Should identical CVD risks in young and old patients be managed identically? Results from two models

OBJECTIVES: To assess whether delaying risk reduction treatment has a different impact on potential life years lost in younger compared with older patients at the same baseline short-term cardiovascular risk. DESIGN: Modelling based on population data. METHODS: Potential years of life lost from a 5-year treatment delay were estimated for patients of different ages but with the same cardiovascular risk (either 5% or 10% 5-year risk). Two models were used: an age-based residual life expectancy model and a Markov simulation model. Age-specific case fatality rates and time preferences were applied to both models, and competing mortality risks were incorporated into the Markov model. RESULTS: Younger patients had more potential life years to lose if untreated, but the maximum difference between 35 and 85 years was <1 year, when models were unadjusted for time preferences or competing risk. When these adjusters were included, the maximum difference fell to about 1 month, although the direction was reversed with older people having more to lose. CONCLUSIONS: Surprisingly, age at onset of treatment has little impact on the likely benefits of interventions that reduce cardiovascular risk because of the opposing effects of life expectancy, case fatality, time preferences and competing risks. These findings challenge the appropriateness of recommendations to use lower risk-based treatment thresholds in younger patients

Promoter hypomethylation of NY-ESO-1, association with clinicopathological features and PD-L1 expression in non-small cell lung cancer.

Cancer-Testis antigens (CTA) are immunogenic molecules with normal tissue expression restricted to testes but with aberrant expression in up to 30% of non-small cell lung cancers (NSCLCs). Regulation of CTA expression is mediated in part through promoter DNA methylation. Recently, immunotherapy has altered treatment paradigms in NSCLC. Given its immunogenicity and ability to be re-expressed through demethylation, NY-ESO-1 promoter methylation, protein expression and its association with programmed death receptor ligand-1 (PD-L1) expression and clinicopathological features were investigated. Lung cancer cell line demethylation resulting from 5-Aza-2'-deoxycytidine treatment was associated with both NY-ESO-1 and PD-L1 re-expression in vitro but not increased chemosensitivity. NY-ESO-1 hypomethylation was observed in 15/94 (16%) of patient samples and associated with positive protein expression (P < 0.0001). In contrast, PD-L1 expression was observed in 50/91 (55%) but strong expression in only 12/91 (13%) cases. There was no association between NY-ESO-1 and PD-L1 expression, despite resultant re-expression of both by 5-Aza-2'-deoxycytidine. Importantly, NY-ESO-1 hypomethylation was found to be an independent marker of poor prognosis in patients not treated with chemotherapy (HR 3.59, P = 0.003) in multivariate analysis. In patients treated with chemotherapy there were no differences in survival associated with NY-ESO-1 hypomethylation. Collectively, these results provided supporting evidence for the potential use of NY-ESO-1 hypomethylation as a prognostic biomarker in stage 3 NSCLCs. In addition, these data highlight the potential to incorporate demethylating agents to enhance immune activation, in tumours currently devoid of immune infiltrates and expression of immune checkpoint genes

Optimisation of a reduced volume PCR amplification for PowerPlex® Fusion kit using FTA™ cards and generation of population genetic data for Brunei population

The commercial PowerPlex® Fusion kit is an autosomal STR multiplex kit that has high discrimination power and is more informative in forensic, paternity and relationship‐testing cases. Key features of this multiplex system are the possibility to direct amplify FTA™ card punches as well as non‐FTA cards and commonly used swabs; optimised inhibitor tolerance and high sensitivity generating full profiles from as little as 100 pg of human DNA. This study focused on the optimization of performance variables such as FTA™ punch sizes, reduced reaction volumes, and FTA™ purification reagent aiming to increase the analytical sensitivity, decrease the sample consumption and cost effectiveness. LOD and LOQ values demonstrated high sensitivity of the PowerPlex® Fusion system. In addition, population databases of Brunei Malay and Chinese from the Brunei Darussalam were established, and parameters of forensic importance were calculated. Overall, the forensic parameters indicated an enhanced utility of the PowerPlex® Fusion kit for forensic evidence analysis and paternity testing in Brunei Malay and Chinese populations

Data-Intensive architecture for scientific knowledge discovery

This paper presents a data-intensive architecture that demonstrates the ability to support applications from a wide range of application domains, and support the different types of users involved in defining, designing and executing data-intensive processing tasks. The prototype architecture is introduced, and the pivotal role of DISPEL as a canonical language is explained. The architecture promotes the exploration and exploitation of distributed and heterogeneous data and spans the complete knowledge discovery process, from data preparation, to analysis, to evaluation and reiteration. The architecture evaluation included large-scale applications from astronomy, cosmology, hydrology, functional genetics, imaging processing and seismology

