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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.
Introduction: A significant gap exists between the number of people waiting for an organ and donors. There are currently 1,628 people awaiting organ donation in Ontario alone. In 2018 to date, 310 donors have donated 858 organs. The purpose of this study was to determine whether there were missed donors in the Emergency Department (ED) and by what percent those missed donors would increase organ donation overall. Methods: This was a health records and organ donation database review of all patients who died in the ED at a large academic tertiary care center with 2 campuses and 160,000 visits per year. Patients were included from November 1, 2014 – October 31, 2017. We collected data on demographics, cause of death, and suitability for organ donation. Data was cross-referenced between hospital records and the provincial organ procurement organization called Trillium Gift of Life Network (TGLN) to determine whether patients were appropriately referred for consideration of donation in a timely manner. Potential missed donors were manually screened for suitability according to TGLN criteria. We calculated simple descriptive statistics for demographic data and the primary outcome. The primary outcome was percentage of potential organ donors missed in the Emergency Department (ED). Results: There were 606 deaths in the ED from November 1, 2014 – October 31, 2017. Patients were an average of 71 years old, 353 (58%) were male, and 75 (12%) died of a traumatic cause. TGLN was not contacted in 12 (2%) of cases. During this period there were two donors from the ED and 92 from the ICU. There were ten missed potential donors. They were an average of 67 years, 7 (70%) were male, and 2 (20%) died of a traumatic cause. In all ten cases, patients had withdrawal of life sustaining measures for medical futility prior to TGLN being contacted for consideration of donation. There could have been an addition seven liver, six pancreatic islet, four small bowel, and seven kidney donors. The ten missed ED donors could have increased total donors by 11%. Conclusion: The ED is a significant source of missed organ donors. In all cases of missed organ donation, patients had withdrawal of life sustaining measures prior to TGLN being called. In the future, it is essential that all patients have an organ procurement organization such as TGLN called prior to withdrawal of life sustaining measures to ensure that no opportunity for consideration of organ donation is missed.
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.
Introduction: There is a significant gap between the number of organ donors and people awaiting an organ transplant; therefore it is essential that all potential donors are identified. Given the nature of Emergency Medicine it is a potential source of organ donors. The purpose of this study is to determine what percent of successful donors come from the Emergency Department (ED) and whether there are any missed potential donors. Methods: Electronic searches of EMBASE, MEDLINE, and CINAHL were performed July 7, 2017 using PRISMA guidelines. Primary literature in human adults were included if they described identification of patients in the ED who went on to become successful solid organ donors, or described missed potential donors in the ED. Data on the total population of actual or missed donors was required to allow calculation of a percentage. Studies describing non-solid organ donation, consent, ethics, survey of attitudes, teaching curricula, procurement techniques, donation outside the ED, and recipient factors were excluded. 2 authors independently screened articles for inclusion and discrepancies were resolved through consensus. Quality was assessed using STROBE for observational studies. Heterogeneity of patient populations precluded pooling of the data to conduct a meta-analysis. Results: 1058 articles were identified, 17 duplicates were removed, 800 articles were excluded based on title and abstract, and 217 full text articles were excluded, yielding 24 articles for the systematic review. For neurologic determination of death (NDD), ED patients comprised 4 44% of successful donors. ED death reviews revealed 0 84% of patients dying in the ED are missed as potential donors and hospital-wide death reviews revealed 13 80.9% of missed donors die in the ED. For donation after cardiac death (DCD), 4 20% of successful donors came from the ED and studies investigating potential donors suggest 2 36% of patients dying the in the ED could be potential DCD donors. The most common population of successful DCD organ donors was in traumatic cardiopulmonary arrest (TCPA), with 3.6 8.9% of TCPA patients presenting to the ED becoming successful donors. Conclusion: Patients dying in the Emergency Department are a significant source of both successful organ donors and missed potential donors. Emergency physicians should be familiar with their local organ donation protocol to ensure potential organ donors are not missed.
Understanding infection dynamics in animal hosts is fundamental to managing spillover and emergence of zoonotic infections. Hendra virus is endemic in Australian pteropodid bat populations and can be lethal to horses and humans. However, we know little about the factors driving Hendra virus prevalence in resevoir bat populations, making spillover difficult to predict. We use Hendra virus prevalence data collected from 13 000 pooled bat urine samples across space and time to determine if pulses of prevalence are periodic and synchronized across sites. We also test whether site-specific precipitation and temperature affect the amplitude of the largest annual prevalence pulses. We found little evidence for a periodic signal in Hendra virus prevalence. Although the largest amplitude pulses tended to occur over winter, pulses could also occur in other seasons. We found that Hendra virus prevalence was weakly synchronized across sites over short distances, suggesting that prevalence is driven by local-scale effects. Finally, we found that drier conditions in previous seasons and the abundance of Pteropus alecto were positively correlated with the peak annual values of Hendra virus prevalence. Our results suggest that in addition to seasonal effects, bat density and local climatic conditions interact to drive Hendra virus infection dynamics.
