It's more than low BMI: prevalence of cachexia and associated mortality in COPD

Background: Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients. However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index. For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE. Methods: In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation. The weight-loss definition incorporated weight-loss > 5% or weight-loss > 2% (if low BMI) in 12-months. The low BMI component in BODE was replaced with the consensus definition to create the CODE (Consensus cachexia, Obstruction, Dyspnea and Exercise) index and the weight-loss definition to create the WODE (Weight loss, Obstruction, Dyspnea and Exercise) index. Mortality was assessed using Kaplan-Meier survival and Cox Regression. Performance of models was compared using C-statistics. Results: Among 1483 COPD cases, the prevalences of cachexia by the consensus and weight-loss definitions were 4.7 and 10.4%, respectively. Cachectic patients had a greater than three-fold increased mortality by either the consensus or the weight-loss definition of cachexia independent of BMI and lung function. The CODE index predicted mortality slightly more accurately than the BODE and WODE indices. Conclusions: Cachexia is associated with increased mortality among COPD patients. Monitoring cachexia using weight-loss criteria is relatively simple and predictive of mortality among COPD cases who may be missed if only low BMI is used

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1

Background: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. Methods: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162). Four GWAS of ΔBMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418 365 single-nucleotide polymorphisms (SNPs). Results: Two SNPs reached a level of genome-wide significance (P < 5 × 10−8) with ΔBMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (β = 0.13, P = 4.3 × 10−8); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (β = 0.10, P = 1.9 × 10−8). The DOCK1 SNP association replicated in the ΔBMI GWAS among COPD cases (βmeta-analyis = 0.10, Pmeta-analyis = 9.3 × 10−10). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion. Conclusions: In sum, one statistically significant common variant in the DOCK1 gene was associated with ΔBMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ΔBMI in complex diseases

GENETIC EPIDEMIOLOGY OF ATOPY AND THE HYGIENE HYPOTHESIS

Decreased exposure to microorganisms may be the reason the prevalence of allergic diseases has been increasing for the past several decades in westernized countries 1. This postulate, the hygiene hypothesis, was formulated by Strachan when he observed after following a large cohort of children for 23 years that being born late in the birth order and being from a large family were protective for allergic diseases'. More recent studies have demonstrated that the prevalence of atopic sensitization is lower in the children of farmers 3-6. Collectively, these studies appear to indicate that an appropriate microbial load is necessary to confer protection from allergic diseases. The Toll-Like Receptor 4 mutation (TLR4 D2990) is known to confer hypo-responsiveness to bacterial endotoxin in some individuals7,8. Individuals who carry this mutation may require additional bacterial challenge to switch to a non-allergic phenotype. Consequently, this thesis investigated the hypotheses that the TLR4 D2990 was a significant predictor of atopic status in Humboldt, SK family-based data and that the effect of parental history on allergic diseases was modified by the environmental covariates: family size, farming exposures, pets and smoking in addition to age and sex. Overall, 734 children participated from Humboldt, SK in the study representing a response rate of 79.1 %. The crude prevalence of atopy in this population of children was 30.4%. TLR4 D2990 was not associated with atopy in this population of children even though the power to detect such an association if it existed was high. Of the 734 children, 309 children had both parents participate in the study representing 111 non-farming and 68 farming families. Based on the variables; total number of siblings, parental smoking, pets, humidity, parental history of allergic diseases and parental atopy, farming families did not differ from non-farming families in this study. Children whose parents farmed, whose parents worked with livestock or whose parents had atopy were not at a decreased or an increased risk of being atopic in this study. The reduced model consisting of the variables age, sex and parental history of allergic disease was the most parsimonious for the outcome variable, atopy

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1.

BackgroundThere have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.MethodsA linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162). Four GWAS of ΔBMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418 365 single-nucleotide polymorphisms (SNPs).ResultsTwo SNPs reached a level of genome-wide significance (P &lt; 5 × 10-8 ) with ΔBMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (β = 0.13, P = 4.3 × 10-8 ); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (β = 0.10, P = 1.9 × 10-8 ). The DOCK1 SNP association replicated in the ΔBMI GWAS among COPD cases (βmeta-analyis  = 0.10, Pmeta-analyis  = 9.3 × 10-10 ). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion.ConclusionsIn sum, one statistically significant common variant in the DOCK1 gene was associated with ΔBMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ΔBMI in complex diseases

Student Work Placement: Friend or Foe? A study of the perceptions of university students on industrial work placement

At the National University of Ireland Maynooth, Computer Science and Software Engineering students are required to undertake an industrial work placement module as part of their course. The work placement is typically six to eighteen months long and takes place in the penultimate year of the degree. This paper evaluates students’ perception of the quality of the learning experience they received through work placement. The voice of many key players involved in the process is captured, including, the students themselves, members of the academic department and the Industrial Work Placement Office; and importantly this paper is authored by representatives of each of these groups. In particular, the paper evaluates the types of preparations students make prior to commencing a placement, the transferable skills acquired and improved during their placement, and student perceptions of the advantages and disadvantages of their placement. A mixed data acquisition model is used for gathering data including questionnaires, interviews and focus groups. The gathered data is analysed and a critique on the findings is presented. The paper concludes with recommendations and considerations for any institution that is interested in offering an industrial work placement component

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1

Background: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. Methods: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162). Four GWAS of ΔBMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418 365 single-nucleotide polymorphisms (SNPs). Results: Two SNPs reached a level of genome-wide significance (P < 5 × 10−8) with ΔBMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (β = 0.13, P = 4.3 × 10−8); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (β = 0.10, P = 1.9 × 10−8). The DOCK1 SNP association replicated in the ΔBMI GWAS among COPD cases (βmeta-analyis = 0.10, Pmeta-analyis = 9.3 × 10−10). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion. Conclusions: In sum, one statistically significant common variant in the DOCK1 gene was associated with ΔBMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ΔBMI in complex diseases