Estimating survival in patients with gastrointestinal cancers and brain metastases: An update of the graded prognostic assessment for gastrointestinal cancers (GI-GPA).

BackgroundPatients with gastrointestinal cancers and brain metastases (BM) represent a unique and heterogeneous population. Our group previously published the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with GI cancers (GI-GPA) (1985-2007, n = 209). The purpose of this study is to update the GI-GPA based on a larger contemporary database.MethodsAn IRB-approved consortium database analysis was performed using a multi-institutional (18), multi-national (3) cohort of 792 patients with gastrointestinal (GI) cancers, with newly-diagnosed BM diagnosed between 1/1/2006 and 12/31/2017. Survival was measured from date of first treatment for BM. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. These factors were incorporated into the updated GI-GPA.ResultsMedian survival (MS) varied widely by primary site and other prognostic factors. Four significant factors (KPS, age, extracranial metastases and number of BM) were used to formulate the updated GI-GPA. Overall MS for this cohort remains poor; 8 months. MS by GPA was 3, 7, 11 and 17 months for GPA 0-1, 1.5-2, 2.5-3.0 and 3.5-4.0, respectively. >30% present in the worst prognostic group (GI-GPA of ≤1.0).ConclusionsBrain metastases are not uncommon in GI cancer patients and MS varies widely among them. This updated GI-GPA index improves our ability to estimate survival for these patients and will be useful for therapy selection, end-of-life decision-making and stratification for future clinical trials. A user-friendly, free, on-line app to calculate the GPA score and estimate survival for an individual patient is available at brainmetgpa.com

Sleep quality in middle-aged and elderly Chinese: distribution, associated factors and associations with cardio-metabolic risk factors

Background Poor sleep quality has been associated with increased risk of heart disease, diabetes and mortality. However, limited information exists on the distribution and determinants of sleep quality and its associations with cardio-metabolic risk factors in Chinese populations. We aimed to evaluate this in the current study. Methods A cross-sectional survey conducted in 2005 of 1,458 men and 1,831 women aged 50–70 years from urban and rural areas of Beijing and Shanghai. Using a questionnaire, sleep quality was measured in levels of well, common and poor. Comprehensive measures of socio-demographical and health factors and biomarkers of cardio-metabolic disease were recorded. These were evaluated in association with sleep quality using logistic regression models. Results Half of the population reported good sleep quality. After adjusting for potential confounders, women and Beijing residents had almost half the probability to report good sleep quality. Good physical and mental health (good levels of self-rated health (OR 2.48; 95%CI 2.08 to 2.96) and no depression (OR 4.05; 95%CI 3.12 to 5.26)) related to an increased chance of reporting good sleep quality, whereas short sleep duration (<7 hrs OR 0.10; 95%CI 0.07 to 0.14)) decreased it substantially. There were significant associations between levels of sleep quality and concentrations of plasma insulin, total and LDL cholesterol, and index of insulin resistance. Conclusion Levels of good sleep quality in middle-age and elderly Chinese were low. Gender, geographical location, self-rated health, depression and sleep quantity were major factors associated with sleep quality. Prospective studies are required to distil the factors that determine sleep quality and the effects that sleep patterns exert on cardio-metabolic health

A survey of assistive technologies and applications for blind users on mobile platforms: a review and foundation for research

This paper summarizes recent developments in audio and tactile feedback based assistive technologies targeting the blind community. Current technology allows applications to be efficiently distributed and run on mobile and handheld devices, even in cases where computational requirements are significant. As a result, electronic travel aids, navigational assistance modules, text-to-speech applications, as well as virtual audio displays which combine audio with haptic channels are becoming integrated into standard mobile devices. This trend, combined with the appearance of increasingly user- friendly interfaces and modes of interaction has opened a variety of new perspectives for the rehabilitation and training of users with visual impairments. The goal of this paper is to provide an overview of these developments based on recent advances in basic research and application development. Using this overview as a foundation, an agenda is outlined for future research in mobile interaction design with respect to users with special needs, as well as ultimately in relation to sensor-bridging applications in genera

Feasibility of trial procedures for a randomised controlled trial of a community based group exercise intervention for falls prevention for visually impaired older people: the VIOLET study

