The Black Hole Mass and Extreme Orbital Structure in NGC1399

The largest galaxies, and in particular central galaxies in clusters, offer unique insight into understanding the mechanism for the growth of nuclear black holes. We present Hubble Space Telescope kinematics for NGC1399, the central galaxy in Fornax. We find the best-fit model contains a black hole of 5.1 +-0.7 x 10^8 Msun (at a distance of 21.1 Mpc), a factor of over 2 below the correlation of black hole mass and velocity dispersion. We also find a dramatic signature for central tangential anisotropy. The velocity profiles on adjacent sides 0.5" away from the nucleus show strong bimodality, and the central spectrum shows a large drop in the dispersion. Both of these observations point to an orbital distribution that is tangentially biased. The best-fit orbital model suggests a ratio of the tangential to radial internal velocity dispersions of three. This ratio is the largest seen in any galaxy to date and will provide an important measure for the mode by which the central black hole has grown.Comment: 9 pages, accepted for publication in the Astrophysical Journa

A nonlinear and time-dependent leak current in the presence of calcium fluoride patch-clamp seal enhancer [version 1; peer review: 2 approved with reservations]

Automated patch-clamp platforms are widely used and vital tools in both academia and industry to enable high-throughput studies such as drug screening. A leak current to ground occurs whenever the seal between a pipette and cell (or internal solution and cell in high-throughput machines) is not perfectly insulated from the bath (extracellular) solution. Over 1 GΩ seal resistance between pipette and bath solutions is commonly used as a quality standard for manual patch work. With automated platforms it can be difficult to obtain such a high seal resistance between the intra- and extra-cellular solutions. One suggested method to alleviate this problem is using an F− containing internal solution together with a Ca2+ containing external solution — so that a CaF2 crystal forms when the two solutions meet which ‘plugs the holes’ to enhance the seal resistance. However, we observed an unexpected nonlinear-in-voltage and time-dependent current using these solutions on an automated patch-clamp platform. We performed manual patch-clamp experiments with the automated patch-clamp solutions, but no biological cell, and observed the same nonlinear time-dependent leak current. The current could be completely removed by washing out F− ions to leave a conventional leak current that was linear and not time-dependent. We therefore conclude fluoride ions interacting with the CaF2 crystal are the origin of the nonlinear time-dependent leak current. The consequences of such a nonlinear and time-dependent leak current polluting measurements should be considered carefully if it cannot be isolated and subtracted

Pre-treatment preferences and characteristics among patients seeking in vitro fertilisation

BACKGROUND: This study sought to describe patient features before beginning fertility treatment, and to ascertain their perceptions relative to risk of twin pregnancy outcomes associated with such therapy. METHODS: Data on readiness for twin pregnancy outcome from in vitro fertilisation (IVF) was gathered from men and women before initiating fertility treatment by anonymous questionnaire. RESULTS: A total of 206 women and 204 men were sampled. Mean (+/- SD) age for women and men being 35.5 +/- 5 and 37.3 +/- 7 yrs, respectively. At least one IVF cycle had been attempted by 27.2% of patients and 33.9% of this subgroup had initiated >/=3 cycles, reflecting an increase in previous failed cycles over five years. Good agreement was noted between husbands and wives with respect to readiness for twins from IVF (77% agreement; Cohen's K = 0.61; 95% CI 0.53 to 0.70). CONCLUSION: Most patients contemplating IVF already have ideas about particular outcomes even before treatment begins, and suggests that husbands and wives are in general agreement on their readiness for twin pregnancy from IVF. However, fertility patients now may represent a more refractory population and therefore carry a more guarded prognosis. Patient preferences identified before IVF remain important, but further studies comparing pre- and post-treatment perceptions are needed

Race/Ethnicity and Retention in Traumatic Brain Injury Outcomes Research: A Traumatic Brain Injury Model Systems National Database Study

Objective: To investigate the contribution of race/ethnicity to retention in traumatic brain injury (TBI) research at 1 to 2 years post-injury. Setting: Community. Participants: 5548 Whites, 1347 Blacks, and 790 Hispanics enrolled in the Traumatic Brain Injury Model Systems National Database with dates of injury between October 1, 2002 and March 31, 2013. Design: Retrospective database analysis. Main Measure: Retention, defined as completion of at least one question on the follow-up interview by the person with TBI or a proxy. Results: Retention rates 1-2 years post-TBI were significantly lower for Hispanic (85.2%) than for White (91.8%) or Black participants (90.5%) and depended significantly on history of problem drug or alcohol use. Other variables associated with low retention included older age, lower education, violent cause of injury, and discharge to an institution versus private residence. Conclusions: The findings emphasize the importance of investigating retention rates separately for Blacks and Hispanics rather than combining them or grouping either with other races or ethnicities. The results also suggest the need for implementing procedures to increase retention of Hispanics in longitudinal TBI researc

Association Between Benign Breast Disease in African American and White American Women and Subsequent Triple-Negative Breast Cancer