Factors affecting the adoption of climate-smart aquaculture (CSAq) in the North Central Coast of Vietnam

Climate-smart aquaculture (CSAq) is considered an appropriate and effective adaptation approach for the coastal aquaculture sector under the climate change phenomenon. This study, applying probit model, aims to assess the influence of several factors on the farmers’ decision to apply CSAq practices in extensive coastal shrimp farming. Data were collected from interviews with 200 households who have both already applied and have yet to apply CSAq practices in five coastal districts of Thanh Hoa Province. The results showed six key factors that influenced the decision of the farmers to apply CSAq practices: availability of household labor; access to information on CSAq practices; market price of products applying CSAq practices; economic efficiency; ability to ensure food security; and improved pond environment when applying CSAq practices. These factors explained 69.41% of their decision to apply CSAq, among which economic efficiency had the greatest impact (30.2%). Market prices and access to information about CSAq are also important factors with respective levels of influence at 16.0% and 14.9%. The result implies that strengthening access to CSAq information and improving technical understanding of CSAq practices are important solutions to upscale CSAq in the North Central Coast of Vietnam

Association of dietary nitrate intake with the 15-year incidence of age-related macular degeneration

Background Dietary nitrate, found predominantly in green leafy vegetables and beetroot, is a precursor of nitric oxide. Under- or overproduction of nitric oxide is implicated in the etiology of several eye diseases. However, the potential influence of dietary nitrate intake on age-related macular degeneration (AMD) risk has not been assessed. Objective To investigate the temporal association between dietary nitrate intake (from both vegetable and nonvegetable sources) and the 15-year incidence of AMD, independent of potential confounders. Design A longitudinal cohort study conducted from 1992-1994 to 2007-2009. Participants/setting The Blue Mountains Eye Study is a population-based study of adults aged 49+ at baseline, from a region west of Sydney, Australia. At baseline, 2,856 participants with complete dietary data and AMD information were examined, and of these, 2,037 participants were re-examined 15 years later and thus included in incidence analysis. Main outcomes measured Incidence of AMD (main outcome) was assessed from retinal photographs. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. Nitrate intake from vegetables and nonvegetable sources was calculated by use of a validated comprehensive database. Results After adjusting for age, sex, smoking, energy intake, fish consumption, and AMD risk alleles (complement factor H and age-related maculopathy susceptibility-2 single nucleotide polymorphisms), participants in the third quartile compared with those in the first quartile (reference group) of total nitrate and total vegetable nitrate intake had reduced risk of incident early AMD: odds ratio (OR) 0.61 (95% CI 0.41 to 0.90) and OR 0.65 (95% CI 0.44 to 0.96), respectively. Significant associations were not observed between the fourth vs first quartile of total nitrate and vegetable nitrate intake with incident early AMD: OR 0.74 (95% CI 0.51 to 1.08) and OR 0.69 (95% CI 0.47 to 1.00), respectively. Nonsignificant associations were also observed with 15-year incidence of late AMD and total nonvegetable nitrate intake. Conclusions These novel findings could have important implications, if the association between total nitrate intake and vegetable nitrate intake and 15-year incidence of early AMD is confirmed in other observational or intervention studies

Dietary flavonoids and the prevalence and 15-y incidence of age-related macular degeneration

