Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality

OBJECTIVES: Height is inversely associated with cardiovascular disease mortality risk and has shown variable associations with cancer incidence and mortality. The interpretation of findings from previous studies has been constrained by data limitations. Associations between height and specific causes of death were investigated in a large general population cohort of men and women from the West of Scotland. DESIGN: Prospective observational study. SETTING: Renfrew and Paisley, in the West of Scotland. SUBJECTS: 7052 men and 8354 women aged 45-64 were recruited into a study in Renfrew and Paisley, in the West of Scotland, between 1972 and 1976. Detailed assessments of cardiovascular disease risk factors, morbidity and socioeconomic circumstances were made at baseline. MAIN OUTCOME MEASURES: Deaths during 20 years of follow up classified into specific causes. RESULTS: Over the follow up period 3347 men and 2638 women died. Height is inversely associated with all cause, coronary heart disease, stroke, and respiratory disease mortality among men and women. Adjustment for socioeconomic position and cardiovascular risk factors had little influence on these associations. Height is strongly associated with forced expiratory volume in one second (FEV1) and adjustment for FEV1 considerably attenuated the association between height and cardiorespiratory mortality. Smoking related cancer mortality is not associated with height. The risk of deaths from cancer unrelated to smoking tended to increase with height, particularly for haematopoietic, colorectal and prostate cancers. Stomach cancer mortality was inversely associated with height. Adjustment for socioeconomic position had little influence on these associations. CONCLUSION: Height serves partly as an indicator of socioeconomic circumstances and nutritional status in childhood and this may underlie the inverse associations between height and adulthood cardiorespiratory mortality. Much of the association between height and cardiorespiratory mortality was accounted for by lung function, which is also partly determined by exposures acting in childhood. The inverse association between height and stomach cancer mortality probably reflects Helicobacter pylori infection in childhood resulting inor being associated withshorter height. The positive associations between height and several cancers unrelated to smoking could reflect the influence of calorie intake during childhood on the risk of these cancers

Brain metastases in gastro-oesophageal adenocarcinoma: Insights into the role of the human epidermal growth factor receptor 2 (HER2)

Background: Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown.Patients and Methods: A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively. Inclusion in the study required a predefined clinical data set, a central neuro-radiological or histopathological confirmation of metastatic CNS involvement and central assessment of HER2 by immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition, expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by IHC. Results: One hundred patients fulfilled the inclusion criteria. The population's median age was 59 years (interquartile range: 54-68), of which 85 (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin. HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from initial diagnosis to the development of brain metastases (BMets) or leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss of expression in at least one DNA MMR proteins in 6%. Conclusions: The proportion of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and CNS involvement was higher than expected. The impact of anti-HER2 therapies should be studied prospectively

In Vitro Fermentation of NUTRIOSE® FB06, a wheat dextrin soluble fibre, in a continuous culture human colonic model system

Wheat dextrin soluble fibre may have metabolic and health benefits, potentially acting via mechanisms governed by the selective modulation of the human gut microbiota. Our aim was to examine the impact of wheat dextrin on the composition and metabolic activity of the gut microbiota. We used a validated in vitro three-stage continuous culture human colonic model (gut model) system comprised of vessels simulating anatomical regions of the human colon. To mimic human ingestion, 7 g of wheat dextrin (NUTRIOSE® FB06) was administered to three gut models, twice daily at 10.00 and 15.00, for a total of 18 days. Samples were collected and analysed for microbial composition and organic acid concentrations by 16S rRNA-based fluorescence in situ hybridisation and gas chromatography approaches, respectively. Wheat dextrin mediated a significant increase in total bacteria in vessels simulating the transverse and distal colon, and a significant increase in key butyrate-producing bacteria Clostridium cluster XIVa and Roseburia genus in all vessels of the gut model. The production of principal short-chain fatty acids, acetate, propionate and butyrate, which have been purported to have protective, trophic and metabolic host benefits, were increased. Specifically, wheat dextrin fermentation had a significant butyrogenic effect in all vessels of the gut model and significantly increased production of acetate (vessels 2 and 3) and propionate (vessel 3), simulating the transverse and distal regions of the human colon, respectively. In conclusion, wheat dextrin NUTRIOSE® FB06 is selectively fermented in vitro by Clostridium cluster XIVa and Roseburia genus and beneficially alters the metabolic profile of the human gut microbiota

The changing global distribution and prevalence of canine transmissible venereal tumour.

