Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network.

Genes disrupted in schizophrenia may be revealed by de novo mutations in affected persons from otherwise healthy families. Furthermore, during normal brain development, genes are expressed in patterns specific to developmental stage and neuroanatomical structure. We identified de novo mutations in persons with schizophrenia and then mapped the responsible genes onto transcriptome profiles of normal human brain tissues from age 13 weeks gestation to adulthood. In the dorsolateral and ventrolateral prefrontal cortex during fetal development, genes harboring damaging de novo mutations in schizophrenia formed a network significantly enriched for transcriptional coexpression and protein interaction. The 50 genes in the network function in neuronal migration, synaptic transmission, signaling, transcriptional regulation, and transport. These results suggest that disruptions of fetal prefrontal cortical neurogenesis are critical to the pathophysiology of schizophrenia. These results also support the feasibility of integrating genomic and transcriptome analyses to map critical neurodevelopmental processes in time and space in the brain.

On the formation of phosphorous polycyclic aromatics hydrocarbons (PAPHs) in astrophysical environments.

The formation of phosphorous-containing polycyclic aromatic hydrocarbons (PAPHs) in astrophysical contexts is proposed and analyzed by means of computational methods [B3LYP-D3BJ/ma-def2-TZVPP, MP2-F12, CCSD-F12b and CCSD(T)-F12b levels of theory]. A "bottom-up" approach based on a radical-neutral reaction scheme between acetylene (C2H2) and the CP radical was used investigating: (a) the synthesis of the first PAPH (C5H5P) "phosphinine"; (b) PAPH growth by addition of C2H2 to the C5H4P radical; (c) PAPH synthesis by addition reactions of one CP radical and nC2H2 to a neutral PAH. Results show: (I) the formation of the phosphinine radical has a strong thermodynamic tendency (-133.3 kcal mol-1) and kinetic barriers ≤5.4 kcal mol-1; (II) PAPH growth by nC2H2 addition on the radical phosphinine easily and exothermically produces radicals (1a- or 1-phospha-naphtalenes with kinetic barriers ≤7.1 kcal mol-1 and reaction free energies ≤-102.5 kcal mol-1); (III) the addition of a single CP + nC2H2 to a neutral benzene generates a complex chemistry where the main product is 2-phospha-naphtalene; (IV) because of the CP radical character, its barrierless addition to a PAH produces a resonant stabilized PAPH, becoming excellent candidates for addition reactions with neutral or radical hydrocarbons and PAHs; (V) the same energy trend between all four levels of theory continues a well-calibrated computational protocol to analyze complex organic reactions with astrochemical interest using electronic structure theory.

Insights into bilaterian evolution from three spiralian genomes.

Current genomic perspectives on animal diversity neglect two prominent phyla, the molluscs and annelids, that together account for nearly one-third of known marine species and are important both ecologically and as experimental systems in classical embryology. Here we describe the draft genomes of the owl limpet (Lottia gigantea), a marine polychaete (Capitella teleta) and a freshwater leech (Helobdella robusta), and compare them with other animal genomes to investigate the origin and diversification of bilaterians from a genomic perspective. We find that the genome organization, gene structure and functional content of these species are more similar to those of some invertebrate deuterostome genomes (for example, amphioxus and sea urchin) than those of other protostomes that have been sequenced to date (flies, nematodes and flatworms). The conservation of these genomic features enables us to expand the inventory of genes present in the last common bilaterian ancestor, establish the tripartite diversification of bilaterians using multiple genomic characteristics and identify ancient conserved long- and short-range genetic linkages across metazoans. Superimposed on this broadly conserved pan-bilaterian background we find examples of lineage-specific genome evolution, including varying rates of rearrangement, intron gain and loss, expansions and contractions of gene families, and the evolution of clade-specific genes that produce the unique content of each genome.

Predicting writing development in dual language instructional contexts: exploring cross-linguistic relationships.

This study examined whether decoding and linguistic comprehension abilities, broadly defined by the Simple View of Reading, in grade 1 each uniquely predicted the grade 6 writing performance of English-speaking children (n = 76) who were educated bilingually in both English their first language and French, a second language. Prediction was made from (1) English to English; (2) French to French; and (3) English to French. Results showed that both decoding and linguistic comprehension scores predicted writing accuracy but rarely predicted persuasive writing. Within the linguistic comprehension cluster of tests, Formulating Sentences was a strong consistent within- and between-language predictor of writing accuracy. In practical terms, the present results indicate that early screening for later writing ability using measures of sentence formulation early in students' schooling, in their L1 or L2, can provide greatest predictive power and allow teachers to differentiate instruction in the primary grades. Theoretically, the present results argue that there are correlations between reading-related abilities and writing abilities not only within the same language but also across languages, adding to the growing body of evidence for facilitative cross-linguistic relationships between bilinguals' developing languages.

