Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial.

BACKGROUND: Aspirin and eicosapentaenoic acid (EPA) have colorectal polyp prevention activity, alone and in combination. This study measured levels of plasma and rectal mucosal oxylipins in participants of the seAFOod 2 × 2 factorial, randomised, placebo-controlled trial, who received aspirin 300 mg daily and EPA 2000 mg free fatty acid, alone and in combination, for 12 months. METHODS: Resolvin (Rv) E1, 15-epi-lipoxin (LX) A4 and respective precursors 18-HEPE and 15-HETE (with chiral separation) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry in plasma taken at baseline, 6 months and 12 months, as well as rectal mucosa obtained at trial exit colonoscopy at 12 months, in 401 trial participants. RESULTS: Despite detection of S- and R- enantiomers of 18-HEPE and 15-HETE in ng/ml concentrations, RvE1 or 15­epi-LXA4 were not detected above a limit of detection of 20 pg/ml in plasma or rectal mucosa, even in individuals randomised to both aspirin and EPA. We have confirmed in a large clinical trial cohort that prolonged (12 months) treatment with EPA is associated with increased plasma 18-HEPE concentrations (median [inter-quartile range] total 18-HEPE 0.51 [0.21-1.95] ng/ml at baseline versus 0.95 [0.46-4.06] ng/ml at 6 months [P<0.0001] in those randomised to EPA alone), which correlate strongly with respective rectal mucosal 18-HEPE levels (r = 0.82; P<0.001), but which do not predict polyp prevention efficacy by EPA or aspirin. CONCLUSION: Analysis of seAFOod trial plasma and rectal mucosal samples has not provided evidence of synthesis of the EPA-derived specialised pro-resolving mediator RvE1 or aspirin-trigged lipoxin 15­epi-LXA4. We cannot rule out degradation of individual oxylipins during sample collection and storage but readily measurable precursor oxylipins argues against widespread degradation.

Comparison of Dietary Intake in UK Adults Aged 50 to 75 Years During the 2020 UK Covid-19 Lockdown Compared to their 2019 Intakes.

The lockdown restrictions imposed as a result of COVID-19 impacted on many areas of daily life including dietary behaviours. A cohort of middle-older age adults (n=17), who had previously provided 3-day food diaries in May 2019 were asked to record their 3 day dietary intake in May 2020 when the UK was under lockdown restrictions. Mean (SD) energy intakes were significantly higher by ~750kilojoules in 2020 (8587kJ (1466.9)) compared to 2019 (7837 kJ (1388.9)). This energy increase is equivalent to ~170kcal; approximately 2 slices of bread. Furthermore, recorded meat/meat products, riboflavin, vitamin B6/B12 and iron intakes were all greater in 2020. No other dietary differences were observed between the two timepoints. This was a small, homogenous but well controlled sample, who exhibited a relatively stable diet during lockdown compared with pre-pandemic intakes 12 months earlier. It can be concluded that there was little evidence of food insecurity in this cohort.

Characterizing the optical response of ultra-low-noise far-infrared 60-110 µm transition edge sensors.

Far-infrared Transition Edge Sensors (TESs) are being developed for the SAFARI grating spectrometer on the cooled-aperture space telescope SPICA. In support of this work, we have devised a cryogenic (90 mK) test facility for carrying out precision optical measurements on ultra-low-noise TESs. Although our facility is suitable for the whole of the SAFARI wavelength range, 34 µm-230 µm, we focus on a representative set of measurements at 60 µm-110 µm using a device having a noise equivalent power of 0.32 aW Hz-1/2. The system is able to perform a range of measurements: (i) dark electrical characterization, (ii) optical efficiency with respect to a partially coherent beam having a modal composition identical to that of an ideal imaging telescope, (iii) optical saturation and dynamic range, (iv) fast optical transient response to a modulated thermal source, and (v) optical transient response in the presence of high-level background loading. We describe dark measurements to determine the operating characteristics of a TES and then compare the predicted optical behavior with the measured optical behavior. By comparing electrical and optical transient responses, we were able to observe thermalization in the device. We comment on the challenge of eliminating stray light.

Investigating the nutritional advice and support given to colorectal cancer survivors in the UK: is it fit for purpose and does it address their needs?

