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Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
There is a requirement in some beef markets to slaughter bulls at under 16 months of age. This requires high levels of concentrate feeding. Increasing the slaughter age of bulls to 19 months facilitates the inclusion of a grazing period, thereby decreasing the cost of production. Recent data indicate few quality differences in longissimus thoracis (LT) muscle from conventionally reared 16-month bulls and 19-month-old bulls that had a grazing period prior to finishing on concentrates. The aim of the present study was to expand this observation to additional commercially important muscles/cuts. The production systems selected were concentrates offered ad libitum and slaughter at under 16 months of age (16-C) or at 19 months of age (19-CC) to examine the effect of age per se, and the cheaper alternative for 19-month bulls described above (19-GC). The results indicate that muscles from 19-CC were more red, had more intramuscular fat and higher cook loss than those from 16-C. No differences in muscle objective texture or sensory texture and acceptability were found between treatments. The expected differences in composition and quality between the muscles were generally consistent across the production systems examined. Therefore, for the type of animal and range of ages investigated, the effect of the production system on LT quality was generally representative of the effect on the other muscles analysed. In addition, the data do not support the under 16- month age restriction, based on meat acceptability, in commercial suckler bull production.
A high dietary fibre intake has been associated with improvements in inflammatory conditions in adults. However, little is known on whether associations between dietary fibre and inflammation are evident during adolescence. We examined the relationship between dietary fibre intake measured by food frequency questionnaire and the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the adipokines leptin and adiponectin cross-sectionally in 17-year-olds participating in the Raine Study (n=621). In weighted analysis using tobit and linear regression, and after excluding participants with hs-CRP>10mg/L, higher total dietary fibre intake (per 5g/day) was significantly associated with lower leptin (β=-0.13, 95% CI -0.17, -0.09) and adiponectin (β=-0.28, 95% CI -0.49, -0.07), but not hs-CRP, in unadjusted analyses. These associations were no longer significant after adjustment for gender, anthropometry and a number of lifestyle factors. However, higher cereal and grain fibre intake was significantly associated with lower leptin (β=-0.06, 95% CI -0.10, -0.01) in fully adjusted analysis. Our findings suggest that a higher intake of cereal and grain fibre may contribute to lower leptin in adolescents. This may contribute to reductions in low-grade chronic inflammation and improved health outcomes.
Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe—primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.
Women with obesity breastfeed for shorter durations than women of normal-weight body mass index (BMI). There is also evidence to suggest that women with obesity are less likely to initiate breastfeeding. This is important because breastfeeding is associated with a small, but significant, reduced risk of obesity among offspring; which may be particularly important for the offspring of mothers with obesity as these infants are at an increased risk of obesity. Using data prospectively collected during 2015 by medical staff in a large maternity hospital, we aimed to explore the association between maternal obesity status and early breastfeeding outcomes: breastfeeding initiation and exclusive breastfeeding at hospital discharge (approx. day 2 of life). Data were obtained from electronic records for all births in The National Maternity Hospital, Dublin in 2015. We included data from mothers who delivered a healthy, full-term, singleton infant (n = 7449). At the booking visit (approx. 12 weeks’ gestation), maternal height and weight were objectively measured by nursing staff and subsequently used to calculate BMI; other demographic data were recorded at this time. At delivery, epidural use, mode of delivery, and infant sex and weight were recorded. At discharge, mode of feeding was recorded. In SPSS, we explored unadjusted and adjusted associations between obesity status (BMI < 30kg/m2 [n = 964] vs. BMI ≥ 30kg/m2 [n = 6485]) and breastfeeding outcomes (dichotomous: yes/no) using Chi-squared analysis and multivariate logistic regression, respectively. In unadjusted analyses, there was a significant association between obesity status and breastfeeding initiation; 76% of women without obesity initiated breastfeeding compared with 59% of women with obesity (P < 0.001). There was also a significant association between obesity status and exclusive breastfeeding; 69% of women without obesity were exclusively breastfeeding at discharge compared with 37% of women with obesity (P < 0.001). In logistic regression analyses adjusted for maternal age, ethnicity, marital status, smoking status, parity, epidural use and delivery mode, the odds of women with obesity initiating breastfeeding were 51% lower than women without obesity (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.42–0.57; P < 0.001). Similarly, in adjusted analyses, the odds of women with obesity exclusively breastfeeding at hospital discharge were 54% lower than women without obesity (OR 0.44, 95% CI 0.38–0.51; P < 0.001). Research is needed to understand whether the negative association between obesity and breastfeeding is biological or cultural in origin, or both. Interventions to promote and support breastfeeding among women with obesity may improve breastfeeding outcomes.
