A modified weighted log-rank test for confirmatory trials with a high proportion of treatment switching

In confirmatory cancer clinical trials, overall survival (OS) is normally a primary endpoint in the intention-to-treat (ITT) analysis under regulatory standards. After the tumor progresses, it is common that patients allocated to the control group switch to the experimental treatment, or another drug in the same class. Such treatment switching may dilute the relative efficacy of the new drug compared to the control group, leading to lower statistical power. It would be possible to decrease the estimation bias by shortening the follow-up period but this may lead to a loss of information and power. Instead we propose a modified weighted log-rank test (mWLR) that aims at balancing these factors by down-weighting events occurring when many patients have switched treatment. As the weighting should be pre-specified and the impact of treatment switching is unknown, we predict the hazard ratio function and use it to compute the weights of the mWLR. The method may incorporate information from previous trials regarding the potential hazard ratio function over time. We are motivated by the RECORD-1 trial of everolimus against placebo in patients with metastatic renal-cell carcinoma where almost 80\% of the patients in the placebo group received everolimus after disease progression. Extensive simulations show that the new test gives considerably higher efficiency than the standard log-rank test in realistic scenarios

Retail Market Prices of Fonio Reveal The Demand For Quality Characteristics in Bamako, Mali

African consumers' expectations concerning the quality of food products are great. In spite of constrained budgets, we showed that market retail prices revealed quality preferences of the consumers and not just production costs. In very poor countries like Mali, food innovation is limited by the very low purchasing power of the population. However, technological food product or process innovations are possible and sometimes valuable. Demand driven innovation may lead to open new markets, opportunities for small and medium scale enterprises and to improve consumers' welfare. Based on this assumption, technical research was done to provide new food products. In this paper, we used both sensory tests and a hedonic price approach, to estimate the consumers' demand for different characteristics of fonio, a West African cereal, and showed that poor consumers have quality requirements and pay for them. We showed that the shadow price or hedonic price paid for quality characteristics is small but significant. A comparison between sensory tests and a market study showed a convergence between what people say they prefer and what they really pay for. Results were consistent and showed directions for technological improvement of the product and its production process. The partial least square method was used to estimate hedonic prices of the different modalities of fonio quality traits. This method was interesting since it solved the ordinary least square method's colinearity problems. ...French Abstract : Les attentes des consommateurs africains concernant la qualité de l'alimentation sont importantes malgré des budgets très contraints. Nous montrons ici que les prix de marchés révèlent des préférences qualitatives et non seulement des coûts de production. Dans des pays très pauvres comme le Mali, l'innovation technologique est limitée par le très faible pouvoir d'achat de la population. Cependant les innovations technologiques sont possibles et parfois payantes. L'innovation en réponse à une demande peut permettre d'ouvrir de nouveaux marchés, de donner des opportunités aux petites et moyennes entreprises et d'améliorer le bien-être des consommateurs. Sur la base de cette hypothèse, la recherche technologique s'applique à fournir de nouveaux produits. Dans cet article, en utilisant à la fois des tests de dégustation et une analyse des prix hédoniques, nous estimons la demande des consommateurs pour différentes caractéristiques du fonio, une céréale d'Afrique de l'Ouest. Nous montrons que des consommateurs pauvres ont des exigences de qualité et paient de fait pour les satisfaire. Nous montrons que les prix hédoniques ou shadow prices payés pour les caractéristiques qualitatives sont faibles mais significatifs. La comparaison des tests sensoriels et de l'étude de marché montre une convergence entre ce que les gens disent et ce pour quoi ils paient réellement. Les résultats sont cohérents et montrent des directions pour l'amélioration technologique des produits et des procédés de transformation. La méthode des moindres carrés ordinaires a été utilisée pour l'estimation des prix hédoniques des différentes modalités des attributs de qualité du fonio. Cette méthode est intéressante car elle résout les problèmes de colinéarité.FONIO; CEREAL; QUALITY; HEDONIC PRICES; PLS METHOD; EMPIRICAL INVESTIGATION

Using personality as a predictor of diet induced weight loss and weight management

<p>Abstract</p> <p>Background</p> <p>A major challenge for successful weight management is tailoring weight loss programs to individual needs. The aim of this study was to investigate whether personality traits could be used to match individuals to a compatible weight loss program that would maximize weight loss.</p> <p>Method</p> <p>Two different weight loss trials were conducted, both with a weight loss greater than 5% the measure of success. Fifty-four individuals, BMI 30-40 kg/m², either followed a slow, healthy eating weight loss diet (HEWLD) of 5000-6000 kJ/day for 12 weeks (n = 22), or a fast, very low energy diet (VLED) of 3000 kJ/day for 4 weeks (n = 32). Anthropometric measurements were recorded at baseline, at the end of the weight loss period and, for VLED, at the end of 10 weeks of weight maintenance. Personality traits were measured at baseline using the Tangney Self Control Scale plus 3 of the scales from the Five Factor Model - Neuroticism, Conscientiousness and Extraversion.</p> <p>Results</p> <p>The percentage weight loss was significantly greater in VLED (-7.38%) compared to HEWLD (-4.11%), (p < 0.001). Weight loss in HEWLD was positively correlated with Anxiety, a facet of Neuroticism. Weight loss in VLED was positively correlated with Neuroticism (r = 0.5, p < 0.01), and negatively correlated with Dutifulness and Discipline, facets of Conscientiousness, (p < 0.05 for both). No link was observed between weight loss and the personality trait, Self Control, in either HEWLD or VLED.</p> <p>Conclusion</p> <p>The personality factor, Neuroticism, was linked to successful weight loss (that is ≥ 5%) with a particular weight loss treatment, suggesting that there is a potential to use measures of personality to identify appropriate weight loss/management strategies for individuals.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12611000716965.aspx">ACTRN12611000716965</a></p