Background: The majority of research performed to date has examined the effects of commonly known antioxidants such as vitamins C, E, and A and carotenoids on age-related macular degeneration (AMD) risk and progression. To date, there is limited research on promising phytochemicals with antioxidant and anti-inflammatory properties, including flavonoids. Objective: In this exploratory study, we aimed to assess the independent associations between dietary intake of total flavonoids and common flavonoid classes with the prevalence and 15-y incidence of AMD. Design: In this population-based cohort study, 2856 adults aged ≥49 y at baseline and 2037 followed up 15 y later were included in prevalence and incidence analyses, respectively. Dietary intake was assessed by using a semiquantitative food-frequency questionnaire (FFQ). Estimates of the flavonoid content of foods in the FFQ were assessed by using the USDA Flavonoid, Isoflavone, and Proanthocyanidin databases. AMD was assessed from retinal photographs. Results: In cross-sectional analysis, each 1-SD increase in total overall flavonoid intake was associated with a reduced likelihood of any AMD (multivariable-adjusted OR: 0.76; 95% CI: 0.58, 0.99). Each 1-SD increase in dietary intake of total flavonols and total flavanones was associated with reduced odds of the prevalence of any AMD [multivariable-adjusted OR (95% CI): 0.75 (0.58, 0.97) and 0.77 (0.60, 0.99), respectively]. A marginally significant trend (P = 0.05) was observed between increasing the intake of total flavanone and hesperidin (from the first to the fourth quartile) and reduced likelihood of incident late AMD, after multivariable adjustment. Participants who reported ≥1 serving of oranges/d compared with those who never consumed oranges at baseline had a reduced risk of late AMD 15 y later (multivariable-adjusted OR: 0.39; 95% CI: 0.18, 0.85). Conclusions: Our findings suggest an independent and protective association between dietary intake of flavonoids and the likelihood of having AMD. Additional prospective cohort studies are needed to validate these findings

Associations between dietary flavonoids and retinal microvasculature in older adults

Purpose In this study, we assessed whether there are independent associations between dietary total flavonoid intake and major flavonoid classes with retinal arteriolar and venular calibre. Methods Blue Mountains Eye Study participants aged 49+ years who had complete data on diet and retinal vessel measures were analysed (n = 2821). Dietary intake was assessed using a semi-quantitative Food-Frequency Questionnaire (FFQ). Flavonoid content of foods in the FFQ was estimated using the US Department of Agriculture Flavonoid, Isoflavone and Proanthocyanidin databases. Fundus photographs were taken and retinal vascular calibre was measured using validated computer-assisted techniques. The associations of intake of dietary flavonoids with retinal vessel calibre were examined in linear regression models and general linear model. Results The highest quartile of intake was compared with the lowest quartile using multivariable-adjustment models. Participants with the highest proanthocyanidin intake had narrower retinal venules (223.9 ± 0.62 versus 226.5 ± 0.63, respectively; Ptrend = 0.01); and the highest isoflavone intake was associated with wider retinal arterioles (188.1 ± 0.55 versus 186.3 ± 0.56, respectively; Ptrend = 0.01). The highest apple/pear consumption (a dietary source of catechin) was associated with narrower retinal venules (223.8 ± 0.57 versus 226.1 ± 0.52; Ptrend = 0.01) and wider retinal arterioles (187.9 ± 0.51 versus 186.2 ± 0.51; Ptrend = 0.02). Further, participants who were in the highest versus lowest quartile of chocolate consumption had ~ 2.1 μm narrower retinal venules (multivariable-adjusted P = 0.03). Conclusions This study shows that higher intakes of specific flavonoid subclasses are associated with a favourable retinal microvascular profile. Greater consumption of flavonoid-rich apples/pears and chocolate was also associated with beneficial variations in retinal vascular calibre

Pain-related fear of movement dynamics in individuals with and without low back pain participating in weightlifting and/or powerlifting training

Purpose Pain-free adults in the general population have been shown to possess unhelpful beliefs that certain movements and postures are harmful to the spine, potentially reinforcing fear-avoidance behaviour. Whether such beliefs occur in individuals undertaking regular powerlifting (PL) and Olympic weightlifting (OWL) training is unclear. Methods In a cross-sectional study design, 67 individuals who participate in OWL and PL training completed an online survey. Demographic characteristics, training history, and self-reported perceptions of harm, on the 40-item Photograph Series of Daily Activities shortened electronic version (PHODA-SeV), were collected. After removing collinear variables, 13 items were entered into a network analysis, in which the adjusted correlations between items, and the centrality indices of each item (i.e., the degree of connection with other symptoms in the network) were quantified. Results Twenty-one (31.3%) participants had LBP symptoms. The pairwise correlations with the greatest magnitudes were between images of ‘leg stretch’ and ‘jumping’ (0.32 [95%CI 0.08 to 0.45]) and two images depicting ironing (0.32 [95%CI 0.05 to 0.54]) respectively. The three most Central (connected) items were ‘stair ascend’, ‘walking with groceries’, and ‘mopping with spine flexion’. Conclusions For individuals training in OWL and PL, images reflecting walking, rather than those depicting high spinal flexion angle, had greater connectivity to other activity items. In addition, the strongest correlations were not between items reflecting high spinal flexion angle. Future studies that investigate the relationship between different intensities of OWL and PL training and the dynamics of pain-related fear are warranted. </jats:sec