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Few personalised medicine investigations have been conducted for mental health. We aimed to generate and validate a risk tool that predicts adult attention-deficit/hyperactivity disorder (ADHD).
Using logistic regression models, we generated a risk tool in a representative population cohort (ALSPAC – UK, 5113 participants, followed from birth to age 17) using childhood clinical and sociodemographic data with internal validation. Predictors included sex, socioeconomic status, single-parent family, ADHD symptoms, comorbid disruptive disorders, childhood maltreatment, ADHD symptoms, depressive symptoms, mother's depression and intelligence quotient. The outcome was defined as a categorical diagnosis of ADHD in young adulthood without requiring age at onset criteria. We also tested Machine Learning approaches for developing the risk models: Random Forest, Stochastic Gradient Boosting and Artificial Neural Network. The risk tool was externally validated in the E-Risk cohort (UK, 2040 participants, birth to age 18), the 1993 Pelotas Birth Cohort (Brazil, 3911 participants, birth to age 18) and the MTA clinical sample (USA, 476 children with ADHD and 241 controls followed for 16 years from a minimum of 8 and a maximum of 26 years old).
The overall prevalence of adult ADHD ranged from 8.1 to 12% in the population-based samples, and was 28.6% in the clinical sample. The internal performance of the model in the generating sample was good, with an area under the curve (AUC) for predicting adult ADHD of 0.82 (95% confidence interval (CI) 0.79–0.83). Calibration plots showed good agreement between predicted and observed event frequencies from 0 to 60% probability. In the UK birth cohort test sample, the AUC was 0.75 (95% CI 0.71–0.78). In the Brazilian birth cohort test sample, the AUC was significantly lower –0.57 (95% CI 0.54–0.60). In the clinical trial test sample, the AUC was 0.76 (95% CI 0.73–0.80). The risk model did not predict adult anxiety or major depressive disorder. Machine Learning approaches did not outperform logistic regression models. An open-source and free risk calculator was generated for clinical use and is available online at https://ufrgs.br/prodah/adhd-calculator/.
The risk tool based on childhood characteristics specifically predicts adult ADHD in European and North-American population-based and clinical samples with comparable discrimination to commonly used clinical tools in internal medicine and higher than most previous attempts for mental and neurological disorders. However, its use in middle-income settings requires caution.
Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high-fat diet in utero, programed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28 days postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (P<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol; however, transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared with wild-type controls (P=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, P<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol two-fold higher than in chow-fed mothers, P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models.
To quantify myocardial blood flow in infants and children with mild or moderate aortic stenosis using adenosine-infusion cardiac magnetic resonance.
It is unclear whether asymptomatic children with mild/moderate aortic stenosis have myocardial abnormalities. In addition, cardiac magnetic resonance-determined normative myocardial blood flow data in children have not been reported.
We studied 31 infants and children with either haemodynamically normal hearts (n=20, controls) or mild/moderate aortic stenosis (n=11). The left ventricular myocardium was divided into six segments, and the change in average segmental signal intensity during contrast transit was used to quantify absolute flow (ml/g/minute) at rest and during adenosine infusion by deconvolution of the tissue curves with the arterial input of contrast.
In all the cases, adenosine was well tolerated without complications. The mean pressure gradient between the left ventricle and the ascending aorta was higher in the aortic stenosis group compared with controls (24 versus 3 mmHg, p<0.001). Left ventricular wall mass was slightly higher in the aortic stenosis group compared with controls (65 versus 50 g/m2, p<0.05). After adenosine treatment, both the absolute increase in myocardial blood flow (p<0.0001) and the hyperaemic flow significantly decreased (p<0.001) in children with mild/moderate aortic stenosis compared with controls.
Abnormal myocardial blood flow in children with mild/moderate aortic stenosis may be an important therapeutic target.
Children with attention-deficit hyperactivity disorder (ADHD) are thought to be at higher risk of psychopathy. Early biological and social adversity may contribute to this risk.
To examine psychopathy traits in ADHD.
In a sample of children with ADHD who had reached adolescence, total psychopathy and ‘emotional-dysfunction’ scores (e.g. callousness, lack of affect) were assessed using the Hare Psychopathy Checklist–Youth Version.
A total of 156 (79%) eligible families participated. Total psychopathy and emotional-dysfunction scores were elevated in comparison to published UK norms but none scored in the clinical range for psychopathy. Adjusting for associated conduct problems, total psychopathy scores were associated with maternal smoking during pregnancy, emotional-dysfunction scores were associated with birth complications, and neither was associated with family adversity.