BACKGROUND: The present study assessed the quantity and quality of nutritional advice and support given to colorectal cancer survivors in the UK. METHODS: A descriptive cross-sectional survey was completed by 75 colorectal cancer survivors recruited through social media and bowel cancer support groups in the UK. The survey consisted of open-ended and closed questions that aimed to explore the nutritional needs, nutritional advice given and other sources of information accessed by colorectal cancer survivors. RESULTS: Sixty-nine percent of respondents reported that they did not receive any nutritional advice or support from their healthcare team throughout diagnosis, treatment and post-treatment. Colorectal cancer survivors accessed nutritional advice from a variety of sources, mainly cancer charity websites. Respondents expressed their desire for individualised advice relating to their nutritional problems. CONCLUSIONS: The results obtained in the present study indicate that a high proportion of colorectal cancer patients are not receiving the nutritional support that they need to overcome nutritional difficulties. There is an urgent need to improve clinical practice to ensure colorectal patients receive nutritional advice that is both consistent between healthcare professionals and personalised throughout each stage of diagnosis, treatment and post-treatment.

Fucosyltransferase gene expression in goat endometrium during the estrous cycle and early pregnancy.

Regulation of the expression of the alpha(1,2)fucosyltransferase (FUT) genes and their enzymatic products, including the H-type 1 antigen (HT1), on the luminal surface of the uterus is believed to be critical for establishment of pregnancy in mammals. The FUT1 gene is a marker for conception rates in dairy cows and HT1 is a marker for uterine receptivity in rodents. To determine the spatiotemporal expression patterns of FUT1 and FUT2 genes in goats, endometrial tissues were obtained on six days spanning the estrous cycle (Days 5, 11, 13, 15, 17 and 19) and seven days spanning early pregnancy (Days 5, 11, 13, 15, 17, 19 and 25). In all data, we found no effect of status (cyclic or pregnant; P > 0.1) and pooled data where appropriate. We cloned FUT1 cDNA from goat endometrium and made probes from it for Northern and slot blot analyses. The analyses indicated that FUT1 gene expression was high until Day 13, and then declined. In situ hybridization revealed a change in the cell-specificity of FUT1 gene expression over the estrous cycle and early pregnancy. In situ hybridization signal intensity scores indicated that FUT1 expression by uterine epithelium was high on Day 5, moderate on Day 11, and minimal on subsequent days. In situ hybridization signals in uterine glandular epithelial cells remained high from Day 5 to Day 13, with weaker signals thereafter. Quantitative reverse transcription-PCR (RT-qPCR) assays were used for quantitation of FUT1 and FUT2 mRNAs. Quantitative RT-qPCR data were generated from endometrium collected from cyclic and pregnant animals on Days 5, 11 and 17. Relative levels of FUT1 mRNA were high on Days 5 and 11, but then fell 5-fold by Day 17 (P < 0.01). FUT2 mRNA concentrations were below the accurate detectable limit of the assay. High levels of HT1 were observed on the apical surface of uterine luminal epithelia on Days 5, 15, 17 and 19, with much lower levels on Days 11 and 13. Thus, data suggests that FUT1 is the primary enzyme responsible for the high levels of HT1 antigen present on the uterine luminal epithelium between Days 5 and 11 of the estrous cycle and early pregnancy. But changes in the expression of the FUT1 gene does not directly correlate to HT1 staining, which increased from Day 13-15. Future studies are required to understand the regulation of the HT1 antigen on the luminal surface of endometrium.

Operationalizing outcome measures of human papillomavirus vaccination among adolescents.

OBJECTIVES: When examining vaccination coverage, researchers must make decisions about how to define outcome measures based on many factors, including the timing of doses. Different operationalizations of the same outcome can often lead to different findings and can affect the ability to make comparisons across studies. This methodological article aimed to illustrate the implications of two options for operationalizing human papillomavirus (HPV) vaccination based on timing: initiation of the first dose at any age vs before the 13th birthday (on time). STUDY DESIGN: Cross-sectional observational design. METHODS: The 2014 National Immunization Survey for Teens (N = 16,439 adolescents aged 13-17 years) was analyzed using multivariate logistic regression for each outcome measure and effect modification by gender. RESULTS: Age was positively associated with initiation at any age but negatively associated with on-time initiation. Gender modified the effect of race/ethnicity for both measures of initiation, but the pattern across groups was different for the two outcomes. Gender modified the effect of provider recommendation for initiation at any age, while gender modified the effects of age and region for on-time initiation. CONCLUSION: Decisions of how to operationalize outcomes of HPV vaccine initiation among adolescents can lead to different conclusions about the role of age and gender differences for several predictive variables. To inform the development of public health efforts that promote on-time HPV vaccination among male and female adolescents, researchers should consider the importance of dose timing when operationalizing outcome measures. We recommend including on-time receipt of the HPV vaccine as an outcome measure.

Protein for Life: Towards a focussed dietary framework for healthy ageing.

