A Relationship between Supermassive Black Hole Mass and the Total Gravitational Mass of the Host Galaxy

We investigate the correlation between the mass of a central supermassive black hole and the total gravitational mass of the host galaxy (M_tot). The results are based on 43 galaxy-scale strong gravitational lenses from the Sloan Lens ACS (SLACS) Survey whose black hole masses were estimated through two scaling relations: the relation between black hole mass and Sersic index (M_bh - n) and the relation between black hole mass and stellar velocity dispersion (M_bh - sigma). We use the enclosed mass within R_200, the radius within which the density profile of the early type galaxy exceeds the critical density of the Universe by a factor of 200, determined by gravitational lens models fitted to HST imaging data, as a tracer of the total gravitational mass. The best fit correlation, where M_bh is determined from M_bh - sigma relation, is log(M_bh) = (8.18 +/- 0.11) + (1.55 +/- 0.31) (log(M_tot) - 13.0) over 2 orders of magnitude in M_bh. From a variety of tests, we find that we cannot reliably infer a connection between M_bh and M_tot from the M_bh - n relation. The M_bh - M_tot relation provides some of the first, direct observational evidence to test the prediction that supermassive black hole properties are determined by the halo properties of the host galaxy.Comment: 29 pages, 10 figures, Accepted for publication in Ap

Scara1 deficiency impairs clearance of soluble Amyloid-β by mononuclear phagocytes and accelerates Alzheimer’s-like disease progression

In Alzheimer’s disease soluble amyloid beta (sAβ) causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of sAβ are not known. Here we use shRNA screening and identify the scavenger receptor Scara1 as a receptor for sAβ expressed on myeloid cells. To determine the role of Scara1 in clearance of sAβ in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer’s disease and generate PS1-APP- Scara1-deficient mice. Scara1 deficiency markedly accelerates Aβ accumulation leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases Aβ clearance. This approach is a potential treatment strategy for Alzheimer’s disease

Scara1 deficiency impairs clearance of soluble Amyloid-β by mononuclear phagocytes and accelerates Alzheimer’s-like disease progression

In Alzheimer’s disease soluble amyloid beta (sAβ) causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of sAβ are not known. Here we use shRNA screening and identify the scavenger receptor Scara1 as a receptor for sAβ expressed on myeloid cells. To determine the role of Scara1 in clearance of sAβ in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer’s disease and generate PS1-APP- Scara1-deficient mice. Scara1 deficiency markedly accelerates Aβ accumulation leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases Aβ clearance. This approach is a potential treatment strategy for Alzheimer’s disease

Targeted expression of a dominant-negative fibroblast growth factor (FGF) receptor in gonadotropin-releasing hormone (GnRH) neurons reduces FGF responsiveness and the size of GnRH neuronal population

Increasing evidence suggests that fibroblast growth factors (FGFs) are neurotrophic in GnRH neurons. However, the extent to which FGFs are involved in establishing a functional GnRH system in the whole organism has not been investigated. In this study, transgenic mice with the expression of a dominant-negative FGF receptor mutant (FGFRm) targeted to GnRH neurons were generated to examine the consequence of disrupted FGF signaling on the formation of the GnRH system. To first test the effectiveness of this strategy, GT1 cells, a GnRH neuronal cell line, were stably transfected with FGFRm. The transfected cells showed attenuated neurite outgrowth, diminished FGF-2 responsiveness in a cell survival assay, and blunted activation of the signaling pathway in response to FGF-2. Transgenic mice expressing FGFRm in a GnRH neuron-specific manner exhibited a 30% reduction in GnRH neuron number, but the anatomical distribution of GnRH neurons was unaltered. Although these mice were initially fertile, they displayed several reproductive defects, including delayed puberty, reduced litter size, and early reproductive senescence. Overall, our results are the first to show, at the level of the organism, that FGFs are one of the important components involved in the formation and maintenance of the GnRH system

