Synthesis and in vitro protozoocidal evaluation of novel diazabicyclic tropolone derivatives.

The synthesis and in vitro antiparasitic activity of twenty-seven novel diazabicycles based on tropolone ethers is presented. The compounds can be readily prepared by means of a high-yielding hetero Diels-Alder reaction using simple and readily available starting materials. Several of the new diazabicycles have in vitro activities against Trypanosoma cruzi, Leishmania donovani, Trypanosoma brucei rhodesiense, and chloroquine-resistant Plasmodium falciparum that are comparable or superior to those of currently employed protozoocidal agents

Augmenting the Space Domain Awareness Ground Architecture via Decision Analysis and Multi-Objective Optimization

Purpose — The US Government is challenged to maintain pace as the world’s de facto provider of space object cataloging data. Augmenting capabilities with nontraditional sensors present an expeditious and low-cost improvement. However, the large tradespace and unexplored system of systems performance requirements pose a challenge to successful capitalization. This paper aims to better define and assess the utility of augmentation via a multi-disiplinary study. Design/methodology/approach — Hypothetical telescope architectures are modeled and simulated on two separate days, then evaluated against performance measures and constraints using multi-objective optimization in a heuristic algorithm. Decision analysis and Pareto optimality identifies a set of high-performing architectures while preserving decision-maker design flexibility. Findings — Capacity, coverage and maximum time unobserved are recommended as key performance measures. A total of 187 out of 1017 architectures were identified as top performers. A total of 29% of the sensors considered are found in over 80% of the top architectures. Additional considerations further reduce the tradespace to 19 best choices which collect an average of 49–51 observations per space object with a 595–630 min average maximum time unobserved, providing redundant coverage of the Geosynchronous Orbit belt. This represents a three-fold increase in capacity and coverage and a 2 h (16%) decrease in the maximum time unobserved compared to the baseline government-only architecture as-modeled. Originality/value — This study validates the utility of an augmented network concept using a physics-based model and modern analytical techniques. It objectively responds to policy mandating cataloging improvements without relying solely on expert-derived point solutions

Planned Missing Data Designs & Small Sample Size: How Small is Too Small?

Utilizing planned missing data (PMD) designs (ex. 3-form surveys) enables researchers to ask participants fewer questions during the data collection process. An important question, however, is just how few participants are needed to effectively employ planned missing data designs in research studies. This paper explores this question by using simulated three-form planned missing data to assess analytic model convergence, parameter estimate bias, standard error bias, mean squared error (MSE), and relative efficiency (RE).Three models were examined: a one-time point, cross-sectional model with 3 constructs; a two-time point model with 3 constructs at each time point; and a three-time point, mediation model with 3 constructs over three time points. Both full-information maximum likelihood (FIML) and multiple imputation (MI) were used to handle the missing data. Models were found to meet convergence rate and acceptable bias criteria with FIML at smaller sample sizes than with MI

Sex Differences in the Perceived Dominance and Prestige of Women With and Without Cosmetics

Human social status has long been of interest to evolutionary and social psychologists. The question of who gets to control resources and be a leader has garnered a lot of attention from these and other fields, and this thesis examines evidence for there being two different mechanisms of achieving high status, and their correlates. The mechanisms are 1) Dominance: being aggressive, manipulative and forcing others to follow you, and 2) Prestige: possessing qualities which make others freely follow you. Chapter 1 is an introductory chapter in which I explain selection pressures, group formation, and the need for social hierarchies; I then describe the two proposed methods of attaining social status and how facial characteristics can give clues as to an individual’s social status. In Chapter 2, my first experimental chapter, I examined how faces created to appear either high in dominance or high in prestige were judged with respect to those traits as well as personality characteristics. Taking this further, in Chapter 3, I looked at how natural variation in real faces would reflect differences in other- and self-perceived ratings of dominance and prestige. Chapter 4 served to examine whether, given a set of words related to social status, I would find differences in what words were placed into dominant or prestige categories. Findings within these chapters are consistent with dominance and prestige being separable methods of attaining high status, from differences in facial appearance (Chapter 2 and 3), to personality characteristics (Chapter 2), to word usage (Chapter 4). Once I had established that these were two distinct routes to achieving high status, I chose to focus on dominance in Chapter 5 and explored the conceptual relationships between dominance and facial expressions. I found that manipulating perceptions of dominance affected how intense expressions of anger, sadness, and fear were perceived (Chapter 5). As there has been a paucity of research in the area of women’s social status, in Chapter 6, I went on to explore what effects cosmetics use in women would have on their perceived social status. I found differences in how men and women perceived women wearing cosmetics, which again points to a distinction between dominance and prestige. My thesis then presents a broad view of the two different mechanisms for attaining high status. Using new methods not otherwise used in exploring dominance and prestige I was able to explore correlates and indicators, as well as perceptions of both strategies. These findings will allow us to determine who might be capable of attaining social status, which of the two methods they might use, as well as what implicit associations we hold about each. They will also open doors for future research into the two strategies, and even help interpret previous research, as many previous studies simply relate to high status and do not distinguish between dominance and prestige

