The Mass Distribution of Stellar-Mass Black Holes

We perform a Bayesian analysis of the mass distribution of stellar-mass black holes using the observed masses of 15 low-mass X-ray binary systems undergoing Roche lobe overflow and five high-mass, wind-fed X-ray binary systems. Using Markov Chain Monte Carlo calculations, we model the mass distribution both parametrically---as a power law, exponential, gaussian, combination of two gaussians, or log-normal distribution---and non-parametrically---as histograms with varying numbers of bins. We provide confidence bounds on the shape of the mass distribution in the context of each model and compare the models with each other by calculating their relative Bayesian evidence as supported by the measurements, taking into account the number of degrees of freedom of each model. The mass distribution of the low-mass systems is best fit by a power-law, while the distribution of the combined sample is best fit by the exponential model. We examine the existence of a "gap" between the most massive neutron stars and the least massive black holes by considering the value, M_1%, of the 1% quantile from each black hole mass distribution as the lower bound of black hole masses. The best model (the power law) fitted to the low-mass systems has a distribution of lower-bounds with M_1% > 4.3 Msun with 90% confidence, while the best model (the exponential) fitted to all 20 systems has M_1% > 4.5 Msun with 90% confidence. We conclude that our sample of black hole masses provides strong evidence of a gap between the maximum neutron star mass and the lower bound on black hole masses. Our results on the low-mass sample are in qualitative agreement with those of Ozel, et al (2010).Comment: 56 pages, 22 figures, 9 tables, as accepted by Ap

Metformin Treatment Does Not Inhibit Growth of Pancreatic Cancer Patient-Derived Xenografts

There is currently tremendous interest in developing anti-cancer therapeutics targeting cell signaling pathways important for both cancer cell metabolism and growth. Several epidemiological studies have shown that diabetic patients taking metformin have a decreased incidence of pancreatic cancer. This has prompted efforts to evaluate metformin, a drug with negligible toxicity, as a therapeutic modality in pancreatic cancer. Preclinical studies in cell line xenografts and one study in patient-derived xenograft (PDX) models were promising, while recently published clinical trials showed no benefit to adding metformin to combination therapy regimens for locally advanced and metastatic pancreatic cancer. PDX models in which patient tumors are directly engrafted into immunocompromised mice have been shown to be excellent preclinical models for biomarker discovery and therapeutic development. We evaluated the response of four PDX tumor lines to metformin treatment and found that all four of our PDX lines were resistant to metformin. We found that the mechanisms of resistance may occur through lack of sustained activation of adenosine monophosphate-activated protein kinase (AMPK) or downstream reactivation of the mammalian target of rapamycin (mTOR). Moreover, combined treatment with metformin and mTOR inhibitors failed to improve responses in cell lines, which further indicates that metformin alone or in combination with mTOR inhibitors will be ineffective in patients, and that resistance to metformin may occur through multiple pathways. Further studies are required to better understand these mechanisms of resistance and inform potential combination therapies with metformin and existing or novel therapeutics

Effectiveness of nurse‐led group CBT for hot flushes and night sweats in women with breast cancer: results of the MENOS4 randomised controlled trial

Objective Troublesome hot flushes and night sweats (HFNS) are experienced by many women after treatment for breast cancer, impacting significantly on sleep and quality of life. Cognitive behavioural therapy (CBT) is known to be effective for the alleviation of HFNS. However, it is not known if it can effectively be delivered by specialist nurses. We investigated whether group CBT delivered by breast care nurses (BCNs) can reduce the impact of HFNS.MethodsWe recruited women with primary breast cancer following primary treatment with seven or more HFNS/week (including 4/10 or above on the HFNS problem rating scale), from six UK hospitals to an open, randomised, phase 3 effectiveness trial. Participants were randomised to Group CBT or usual care (UC). The primary endpoint was HFNS problem rating at 26 weeks post randomisation. Secondary outcomes included sleep, depression, anxiety and quality of life. ResultsBetween 2017-2018, 130 participants were recruited (CBT:63, control:67). We found a 46% (6.9 to 3.7) reduction in the mean HFNS problem rating score from randomisation to 26 weeks in the CBT arm and a 15% (6.5 to 5.5) reduction in the UC arm (adjusted mean difference -1.96, CI -3.68 to -0.23, p=0.039). Secondary outcomes, including frequency of HFNS, sleep, anxiety and depression all improved significantly.ConclusionOur results suggest that specialist nurses can be trained to deliver CBT effectively to alleviate troublesome menopausal hot flushes in women following breast cancer in the NHS setting

An orthogonal C-H borylation - cross-coupling strategy for the preparation of tetrasubstituted "A(2)B(2)''-chrysene derivatives with tuneable photophysical properties

Cl-substituents serve as a functionalisable regiocontrol element for the orthogonal functionalisation of chrysene.</p

A Conversation about COVID-19 with Economists, Sociologists, Statisticians, and Operations Researchers

