Clustering of Local Group distances: publication bias or correlated measurements? I. The Large Magellanic Cloud

The distance to the Large Magellanic Cloud (LMC) represents a key local rung of the extragalactic distance ladder. Yet, the galaxy's distance modulus has long been an issue of contention, in particular in view of claims that most newly determined distance moduli cluster tightly - and with a small spread - around the "canonical" distance modulus, (m-M)_0 = 18.50 mag. We compiled 233 separate LMC distance determinations published between 1990 and 2013. Our analysis of the individual distance moduli, as well as of their two-year means and standard deviations resulting from this largest data set of LMC distance moduli available to date, focuses specifically on Cepheid and RR Lyrae variable-star tracer populations, as well as on distance estimates based on features in the observational Hertzsprung-Russell diagram. We conclude that strong publication bias is unlikely to have been the main driver of the majority of published LMC distance moduli. However, for a given distance tracer, the body of publications leading to the tightly clustered distances is based on highly non-independent tracer samples and analysis methods, hence leading to significant correlations among the LMC distances reported in subsequent articles. Based on a careful, weighted combination, in a statistical sense, of the main stellar population tracers, we recommend that a slightly adjusted canonical distance modulus of (m-M)_0 = 18.49 +- 0.09 mag be used for all practical purposes that require a general distance scale without the need for accuracies of better than a few percent.Comment: 35 pages (AASTeX preprint format), 5 postscript figures; AJ, in press. For full database of LMC distance moduli, see http://astro-expat.info/Data/pubbias.htm

Cepheid Mass-loss and the Pulsation -- Evolutionary Mass Discrepancy

I investigate the discrepancy between the evolution and pulsation masses for Cepheid variables. A number of recent works have proposed that non-canonical mass-loss can account for the mass discrepancy. This mass-loss would be such that a 5Mo star loses approximately 20% of its mass by arriving at the Cepheid instability strip; a 14Mo star, none. Such findings would pose a serious challenge to our understanding of mass-loss. I revisit these results in light of the Padova stellar evolutionary models and find evolutionary masses are ($17\pm5$)% greater than pulsation masses for Cepheids between 5<M/Mo<14. I find that mild internal mixing in the main-sequence progenitor of the Cepheid are able to account for this mass discrepancy.Comment: 15 pages, 3 figures, ApJ accepte

(E)motion and creativity: Hacking the function of motor expressions in emotion regulation to augment creativity

Positive emotion can help augment human creativity. To utilize this potential in an interactive system, we propose that such a system should be designed to regulate the emotions that are caused by a creative task. We argue that this can be done by hacking the function of motor expressions in emotion regulation. To this end, we have conceived and made an interactive system that is designed to regulate positive emotion during an idea generation and an insight problem solving task. The system regulates emotion by letting users interact using arm gestures that are designed based on motor expressions, choreographed in a way that enables emotion regulation. Using this interactive system we experimentally test the hypotheses that positive approaching, rather than negative avoiding arm gestures, used to interact with a system, can heighten positive emotion, and augment creativity. The findings demonstrate that an interactive system can be designed to use the function of motor expressions in emotion regulation to help people perform better on certain creative tasks

Meeting patient expectations in migraine treatment: what are the key endpoints?

Clinical outcomes of migraine treatment are generally based on two major endpoints: acute pain resolution and effects on quality of life (QOL). Resolution of acute pain can be evaluated in a number of ways, each increasingly challenging to achieve; pain relief, pain freedom at 2 h, sustained pain-freedom, and SPF plus no adverse events (SNAE, the most challenging). QOL questionnaires help assess the burden of migraine and identify optimal treatments. Pain resolution and improved QOL form the basis of the ultimate target-meeting patient expectations, to achieve patient satisfaction. To achieve this, it is crucial to choose appropriate endpoints that reflect realistic treatment goals for individual patients. Moreover, SNAE can help discriminate between triptans, with almotriptan having the highest SNAE score. Kaplan-Meier plots are also relevant when evaluating migraine treatments. The use of symptomatic medication may lead to the paradoxical development of medication-overuse headache. In general practice, patients should use simple tools for pain measurement (e.g. headache diary) and a QOL questionnaire. A composite endpoint of pain resolution and QOL restoration would constitute a step forward in migraine management

Chromatin to Clinic: The Molecular Rationale for PARP1 Inhibitor Function.

Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors were recently shown to have potential clinical impact in a number of disease settings, particularly as related to cancer therapy, treatment for cardiovascular dysfunction, and suppression of inflammation. The molecular basis for PARP1 inhibitor function is complex, and appears to depend on the dual roles of PARP1 in DNA damage repair and transcriptional regulation. Here, the mechanisms by which PARP-1 inhibitors elicit clinical response are discussed, and strategies for translating the preclinical elucidation of PARP-1 function into advances in disease management are reviewed

No man’s land: information needs and resources of men with metastatic castrate resistant prostate cancer

The majority of men treated for prostate cancer will eventually develop castrate resistant disease (CRPC) with metastases (mCRPC). There are several options for further treatment: chemotherapy, third-line hormone therapy, radium, immunotherapy and palliation. Current ASCO guidelines for survivors of prostate cancer recommend that an individual’s information needs at all stages of disease are assessed, and that patients are provided with or referred to the appropriate sources for information and support. Earlier reviews have highlighted the dearth of such services and we wished to see if the situation had improved more recently. Unfortunately we conclude that there is still a lack of good quality congruent information easily accessible specifically for men with mCRPC and insufficient data regarding the risks, harms and benefits of different management plans. More research providing a clear evidence base about treatment consequences using patient reported outcome measures is required

On the distance and reddening of the starburst galaxy IC10

We present deep and accurate optical photometry of the Local Group starburst galaxy IC10. The photometry is based on two sets of images collected with the Advanced Camera for Surveys and with the Wide Field Planetary Camera 2 on board the Hubble Space Telescope. We provide new estimates of the Red Giant Branch tip (TRGB) magnitude, m_{F814W}^{TRGB}=21.90+-0.03, and of the reddening, E(B-V)=0.78+-0.06, using field stars in the Small Magellanic Cloud (SMC) as a reference. Adopting the SMC and two globulars, Omega Centauri and 47 Tucanae, as references we estimate the distance modulus to IC10: independent calibrations give weighted average distances of mu=24.51+-0.08 (TRGB) and mu=24.56+-0.08 (RR Lyrae). We also provide a new theoretical calibration for the TRGB luminosity, and using these predictions we find a very similar distance to IC10 (mu~24.60+-0.15). These results suggest that IC10 is a likely member of the M31 subgroup.Comment: 4 pages, 4 figures, ApJ Letters accepte

A Phase I Study Investigating AZD8186, a Potent and Selective Inhibitor of PI3Kβ/δ, in Patients with Advanced Solid Tumors

Advanced Solid Tumors; PI3K beta/delta inhibitorTumores sólidos avanzados; Inhibidor de PI3K beta/deltaTumors sòlids avançats; Inhibidor de PI3K beta/deltaPurpose: To characterize safety and tolerability of the selective PI3Kβ inhibitor AZD8186, identify a recommended phase II dose (RP2D), and assess preliminary efficacy in combination with abiraterone acetate or vistusertib. Patients and Methods: This phase I open-label study included patients with advanced solid tumors, particularly prostate cancer, triple-negative breast cancer, and squamous non–small cell lung cancer. The study comprised four arms: (i) AZD8186 monotherapy dose finding; (ii) monotherapy dose expansion; (iii) AZD8186/abiraterone acetate (with prednisone); and (iv) AZD8186/vistusertib. The primary endpoints were safety, tolerability, and identification of the RP2D of AZD8186 monotherapy and in combination. Secondary endpoints included pharmacokinetics (PK), pharmacodynamics, and tumor and prostate-specific antigen (PSA) responses. Results: In total, 161 patients were enrolled. AZD8186 was well tolerated across all study arms, the most common adverse events being gastrointestinal symptoms. In the monotherapy dose-finding arm, four patients experienced dose-limiting toxicities (mainly rash). AZD8186 doses of 60-mg twice daily [BID; 5 days on, 2 days off (5:2)] and 120-mg BID (continuous and 5:2 dosing) were taken into subsequent arms. The PKs of AZD8186 were dose proportional, without interactions with abiraterone acetate or vistusertib, and target inhibition was observed in plasma and tumor tissue. Monotherapy and combination therapy showed preliminary evidence of limited antitumor activity by imaging and, in prostate cancer, PSA reduction. Conclusions: AZD8186 monotherapy had an acceptable safety and tolerability profile, and combination with abiraterone acetate/prednisone or vistusertib was also tolerated. There was preliminary evidence of antitumor activity, meriting further exploration of AZD8186 in subsequent studies in PI3Kβ pathway–dependent cancers.This study was sponsored by AstraZeneca. We thank the patients and their doctors and caregivers who participated in this study. We acknowledge support in Cambridge from Cancer Research UK, Experimental Cancer Medicine Center, NIHR Biomedical Research Center, and NIHR Cambridge Clinical Research Center. Research at the Christie NHS Foundation Trust was supported by the NIHR Manchester Clinical Research Facility and Manchester Experimental Cancer Medicine Center award. We also thank Martine Roudier (AstraZeneca) for providing analysis data of tumor tissue biopsies, and Wolfram Brugger and Caroline Kennedy (AstraZeneca, Cambridge, UK). Abiraterone acetate was kindly provided by Janssen. Medical writing and editorial assistance were provided by Bioscript Medical, Macclesfield, UK, and funded by AstraZeneca