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Autism spectrum disorders (ASD) often go undetected in toddlers. The Modified Checklist for Autism in Toddlers (M-CHAT) was used to screen 3,793 children aged 16–30 months from low- and high-risk sources; screen positive cases were diagnostically evaluated. Re-screening was performed on 1,416 children aged 42–54 months. Time1 Positive Predictive Value (PPV) was .36 for the initial screening and .74 for the screening plus follow-up telephone interview; values were similar for Time2 PPV. When separating referral sources, PPV was low for the low-risk sample but acceptable with the follow-up telephone interview. Children with ASD from the low-risk and high-risk samples were highly similar. Results indicate that the M-CHAT continues to be a promising instrument for the early detection of ASD.

A diagnosis of autism spectrum disorder (ASD) is usually taken to be permanent. In this study, 13 two-year-old children with ASD lost the diagnosis by age 4, at which time they scored within the normal range on standardized measures of cognitive and adaptive functioning. No differences were found in symptom severity, socialization, or communication between children who lost the ASD diagnosis and children who did not, but children with PDD-NOS were significantly more likely than those with full autistic disorder to move off the spectrum. The clearest distinguishing factor was motor skills at age 2. Results support the idea that some toddlers with ASD can lose their diagnosis and suggest that this is difficult to predict.

This study compared behavioral presentation of toddlers with autistic spectrum disorders (ASD) and toddlers with global developmental delay (DD) or developmental language disorder (DLD) who display some characteristics of ASD using the diagnostic algorithm items from the Autism Diagnostic Observation Schedule, Generic (ADOS), the Childhood Autism Rating Scale (CARS), and Modified Checklist for Autism in Toddlers (M-CHAT). To date, 195 children have failed the M-CHAT and have been diagnosed with ASD, DD or DLD. Children with ASD had prominent and consistent impairments in socialization skills, especially joint attention skills and were more impaired in some aspects of communication, play, and sensory processing. Children with ASD and children with DD/DLD shared common features, but certain behavioral markers differentiated the two groups.

IntroductionAutism is a highly heritable disorder with variable physiological, behavioral, and cognitive expression, and a widely variable set of outcomes. In some ways, not enough is known about each of these levels of expression of the disorder; in some ways, however, too much is known – many findings at the genetic, anatomical, and neurochemical levels have been reported, but are often not replicated or are directly opposite to each other (low vs. high chemical levels, increased vs. decreased volume of particular brain structures), and no successful synthesis of findings across or within levels has yet been made. Given this complex and disjointed set of studies, we have not attempted a comprehensive or synthetic review.We will not address studies on neurochemistry or other physiological factors that have been raised as possibilities in autism, such as inflammatory processes (Vargas et al., 2005), but will focus on genetics, anatomy, and behavioral/cognitive outcome. We will first describe the basic phenomenology and epidemiology of the autistic syndromes. Second, we will review what is known about the genetic basis of autism. Third, we will describe the current state of knowledge about the neuroanatomy of autism. Finally, we will address outcome: what is known about the outcome of affected children; and most intriguingly, if autism has a genetic basis, which seems to affect basic neuroanatomy, how is it possible that some children “recover” from their autism? (Discussion of autism associated with fragile X syndrome can be found in Chapter 1.)

Alterations in mitochondrial metabolism in obesity may indicate disrupted communication between mitochondria and nucleus, and DNA methylation may influence this interplay. Here, we leverage data from the Finnish Twin Cohort study subcohort ( n  = 173; 86 full twin pairs, 1 singleton), including comprehensive measurements of obesity-related outcomes, mitochondrial DNA quantity and nuclear DNA methylation levels in adipose and muscle tissue, to identify one CpG at SH3BP4 significantly associated with mitochondrial DNA quantity in adipose tissue (FDR < 0.05). We also show that SH3BP4 methylation correlates with its gene expression. Additionally, we find that 14 out of the 35 obesity-related traits display significant associations with both SH3BP4 methylation and mitochondrial DNA quantity in adipose tissue. We use data from TwinsUK and the Scandinavian T2D-discordant monozygotic twin cohort, to validate the observed associations. Further analysis using ICE FALCON suggests that mitochondrial DNA quantity, insulin sensitivity and certain body fat measures are causal to SH3BP4 methylation. Examining mitochondrial DNA quantity and obesity-related traits suggests causation from mitochondrial DNA quantity to obesity, but unmeasured within-individual confounding cannot be ruled out. Our findings underscore the impact of mitochondrial DNA quantity on DNA methylation and expression of the SH3BP4 gene within adipose tissue, with potential implications for obesity. In obesity, mitochondrial communication with the nucleus may be disrupted. Here, the authors use Finnish twin data to link obesity-related changes in mitochondrial DNA quantity with the methylation and expression of SH3BP4 in adipose tissue.

