Analytic Gradients for Complete Active Space Pair-Density Functional Theory

Analytic gradient routines are a desirable feature for quantum mechanical methods, allowing for efficient determination of equilibrium and transition state structures and several other molecular properties. In this work, we present analytical gradients for multiconfiguration pair-density functional theory (MC-PDFT) when used with a state-specific complete active space self-consistent field reference wave function. Our approach constructs a Lagrangian that is variational in all wave function parameters. We find that MC-PDFT locates equilibrium geometries for several small- to medium-sized organic molecules that are similar to those located by complete active space second-order perturbation theory but that are obtained with decreased computational cost

Exploring the Structures and Substructures of the Andromeda Satellite Dwarf Galaxies Cassiopeia III, Perseus I, and Lacerta I

We present results from wide-field imaging of the resolved stellar populations of the dwarf spheroidal galaxies Cassiopeia III (And XXXII) and Perseus I (And XXXIII), two satellites in the outer stellar halo of the Andromeda galaxy (M31). Our WIYN pODI photometry traces the red giant star population in each galaxy to ∼2.5−3 half-light radii from the galaxy center. We use the tip of the red giant branch (TRGB) method to derive distances of (m − M) = 24.62 ± 0.12 mag (839 kpc, or 156 kpc from M31) for Cas III and 24.47 ± 0.13 mag (738 kpc, or 351 kpc from M31) for Per I. These values are consistent within the errors with TRGB distances derived from a deeper Hubble Space Telescope study of the galaxies’ inner regions. For each galaxy, we derive structural parameters, total magnitude, and central surface brightness. We also place upper limits on the ratio of neutral hydrogen gas mass to optical luminosity, confirming the gas-poor nature of both galaxies. We combine our data set with corresponding data for the M31 satellite galaxy Lacerta I (And XXXI) from earlier work and search for substructure within the RGB star populations of Cas III, Per I, and Lac I. We find an overdense region on the west side of Lac I at a significance level of 2.5σ–3σ and a low-significance filament extending in the direction of M31. In Cas III, we identify two modestly significant overdensities near the center of the galaxy and another at two half-light radii. Per I shows no evidence for substructure in its RGB star population, which may reflect this galaxy’s isolated nature. © 2023 Institute of Physics Publishing. All rights reservedThe authors wish to thank the anonymous referee for providing valuable comments and suggestions for improvements to the manuscript. We are grateful to the staff of the WIYN 3.5 m Observatory and Kitt Peak National Observatory for their help during our WIYN pODI observing runs. We also thank the staff members at WIYN, NOIRLab, and Indiana University Pervasive Technology Institute for designing and implementing the ODI Pipeline, Portal, and Archive (ODI-PPA) and assisting us with the pODI data reduction. We made use of the odi-tools python package, written by William Janesh and Owen Boberg, to produce final stacked science-ready WIYN pODI images for this study. K.L.R. and N.J.S. were supported by NSF Astronomy & Astrophysics Research grant No. AST-1615483 during part of the period when this research was carried out. Research by D.C. is supported by NSF grant AST-1814208. K.S. acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC). We are grateful to the Indiana University (IU) College of Arts and Sciences for funding IU's share of the WIYN 3.5 m telescope. This research has made use of the NASA/IPAC Extragalactic Database (NED), which is funded by the National Aeronautics and Space Administration and operated by the California Institute of Technology

Exploring the Structures and Substructures of the Andromeda Satellite Dwarf Galaxies Cassiopeia III, Perseus I, and Lacerta I