'Ageing well' has been highlighted as an important research area by the World Health Organization. In the UK, healthy ageing has been identified as a priority research area by multiple Research Councils and is a key NHS priority. Sarcopaenia, the decline of muscle mass/strength and a key component of healthy ageing, can have a major impact on quality of life and is associated with premature mortality. Increasing protein intake at all stages of the life course may help to reduce the rate of muscle decline and the onset of associated health conditions. However, there is a lack of understanding of the social, demographic and psychological drivers of food choices surrounding protein intake. This report describes the multidisciplinary approach that has been adopted by the Protein for Life project to create a framework for the development of palatable, cost-effective higher-protein foods suitable for an ageing population.

A Comparison of Food Portion Size Estimation by Older Adults, Young Adults and Nutritionists.

OBJECTIVES: To investigate the ability of older adults, younger adults and nutritionists to assess portion size using traditional methods versus a computer-based method. This was to inform the development of a novel dietary assessment method for older adults "The NANA system". DESIGN: Older and younger adults assessed the portion size of self-served portions of foods from a buffet style set up using traditional and computerised portion size assessment aids. Nutritionists assessed the portion size of foods from digital photographs using computerised portion size aids. These estimates were compared to known weights of foods using univariate analyses of covariance (ANCOVA). SETTING: The University of Sheffield, United Kingdom. SUBJECTS: Forty older adults (aged 65 years and over), 41 younger adults (aged between 18 and 40 years) and 25 nutritionists. RESULTS: There was little difference in the abilities of older and younger adults to assess portion size using both assessment aids with the exception of small pieces morphology. Even though the methods were not directly comparable among the test groups, there was less variability in portion size estimates made by the nutritionists. CONCLUSION: Older adults and younger adults are similar in their ability to assess food portion size and demonstrate wide variability of estimation compared to the ability of nutritionists to estimate portion size from photographs. The results suggest that the use of photographs of meals consumed for portion size assessment by a nutritionist may improve the accuracy of dietary assessment. Improved portion size assessment aids are required for all age groups.

Using the NANA toolkit at home to predict older adults' future depression.

BACKGROUND: Depression is currently underdiagnosed among older adults. As part of the Novel Assessment of Nutrition and Aging (NANA) validation study, 40 older adults self-reported their mood using a touchscreen computer over three, one-week periods. Here, we demonstrate the potential of these data to predict future depression status. METHODS: We analysed data from the NANA validation study using a machine learning approach. We applied the least absolute shrinkage and selection operator with a logistic model to averages of six measures of mood, with depression status according to the Geriatric Depression Scale 10 weeks later as the outcome variable. We tested multiple values of the selection parameter in order to produce a model with low deviance. We used a cross-validation framework to avoid overspecialisation, and receiver operating characteristic (ROC) curve analysis to determine the quality of the fitted model. RESULTS: The model we report contained coefficients for two variables: sadness and tiredness, as well as a constant. The cross-validated area under the ROC curve for this model was 0.88 (CI: 0.69-0.97). LIMITATIONS: While results are based on a small sample, the methodology for the selection of variables appears suitable for the problem at hand, suggesting promise for a wider study and ultimate deployment with older adults at increased risk of depression. CONCLUSIONS: We have identified self-reported scales of sadness and tiredness as sensitive measures which have the potential to predict future depression status in older adults, partially addressing the problem of underdiagnosis.

Validation of the NANA (Novel Assessment of Nutrition and Ageing) touch screen system for use at home by older adults.

Prospective measurement of nutrition, cognition, and physical activity in later life would facilitate early detection of detrimental change and early intervention but is hard to achieve in community settings. Technology can simplify the task and facilitate daily data collection. The Novel Assessment of Nutrition and Ageing (NANA) toolkit was developed to provide a holistic picture of an individual's function including diet, cognition and activity levels. This study aimed to validate the NANA toolkit for data collection in the community. Forty participants aged 65 years and over trialled the NANA toolkit in their homes for three 7-day periods at four-week intervals. Data collected using the NANA toolkit were compared with standard measures of diet (four-day food diary), cognitive ability (processing speed) and physical activity (self-report). Bland-Altman analysis of dietary intake (energy, carbohydrates, protein fat) found a good relationship with the food diary and cognitive processing speed and physical activity (hours) were significantly correlated with their standard counterparts. The NANA toolkit enables daily reporting of data that would otherwise be collected sporadically while reducing demands on participants; older adults can complete the daily reporting at home without a researcher being present; and it enables prospective investigation of several domains at once.

Probiotic supplement consumption alters cytokine production from peripheral blood mononuclear cells: a preliminary study using healthy individuals.

