Equipoise across the patient population: Optimising recruitment to a randomised controlled trial

© 2016 The Author(s). Background: This paper proposes a novel perspective on the value of qualitative research for improving trial design and optimising recruitment. We report findings from a qualitative study set within the OPEN trial, a surgical randomised controlled trial (RCT) comparing two interventions for recurrent bulbar urethral stricture, a common cause of urinary problems in men. Methods: Interviews were conducted with men meeting trial eligibility criteria (n = 19) to explore reasons for accepting or declining participation and with operating urologists (n = 15) to explore trial acceptability. Results: Patients expressed various preferences and understood these in the context of relative severity and tolerability of their symptoms. Accounts suggest a common trajectory of worsening symptoms with a particular window within which either treatment arm would be considered acceptable. Interviews with clinician recruiters found that uncertainty varied between general and specialist sites, which reflect clinicians' relative exposure to different proportions of the patient population. Conclusion: Recruitment post referral, at specialist sites, was challenging due to patient (and clinician) expectations. Trial design, particularly where there are fixed points for recruitment along the care pathway, can enable or constrain the possibilities for effective accrual depending on how it aligns with the optimum point of patient equipoise. Qualitative recruitment investigations, often focussed on information provision and patient engagement, may also look to better understand the target patient population in order to optimise the point at which patients are approached. Trial registration: ISRCTN Registry, ISRCTN98009168. Registered on 29 November 2012

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer

Boring bivalve traces in modern reef and deeper-water macroid and rhodolith beds

Macroids and rhodoliths, made by encrusting acervulinid foraminifera and coralline algae, are widely recognized as bioengineers providing relatively stable microhabitats and increasing biodiversity for other species. Macroid and rhodolith beds occur in different depositional settings at various localities and bathymetries worldwide. Six case studies of macroid/rhodolith beds from 0 to 117m water depth in the Pacific Ocean (northern Central Ryukyu Islands, French Polynesia), eastern Australia (Fraser Island, One Tree Reef, Lizard Island), and the Mediterranean Sea (southeastern Spain) show that nodules in the beds are perforated by small-sized boring bivalve traces (Gastrochanolites). On average, boring bivalve shells (gastrochaenids and mytilids) are more slender and smaller than those living inside shallow-water rocky substrates. In the Pacific, Gastrochaena cuneiformis, Gastrochaena sp., Leiosolenus malaccanus, L. mucronatus, L. spp., and Lithophaga/Leiosolenus sp., for the first time identified below 20m water depth, occur as juvenile forms along with rare small-sized adults. In deep-water macroids and rhodoliths the boring bivalves are larger than the shallower counterparts in which growth of juveniles is probably restrained by higher overturn rates of host nodules. In general, most boring bivalves are juveniles that grew faster than the acervulinid foraminiferal and coralline red algal hosts and rarely reached the adult stage. As a consequence of phenotypic plasticity, small-sized adults with slow growth rates coexist with juveniles. Below wave base macroids and rhodoliths had the highest amounts of bioerosion, mainly produced by sponges and polychaete worms. These modern observations provide bases for paleobiological inferences in fossil occurrences.Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) 25247083Erasmus+FAR2012-2017FIR2016FIR2018PRIN "Biotic resilience to global change: biomineralization of planktonic and benthic calcifiers in the past, present and future" 2017RX9XXXYBioMed Central-Prepay Membership at the University of FerraraJunta de Andalucía RNM 190Committee on ResearchMuseum of PaleontologyDepartment of Integrative Biology, UC BerkeleyUC Pacific Rim Projec

Of cattle, sand flies and men : a systematic review of risk factor analyses for South Asian visceral leishmaniasis and implications for elimination

Background: Studies performed over the past decade have identified fairly consistent epidemiological patterns of risk factors for visceral leishmaniasis (VL) in the Indian subcontinent. Methods and Principal Findings: To inform the current regional VL elimination effort and identify key gaps in knowledge, we performed a systematic review of the literature, with a special emphasis on data regarding the role of cattle because primary risk factor studies have yielded apparently contradictory results. Because humans form the sole infection reservoir, clustering of kala-azar cases is a prominent epidemiological feature, both at the household level and on a larger scale. Subclinical infection also tends to show clustering around kala-azar cases. Within villages, areas become saturated over a period of several years; kala-azar incidence then decreases while neighboring areas see increases. More recently, post kalaazar dermal leishmaniasis (PKDL) cases have followed kala-azar peaks. Mud walls, palpable dampness in houses, and peridomestic vegetation may increase infection risk through enhanced density and prolonged survival of the sand fly vector. Bed net use, sleeping on a cot and indoor residual spraying are generally associated with decreased risk. Poor micronutrient status increases the risk of progression to kala-azar. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting the complexity of the effect of bovines on sand fly abundance, aggregation, feeding behavior and leishmanial infection rates. Poverty is an overarching theme, interacting with individual risk factors on multiple levels. Conclusions: Carefully designed demonstration projects, taking into account the complex web of interconnected risk factors, are needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid resurgence when interventions are scaled back. More effective, short-course treatment regimens for PKDL are urgently needed to enable the elimination initiative to succeed