We present results from wide-field imaging of the resolved stellar populations of the dwarf spheroidal galaxies Cassiopeia III (And XXXII) and Perseus I (And XXXIII), two satellites in the outer stellar halo of the Andromeda galaxy (M31). Our WIYN pODI photometry traces the red giant star population in each galaxy to ~2.5-3 half-light radii from the galaxy center. We use the Tip of the Red Giant Branch (TRGB) method to derive distances of (m-M)_0 = 24.62+/-0.12 mag (839 (+48,-450) kpc, or 156 (+16,-13) kpc from M31) for Cas III and 24.47+/-0.13 mag (738 (+48,-45) kpc, or 351 (+17,-16) kpc from M31) for Per I. These values are consistent within the errors with TRGB distances derived from a deeper Hubble Space Telescope study of the galaxies' inner regions. For each galaxy, we derive structural parameters, total magnitude, and central surface brightness. We also place upper limits on the ratio of neutral hydrogen gas mass to optical luminosity, confirming the gas-poor nature of both galaxies. We combine our data set with corresponding data for the M31 satellite galaxy Lacerta I (And XXXI) from earlier work, and search for substructure within the RGB star populations of Cas III, Per I, and Lac I. We find an overdense region on the west side of Lac I at a significance level of 2.5-3-sigma and a low-significance filament extending in the direction of M31. In Cas III, we identify two modestly significant overdensities near the center of the galaxy and another at two half-light radii. Per I shows no evidence for substructure in its RGB star population, which may reflect this galaxy's isolated nature.Comment: 26 pages, 15 figures, 5 tables. Accepted for publication in The Astronomical Journa

Strength in numbers : patient experiences of group exercise within hospice palliative care

Background: Exercise is increasingly recognized as a core component of palliative rehabilitation. The group exercise model is often adopted as a means of reaching more patients with limited resource. Despite the growth of quantitative research examining this area of practice, few qualitative studies have looked at the patient experience of participating in group exercise in a palliative setting, and most exclude patients with a non-cancer diagnosis. Methods: The aim of this study was to explore patients’ experiences of participating in group exercise classes in a hospice setting. In this qualitative, phenomenological study, nine patients participating in a group exercise programme at a South London hospice completed semi-structured interviews. Participants were purposively sampled by gender, age, ethnicity and diagnosis; to include diagnoses across cancer, respiratory and neurological conditions. Transcripts were interpreted using thematic analysis. Results: All patients reported positive experiences of participating in group exercise classes. Improvements reported in physical function had a positive effect on ability to complete activities of daily living and enhanced patient mood. Other reported psychosocial benefits included: promotion of self-management; space and opportunity for reflection; supportive relationships; sharing of information; and a deeper appreciation of patients’ own abilities. Conclusion: This study highlights the positive experiences and value of group exercise classes to groups of people with diverse cancer and non-cancer conditions. The physical, emotional and psychosocial benefits suggest hospices and other palliative services should explore similar programmes as part of their rehabilitation services. The recognition that exercise groups can be mixed and need not be bespoke to one condition has positive cost and staff resource ramifications

Store-operated calcium entry controls innate and adaptive immune cell function in inflammatory bowel disease

Inflammatory bowel disease (IBD) is characterized by dysregulated intestinal immune responses. Using mass cytometry (CyTOF) to analyze the immune cell composition in the lamina propria (LP) of patients with ulcerative colitis (UC) and Crohn's disease (CD), we observed an enrichment of CD(4+) effector T cells producing IL-17A and TNF, CD(8+) T cells producing IFNγ, T regulatory (Treg) cells, and innate lymphoid cells (ILC). The function of these immune cells is regulated by store-operated Ca(2+) entry (SOCE), which results from the opening of Ca(2+) release-activated Ca(2+) (CRAC) channels formed by ORAI and STIM proteins. We observed that the pharmacologic inhibition of SOCE attenuated the production of proinflammatory cytokines including IL-2, IL-4, IL-6, IL-17A, TNF, and IFNγ by human colonic T cells and ILCs, reduced the production of IL-6 by B cells and the production of IFNγ by myeloid cells, but had no effect on the viability, differentiation, and function of intestinal epithelial cells. T cell-specific deletion of CRAC channel genes in mice showed that Orai1, Stim1, and Stim2-deficient T cells have quantitatively distinct defects in SOCE, which correlate with gradually more pronounced impairment of cytokine production by Th1 and Th17 cells and the severity of IBD. Moreover, the pharmacologic inhibition of SOCE with a selective CRAC channel inhibitor attenuated IBD severity and colitogenic T cell function in mice. Our data indicate that SOCE inhibition may be a suitable new approach for the treatment of IBD

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD.

