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The prevalence and impact of motor coordination difficulties in children with copy number variants associated with neurodevelopmental disorders (ND-CNVs) remains unknown. This study aims to advance understanding of motor coordination difficulties in children with ND-CNVs and establish relationships between intelligence quotient (IQ) and psychopathology.
169 children with an ND-CNV (67% male, median age = 8.88 years, range 6.02–14.81) and 72 closest-in-age unaffected siblings (controls; 55% male, median age = 10.41 years, s.d. = 3.04, range 5.89–14.75) were assessed with the Developmental Coordination Disorder Questionnaire, alongside psychiatric interviews and standardised assessments of IQ.
The children with ND-CNVs had poorer coordination ability (b = 28.98, p < 0.001) and 91% of children with an ND-CNV screened positive for suspected developmental coordination disorder, compared to 19% of controls (OR = 42.53, p < 0.001). There was no difference in coordination ability between ND-CNV genotypes (F = 1.47, p = 0.184). Poorer coordination in children with ND-CNV was associated with more attention deficit hyperactivity disorder (ADHD) (β = −0.18, p = 0.021) and autism spectrum disorder trait (β = −0.46, p < 0.001) symptoms, along with lower full-scale (ß = 0.21, p = 0.011), performance (β = −0.20, p = 0.015) and verbal IQ (β = 0.17, p = 0.036). Mediation analysis indicated that coordination ability was a full mediator of anxiety symptoms (69% mediated, p = 0.012), and a partial mediator of ADHD (51%, p = 0.001) and autism spectrum disorder trait symptoms (66%, p < 0.001) as well as full scale IQ (40%, p = 0.002), performance IQ (40%, p = 0.005) and verbal IQ (38%, p = 0.006) scores.
The findings indicate that poor motor coordination is highly prevalent and closely linked to risk of mental health disorder and lower intellectual function in children with ND-CNVs. Future research should explore whether early interventions for poor coordination ability could ameliorate neurodevelopmental risk.
There was a time when we were all six-sigma-ing. We did so because Jack Welch had bought into the six-sigma phenomenon and he had created a phenomenally performing General Electric (GE). Then we moved along from good to great to the search for excellence to becoming great by choice to whatever superlative Jim Collins told us was the way to a company that was built to last. Then someone moved our cheese. We had no time for that because we were just one-minute managers. We smoothed earnings, incentivized employees, and created three tiers of employees – including getting rid of the bottom tier of employees, whether they deserved termination or kudos. We all wanted to be part of the Fortune 100, the Fortune Most Admired Companies, even as we were led by Fortune CEOs and CFOs of the year – many of whom ended up doing time.
The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the USA. It comprises 15,924 White male twin pairs born in the years 1917–1927 (N = 31.848), both of whom served in the armed forces, chiefly during World War II. This article updates activities in this registry since the most recent report in Twin Research and Human Genetics (Page, 2006). Records-based data include information from enlistment charts and Veterans Administration data linkages. There have been three major epidemiologic questionnaires and an education and earnings survey. Separate data collection efforts with the NAS-NRC registry include the National Heart, Lung, and Blood Institute (NHLBI) subsample, the Duke Twins Study of Memory in Aging and a clinically based study of Parkinson’s disease. Progress has been made on consolidating the various data holdings of the NAS-NRC Twin Registry. Data that had been available through the National Academy of Sciences are now freely available through National Archive of Computerized Data on Aging (NACDA).
The association between intake of different dairy products and the risk of stroke remains unclear. We therefore investigated substitutions between dairy product subgroups and risk of stroke. We included 36 886 Dutch men and women. Information about dairy product intake was collected through a FFQ. Dairy products were grouped as low-fat milk, whole-fat milk, buttermilk, low-fat yogurt, whole-fat yogurt, cheese and butter. Incident stroke cases were identified in national registers. We used Cox proportional hazards regression to calculate associations for substitutions between dairy products with the rate of stroke. During a median follow-up of 15·2 years we identified 884 stroke cases (503 ischaemic and 244 haemorrhagic). Median intake of total dairy products was four servings/d. Low-fat yogurt substituted for whole-fat yogurt was associated with a higher rate of ischaemic stroke (hazard ratio (HR) = 2·58 (95 % CI 1·11, 5·97)/serving per d). Whole-fat yogurt as a substitution for any other subgroup was associated with a lower rate of ischaemic stroke (HR between 0·33 and 0·36/serving per d). We did not observe any associations for haemorrhagic stroke. In conclusion, whole-fat yogurt as a substitution for low-fat yogurt, cheese, butter, buttermilk or milk, regardless of fat content, was associated with a lower rate of ischaemic stroke.