Most reports on the outcome of children who present with heart failure, due to heart muscle disease, are from an era when ventricular assist devices were not available. This study provides outcome data for the current era where prolonged circulatory support can be considered for most children.
Methods & Results:
Data was retrieved on 100 consecutive children, who presented between 2010 – 2016, with a first diagnosis of unexplained heart failure. Hospital outcome was classified as either death, transplantation, recovery of function or persistent heart failure. Median age at presentation was 24 months and 58% were < 5 years old. Hospital mortality was 12% and 59% received a heart transplant. Most, 79%, of the transplants were carried out on patients with a device. Recovery of function was observed in 18% and 10% stabilised on oral therapy. Eighty-four percent of the deaths occurred in the <5 year old group. Shorter duration of support was associated with survival (34 days in survivors versus 106 in non-survivors, p = 0.01) and 72% were on an assist device at time of death.
Heart failure in children who require referral to a transplant unit is a serious illness with a high chance of either transplantation or death. Modifications in assist devices will be required to improve safety, especially for children < 5 years old where the donor wait may be prolonged. The identification of children who may recover function requires further study.
Introduction: Optimizing naloxone dosing in the context of increasing fentanyl and ultra-potent opioid (UPO) prevalence is an important consideration for emergency health care providers. The goal of this systematic review was to evaluate the association between initial and cumulative naloxone doses on effective reversal and adverse events in undifferentiated and fentanyl/UPO overdoses. Methods: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings from July to October 2018 and back to 1972. Our search included pertinent indexing terms for UPOs. We included interventional and observational studies reporting on naloxone administration for opioid toxicity reversal in people ≥12 years old. Additionally, we accessed non-traditional evidence sources (case reports and series) given this rapidly changing field. We conducted inclusion screens, data extraction and quality assessments in duplicate. We summarized study characteristics and where reported, analyzed number of patients with clinical response. Response was defined as not receiving further naloxone doses and remaining alive. Results: We included 174 studies (108 case reports and series, 55 observational, 9 interventional) with 26,660 subjects (median age 35.1; 74.2% male). We observed lower response among patients exposed to fentanyl/UPO versus heroin for initial naloxone doses ≤0.4mg (56.8% versus 80.2%) and > 0.4mg (27.0% versus 82.1%). Mean cumulative doses were higher for fentanyl/UPO (2.10 mg, SD 1.80 mg) versus heroin (1.48 mg, SD 1.68 mg) overdoses. In North American studies the median cumulative dose used was higher for fentanyl/UPO versus heroin overdoses. A dose-response curve for fentanyl/UPO studies showed marked variability in doses among responders, indicating heterogeneity. Adverse events reporting was inconsistent; 10% of subjects experienced withdrawal based on studies in which they were reported. Conclusion: This is the first systematic review to summarize proportion of patients with clinical response by naloxone dose provided. While variable reporting, study quality, heterogeneity, and our outcome definitions limit the conclusions we can draw, it appears that higher initial doses and in some cases, higher cumulative naloxone doses were used and may be necessary to reverse toxicity due to fentanyl/UPO compared to other opioids. High-quality prospective studies assessing effectiveness and safety are needed.
Uncontrolled bleeding is a leading cause of preventable death in trauma. The “Stop the Bleed” campaign has trained over 130,000 lay people in the US to act to control bleeding. Current hemorrhage control courses, the most well-known being the American College of Surgeon’s Basic Bleeding Control (ACS B-con) course, require in-person training. Scaling this course nationwide is time and resource intensive. Furthermore, groups have advocated that young people, who are disproportionately affected by physical trauma, be universally trained in hemorrhage control.
