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There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.
Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and wingless/integrated (WNT)-pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory microRNA (miRNA), secreted frizzled-related protein 1 (SFRP1) methylation and colonic crypt proliferative state in colorectal mucosal biopsies. Dietary and lifestyle data from seventy-five healthy participants recruited as part of the DISC Study were used. A scoring system was devised including seven of the cancer prevention recommendations and smoking status. The effects of total adherence score and scores for individual recommendations on the measured outcomes were assessed using Spearman’s rank correlation analysis and unpaired t tests, respectively. Total adherence score correlated negatively with expression of Myc proto-oncogene (c-MYC) (P=0·039) and WNT11 (P=0·025), and high adherers had significantly reduced expression of cyclin D1 (CCND1) (P=0·042), WNT11 (P=0·012) and c-MYC (P=0·048). Expression of axis inhibition protein 2 (AXIN2), glycogen synthase kinase (GSK3β), catenin β1 (CTNNB1) and WNT11 and of the oncogenic miRNA miR-17 and colonic crypt kinetics correlated significantly with scores for individual recommendations, including body fatness, red meat intake, plant food intake and smoking status. The findings from this study provide evidence for positive effects of adherence to the WCRF/AICR cancer prevention recommendations on WNT-pathway-related markers of bowel cancer risk.
Clinical databases in congenital and paediatric cardiac care provide a foundation for quality improvement, research, policy evaluations and public reporting. Structured audits verifying data integrity allow database users to be confident in these endeavours. We report on the initial audit of the Pediatric Cardiac Critical Care Consortium (PC4) clinical registry.
Materials and methods
Participants reviewed the entire registry to determine key fields for audit, and defined major and minor discrepancies for the audited variables. In-person audits at the eight initial participating centres were conducted during a 12-month period. The data coordinating centre randomly selected intensive care encounters for review at each site. The audit consisted of source data verification and blinded chart abstraction, comparing findings by the auditors with those entered in the database. We also assessed completeness and timeliness of case submission. Quantitative evaluation of completeness, accuracy, and timeliness of case submission is reported.
We audited 434 encounters and 29,476 data fields. The aggregate overall accuracy was 99.1%, and the major discrepancy rate was 0.62%. Across hospitals, the overall accuracy ranged from 96.3 to 99.5%, and the major discrepancy rate ranged from 0.3 to 0.9%; seven of the eight hospitals submitted >90% of cases within 1 month of hospital discharge. There was no evidence for selective case omission.
Based on a rigorous audit process, data submitted to the PC4 clinical registry appear complete, accurate, and timely. The collaborative will maintain ongoing efforts to verify the integrity of the data to promote science that advances quality improvement efforts.
Despite many advances in recent years for patients with critical paediatric and congenital cardiac disease, significant variation in outcomes remains across hospitals. Collaborative quality improvement has enhanced the quality and value of health care across specialties, partly by determining the reasons for variation and targeting strategies to reduce it. Developing an infrastructure for collaborative quality improvement in paediatric cardiac critical care holds promise for developing benchmarks of quality, to reduce preventable mortality and morbidity, optimise the long-term health of patients with critical congenital cardiovascular disease, and reduce unnecessary resource utilisation in the cardiac intensive care unit environment. The Pediatric Cardiac Critical Care Consortium (PC4) has been modelled after successful collaborative quality improvement initiatives, and is positioned to provide the data platform necessary to realise these objectives. We describe the development of PC4 including the philosophical, organisational, and infrastructural components that will facilitate collaborative quality improvement in paediatric cardiac critical care.