The past decade has seen the development of services for adults presenting with symptoms of autism spectrum disorder (ASD) in the UK. Compared with children, little is known about the phenotypic and genetic characteristics of these patients.
This e-cohort study aimed to examine the phenotypic and genetic characteristics of a clinically presenting sample of adults diagnosed with ASD by specialist services.
Individuals diagnosed with ASD as adults were recruited by the National Centre for Mental Health and completed self-report questionnaires, interviews and provided DNA; 105 eligible individuals were matched to 76 healthy controls. We investigated demographics, social history and comorbid psychiatric and physical disorders. Samples were genotyped, copy number variants (CNVs) were called and polygenic risk scores were calculated.
Of individuals with ASD, 89.5% had at least one comorbid psychiatric diagnosis, with depression (62.9%) and anxiety (55.2%) being the most common. The ASD group experienced more neurological comorbidities than controls, particularly migraine headache. They were less likely to have married or be in work, and had more alcohol-related problems. There was a significantly higher load of autism common genetic variants in the adult ASD group compared with controls, but there was no difference in the rate of rare CNVs.
This study provides important information about psychiatric comorbidity in adult ASD, which may inform clinical practice and patient counselling. It also suggests that the polygenic load of common ASD-associated variants may be important in conferring risk within the non-intellectually disabled population of adults with ASD.
Strategies are needed to improve the dietary habits of children. The aim of the present study was to evaluate the effect of implementing a school food programme on the dietary quality of lunches consumed by school children aged 7–13 years compared with packed lunches brought from home. A secondary objective was to investigate if a possible effect would differ between the younger children and the older. A quasi-experimental study design with four intervention schools and four matched control schools was conducted. In total, 984 school children participated. Data on packed lunches were collected at baseline. At the 1st follow-up the children in the intervention schools were offered free school meals and at the 2nd follow-up children paid for their school meals. The control group had packed lunches at all measurements. A digital photographic method combined with a Meal Index of dietary Quality (Meal IQ) was used for dietary assessment. Multilevel modelling was employed for data analyses. The quality of dietary intake was improved when free school meals were offered (P = 0·004); if the school meals were paid for the use was limited and no difference in change in dietary quality was found (P = 0·343). The school food programme had no difference in effect according to age (P = 0·083). In conclusion, offering a free school meal had a positive effect on dietary quality of the lunches consumed by school children aged 7–13 years. No effect was measured when the school meals were not provided for free. The dietary effect did not depend on age.
The fetal phase of life has long been recognized as a sensitive period of development. Here we posit that pregnancy represents a simultaneous sensitive period for the adult female with broad and persisting consequences for her health and development, including risk for psychopathology. In this review, we examine the transition to motherhood through the lens of developmental psychopathology. Specifically, we summarize the typical and atypical changes in brain and behavior that characterize the perinatal period. We highlight how the exceptional neuroplasticity exhibited by women during this life phase may account for increased vulnerability for psychopathology. Further, we discuss several modes of signaling that are available to the fetus to affect maternal phenotypes (hormones, motor activity, and gene transfer) and also illustrate how evolutionary perspectives can help explain how and why fetal functions may contribute to maternal psychopathology. The developmental psychopathology perspective has spurred advances in understanding risk and resilience for mental health in many domains. As such, it is surprising that this major epoch in the female life span has yet to benefit fully from similar applications.
22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of neurodevelopmental disorder, however, the links between developmental coordination disorder (DCD), intellectual function and psychiatric disorder remain unexplored.
To establish the prevalence of indicative DCD in children with 22q11.2DS and examine associations with IQ, neurocognition and psychopathology.
Neurocognitive assessments and psychiatric interviews of 70 children with 22q11.2DS (mean age 11.2, s.d. = 2.2) and 32 control siblings (mean age 11.5, s.d. = 2.1) were carried out in their homes. Nine children with 22q11.2DS and indicative DCD were subsequently assessed in an occupational therapy clinic.
Indicative DCD was found in 57 (81.4%) children with 22q11.2DS compared with 2 (6.3%) control siblings (odds ratio (OR) = 36.7, P < 0.001). Eight of nine (89%) children with indicative DCD met DSM-5 criteria for DCD. Poorer coordination was associated with increased numbers of anxiety, (P < 0.001), attention-deficit hyperactivity disorder (ADHD) (P < 0.001) and autism-spectrum disorder (ASD) symptoms (P < 0.001) in children with 22q11.2DS. Furthermore, 100% of children with 22q11.2DS and ADHD had indicative DCD (20 of 20), as did 90% of children with anxiety disorder (17 of 19) and 96% of children who screened positive for ASD (22 of 23). The Developmental Coordination Disorder Questionnaire score was related to sustained attention (P = 0.006), even after history of epileptic fits (P = 0.006) and heart problems (P = 0.009) was taken into account.
