Association of Relative Age in the School Year With Diagnosis of Intellectual Disability, Attention-Deficit/Hyperactivity Disorder, and Depression

IMPORTANCE: Young relative age within the school year has previously been associated with attention-deficit/hyperactivity disorder (ADHD) diagnosis and, based on limited evidence, diagnosis of intellectual disability. No study to date has examined the association between relative age and diagnosis of depression. OBJECTIVE: To estimate the associations with intellectual disability and ADHD and investigate a potential novel association between relative age and childhood depression. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study of 1 042 106 children aged 4 to 15 years used electronic record data collected before January 3, 2017, from more than 700 general practices contributing to the UK Clinical Practice Research Datalink. Multivariable Cox proportional hazards regression modeling was used to explore the association between relative age and the incidence of intellectual disability, ADHD, and depression before age 16 years. Data were analyzed between July 2017 and January 2019. EXPOSURES: Relative age within school year determined by month of birth and categorized into four 3-month groups. MAIN OUTCOMES AND MEASURES: Intellectual disability, ADHD, and depression. RESULTS: In the total cohort of 1 042 106 children, 532 876 were male (51.1%) and the median age at study entry was 4.0 years (interquartile range, 4.0-5.0). There was evidence that being born in the last quarter of the school year (ie, being the youngest group in a school year) was associated with diagnosis of intellectual disability (adjusted hazard ratio [aHR], 1.30; 95% CI, 1.18-1.42), ADHD (aHR, 1.36; 95% CI, 1.28-1.45), and depression (aHR, 1.31; 95% CI, 1.08-1.59) compared with being born in the first quarter. A graded association was seen with intermediate age groups at a smaller increased risk of each diagnosis compared with the oldest group, with aHRs for intellectual disability for those born in the second quarter of 1.06 (95% CI, 0.96-1.17) and for those born in the third quarter of 1.20 (95% CI, 1.09-1.32); aHRs for ADHD for those born in the second quarter of 1.15 (95% CI, 1.08-1.23) and for those born in the third quarter of 1.31 (95% CI, 1.23-1.40); and aHRs for depression for those born in the second quarter of 1.05 (95% CI, 0.85-1.29) and for those born in the third quarter of 1.13 (95% CI, 0.92-1.38). CONCLUSIONS AND RELEVANCE: In this study, relative youth status in the school year is associated with an increased risk of diagnosis of ADHD, intellectual disability, and depression in childhood. Further research into clinical and policy interventions to minimize these associations appears to be needed

Foot kinematics in patients with two patterns of pathological plantar hyperkeratosis

Background: The Root paradigm of foot function continues to underpin the majority of clinical foot biomechanics practice and foot orthotic therapy. There are great number of assumptions in this popular paradigm, most of which have not been thoroughly tested. One component supposes that patterns of plantar pressure and associated hyperkeratosis lesions should be associated with distinct rearfoot, mid foot, first metatarsal and hallux kinematic patterns. Our aim was to investigate the extent to which this was true. Methods: Twenty-seven subjects with planter pathological hyperkeratosis were recruited into one of two groups. Group 1 displayed pathological plantar hyperkeratosis only under metatarsal heads 2, 3 and 4 (n = 14). Group 2 displayed pathological plantar hyperkeratosis only under the 1st and 5th metatarsal heads (n = 13). Foot kinematics were measured using reflective markers on the leg, heel, midfoot, first metatarsal and hallux. Results: The kinematic data failed to identify distinct differences between these two groups of subjects, however there were several subtle (generally <3°) differences in kinematic data between these groups. Group 1 displayed a less everted heel, a less abducted heel and a more plantarflexed heel compared to group 2, which is contrary to the Root paradigm. Conclusions: There was some evidence of small differences between planter pathological hyperkeratosis groups. Nevertheless, there was too much similarity between the kinematic data displayed in each group to classify them as distinct foot types as the current clinical paradigm proposes

Movement of the human foot in 100 pain free individuals aged 18–45 : implications for understanding normal foot function

