Correlation of an epigenetic mitotic clock with cancer risk.

BACKGROUND: Variation in cancer risk among somatic tissues has been attributed to variations in the underlying rate of stem cell division. For a given tissue type, variable cancer risk between individuals is thought to be influenced by extrinsic factors which modulate this rate of stem cell division. To date, no molecular mitotic clock has been developed to approximate the number of stem cell divisions in a tissue of an individual and which is correlated with cancer risk. RESULTS: Here, we integrate mathematical modeling with prior biological knowledge to construct a DNA methylation-based age-correlative model which approximates a mitotic clock in both normal and cancer tissue. By focusing on promoter CpG sites that localize to Polycomb group target genes that are unmethylated in 11 different fetal tissue types, we show that increases in DNA methylation at these sites defines a tick rate which correlates with the estimated rate of stem cell division in normal tissues. Using matched DNA methylation and RNA-seq data, we further show that it correlates with an expression-based mitotic index in cancer tissue. We demonstrate that this mitotic-like clock is universally accelerated in cancer, including pre-cancerous lesions, and that it is also accelerated in normal epithelial cells exposed to a major carcinogen. CONCLUSIONS: Unlike other epigenetic and mutational clocks or the telomere clock, the epigenetic clock proposed here provides a concrete example of a mitotic-like clock which is universally accelerated in cancer and precancerous lesions

Effectiveness of a Positive Youth Development Program for Secondary 1 Students in Macau: A Pilot Study

With the rapid change to society after the opening of the gaming licensure by the government and the potential attraction to youth caused by the casinos, a well-tested and comprehensive adolescent development program previously established in Hong Kong was adopted and modified to be used in Macau. It is expected to help our adolescents achieve positive growth and be better prepared for future challenges. The aim of this study is to examine the effectiveness of the modified positive youth development program for Secondary 1 Students in Macau. Specifically, two research questions will be asked: (1) How does the positive youth development program affect positive growth for youth in Macau?; and (2) Is youth growth related to different factors such as gender, age, family financial condition, and parents' marital status? A mixed research method with a quantitative approach using a pre- and post-test pre-experimental design, and a qualitative approach using a focus group for the participants is carried out. The study sample included 232 Secondary 1 Students in two schools. The objective outcome evaluation showed that, overall, 123 (53%) of the participants had significant improvement on the total scores of the Chinese Positive Youth Development Scale (CPYDS) and the two composite scores. However, there were some increases in the behavioral intention of alcohol drinking and participation in gambling activities. The “happiness of the family life” was found to have significant differences in the score of the CPYDS, which was shown to be the factor related to youth growth. The focus group interviews revealed that both positive and negative feedback was obtained from the discussion; however, the majority of the participants perceived benefits to themselves from the program. With reference to the principle of triangulation, the present study suggests that, based on both quantitative and qualitative evaluation findings, it should be concluded that there is positive evidence supporting the effectiveness of the Tier 1 Program of the Hong Kong Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes), which was adopted and modified for Macau. In addition, special attention should be paid to the behavioral intention of alcohol drinking and participation in gambling activities in the local context

Characterizing the entanglement of symmetric many-particle spin-1/2 systems

Analyzing the properties of entanglement in many-particle spin-1/2 systems is generally difficult because the system's Hilbert space grows exponentially with the number of constituent particles, $N$. Fortunately, it is still possible to investigate many-particle entanglement when the state of the system possesses sufficient symmetry. In this paper, we present a practical method for efficiently computing various bipartite entanglement measures for states in the symmetric subspace and perform these calculations for $N\sim 10^3$. By considering all possible bipartite splits, we construct a picture of the multiscale entanglement in large symmetric systems. In particular, we characterize dynamically generated spin-squeezed states by comparing them to known reference states (e.g., GHZ and Dicke states) and new families of states with near-maximal bipartite entropy. We quantify the trade-off between the degree of entanglement and its robustness to particle loss, emphasizing that substantial entanglement need not be fragile.Comment: Updated version reflects changes made in January 200