BACKGROUND: The canine transmissible venereal tumour (CTVT) is a contagious cancer that is naturally transmitted between dogs by the allogeneic transfer of living cancer cells during coitus. CTVT first arose several thousand years ago and has been reported in dog populations worldwide; however, its precise distribution patterns and prevalence remain unclear. RESULTS: We analysed historical literature and obtained CTVT prevalence information from 645 veterinarians and animal health workers in 109 countries in order to estimate CTVT's former and current global distribution and prevalence. This analysis confirmed that CTVT is endemic in at least 90 countries worldwide across all inhabited continents. CTVT is estimated to be present at a prevalence of one percent or more in dogs in at least 13 countries in South and Central America as well as in at least 11 countries in Africa and 8 countries in Asia. In the United States and Australia, CTVT was reported to be endemic only in remote indigenous communities. Comparison of current and historical reports of CTVT indicated that its prevalence has declined in Northern Europe, possibly due to changes in dog control laws during the nineteenth and twentieth centuries. Analysis of factors influencing CTVT prevalence showed that presence of free-roaming dogs was associated with increased CTVT prevalence, while dog spaying and neutering were associated with reduced CTVT prevalence. Our analysis indicated no gender bias for CTVT and we found no evidence that animals with CTVT frequently harbour concurrent infectious diseases. Vincristine was widely reported to be the most effective therapy for CTVT. CONCLUSIONS: Our results provide a survey of the current global distribution of CTVT, confirming that CTVT is endemic in at least 90 countries worldwide. Additionally, our analysis highlights factors that continue to modify CTVT's prevalence around the world and implicates free-roaming dogs as a reservoir for the disease. Our analysis also documents the disappearance of the disease from the United Kingdom during the twentieth century, which appears to have been an unintentional result of the introduction of dog control policies.This is the author's accepted manuscript. The final version of this article has been published by BioMed Central: http://www.biomedcentral.com/1746-6148/10/168

Improved Sézary cell detection and novel insights into immunophenotypic and molecular heterogeneity in Sézary syndrome

Sézary syndrome (SS) is an aggressive leukemic form of cutaneous T-cell lymphoma with neoplastic CD4+ T cells present in skin, lymph nodes, and blood. Despite advances in therapy, prognosis remains poor, with a 5-year overall survival of 30%. The immunophenotype of Sézary cells is diverse, which hampers efficient diagnosis, sensitive disease monitoring, and accurate assessment of treatment response. Comprehensive immunophenotypic profiling of Sézary cells with an in-depth analysis of maturation and functional subsets has not been performed thus far. We immunophenotypically profiled 24 patients with SS using standardized and sensitive EuroFlow-based multiparameter flow cytometry. We accurately identified and quantified Sézary cells in blood and performed an in-depth assessment of their phenotypic characteristics in comparison with their normal counterparts in the blood CD4+ T-cell compartment. We observed inter- and intrapatient heterogeneity and phenotypic changes over time. Sézary cells exhibited phenotypes corresponding with classical and nonclassical T helper subsets with different maturation phenotypes. We combined multiparameter flow cytometry analyses with fluorescence-activated cell sorting and performed RNA sequencing studies on purified subsets of malignant Sézary cells and normal CD4+ T cells of the same patients. We confirmed pure monoclonality in Sézary subsets, compared transcriptomes of phenotypically distinct Sézary subsets, and identified novel downregulated genes, most remarkably THEMIS and LAIR1, which discriminate Sézary cells from normal residual CD4+ T cells. Together, these findings further unravel the heterogeneity of Sézary cell subpopulations within and between patients. These new data will support improved blood staging and more accurate disease monitoring

Decisional Conflict and User Acceptance of Multicriteria Decision-Making Aids *

Despite the development of increasingly sophisticated and refined multicriteria decision-making (MCDM) methods, an examination of the experimental evidence indicates that users most often prefer relatively unsophisticated methods. In this paper, we synthesize theories and empirical findings from the psychology of judgment and choice to provide a new theoretical explanation for such user preferences. Our argument centers on the assertion that the MCDM method preferred by decision makers is a function of the degree to which the method tends to introduce decisional conflict. The model we develop relates response mode, decision strategy, and the salience of decisional conflict to user preferences among decision aids. We then show that the model is consistent with empirical results in MCDM studies. Next, the role of decisional conflict in problem formulation aids is briefly discussed. Finally, we outline future research needed to thoroughly test the theoretical mechanisms we have proposed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73461/1/j.1540-5915.1991.tb00371.x.pd