Children with ADHD show psychopathy traits but are not ‘psychopaths’. Early adversity, indexed by pre- or perinatal adversity but not family factors, appears to be associated.
Poor quality of nutrition during fetal development is associated with adverse health outcomes in adult life. Epidemiological studies suggest that markers of fetal undernutrition are predictive of risk of the metabolic syndrome and CHD. Here we show that feeding a low-protein diet during pregnancy programmed the development of atherosclerosis in ApoE*3-Leiden mice. ApoE*3-Leiden mice carry a mutation of human ApoE*3 rendering them prone to atherosclerosis when fed a diet rich in cholesterol. It was noted that fetal exposure to protein restriction led to a greater degree of dyslipidaemia in mice when fed an atherogenic diet, with low-protein-exposed ApoE*3 mice having elevated total plasma cholesterol (34 % higher; P < 0·001) and TAG (39 % higher; P < 0·001) relative to offspring exposed to a control diet in utero. The low-protein group developed more severe atherosclerotic lesions within the aortic arch (2·61-fold greater lesion area; P < 0·001). Analysis of a targeted gene array suggested a potential role for members of the LDL receptor superfamily, along with similar programmed suppression of the mRNA expression of hepatic sterol regulatory element-binding protein-1c. This indicates that disordered lipid metabolism may play a role in the fetal programming of atherosclerosis in this model. Whereas earlier studies have shown early programming of cardiovascular risk factors, these results demonstrate for the first time that the interaction of prenatal undernutrition with a postnatal atherogenic diet increases the extent of atherosclerotic disease.
The snow surface roughness at centimetre and millimetre scales is an important parameter related to wind transport, snowdrifts, snowfall, snowmelt and snow grain size. Knowledge of the snow surface roughness is also of high interest for analyzing the signal from radar sensors such as SAR, altimeters and scatterometers. Unfortunately, this parameter has seldom been measured over snow surfaces. The techniques used to measure the roughness of other surfaces, such as agricultural or sand soils, are difficult to implement in polar regions because of the harsh climatic conditions. In this paper we develop a device based on a laser profiler coupled with a GPS receiver on board a snowmobile. This instrumentation was tested successfully in midre Lovénbreen, Svalbard, in April 2006. It allowed us to generate profiles of 3 km sections of the snow-covered glacier surface. Because of the motion of the snowmobile, the roughness signal is mixed with the snowmobile signal. We use a distance/frequency analysis (the empirical mode decomposition) to filter the signal. This method allows us to recover the snow surface structures of wavelengths between 4 and 50 cm with amplitudes of >1 mm. Finally, the roughness parameters of snow surfaces are retrieved. The snow surface roughness is found to be dependent on the scales of the observations. The retrieved RMS of the height distribution is found to vary between 0.5 and 9.2 mm, and the correlation length is found to be between 0.6 and 46 cm. This range of measurements is particularly well adapted to the analysis of GHz radar response on snow surfaces.
The number of deaths attributable to influenza is believed to be considerably higher than the number certified by vital statistics registration as due to influenza. Weekly mortality data for Canada from the 1989/1990 to the 1998/1999 influenza seasons were analysed by cause of death, age group, and place of death to estimate the impact of influenza on mortality. A Poisson regression model was found to accurately predict all-cause, as well as cause-specific mortality, as a function of influenza-certified deaths, after controlling for seasonality, and trend. Influenza-attributable deaths were calculated as predicted less baseline-predicted deaths. In summary, throughout the 1990s there were on average just under 4000 deaths attributable to influenza annually (for an influenza-attributable mortality rate of 13/100 000 persons), varying from no detectable excess mortality for the 1990/1991 influenza season, to 6000–8000 influenza-attributable deaths for the more severe influenza seasons of 1997/1998 and 1998/1999. On average, 8% (95% CI 7–10) of influenza-attributable deaths were certified as influenza, although this percentage varied from 4% to 12% from year to year. Only 15% of the influenza-attributable deaths were certified as pneumonia, and for all respiratory causes, 40%. Deaths were distributed over most causes. The weekly pattern of influenza-certified deaths was a good predictor of excess all-cause mortality.