Perimortem trauma in King Richard III: a skeletal analysis.

BACKGROUND: Richard III was the last king of England to die in battle, but how he died is unknown. On Sept 4, 2012, a skeleton was excavated in Leicester that was identified as Richard. We investigated the trauma to the skeleton with modern forensic techniques, such as conventional CT and micro-CT scanning, to characterise the injuries and establish the probable cause of death. METHODS: We assessed age and sex through direct analysis of the skeleton and from CT images. All bones were examined under direct light and multi-spectral illumination. We then scanned the skeleton with whole-body post-mortem CT. We subsequently examined bones with identified injuries with micro-CT. We deemed that trauma was perimortem when we recorded no evidence of healing and when breakage characteristics were typical of fresh bone. We used previous data to identify the weapons responsible for the recorded injuries. FINDINGS: The skeleton was that of an adult man with a gracile build and severe scoliosis of the thoracic spine. Standard anthropological age estimation techniques based on dry bone analysis gave an age range between 20s and 30s. Standard post-mortem CT methods were used to assess rib end morphology, auricular surfaces, pubic symphyseal face, and cranial sutures, to produce a multifactorial narrower age range estimation of 30-34 years. We identified nine perimortem injuries to the skull and two to the postcranial skeleton. We identified no healed injuries. The injuries were consistent with those created by weapons from the later medieval period. We could not identify the specific order of the injuries, because they were all distinct, with no overlapping wounds. Three of the injuries-two to the inferior cranium and one to the pelvis-could have been fatal. INTERPRETATION: The wounds to the skull suggest that Richard was not wearing a helmet, although the absence of defensive wounds on his arms and hands suggests he was still otherwise armoured. Therefore, the potentially fatal pelvis injury was probably received post mortem, meaning that the most likely injuries to have caused his death are the two to the inferior cranium. FUNDING: The University of Leicester.

Whole-body vibration and occupational physical performance: a review.

INTRODUCTION: In the occupational environment, there are a considerable number of stressors that can affect physical performance in job tasks. Whole-body vibration (WBV), which arises from vehicle transit, is one such stressor that has been demonstrated to alter human function in several ways. This study identifies the known physical changes to human function which result from WBV, to comment on changes which may translate to performance in physically demanding occupational tasks. METHODS: A systematic review is performed on the literature relating to changes in the neuromuscular, physiological and biomechanical properties of the human body, when exposed to WBV. Selection criteria are constructed to synthesise articles which strictly relate to in-vehicle WBV and physical responses. RESULTS: In total, 29 articles were identified which satisfied the criteria for inclusion. A range of physical responses produced from WBV are presented; however, little consistency exists in study design and the responses reported. DISCUSSION: Given the inconsistency in the reported responses, the precise changes to human function remain unknown. However, there is sufficient evidence to warrant the design of studies which investigate occupationally relevant physical performance changes following WBV.

Social comparison, competition and teacher-student relationships in junior high school classrooms predicts bullying and victimization.

This cross-sectional research examines how social comparison, competition and teacher-student relationships as classroom characteristics are associated with bullying and victimization among junior high school students in grades 7 and 8 in Canada. The study tests a conceptual model of youth outcomes that highlights the importance of modeling the effects of teaching practices as proximal structural conditions at the classroom level (N = 38) that affect bullying outcomes at the individual level (N = 687). Results of Hierarchal linear modeling (HLM) revealed significant classroom-level effects in that increased social comparison, competition and teacher-student relationships were related to bullying and victimization. An interaction for teacher-student relationships and gender also emerged. These findings may guide future intervention programs for junior high schools that focus on enhancing cooperation and pro-social behavior in classrooms. The findings could also inform programs that focus on building strong relationships between students and teachers to help prevent bullying and victimization, particularly among boys.

History and Nomenclature of Multistrand Repairs in Digital Flexor Tendons.

Multistrand core suture repairs have become the mainstay of digital flexor tendon repair in recent decades. Here we briefly describe the history of the development of these multistrand repair methods and their correct nomenclature. A historical account, their evolution, the correct use of nomenclature, and some technical points are reviewed.