Management system for optimizing public transport networks: GPS record

As cities continue to grow in size and population, the design of public transport networks becomes complicated, given the wide diversity in the origins and destinations of users [1], as well as the saturation of vehicle infrastructure in large cities despite their attempts to adapt it according to population distribution. This indicates that, in order to reduce users’ travel time, it is necessary to implement alternative road solutions to the use of cars, increasing investment in public transportation [2, 3] by conducting a comprehensive analysis of the state of transportation. This situation has made appear the solutions and development oriented to transportation based on Internet of Things (IoT) which allows, in a first stage, monitoring of public transport systems, in order to optimize the deployment of transport units and thus reduce the time of transfer of users through the cities [4]. These solution proposals are focused on information collected from user resources (data collected through smart phones) to create a common database [5]. The present study proposes the development of an intelligent monitoring and management system for public transportation networks using a hybrid communication architecture based on wireless node networks using IPv6 and cellular networks (LTE, LTE-M)

Costs of shoulder pain in primary care consulters: a prospective cohort study in The Netherlands

BACKGROUND: Shoulder pain is common in primary care, and has an unfavourable outcome in many patients. Information on the costs associated with health care use and loss of productivity in patients with shoulder pain is very scarce. The objective of this study was to determine shoulder pain related costs during the 6 months after first consultation in general practice METHODS: A prospective cohort study consisting of 587 patients with a new episode of shoulder pain was conducted with a follow-up period of 6 months. Data on costs were collected by means of a cost diary during 6 months. RESULTS: 84% of the patients completed all cost diaries. The mean consumption of direct health care and non-health related care was low. During 6 months after first consultation for shoulder pain, the mean total costs a patient generated were €689. Almost 50% of this total concerned indirect costs, caused by sick leave from paid work. A small proportion (12%) of the population generated 74% of the total costs. CONCLUSION: The total costs in the 6 months after first consultation for shoulder pain in primary care, mostly generated by a small part of the population, are not alarmingly high

Clinical syndromes linked to biallelic germline variants in <i>MCM8</i> and <i>MCM9</i>

MCM8 and MCM9 are newly proposed cancer predisposition genes, linked to polyposis and early-onset cancer, in addition to their previously established association with hypogonadism. Given the uncertain range of phenotypic manifestations and unclear cancer risk estimates, this study aimed to delineate the molecular and clinical characteristics of biallelic germline MCM8/MCM9 variant carriers. We found significant enrichment of biallelic MCM9 variants in individuals with colonic polyps (OR 6.51, 95% CI 1.24–34.11; P=0.03), rectal polyps (OR 8.40, 95% CI 1.28–55.35; P=0.03), and gastric cancer (OR 27.03, 95% CI 2.93–248.5; P=0.004) in data from the 100K Genomes Project, compared to controls. No similar enrichment was found for biallelic MCM8 variants or in the 200K UK Biobank. Likewise, in our case series, which included 26 MCM8 and 28 MCM9 variant carriers, we documented polyposis, gastric cancer, and early-onset colorectal cancer in MCM9 carriers, but not in MCM8 carriers. Moreover, our case series indicates that, beyond hypogonadism, biallelic MCM8 and MCM9 variants are associated with early-onset germ cell tumors (occurring before age 15). Tumors from MCM8/MCM9 variant carriers predominantly displayed clock-like mutational processes, without evidence of DNA repair deficiency-associated signatures. Collectively, our data indicates that biallelic MCM9 variants are associated with polyposis, gastric cancer, and early-onset CRC, while both biallelic MCM8 and MCM9 variants are linked to hypogonadism and the early development of germ cell tumors. These findings underscore the importance of including MCM8/MCM9 in diagnostic gene panels for certain clinical contexts and suggest that biallelic carriers may benefit from cancer surveillance

A Meta-Analysis of Probiotic Efficacy for Gastrointestinal Diseases

Background: Meta-analyses on the effects of probiotics on specific gastrointestinal diseases have generally shown positive effects on disease prevention and treatment; however, the relative efficacy of probiotic use for treatment and prevention across different gastrointestinal diseases, with differing etiology and mechanisms of action, has not been addressed. Methods/Principal Findings: We included randomized controlled trials in humans that used a specified probiotic in the treatment or prevention of Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, Antibiotic Associated Diarrhea, Traveler’s Diarrhea, or Necrotizing Enterocolitis. Random effects models were used to evaluate efficacy as pooled relative risks across the eight diseases as well as across probiotic species, single vs. multiple species, patient ages, dosages, and length of treatment. Probiotics had a positive significant effect across all eight gastrointestinal diseases with a relative risk of 0.58 (95 % (CI) 0.51–0.65). Six of the eight diseases: Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, and Antibiotic Associated Diarrhea, showed positive significant effects. Traveler’s Diarrhea and Necrotizing Enterocolitis did not show significant effects of probiotcs. Of the 11 species and species mixtures, all showed positive significant effects except for Lactobacillus acidophilus, Lactobacillus plantarum, and Bifidobacterium infantis. Across all diseases and probiotic species, positive significant effects of probiotics were observed for all age groups, single vs. multiple species, and treatment lengths