Evaluating Patient Preferences of Maintenance Therapy for the Treatment of Chronic Obstructive Pulmonary Disease: A Discrete Choice Experiment in the UK, USA and Germany.

Introduction: With increasing availability of different treatments for chronic obstructive pulmonary disease (COPD), we sought to understand patient preferences for COPD treatment in the UK, USA, and Germany using a discrete choice experiment (DCE). Methods: Qualitative research identified six attributes associated with COPD maintenance treatments: ease of inhaler use, exacerbation frequency, frequency of inhaler use, number of different inhalers used, side effect frequency, and out-of-pocket costs. A DCE using these attributes, with three levels each, was designed and tested through cognitive interviews and piloting. It comprised 18 choice sets, selected using a D-efficient experimental design. Demographics and disease history were collected and the final DCE survey was completed online by participants recruited from panels in the UK, USA and Germany. Responses were analyzed using mixed logit models, with results expressed as odds ratios (ORs). Results: Overall, 450 participants (150 per country) completed the DCE; most (UK and Germany, 97.3%; USA, 98.0%) were included in the final analysis. Based on relative attribute importance, avoidance of side effects was found to be most important (UK: OR 11.65; USA: OR 7.17; Germany: OR 11.45; all p<0.0001), followed by the likelihood of fewer exacerbations (UK: OR 2.22; USA: OR 1.63; Germany: OR 2.54; all p<0.0001) and increased ease of use (UK: OR 1.84; USA: OR 1.84; Germany: OR 1.60; all p<0.0001). Number of inhalers, out-of-pocket costs, and frequency of inhaler use were found to be less important. Preferences were relatively consistent across the three countries. All participants required a reduction in exacerbations to accept more frequent inhaler use or use of more inhalers. Conclusion: When selecting COPD treatment, individuals assigned the highest value to the avoidance of side effects, experiencing fewer exacerbations, and ease of inhaler use. Ensuring that patients' preferences are considered may encourage treatment compliance

Personal and social norms for food portion sizes in lean and obese adults.

BACKGROUND: Portion size is an important component of dietary advice for weight control, but little is known about what portion sizes people consider 'normal'. This study determined the effect of body mass index (BMI), gender, dietary restraint and liking of the food on personal and social portion size norms for a range of foods and the degree of certainty over the norms. METHODS: Thirty lean (BMI 20-25 kg m(-)(2)) and 30 obese (BMI 30-35 kg m(-)(2)) men and women (aged 18-60 years) viewed 17 different portion sizes of 12 foods on a computer screen on two occasions a week apart. Participants responded 'more' or 'less' to each photograph reflecting personal portion size preference or perceived portion sizes of others. Personal and social norms for portion sizes of each food were determined using the method of constant stimuli giving a sigmoidal curve of the probability of answering 'less' over a range of portion sizes. The slope of the sigmoid at the norm gave a measure of certainty about the norm. Regression models were used to examine the effect of BMI, gender, dietary restraint and liking of the food on personal norms, social norms, the relationship between norms, and the slopes. RESULTS: Personal norms were significantly larger in the obese (P=0.026), men (P<0.001), those with lower dietary restraint (P<0.001), and those with higher liking for the food (P<0.001). Social norms were larger for women (P=0.012). The slopes at the norms were 30% shallower in the obese and in men (P<0.001). CONCLUSION: Larger personal norms for portion size among the obese, men, those with lower dietary restraint and those with higher liking for a food imply greater consumption, which may undermine weight control. Shallower slopes for norms in the obese and in men may imply less clearly defined habitual portion sizes.This study was supported by a program grant from the UK Medical Research Council (U105960389).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ijo.2015.4

Effect of reducing portion size at a compulsory meal on later energy intake, gut hormones, and appetite in overweight adults.