Objective: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

ngVLA Key Science Goal 5 Understanding the Formation and Evolution of Black Holes in the Era of Multi-Messenger Astronomy

The next-generation Very Large Array (ngVLA) will be a powerful telescope for finding and studying black holes across the entire mass range. High-resolution imaging abilities will allow the separation of low-luminosity black holes in the local Universe from background sources, thereby providing critical constraints on the mass function, formation, and growth of black holes. Its combination of sensitivity and angular resolution will provide new constraints on the physics of black hole accretion and jet formation. Combined with facilities across the spectrum and gravitational wave observatories, the ngVLA will provide crucial constraints on the interaction of black holes with their environments, with specific implications for the relationship between evolution of galaxies and the emission of gravitational waves from in-spiraling supermassive black holes and potential implications for stellar mass and intermediate mass black holes. The ngVLA will identify the radio counterparts to transient sources discovered by electromagnetic, gravitational wave, and neutrino observatories, and its high-resolution, fast-mapping capabilities will make it the preferred instrument to pinpoint electromagnetic counterparts to events such as supermassive black hole mergers. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration

Connecting the Dots: a cluster-randomized clinical trial integrating standardized autism spectrum disorders screening, high-quality treatment, and long-term outcomes.

BackgroundAutism spectrum disorder (ASD) affects one in 54 children in the United States of America, and supporting people with ASD across the lifespan presents challenges that impact individuals, families, and communities and can be quite costly. The American Academy of Pediatrics has issued recommendations for routine ASD screening at 18 and 24 months, but some research suggests that few pediatricians perform high-fidelity, standardized screening universally. Furthermore, the United States Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against universal ASD screening. The objective of this study is to test the hypothesis that children with ASD who have high fidelity; standardized screening will achieve superior outcomes at 5 years of age compared to children receiving usual care ASD detection strategies.MethodsThis is a cluster-randomized, controlled clinical trial in 3 sites in the USA. Pediatric practices will be randomized to implement universal, standardized, high-fidelity toddler screening or usual care, with randomization stratified by the practice size. The study will enroll 3450 children, approximately half in each group. From this sample, we anticipate 100 children to be diagnosed with ASD. Children in both groups receiving an ASD diagnosis will be administered the Early Start Denver Model, an evidence-based early intervention addressing social, communication, and cognitive functioning. Treatment will last for 1 year, with up to 20 h per week of therapy for children with ASD.ResultsPrimary outcomes measured at baseline, following treatment, and at 4 and 5 years of age include ASD symptom severity (Brief Observation of Social Communication Change (BOSCC)) and cognitive functioning (Mullen Scales of Early Learning (MSEL) and Differential Abilities Scale-II (DAS-II)). Secondary outcomes in children include measures of adaptive functioning, ASD symptoms, and kindergarten readiness; secondary analyses will also examine stress and empowerment among parents. Several novel exploratory measures will be included as well. The study will utilize a modified intention-to-treat analysis.ConclusionsThis trial will evaluate the impact of universal, standardized, high-fidelity screening for ASD among children at 18 months of age, with a goal of providing evidence to support this strategy to detect ASD in toddlers in order to start treatment as young as possible and maximize outcomes.Ethics and disseminationThis study was approved by the Institutional Review Board at Drexel University (IRB protocol: 1607004653). All findings will be provided by the principal investigator via email; data will be available through the NIMH Data Archive ( https://nda.nih.gov/ ).Trial registrationClinicalTrials.gov NCT03333629 . Registered on November 7, 2017