Galaxy Cluster Pressure Profiles as Determined by Sunyaev Zel'dovich Effect Observations with MUSTANG and Bolocam I: Joint Analysis Technique

We present a technique to constrain galaxy cluster pressure profiles by jointly fitting Sunyaev-Zel'dovich effect (SZE) data obtained with MUSTANG and Bolocam for the clusters Abell 1835 and MACS0647. Bolocam and MUSTANG probe different angular scales and are thus highly complementary. We find that the addition of the high resolution MUSTANG data can improve constraints on pressure profile parameters relative to those derived solely from Bolocam. In Abell 1835 and MACS0647, we find gNFW inner slopes of $\gamma = 0.36_{-0.21}^{+0.33}$ and $\gamma = 0.38_{-0.25}^{+0.20}$, respectively when $\alpha$ and $\beta$ are constrained to 0.86 and 4.67 respectively. The fitted SZE pressure profiles are in good agreement with X-ray derived pressure profiles.Comment: 12 pages, 12 figures. Submitted to Ap

Finding New Cell Wall Regulatory Genes in Populus trichocarpa Using Multiple Lines of Evidence.

Understanding the regulatory network controlling cell wall biosynthesis is of great interest in Populus trichocarpa, both because of its status as a model woody perennial and its importance for lignocellulosic products. We searched for genes with putatively unknown roles in regulating cell wall biosynthesis using an extended network-based Lines of Evidence (LOE) pipeline to combine multiple omics data sets in P. trichocarpa, including gene coexpression, gene comethylation, population level pairwise SNP correlations, and two distinct SNP-metabolite Genome Wide Association Study (GWAS) layers. By incorporating validation, ranking, and filtering approaches we produced a list of nine high priority gene candidates for involvement in the regulation of cell wall biosynthesis. We subsequently performed a detailed investigation of candidate gene GROWTH-REGULATING FACTOR 9 (PtGRF9). To investigate the role of PtGRF9 in regulating cell wall biosynthesis, we assessed the genome-wide connections of PtGRF9 and a paralog across data layers with functional enrichment analyses, predictive transcription factor binding site analysis, and an independent comparison to eQTN data. Our findings indicate that PtGRF9 likely affects the cell wall by directly repressing genes involved in cell wall biosynthesis, such as PtCCoAOMT and PtMYB.41, and indirectly by regulating homeobox genes. Furthermore, evidence suggests that PtGRF9 paralogs may act as transcriptional co-regulators that direct the global energy usage of the plant. Using our extended pipeline, we show multiple lines of evidence implicating the involvement of these genes in cell wall regulatory functions and demonstrate the value of this method for prioritizing candidate genes for experimental validation

GBT/MUSTANG-2 9" resolution imaging of the SZ effect in MS0735.6+7421: Confirmation of the SZ Cavities through direct imaging

Mechanical feedback from active galactic nuclei (AGN) is thought to be the dominant feedback mechanism quenching cooling flows and star formation in galaxy cluster cores. However, the mechanisms by which AGN couple to the intracluster medium (ICM) are not well understood. The nature of pressure supporting the cavities is not known. Using the MUSTANG-2 instrument on the Green Bank Telescope (GBT), we aimed to measure thermal Sunyaev-Zeldovich (SZ) effect signals associated with the X-ray cavities in MS0735.6+7421, a moderate mass cluster hosting one of the most energetic AGN outbursts known. We use these measurements to infer the level of non-thermal sources of pressure, such as magnetic fields and turbulence, as well as relativistic and cosmic ray components, supporting the cavities. We used preconditioned gradient descent to fit a model for the cluster, cavities, and central point source directly to the time ordered data of the MUSTANG-2 signal. We use this model to probe the thermodynamic state of the cavities. We have shown that the SZ signal associated with the cavities is suppressed compared to the expectations for a thermal plasma with the temperature $\sim$few tens keV. The smallest value of the suppression factor $f$ that is consistent with the data is $\sim$0.4, lower than inferred in earlier work. Larger values of $f$ are possible once the contribution of the cocoon shock surrounding the bubbles is taken into account. The baseline model with this particular geometrical setup yields best-fitting value f~0.5, which at face value implies a mix of thermal and non-thermal pressure support. Larger values of $f$ (up to 1, i.e. no tSZ signal from the bubbles) are still possible when allowing for variations in the line-of-sight geometry.Comment: 8 pages, 3 figure

NASA Probe Study Report: Farside Array for Radio Science Investigations of the Dark ages and Exoplanets (FARSIDE)