The objective of this study was to examine the effect of daily probiotic supplementation upon the immune profile of healthy participants by the assessment of ex vivo cytokine production. Twenty healthy adult volunteers received a multi-strain probiotic supplement consisting of two strains of Lactobacillus acidophilus (CUL60 and CUL21), Bifidobacterium lactis (CUL34) and Bifidobacterium bifidum (CUL20) and fructooligosaccharide for 12 weeks. Blood samples were collected at baseline, 6 and 12 weeks. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured ex vivo in the presence or absence of lipopolysaccharide and cytokine production was assessed. Postintervention, a significant decrease in the production of interleukin-6 and interleukin-1ß was apparent when PBMCs were incubated in the presence of lipopolysaccharide, whilst a significant increase in IL-10 and transforning growth factor-ß production was seen when the cells were incubated without an additional stimulus. This preliminary study demonstrates the potential of a multi-strain probiotic supplement to alter the immune response as demonstrated by changes in ex vivo cytokine production. Such results demonstrate the potential benefit of probiotic supplementation for healthy individuals and warrants further investigation.

Raman backscatter as a remote laser power sensor in high-energy-density plasmas.

Stimulated Raman backscatter is used as a remote sensor to quantify the instantaneous laser power after transfer from outer to inner cones that cross in a National Ignition Facility (NIF) gas-filled hohlraum plasma. By matching stimulated Raman backscatter between a shot reducing outer versus a shot reducing inner power we infer that about half of the incident outer-cone power is transferred to inner cones, for the specific time and wavelength configuration studied. This is the first instantaneous nondisruptive measure of power transfer in an indirect drive NIF experiment using optical measurements.

Kinetic theory and Vlasov simulation of nonlinear ion-acoustic waves in multi-ion species plasmas.

The theory of damping and nonlinear frequency shifts from particles resonant with ion-acoustic waves (IAWs) is presented for multi-ion species plasma and compared to driven wave Vlasov simulations. Two distinct IAW modes may be supported in multi-ion species plasmas, broadly classified as fast and slow by their phase velocity relative to the constituent ion thermal velocities. In current fusion-relevant long pulse experiments, the ion to electron temperature ratio, T(i)/T(e), is expected to reach a level such that the least damped and thus more readily driven mode is the slow mode, with both linear and nonlinear properties that are shown to differ significantly from the fast mode. The lighter ion species of the slow mode is found to make no significant contribution to the IAW frequency shift despite typically being the dominant contributor to the Landau damping.

Stochastic ion heating from many overlapping laser beams in fusion plasmas.

In this Letter, we show through numerical simulations and analytical results that overlapping multiple (N) laser beams in plasmas can lead to strong stochastic ion heating from many (~N(2)) electrostatic perturbations driven by beat waves between pairs of laser beams. For conditions typical of inertial-confinement-fusion experiment conditions, hundreds of such beat waves are driven in mm(3)-scale plasmas, leading to ion heating rates of several keV/ns. This mechanism saturates cross-beam energy transfer, with a reduction of linear gains by a factor ~4-5 and can strongly modify the overall hydrodynamics evolution of such laser-plasma systems.

Three-wavelength scheme to optimize hohlraum coupling on the National Ignition Facility.

By using three tunable wavelengths on different cones of laser beams on the National Ignition Facility, numerical simulations show that the energy transfer between beams can be tuned to redistribute the energy within the cones of beams most prone to backscatter instabilities. These radiative hydrodynamics and laser-plasma interaction simulations have been tested against large-scale hohlraum experiments with two tunable wavelengths and reproduce the hohlraum energetics and symmetry. Using a third wavelength provides a greater level of control of the laser energy distribution and coupling in the hohlraum, and could significantly reduce stimulated Raman scattering losses and increase the hohlraum radiation drive while maintaining a good implosion symmetry.

Observation of high soft x-ray drive in large-scale hohlraums at the National Ignition Facility.

The first soft x-ray radiation flux measurements from hohlraums using both a 96 and a 192 beam configuration at the National Ignition Facility have shown high x-ray conversion efficiencies of ∼85%-90%. These experiments employed gold vacuum hohlraums, 6.4 mm long and 3.55 mm in diameter, heated with laser energies between 150-635 kJ. The hohlraums reached radiation temperatures of up to 340 eV. These hohlraums for the first time reached coronal plasma conditions sufficient for two-electron processes and coronal heat conduction to be important for determining the radiation drive.

The first measurements of soft x-ray flux from ignition scale Hohlraums at the National Ignition Facility using DANTE (invited).