Gradient microfluidics enables rapid bacterial growth inhibition testing

Bacterial growth inhibition tests have become a standard measure of the adverse effects of inhibitors for a wide range of applications, such as toxicity testing in the medical and environmental sciences. However, conventional well-plate formats for these tests are laborious and provide limited information (often being restricted to an end-point assay). In this study, we have developed a microfluidic system that enables fast quantification of the effect of an inhibitor on bacteria growth and survival, within a single experiment. This format offers a unique combination of advantages, including long-term continuous flow culture, generation of concentration gradients, and single cell morphology tracking. Using Escherichia coli and the inhibitor amoxicillin as one model system, we show excellent agreement between an on-chip single cell-based assay and conventional methods to obtain quantitative measures of antibiotic inhibition (for example, minimum inhibition concentration). Furthermore, we show that our methods can provide additional information, over and above that of the standard well-plate assay, including kinetic information on growth inhibition and measurements of bacterial morphological dynamics over a wide range of inhibitor concentrations. Finally, using a second model system, we show that this chip-based systems does not require the bacteria to be labeled and is well suited for the study of naturally occurring species. We illustrate this using Nitrosomonas europaea, an environmentally important bacteria, and show that the chip system can lead to a significant reduction in the period required for growth and inhibition measurements (<4 days, compared to weeks in a culture flask)

Isotopes of nitrogen on Mars: Atmospheric measurements by Curiosity's mass spectrometer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102173/1/wong_readme.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102173/2/wong2013_SM_v4b.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102173/3/grl51166.pd

The effectiveness of dietary approaches to stop hypertension (DASH) counselling on estimated 10-year cardiovascular risk among patients with newly diagnosed grade 1 hypertension : a randomised clinical trial

The Dietary Approaches to Stop Hypertension (DASH) has been shown to lower blood pressure in the West. However, the real-life impact of DASH on reducing cardiovascular (CV) risk in routine clinical setting has not been studied. Methods A parallel-group, open-labelled, physician-blinded, randomised controlled trial was conducted in January–June 2013 and followed up for 6- and 12-months in primary care settings in Hong Kong. Patients newly diagnosed with grade 1 hypertension (aged 40–70 years) who had no concomitant medical conditions requiring dietary modifications were consecutively recruited. Subjects were randomised to standard education (usual care) (n = 275), or usual care plus dietitian-delivered DASH-based dietary counselling in a single one-to-one session (intervention) (n = 281). Primary outcomes were the changes in estimated 10-year CV risk. Results Outcome data were available for 504 (90.6%) and 485 (87.2%) patients at 6 and 12 months, respectively. There was no difference in the reduction of 10-year CV risk between the two groups at 6 months (−0.13%, 95% confidence interval [95% CI] −0.50% to 0.23%, p = 0.477) and 12 months (−0.08%, 95% CI −0.33% to 0.18%, p = 0.568). Multivariate regression analyses showed that male subjects, younger patients, current smokers, subjects with lower educational level, and those who dined out for main meals for ≥4 times in a typical week were significantly associated with no improvements in CV risk. Conclusions The findings may not support automatic referral of newly diagnosed grade 1 hypertensive patients for further one-to-one dietitian counselling on top of primary care physician's usual care. Patients with those risk factors identified should receive more clinical attention to reduce their CV risk

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Improving recognition of delirium in clinical practice: a call for action

The purpose of this correspondence article is to report opinion amongst experts in the delirium field as to why, despite on-going training for all health professionals, delirium continues to be under recognised. Consensus was obtained by means of two conference workshops and an online survey of members of the European Delirium Association. Major barriers to recognition at an individual level include ignorance about the benefit of treating delirium. At an organisational level, reflecting socio-cultural attitudes, barriers include a low strategic and financial priority and the fact that delirium is an orphan condition falling between specialties