Background Visually impaired older people (VIOP) have a higher risk of falling than their sighted peers, and are likely to avoid physical activity. The aim was to adapt the existing Falls Management Exercise (FaME) programme for VIOP, delivered in the community, and to investigate the feasibility of conducting a definitive randomised controlled trial (RCT) of this adapted intervention. Methods Two-centre randomised mixed methods pilot trial and economic evaluation of the adapted group-based FaME programme for VIOP versus usual care. A one hour exercise programme ran weekly over 12 weeks at the study sites (Newcastle and Glasgow), delivered by third sector (voluntary and community) organisations. Participants were advised to exercise at home for an additional two hours over the week. Those randomised to the usual activities group received no intervention. Outcome measures were completed at baseline, 12 and 24 weeks. The potential primary outcome was the Short Form Falls Efficacy Scale – International (SFES-I). Participants’ adherence was assessed by reviewing attendance records and self-reported compliance to the home exercises. Adherence with the course content (fidelity) by instructors was assessed by a researcher. Adverse events were collected in a weekly phone call. Results Eighteen participants, drawn from community-living VIOP were screened; 68 met the inclusion criteria; 64 participants were randomised with 33 allocated to the intervention and 31 to the usual activities arm. 94% of participants provided data at the 12 week visit and 92% at 24 weeks. Adherence was high. The intervention was found to be safe with 76% attending nine or more classes. Median time for home exercise was 50 min per week. There was little or no evidence that fear of falling, balance and falls risk, physical activity, emotional, attitudinal or quality of life outcomes differed between trial arms at follow-up. Conclusions The intervention, FaME, was implemented successfully for VIOP and all progression criteria for a main trial were met. The lack of difference between groups on fear of falling was unsurprising given it was a pilot study but there may have been other contributory factors including suboptimal exercise dose and apparent low risk of falls in participants. These issues need addressing for a future trial

Hydraulic & Design Parameters in Full-Scale Constructed Wetland & Treatment Units: Six Case Studies

The efficiency of pond and constructed wetland (CW) treatment systems, is influenced by the internal hydrodynamics and mixing interactions between water and aquatic vegetation. In order to contribute to current knowledge of how emergent real vegetation affects solute mixing, and on what the shape and size effects are on the mixing characteristics, an understanding and quantification of those physical processes and interactions was evaluated. This paper presents results from tracer tests conducted during 2015-2016 in six full-scale systems in the UK under different flow regimes, operational depths, shapes and sizes, and in-/outlet configurations. The aim is to quantify the hydraulic performance and mixing characteristics of the treatment units, and to investigate the effect of size and shape on the mixing processes. Relative comparison of outlet configuration, inflow conditions, and internal features between the six different treatment units showed variations in residence times of up to a factor of 3. A key outcome of this study, demonstrated that the width is a more important dimension for the efficiency of the unit compared to the depth. Results underlined the importance of investigating hydrodynamics and physics of flow in full-size units to enhance treatment efficiency and predictions of water quality models

How do patients with inflammatory bowel disease want their biological therapy administered?

<p>Abstract</p> <p>Background</p> <p>Infliximab is usually administered by two monthly intravenous (iv) infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc) injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn's Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration.</p> <p>The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD) patients for two currently available anti-TNF agents and the reasons for their choices.</p> <p>Methods</p> <p>An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK) between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous) were available, which drug route of administration would they choose.</p> <p>Results</p> <p>One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response). The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent) preferred infliximab and 19 patients (24 percent) preferred adalimumab (p = 0.07). Twenty-six patients (33 percent) did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv) was: <it>"I do not like the idea of self-injecting," </it>(67 percent). For those patients who preferred adalimumab (sc) the commonest reason cited was: <it>"I prefer the convenience of injecting at home," </it>(79 percent). Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab) six patients stated that they would prefer infliximab if given the choice in the future (p = 0.75).</p> <p>Conclusions</p> <p>There was a trend towards patient preference for infliximab (iv) treatment as opposed to adalimumab (sc) in patients with IBD. This difference may be due to the frequency of administration, mode of administration or differing 'times in the market-place', as infliximab had been approved for a longer period of time in Crohn's disease. Further studies are required in IBD patients to investigate whether patient choice will affect compliance, patient satisfaction and efficacy of treatment with anti-TNF therapies.</p