Technology-Delivered Mental Health Interventions for People Living with HIV/AIDS (PLWHA): a Review of Recent Advances.

HIV/AIDS infection and psychiatric diagnoses are closely linked, with an estimated 50 % of HIV-infected individuals diagnosed with co-occurring mental health disorders. Mental health disorders have been shown to be associated with HIV acquisition as well as poor treatment outcomes for those infected with HIV. Therefore, behavioral interventions to improve HIV/AIDS health outcomes have included interventions addressing mental health co-morbidities, such as depression and anxiety, and the use of technology to facilitate such intervention is growing. The current review focuses on research published between January 2011 and April 2015, exploring technology-based interventions aimed to improve health outcomes among HIV/AIDS individuals with co-occurring mental health symptoms. Technologies identified in this review included telephone-delivered and computer-delivered interventions. Despite rapid advances in technology use in the medical professions, particularly in the area of psychiatric treatment, little has been translated into the area of mental health research in the context of HIV disease. This review reveals that the widespread dissemination of various technologies, especially technologies facilitating access to care among vulnerable and marginalized populations, may be a necessary way to offer evidence-based mental health interventions to HIV/AIDS populations in need.

Maximal and sub-maximal functional lifting performance at different platform heights.

Introducing valid physical employment tests requires identifying and developing a small number of practical tests that provide broad coverage of physical performance across the full range of job tasks. This study investigated discrete lifting performance across various platform heights reflective of common military lifting tasks. Sixteen Australian Army personnel performed a discrete lifting assessment to maximal lifting capacity (MLC) and maximal acceptable weight of lift (MAWL) at four platform heights between 1.30 and 1.70 m. There were strong correlations between platform height and normalised lifting performance for MLC (R(2) = 0.76 ± 0.18, p < 0.05) and MAWL (R(2) = 0.73 ± 0.21, p < 0.05). The developed relationship allowed prediction of lifting capacity at one platform height based on lifting capacity at any of the three other heights, with a standard error of < 4.5 kg and < 2.0 kg for MLC and MAWL, respectively.

On the relationship between discrete and repetitive lifting performance in military tasks.

Military manual handling requirements range from discrete lifts to continuous and repetitive lifting tasks. For the military to introduce a discrete lifting assessment, the assessment must be predictive of the various submaximum lifting tasks personnel are required to perform. This study investigated the relationship between discrete and repetitive military lifting to assess the validity of implementing a discrete lifting test. Twenty-one soldiers from the Australian Army completed a whole-body box-lifting assessment as a one repetition maximum (1RM) and a series of submaximal lifting repetitions (% 1RM). Performance was measured between the number of lifting repetitions that could be performed at different intensities between 58 and 95% 1RM. A strong curvilinear relationship existed across the entire submaximal lifting range (r = 0.72, p ≤ 0.05). The model developed demonstrated a low predictive error (standard error of the estimate = 7.2% 1RM) with no differences detected in the relationship when comparing individuals of high and low strength. Findings support the use of a discrete functional lifting assessment in providing coverage of a broad range of military lifting tasks. Parallels can be drawn between the trend reported in the current study and weight-training exercises reported in the literature.

The N400 in readers with dyslexia: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to assess whether (i) significant differences exist in the N400 response to lexico-semantic tasks between typically developing (TD) readers and readers with dyslexia, and (ii) whether these differences are moderated by the modality of task presentation (visual vs. auditory), the type of task, age, or opaque orthography (shallow and transparent alphabets vs Chinese morpho-syllabary). Twenty studies were included in the meta-analysis, and the analysis did not demonstrate strong evidence of publication bias. An overall effect size of Hedge's g = 0.66, p < .001, was found between typically developing readers and readers with dyslexia. All moderators were found to be significant; larger effects were associated with visual modality (g = 0.692, p < .001), semantically incongruent sentence tasks (g = 0.948, p < .001), pseudowords/characters tasks (g = 0.971, p < .001), and orthography [Chinese (g = 1.015, p < .001) vs. alphabets (g = 0.539, p < .001)]. Analysis of reaction time showed Hedge's g = 1.613, p < .001. Results suggest that the N400 reliably differentiated between typically developing readers and readers with dyslexia. Implications for future research and practice are discussed.

Contrasting Direct Instruction in Morphological Decoding and Morphological Inquiry-Analysis Interventions in Grade 3 Children With Poor Morphological Awareness.