Engagement and Action for Health: The Contribution of Leaders’ Collaborative Skills to Partnership Success

A multi-site evaluation (survey) of five Kellogg-funded Community Partnerships (CPs) in South Africa was undertaken to explore the relationship between leadership skills and a range of 30 operational, functional and organisational factors deemed critical to successful CPs. The CPs were collaborative academic-health service-community efforts aimed at health professions education reforms. The level of agreement to eleven dichotomous (‘Yes/No’) leadership skills items was used to compute two measures of members’ appreciation of their CPs’ leadership. The associations between these measures and 30 CPs factors were explored, and the partnership factors that leadership skills explained were assessed after controlling. Respondents who perceived the leadership of their CPs favourably had more positive ratings across 30 other partnership factors than those who rated leadership skills less favourably, and were more likely to report a positive cost/ benefit ratio. In addition, respondents who viewed their CPs’ leadership positively also rated the operational understanding, the communication mechanisms, as well as the rules and procedures of the CPs more favourably. Leadership skills explained between 20% and 7% of the variance of 10 partnership factors. The influence of leaders’ skills in effective health-focussed partnerships is much broader than previously conceptualised

Halo density reduction by baryonic settling?

We test the proposal by El-Zant et al that the dark matter density of halos could be reduced through dynamical friction acting on heavy baryonic clumps in the early stages of galaxy formation. Using N-body simulations, we confirm that the inner halo density cusp is flattened to 0.2 of the halo break radius by the settling of a single clump of mass \ga 0.5% of the halo mass. We also find that an ensemble of 50 clumps each having masses \ga 0.2% can flatten the cusp to almost the halo break radius on a time scale of \sim9 Gyr, for an NFW halo of concentration 15. We summarize some of the difficulties that need to be overcome if this mechanism is to resolve the apparent conflict between the observed inner densities of galaxy halos and the predictions of LCDM.Comment: 7 pages, 6 figures, uses emulateap

Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease : a prospective cohort study

Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function. Patients and methods : In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates. Results : During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1. Conclusion : sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease

Acquired Rifamycin Resistance with Twice-Weekly Treatment of HIV-related Tuberculosis

Rationale: Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study. Objective: To evaluate the activity of intermittent rifabutin-based therapy. Methods: Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly, or twice-weekly per the local tuberculosis control program), followed by 4 mo of twice-weekly rifabutin plus isoniazid. Measurements: Culture-positive treatment failure or relapse. Main Results: A total of 169 eligible patients were enrolled. Most had advanced HIV disease; the median CD4 cell count and HIV-RNA level were 90 cells/mm3 (interquartile range, 35–175) and 5.3 log10 copies/ml (interquartile range, 4.8–5.7), respectively. Nine (5.3%) patients had culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these nine (89%) cases had isolates with acquired rifamycin resistance. Treatment failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3% (9/73; 95% confidence interval, 6.5–22.0%) among patients with CD4 < 100 cells/mm3 versus 0% (0/65; 95% confidence interval, 0.0–4.5%) among those with higher CD4 lymphocyte counts (p < 0.01). One hundred thirty-seven (81%) patients received antiretroviral therapy during TB treatment. Adverse events were common, but only two patients (1%) permanently discontinued study drugs

