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Metabolites produced by microbial fermentation in the human intestine, especially short-chain fatty acids (SCFAs), are known to play important roles in colonic and systemic health. Our aim here was to advance our understanding of how and why their concentrations and proportions vary between individuals. We have analysed faecal concentrations of microbial fermentation acids from 10 human volunteer studies, involving 163 subjects, conducted at the Rowett Institute, Aberdeen, UK over a 7-year period. In baseline samples, the % butyrate was significantly higher, whilst % iso-butyrate and % iso-valerate were significantly lower, with increasing total SCFA concentration. The decreasing proportions of iso-butyrate and iso-valerate, derived from amino acid fermentation, suggest that fibre intake was mainly responsible for increased SCFA concentrations. We propose that the increase in % butyrate among faecal SCFA is largely driven by a decrease in colonic pH resulting from higher SCFA concentrations. Consistent with this, both total SCFA and % butyrate increased significantly with decreasing pH across five studies for which faecal pH measurements were available. Colonic pH influences butyrate production through altering the stoichiometry of butyrate formation by butyrate-producing species, resulting in increased acetate uptake and butyrate formation, and facilitating increased relative abundance of butyrate-producing species (notably Roseburia and Eubacterium rectale).
Nutritional therapy is a cornerstone of burns management. The optimal macronutrient intake for wound healing after burn injury has not been identified, although high-energy, high-protein diets are favoured. The present study aimed to identify the optimal macronutrient intake for burn wound healing. The geometric framework (GF) was used to analyse wound healing after a 10 % total body surface area contact burn in mice ad libitum fed one of the eleven high-energy diets, varying in macronutrient composition with protein (P5−60 %), carbohydrate (C20−75 %) and fat (F20−75 %). In the GF study, the optimal ratio for wound healing was identified as a moderate-protein, high-carbohydrate diet with a protein:carbohydrate:fat (P:C:F) ratio of 1:4:2. High carbohydrate intake was associated with lower mortality, improved body weight and a beneficial pattern of body fat reserves. Protein intake was essential to prevent weight loss and mortality, but a protein intake target of about 7 kJ/d (about 15 % of energy intake) was identified, above which no further benefit was gained. High protein intake was associated with delayed wound healing and increased liver and spleen weight. As the GF study demonstrated that an initial very high protein intake prevented mortality, a very high-protein, moderate-carbohydrate diet (P40:C42:F18) was specifically designed. The dynamic diet study was also designed to combine and validate the benefits of an initial very high protein intake for mortality, and subsequent moderate protein, high carbohydrate intake for optimal wound healing. The dynamic feeding experiment showed switching from an initial very high-protein diet to the optimal moderate-protein, high-carbohydrate diet accelerated wound healing whilst preventing mortality and liver enlargement.
We present ongoing work on the spectral energy distributions (SEDs) of active galactic nuclei (AGNs), derived from X-ray, ultraviolet, optical, infrared and radio photometry and spectroscopy. Our work is motivated by new wide-field imaging surveys that will identify vast numbers of AGNs, and by the need to benchmark AGN SED fitting codes. We have constructed 41 SEDs of individual AGNs and 80 additional SEDs that mimic Seyfert spectra. All of our SEDs span 0.09 to 30μm, while some extend into the X-ray and/or radio. We have tested the utility of the SEDs by using them to generate AGN photometric redshifts, and they outperform SEDs from the prior literature, including reduced redshift errors and flux density residuals.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Soldier operational performance is determined by their fitness, nutritional status, quality of rest/recovery, and remaining injury/illness free. Understanding large fluctuations in nutritional status during operations is critical to safeguarding health and well-being. There are limited data world-wide describing the effect of extreme climate change on nutrient profiles. This study investigated the effect of hot-dry deployments on vitamin D status (assessed from 25-hydroxyvitamin D (25(OH)D) concentration) of young, male, military volunteers. Two data sets are presented (pilot study, n 37; main study, n 98), examining serum 25(OH)D concentrations before and during 6-month summer operational deployments to Afghanistan (March to October/November). Body mass, percentage of body fat, dietary intake and serum 25(OH)D concentrations were measured. In addition, parathyroid hormone (PTH), adjusted Ca and albumin concentrations were measured in the main study to better understand 25(OH)D fluctuations. Body mass and fat mass (FM) losses were greater for early (pre- to mid-) deployment compared with late (mid- to post-) deployment (P<0·05). Dietary intake was well-maintained despite high rates of energy expenditure. A pronounced increase in 25(OH)D was observed between pre- (March) and mid-deployment (June) (pilot study: 51 (sd 20) v. 212 (sd 85) nmol/l, P<0·05; main study: 55 (sd 22) v. 167 (sd 71) nmol/l, P<0·05) and remained elevated post-deployment (October/November). In contrast, PTH was highest pre-deployment, decreasing thereafter (main study: 4·45 (sd 2·20) v. 3·79 (sd 1·50) pmol/l, P<0·05). The typical seasonal cycling of vitamin D appeared exaggerated in this active male population undertaking an arduous summer deployment. Further research is warranted, where such large seasonal vitamin D fluctuations may be detrimental to bone health in the longer-term.
