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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.
The generation of high-order harmonics in ultraviolet spectral range by targets of periodic modulation interacting with relativistic, high contrast laser pulse (Iλ2 = 1020 W/cm2 · μm2) was investigated experimentally and numerically. The spectral intensity of the 2nd- and 3rd-order harmonic emission from grating of different periodicities (250, 410, and 480 nm) is presented. The enhancement of the 3rd harmonic order compared with 2nd was observed for a grating of 480 nm periodicity. The experimental results indicate the role of the grating periodicity on the emission efficiency of different higher order harmonics in the UV spectral range. The higher order harmonics are emitted at the grating surface separated from the specular reflection of the laser pulse, due of the interference effects. In addition, 2D numerical PIC simulations demonstrate a complex angular distribution of the higher harmonics (HH) spectral intensity and confirm the strong dependence of the HH efficiency of a specific order on the grating periodicity, as observed experimentally. These special features of the high harmonic emission by periodically modulated targets open the route toward the control of HH spectral composition and of the emission efficiency of the lower order harmonics.
With the latest configuration, the Ti:Sa laser system ARCTURUS (Düsseldorf University, Germany) operates with a double-chirped pulse amplification (CPA) architecture delivering pulses with an energy of 7 J before compression in each of the two high-power beams. By the implementation of a plasma mirror system, the intrinsic laser contrast is enhanced up to
on a time scale of hundreds of picoseconds, before the main peak. The laser system has been used in various configurations for advanced experiments and different studies have been carried out employing the high-power laser beams as a single, high-intensity interaction beam (
), in dual- and multi-beam configurations or in a pump–probe arrangement.
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.
Polymer-containing solutions used across research and industry are commonly exposed to mechanically harsh fluid processes, for example shear and extensional forces during flow through porous media or rapid microdispensing of biopharmaceutical molecules. These forces are strong enough to break the covalent bonds in the polymer backbone. As this scission phenomenon can change the functional and fluid-flow properties as well as introduce reactive radicals into the solution, it must be understood and controlled. Experiments and models to date have only provided partial or qualitative insights into this behaviour. Here we build a link between the molecular-scale degradation models and the macroscale laminar flow of dilute solutions in any given geometry. A free-draining bead–rod model is used to investigate rupture events at the molecular scale. It is shown by uniaxial extension simulations of an ensemble of chains that scission can be conveniently described at the macroscopic scale as a first-order reaction whose rate is a function of the conformation tensor of the macromolecules and the velocity gradient of the flow. This approach is implemented in the finite volume code OpenFOAM by elaborating an appropriate constitutive equation for the conformation tensor. The macroscopic model is run and analysed for ultra-dilute solutions of poly(methyl methacrylate) in ethyl acetate and polyethylene oxide in water, using the geometry of an abrupt contraction flow and neglecting any viscoelastic effect. This multiscale approach bridges the gap between phenomenological observations of mechanically induced chemical degradation in large-scale applications and the rich field of molecular-scale models of macromolecules under flow.
Back-diffusion is the phenomenon by which random walkers revisit binding sites on a lattice. This phenomenon must occur on interstellar dust particles, slowing down dust-grain reactions, but it is not accounted for by standard rate-equation models. Microscopic kinetic Monte Carlo models have been used to investigate the effect of back-diffusion on reaction rates on interstellar dust grains. Grain morphology, size, and grain-surface coverage were varied and the effects of these variations on the magnitude of the back-diffusion effect were studied for the simple H+H reaction system. This back-diffusion effect is seen to reduce reaction rates by a maximum factor of ∼5 for the canonical grain of 106 binding sites. The resulting data were fit to logarithmic functions that can be used to reproduce the effects of back-diffusion in rate-equation models.
Five cases of STEC O157 phage type (PT) 21/28 reported consumption of raw cows' drinking milk (RDM) produced at a dairy farm in the South West of England. STEC O157 PT21/28 was isolated from faecal specimens from milking cows on the implicated farm. Whole genome sequencing (WGS) showed that human and cattle isolates were the same strain. Further analysis of WGS data confirmed that sequences of isolates from an additional four cases (who did not report consumption of RDM when first questioned) fell within the same five single nucleotide polymorphism cluster as the initial five cases epidemiologically linked to the consumption of RDM. These four additional cases identified by WGS were investigated further and were, ultimately, associated with the implicated farm. The RDM outbreak strain encoded stx2a, which is associated with increased pathogenicity and severity of symptoms. Further epidemiological analysis showed that 70% of isolates within a wider cluster containing the outbreak strain were from cases residing in, or linked to, the same geographical region of England. During this RDM outbreak, use of WGS improved case ascertainment and provided insights into the evolution of a highly pathogenic clade of STEC O157 PT21/28 stx2a associated with the South West of England.
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.
The Dominion Radio Astrophysical Observatory (DRAO) is carrying out a survey as part of an international collaboration to image the northe, at a common resolution, in emission from all major constituents of the interstellar medium; the neutral atomic gas, the molecular gas, the ionised gas, dust and relativistic plasma. For many of these constituents the angular resolution of the images (1 arcmin) will be more than a factor of 10 better than any previous studies. The aim is to produce a publicly-available database of high resolution, high-dynamic range images of the Galaxy for multi-phase studies of the physical states and processes in the interstellar medium. We will sketch the main scientific motivations as well as describe some preliminary results from the Canadian Galactic Plane Survey/Releve Canadien du Plan Galactique (CGPS/RCPG).