OBJECTIVE: Larger portion sizes (PS) are associated with greater energy intake (EI), but little evidence exists on the appetitive effects of PS reduction. This study investigated the impact of reducing breakfast PS on subsequent EI, postprandial gastrointestinal hormone responses, and appetite ratings. METHODS: In a randomized crossover design (n = 33 adults; mean BMI 29 kg/m(2) ), a compulsory breakfast was based on 25% of gender-specific estimated daily energy requirements; PS was reduced by 20% and 40%. EI was measured at an ad libitum lunch (240 min) and snack (360 min) and by weighed diet diaries until bed. Blood was sampled until lunch in 20 participants. Appetite ratings were measured using visual analogue scales. RESULTS: EI at lunch (control: 2,930 ± 203; 20% reduction: 2,853 ± 198; 40% reduction: 2,911 ± 179 kJ) and over the whole day except breakfast (control: 7,374 ± 361; 20% reduction: 7,566 ± 468; 40% reduction: 7,413 ± 417 kJ) did not differ. Postprandial PYY, GLP-1, GIP, insulin, and fullness profiles were lower and hunger, desire to eat, and prospective consumption higher following 40% reduction compared to control. Appetite ratings profiles, but not hormone concentrations, were associated with subsequent EI. CONCLUSIONS: Smaller portions at breakfast led to reductions in gastrointestinal hormone secretion but did not affect subsequent energy intake, suggesting small reductions in portion size may be a useful strategy to constrain EI

Evidence-based practice profiles of physiotherapists transitioning into the workforce: a study of two cohorts

<p>Abstract</p> <p>Background</p> <p>Training in the five steps of evidence-based practice (EBP) has been recommended for inclusion in entry-level health professional training. The effectiveness of EBP education has been explored predominantly in the medical and nursing professions and more commonly in post-graduate than entry-level students. Few studies have investigated longitudinal changes in EBP attitudes and behaviours. This study aimed to assess the changes in EBP knowledge, attitudes and behaviours in entry-level physiotherapy students transitioning into the workforce.</p> <p>Methods</p> <p>A prospective, observational, longitudinal design was used, with two cohorts. From 2008, 29 participants were tested in their final year in a physiotherapy program, and after the first and second workforce years. From 2009, 76 participants were tested in their final entry-level and first workforce years. Participants completed an Evidence-Based Practice Profile questionnaire (EBP²), which includes self-report EBP domains [Relevance, Terminology (knowledge of EBP concepts), Confidence, Practice (EBP implementation), Sympathy (disposition towards EBP)]. Mixed model analysis with sequential Bonferroni adjustment was used to analyse the matched data. Effect sizes (ES) (95% CI) were calculated for all changes.</p> <p>Results</p> <p>Effect sizes of the changes in EBP domains were small (ES range 0.02 to 0.42). While most changes were not significant there was a consistent pattern of decline in scores for Relevance in the first workforce year (ES -0.42 to -0.29) followed by an improvement in the second year (ES +0.27). Scores in Terminology improved (ES +0.19 to +0.26) in each of the first two workforce years, while Practice scores declined (ES -0.23 to -0.19) in the first year and improved minimally in the second year (ES +0.04). Confidence scores improved during the second workforce year (ES +0.27). Scores for Sympathy showed little change.</p> <p>Conclusions</p> <p>During the first two years in the workforce, there was a transitory decline in the self-reported practice and sense of relevance of EBP, despite increases in confidence and knowledge. The pattern of progression of EBP skills beyond these early professional working years is unknown.</p

Genome-wide signatures of convergent evolution in echolocating mammals

Evolution is typically thought to proceed through divergence of genes, proteins, and ultimately phenotypes(1-3). However, similar traits might also evolve convergently in unrelated taxa due to similar selection pressures(4,5). Adaptive phenotypic convergence is widespread in nature, and recent results from a handful of genes have suggested that this phenomenon is powerful enough to also drive recurrent evolution at the sequence level(6-9). Where homoplasious substitutions do occur these have long been considered the result of neutral processes. However, recent studies have demonstrated that adaptive convergent sequence evolution can be detected in vertebrates using statistical methods that model parallel evolution(9,10) although the extent to which sequence convergence between genera occurs across genomes is unknown. Here we analyse genomic sequence data in mammals that have independently evolved echolocation and show for the first time that convergence is not a rare process restricted to a handful of loci but is instead widespread, continuously distributed and commonly driven by natural selection acting on a small number of sites per locus. Systematic analyses of convergent sequence evolution in 805,053 amino acids within 2,326 orthologous coding gene sequences compared across 22 mammals (including four new bat genomes) revealed signatures consistent with convergence in nearly 200 loci. Strong and significant support for convergence among bats and the dolphin was seen in numerous genes linked to hearing or deafness, consistent with an involvement in echolocation. Surprisingly we also found convergence in many genes linked to vision: the convergent signal of many sensory genes was robustly correlated with the strength of natural selection. This first attempt to detect genome-wide convergent sequence evolution across divergent taxa reveals the phenomenon to be much more pervasive than previously recognised