Compare the effectiveness of teaching the ACS B-con course to high school (HS) students utilizing three different delivery mechanisms: in-person live, video-recorded, and virtual-live training.
432 students (aged 15-18) will be recruited from two HS settings: 300 from a local HS and 132 from a national online HS platform. Local HS students will be randomized into two arms: a control arm (in-person live training) and virtual training through a pre-recorded lecture. Online HS students will undergo virtual-live training. The primary outcome is correct tourniquet application following training. Secondary outcomes are the acquisition of personal resilience-associated traits using a validated instrument, motivation for further training, and perception of the importance of live training. Tourniquet application data will be assessed using a non-inferiority design using two pairwise comparisons of the intervention arms to the control (in-person). Pre- to post-training survey data will be assessed using paired univariates tests. Sub-analysis of the impact of demographic variables on these relationships will be assessed.
In addition to integration of cardiopulmonary resuscitation courses into HS curricula, there is momentum to develop effective programs to educate HS students to provide care for the injured and control bleeding before first responders arrive. This trial will help determine the most effective delivery mechanism to teach a hemorrhage control course to HS students at scale.
The Stac Fada Member of the Stoer Group, within the Torridonian succession of NW Scotland, is a melt-rich, impact-related deposit that has not been conclusively correlated with any known impact structure. However, a gravity low approximately 50 km east of the preserved Stac Fada Member outcrops has recently been proposed as the associated impact site. We investigate the location of the impact structure through a provenance study of detrital zircon and apatite in five samples from the Stoer Group. Our zircon U–Pb data are dominated by Archaean grains (> 2.5 Ga), consistent with earlier interpretations that the detritus was largely derived from local Lewisian Gneiss Complex, whereas the apatite data (the first for the Stoer Group) display a single major peak at c. 1.7 Ga, consistent with regional Laxfordian metamorphism. The almost complete absence of Archaean-aged apatite is best explained by later heating of the > 2.5 Ga Lewisian basement (the likely source region) above the closure temperature of the apatite U–Pb system (c. 375–450°C). The U–Pb age distributions for zircon and apatite show no significant variation with stratigraphic height. This may be interpreted as evidence that there was no major change in provenance during the course of deposition of the Stoer Group or, if there was any significant change, the different source regions were characterized by similar apatite and zircon U–Pb age populations. Consequently, the new data do not provide independent constraints on the location of the structure associated with the Stac Fada Member impact event.
Since its introduction to the United States in 1852, Chinese privet (Ligustrum sinense Lour.) has spread throughout the Southeast, invading many natural areas. Manual control by cutting or shredding is one of the most common strategies many land managers employ. However, rapid sprouting from the root collar and lateral roots commonly results in poor control. Cutting followed by either glyphosate or triclopyr application to the stumps is generally effective, but the efficacy of these herbicides in relation to treatment timing and L. sinense root collar diameter has not been evaluated. The objective of this experiment was to determine the effectiveness of glyphosate and triclopyr cut stump treatments compared with cutting alone at spring and fall timings across a range of L. sinense size classes. Studies were conducted at two locations in Auburn, AL. Treatments included cut stump+no herbicide, cut stump+ glyphosate (120 g L−1), or cut stump+triclopyr (90 g L−1). Treatments were applied to at least 50 experimental units each at April and November timings. Root collar diameter was recorded for each stem, stems were cut 2.5 cm above the ground, and herbicide treatments were applied within 30 s. Ligustrum sinense mortality and sprouting were quantified 6, 12, and 18 mo after treatment. Both glyphosate and triclopyr amine were very effective in controlling L. sinense at both spring and fall timings. However, glyphosate provided slightly better results than triclopyr when lateral sprouting was included. Application timing also was significant, with a lower percentage of sprouting following November treatments than April treatments. Stem size influenced treatment success, as larger stumps tended to sprout more than smaller stumps. These results indicate L. sinense can be controlled with cut stump herbicide treatment using either glyphosate or triclopyr with spring or fall timings at concentrations much lower than typically used.