We report on a school-based randomized control trial study comparing two morphological interventions with untaught controls: one focusing on direct instruction targeting print morphological decoding (direct decoding condition) and the other on inquiry-focused pedagogy using oral morphological analysis (inquiry-analysis condition). We identified 63 Grade 3 children with below-average morphological awareness following screening (from N = 163). This sub-sample showed average pseudoword decoding but poor language and word reading abilities. Following a 13-week supplemental intervention randomized within the 63 children, results showed a statistically significant main effect of intervention on standardized reading vocabulary measures at immediate post-test in the direct decoding condition. Pre-test morphological awareness moderated reading vocabulary effects for the untaught control group. Statistically significant moderation of growth in sentence comprehension at post- by pre-test morphological awareness was also evident in the inquiry-analysis condition. Universal screening for below-average morphological awareness followed by inquiry-based or direct instruction interventions focusing on the meaning dimensions of morphemes may be modestly efficacious for supporting reading vocabulary and sentence comprehension in such at risk learners, potentially aiding school-wide literacy improvement.

The Alabama Coalition for a Healthier Black belt: a proof of concept project.

The Alabama Coalition for a Healthier Black was a demonstration of concept project. This paper is a descriptive and qualitative overview of this 2.5 year project. Limited key project results are reported here. Located in the rural Black Belt region of Alabama this coalition had several key aims: to develop a collaboration between primary care and mental health care through co-location of services; use of video-conferencing capability to provide mental health services more efficiently; enhanced training in rural healthcare; and development of stigma reduction campaigns along with other coalition partner specific initiatives. Co-location and telepsychiatry implementation produced the major challenges and resulting adaptations to original aims. Despite many challenges these new service patterns were put into place and appear to be sustainable.

Home and school interventions aided at-risk students' literacy during Covid-19: a longitudinal analysis.

We examined whether different parent- and teacher-related factors had an effect on at-risk children's reading development during the first six months of the Covid-19 pandemic. Seventy Grade 1 English-speaking Canadian children (28 females, 42 males; M age = 6.60, SD = 0.46) who were at-risk for reading difficulties were administered word and pseudoword reading, nonverbal IQ, and phonological awareness tasks before the school closures (February 2020; Time 1). Reading tasks were administered again when they returned to school in September 2020 (Time 2). In April-May 2020, their parents (n = 70) and teachers (n = 40) filled out a questionnaire on the home literacy environment and the frequency of teaching reading and providing reading materials, respectively. Results of multilevel regression analyses showed that children's reading enjoyment and home learning activities predicted both word and pseudoword reading at Time 2. Differentiation of instruction for struggling readers also predicted children's pseudoword reading at Time 2. These findings reinforce the important role of parents in their children's early reading development particularly when the typical agents of instruction (i.e., teachers) have less time and opportunities to interact with their students because of the pandemic.

The relationship between maximal lifting capacity and maximum acceptable lift in strength-based soldiering tasks.

Psychophysical assessments, such as the maximum acceptable lift, have been used to establish worker capability and set safe load limits for manual handling tasks in occupational settings. However, in military settings, in which task demand is set and capable workers must be selected, subjective measurements are inadequate, and maximal capacity testing must be used to assess lifting capability. The aim of this study was to establish and compare the relationship between maximal lifting capacity and a self-determined tolerable lifting limit, maximum acceptable lift, across a range of military-relevant lifting tasks. Seventy male soldiers (age 23.7 ± 6.1 years) from the Australian Army performed 7 strength-based lifting tasks to determine their maximum lifting capacity and maximum acceptable lift. Comparisons were performed to identify maximum acceptable lift relative to maximum lifting capacity for each individual task. Linear regression was used to identify the relationship across all tasks when the data were pooled. Strong correlations existed between all 7 lifting tasks (rrange = 0.87-0.96, p < 0.05). No differences were found in maximum acceptable lift relative to maximum lifting capacity across all tasks (p = 0.46). When data were pooled, maximum acceptable lift was equal to 84 ± 8% of the maximum lifting capacity. This study is the first to illustrate the strong and consistent relationship between maximum lifting capacity and maximum acceptable lift for multiple single lifting tasks. The relationship developed between these indices may be used to help assess self-selected manual handling capability through occupationally relevant maximal performance tests.

Decoding and comprehension skills mediate the link between a small-group reading programme and English national literacy assessments.