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance

Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial

BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection worldwide. National screening programmes and antibiotic treatment have failed to decrease incidence, and to date no vaccines against genital chlamydia have been tested in clinical trials. We aimed to assess the safety and immunogenicity, in humans, of a novel chlamydia vaccine based on a recombinant protein subunit (CTH522) in a prime-boost immunisation schedule. METHODS: This phase 1, first-in-human, double-blind, parallel, randomised, placebo-controlled trial was done at Hammersmith Hospital in London, UK, in healthy women aged 19-45 years. Participants were randomly assigned (3:3:1) to three groups: CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminium hydroxide (CTH522:AH), or placebo (saline). Participants received three intramuscular injections of 85 μg vaccine (with adjuvant) or placebo to the deltoid region of the arm at 0, 1, and 4 months, followed by two intranasal administrations of 30 μg unadjuvanted vaccine or placebo (one in each nostril) at months 4·5 and 5·0. The primary outcome was safety and the secondary outcome was humoral immunogenicity (anti-CTH522 IgG seroconversion). This study is registered with Clinicaltrials.gov, number NCT02787109. FINDINGS: Between Aug 15, 2016, and Feb 13, 2017, 35 women were randomly assigned (15 to CTH522:CAF01, 15 to CTH522:AH, and five to placebo). 32 (91%) received all five vaccinations and all participants were included in the intention-to-treat analyses. No related serious adverse reactions were reported, and the most frequent adverse events were mild local injection-site reactions, which were reported in all (15 [100%] of 15) participants in the two vaccine groups and in three (60%) of five participants in the placebo group (p=0·0526 for both comparisons). Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in seven [47%] of 15 participants in the active treatment groups vs three [60%] of five in the placebo group; p=1·000). Both CTH522:CAF01 and CTH522:AH induced anti-CTH522 IgG seroconversion in 15 (100%) of 15 participants after five immunisations, whereas no participants in the placebo group seroconverted. CTH522:CAF01 showed accelerated seroconversion, increased IgG titres, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response profile compared with CTH522:AH. INTERPRETATION: CTH522 adjuvanted with either CAF01 or aluminium hydroxide appears to be safe and well tolerated. Both vaccines were immunogenic, although CTH522:CAF01 had a better immunogenicity profile, holding promise for further clinical development. FUNDING: European Commission and The Innovation Fund Denmark

Natural images from the birthplace of the human eye

Here we introduce a database of calibrated natural images publicly available through an easy-to-use web interface. Using a Nikon D70 digital SLR camera, we acquired about 5000 six-megapixel images of Okavango Delta of Botswana, a tropical savanna habitat similar to where the human eye is thought to have evolved. Some sequences of images were captured unsystematically while following a baboon troop, while others were designed to vary a single parameter such as aperture, object distance, time of day or position on the horizon. Images are available in the raw RGB format and in grayscale. Images are also available in units relevant to the physiology of human cone photoreceptors, where pixel values represent the expected number of photoisomerizations per second for cones sensitive to long (L), medium (M) and short (S) wavelengths. This database is distributed under a Creative Commons Attribution-Noncommercial Unported license to facilitate research in computer vision, psychophysics of perception, and visual neuroscience.Comment: Submitted to PLoS ON

Quantitative Changes in Hydrocarbons over Time in Fecal Pellets of Incisitermes minor May Predict Whether Colonies Are Alive or Dead

Hydrocarbon mixtures extracted from fecal pellets of drywood termites are species-specific and can be characterized to identify the termites responsible for damage, even when termites are no longer present or are unable to be recovered easily. In structures infested by drywood termites, it is common to find fecal pellets, but difficult to sample termites from the wood. When fecal pellets appear after remedial treatment of a structure, it is difficult to determine whether this indicates that termites in the structure are still alive and active or not. We examined the hydrocarbon composition of workers, alates, and soldiers of Incisitermes minor (Hagen) (family Kalotermitidae) and of fecal pellets of workers. Hydrocarbons were qualitatively similar among castes and pellets. Fecal pellets that were aged for periods of 0, 30, 90, and 365 days after collection were qualitatively similar across all time periods, however, the relative quantities of certain individual hydrocarbons changed over time, with 19 of the 73 hydrocarbon peaks relatively increasing or decreasing. When the sums of the positive and negative slopes of these 19 hydrocarbons were indexed, they produced a highly significant linear correlation (R2 = 0.89). Consequently, the quantitative differences of these hydrocarbons peaks can be used to determine the age of worker fecal pellets, and thus help determine whether the colony that produced them is alive or dead