OBJECTIVE—Traditional risk factors for coronary artery disease (CAD) fail to adequately distinguish patients who have atherosclerotic plaques susceptible to instability from those who have more ...benign forms. Using plasma lipid profiling, this study aimed to provide insight into disease pathogenesis and evaluate the potential of lipid profiles to assess risk of future plaque instability.
METHODS AND RESULTS—Plasma lipid profiles containing 305 lipids were measured on 220 individuals (matched healthy controls, n=80; stable angina, n=60; unstable coronary syndrome, n=80) using electrospray-ionisation tandem mass spectrometry. ReliefF feature selection coupled with an L2-regularized logistic regression based classifier was used to create multivariate classification models which were verified via 3-fold cross-validation (1000 repeats). Models incorporating both lipids and traditional risk factors provided improved classification of unstable CAD from stable CAD (C-statistic=0.875, 95% CI 0.874–0.877) compared with models containing only traditional risk factors (C-statistic=0.796, 95% CI 0.795–0.798). Many of the lipids identified as discriminatory for unstable CAD displayed an association with disease acuity (severity), suggesting that they are antecedents to the onset of acute coronary syndrome.
CONCLUSION—Plasma lipid profiling may contribute to a new approach to risk stratification for unstable CAD.
A previous paper reported the 6-month comparison of weight loss and metabolic changes in obese adults randomly assigned to either a low-carbohydrate diet or a conventional weight loss diet.
To review ...the 1-year outcomes between these diets.
Randomized trial.
Philadelphia Veterans Affairs Medical Center.
132 obese adults with a body mass index of 35 kg/m2 or greater; 83% had diabetes or the metabolic syndrome.
Participants received counseling to either restrict carbohydrate intake to <30 g per day (low-carbohydrate diet) or to restrict caloric intake by 500 calories per day with <30% of calories from fat (conventional diet).
Changes in weight, lipid levels, glycemic control, and insulin sensitivity.
By 1 year, mean (+/-SD) weight change for persons on the low-carbohydrate diet was -5.1 +/- 8.7 kg compared with -3.1 +/- 8.4 kg for persons on the conventional diet. Differences between groups were not significant (-1.9 kg 95% CI, -4.9 to 1.0 kg; P = 0.20). For persons on the low-carbohydrate diet, triglyceride levels decreased more (P = 0.044) and high-density lipoprotein cholesterol levels decreased less (P = 0.025). As seen in the small group of persons with diabetes (n = 54) and after adjustment for covariates, hemoglobin A1c levels improved more for persons on the low-carbohydrate diet. These more favorable metabolic responses to a low-carbohydrate diet remained significant after adjustment for weight loss differences. Changes in other lipids or insulin sensitivity did not differ between groups.
These findings are limited by a high dropout rate (34%) and by suboptimal dietary adherence of the enrolled persons.
Participants on a low-carbohydrate diet had more favorable overall outcomes at 1 year than did those on a conventional diet. Weight loss was similar between groups, but effects on atherogenic dyslipidemia and glycemic control were still more favorable with a low-carbohydrate diet after adjustment for differences in weight loss.
Interaction analysis of GWAS can detect signal that would be ignored by single variant analysis, yet few robust interactions in humans have been detected. Recent work has highlighted interactions in ...the MHC region between known HLA risk haplotypes for various autoimmune diseases. To better understand the genetic interactions underlying celiac disease (CD), we have conducted exhaustive genome-wide scans for pairwise interactions in five independent CD case-control studies, using a rapid model-free approach to examine over 500 billion SNP pairs in total. We found 14 independent interaction signals within the MHC region that achieved stringent replication criteria across multiple studies and were independent of known CD risk HLA haplotypes. The strongest independent CD interaction signal corresponded to genes in the HLA class III region, in particular PRRC2A and GPANK1/C6orf47, which are known to contain variants for non-Hodgkin's lymphoma and early menopause, co-morbidities of celiac disease. Replicable evidence for statistical interaction outside the MHC was not observed. Both within and between European populations, we observed striking consistency of two-locus models and model distribution. Within the UK population, models of CD based on both interactions and additive single-SNP effects increased explained CD variance by approximately 1% over those of single SNPs. The interactions signal detected across the five cohorts indicates the presence of novel associations in the MHC region that cannot be detected using additive models. Our findings have implications for the determination of genetic architecture and, by extension, the use of human genetics for validation of therapeutic targets.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
6.
Four Poems from Israel Antman, Avigail; Zisquit, Linda Stern
World literature today,
2024, 2024-01-00, 20240101, Letnik:
98, Številka:
1
Journal Article
Recenzirano
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
7.
IS IT A TEST? Zisquit, Linda Stern
Nashim : a journal of Jewish women's studies & gender issues,
09/2021
39
Journal Article
Recenzirano
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Technologies are introduced into an organization with the aim of improving productivity. However, persistent use of an information system is required to enhance productivity and user satisfaction. In ...this paper, we examine the process of technology appropriation and the factors that encourage and discourage use of an information system over time. In a longitudinal field study in an educational setting, we identify changing expectations and influences that encourage persistent use of a technology above and beyond adoption. Our work indicates that stabilization of a technology may only be a temporary plateau. Further appropriation may occur beyond initial stabilization as expectations and influences encourage persistent use of a technology. We have found that the driving forces in encouraging productive use of a technology are the ability for users to experience the technology as useful and to have easy access to ongoing training.
We examined the impact of patient adherence and screening test performance on the cost-effectiveness of visual inspection with acetic acid (VIA) and Pap smears when used with colposcopy for ...diagnosis.
Cost-effectiveness analysis was performed using computer modeling. The primary outcome was cancer prevalence in the 10 years after screening. Three hypothetical populations of 35-year-old women were compared: never-screened women, women screened with VIA, and women screened with Pap smears. We used community-based data from our screening program in Honduras to estimate screening test sensitivity and specificity, adherence to follow-up, and costs of screening and colposcopy services. Published data were used to model disease outcomes.
VIA was more sensitive than Pap smears (70% vs. 4%), less expensive (U.S. 0.23 dollars vs. 3.17 dollars), and the 2-vist VIA system had a higher rate of adherence to follow-up than the 3-visit Pap smear system (84% vs. 38%). VIA had a higher false-positive rate than Pap smears resulting in higher colposcopy referral rates, but more dysplasia was detected and treated. Cost-effectiveness analysis revealed that screening with VIA would cost U.S. 3,198 dollars per cancer case avoided and reduce cancer cases by 42%, versus U.S. 36,802 dollars and 2% for Pap screening. Although Pap smear quality was low in Honduras, sensitivity analysis showed that VIA was more cost-effective than Pap smears, even when test accuracy was equivalent.
In developing countries, systems barriers can limit the cost-effectiveness of Pap smears. VIA may be a cost-effective alternative for some resource-poor settings, although systems barriers, quality control, and feasibility issues must be considered.