Service Selection using Predictive Models and Monte-Carlo Tree Search

This article proposes a method for automated service selection to improve treatment efficacy and reduce re-hospitalization costs. A predictive model is developed using the National Home and Hospice Care Survey (NHHCS) dataset to quantify the effect of care services on the risk of re-hospitalization. By taking the patient's characteristics and other selected services into account, the model is able to indicate the overall effectiveness of a combination of services for a specific NHHCS patient. The developed model is incorporated in Monte-Carlo Tree Search (MCTS) to determine optimal combinations of services that minimize the risk of emergency re-hospitalization. MCTS serves as a risk minimization algorithm in this case, using the predictive model for guidance during the search. Using this method on the NHHCS dataset, a significant reduction in risk of re-hospitalization is observed compared to the original selections made by clinicians. An 11.89 percentage points risk reduction is achieved on average. Higher reductions of roughly 40 percentage points on average are observed for NHHCS patients in the highest risk categories. These results seem to indicate that there is enormous potential for improving service selection in the near future

Diagnosing Clostridioides difficile infections with molecular diagnostics: multicenter evaluation of revogene C. difficile assay

Clostridioides difficile infections are a significant threat to our healthcare system, and rapid and accurate diagnostics are crucial to implement the necessary infection prevention and control measurements. Nucleic acid amplification tests are such reliable diagnostic tools for the detection of toxigenic Clostridioides difficile strains directly from stool specimens. In this multicenter evaluation, we determined the performance of the revogene C. difficile assay. The analysis was conducted on prospective stool specimens collected from six different sites in Europe. The performance of the revogene C. difficile assay was compared to the different routine diagnostic methods and, for a subset of the specimens, against toxigenic culture. In total, 2621 valid stool specimens were tested, and the revogene C. difficile assay displayed a sensitivity/specificity of 97.1% [93.3-99.0] and 98.9% [98.5-99.3] for identification of Clostridioides difficile infection. Discrepancy analysis using additional methods improved this performance to 98.8% [95.8-99.9] and 99.6% [99.2-99.8], respectively. In comparison to toxigenic culture, the revogene C. difficile assay displayed a sensitivity/specificity of 93.0% [86.1-97.1] and 99.5% [98.7-99.9], respectively. These results indicate that the revogene C. difficile assay is a robust and reliable aid in the diagnosis of Clostridioides difficile infections.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This study was supported by grants from GenePOC, now part of Meridian Biosciences.published version, accepted versio

Does telomere elongation lead to a longer lifespan if cancer is considered?

As cell proliferation is limited due to the loss of telomere repeats in DNA of normal somatic cells during division, telomere attrition can possibly play an important role in determining the maximum life span of organisms as well as contribute to the process of biological ageing. With computer simulations of cell culture development in organisms, which consist of tissues of normal somatic cells with finite growth, we otain an increase of life span and life expectancy for longer telomeric DNA in the zygote. By additionally considering a two-mutation model for carcinogenesis and indefinite proliferation by the activation of telomerase, we demonstrate that the risk of dying due to cancer can outweigh the positive effect of longer telomeres on the longevity.Comment: 9 pages including 5 figure

Leukocyte Telomere Dynamics: Longitudinal Findings Among Young Adults in the Bogalusa Heart Study

Leukocyte telomere length (LTL) is ostensibly a biomarker of human aging. Cross-sectional analyses have found that LTL is relatively short in a host of aging-related diseases. These studies have also provided indirect estimates of age-dependent LTL shortening. In this paper, the authors report findings of the first comprehensive longitudinal study of 450 whites and 185 African Americans in Louisiana (aged 31.4 and 37.4 years at baseline (1995–1996) and follow-up (2001–2006) examinations, respectively) participating in the Bogalusa Heart Study. Rate of change in LTL was highly variable among individuals, with some displaying a paradoxical gain in LTL during the follow-up period. The most striking observation was that age-dependent LTL shortening was proportional to LTL at baseline examination. At both baseline and follow-up examinations, African Americans had longer LTLs than whites, and smokers had shorter LTLs than nonsmokers. The longer LTL in African Americans than in whites explained in part the faster rate of LTL shortening observed among African Americans. These findings underscore the complexity of leukocyte telomere dynamics in vivo and suggest that determinants in addition to the “end-replication problem” contribute to telomere shortening in vivo