Randomised controlled feasibility trial of a web-based weight management intervention with nurse support for obese patients in primary care

<b>Background</b><p></p> There is a need for cost-effective weight management interventions that primary care can deliver to reduce the morbidity caused by obesity. Automated web-based interventions might provide a solution, but evidence suggests that they may be ineffective without additional human support. The main aim of this study was to carry out a feasibility trial of a web-based weight management intervention in primary care, comparing different levels of nurse support, to determine the optimal combination of web-based and personal support to be tested in a full trial.<p></p> <b>Methods</b><p></p> This was an individually randomised four arm parallel non-blinded trial, recruiting obese patients in primary care. Following online registration, patients were randomly allocated by the automated intervention to either usual care, the web-based intervention only, or the web-based intervention with either basic nurse support (3 sessions in 3 months) or regular nurse support (7 sessions in 6 months). The main outcome measure (intended as the primary outcome for the main trial) was weight loss in kg at 12 months. As this was a feasibility trial no statistical analyses were carried out, but we present means, confidence intervals and effect sizes for weight loss in each group, uptake and retention, and completion of intervention components and outcome measures.<p></p> <b>Results</b><p></p> All randomised patients were included in the weight loss analyses (using Last Observation Carried Forward). At 12 months mean weight loss was: usual care group (n = 43) 2.44 kg; web-based only group (n = 45) 2.30 kg; basic nurse support group (n = 44) 4.31 kg; regular nurse support group (n = 47) 2.50 kg. Intervention effect sizes compared with usual care were: d = 0.01 web-based; d = 0.34 basic nurse support; d = 0.02 regular nurse support. Two practices deviated from protocol by providing considerable weight management support to their usual care patients.<p></p> <b>Conclusions</b><p></p> This study demonstrated the feasibility of delivering a web-based weight management intervention supported by practice nurses in primary care, and suggests that the combination of the web-based intervention with basic nurse support could provide an effective solution to weight management support in a primary care context

Mechanistic role of a disease-associated genetic variant within the ADAM33 asthma susceptibility gene

<p>Abstract</p> <p>Background</p> <p>ADAM33 has been identified as an asthma-associated gene in an out-bred population. Genetic studies suggested that the functional role of this metalloprotease was in airway remodeling. However, the mechanistic roles of the disease-associated SNPs have yet to be elucidated especially in the context of the pathophysiology of asthma. One disease-associated SNP, BC+1, which resides in intron BC toward the 5' end of ADAM33, is highly associated with the disease.</p> <p>Methods</p> <p>The region surrounding this genetic variant was cloned into a model system to determine if there is a regulatory element within this intron that influences transcription.</p> <p>Results</p> <p>The BC+1 protective allele did not impose any affect on the transcription of the reporter gene. However, the at-risk allele enforced such a repressive affect on the promoter that no protein product from the reporter gene was detected. These results indicated that there exists within intron BC a regulatory element that acts as a repressor for gene expression. Moreover, since SNP BC+1 is a common genetic variant, this region may interact with other undefined regulatory elements within ADAM33 to provide a rheostat effect, which modulates pre-mRNA processing. Thus, SNP BC+1 may have an important role in the modulation of ADAM33 gene expression.</p> <p>Conclusion</p> <p>These data provide for the first time a functional role for a disease-associated SNP in ADAM33 and begin to shed light on the deregulation of this gene in the pathophysiology of asthma.</p