Background: Understanding motion in the normal healthy foot is a prerequisite for understanding the effects of pathology and thereafter setting targets for interventions. Quality foot kinematic data from healthy feet will also assist the development of high quality and research based clinical models of foot biomechanics. To address gaps in the current literature we aimed to describe 3D foot kinematics using a 5 segment foot model in a population of 100 pain free individuals. Methods: Kinematics of the leg, calcaneus, midfoot, medial and lateral forefoot and hallux were measured in 100 self reported healthy and pain free individuals during walking. Descriptive statistics were used to characterise foot movements. Contributions from different foot segments to the total motion in each plane were also derived to explore functional roles of different parts of the foot. Results: Foot segments demonstrated greatest motion in the sagittal plane, but large ranges of movement in all planes. All foot segments demonstrated movement throughout gait, though least motion was observed between the midfoot and calcaneus. There was inconsistent evidence of movement coupling between joints. There were clear differences in motion data compared to foot segment models reported in the literature. Conclusions: The data reveal the foot is a multiarticular structure, movements are complex, show incomplete evidence of coupling, and vary person to person. The data provide a useful reference data set against which future experimental data can be compared and may provide the basis for conceptual models of foot function based on data rather than anecdotal observations

Antecedents and consequences of effectuation and causation in the international new venture creation process

The selection of the entry mode in an international market is of key importance for the venture. A process-based perspective on entry mode selection can add to the International Business and International Entrepreneurship literature. Framing the international market entry as an entrepreneurial process, this paper analyzes the antecedents and consequences of causation and effectuation in the entry mode selection. For the analysis, regression-based techniques were used on a sample of 65 gazelles. The results indicate that experienced entrepreneurs tend to apply effectuation rather than causation, while uncertainty does not have a systematic influence. Entrepreneurs using causation-based international new venture creation processes tend to engage in export-type entry modes, while effectuation-based international new venture creation processes do not predetermine the entry mod

The instantaneous helical axis of the subtalar and talocrural joints: a non-invasive in vivo dynamic study

<p>Abstract</p> <p>Background</p> <p>An understanding of rear-foot (talocrural and subtalar joints) kinematics is critical for diagnosing foot pathologies, designing total ankle implants, treating rear-foot injuries and quantifying gait abnormalities. The majority of kinematic data available have been acquired through static cadaver work or passive <it>in vivo </it>studies. The applicability of these data to dynamic <it>in vivo </it>situations remains unknown. Thus, the purpose of this study was to fully quantify subtalar, talocrural and calcaneal-tibial <it>in vivo </it>kinematics in terms of the instantaneous helical axis (IHA) in twenty-five healthy ankles during a volitional activity that simulated single-leg toe-raises with partial-weight support, requiring active muscle control.</p> <p>Methods</p> <p>Subjects were each placed supine in a 1.5 T MRI and asked to repeat this simulated toe-raise while a full sagittal-cine-phase contrast (dynamic) MRI dataset was acquired. From the cine-phase contrast velocity a full kinematic description for each joint was derived.</p> <p>Results</p> <p>Nearly all motion quantified at the calcaneal-tibial joint was attributable to the talocrural joint. The subtalar IHA orientation and position were highly variable; whereas, the talocrural IHA orientation and position were extremely consistent.</p> <p>Conclusion</p> <p>The talocrural was well described by the IHA and could be modeled as a fixed-hinge joint, whereas the subtalar could not be.</p

High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.National Institutes of Health (U.S.) (MH095096)National Institutes of Health (U.S.) (R01 GM089652

Studies of the Decay B+- -> D_CP K+-

We report studies of the decay B+- -> D_CP K+-, where D_CP denotes neutral D mesons that decay to CP eigenstates. The analysis is based on a 29.1/fb data sample of collected at the \Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e+ e- storage ring. Ratios of branching fractions of Cabibbo-suppressed to Cabibbo-favored processes involving D_CP are determined to be B(B- -> D_1 K-)/B(B- -> D_1 pi-)=0.125 +- 0.036 +- 0.010 and B(B- -> D_2 K-)/B(B- -> D_2 pi-)=0.119 +- 0.028 +- 0.006, where indices 1 and 2 represent the CP=+1 and CP=-1 eigenstates of the D0 - anti D0 system, respectively. We also extract the partial rate asymmetries for B+- -> D_CP K+-, finding A_1 = 0.29 +- 0.26 +- 0.05 and A_2 = -0.22 +- 0.24 +- 0.04.Comment: 10 pages, 2 figures, submitted to Physical Review Letter