Importance: Compared with white American (WA) women, African American (AA) women have a 2-fold higher incidence of breast cancers that are negative for estrogen receptor, progesterone receptor, and ERBB2 (triple-negative breast cancer [TNBC]). Triple-negative breast cancer, compared with non-TNBC, likely arises from different pathogenetic pathways, and benign breast disease (BBD) predicts future non-TNBC. Objective: To determine whether AA identity remains associated with TNBC for women with a prior diagnosis of BBD. Design, Setting, and Participants: This study is a retrospective analysis of data of a cohort of 2588 AA and 3566 WA women aged between 40 and 70 years with a biopsy-proven BBD diagnosis. The data-obtained from the Pathology Information System of Henry Ford Health System (HFHS), an integrated multihospital and multispecialty health care system headquartered in Detroit, Michigan-include specimens of biopsies performed between January 1, 1994, and December 31, 2005. Data analysis was performed from November 1, 2015, to June 15, 2016. Main Outcomes and Measures: Subsequent breast cancer was stratified on the basis of combinations of hormone receptor and ERBB2 expression. Results: Case management, follow-up, and outcomes received or obtained by our cohort of 2588 AA and 3566 WA patients were similar, demonstrating that HFHS delivered care equitably. Subsequent breast cancers developed in 103 (4.1%) of AA patients (mean follow-up interval of 6.8 years) and 143 (4.0%) of WA patients (mean follow-up interval of 6.1 years). More than three-quarters of subsequent breast cancers in each subset were ductal carcinoma in situ or stage I. The 10-year probability estimate for developing TNBC was 0.56% (95% CI, 0.32%-1.0%) for AA patients and 0.25% (95% CI, 0.12%-0.53%) for WA patients. Among the 66 AA patients who developed subsequent invasive breast cancer, 16 (24.2%) developed TNBC compared with 7 (7.4%) of the 94 WA patients who developed subsequent invasive breast cancers and had complete biomarker data (P = .01). Conclusions and Relevance: This study is the largest analysis to date of TNBC in the context of racial/ethnic identity and BBD as risk factors. The study found that AA identity persisted as a significant risk factor for TNBC. This finding suggests that AA identity is associated with inherent susceptibility for TNBC pathogenetic pathways

Empirical Quantification of Predictive Uncertainty Due to Model Discrepancy by Training with an Ensemble of Experimental Designs: An Application to Ion Channel Kinetics

When using mathematical models to make quantitative predictions for clinical or industrial use, it is important that predictions come with a reliable estimate of their accuracy (uncertainty quantification). Because models of complex biological systems are always large simplifications, model discrepancy arises—models fail to perfectly recapitulate the true data generating process. This presents a particular challenge for making accurate predictions, and especially for accurately quantifying uncertainty in these predictions. Experimentalists and modellers must choose which experimental procedures (protocols) are used to produce data used to train models. We propose to characterise uncertainty owing to model discrepancy with an ensemble of parameter sets, each of which results from training to data from a different protocol. The variability in predictions from this ensemble provides an empirical estimate of predictive uncertainty owing to model discrepancy, even for unseen protocols. We use the example of electrophysiology experiments that investigate the properties of hERG potassium channels. Here, ‘information-rich’ protocols allow mathematical models to be trained using numerous short experiments performed on the same cell. In this case, we simulate data with one model and fit it with a different (discrepant) one. For any individual experimental protocol, parameter estimates vary little under repeated samples from the assumed additive independent Gaussian noise model. Yet parameter sets arising from the same model applied to different experiments conflict—highlighting model discrepancy. Our methods will help select more suitable ion channel models for future studies, and will be widely applicable to a range of biological modelling problems

Outcome Assessment of a Dedicated HIV Positive Health Care Worker Clinic at a Central Hospital in Malawi: A Retrospective Observational Study

BACKGROUND: Malawi has one of the world's lowest densities of Health Care Workers (HCW) per capita. This study evaluates outcomes of a dedicated HCW HIV clinic in Malawi, created at Zomba Central Hospital in January 2007. METHODS AND FINDINGS: Retrospective cohort data was analyzed comparing HCW clinic patient baseline characteristics and treatment outcomes at 18 months after inception, against those attending the general HIV clinic. In-depth interviews and focus group discussions were conducted to explore perceptions of patients and caregivers regarding program value, level of awareness and barriers for uptake amongst HCW. 306 patients were enrolled on antiretroviral therapy (ART) in the HCW HIV clinic, 6784 in the general clinic. Significantly (p<0.01) more HCW clients were initiated on ART on the basis of CD4 as opposed to WHO Stage 3/4 (36% vs.23%). Significantly fewer HCW clients defaulted (6% vs.17%), and died (4% vs.12%). The dedicated HCW HIV clinic was perceived as important and convenient in terms of reduced waiting times, and prompt and high quality care. Improved confidentiality was an appreciated quality of the HCW clinic however barriers included fear of being recognized. CONCLUSIONS/SIGNIFICANCE: Outcomes at the HCW clinic appear better compared to the general HIV clinic. The strategy of dedicated clinics to care for health providers is a means of HIV impact mitigation within human resource constrained health systems in high prevalence settings