Background Pupils in secondary schools do not meet the targets for physical activity levels during physical education (PE) sessions, and there is a lack of data on the vigorous physical activity domain (VPA) in PE known to be positively associated with cardio metabolic health While PE session intensity depends on a variety of factors, the large majority of studies investigating these factors have not taken into account the nested structure of this type of data set. Therefore, the aim of this study was to investigate the relationship between various factors (gender, activity type, class location and class composition) and various activity levels during PE classes in secondary schools, using a multi-level statistical approach. Methods Year eight (12–13 years old) adolescents (201 boys and 106 girls) from six schools were fitted with accelerometers during one PE session each, to determine the percentage (%) of the PE session time spent in sedentary (SPA), light (LPA), moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) intensity levels. Two- and three-level (pupils, n  = 307; classes, n  = 13, schools, n  = 6) mixed-effect models were used to assess the relationship between accelerometer-measured physical activity levels (% of class time spent in various activity levels) and gender, activity type, class location and composition. Results Participants engaged in MVPA and VPA for 30.7 ± 1.2% and 11.5 ± 0.8% of PE classes, respectively. Overall, no significant association between gender or class composition and PA was shown. A significant relationship between activity type and PA was observed, with Artistic classes significantly less active than Fitness classes for VPA (5.4 ± 4.5 vs. 12.5 ± 7.1%, p  = 0.043, d :1.19). We also found a significant association between class location and PA, with significantly less time spent in SPA (24.8 ± 4.8% vs. 30.0 ± 3.4%, p  = 0.042, d :0.77) and significantly more time spent in VPA (12.4 ± 3.7% vs. 7.6 ± 2.0%, p  = 0.022, d :1.93) and MVPA (32.3 ± 6.7% vs.24.8 ± 3.8%, p  = 0.024, d :1.33) in outdoors vs. indoors classes. Conclusions The results suggest that class location and activity type could be associated with the intensity of PA in PE. It is essential to take into account the clustered nature of this type of data in similar studies if the sample size allows it.

Stimulation of the innate immune system is crucial in both effective vaccinations and immunotherapies. This is often achieved through adjuvants, molecules that usually activate pattern recognition receptors (PRRs) and stimulate two innate immune signaling pathways: the nuclear factor kappa-light-chain-enhancer of activated B-cells pathway (NF-κB) and the interferon regulatory factors pathway (IRF). Here, we demonstrate the ability to alter and improve adjuvant activity via the addition of small molecule “immunomodulators”. By modulating signaling activity instead of receptor binding, these molecules allow the customization of select innate responses. We demonstrate both inhibition and enhancement of the products of the NF-κB and IRF pathways by several orders of magnitude. Some modulators apply generally across many receptors, while others focus specifically on individual receptors. Modulators boost correlates of a protective immune responses in a commercial flu vaccine model and reduced correlates of reactogenicity in a typhoid vaccine model. These modulators have a range of applications: from adjuvanticity in prophylactics to enhancement of immunotherapy.

ObjectivesTo establish pupil fitness levels, and the relationship to global norms and physical education (PE) enjoyment. To measure and describe physical activity (PA) levels during secondary school PE lessons, in the context of recommended levels, and how levels vary with activity and lesson type.MethodsA cross-sectional design; 10 697 pupils aged 12.5 (SD 0.30) years; pupils who completed a multistage fitness test and wore accelerometers to measure PA during PE lessons. Multilevel models estimated fitness and PE activity levels, accounting for school and class-level clustering.ResultsCardiorespiratory fitness was higher in boys than girls (ß=−0.48; 95% CI −0.56 to −0.39, p<0.001), within absolute terms 51% of boys and 54% of girls above the 50th percentile of global norms. On average, pupils spent 23.8% of PE lessons in moderate-to-vigorous PA (MVPA), and 7.1% in vigorous PA (VPA). Fitness-focused lessons recorded most VPA in co-educational (ß=1.09; 95% CI 0.43 to 1.74) and boys-only lessons (ß=0.32; 95% CI −0.21 to 0.85). In girls-only lessons, track athletics recorded most VPA (ß=0.13; 95% CI −0.50 to 0.75) and net/wall/racket games (ß=0.97; 95% CI 0.12 to 1.82) the most MVPA. For all lesson types, field athletics was least active (ß=−0.85; 95% CI −1.33 to −0.36). There was a relationship of enjoyment of PE to fitness (ß=1.03; 95% CI 0.83 to 1.23), and this relationship did not vary with sex (ß=−0.14 to 0.23; 95% CI −0.16 to 0.60).ConclusionsPE lessons were inactive compared with current guidelines. We propose that if we are to continue to develop a range of sporting skills in schools at the same time as increasing levels of fitness and PA, there is a need to introduce additional sessions of PE activity focused on increasing physical activity.Trial registration numberNCT03286725.

Background Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. Methods Patients ( n  = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale – Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury – Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. Results Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL. Conclusions Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach. Trial registration ClinicalTrials.gov NCT02210221.