The impact of a deep-water plunging breaker on a finite height two-dimensional structure with a vertical front face is studied experimentally. The structure is located at a fixed horizontal position relative to a wave maker and the structure’s bottom surface is located at a range of vertical positions close to the undisturbed water surface. Measurements of the water surface profile history and the pressure distribution on the front surface of the structure are performed. As the vertical position, $z_{b}$ (the $z$ axis is positive up and $z=0$ is the mean water level), of the structure’s bottom surface is varied from one experimental run to another, the water surface evolution during impact can be categorized into three classes of behaviour. In class I, with $z_{b}$ in a range of values near $-0.1\unicode[STIX]{x1D706}_{0}$, where $\unicode[STIX]{x1D706}_{0}$ is the nominal wavelength of the breaker, the behaviour of the water surface is similar to the flip-through phenomena first described in studies with shallow water and a structure mounted on the sea bed. In the present work, it is found that the water surface between the front face of the structure and the wave crest is well fitted by arcs of circles with a decreasing radius and downward moving centre as the impact proceeds. A spatially and temporally localized high-pressure region was found on the impact surface of the structure and existing theory is used to explore the physics of this phenomenon. In class II, with $z_{b}$ in a range of values near the mean water level, the bottom of the structure exits and re-enters the water phase at least once during the impact process. These air–water transitions generate large-amplitude ripple packets that propagate to the wave crest and modify its behaviour significantly. At $z_{b}=0$, all sensors submerged during the impact record a nearly in-phase high-frequency pressure oscillation indicating possible air entrainment. In class III, with $z_{b}$ in a range of values near $0.03\unicode[STIX]{x1D706}_{0}$, the bottom of the structure remains in air before the main crest hits the bottom corner of the structure. The subsequent free surface behaviour is strongly influenced by the instantaneous momentum of the local flow just before impact and the highest wall pressures of all experimental conditions are found.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Driving in persons with dementia poses risks that must be counterbalanced with the importance of the care for autonomy and mobility. Physicians often find substantial challenges in the assessment and reporting of driving safety for persons with dementia. This paper describes a driving in dementia decision tool (DD-DT) developed to aid physicians in deciding when to report older drivers with either mild dementia or mild cognitive impairment to local transportation administrators.
Methods:
A multi-faceted, computerized decision support tool was developed, using a systematic literature and guideline review, expert opinion from an earlier Delphi study, as well as qualitative interviews and focus groups with physicians, caregivers of former drivers with dementia, and transportation administrators. The tool integrates inputs from the physician-user about the patient's clinical and driving history as well as cognitive findings, and it produces a recommendation for reporting to transportation administrators. This recommendation is translated into a customized reporting form for the transportation authority, if applicable, and additional resources are provided for the patient and caregiver.
Conclusions:
An innovative approach was needed to develop the DD-DT. The literature and guideline review confirmed the algorithm derived from the earlier Delphi study, and barriers identified in the qualitative research were incorporated into the design of the tool.
The Protoplanetary Discussions conference—held in Edinburgh, UK, from 2016 March 7th–11th—included several open sessions led by participants. This paper reports on the discussions collectively concerned with the multi-physics modelling of protoplanetary discs, including the self-consistent calculation of gas and dust dynamics, radiative transfer, and chemistry. After a short introduction to each of these disciplines in isolation, we identify a series of burning questions and grand challenges associated with their continuing development and integration. We then discuss potential pathways towards solving these challenges, grouped by strategical, technical, and collaborative developments. This paper is not intended to be a review, but rather to motivate and direct future research and collaboration across typically distinct fields based on community-driven input, to encourage further progress in our understanding of circumstellar and protoplanetary discs.
With an increasing number of older drivers who are prescribed antidepressants, the potential consequences of antidepressant use on driving skills in an aging population are becoming a pressing issue. We conducted a systematic review using MEDLINE, targeting articles specifically pertaining to antidepressants and driving in a population or subgroup of older adults (≥ 55 years of age). The search yielded 267 references, nine of which pertained to the effects of antidepressants on driving in older adults. The single experimental study found imipramine to have detrimental effects on highway driving, whereas nefazodone did not. Seven of eight population-based studies reported a significant increased risk of involvement in a collision associated with antidepressant use. Although the studies indicated a negative effect of antidepressants on driving, the epidemiological designs cannot exclude the possibility that the underlying illness, generally major depression, is the culprit.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Ree, Carretta, and Teachout (2015) raise the need for further investigation into dominant general factors (DGFs) and their prevalence in measures used for the purposes of employee selection, development, and performance measurement. They imply that a method of choice for estimating the contribution of DGFs is principal components analysis (PCA), and they interpret the variance accounted for by the first component of the PCA solution as indicative of the contribution of a general factor. In this response, we illustrate the hazard of equating the first component of a PCA with a general factor, and we illustrate how this becomes particularly problematic when applying PCA to multifaceted variables. Rather than simply critique this use of PCA, we offer an alternative approach that helps to address and illustrate the problem that we raise.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
There is evidence for health benefits from ‘Palaeolithic’ diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.
The effects of dietary carbohydrate and fat on feline health are not well understood. The effects of feeding diets moderately high in fat (HF; n 10; 30 % fat, 26 % carbohydrate as fed) or carbohydrate (HC; n 10; 11 % fat, 47 % carbohydrate), for 84 d, were investigated in healthy, adult cats (3·5 (sd 0·5) years). Data on indirect calorimetry, blood biomarkers, activity, play and cognition were collected at baseline, and at intervals throughout the study. Body composition was measured by dual-energy X-ray absorptiometry at baseline and on day 85. There were no significant main effects of diet on body weight and composition. When data were analysed over study day within diet, cats fed HF diets experienced a significant increase in body fat (P = 0·001) and body weight (P = 0·043) in contrast to cats consuming the HC diet that experienced no change in body fat or body weight (P = 0·762) throughout the study. Overall, energy expenditure was similar between diets (P = 0·356 (fasted), P = 0·086 (postprandial)) and respiratory quotient declined with exposure to the HF diet and increased with exposure to the HC diet (P < 0·001; fasted and postprandial). There was no difference in insulin sensitivity as an overall effect of diet (P = 0·266). Activity declined from baseline with exposure to both diets (HC: P = 0·002; HF: P = 0·01) but was not different between diets (P = 0·247). There was no effect of diet on play (P = 0·387) and cats consuming either the HF or HC diet did not successfully learn the cognitive test. Overall, cats adapt to dietary macronutrient content, and the implications of feeding HC and HF diets on risk for adiposity as driven by metabolic and behavioural mechanisms are discussed.
The gut microbiota and its metabolic products interact with the host in many different ways, influencing gut homoeostasis and health outcomes. The species composition of the gut microbiota has been shown to respond to dietary change, determined by competition for substrates and by tolerance of gut conditions. Meanwhile, the metabolic outputs of the microbiota, such as SCFA, are influenced both by the supply of dietary components and via diet-mediated changes in microbiota composition. There has been significant progress in identifying the phylogenetic distribution of pathways responsible for formation of particular metabolites among human colonic bacteria, based on combining cultural microbiology and sequence-based approaches. Formation of butyrate and propionate from hexose sugars, for example, can be ascribed to different bacterial groups, although propionate can be formed via alternative pathways from deoxy-sugars and from lactate by a few species. Lactate, which is produced by many gut bacteria in pure culture, can also be utilised by certain Firmicutes to form butyrate, and its consumption may be important for maintaining a stable community. Predicting the impact of diet upon such a complex and interactive system as the human gut microbiota not only requires more information on the component groups involved but, increasingly, the integration of such information through modelling approaches.