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Phenylalanine (PHE) and to a lesser extent TYR are two commonly used amino acid tracers for measuring protein metabolism in a variety of species and tissues. The model examined in this paper was developed to resolve trans-organ and stable isotope dilution data collected from experiments with lactating dairy cows using these tracers. Two methods of solving the model, i.e. as two four-pool submodels, one representing PHE and the other TYR, or as an integrated eight-pool model, are investigated and the alternative solutions are contrasted. Solving the model as the two four-pool submodels rather than the integrated 8-pool model is preferred as the equations are slightly simpler and their application less susceptible to any compounding of measurement errors. The data used to illustrate the model were taken from experiments conducted to investigate the effects of high and low protein diets on the partitioning of PHE and TYR between milk protein synthesis and other metabolic fates by the mammary gland.
Differential susceptibility theory stipulates that individuals vary in their susceptibility to environmental effects, often implying that the same individuals differ in the same way in their susceptibility to different environmental exposures. The latter point is addressed herein by evaluating the extent to which early-life harshness and unpredictability affect mother's psychological well-being and parenting, as well as their adolescent's life-history strategy, as reflected in number of sexual partners by age 15 years, drawing on data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development. Results indicated that mothers whose well-being and parenting proved more susceptible to harshness also proved somewhat more susceptible to environmental unpredictability, with the same being true of adolescent sexual behavior. Nevertheless, findings caution against overgeneralizing sample-level findings to all individuals.
As the pathophysiology of Covid-19 emerges, this paper describes dysphagia as a sequela of the disease, including its diagnosis and management, hypothesised causes, symptomatology in relation to viral progression, and concurrent variables such as intubation, tracheostomy and delirium, at a tertiary UK hospital.
During the first wave of the Covid-19 pandemic, 208 out of 736 patients (28.9 per cent) admitted to our institution with SARS-CoV-2 were referred for swallow assessment. Of the 208 patients, 102 were admitted to the intensive treatment unit for mechanical ventilation support, of which 82 were tracheostomised. The majority of patients regained near normal swallow function prior to discharge, regardless of intubation duration or tracheostomy status.
Dysphagia is prevalent in patients admitted either to the intensive treatment unit or the ward with Covid-19 related respiratory issues. This paper describes the crucial role of intensive swallow rehabilitation to manage dysphagia associated with this disease, including therapeutic respiratory weaning for those with a tracheostomy.
Prenatal alcohol exposure (PAE) produces physiological and behavioural abnormalities that are consistent with altered serotonin (5-HT) function in male rats. Whether alterations in the 5-HT system persist into adulthood and are present in females remains unknown.
1) the effects of PAE on the number of 5-HT neurons in the brainstem in female adult rats;
2) the potential influence of ovarian sex steroids, estradiol (E2) and progesterone (P4) on this population of 5-HT neurons.
Female offspring from prenatal ethanol (PAE), pair-fed (PF) and ad lib-fed control (C) dams were studied in adulthood. Females were assigned to the following groups: 1) ovariectomized (OVX); 2) ovariectomized with estradiol replacement (OVX+E2; mean plasma concentration: 64 pg/ml); 3) ovariectomized and replaced with estradiol (as above) and progesterone (OVX+E2+P4; mean plasma concentration for P4:12 ng/ml); 4) Sham surgery (SHAM). Immunocytochemistry for 5-HT was performed.
PAE decreased the number of 5-HT-ir neurons in the dorsal raphe (DR) in OVX females. There was no effect of PAE the number of DR 5HT-ir neurons in OVX+E2 group, suggesting a possible neuroprotective role of estradiol in PAE animals. Treatment with both progesterone and estradiol compared to estradiol alone caused a further decrease in number of DR 5-HT-ir neurons in PAE but not C or PF animals.
These results provide evidence of the enduring effects of PAE on the serotonergic system, and suggest a role for the ovarian sex steroids in mediating these effects.
IMPART (CIHR) to JHS, NIH/NIAAA AA007789 and HELP to JW.
Mechanistic models (MMs) have served as causal pathway analysis and ‘decision-support’ tools within animal production systems for decades. Such models quantitatively define how a biological system works based on causal relationships and use that cumulative biological knowledge to generate predictions and recommendations (in practice) and generate/evaluate hypotheses (in research). Their limitations revolve around obtaining sufficiently accurate inputs, user training and accuracy/precision of predictions on-farm. The new wave in digitalization technologies may negate some of these challenges. New data-driven (DD) modelling methods such as machine learning (ML) and deep learning (DL) examine patterns in data to produce accurate predictions (forecasting, classification of animals, etc.). The deluge of sensor data and new self-learning modelling techniques may address some of the limitations of traditional MM approaches – access to input data (e.g. sensors) and on-farm calibration. However, most of these new methods lack transparency in the reasoning behind predictions, in contrast to MM that have historically been used to translate knowledge into wisdom. The objective of this paper is to propose means to hybridize these two seemingly divergent methodologies to advance the models we use in animal production systems and support movement towards truly knowledge-based precision agriculture. In order to identify potential niches for models in animal production of the future, a cross-species (dairy, swine and poultry) examination of the current state of the art in MM and new DD methodologies (ML, DL analytics) is undertaken. We hypothesize that there are several ways via which synergy may be achieved to advance both our predictive capabilities and system understanding, being: (1) building and utilizing data streams (e.g. intake, rumination behaviour, rumen sensors, activity sensors, environmental sensors, cameras and near IR) to apply MM in real-time and/or with new resolution and capabilities; (2) hybridization of MM and DD approaches where, for example, a ML framework is augmented by MM-generated parameters or predicted outcomes and (3) hybridization of the MM and DD approaches, where biological bounds are placed on parameters within a MM framework, and the DD system parameterizes the MM for individual animals, farms or other such clusters of data. As animal systems modellers, we should expand our toolbox to explore new DD approaches and big data to find opportunities to increase understanding of biological systems, find new patterns in data and move the field towards intelligent, knowledge-based precision agriculture systems.
England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case–control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2–16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015–2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3–54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3–63.6) and 28.8% (95% CI −31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015–2016 and continues to support the rollout of the LAIV childhood programme.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
The aim of this study was to assess the impact of a urinary tract infection (UTI) management bundle to reduce the treatment of asymptomatic bacteriuria (AB) and to improve the management of symptomatic UTIs.
Before-and-after intervention study.
Consecutive sample of inpatients with positive single or mixed-predominant urine cultures collected and reported while admitted to the hospital.
The UTI management bundle consisted of nursing and prescriber education, modification of the reporting of positive urine cultures, and pharmacists’ prospective audit and feedback. A retrospective chart review of consecutive inpatients with positive urinary cultures was performed before and after implementation of the management bundle.
Prior to the implementation of the management bundle, 276 patients were eligible criteria for chart review. Of these 276 patients, 165 (59·8%) were found to have AB; of these 165 patients with AB, 111 (67·3%) were treated with antimicrobials. Moreover, 268 patients met eligibility criteria for postintervention review. Of these 268, 133 patients (49·6%) were found to have AB; of these 133 with AB, 22 (16·5%) were treated with antimicrobials. Thus, a 75·5% reduction of AB treatment was achieved. Educational components of the bundle resulted in a substantial decrease in nonphysician-directed urine sample submission. Adherence to a UTI management algorithm improved substantially in the intervention period, with a notable decrease in fluoroquinolone prescription for empiric UTI treatment.
A UTI management bundle resulted in a dramatic improvement in the management of urinary tract infection, particularly a reduction in the treatment of AB and improved management of symptomatic UTI.
Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.
To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.
Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.
ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.
The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.
We present the concept of a novel facility dedicated to massively-multiplexed spectroscopy. The telescope has a very wide field Cassegrain focus optimised for fibre feeding. With a Field of View (FoV) of 2.5 degrees diameter and a 11.4m pupil, it will be the largest etendue telescope. The large focal plane can easily host up to 16.000 fibres. In addition, a gravity invariant focus for the central 10 arc-minutes is available to host a giant integral field unit (IFU). The 3 lenses corrector includes an ADC, and has good performance in the 360-1300 nm wavelength range. The top level science requirements were developed by a dedicated ESO working group, and one of the primary cases is high resolution spectroscopy of GAIA stars and, in general, how our Galaxy formed and evolves. The facility will therefore be equipped with both, high and low resolution spectrographs. We stress the importance of developing the telescope and instrument designs simultaneously. The most relevant R&D aspect is also briefly discussed.
Unusual speleothems, associated with hyperalkaline (pH > 12) groundwaters have formed within a shallow, abandoned railway tunnel at Peak Dale, Derbyshire, UK. The hyperalkaline groundwaters are produced by the leaching of a thin layer (<2 m) of old lime-kiln waste on the soil-bedrock surface above the tunnel by rainwater. This results in a different reaction and chemical process to that more commonly associated with the formation of calcium carbonate speleothems from Ca-HCO3-type groundwaters and degassing of CO2. Stalagmites within the Peak Daletunnel have grown rapidly (averaging 33 mm y–1), following the closure of the tunnel 70 years ago. They have an unusual morphology comprising a central sub-horizontally-laminated column of micro- to nano-crystalline calcium carbonate encompassed by an outer sub-vertical assymetricripple-laminated layer. The stalagmites are composed largely of secondary calcite forming pseudomorphs (<1 mm) that we believe to be predominantly after the 'cold climate' calcium carbonate polymorph, ikaite (calcium carbonate hexahydrate: CaCO3·6H2O), withminor volumes of small (<5 μm) pseudomorphs after vaterite. The tunnel has a near constant temperature of 8–9°C, which is slightly above the previously published crystallization temperatures for ikaite (<6°C). Analysis of a stalagmite actively growing at the time ofsampling, and preserved immediately within a dry nitrogen cryogenic vessel, indicates that following crystallization of ikaite, decomposition to calcite occurs rapidly, if not instantaneously. We believe this is the first occurrence of this calcium carbonate polymorph observed within speleothems.
Sufficient I intake is important for the synthesis of thyroid hormones, which play an important role in normal growth and development. Our aim was to estimate habitual I intake for the Dutch population and the risk of inadequate or excessive intakes. Further, we aimed to provide an insight into the dietary sources of I and the association with socio-demographic factors. Data from the Dutch National Food Consumption Survey 2007–2010 (n 3819; 7–69 years), and from the Dutch food and supplement composition tables were used to estimate habitual I intake with a calculation model. Contribution of food groups to I intake were computed and multiple linear regression was used to examine associations of intakes with socio-demographic factors. A total of ≤2 % of the population had an intake below the estimated average requirement or above the upper level. The main sources of I were bread containing iodised salt (39 %), dairy products (14 %) and non-alcoholic drinks (6 %). I intake (natural sources only, excluding iodised salt and supplements) was positively associated with (parental) education, which could at least partly be attributed to a higher consumption of dairy products. Among children, the consumption of bread, often containing iodised bakery salt, was positively associated with parental education. The I intake of the Dutch population (7–69 years) seems adequate, although it has decreased since the period before 2008. With the current effort to reduce salt intake and changing dietary patterns (i.e. less bread, more organic foods) it is important to keep a close track on the I status, important sources and potential risk groups.
To investigate the feasibility of a national audit of epistaxis management led and delivered by a multi-region trainee collaborative using a web-based interface to capture patient data.
Six trainee collaboratives across England nominated one site each and worked together to carry out this pilot. An encrypted data capture tool was adapted and installed within the infrastructure of a university secure server. Site-lead feedback was assessed through questionnaires.
Sixty-three patients with epistaxis were admitted over a two-week period. Site leads reported an average of 5 minutes to complete questionnaires and described the tool as easy to use. Data quality was high, with little missing data. Site-lead feedback showed high satisfaction ratings for the project (mean, 4.83 out of 5).
This pilot showed that trainee collaboratives can work together to deliver an audit using an encrypted data capture tool cost-effectively, whilst maintaining the highest levels of data quality.
Recent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.
To systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).
Analysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD–ASD (n = 16) and healthy controls (n = 78).
Weighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures.
Our results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors.
The positive effects of dietary fibre on health are now widely recognised; however, our understanding of the mechanisms involved in producing such benefits remains unclear. There are even uncertainties about how dietary fibre in plant foods should be defined and analysed. This review attempts to clarify the confusion regarding the mechanisms of action of dietary fibre and deals with current knowledge on the wide variety of dietary fibre materials, comprising mainly of NSP that are not digested by enzymes of the gastrointestinal (GI) tract. These non-digestible materials range from intact cell walls of plant tissues to individual polysaccharide solutions often used in mechanistic studies. We discuss how the structure and properties of fibre are affected during food processing and how this can impact on nutrient digestibility. Dietary fibre can have multiple effects on GI function, including GI transit time and increased digesta viscosity, thereby affecting flow and mixing behaviour. Moreover, cell wall encapsulation influences macronutrient digestibility through limited access to digestive enzymes and/or substrate and product release. Moreover, encapsulation of starch can limit the extent of gelatinisation during hydrothermal processing of plant foods. Emphasis is placed on the effects of diverse forms of fibre on rates and extents of starch and lipid digestion, and how it is important that a better understanding of such interactions with respect to the physiology and biochemistry of digestion is needed. In conclusion, we point to areas of further investigation that are expected to contribute to realisation of the full potential of dietary fibre on health and well-being of humans.
We present the first experimentally determined oscillator strengths for the Pb ii transitions at 1203.6 Å and 1433.9 Å, obtained from lifetime measurements made using beam-foil techniques. We also present new detections of these lines in the interstellar medium from an analysis of archival spectra acquired by the Space Telescope Imaging Spectrograph onboard the Hubble Space Telescope. Our observations of the Pb ii λ1203 line represent the first detection of this transition in interstellar gas. Our experimental f-values for the Pb ii λ1203 and λ1433 transitions are consistent with recent theoretical results, including our own relativistic calculations, but are significantly smaller than previous values based on older calculations. Our new f-value for Pb ii λ1433 (0.321 ± 0.034) yields an increase in the interstellar abundance of Pb of 0.43 dex over estimates based on the f-value listed by Morton. With our revised f-values, and with our new detections of Pb ii λ1203 and λ1433, we find that the depletion of Pb onto interstellar grains is not nearly as severe as previously thought, and is very similar to the depletions seen for elements such as Zn and Sn, which have similar condensation temperatures.
Personalised nutrition (PN) has the potential to reduce disease risk and optimise health and performance. Although previous research has shown good acceptance of the concept of PN in the UK, preferences regarding the delivery of a PN service (e.g. online v. face-to-face) are not fully understood. It is anticipated that the presence of a free at point of delivery healthcare system, the National Health Service (NHS), in the UK may have an impact on end-user preferences for deliverances. To determine this, supplementary analysis of qualitative data obtained from focus group discussions on PN service delivery, collected as part of the Food4Me project in the UK and Ireland, was undertaken. Irish data provided comparative analysis of a healthcare system that is not provided free of charge at the point of delivery to the entire population. Analyses were conducted using the ‘framework approach’ described by Rabiee (Focus-group interview and data analysis. Proc Nutr Soc 63, 655-660). There was a preference for services to be led by the government and delivered face-to-face, which was perceived to increase trust and transparency, and add value. Both countries associated paying for nutritional advice with increased commitment and motivation to follow guidelines. Contrary to Ireland, however, and despite the perceived benefit of paying, UK discussants still expected PN services to be delivered free of charge by the NHS. Consideration of this unique challenge of free healthcare that is embedded in the NHS culture will be crucial when introducing PN to the UK.
A number of studies have demonstrated that consuming almonds increases satiety but does not result in weight gain, despite their high energy and lipid content. To understand the mechanism of almond digestion, in the present study, we investigated the bioaccessibility of lipids from masticated almonds during in vitro simulated human digestion, and determined the associated changes in cell-wall composition and cellular microstructure. The influence of processing on lipid release was assessed by using natural raw almonds (NA) and roasted almonds (RA). Masticated samples from four healthy adults (two females, two males) were exposed to a dynamic gastric model of digestion followed by simulated duodenal digestion. Between 7·8 and 11·1 % of the total lipid was released as a result of mastication, with no significant differences between the NA and RA samples. Significant digestion occurred during the in vitro gastric phase (16·4 and 15·9 %) and the in vitro duodenal phase (32·2 and 32·7 %) for the NA and RA samples, respectively. Roasting produced a smaller average particle size distribution post-mastication; however, this was not significant in terms of lipid release. Light microscopy showed major changes that occurred in the distribution of lipid in all cells after the roasting process. Further changes were observed in the surface cells of almond fragments and in fractured cells after exposure to the duodenal environment. Almond cell walls prevented lipid release from intact cells, providing a mechanism for incomplete nutrient absorption in the gut. The composition of almond cell walls was not affected by processing or simulated digestion.
Although beta-amyloid, anxiety and depression have been linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data from an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety symptoms significantly moderated the relationship between beta-amyloid level and decline in verbal (Cohen's d = 0.65) and episodic (Cohen's d = 0.38) memory. Anxiety symptoms were additionally linked to greater decline in executive function, irrespective of beta-amyloid and other risk factors. These findings suggest that interventions to mitigate anxiety symptoms may help delay memory decline in otherwise healthy older adults with elevated beta-amyloid.
In view of environmental concerns with regard to phosphorus (P) pollution and the expected global P scarcity, there is increasing interest in improving P utilization in dairy cattle. In high-producing dairy cows, P requirements for milk production comprise a significant fraction of total dietary P requirements. Although variation in P content of milk can affect the efficiency of P utilization for milk production (i.e. the fraction of ingested P that is incorporated in milk), this variation is poorly understood. It was hypothesized that the P content of milk is related to both milk protein and milk lactose content, but not necessarily to milk fat content. Three existing experiments comprising individual animal data on milk yield and fat, protein, lactose and P content of milk (in total 278 observations from 121 cows) were analysed to evaluate this hypothesis using a mixed model analysis. The models including the effects of both protein and lactose content of milk yielded better prediction of milk P content in terms of root-mean-square prediction error (RMSPE) and concordance correlation coefficient (CCC) statistics than models with only protein included as prediction variable; however, estimates of effect sizes varied between studies. The inclusion of milk fat content in equations already including protein and lactose did not further improve prediction of milk P content. Equations developed to describe the relationship between milk protein and lactose contents (g/kg) and milk P content (g/kg) were: (Expt 1) P in milk=−0·44(±0·179)+0·0253(±0·00300)×milk protein+0·0133(±0·00382)×milk lactose (RMSPE: 5·2%; CCC: 0·71); (Expt 2) P in milk=−0·26 (±0·347)+0·0174(±0·00328)×milk protein+0·0143 (±0·00611)×milk lactose (RMSPE: 6·3%; CCC: 0·40); and (Expt 3) P in milk=−0·36(±0·255)+0·0131(±0·00230)×milk protein+0·0193(±0·00490)×milk lactose (RMSPE: 6·5%; CCC: 0·55). Analysis of the three experiments combined, treating study as a random effect, resulted in the following equation to describe the same relationship as in the individual study equations: P in milk=−0·64(±0·168)+0·0223(±0·00236)×milk protein+0·0191(±0·00316)×milk lactose (RMSPE: 6·2%; CCC: 0·61). Although significant relationships between milk protein, milk lactose and milk P were found, a considerable portion of the observed variation remained unexplained, implying that factors other than milk composition may affect the P content of milk. The equations developed may be used to replace current fixed milk P contents assumed in P requirement systems for cattle.