Distribution and correlates of plantar hyperkeratotic lesions in older people

<p>Abstract</p> <p>Background</p> <p>Plantar hyperkeratotic lesions are common in older people and are associated with pain, mobility impairment and functional limitations. However, little has been documented in relation to the frequency or distribution of these lesions. The aim of this study was to document the occurrence of plantar hyperkeratotic lesions and the patterns in which they occur in a random sample of older people.</p> <p>Methods</p> <p>A medical history questionnaire was administered to a random sample of 301 people living independently in the community (117 men, 184 women) aged between 70 and 95 years (mean 77.2, SD 4.9), who also underwent a clinical assessment of foot problems, including the documentation of plantar lesion locations, toe deformities and the presence and severity of hallux valgus.</p> <p>Results</p> <p>Of the 301 participants, 180 (60%) had at least one plantar hyperkeratotic lesion. Those with plantar lesions were more likely to be female (χ²= 18.75, <it>p </it>< 0.01; OR = 2.86), have moderate to severe hallux valgus (χ²= 6.15, <it>p </it>< 0.02; OR = 2.95), a larger dorsiflexion range of motion at the ankle (39.4 ± 9.3 <it>vs </it>36.3 ± 8.4°; <it>t </it>= 2.68, <it>df </it>= 286, <it>p </it>< 0.01), and spent more time on their feet at home (5.1 ± 1.0 <it>vs </it>4.8 ± 1.3 hours, <it>t </it>= -2.46, <it>df </it>= 299, <it>p </it>= 0.01). No associations were found between the presence of plantar lesions and body mass index, obesity, foot posture, dominant foot or forefoot pain. A total of 53 different lesions patterns were observed, with the most common lesion pattern being "roll-off" hyperkeratosis on the medial aspect of the 1^stmetatarsophalangeal joint (MPJ), accounting for 12% of all lesion patterns. "Roll-off" lesions under the 1^stMPJ and interphalangeal joint were significantly associated with moderate to severe hallux valgus (<it>p </it>< 0.05), whereas lesions under the central MPJs were significantly associated with deformity of the corresponding lesser toe (<it>p </it>< 0.05). Factor analysis indicated that 62% of lesion patterns could be grouped under three broad categories, relating to medial, central and lateral locations.</p> <p>Conclusion</p> <p>Plantar hyperkeratotic lesions affect 60% of older people and are associated with female gender, hallux valgus, toe deformity, increased ankle flexibility and time spent on feet, but are not associated with obesity, limb dominance, forefoot pain or foot posture. Although there are a wide range of lesion distribution patterns, most can be classified into medial, central or lateral groups. Further research is required to determine whether these patterns are related to the dynamic function of the foot or other factors such as foot pathology or morphology.</p

Plague Circulation and Population Genetics of the Reservoir Rattus rattus: The Influence of Topographic Relief on the Distribution of the Disease within the Madagascan Focus.

International audienceBACKGROUND: Landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. Plague (Yersinia pestis infection) is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in Africa. Human seroprevalence data for the major plague focus of Madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. Plague is primarily a disease of rodents. We therefore investigated the relationship between disease distribution and the population genetic structure of the black rat, Rattus rattus, the main reservoir of plague in Madagascar. METHODOLOGYPRINCIPAL FINDINGS: We conducted a comparative study of plague seroprevalence and genetic structure (15 microsatellite markers) in rat populations from four geographic areas differing in topology, each covering about 150-200 km(2) within the Madagascan plague focus. The seroprevalence levels in the rat populations mimicked those previously reported for humans. As expected, rat populations clearly displayed a more marked genetic structure with increasing relief. However, the relationship between seroprevalence data and genetic structure differs between areas, suggesting that plague distribution is not related everywhere to the effective dispersal of rats. CONCLUSIONSSIGNIFICANCE: Genetic diversity estimates suggested that plague epizootics had only a weak impact on rat population sizes. In the highlands of Madagascar, plague dissemination cannot be accounted for solely by the effective dispersal of the reservoir. Human social activities may also be involved in spreading the disease in rat and human populations