Easy detection of chromatin binding proteins by the histone association assay

The Histone Association Assay provides an easy approach for detecting proteins that bind chromatin in vivo. This technique is based on a chromatin immunoprecipitation protocol using histone H3-specific antibodies to precipitate bulk chromatin from crosslinked whole cell extracts. Proteins that co-precipitate with chromatin are subsequently detected by conventional SDS-PAGE and Western blot analysis. Unlike techniques that separate chromatin and non-chromatin interacting proteins by centrifugation, this method can be used to delineate whether a protein is chromatin associated regardless of its innate solubility. Moreover, the relative amount of protein bound to DNA can be ascertained under quantitative conditions. Therefore, this technique may be utilized for analyzing the chromatin association of proteins involved in diverse cellular processes

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed

Liquid-liquid critical point in supercooled silicon

A novel liquid-liquid phase transition has been proposed and investigated in a wide variety of pure substances recently, including water, silica and silicon. From computer simulations using the Stillinger-Weber classical empirical potential, Sastry and Angell [1] demonstrated a first order liquid-liquid transition in supercooled silicon, subsequently supported by experimental and simulation studies. Here, we report evidence for a liquid-liquid critical end point at negative pressures, from computer simulations using the SW potential. Compressibilities exhibit a growing maximum upon lowering temperature below 1500 K and isotherms exhibit density discontinuities below 1120 K, at negative pressure. Below 1120 K, isotherms obtained from constant volume-temperature simulations exhibit non-monotonic, van der Waals-like behavior signaling a first order transition. We identify Tc ~ 1120 +/- 12 K, Pc -0.60 +/- 0.15 GPa as the critical temperature and pressure for the liquid-liquid critical point. The structure of the liquid changes dramatically upon decreasing the temperature and pressure. Diffusivities vary over 4 orders of magnitude, and exhibit anomalous pressure dependence near the critical point. A strong relationship between local geometry quantified by the coordination number, and diffusivity, is seen, suggesting that atomic mobility in both low and high density liquids can usefully be analyzed in terms of defects in the tetrahedral network structure. We have constructed the phase diagram of supercooled silicon. We identify the lines of compressibility, density extrema (maxima and minima) and the spinodal which reveal the interconnection between thermodynamic anomalies and the phase behaviour of the system as suggested in previous works [2-9]Comment: (to be published in revised form); small corrections to previous version; Nature Physics 201

Acceptability of the Distress Thermometer and Problem List to community-based telephone cancer helpline operators, and to cancer patients and carers

Background Cancer can be a distressing experience for cancer patients and carers, impacting on psychological, social, physical and spiritual functioning. However, health professionals often fail to detect distress in their patients due to time constraints and a lack of experience. Also, with the focus on the patient, carer needs are often overlooked. This study investigated the acceptability of brief distress screening with the Distress Thermometer (DT) and Problem List (PL) to operators of a community-based telephone helpline, as well as to cancer patients and carers calling the service. Methods Operators (n = 18) monitored usage of the DT and PL with callers (cancer patients/carers, >18 years, and English-speaking) from September-December 2006 (n = 666). The DT is a single item, 11-point scale to rate level of distress. The associated PL identifies the cause of distress. Results The DT and PL were used on 90% of eligible callers, most providing valid responses. Benefits included having an objective, structured and consistent means for distress screening and triage to supportive care services. Reported challenges included apparent inappropriateness of the tools due to the nature of the call or level of caller distress, the DT numeric scale, and the level of operator training. Conclusions We observed positive outcomes to using the DT and PL, although operators reported some challenges. Overcoming these challenges may improve distress screening particularly by less experienced clinicians, and further development of the PL items and DT scale may assist with administration. The DT and PL allow clinicians to direct/prioritise interventions or referrals, although ongoing training and support is critical in distress screening