BACKGROUND: Despite the fact that literacy instruction is a main focus of primary education, many children struggle to meet nationally set standards. AIMS: We aimed to test which components of a comprehensive reading programme (ABRACADABRA: https://eur03.safelinks.protection. OUTLOOK: com/?url=https%3A%2F%2Fdoi.org%2F10.1186%2FISRCTN18254678&data=04%7C01%7Cjanet.vousden%40ntu.ac.uk%7C880280e0b00749df855308d94068a0bb%7C8acbc2c5c8ed42c78169ba438a0dbe2f%7C1%7C0%7C637611640381216902%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=%2B4U9sGfofkyCPEY7lWz8n3TPoMOAeJMXyFwdhW6EpUw%3D&reserved=0) mediated the effect of the programme on nationally assessed literacy outcomes. SAMPLE: Following blind allocation, 516 Year 1 pupils from 40 schools were randomized to the programme group, and 908 Year 1 pupils, to a control condition. METHODS: Pupils in the programme completed 20 weeks of instruction in grapheme/phoneme knowledge, decoding, and comprehension. Control children received regular classroom instruction. RESULTS: Children in the programme group were significantly better at these taught skills after the programme finished (effect sizes: grapheme/phoneme knowledge, ß = .33, 95% CI [0.09-0.57]; decoding, ß = .26, 95% CI [0.09-0.43]; and comprehension, ß = .26, 95% CI [0.05-0.47]). Improvements in the programme group's decoding and comprehension skills fully mediated the improvements in national literacy assessments serving as a delayed post-test 12 months after the programme. Programme group pupils were 2.3 (95% CI [1.4-4.1]) times more likely to achieve/exceed the expected standard in reading, and 1.8 (95% CI [1.2-2.6]) times more likely to achieve/exceed the expected standard in writing due to an increase in the trained skills. CONCLUSIONS: These results provide strong evidence that a programme that incorporates decoding and comprehension instruction for typically developing beginning readers improves distal educational outcomes in reading and writing through increasing proficiencies targeted by the reading programme.

Association of the DAT1 genotype with inattentive behavior is mediated by reading ability in a general population sample.

Attention deficit hyperactivity disorder (ADHD) and reading disability (RD) frequently co-occur in the child population and therefore raise the possibility of shared genetic etiology. We used a quantitative trait loci (QTL) approach to assess the involvement of the dopamine transporter (DAT1) gene polymorphism in mediating reading disability and poor attention in a general population sample of primary school children aged 6-11 years in the UK. The potential confounding effects of IQ and chronological age were also investigated. We found an independent association between the homozygous DAT1 10/10 repeat genotype and RD that was not accounted for by the level of ADHD symptoms. This finding suggests that the DAT1 gene polymorphism may influence a common neural mechanism underlying both reading acquisition and ADHD symptoms.

A Commentary on Bowers (2020) and the Role of Phonics Instruction in Reading.

Bowers (2020) reviewed 12 meta-analytic syntheses addressing the effects of phonics instruction, concluding that the evidence is weak to nonexistent in supporting the superiority of systematic phonics to alternative reading methods. We identify five issues that limit Bowers' conclusions: 1. Definition issues; 2. What is the right question? 3. The assumption of "phonics first"; and 4. Simplification of issues around systematic versus explicit phonics. We then go on to consider 5. Empirical issues in the data from meta-analyses, where Bowers misconstrues the positive effects of explicit phonics instruction. We conclude that there is consistent evidence in support of explicitly teaching phonics as part of a comprehensive approach to reading instruction that should be differentiated to individual learner needs. The appropriate question to ask of a 21st science of teaching is not the superiority of phonics versus alternative reading methods, including whole language and balanced literacy, but how best to combine different components of evidence-based reading instruction into an integrated and customized approach that addresses the learning needs of each child.

Feasibility, acceptability, and preliminary impact of telemedicine-administered cognitive behavioral therapy for adherence and depression among African American women living with HIV in the rural South.

Women living with HIV are disproportionally affected by depression and mental healthcare access. A pilot feasibility trial using videoconferencing compared cognitive behavioral therapy for antiretroviral therapy adherence and depression (N = 11) to supportive psychotherapy (N = 11). Participants completed 10-12 weekly therapy sessions and 6-month follow-up. Retention at 6 months was 95 percent. Depression symptoms significantly decreased in both arms; antiretroviral therapy adherence remained high as measured via self-report and Wisepill. Satisfaction with intervention components was high; videoconferencing was highly acceptable and comparable to face-to-face counseling. This study demonstrates the feasibility of telemedicine-administered psychotherapy addressing mental health needs among women living with HIV.