X-ray micro-computed tomography (μCT) is a technique which can obtain three-dimensional images of a sample, including its internal structure, without the need for destructive sectioning. Here, we review the capability of the technique and examine its potential to provide novel insights into the lifestyles of parasites embedded within host tissue. The current capabilities and limitations of the technology in producing contrast in soft tissues are discussed, as well as the potential solutions for parasitologists looking to apply this technique. We present example images of the mouse whipworm Trichuris muris and discuss the application of μCT to provide unique insights into parasite behaviour and pathology, which are inaccessible to other imaging modalities.
Accurate and reproducible patient positioning is a critical step in radiotherapy for breast cancer. This has seen the use of permanent skin markings becoming standard practice in many centres. Permanent skin markings may have a negative impact on long-term cosmetic outcome, which may in turn, have psychological implications in terms of body image. The aim of this study was to investigate the feasibility of using a semi-permanent tattooing device for the administration of skin marks for breast radiotherapy set-up.
Materials and methods
This was designed as a phase II double-blinded randomised-controlled study comparing our standard permanent tattoos with the Precision Plus Micropigmentation (PPMS) device method. Patients referred for radical breast radiotherapy were eligible for the study. Each study participant had three marks applied using a randomised combination of the standard permanent and PPMS methods and was blinded to the type of each mark. Follow up was at routine appointments until 24 months post radiotherapy. Participants and a blind assessor were invited to score the visibility of each tattoo at each follow-up using a Visual Analogue Scale. Tattoo scores at each time point and change in tattoo scores at 24 months were analysed by a general linear model using the patient as a fixed effect and the type of tattoo (standard or research) as covariate. A simple questionnaire was used to assess radiographer feedback on using the PPMS.
In total, 60 patients were recruited to the study, of which 55 were available for follow-up at 24 months. Semi-permanent tattoos were more visible at 24 months than the permanent tattoos. Semi-permanent tattoos demonstrated a greater degree of fade than the permanent tattoos at 24 months (final time point) post completion of radiotherapy. This was not statistically significant, although it was more apparent for the patient scores (p=0·071) than the blind assessor scores (p=0·27). No semi-permanent tattoos required re-marking before the end of radiotherapy and no adverse skin reactions were observed.
The PPMS presents a safe and feasible alternative to our permanent tattooing method. An extended period of follow-up is required to fully assess the extent of semi-permanent tattoo fade.
Two highly pathogenic avian influenza (HPAI) outbreaks have affected commercial egg production flocks in the American continent in recent years; a H7N3 outbreak in Mexico in 2012 that caused 70% to 85% mortality and a H5N2 outbreak in the United States in 2015 with over 99% mortality. Blood samples were obtained from survivors of each outbreak and from age and genetics matched non-affected controls. A total of 485 individuals (survivors and controls) were genotyped with a 600 k single nucleotide polymorphism (SNP) array to detect genomic regions that influenced the outcome of highly pathogenic influenza infection in the two outbreaks. A total of 420458 high quality, segregating SNPs were identified across all samples. Genetic differences between survivors and controls were analyzed using a logistic model, mixed models and a Bayesian variable selection approach. Several genomic regions potentially associated with resistance to HPAI were identified, after performing multidimensional scaling and adjustment for multiple testing. Analysis conducted within each outbreak identified different genomic regions for resistance to the two virus strains. The strongest signals for the Iowa H5N2 survivor samples were detected on chromosomes 1, 7, 9 and 15. Positional candidate genes were mainly coding for plasma membrane proteins with receptor activity and were also involved in immune response. Three regions with the strongest signal for the Mexico H7N3 samples were located on chromosomes 1 and 5. Neuronal cell surface, signal transduction and immune response proteins coding genes were located in the close proximity of these regions.
The Rockefeller Clinical Scholars (KL2) program began in 1976 and transitioned into a 3-year Master’s degree program in 2006 when Rockefeller joined the National Institute of Health Clinical and Translational Science Award program. The program consists of ∼15 trainees supported by the Clinical and Translational Science Award KL2 award and University funds. It is designed to provide an optimal environment for junior translational investigators to develop team science and leadership skills by designing and performing a human subjects protocol under the supervision of a distinguished senior investigator mentor and a team of content expert educators. This is complemented by a tutorial focused on important translational skills.