This is the final report submitted to NASA for a Probe-class concept study of the "Farside Array for Radio Science Investigations of the Dark ages and Exoplanets" (FARSIDE), a low radio frequency interferometric array on the farside of the Moon. The design study focused on the instrument, a deployment rover, the lander and base station, and delivered an architecture broadly consistent with the requirements for a Probe mission. This notional architecture consists of 128 dipole antennas deployed across a 10 km area by a rover, and tethered to a base station for central processing, power and data transmission to the Lunar Gateway, or an alternative relay satellite. FARSIDE would provide the capability to image the entire sky each minute in 1400 channels spanning frequencies from 150 kHz to 40 MHz, extending down two orders of magnitude below bands accessible to ground-based radio astronomy. The lunar farside can simultaneously provide isolation from terrestrial radio frequency interference, auroral kilometric radiation, and plasma noise from the solar wind. This would enable near-continuous monitoring of the nearest stellar systems in the search for the radio signatures of coronal mass ejections and energetic particle events, and would also detect the magnetospheres for the nearest candidate habitable exoplanets. Simultaneously, FARSIDE would be used to characterize similar activity in our own solar system, from the Sun to the outer planets. Through precision calibration via an orbiting beacon, and exquisite foreground characterization, FARSIDE would also measure the Dark Ages global 21-cm signal at redshifts from 50-100. It will also be a pathfinder for a larger 21-cm power spectrum instrument by carefully measuring the foreground with high dynamic range

Finding New Cell Wall Regulatory Genes in Populus trichocarpa Using Multiple Lines of Evidence

Understanding the regulatory network controlling cell wall biosynthesis is of great interest in Populus trichocarpa, both because of its status as a model woody perennial and its importance for lignocellulosic products. We searched for genes with putatively unknown roles in regulating cell wall biosynthesis using an extended network-based Lines of Evidence (LOE) pipeline to combine multiple omics data sets in P. trichocarpa, including gene coexpression, gene comethylation, population level pairwise SNP correlations, and two distinct SNP-metabolite Genome Wide Association Study (GWAS) layers. By incorporating validation, ranking, and filtering approaches we produced a list of nine high priority gene candidates for involvement in the regulation of cell wall biosynthesis. We subsequently performed a detailed investigation of candidate gene GROWTH-REGULATING FACTOR 9 (PtGRF9). To investigate the role of PtGRF9 in regulating cell wall biosynthesis, we assessed the genome-wide connections of PtGRF9 and a paralog across data layers with functional enrichment analyses, predictive transcription factor binding site analysis, and an independent comparison to eQTN data. Our findings indicate that PtGRF9 likely affects the cell wall by directly repressing genes involved in cell wall biosynthesis, such as PtCCoAOMT and PtMYB.41, and indirectly by regulating homeobox genes. Furthermore, evidence suggests that PtGRF9 paralogs may act as transcriptional co-regulators that direct the global energy usage of the plant. Using our extended pipeline, we show multiple lines of evidence implicating the involvement of these genes in cell wall regulatory functions and demonstrate the value of this method for prioritizing candidate genes for experimental validation

FARSIDE: A Low Radio Frequency Interferometric Array on the Lunar Farside

FARSIDE (Farside Array for Radio Science Investigations of the Dark ages and Exoplanets) is a Probe-class concept to place a low radio frequency interferometric array on the farside of the Moon. A NASA-funded design study, focused on the instrument, a deployment rover, the lander and base station, delivered an architecture broadly consistent with the requirements for a Probe mission. This notional architecture consists of 128 dual polarization antennas deployed across a 10 km area by a rover, and tethered to a base station for central processing, power and data transmission to the Lunar Gateway. FARSIDE would provide the capability to image the entire sky each minute in 1400 channels spanning frequencies from 100 kHz to 40 MHz, extending down two orders of magnitude below bands accessible to ground-based radio astronomy. The lunar farside can simultaneously provide isolation from terrestrial radio frequency interference, auroral kilometric radiation, and plasma noise from the solar wind. This would enable near-continuous monitoring of the nearest stellar systems in the search for the radio signatures of coronal mass ejections and energetic particle events, and would also detect the magnetospheres for the nearest candidate habitable exoplanets. Simultaneously, FARSIDE would be used to characterize similar activity in our own solar system, from the Sun to the outer planets, including the hypothetical Planet Nine. Through precision calibration via an orbiting beacon, and exquisite foreground characterization, FARSIDE would also measure the Dark Ages global 21-cm signal at redshifts z=50-100. The unique observational window offered by FARSIDE would enable an abundance of additional science ranging from sounding of the lunar subsurface to characterization of the interstellar medium in the solar system neighborhood

Treatment outcomes 24 months after initiating short, all-oral bedaquiline-containing or injectable-containing rifampicin-resistant tuberculosis treatment regimens in South Africa : a retrospective cohort study