An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial

Background The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care. Methods We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m2 or more (or ≥28 kg/m2 with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+—a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face [POWeR+F]; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote [POWeR+R]; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703. Findings Between Jan 30, 2013, and March 20, 2014, 818 participants were randomly assigned to the control group (n=279), the POWeR+F group (n=269), or the POWeR+R group (n=270). Weight loss averaged over 12 months was recorded in 666 (81%) participants. The control group lost almost 3 kg over 12 months (crude mean weight: baseline 104·38 kg [SD 21·11; n=279], 6 months 101·91 kg [19·35; n=136], 12 months 101·74 kg [19·57; n=227]). The primary imputed analysis showed that compared with the control group, patients in the POWeR+F group achieved an additional weight reduction of 1·5 kg (95% CI 0·6–2·4; p=0·001) averaged over 12 months, and patients in the POWeR+R group achieved an additional 1·3 kg (0·34–2·2; p=0·007). 21% of patients in the control group had maintained a clinically important 5% weight reduction at month 12, compared with 29% of patients in the POWeR+F group (risk ratio 1·56, 0·96–2·51; p=0·070) and 32% of patients in the POWeR+R group (1·82, 1·31–2·74; p=0·004). The incremental overall cost to the health service per kg weight lost with the POWeR+ interventions versus the control strategy was £18 (95% CI −129 to 195) for POWeR+F and –£25 (−268 to 157) for POWeR+R; the probability of being cost-effective at a threshold of £100 per kg lost was 88% and 98%, respectively. No adverse events were reported. Interpretation Weight loss can be maintained in some individuals by use of novel written material with occasional brief nurse follow-up. However, more people can maintain clinically important weight reductions with a web-based behavioural program and brief remote follow-up, with no increase in health service costs. Future research should assess the extent to which clinically important weight loss can be maintained beyond 1 year

Nutritional characterisation of European aquaculture processing by-products to facilitate strategic utilisation

Sustainability analyses of aquaculture typically ignore the fate and value of processing by-products. The aim of this study was to characterise the nutritional content of the common processing by-products (heads, frames, trimmings, skin and viscera) of five important finfish species farmed in Europe; Atlantic salmon (Salmo salar), European seabass (Dicentrarchus labrax), gilthead seabream (Sparus aurata), common carp (Cyprinus carpio) and turbot (Psetta maxima) to inform on best utilisation strategies. Our results indicate a substantially higher total flesh yield (64–77 %) can be achieved if fully processed, compared to fillet only (30–56 %). We found that heads, frames, trimmings and skin from Atlantic salmon, European seabass, gilthead seabream and turbot frames showed medium to high edible yields, medium to high lipid, and medium to high eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, indicating significant potential for direct use in human food. By-products which are unattractive for use in food directly but have low ash content and medium to high crude protein, lipid and EPA and DHA content, such as viscera, could be directed to animal feed. Skin showed interesting nutritional values, but has more potential in non-food applications, such as the fashion, cosmetic and pharmaceutical industries. The results indicate potential to increase the direct food, animal feed and non-food value of European aquaculture, without an increase in production volumes or the use of additional resources. The importance of changing consumer perceptions and addressing infrastructure and legislative barriers to maximize utilisation is emphasised

Detection of CI in absorption towards PKS 1830-211 with the eSMA

We report the first science observations and results obtained with the "extended" SMA (eSMA), which is composed of the SMA (Submillimeter Array), JCMT (James Clerk Maxwell Telescope) and CSO (Caltech Submillimeter Observatory). Redshifted absorptions at z=0.886 of CI (^3P_1 - ^3P_0) were observed with the eSMA with an angular resolution of 0.55"x0.22" at 1.1 mm toward the southwestern image of the remarkable lensed quasar PKS 1830-211, but not toward the northeastern component at a separation of ~1". Additionally, SMA observations of CO, 13CO and C18O (all J=4-3) were obtained toward this object: CO was also detected toward the SW component, but none of the isotopologues were. This is the first time [CI] is detected in this object, allowing the first direct determination of relative abundances of neutral atomic carbon to CO in the molecular clouds of a spiral galaxy at z>0.1. The [CI] and CO profiles can be decomposed into two and three velocity components respectively. We derive C/CO column density ratios ranging from <0.5 (representative of dense cores) to ~2.5 (close to translucent clouds values). This could indicate that we are seeing environments with different physical conditions or that we are witnessing chemical evolution of regions where C has not completely been converted into CO.Comment: 6 pages using emulateapj, 3 tables, 2 figures ; accepted for publication in ApJ