Since 2006, 40 Clinical Scholars have graduated from the programs and gone on to careers in academia (72%), government service (5%), industry (15%), and private medical practice (3%); 2 (5%) remain in training programs; 39/40 remain in translational research careers with 23 National Institute of Health awards totaling $23 million, foundation and philanthropic support of $20.3 million, and foreign government and foundation support of $6 million. They have made wide ranging scientific discoveries and have endeavored to translate those discoveries into improved human health.
The Rockefeller Clinical Scholars (KL2) program provides one model for translational science training.
This experiment aimed to assess the effect of different indoor winter growth rates (WGR) followed by different concentrate supplementation levels at pasture on meat quality of 90 bulls. During the first winter, bulls were offered grass silage ad libitum and either 3 kg (WGR3) or 6 kg (WGR6) of concentrates. After turn-out to pasture, bulls were offered: grass without supplementation (PO), grass plus 0.2 predicted dry matter intake (DMI) as concentrates (PL) or grass plus 0.4 predicted DMI as concentrates (PH). After finishing, colour, chemical composition (unaged), instrumental texture and sensory characteristics (14 days of ageing) of longissimus thoracis were measured. WGR6 bulls had heavier carcasses than WGR3 bulls. There was an interaction between WGR and supplementation for instrumental texture and redness (a). Within WGR3, PO beef was the most tender, whereas within WRG6, PL was the most tender. However, these differences were not detected by the sensory panel. Within WGR3, redness was the lowest for PL, whereas within WRG6, PO was the least red. No differences were found for chemical composition. The multivariate analysis highlighted WGR as the main variable affecting meat quality characteristics. In conclusion, variations in growth path exerted minor effects on appearance and instrumental texture which did not affect the perception of bull beef by a trained sensory panel.
The effects of shape and thickness of a tin surface layer and of the energy of a 170 ps neodymium:yttrium-aluminum-garnet laser pulse on the conversion efficiency (CE) into extreme ultraviolet emission in the 13.5 nm region is investigated. Whereas a CE of up to 1.16% into the 2% reflection band of multilayer Mo/Si optics was measured for a bulk Sn target at a laser energy of 25 mJ, significant CE enhancement up to 1.49% is demonstrated for a 200-nm-thick Sn layer on a microstructured porous alumina substrate.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.
An adverse early life environment can increase the risk of metabolic and other disorders later in life. Genetic variation can modify an individual’s susceptibility to these environmental challenges. These gene by environment interactions are important, but difficult, to dissect. The nucleus is the primary organelle where environmental responses impact directly on the genetic variants within the genome, resulting in changes to the biology of the genome and ultimately the phenotype. Understanding genome biology requires the integration of the linear DNA sequence, epigenetic modifications and nuclear proteins that are present within the nucleus. The interactions between these layers of information may be captured in the emergent spatial genome organization. As such genome organization represents a key research area for decoding the role of genetic variation in the Developmental Origins of Health and Disease.
Antenatal healthy lifestyle interventions are frequently implemented in overweight and obese pregnancy, yet there is inconsistent reporting of the behaviour-change methods and behavioural outcomes. This limits our understanding of how and why such interventions were successful or not.
The current paper discusses the application of behaviour-change theories and techniques within complex lifestyle interventions in overweight and obese pregnancy. The authors propose a decision tree to help guide researchers through intervention design, implementation and evaluation. The implications for adopting behaviour-change theories and techniques, and using appropriate guidance when constructing and evaluating interventions in research and clinical practice are also discussed.
To enhance the evidence base for successful behaviour-change interventions during pregnancy, adoption of behaviour-change theories and techniques, and use of published guidelines when designing lifestyle interventions are necessary. The proposed decision tree may be a useful guide for researchers working to develop effective behaviour-change interventions in clinical settings. This guide directs researchers towards key literature sources that will be important in each stage of study development.