Plasmodium falciparum Merozoite Invasion Is Inhibited by Antibodies that Target the PfRh2a and b Binding Domains

Plasmodium falciparum, the causative agent of the most severe form of malaria in humans invades erythrocytes using multiple ligand-receptor interactions. The P. falciparum reticulocyte binding-like homologue proteins (PfRh or PfRBL) are important for entry of the invasive merozoite form of the parasite into red blood cells. We have analysed two members of this protein family, PfRh2a and PfRh2b, and show they undergo a complex series of proteolytic cleavage events before and during merozoite invasion. We show that PfRh2a undergoes a cleavage event in the transmembrane region during invasion consistent with activity of the membrane associated PfROM4 protease that would result in release of the ectodomain into the supernatant. We also show that PfRh2a and PfRh2b bind to red blood cells and have defined the erythrocyte-binding domain to a 15 kDa region at the N-terminus of each protein. Antibodies to this receptor-binding region block merozoite invasion demonstrating the important function of this domain. This region of PfRh2a and PfRh2b has potential in a combination vaccine with other erythrocyte binding ligands for induction of antibodies that would block a broad range of invasion pathways for P. falciparum into human erythrocytes

Thinking outside the curve, part I: modeling birthweight distribution

<p>Abstract</p> <p>Background</p> <p>Greater epidemiologic understanding of the relationships among fetal-infant mortality and its prognostic factors, including birthweight, could have vast public health implications. A key step toward that understanding is a realistic and tractable framework for analyzing birthweight distributions and fetal-infant mortality. The present paper is the first of a two-part series that introduces such a framework.</p> <p>Methods</p> <p>We propose describing a birthweight distribution via a normal mixture model in which the number of components is determined from the data using a model selection criterion rather than fixed <it>a priori</it>.</p> <p>Results</p> <p>We address a number of methodological issues, including how the number of components selected depends on the sample size, how the choice of model selection criterion influences the results, and how estimates of mixture model parameters based on multiple samples from the same population can be combined to produce confidence intervals. As an illustration, we find that a 4-component normal mixture model reasonably describes the birthweight distribution for a population of white singleton infants born to heavily smoking mothers. We also compare this 4-component normal mixture model to two competitors from the existing literature: a contaminated normal model and a 2-component normal mixture model. In a second illustration, we discover that a 6-component normal mixture model may be more appropriate than a 4-component normal mixture model for a general population of black singletons.</p> <p>Conclusions</p> <p>The framework developed in this paper avoids assuming the existence of an interval of birthweights over which there are no compromised pregnancies and does not constrain birthweights within compromised pregnancies to be normally distributed. Thus, the present framework can reveal heterogeneity in birthweight that is undetectable via a contaminated normal model or a 2-component normal mixture model.</p

Towards a comprehensive structural coverage of completed genomes: a structural genomics viewpoint

BACKGROUND: Structural genomics initiatives were established with the aim of solving protein structures on a large-scale. For many initiatives, such as the Protein Structure Initiative (PSI), the primary aim of target selection is focussed towards structurally characterising protein families which, so far, lack a structural representative. It is therefore of considerable interest to gain insights into the number and distribution of these families, and what efforts may be required to achieve a comprehensive structural coverage across all protein families. RESULTS: In this analysis we have derived a comprehensive domain annotation of the genomes using CATH, Pfam-A and Newfam domain families. We consider what proportions of structurally uncharacterised families are accessible to high-throughput structural genomics pipelines, specifically those targeting families containing multiple prokaryotic orthologues. In measuring the domain coverage of the genomes, we show the benefits of selecting targets from both structurally uncharacterised domain families, whilst in addition, pursuing additional targets from large structurally characterised protein superfamilies. CONCLUSION: This work suggests that such a combined approach to target selection is essential if structural genomics is to achieve a comprehensive structural coverage of the genomes, leading to greater insights into structure and the mechanisms that underlie protein evolution