Understanding viral transmission dynamics within populations of reservoir hosts can facilitate greater knowledge of the spillover of emerging infectious diseases. While bat-borne viruses are of concern to public health, investigations into their dynamics have been limited by a lack of longitudinal data from individual bats. Here, we examine capture–mark–recapture (CMR) data from a species of Australian bat (Myotis macropus) infected with a putative novel Alphacoronavirus within a Bayesian framework. Then, we developed epidemic models to estimate the effect of persistently infectious individuals (which shed viruses for extensive periods) on the probability of viral maintenance within the study population. We found that the CMR data analysis supported grouping of infectious bats into persistently and transiently infectious bats. Maintenance of coronavirus within the study population was more likely in an epidemic model that included both persistently and transiently infectious bats, compared with the epidemic model with non-grouping of bats. These findings, using rare CMR data from longitudinal samples of individual bats, increase our understanding of transmission dynamics of bat viral infectious diseases.
We present results from a multiwavelength study of the blazar PKS 1954–388 at radio, UV, X-ray, and gamma-ray energies. A RadioAstron observation at 1.66 GHz in June 2012 resulted in the detection of interferometric fringes on baselines of 6.2 Earth-diameters. This suggests a source frame brightness temperature of greater than 2 × 1012 K, well in excess of both equipartition and inverse Compton limits and implying the existence of Doppler boosting in the core. An 8.4-GHz TANAMI VLBI image, made less than a month after the RadioAstron observations, is consistent with a previously reported superluminal motion for a jet component. Flux density monitoring with the Australia Telescope Compact Array confirms previous evidence for long-term variability that increases with observing frequency. A search for more rapid variability revealed no evidence for significant day-scale flux density variation. The ATCA light-curve reveals a strong radio flare beginning in late 2013, which peaks higher, and earlier, at higher frequencies. Comparison with the Fermi gamma-ray light-curve indicates this followed ~ 9 months after the start of a prolonged gamma-ray high-state—a radio lag comparable to that seen in other blazars. The multiwavelength data are combined to derive a Spectral Energy Distribution, which is fitted by a one-zone synchrotron-self-Compton (SSC) model with the addition of external Compton (EC) emission.
Vanadium dioxide (VO2) is a promising material for an optical switch due to the ultrafast and reversible transition between its two phases with contrasting optical, as well as electronic, properties. Meanwhile, erbium (Er3+) has been a standard optical amplifier for the current fiber-optic communication system. Hence, a combination of the two could be expected to make an optical switch capable of simultaneous optical amplification. In the present work, the optical switching and photoluminescence of Er-implanted VO2 were successfully demonstrated. Post-implantation annealing at 800°C or above was seen crucial for the activation of the Er centers in the VO2 crystals.
Hydrogen blister rates in Si (100), Si (111) and Ge (100) substrates are compared as a function of annealing temperature and time, for a range of implant energies and fluences. For each material, the rate of blister formation was found to exhibit Arrhenius behavior and to be characterised by a single activation energy over the temperature range examined. The extracted activation energies were 2.28±0.03 eV, 2.17±0.06 eV and 1.4±0.03 eV for (100) Si; (111) Si and (100) Ge, respectively. These results are compared with reported measurements and discussed in relation to proposed models of hydrogen blistering.
The kinetics of intrinsic and dopant-enhanced solid phase epitaxy (SPE) are studied in thick amorphous germanium (a-Ge) layers formed by ion implantation on <100> Ge substrates. The SPE rates for H-free Ge were measured with a time-resolved reflectivity (TRR) system in the temperature range 300 – 540 °C and found to have an activation energy of (2.15 ± 0.04) eV. Dopant enhanced SPE was measured in a-Ge layers containing a uniform concentration profile of implanted As spanning the concentration regime 1 – 10 × 1019 cm3. The generalized Fermi level shifting model shows excellent fits to the data.
Boron enhanced H diffusion in amorphous Si (a-Si) layers formed by ion implantation is observed using secondary ion mass spectroscopy (SIMS). Constant concentrations of B were achieved using multiple energy B implantations into thick a-Si layers. The evolution of single H implanted profiles centered on the uniformly B-implanted regions was studied for partial anneals at temperatures in the range 380 – 640 °C. Boron enhanced diffusion is observed and the enhanced diffusion coefficient shows trends with temperature typically associated with a Fermi level shifting dependence. A modified form of the generalized Fermi level shifting model is considered in light of these results.