448 IRS2E. In the SVS13 system, SVS13A certainly appears to be the most evolved source, while SVS13C appears to be hotter and more evolved than SVS13B. The MASSES survey is the largest publicly available interferometric continuum and spectral line protostellar survey to date, and is largely unbiased as it only targets protostars in Perseus. All visibility ($uv$) data and imaged data are publicly available at https://dataverse.harvard.edu/dataverse/full_MASSES/.Comment: Accepted to ApJ

Assessment of the Effect of High or Low Protein Diet on the Human Urine Metabolome as Measured by NMR

The objective of this study was to identify urinary metabolite profiles that discriminate between high and low intake of dietary protein during a dietary intervention. Seventy-seven overweight, non-diabetic subjects followed an 8-week low-calorie diet (LCD) and were then randomly assigned to a high (HP) or low (LP) protein diet for 6 months. Twenty-four hours urine samples were collected at baseline (prior to the 8-week LCD) and after dietary intervention; at months 1, 3 and 6, respectively. Metabolite profiling was performed by 1H NMR and chemometrics. Using partial least squares regression (PLS), it was possible to develop excellent prediction models for urinary nitrogen (root mean square error of cross validation (RMSECV) = 1.63 mmol/L; r = 0.89) and urinary creatinine (RMSECV = 0.66 mmol/L; r = 0.98). The obtained high correlations firmly establish the validity of the metabolomic approach since urinary nitrogen is a well established biomarker for daily protein consumption. The models showed that trimethylamine-N-oxide (TMAO) is correlated to urinary nitrogen. Furthermore, urinary creatine was found to be increased by the HP diet whereas citric acid was increased by the LP diet. Despite large variations in individual dietary intake, differentiated metabolite profiles were observed at the dietary group-level

Adverse events from spinal manipulation in the pregnant and postpartum periods: a critical review of the literature

<p>Abstract</p> <p>Background</p> <p>The safety of spinal manipulation during pregnancy and the postpartum periods has been a matter of debate among manual therapists. Spinal manipulative therapy during these periods is a commonly performed intervention as musculoskeletal pain is common in these patients. To date there has not been an evaluation of the literature on this topic exclusively.</p> <p>Methods</p> <p>A literature search was conducted on PubMed, CINAHL and the Index to Chiropractic Literature along with reference searching for articles published in English and French in the peer-reviewed literature that documented adverse effects of spinal manipulation during either pregnancy or postpartum. Case reports, case series, and any other clinical study designs were deemed acceptable for inclusion, as were systematic reviews. The appropriate Scottish Intercollegiate Guidelines Network (SIGN) tools were used to rate included articles for quality when applicable.</p> <p>Results</p> <p>Five articles identifying adverse events in seven subjects following spinal manipulation were included in this review, along with two systematic reviews. The articles were published between 1978 and 2009. Two articles describing adverse effects from spinal manipulation on two postpartum patients were included, while the remaining three articles on five patients with adverse effects following spinal manipulation were on pregnant patients. Injury severity ranged from minor injury such as increasing pain after treatment that resolved within a few days to more severe injuries including fracture, stroke, and epidural hematoma. SIGN scores of the prospective observational cohort study and systematic reviews indicated acceptable quality.</p> <p>Conclusions</p> <p>There are only a few reported cases of adverse events following spinal manipulation during pregnancy and the postpartum period identified in the literature. While improved reporting of such events is required in the future, it may be that such injuries are relatively rare.</p

Mass Assembly of Stellar Systems and Their Evolution With the Sma (Masses). Multiplicity and the Physical Environment in L1448n

We present continuum and molecular line observations at 230 and 345 GHz from the Submillimeter Array (SMA) toward three protostars in the Perseus L1448N region. The data are from the large project "Mass Assembly of Stellar Systems and their Evolution with the SMA." Three dust continuum sources, Source B, Source NW, and Source A, are detected at both frequencies. These sources have corresponding emission peaks in C18O ($J=2\to 1$), 13CO ($J=2\to 1$), and HCO+ ($J=4\to 3$), and have offsets with N2D+ ($J=3\to 2$) peaks. High angular resolution data from a complementary continuum survey with the Karl G. Jansky Very Large Array show that Source B is associated with three 8 mm continuum objects, Source NW with two, and Source A remains single. These results suggest that multiplicity in L1448N exists at different spatial scales from a few thousand AU to <100 AU. Velocity gradients in each source obtained from two-dimensional fits to the SMA C18O emission are found to be perpendicular to within 20° of the outflow directions as revealed by 12CO ($J=2\to 1$). We have observed that Sources B and NW with multiplicity have higher densities than Source A without multiplicity. This suggests that thermal Jeans fragmentation can be relevant in the fragmentation process. However, we have not observed a difference in the ratio between rotational and gravitational energy between sources with and without multiplicity. We also have not observed a trend between non-thermal velocity dispersions and the level of fragmentation. Our study has provided the first direct and comprehensive comparison between multiplicity and core properties in low-mass protostars, although based on small number statistics.Astronom

Rare germline copy number variants (CNVs) and breast cancer risk.

Funder: CIHRGermline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance

A likelihood ratio approach for utilizing case-control data in the clinical classification of rare sequence variants:Application to BRCA1 and BRCA2

A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.</p

Mendelian randomisation study of smoking exposure in relation to breast cancer risk

Background Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Results Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 x 10(-2)), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.Peer reviewe

Common variants in breast cancer risk loci predispose to distinct tumor subtypes.

BACKGROUND: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. METHODS: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. RESULTS: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. CONCLUSION: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction