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Little is known about who would benefit from internet-based personalised nutrition (PN) interventions. This study aimed to evaluate the characteristics of participants who achieved greatest improvements (i.e. benefit) in diet, adiposity and biomarkers following an internet-based PN intervention. Adults (n=1607) from seven European countries were recruited into a 6-month, randomized controlled trial (Food4Me) and randomized to receive conventional dietary advice (control) or PN advice. Information on dietary intake, adiposity, physical activity, blood biomarkers and participant characteristics was collected at baseline and month 6. Benefit from the intervention was defined as ≥5% change in the primary outcome (Healthy Eating Index) and secondary outcomes (waist circumference and BMI, physical activity, sedentary time and plasma concentrations of cholesterol, carotenoids and omega-3 index) at month 6. For our primary outcome, benefit from the intervention was greater in older participants and women. Benefit was greater for individuals reporting greater self-efficacy for “sticking to healthful foods” and who “felt weird if [they] didn’t eat healthily”. Participants benefited more if they reported wanting to improve their health and wellbeing. The characteristics of individuals benefiting did not differ by other demographic, health-related, anthropometric or genotypic characteristics. Findings were similar for secondary outcomes. Older individuals, women and individuals with less healthy diets at baseline benefitted more from PN advice. The odds of benefiting did not differ by weight status, genetic risk or socio-economic position. These findings have implications for the design of more effective future PN intervention studies and for tailored nutritional advice in public health and clinical settings.
The addition of Cr2O3 to modern UO2 fuel modifies the microstructure so that, through the generation of larger grains during fission, a higher proportion of fission gases can be accommodated. This reduces the pellet-cladding mechanical interaction of the fuel rods, allowing the fuels to be “burned” for longer than traditional UO2 fuel, thus maximising the energy obtained. We here describe the preparation of UO2 and Cr-doped UO2 using Hot Isostatic Pressing (HIP), as a potential method for fuel fabrication, and for development of analogue materials for spent nuclear fuel research. Characterization of the synthesised materials confirmed that high density UO2 was successfully formed, and that Cr was present as particles at grain boundaries and also within the UO2 matrix, possibly in a reduced form due to the processing conditions. In contrast to studies of Cr-doped UO2 synthesised by other methods, no significant changes to the grain size were observed in the presence of Cr.
To determine the effectiveness and ease of use of an electronic reminder device in reducing urinary catheterization duration.
A randomized controlled trial with a cross-sectional anonymous online survey and focus group.
Ten wards in an Australian hospital.
All hospitalized patients with a urinary catheter.
An electronic reminder system, the CATH TAG, applied to urinary catheter bags to prompt removal of urinary catheters.
Catheterization duration and perceptions of nurses about the ease of use.
A Cox proportional hazards model was used to assess the rate of removal of catheters. A phenomenological approach underpinned data collection and analysis methods associated with the focus group.
In total, 1,167 patients with a urinary catheter were included. The mean durations in control and intervention phases were 5.51 days (95% confidence interval [CI], 4.9–6.2) and 5.08 days (95% CI, 4.6–5.6), respectively. For patients who had a CATH TAG applied, the hazard ratio (HR) was 1.02 (95% CI, 0.91–1.14; P = .75). A subgroup analysis excluded patients in an intensive care unit (ICU), and the use of the CATH TAG was associated with a 23% decrease in the mean, from 5.00 days (95% CI, 4.44–5.56) to 3.84 days (95% CI, 3.47–4.21). Overall, 82 nurses completed a survey and 5 nurses participated in a focus group. Responses regarding the device were largely positive, and benefits for patient care were identified.
The CATH TAG did not reduce the duration of catheterization, but potential benefits in patients outside the ICU were identified. Electronic reminders may be useful to aid prompt removal of urinary catheters in the non-ICU hospital setting.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
Release methods can influence the outcome of reintroductions. We tested the effect of delayed, immediate and supplementary food/shelter release treatments on the reintroduction of brushtail possums Trichosurus vulpecula to an environment in which introduced predators, particularly foxes, were subject to control. Monitoring of 48 radio-collared possums over 3 months revealed that immediate release possums settled into a stable range significantly faster than other groups, but there were no differences in survival, dispersal distance, reproduction or body condition. Ten days after release possums from all treatment groups had lost body mass, but by day 60 most were heavier than at the time of translocation. After release, possums sometimes used shelter sites easily accessible to predators, but within 3 weeks they regularly selected safer shelter. Risky shelter selection and loss of condition immediately after release suggests that supplementary food and shelter could be beneficial, but supportive measures were rarely used or did not have the desired effect. In an environment with higher predator densities, risky shelter selection could lead to high post-release predation, and mass loss could encourage animals to forage in riskier ways, further increasing vulnerability. In these environments effective uptake of supplementary food and shelter could reduce predation risk, but supplementary measures would need to be presented in a way that maximises uptake. In contrast, if post-release predation risk is low then supportive measures may not be required. Innovative methods for providing post-release support should continue to be developed for reintroductions to areas where supportive measures are needed.
Hannah C Kinney, Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, USA,
Robin L Haynes, Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, USA,
Dawna D Armstrong, Retired Professor Pathology Baylor College of Medicine, Department of Pathology, Houston, USA,
Richard D Goldstein, Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, USA
The terrifying aspect of the sudden infant death syndrome (SIDS) is that it occurs in infants who seem healthy and then die without warning when put down to sleep. SIDS is not typically witnessed and it is surmized that death occurs during sleep, or during one of the many transitions to waking that occur during normal infant sleep-wake cycles (1). Multiple sleep-related mechanisms have been proposed to cause SIDS (1, 2). These mechanisms include suffocation/asphyxiation in the face-down sleep position, central and/or obstructive sleep apnea, impaired-state-dependent responses to hypoxia and/ or hypercarbia, inadequate autoresuscitation, defective autonomic regulation of blood pressure or thermal responses, and abnormal arousal to life-threatening challenges during sleep.
In this chapter, we review the hypothesis and the neuropathologic evidence that SIDS is precipitated by a dentate gyrus-related seizure or a limbic-related instability that involves the central homeostatic network (CHN). We begin with an overview of this hypothesis, and then review our neuropathologic evidence for an epileptiform hippocampal lesion in the brain of a subset of SIDS infants and young children (41-50% respectively) who died suddenly and unexpectedly (3-5). We then consider the putative mechanism whereby dentate lesions cause seizures, the role of the hippocampus as part of the CHN in stress responses (such as the face-down sleep position), and the potential interactions of brainstem serotonergic (5-HT) deficits and the hippocampus in the pathogenesis of sudden death in infants. We conclude with further directions for research into the role of the hippocampus in sudden and unexpected death in early life.
The Limbic Seizure-Related Hypothesis in SIDS
In 1986, Harper suggested that some SIDS deaths may be due to a fatal seizure during sleep that arises in forebrain-limbic-related circuits (6). This hypothesis arose from the recognition of the following inter-related phenomena: limbic regions are particularly susceptible to epileptogenesis; sleep states lower the threshold for seizure; and SIDS is linked to sleep and arousal. Sleep itself is thought to be a precarious state, in part because of the loss of the major “back-up” forebrain systems of waking which influence the final common pathways in the brainstem that mediate central cardiorespiratory function during sleep. Forebrain limbic regions, such as the hippocampus and amygdala, which are part of the CHN, modulate brainstem cardiorespiratory control in a manner influenced by the sleep-waking cycles.
Research on the cities of the Classical Greek world has traditionally focused on mapping the organisation of urban space and studying major civic or religious buildings. More recently, newer techniques such as field survey and geophysical survey have facilitated exploration of the extent and character of larger areas within urban settlements, raising questions about economic processes. At the same time, detailed analysis of residential buildings has also supported a change of emphasis towards understanding some of the functional and social aspects of the built environment as well as purely formal ones. This article argues for the advantages of analysing Greek cities using a multidisciplinary, multi-scalar framework which encompasses all of these various approaches and adds to them other analytical techniques (particularly micro-archaeology). We suggest that this strategy can lead towards a more holistic view of a city, not only as a physical place, but also as a dynamic community, revealing its origins, development and patterns of social and economic activity. Our argument is made with reference to the research design, methodology and results of the first three seasons of fieldwork at the city of Olynthos, carried out by the Olynthos Project.
Traditionally, personalised nutrition was delivered at an individual level. However, the concept of delivering tailored dietary advice at a group level through the identification of metabotypes or groups of metabolically similar individuals has emerged. Although this approach to personalised nutrition looks promising, further work is needed to examine this concept across a wider population group. Therefore, the objectives of this study are to: (1) identify metabotypes in a European population and (2) develop targeted dietary advice solutions for these metabotypes. Using data from the Food4Me study (n 1607), k-means cluster analysis revealed the presence of three metabolically distinct clusters based on twenty-seven metabolic markers including cholesterol, individual fatty acids and carotenoids. Cluster 2 was identified as a metabolically healthy metabotype as these individuals had the highest Omega-3 Index (6·56 (sd 1·29) %), carotenoids (2·15 (sd 0·71) µm) and lowest total saturated fat levels. On the basis of its fatty acid profile, cluster 1 was characterised as a metabolically unhealthy cluster. Targeted dietary advice solutions were developed per cluster using a decision tree approach. Testing of the approach was performed by comparison with the personalised dietary advice, delivered by nutritionists to Food4Me study participants (n 180). Excellent agreement was observed between the targeted and individualised approaches with an average match of 82 % at the level of delivery of the same dietary message. Future work should ascertain whether this proposed method could be utilised in a healthcare setting, for the rapid and efficient delivery of tailored dietary advice solutions.
Through this study we aimed to assess the educational level and employment status of adults with CHD in Germany.
Data were acquired from an online survey carried out in 2015 by the German National Register for Congenital Heart Defects. A total of 1458 adults with CHD participated in the survey (response rate: 37.6%). For 1198 participants, detailed medical information, such as main cardiac diagnosis and information from medical reports, was available.
Of the participants surveyed (n=1198), 54.5% (n=653) were female, and the mean age was 30 years. The majority of respondents (59.4%) stated that they had high education levels and that they were currently employed (51.1%). Patients with simple CHD had significantly higher levels of education (p<0.001) and were more likely to be employed (p=0.01) than were patients with complex CHD.
More than half of the participants had high education levels and the majority were employed. The association between CHD and its severity and individuals’ educational attainment should be investigated more closely in future studies.
A core challenge of a multidisciplinary and multi-organizational translational research enterprise such as a Clinical and Translational Research Award (CTSA) is coordinating and integrating the work of individuals, workgroups, and organizations accustomed to working independently and autonomously. Tufts Clinical and Translational Science Institute (CTSI) undertook and studied a multifacted intervention to address this challenge and to create a culture of systems thinking, process awareness, responsive to others' needs, and shared decision-making.
The intervention, based on relational coordination, included 1) relational interventions, in three staff retreats and a diagnostic survey to provide feedback on the current quality of relational coordination, and 2) structural interventions, in the launching of five new cross-functional teams with regular meeting structures.
A mixed-methods evaluation yielded quantitative data via two types of team surveys and qualitative data via interviews and meeting observations.
The findings suggest that interventions to improve relational coordination are feasible for CTSAs, including good fidelity to the model and staff/physician engagement. Survey and interview data suggest model improvements in coordination and alignment. Further research about their optimal design is warranted.
To characterise clusters of individuals based on adherence to dietary recommendations and to determine whether changes in Healthy Eating Index (HEI) scores in response to a personalised nutrition (PN) intervention varied between clusters.
Food4Me study participants were clustered according to whether their baseline dietary intakes met European dietary recommendations. Changes in HEI scores between baseline and month 6 were compared between clusters and stratified by whether individuals received generalised or PN advice.
Individuals in cluster 1 (C1) met all recommended intakes except for red meat, those in cluster 2 (C2) met two recommendations, and those in cluster 3 (C3) and cluster 4 (C4) met one recommendation each. C1 had higher intakes of white fish, beans and lentils and low-fat dairy products and lower percentage energy intake from SFA (P<0·05). C2 consumed less chips and pizza and fried foods than C3 and C4 (P<0·05). C1 were lighter, had lower BMI and waist circumference than C3 and were more physically active than C4 (P<0·05). More individuals in C4 were smokers and wanted to lose weight than in C1 (P<0·05). Individuals who received PN advice in C4 reported greater improvements in HEI compared with C3 and C1 (P<0·05).
The cluster where the fewest recommendations were met (C4) reported greater improvements in HEI following a 6-month trial of PN whereas there was no difference between clusters for those randomised to the Control, non-personalised dietary intervention.
To characterise participants who dropped out of the Food4Me Proof-of-Principle study.
The Food4Me study was an Internet-based, 6-month, four-arm, randomised controlled trial. The control group received generalised dietary and lifestyle recommendations, whereas participants randomised to three different levels of personalised nutrition (PN) received advice based on dietary, phenotypic and/or genotypic data, respectively (with either more or less frequent feedback).
Seven recruitment sites: UK, Ireland, The Netherlands, Germany, Spain, Poland and Greece.
Adults aged 18–79 years (n 1607).
A total of 337 (21 %) participants dropped out during the intervention. At baseline, dropouts had higher BMI (0·5 kg/m2; P<0·001). Attrition did not differ significantly between individuals receiving generalised dietary guidelines (Control) and those randomised to PN. Participants were more likely to drop out (OR; 95 % CI) if they received more frequent feedback (1·81; 1·36, 2·41; P<0·001), were female (1·38; 1·06, 1·78; P=0·015), less than 45 years old (2·57; 1·95, 3·39; P<0·001) and obese (2·25; 1·47, 3·43; P<0·001). Attrition was more likely in participants who reported an interest in losing weight (1·53; 1·19, 1·97; P<0·001) or skipping meals (1·75; 1·16, 2·65; P=0·008), and less likely if participants claimed to eat healthily frequently (0·62; 0·45, 0·86; P=0·003).
Attrition did not differ between participants receiving generalised or PN advice but more frequent feedback was related to attrition for those randomised to PN interventions. Better strategies are required to minimise dropouts among younger and obese individuals participating in PN interventions and more frequent feedback may be an unnecessary burden.
New growth rate estimates for nine species from three genera of New Zealand Crassatellidae (Mollusca: Bivalvia), combined with existing morphometric ontogenetic descriptions, allow identification of heterochronic processes in the evolution of these genera. Both paedomorphosis (progenesis and neoteny) and peramorphosis (hypermorphosis and acceleration) have occurred within the clade. Overall, morphological variability and response to environmental pressure in this nonsiphonate group is restricted by the interplay of anatomical and life habit constraints. Stability in the substrate, predator avoidance, sluggish burrowing speed, and inability to escape by deep burial are suggested as key drivers of, or constraints on, morphological change. Two groups of shell characters are identified: heavy, armored “anchors” and elongate “snorkels,” which combine juvenile and adult traits in shells of different sizes and ages, produced by heterochronic variation in developmental timing. Anchors and snorkels both represent different “solutions” to the problems of life as a nonsiphonate, infaunal bivalve.
The interplay between the fat mass- and obesity-associated (FTO) gene variants and diet has been implicated in the development of obesity. The aim of the present analysis was to investigate associations between FTO genotype, dietary intakes and anthropometrics among European adults. Participants in the Food4Me randomised controlled trial were genotyped for FTO genotype (rs9939609) and their dietary intakes, and diet quality scores (Healthy Eating Index and PREDIMED-based Mediterranean diet score) were estimated from FFQ. Relationships between FTO genotype, diet and anthropometrics (weight, waist circumference (WC) and BMI) were evaluated at baseline. European adults with the FTO risk genotype had greater WC (AAv. TT: +1·4 cm; P=0·003) and BMI (+0·9 kg/m2; P=0·001) than individuals with no risk alleles. Subjects with the lowest fried food consumption and two copies of the FTO risk variant had on average 1·4 kg/m2 greater BMI (Ptrend=0·028) and 3·1 cm greater WC (Ptrend=0·045) compared with individuals with no copies of the risk allele and with the lowest fried food consumption. However, there was no evidence of interactions between FTO genotype and dietary intakes on BMI and WC, and thus further research is required to confirm or refute these findings.
An efficient and robust method to measure vitamin D (25-hydroxy vitamin D3 (25(OH)D3) and 25-hydroxy vitamin D2 in dried blood spots (DBS) has been developed and applied in the pan-European multi-centre, internet-based, personalised nutrition intervention study Food4Me. The method includes calibration with blood containing endogenous 25(OH)D3, spotted as DBS and corrected for haematocrit content. The methodology was validated following international standards. The performance characteristics did not reach those of the current gold standard liquid chromatography-MS/MS in plasma for all parameters, but were found to be very suitable for status-level determination under field conditions. DBS sample quality was very high, and 3778 measurements of 25(OH)D3 were obtained from 1465 participants. The study centre and the season within the study centre were very good predictors of 25(OH)D3 levels (P<0·001 for each case). Seasonal effects were modelled by fitting a sine function with a minimum 25(OH)D3 level on 20 January and a maximum on 21 July. The seasonal amplitude varied from centre to centre. The largest difference between winter and summer levels was found in Germany and the smallest in Poland. The model was cross-validated to determine the consistency of the predictions and the performance of the DBS method. The Pearson’s correlation between the measured values and the predicted values was r 0·65, and the sd of their differences was 21·2 nmol/l. This includes the analytical variation and the biological variation within subjects. Overall, DBS obtained by unsupervised sampling of the participants at home was a viable methodology for obtaining vitamin D status information in a large nutritional study.
Over the past 50 years, increases in dietary n-6 PUFA, such as linoleic acid, have been hypothesised to cause or exacerbate chronic inflammatory diseases. The present study examines an individual's innate capacity to synthesise n-6 long-chain PUFA (LC-PUFA) with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes or the metabolic syndrome. Compared with European Americans (EAm), African Americans (AfAm) exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 7·9 (sd 2·1), AfAm 9·8 (sd 1·9) % of total fatty acids; P < 2·29 × 10− 9) and the AA:n-6-precursor fatty acid ratio, which estimates FADS1 activity (EAm 5·4 (sd 2·2), AfAm 6·9 (sd 2·2); P = 1·44 × 10− 5). In all, seven SNP mapping to the FADS locus revealed strong association with AA, EPA and dihomo-γ-linolenic acid (DGLA) in the EAm. Importantly, EAm homozygous for the minor allele (T) had significantly lower AA levels (TT 6·3 (sd 1·0); GG 8·5 (sd 2·1); P = 3·0 × 10− 5) and AA:DGLA ratios (TT 3·4 (sd 0·8), GG 6·5 (sd 2·3); P = 2·2 × 10− 7) but higher DGLA levels (TT 1·9 (sd 0·4), GG 1·4 (sd 0·4); P = 3·3 × 10− 7) compared with those homozygous for the major allele (GG). Allele frequency patterns suggest that the GG genotype at rs174537 (associated with higher circulating levels of AA) is much higher in AfAm (0·81) compared with EAm (0·46). Similarly, marked differences in rs174537 genotypic frequencies were observed in HapMap populations. These data suggest that there are probably important differences in the capacity of different populations to synthesise LC-PUFA. These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent.
More than 60% of newborns with severe congenital cardiac disease develop perioperative brain injuries. Known risk factors include: pre-operative hypoxemia, cardiopulmonary bypass characteristics, and post-operative hypotension. Infection is an established risk factor for white matter injury in premature newborns. In this study, we examined term infants with congenital cardiac disease requiring surgical repair to determine whether infection is associated with white matter injury. Acquired infection was specified by site – bloodstream, pneumonia, or surgical site infection – according to strict definitions. Infection was present in 23 of 127 infants. Pre- and post-operative imaging was evaluated for acquired injury by a paediatric neuroradiologist. Overall, there was no difference in newly acquired post-operative white matter injury in infants with infection (30%), compared to those without (31%). When stratified by anatomy, infants with transposition of the great arteries, and bloodstream infection had an estimated doubling of risk of white matter injury that was not significant, whereas those with single ventricle anatomy had no apparent added risk. When considering only infants without stroke, the estimated association was higher, and became significant after adjusting for duration of inotrope therapy. In this study, nosocomial infection was not associated with white matter injury. Nonetheless, when controlling for risk factors, there was an association between bloodstream infection and white matter injury in selected sub-populations. Infection prevention may have the potential to mitigate long-term neurologic impairment as a consequence of white matter injury, which underscores the importance of attention to infection control for these patients.