Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

Linking CHHiP prostate cancer RCT with GP records: A study proposal to investigate the effect of co-morbidities and medications on long-term symptoms and radiotherapy-related toxicity.

Background Patients receiving cancer treatment often have one or more co-morbid conditions that are treated pharmacologically. Co-morbidities are recorded in clinical trials usually only at baseline. However, co-morbidities evolve and new ones emerge during cancer treatment. The interaction between multi-morbidity and cancer recovery is significant but poorly understood.Purpose To investigate the effect of co-morbidities (e.g. cardiovascular and diabetes) and medications (e.g. statins, antihypertensives, metformin) on radiotherapy-related toxicity and long-term symptoms in order to identify potential risk factors. The possible protective effect of medications such as statins or antihypertensives in reducing radiotherapy-related toxicity will also be explored.Methods Two datasets will be linked. (1) CHHiP (Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer) randomised control trial. CHHiP contains pelvic symptoms and radiation-related toxicity reported by patients and clinicians. (2) GP (General Practice) data from RCGP RSC (Royal College of General Practitioners Research and Surveillance Centre). The GP records of CHHiP patients will be extracted, including cardiovascular co-morbidities, diabetes and prescription medications. Statistical analysis of the combined dataset will be performed in order to investigate the effect.Conclusions Linking two sources of healthcare data is an exciting area of big healthcare data research. With limited data in clinical trials (not all clinical trials collect information on co-morbidities or medications) and limited lengths of follow-up, linking different sources of information is increasingly needed to investigate long-term outcomes. With increasing pressures to collect detailed information in clinical trials (e.g. co-morbidities, medications), linkage to routinely collected data offers the potential to support efficient conduct of clinical trials

Proactive environmental strategy in a supply chain context: The mediating role of investments

Abstract: There is a growing body of knowledge on the link between environmental management and supply chain management, but there is contradicting evidence on the impact of a proactive environmental strategy on environmental performance. Therefore, this paper investigates the impact of proactive environmental strategy on environmental performance as mediated by environmental investments. We also consider the antecedents of the adoption of proactive environmental strategy. We develop and test hypotheses, using data collected from 96 Turkish manufacturers through an online questionnaire. The model was tested using Partial Least Squares (PLS), a structural equation modelling method. The results show that a proactive environmental strategy leads to higher environmental investments; both internally and externally in collaboration with suppliers. Our findings support our hypothesis that environmental investments acts as a mediating variable between proactive environmental strategy and environmental performance. The results also show that customer pressure and, particularly, organizational commitment positively impact the extent to which firms adopt a proactive environmental strategy

Surprisingly Simple Spectra

The large N limit of the anomalous dimensions of operators in ${\cal N}=4$ super Yang-Mills theory described by restricted Schur polynomials, are studied. We focus on operators labeled by Young diagrams that have two columns (both long) so that the classical dimension of these operators is O(N). At large N these two column operators mix with each other but are decoupled from operators with $n\ne 2$ columns. The planar approximation does not capture the large N dynamics. For operators built with 2, 3 or 4 impurities the dilatation operator is explicitly evaluated. In all three cases, in a certain limit, the dilatation operator is a lattice version of a second derivative, with the lattice emerging from the Young diagram itself. The one loop dilatation operator is diagonalized numerically. All eigenvalues are an integer multiple of $8g_{YM}^2$ and there are interesting degeneracies in the spectrum. The spectrum we obtain for the one loop anomalous dimension operator is reproduced by a collection of harmonic oscillators. This equivalence to harmonic oscillators generalizes giant graviton results known for the BPS sector and further implies that the Hamiltonian defined by the one loop large $N$ dilatation operator is integrable. This is an example of an integrable dilatation operator, obtained by summing both planar and non-planar diagrams.Comment: 34 page

Quantum Spectral Curve at Work: From Small Spin to Strong Coupling in N=4 SYM

We apply the recently proposed quantum spectral curve technique to the study of twist operators in planar N=4 SYM theory. We focus on the small spin expansion of anomalous dimensions in the sl(2) sector and compute its first two orders exactly for any value of the 't Hooft coupling. At leading order in the spin S we reproduced Basso's slope function. The next term of order S^2 structurally resembles the Beisert-Eden-Staudacher dressing phase and takes into account wrapping contributions. This expansion contains rich information about the spectrum of local operators at strong coupling. In particular, we found a new coefficient in the strong coupling expansion of the Konishi operator dimension and confirmed several previously known terms. We also obtained several new orders of the strong coupling expansion of the BFKL pomeron intercept. As a by-product we formulated a prescription for the correct analytical continuation in S which opens a way for deriving the BFKL regime of twist two anomalous dimensions from AdS/CFT integrability.Comment: 53 pages, references added; v3: due to a typo in the coefficients C_2 and D_2 on page 29 we corrected the rational part of the strong coupling predictions in equations (1.5-6), (6.22-24), (6.27-30) and in Table

Association between Selected Oral Pathogens and Gastric Precancerous Lesions

We examined whether colonization of selected oral pathogens is associated with gastric precancerous lesions in a cross-sectional study. A total of 119 participants were included, of which 37 were cases of chronic atrophic gastritis, intestinal metaplasia, or dysplasia. An oral examination was performed to measure periodontal indices. Plaque and saliva samples were tested with real-time quantitative PCR for DNA levels of pathogens related to periodontal disease (Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Actinobacillus actinomycetemcomitans) and dental caries (Streptococcus mutans and S. sobrinus). There were no consistent associations between DNA levels of selected bacterial species and gastric precancerous lesions, although an elevated but non-significant odds ratio (OR) for gastric precancerous lesions was observed in relation to increasing colonization of A. actinomycetemcomitans (OR = 1.36 for one standard deviation increase, 95% Confidence Interval = 0.87–2.12), P. gingivalis (OR = 1.12, 0.67–1.88) and T. denticola (OR = 1.34, 0.83–2.12) measured in plaque. To assess the influence of specific long-term infection, stratified analyses by levels of periodontal indices were conducted. A. actinomycetemcomitans was significantly associated with gastric precancerous lesions (OR = 2.51, 1.13–5.56) among those with ≥ median of percent tooth sites with PD≥3 mm, compared with no association among those below the median (OR = 0.86, 0.43–1.72). A significantly stronger relationship was observed between the cumulative bacterial burden score of periodontal disease-related pathogens and gastric precancerous lesions among those with higher versus lower levels of periodontal disease indices (p-values for interactions: 0.03–0.06). Among individuals with periodontal disease, high levels of colonization of periodontal pathogens are associated with an increased risk of gastric precancerous lesions