The Impact of Feedback on Disk Galaxy Scaling Relations

We use a disk galaxy evolution model to investigate the impact of mass outflows (a.k.a. feedback) on disk galaxy scaling relations. Our model follows the accretion, cooling, star formation and ejection of baryonic mass inside growing dark matter haloes, with cosmologically motivated specific angular momentum distributions. Models without feedback produce disks that are too small and rotate too fast. Feedback reduces the baryonic masses of galaxies, resulting in larger disks with lower rotation velocities. Models with feedback can reproduce the zero points of the scaling relations between rotation velocity, stellar mass and disk size, but only in the absence of adiabatic contraction. Our feedback mechanism is maximally efficient in expelling mass, but our successful models require 25% of the SN energy, or 100% of the SN momentum, to drive the outflows. It remains to be seen whether such high efficiencies are realistic or not. Our energy and momentum driven wind models result in different slopes of various scaling relations, such as size - stellar mass, stellar mass - halo mass, and metallicity - stellar mass. Observations favor the energy driven wind at stellar masses below Mstar = 10^{10.5} Msun, but the momentum driven wind model at high masses. The ratio between the specific angular momentum of the baryons to that of the halo, (j_gal/m_gal), is not unity in our models. Yet this is the standard assumption in models of disk galaxy formation. Feedback preferentially ejects low angular momentum material because star formation is more efficient at smaller galactic radii. This results in (j_gal/m_gal) increasing with decreasing halo mass. This effect helps to resolve the discrepancy between the high spin parameters observed for dwarf galaxies with the low spin parameters predicted from LCDM. [Abridged]Comment: 27 pages, 16 figures, accepted to MNRAS, two new figure

Factors Associated with Opioid Overdose after an Initial Opioid Prescription

Importance: The opioid epidemic continues to be a public health crisis in the US. Objective: To assess the patient factors and early time-varying prescription-related factors associated with opioid-related fatal or nonfatal overdose. Design, Setting, and Participants: This cohort study evaluated opioid-naive adult patients in Oregon using data from the Oregon Comprehensive Opioid Risk Registry, which links all payer claims data to other health data sets in the state of Oregon. The observational, population-based sample filled a first (index) opioid prescription in 2015 and was followed up until December 31, 2018. Data analyses were performed from March 1, 2020, to June 15, 2021. Exposures: Overdose after the index opioid prescription. Main Outcomes and Measures: The outcome was an overdose event. The sample was followed up to identify fatal or nonfatal opioid overdoses. Patient and prescription characteristics were identified. Prescription characteristics in the first 6 months after the index prescription were modeled as cumulative, time-dependent measures that were updated monthly through the sixth month of follow-up. A time-dependent Cox proportional hazards regression model was used to assess patient and prescription characteristics that were associated with an increased risk for overdose events. Results: The cohort comprised 236921 patients (133 839 women [56.5%]), of whom 667 (0.3%) experienced opioid overdose. Risk of overdose was highest among individuals 75 years or older (adjusted hazard ratio [aHR], 3.22; 95% CI, 1.94-5.36) compared with those aged 35 to 44 years; men (aHR, 1.29; 95% CI, 1.10-1.51); those who were dually eligible for Medicaid and Medicare Advantage (aHR, 4.37; 95% CI, 3.09-6.18), had Medicaid (aHR, 3.77; 95% CI, 2.97-4.80), or had Medicare Advantage (aHR, 2.18; 95% CI, 1.44-3.31) compared with those with commercial insurance; those with comorbid substance use disorder (aHR, 2.74; 95% CI, 2.15-3.50), with depression (aHR, 1.26; 95% CI, 1.03-1.55), or with 1 to 2 comorbidities (aHR, 1.32; 95% CI, 1.08-1.62) or 3 or more comorbidities (aHR, 1.90; 95% CI, 1.42-2.53) compared with none. Patients were at an increased overdose risk if they filled oxycodone (aHR, 1.70; 95% CI, 1.04-2.77) or tramadol (aHR, 2.80; 95% CI, 1.34-5.84) compared with codeine; used benzodiazepines (aHR, 1.06; 95% CI, 1.01-1.11); used concurrent opioids and benzodiazepines (aHR, 2.11; 95% CI, 1.70-2.62); or filled opioids from 3 or more pharmacies over 6 months (aHR, 1.38; 95% CI, 1.09-1.75). Conclusions and Relevance: This cohort study used a comprehensive data set to identify patient and prescription-related risk factors that were associated with opioid overdose. These findings may guide opioid counseling and monitoring, the development of clinical decision-making tools, and opioid prevention and treatment resources for individuals who are at greatest risk for opioid overdose