Can Polarity-Inverted Surfactants Self-Assemble in Nonpolar Solvents

We investigate the self-assembly process of a surfactant with inverted polarity in water and cyclohexane using both all-atom and coarse grained hybrid particle-field molecular dynamics simulations. Unlike conventional surfactants, the molecule under study, proposed in a recent experiment, is formed by a rigid and compact hydrophobic adamantane moiety, and a long and floppy triethylene glycol tail. In water, we report the formation of stable inverted micelles with the adamantane heads grouping together into a hydrophobic core, and the tails forming hydrogen bonds with water. By contrast, microsecond simulations do not provide evidence of stable micelle formation in cyclohexane. Validating the computational results by comparison with experimental diffusion constant and small-angle X-ray scattering intensity, we show that at laboratory thermodynamic conditions the mixture resides in the supercritical region of the phase diagram, where aggregated and free surfactant states co-exist in solution. Our simulations also provide indications about how to escape this region, to produce thermodynamically stable micellar aggregates.Comment: 14 pages, 10 Figures, accepted for publication (2020

Tradeoffs in jet inlet design: a historical perspective

The design of the inlet(s) is one of the most demanding tasks of the development process of any gas turbine-powered aircraft. This is mainly due to the multi-objective and multidisciplinary nature of the exercise. The solution is generally a compromise between a number of conflicting goals and these conflicts are the subject of the present paper. We look into how these design tradeoffs have been reflected in the actual inlet designs over the years and how the emphasis has shifted from one driver to another. We also review some of the relevant developments of the jet age in aerodynamics and design and manufacturing technology and we examine how they have influenced and informed inlet design decision

New South Wales Child Development Study (NSW-CDS): an Australian multiagency, multigenerational, longitudinal record linkage study

Purpose: The initial aim of this multiagency, multigenerational record linkage study is to identify childhood profiles of developmental vulnerability and resilience, and to identify the determinants of these profiles. The eventual aim is to identify risk and protective factors for later childhood-onset and adolescent-onset mental health problems, and other adverse social outcomes, using subsequent waves of record linkage. The research will assist in informing the development of public policy and intervention guidelines to help prevent or mitigate adverse long-term health and social outcomes. Participants: The study comprises a population cohort of 87,026 children in the Australian State of New South Wales (NSW). The cohort was defined by entry into the first year of full-time schooling in NSW in 2009, at which time class teachers completed the Australian Early Development Census (AEDC) on each child (with 99.7% coverage in NSW). The AEDC data have been linked to the children's birth, health, school and child protection records for the period from birth to school entry, and to the health and criminal records of their parents, as well as mortality databases. Findings to date: Descriptive data summarising sex, geographic and socioeconomic distributions, and linkage rates for the various administrative databases are presented. Child data are summarised, and the mental health and criminal records data of the children's parents are provided. Future plans: In 2015, at age 11 years, a self-report mental health survey was administered to the cohort in collaboration with government, independent and Catholic primary school sectors. A second record linkage, spanning birth to age 11 years, will be undertaken to link this survey data with the aforementioned administrative databases. This will enable a further identification of putative risk and protective factors for adverse mental health and other outcomes in adolescence, which can then be tested in subsequent record linkages.Vaughan J Carr, Felicity Harris, Alessandra Raudino, Luming Luo, Maina Kariuki, Enwu Liu, Stacy Tzoumakis, Maxwell Smith, Allyson Holbrook, Miles Bore, Sally Brinkman, Rhoshel Lenroot, Katherine Dix, Kimberlie Dean, Kristin R Laurens, Melissa J Gree

Graduate entry to medicine: widening psychological diversity

At Nottingham University more than 95% of entrants to the traditional 5-year medical course are school leavers. Since 2003 we have admitted graduate entrants (GEM) to a shortened (4-year) course to 'widen access to students from more disadvantaged backgrounds'. We have recently shown that the GEM course widens academic and socio-demographic diversity of the medical student population. This study explored whether GEM students also bring psychological diversity and whether this could be beneficial. We studied: a) 217 and 96 applicants to the Nottingham 5- and 4-year courses respectively, applying in the 2002-3 UCAS cycle, and, b) 246 school leavers starting the 5-year course and 39 graduate entrants to the 4-year course in October 2003. The psychological profiles of the two groups of applicants and two groups of entrants were compared using their performance in the Goldberg 'Big 5' Personality test, the Personal Qualities Assessment (PQA; measuring interpersonal traits and interpersonal values), and the Lovibond and Lovibond measure of depression, anxiety and stress. For the comparison of the Entrants we excluded the 33 school leavers and seven graduates who took the tests as Applicants. Statistical analyses were undertaken using SPSS software (version 16.0). Graduate applicants compared to school leaver applicants were significantly more conscientious, more confident, more self controlled, more communitarian in moral orientation and less anxious. Only one of these differences was preserved in the entrants with graduates being less anxious. However, the graduate entrants were significantly less empathetic and conscientious than the school leavers. This study has shown that school leaver and graduate entrants to medical school differ in some psychological characteristics. However, if confirmed in other studies and if they were manifest in the extreme, not all the traits brought by graduates would be desirable for someone aiming for a medical career

Do personality traits assessed on medical school admission predict exit performance?:A UK-wide longitudinal cohort studyA2

We thank the UKCAT Research Group for funding this independent evaluation and thank Rachel Greatrix and Sandra Nicholson of the UKCAT Consortium for their support throughout this project, and their feedback on the draft paper. We also thank Professor Amanda Lee and Ms Katie Wilde for their input into the application for funding, and ongoing support.Peer reviewedPublisher PD