The prenatal diet can program an individual's cardiovascular system towards later higher resting blood pressure and kidney dysfunction, but the extent to which these programmed responses are directly determined by the timing of maternal nutritional manipulation is unknown. In the present study we examined whether maternal nutrient restriction targeted over the period of maximal placental growth, i.e. days 28–80 of gestation, resulted in altered blood pressure or kidney development in the juvenile offspring. This was undertaken in 6-month-old sheep born to mothers fed control (100–150 % of the recommended metabolisable energy (ME) intake for that stage of gestation) or nutrient-restricted (NR; 50 % ME; n 6) diets between days 28 and 80 of gestation. Controls were additionally grouped according to normal (>3, n 7) or low body condition score (LBCS; <2, n 6), thereby enabling us to examine the effect of maternal body composition on later cardiovascular function. From day 80 to term (approximately 147 d) all sheep were fed to 100 % ME. Offspring were weaned at 12 weeks and pasture-reared until 6 months of age when cardiovascular function was determined. Both LBCS and NR sheep tended to have lower resting systolic (control, 85 (SE 2); LBCS, 77 (SE 3); NR, 77 (SE 3) mmHg) and diastolic blood pressure relative to controls. Total nephron count was markedly lower in both LBCS and NR relative to controls (LBCS, 59 (SE 6); NR, 56 (SE 12) %). Our data suggest that maternal body composition around conception is as important as the level of nutrient intake during early pregnancy in programming later cardiovascular health.
Standard curves for the regression of pteridine fluorescence in the head upon chronological age were constructed for laboratory-reared Glossina adults. Of the five species investigated, the technique was a reliable predictor of age in G. morsitans morsitans Westwood, G. pallidipes Austen, G. palpalis palpalis (Robineau-Desvoidy) and G. tachinoides Westwood, but was not reliable for G. austeni Newstead. Field-caught tenerals of both sexes of G. p. palpalis, field-caught teneral females of G. pallidipes and tenerals of both sexes of G. m. morsitans released on an island in Lake Kariba, Zimbabwe, had significantly higher pteridine fluorescence levels than tenerals hatched in the laboratory. However, the regression of fluorescence on age produced similar slopes for both laboratory-reared and field-caught flies. From this, it is concluded that estimates of the ages of field-caught flies can be corrected by simply subtracting the difference in fluorescence values between field-caught and laboratory-reared tenerals. In practice, this amounts to shifting the frequency distribution of different age categories to bring the youngest age group back to day zero. A comparison of the fluorescence technique and the ovarian dissection method of determining the ages of females showed that over a wide range of ages the former was at least as accurate as the latter and should be the technique of choice for most field investigations.
The importance of maximum rates of insemination in female tsetse is emphasized in relation to their low rate of reproduction and to the possibility that density dependent regulation of tsetse populations may not be as rigorous as in many oviparous insects. Observations on the mating behaviour of tsetse are described and its regulation by sex pheromones which serve to identify females of the species is discussed. Laboratory and field experiments have shown that the sexual activity of G. m. morsitans males can be manipulated by presentation of synthetic sex pheromone on suitable decoys in the laboratory and in the field. Males that respond to decoys in the field are in the same nutritional state as others which are attracted to the models upon which the decoys are placed and are presumably seeking food. There is no reason to believe that sexual activity is restricted to a particular section of the population, and given a choice, it is proposed that mating is preferable to feeding in terms of gene survival for the individual male. The durations of copulatory responses are dose dependent and there is some evidence that they are inversely proportional to the frequency of encounters with decoys and hence to the density of flies. Techniques for the reduction of tsetse populations using sex pheromones in conjunction with suitable decoys and chemosterilants are being developed. The availability of pheromones in large quantities will permit their testing as sexual confusants among males and may lead to interspecific matings where more than one species occupies the same habitat.
Male and female Glossina morsitans morsitans Westw. which emerged from puparia produced by animal-fed and in vitro-fed colonies in England were marked distinctively with non-toxic paint and released into a natural habitat of G. morsitans and G. pallidipes Aust. in Rhodesia. Concurrently, adults of both species which emerged from locally-collected puparia were marked and released. Recaptures from artificial refuges, odour attractants and mobile baits at periods up to 59 days after release and at distances up to 1800 m from the release site indicated no clear differences between native G. morsitans and the two laboratory-reared groups in respect of body size, amount of fat present at emergence, survival, dispersal, availability to a range of baits, diet, speed of taking a first meal, wing damage and insemination rate. Although the blood-meal identifications for marked female G. morsitans were similar to those for both sexes of unmarked flies, blood-meals from marked males showed a relatively high proportion of bovid identifications. Unmarked flies caught were generally older than marked catches. The ratio of females to males in unmarked samples (1:1 for G. morsitans, 2:1 for G. pallidipes) was roughly double that in marked catches.