DATA SHARING : The data used for this analysis in the form of deidentified participant data and a data dictionary will be made available after publication. Investigators wishing to access these data will need to have an approved research proposal and complete a data access agreement. All inquiries should be sent to the corresponding author ([email protected] or [email protected]).SUPPLEMENTARY MATERIAL 1 : French translation of the abstract. SUPPLEMENTARY MATERIAL 2 : Appendices.BACKGROUND : There is a need for short and safe all-oral treatment of rifampicin-resistant tuberculosis. We compared outcomes up to 24 months after treatment initiation for patients with rifampicin-resistant tuberculosis in South Africa treated with a short, all-oral bedaquiline-containing regimen (bedaquiline group), or a short, injectable-containing regimen (injectable group). METHODS : Patients with rifampicin-resistant tuberculosis, aged 18 years or older, eligible for a short regimen starting treatment between Jan 1 and Dec 31, 2017, with a bedaquiline-containing or WHO recommended injectable-containing treatment regimen of 9–12 months, registered in the drug-resistant tuberculosis database (EDRWeb), and with known age, sex, HIV status, and national identification number were eligible for study inclusion; patients receiving linezolid, carbapenems, terizidone or cycloserine, delamanid, or para-aminosalicylic acid were excluded. Bedaquiline was given at a dose of 400 mg once daily for two weeks followed by 200 mg three times a week for 22 weeks. To compare regimens, patients were exactly matched on HIV and ART status, previous tuberculosis treatment history, and baseline acid-fast bacilli smear and culture result, while propensity score matched on age, sex, province of treatment, and isoniazid-susceptibility status. We did binomial linear regression to estimate adjusted risk differences (aRD) and 95% CIs for 24-month outcomes, which included: treatment success (ie, cure or treatment completion without evidence of recurrence) versus all other outcomes, survival versus death, disease free survival versus survival with treatment failure or recurrence, and loss to follow-up versus all other outcomes. FINDINGS : Overall, 1387 (14%) of 10152 patients with rifampicin-resistant tuberculosis treated during 2017 met inclusion criteria; 688 in the bedaquiline group and 699 in the injectable group. Four patients (1%) had treatment failure or recurrence, 44 (6%) were lost to follow-up, and 162 (24%) died in the bedaquiline group, compared with 17 (2%), 87 (12%), and 199 (28%), respectively, in the injectable group. In adjusted analyses, treatment success was 14% (95% CI 8–20) higher in the bedaquiline group than in the injectable group (70% vs 57%); loss to follow-up was 4% (1–8) lower in the bedaquiline group (6% vs 12%); and disease-free survival was 2% (0–5) higher in the bedaquiline group (99% vs 97%). The bedaquiline group had 8% (4–11) lower risk of mortality during treatment (17·0% vs 22·4%), but there was no difference in mortality post-treatment. INTERPRETATION : Patients in the bedaquiline group experienced significantly higher rates of treatment success at 24 months. This finding supports the use of short bedaquiline-containing regimens in eligible patients.WHO Global TB Programme.http://www.thelancet.com/infectionhj2023Medical Microbiolog

Using iterative random forest to find geospatial environmental and Sociodemographic predictors of suicide attempts

IntroductionDespite a recent global decrease in suicide rates, death by suicide has increased in the United States. It is therefore imperative to identify the risk factors associated with suicide attempts to combat this growing epidemic. In this study, we aim to identify potential risk factors of suicide attempt using geospatial features in an Artificial intelligence framework.MethodsWe use iterative Random Forest, an explainable artificial intelligence method, to predict suicide attempts using data from the Million Veteran Program. This cohort incorporated 405,540 patients with 391,409 controls and 14,131 attempts. Our predictive model incorporates multiple climatic features at ZIP-code-level geospatial resolution. We additionally consider demographic features from the American Community Survey as well as the number of firearms and alcohol vendors per 10,000 people to assess the contributions of proximal environment, access to means, and restraint decrease to suicide attempts. In total 1,784 features were included in the predictive model.ResultsOur results show that geographic areas with higher concentrations of married males living with spouses are predictive of lower rates of suicide attempts, whereas geographic areas where males are more likely to live alone and to rent housing are predictive of higher rates of suicide attempts. We also identified climatic features that were associated with suicide attempt risk by age group. Additionally, we observed that firearms and alcohol vendors were associated with increased risk for suicide attempts irrespective of the age group examined, but that their effects were small in comparison to the top features.DiscussionTaken together, our findings highlight the importance of social determinants and environmental factors in understanding suicide risk among veterans

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text