We provide a high-resolution map of elevation change rates at the Juneau Icefield (JIF), southeastern Alaska, in order to quantify its contribution to sea-level rise between 2000 and 2009/2013. We also produce the first high-resolution map of ice speeds at the JIF, which we use to constrain flux and look for acceleration. We calculate using stacked digital elevation models (DEMs) from the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) instrument and the Shuttle Radar Topography Mission (SRTM), taking into account SRTM C-band penetration via comparison with SRTM X-band elevations. Overall, the JIF is losing mass less rapidly (0.13 ± 0.12 m w.e. a–1) than other Alaskan icefields (0.79 m w.e. a–1). We determine glacier speeds using pixel-tracking on optical image pairs acquired from 2001 to 2010 by ASTER, from radar image pairs acquired between 2007 and 2011 and from radar interferometry in 1995. We detect seasonal speed variations but no interannual acceleration, ruling out dynamics as the cause of the observed thinning. Thinning must therefore be due to the documented warming in the region. Flux measurements confirm this for Mendenhall Glacier, showing that calving constitutes only 2.5–5% of mass loss there.
There is growing basic-science interest in the mechanisms underpinning the positive effects of exercise on brain function and cognitive-affective performance. There is also increasing clinical evidence that exercise may prevent and treat various neuropsychiatric disorders. At the same time, there is growing awareness that athletic performance is mediated in crucial ways by central nervous system mechanisms. The relevant mechanisms in all these cases requires further exploration, but likely includes neurotrophic, neuroendocrine, and neurotransmitter systems, which in turn are crucial mediators of psychopathology and resilience. The hypothesis that Homo sapiens evolved as a specialist endurance runner provides an intriguing context against which to research the proximal mechanisms relevant to a cognitive-affective neuroscience of exercise.
Pregnancy outcome and characteristics of women who conceive following subfertility treatment remains a subject of great interest. We analyzed these variables among 199 women who delivered a registerable twin birth compared with 1773 women who delivered a naturally conceived twin birth in a population-based obstetric cohort drawn from around Oxford, England. Treatment was restricted to conceptions involving simple ovulation induction only. Treated mothers were of significantly higher social class and older, more likely to deliver girls and to be delivered by cesarean section, and significantly less likely to be smokers at the time of antenatal booking and to have delivered previous pregnancies. Pregnancy outcome was similar between the two groups for most measures, with the exception of birthweight which was lower in treated twins, though not significantly so. Overall the results are reassuring with respect to outcome in twin pregnancies following simple ovulation induction.
We describe detailed studies of ionically self-assembled monolayer (ISAM) photovoltaic (PV) devices incorporating various electron acceptor materials, such as fullerenes and phthalocyanines. Excitons are generated when the conducting polymer is irradiated, and the electron acceptors aid in dissociating the electron/hole pairs before they can radiatively recombine, thus improving the efficiency of the PV process. The ISAM technique allows the deposition of conducting polymer and electron acceptor materials in alternating layers of nanometer-scale thickness. This ensures that every photoexcited electron-hole pair is in proximity to an electron acceptor, thus minimizing electron-hole recombination and increasing the photocurrent. The individual thickness of each monolayer and the interpenetration of adjacent layers can be precisely controlled through the parameters of the electrolyte solutions. Using the ISAM technique, we have demonstrated that it is possible to create ultrathin films (100 nm) of PV material that have enhanced efficiencies.
14C ages were determined on samples of foraminifera separated from cores from three areas of the tropical Pacific (East Pacific Rise, Oontong Java Plateau, and South China Sea). Analyses were made on four planktonic species and on mixed benthics. The purpose of the multiple analysis on planktonic species is to assess the importance of artifacts resulting from the bioturbation-abundance change couple, from the bioturbation-partial dissolution couple and from redeposition by bottom currents. The goal is to use the benthic-planktonic age difference as a means of establishing changes in deep sea ventilation rate over the past 25,000 years. Results of a part of this work are presented in this paper.
Results of 14C/12C ratio measurements on CO2 extracted from air bubbles in polar ice are presented. The samples investigated originate from the Dye 3, South Greenland, deep ice core and span approximately the last 10,000 years. The results are calibrated with tree-ring records. The 14C ages are compared with information obtained from seasonal variations of ice-core parameters and rheologic model calculation.
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