The first 96 and 192 beam vacuum Hohlraum target experiments have been fielded at the National Ignition Facility demonstrating radiation temperatures up to 340 eV and fluxes of 20 TW/sr as viewed by DANTE representing an ∼20 times flux increase over NOVA/Omega scale Hohlraums. The vacuum Hohlraums were irradiated with 2 ns square laser pulses with energies between 150 and 635 kJ. They produced nearly Planckian spectra with about 30±10% more flux than predicted by the preshot radiation hydrodynamic simulations. To validate these results, careful verification of all component calibrations, cable deconvolution, and software analysis routines has been conducted. In addition, a half Hohlraum experiment was conducted using a single 2 ns long axial quad with an irradiance of ∼2×10(15) W/cm(2) for comparison with NIF Early Light experiments completed in 2004. We have also completed a conversion efficiency test using a 128-beam nearly uniformly illuminated gold sphere with intensities kept low (at 1×10(14) W/cm(2) over 5 ns) to avoid sensitivity to modeling uncertainties for nonlocal heat conduction and nonlinear absorption mechanisms, to compare with similar intensity, 3 ns OMEGA sphere results. The 2004 and 2009 NIF half-Hohlraums agreed to 10% in flux, but more importantly, the 2006 OMEGA Au Sphere, the 2009 NIF Au sphere, and the calculated Au conversion efficiency agree to ±5% in flux, which is estimated to be the absolute calibration accuracy of the DANTEs. Hence we conclude that the 30±10% higher than expected radiation fluxes from the 96 and 192 beam vacuum Hohlraums are attributable to differences in physics of the larger Hohlraums.

Tuning the implosion symmetry of ICF targets via controlled crossed-beam energy transfer.

Radiative hydrodynamics simulations of ignition experiments show that energy transfer between crossing laser beams allows tuning of the implosion symmetry. A new full-scale, three-dimensional quantitative model has been developed for crossed-beam energy transfer, allowing calculations of the propagation and coupling of multiple laser beams and their associated plasma waves in ignition hohlraums. This model has been implemented in a radiative-hydrodynamics code, demonstrating control of the implosion symmetry by a wavelength separation between cones of laser beams.

Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study.

BACKGROUND: The efficacy of probiotics in alleviating the symptoms of irritable bowel syndrome (IBS) appears to be both strain- and dose-related. AIM: To investigate the effect of LAB4, a multistrain probiotic preparation on symptoms of IBS. This probiotic preparation has not previously been assessed in IBS. METHODS: Fifty-two participants with IBS, as defined by the Rome II criteria, participated in this double blind, randomized, placebo-controlled study. Participants were randomized to receive either a probiotic preparation comprising two strains of Lactobacillus acidophilus CUL60 (NCIMB 30157) and CUL21 (NCIMB 30156), Bifidobacterium lactis CUL34 (NCIMB 30172) and Bifidobacterium bifidum CUL20 (NCIMB 30153) at a total of 2.5 × 10(10) cfu/capsule or a placebo for 8 weeks. Participants reported their IBS symptoms using a questionnaire fortnightly during the intervention and at 2 weeks post-intervention. RESULTS: A significantly greater improvement in the Symptom Severity Score of IBS and in scores for quality of life, days with pain and satisfaction with bowel habit was observed over the 8-week intervention period in the volunteers receiving the probiotic preparation than in the placebo group. CONCLUSION: LAB4 multistrain probiotic supplement may benefit subjects with IBS.

Using a short-pulse diffraction-limited laser beam to probe filamentation of a random phase plate smoothed beam.

A short pulse (few picoseconds) laser probe provides high temporal resolution measurements to elucidate details of fast dynamic phenomena not observable with typical longer laser pulse probes and gated diagnostics. Such a short pulse laser probe (SPLP) has been used to measure filamentation of a random phase plate (RPP) smoothed laser beam in a gas-jet plasma. The plasma index of refraction due to driven density and temperature fluctuations by the RPP beam perturbs the phase front of a SPLP propagating at a 90 degree angle with respect to the RPP interaction beam. The density and temperature fluctuations are quasistatic on the time scale of the SPLP (approximately 2 ps). The transmitted near-field intensity distribution from the SPLP provides a measure of the phase front perturbation. At low plasma densities, the transmitted intensity pattern is asymmetric with striations across the entire probe beam in the direction of the RPP smoothed beam. As the plasma density increases, the striations break up into smaller sizes along the direction of the RPP beam propagation. The breakup of the intensity pattern is consistent with self-focusing of the RPP smoothed interaction beam. Simulations of the experiment using the wave propagation code, PF3D, are in qualitative agreement demonstrating that the asymmetric striations can be attributed to the RPP driven density fluctuations. Quantification of the beam breakup measured by the transmitted SPLP could lead to a new method for measuring self-focusing of lasers in underdense plasmas.