Telomere Length Trajectory and Its Determinants in Persons with Coronary Artery Disease: Longitudinal Findings from the Heart and Soul Study

Background: Leukocyte telomere length, an emerging marker of biological age, has been shown to predict cardiovascular morbidity and mortality. However, the natural history of telomere length in patients with coronary artery disease has not been studied. We sought to investigate the longitudinal trajectory of telomere length, and to identify the independent predictors of telomere shortening, in persons with coronary artery disease. Methodology/Principal Findings: In a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline, and again after five years of follow-up. We used multivariable linear and logistic regression models to identify the independent predictors of leukocyte telomere trajectory. Baseline and follow-up telomere lengths were normally distributed. Mean telomere length decreased by 42 base pairs per year (p,0.001). Three distinct telomere trajectories were observed: shortening in 45%, maintenance in 32%, and lengthening in 23 % of participants. The most powerful predictor of telomere shortening was baseline telomere length (OR per SD increase = 7.6; 95 % CI 5.5, 10.6). Other independent predictors of telomere shortening were age (OR per 10 years = 1.6; 95 % CI 1.3, 2.1), male sex (OR = 2.4; 95 % CI 1.3, 4.7), and waist-to-hip ratio (OR per 0.1 increase = 1.4; 95 % CI 1.0, 2.0). Conclusions/Significance: Leukocyte telomere length may increase as well as decrease in persons with coronary arter

Quantifying the Evolution of Vascular Barrier Disruption in Advanced Atherosclerosis with Semipermeant Nanoparticle Contrast Agents

Acute atherothrombotic occlusion in heart attack and stroke implies disruption of the vascular endothelial barrier that exposes a highly procoagulant intimal milieu. However, the evolution, severity, and pathophysiological consequences of vascular barrier damage in atherosclerotic plaque remain unknown, in part because quantifiable methods and experimental models are lacking for its in vivo assessment.To develop quantitative nondestructive methodologies and models for detecting vascular barrier disruption in advanced plaques.Sustained hypercholesterolemia in New Zealand White (NZW) rabbits for >7-14 months engendered endothelial barrier disruption that was evident from massive and rapid passive penetration and intimal trapping of perfluorocarbon-core nanoparticles (PFC-NP: ∼250 nm diameter) after in vivo circulation for as little as 1 hour. Only older plaques (>7 mo), but not younger plaques (<3 mo) demonstrated the marked enhancement of endothelial permeability to these particles. Electron microscopy revealed a complex of subintimal spongiform channels associated with endothelial apoptosis, superficial erosions, and surface-penetrating cholesterol crystals. Fluorine ((19)F) magnetic resonance imaging and spectroscopy (MRI/MRS) enabled absolute quantification (in nanoMolar) of the passive permeation of PFC-NP into the disrupted vascular lesions by sensing the unique spectral signatures from the fluorine core of plaque-bound PFC-NP.The application of semipermeant nanoparticles reveals the presence of profound barrier disruption in later stage plaques and focuses attention on the disrupted endothelium as a potential contributor to plaque vulnerability. The response to sustained high cholesterol levels yields a progressive deterioration of the vascular barrier that can be quantified with fluorine MRI/MRS of passively permeable nanostructures. The possibility of plaque classification based on the metric of endothelial permeability to nanoparticles is suggested

Can posttraumatic stress disorder be prevented?

This article gives an insight in the possibilities and limitations of the prevention of Posttraumatic Stress Disorder (PTSD). An elaboration upon the diagnosis, criteria, onset and prevalence demonstrates the enormous impact of PTSD. Prevalence rates vary between countries and with the intensity of missions, but are lower in non-US Western countries. The risk factors for PTSD are well documented, as well as relationships between PTSD and an individuals psychological, biological, and social functioning. Less research is focused on protective factors for PTSD. Although resilience is an important protective factor for early prevention, current prevention strategies based on this concept are not very effective. The time frame after the trauma (golden hours) is important for applying psychological and pharmacological preventing strategies. It is not clear yet what kind of prevention will be effective in the future