Clinicians should be aware of the high risk of coordination difficulties in children with 22q11.2DS and its association with risk of mental disorder and specific neurocognitive deficits.
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.
22q11.2 deletion syndrome (22q11.2DS) is associated with a high risk of childhood as well as adult psychiatric disorders, in particular schizophrenia. Childhood cognitive deterioration in 22q11.2DS has previously been reported, but only in studies lacking a control sample.
To compare cognitive trajectories in children with 22q11.2DS and unaffected control siblings.
A longitudinal study of neurocognitive functioning (IQ, executive function, processing speed and attention) was conducted in children with 22q11.2DS (n = 75, mean age time 1 (T1) 9.9, time 2 (T2) 12.5) and control siblings (n = 33, mean age T1 10.6, T2 134).
Children with 22q11.2DS exhibited deficits in all cognitive domains. However, mean scores did not indicate deterioration. When individual trajectories were examined, some participants showed significant decline over time, but the prevalence was similar for 22q11.2DS and control siblings. Findings are more likely to reflect normal developmental fluctuation than a 22q11.2DS-specific abnormality.
Childhood cognitive deterioration is not associated with 22q11.2DS. Contrary to previous suggestions, we believe it is premature to recommend repeated monitoring of cognitive function to identifying individual children with 22q11.2DS at high risk of developing schizophrenia.
Individual response to dietary interventions can be highly variable. The phenotypic characteristics of those who will respond positively to personalised dietary advice are largely unknown. The objective of this study was to compare the phenotypic profiles of differential responders to personalised dietary intervention, with a focus on total circulating cholesterol. Subjects from the Food4Me multi-centre study were classified as responders or non-responders to dietary advice on the basis of the change in cholesterol level from baseline to month 6, with lower and upper quartiles defined as responder and non-responder groups, respectively. There were no significant differences between demographic and anthropometric profiles of the groups. Furthermore, with the exception of alcohol, there was no significant difference in reported dietary intake, at baseline. However, there were marked differences in baseline fatty acid profiles. The responder group had significantly higher levels of stearic acid (18 : 0, P=0·034) and lower levels of palmitic acid (16 : 0, P=0·009). Total MUFA (P=0·016) and total PUFA (P=0·008) also differed between the groups. In a step-wise logistic regression model, age, baseline total cholesterol, glucose, five fatty acids and alcohol intakes were selected as factors that successfully discriminated responders from non-responders, with sensitivity of 82 % and specificity of 83 %. The successful delivery of personalised dietary advice may depend on our ability to identify phenotypes that are responsive. The results demonstrate the potential use of metabolic profiles in identifying response to an intervention and could play an important role in the development of precision nutrition.
Regular consumption of long-chain n-3 fatty acids (LC n-3 FA) reduces postprandial triacylglycerolaemia. Functional foods and supplements are alternative sources of LC n-3 FA; however, emulsification technologies, food matrices and altered lipid oxidation levels affect their bioavailability. Moreover, which functional foods are optimal LC n-3 FA carriers is unknown. The aim of the study was to determine the bioavailability of LC n-3 FA and the postprandial TAG response after the intake of oxidised or non-oxidised cod liver oil and after the intake of emulsified or non-emulsified LC n-3 FA using novel functional food items as LC n-3 FA carriers in a randomised cross-over acute study. A total of twenty-four healthy subjects completed the study in which subjects consumed one of four different test meals containing 1·5 g LC n-3 FA, or a control meal with no LC n-3 FA. Postprandial TAG-rich lipoproteins were isolated and their fatty acid composition was measured. The LC n-3 FA from emulsified foods were more rapidly incorporated into TAG-rich lipoproteins compared with non-emulsified foods. The incorporation of LC n-3 FA was similar for oils emulsified in yogurt or juice and was unaffected by the oxidative status of the oil. Postprandial TAG levels did not differ among the various test meals. In conclusion, emulsification increases the bioavailability of LC n-3 FA through a more rapid incorporation into TAG-rich lipoproteins, and juice and yogurt are equally suited as LC n-3 FA carriers. The acute intake of oxidised cod liver oil does not influence the incorporation of LC n-3 FA into TAG-rich lipoproteins.