The COVID-19 pandemic is causing economic and social change. Moderated by David Banks, the Director of the Statistical and Applied Mathematical Sciences Institute (SAMSI), six eminent scientists who study different aspects of social change and public policy came together to discuss the impacts of the COVID-19 pandemic on the U.S. and the world. The discussion took a range of quantitative perspectives on how to respond to the crisis and to forecast what challenges lie ahead. Specific topics include the role of data science, strategies for beginning to reopen the economy, the international impact of the disease, and its effect upon universities

Impact of a hospice rapid response service on preferred place of death, and costs

Background: Many people with a terminal illness would prefer to die at home. A new palliative rapid response service (RRS) provided by a large hospice provider in South East England was evaluated (2010) to provide evidence of impact on achieving preferred place of death and costs. The RRS was delivered by a team of trained health care assistants and available 24/7. The purpose of this study was to (i) compare the characteristics of RRS users and non-users, (ii) explore differences in the proportions of users and non-users dying in the place of their choice, (iii) monitor the whole system service utilisation of users and non-users, and compare costs. Methods: All hospice patients who died with a preferred place of death recorded during an 18 month period were included. Data (demographic, preferences for place of death) were obtained from hospice records. Dying in preferred place was modelled using stepwise logistic regression analysis. Service use data (period between referral to hospice and death) were obtained from general practitioners, community providers, hospitals, social services, hospice, and costs calculated using validated national tariffs. Results: Of 688 patients referred to the hospice when the RRS was operational, 247 (35.9 %) used it. Higher proportions of RRS users than non-users lived in their own homes with a co-resident carer (40.3 % vs. 23.7 %); more non-users lived alone or in residential care (58.8 % vs. 76.3 %). Chances of dying in the preferred place were enhanced 2.1 times by being a RRS user, compared to a non-user, and 1.5 times by having a co-resident carer, compared to living at home alone or in a care home. Total service costs did not differ between users and non-users, except when referred to hospice very close to death (users had higher costs). Conclusions: Use of the RRS was associated with increased likelihood of dying in the preferred place. The RRS is cost neutral

Qualitative process study to explore the perceived burdens and benefits of a digital intervention for self-managing high blood pressure in Primary Care in the UK.

OBJECTIVES: Digital interventions can change patients' experiences of managing their health, either creating additional burden or improving their experience of healthcare. This qualitative study aimed to explore perceived burdens and benefits for patients using a digital self-management intervention for reducing high blood pressure. A secondary aim was to further our understanding of how best to capture burdens and benefits when evaluating health interventions. DESIGN: Inductive qualitative process study nested in a randomised controlled trial. SETTING: Primary Care in the UK. PARTICIPANTS: 35 participants taking antihypertensive medication and with uncontrolled blood pressure at baseline participated in semistructured telephone interviews. INTERVENTION: Digital self-management intervention to support blood pressure self-monitoring and medication change when recommended by the healthcare professional. ANALYSIS: Data were analysed using inductive thematic analysis with techniques from grounded theory. RESULTS: Seven themes were developed which reflected perceived burdens and benefits of using the intervention, including worry about health, uncertainty about self-monitoring and reassurance. The analysis showed how beliefs about their condition and treatment appeared to influence participants' appraisal of the value of the intervention. This suggested that considering illness and treatment perceptions in Burden of Treatment theory could further our understanding of how individuals appraise the personal costs and benefits of self-managing their health. CONCLUSIONS: Patients' appraisal of the burden or benefit of using a complex self-management intervention seemed to be influenced by experiences within the intervention (such as perceived availability of support) and beliefs about their condition and treatment (such as perceived control and risk of side effects). Developing our ability to adequately capture these salient burdens and benefits for patients could help enhance evaluation of self-management interventions in the future. Many participants perceived important benefits from using the intervention, highlighting the need for theory to recognise that engaging in self-management can include positive as well as negative aspects. TRIAL REGISTRATION NUMBER: ISRCTN13790648; Pre-results

A Phase I Study of Bortezomib in Combination With Standard 5-Fluorouracil and External-Beam Radiation Therapy for the Treatment of Locally Advanced or Metastatic Rectal Cancer

Standard therapy for stage II/III rectal cancer consists of a fluoropyrimidine and radiation therapy followed by surgery. Preclinical data demonstrated that bortezomib functions as a radiosensitizer in colorectal cancer models. The purpose of this study was to determine the maximum tolerated dose (MTD) of bortezomib in combination with chemotherapy and radiation

A Two-cohort Phase I Study of Weekly Oxaliplatin and Gemcitabine, Then Oxaliplatin, Gemcitabine, and Erlotinib During Radiotherapy for Unresectable Pancreatic Carcinoma

Gemcitabine is a potent radiosensitizer. When combined with standard radiotherapy (XRT) the gemcitabine dose must be reduced to about 10% of its conventional dose. Oxaliplatin and erlotinib also have radiosensitizing properties. In vitro, oxaliplatin and gemcitabine have demonstrated synergy. We aimed to determine the maximum tolerated dose of oxaliplatin and gemcitabine with concurrent XRT, then oxaliplatin, gemcitaibine and erlotinib with XRT in the treatment of locally advanced and low volume metastatic pancreatic or biliary cancer