Red meat has been suggested to be adversely associated with risk of myocardial infarction (MI), whereas vegetable consumption has been found to be protective. The aim of this study was to investigate substitutions of red meat, poultry and fish with vegetables or potatoes for MI prevention. We followed up 29 142 women and 26 029 men in the Danish Diet, Cancer and Health study aged 50–64 years with no known history of MI at baseline. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for MI associated with specified food substitutions of 150 g/week. During a median follow-up of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for MI when replacing red meat with vegetables was 0·94 (95 % CI 0·90, 0·98). Replacing fatty fish with vegetables was associated with a higher risk of MI (HR 1·23; 95 % CI 1·05, 1·45), whereas an inverse, statistically non-significant association was found for lean fish (HR 0·93; 95 % CI 0·83, 1·05). Substituting poultry with vegetables was not associated with risk of MI (HR 1·00; 95 % CI 0·90, 1·11). Findings for substitution with potatoes were similar to findings for vegetables. Among men, a similar pattern was observed, but the associations were weak and mostly statistically non-significant. This study suggests that replacing red meat with vegetables or potatoes is associated with a lower risk of MI, whereas replacing fatty fish with vegetables or potatoes is associated with a higher risk of MI.
The healthy Nordic diet has been previously shown to have health beneficial effects among subjects at risk of CVD. However, the extent of food changes needed to achieve these effects is less explored. The aim of the present study was to investigate the effects of exchanging a few commercially available, regularly consumed key food items (e.g. spread on bread, fat for cooking, cheese, bread and cereals) with improved fat quality on total cholesterol, LDL-cholesterol and inflammatory markers in a double-blind randomised, controlled trial. In total, 115 moderately hypercholesterolaemic, non-statin-treated adults (25–70 years) were randomly assigned to an experimental diet group (Ex-diet group) or control diet group (C-diet group) for 8 weeks with commercially available food items with different fatty acid composition (replacing SFA with mostly n-6 PUFA). In the Ex-diet group, serum total cholesterol (P<0·001) and LDL-cholesterol (P<0·001) were reduced after 8 weeks, compared with the C-diet group. The difference in change between the two groups at the end of the study was −9 and −11 % in total cholesterol and LDL-cholesterol, respectively. No difference in change in plasma levels of inflammatory markers (high-sensitive C-reactive protein, IL-6, soluble TNF receptor 1 and interferon-γ) was observed between the groups. In conclusion, exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol, with no negative effect on levels of inflammatory markers. This shows that an exchange of a few commercially available food items was easy and manageable and led to clinically relevant cholesterol reduction, potentially affecting future CVD risk.
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.
In recent decades, cultural protocols have emerged as a non-judicial alternative to the inadequate legal protection of Indigenous cultural heritage. They are meant to protect Indigenous peoples from the misappropriation of their heritage by outsiders and enhance Indigenous peoples’ control over their own domain. This article examines the functioning of Indigenous cultural protocols within Australia’s contemporary art world. As we will demonstrate, cultural protocols have clear practical utility. They can raise awareness, instigate changes in behaviour, and operate as a conduit for correcting the unauthorized use of Indigenous cultural materials. Yet, a disjunction exists between codified ideals and a messy reality. Our analysis of two protocol transgressions shows that protocols do not automatically protect Indigenous individuals equally. Furthermore, although discussions about compliance are infused with rhetoric about the authority of “the Indigenous community,” Indigenous people with cultural connections to contested heritage objects do not always have a clear voice in decisions made about their use.
The objective of this study was to verify possible associations between heart rate variability indices and physical activity, body composition, and metabolic and cardiovascular parameters in individuals with type 1 diabetes.
A total of 39 young patients with type 1 diabetes were included. Body composition, physical activity, cardiovascular parameters, and metabolic parameters were assessed. For the heart rate variability analysis, heart rate was recorded beat-by-beat using a Polar S810i heart rate monitor for 30 minutes, with the volunteers in the supine position; subsequently, the following indices were considered: standard deviation of all normal RR intervals; root-mean square of differences between adjacent normal RR intervals in a time interval; percentage of adjacent RR intervals with a difference of duration >50 ms; high frequency component in milliseconds squared; high frequency component in normalised units; standard deviation of the instantaneous variability beat-to-beat; and standard deviation of the long-term variability. The association between the heart rate variability indices and independent variables was verified through linear regression in unadjusted and adjusted models (considering gender and age). The statistical significance was set at 5% and the confidence interval at 95%.
High values of at-rest heart rate were associated with reduced parasympathetic activity and global heart rate variability, and higher values of waist-to-hip ratio were related to lower parasympathetic activity, independent of age or gender.
For young patients with type 1 diabetes, increases in at-rest heart rate values are associated with reduced parasympathetic activity and global heart rate variability, whereas higher waist-to-hip ratio values are related to lower parasympathetic activity, both independent of age and gender.