Five-minute Apgar score and educational outcomes: retrospective cohort study of 751 369 children

Background: The Apgar score is used worldwide for assessing the clinical condition and short-term prognosis of newborn infants. Evidence for a relationship with long-term educational outcomes is conflicting. We investigated whether Apgar score at 5 min after birth was associated with additional support needs (ASN) and educational attainment. Methods: Data on pregnancy, delivery and later educational outcomes for children attending Scottish schools between 2006 and 2011 were collated by linking individual-level data from national educational and maternity databases. The relationship between Apgar score and overall ASN, type-specific ASN and educational attainment was assessed using binary, multinomial and generalised ordinal logistic regression models, respectively. Missing covariate data were imputed. Results: Of the 751 369 children eligible, 9741 (1.3%) had a low or intermediate Apgar score and 49 962 (6.6%) had ASN. Low Apgar score was independently associated with overall ASN status (adjusted OR for Apgar ≤3, OR 1.52 95% CI 1.35 to 1.70), as well as ASN due to cognitive (OR 1.26, 95% CI 1.09 to 1.47), sensory (OR 2.49 95% CI 1.66 to 3.73) and motor (OR 3.57, 95% CI 2.86 to 4.47) impairments. There was a dose-response relationship between Apgar score and overall ASN status: of those scoring 0–3, 10.1% had ASN, compared with 9.1% of those scoring 4–7 and 6.6% of those scoring 7–10. A low Apgar score was associated with lower educational attainment, but this was not robust to adjustment for confounders. Conclusions: Apgar scores are associated with long-term as well as short-term prognoses, and with educational as well as clinical outcomes at the population level

Removing Barriers for Seniors at Transit Stops and Stations and the Potential for Transit Ridership Growth

The focus of this study was on the identification of barriers to transit use by older adults and on testing improvements and interventions that hold promise for increasing ridership. Baseline measurements of ridership and perceptions of transit use were gathered at two study sites in the San Francisco Bay Area. Among the challenges and barriers to transit use by older adults are lack of information about service and schedules; waiting outdoors in uncomfortable station areas; lack of security and perception of crime; inconvenient pedestrian access to stops; and lack of training for drivers in the needs of older riders. The report includes a summary of surveys of seniors' perspectives, results of two travel training interventions, and a handbook to be used by transit and senior services agencies

Identification of T-cell receptor a-chain genes in the chicken

T-cell receptor (TCR) -chain (TCR) and ß-chain (TCRß) genes are well characterized in mammals, while only TCRß genes have been identified in other vertebrates. To identify avian TCR genes, we used monoclonal anti-CD3 antibodies to isolate chicken TCR for peptide sequence analysis. Degenerate oligonucleotide probes were then used to isolate a candidate TCR cDNA clone that hybridized with a 1.7-kb mRNA species present only in ß T cells and in tissues populated by these cells. Southern blot analysis revealed gene rearrangement in thymocytes and ß T-cell lines. The TCR cDNA candidate encoded an openreading frame of 275 amino acids, the predicted variable (V)-, joining (J)-, and constant (C)-region amino acid sequences of which shared 40%, 60%, and 25% homology with corresponding mammalian sequences. A single C gene and 25 V genes were identified by using region-specific probes. The V cDNA probe isolated from a Vß1+ cell line reacted with transcripts from one of five Vß2+ cell lines, suggesting shared use of V genes by Vß1+ and Vß2+ T cells and the existence of other V gene families. A genomic V sequence was flanked by classical recombination signal sequences but, unlike previously defined V genes, the leader and V region were encoded by a single exon. The data indicate evolutionary conservation of the basic TCR gene structure in birds and mammal

Month of Conception and Learning Disabilities: A Record-Linkage Study of 801,592 Children.

Learning disabilities have profound, long-lasting health sequelae. Affected children born over the course of 1 year in the United States of America generated an estimated lifetime cost of $51.2 billion. Results from some studies have suggested that autistic spectrum disorder may vary by season of birth, but there have been few studies in which investigators examined whether this is also true of other causes of learning disabilities. We undertook Scotland-wide record linkage of education (annual pupil census) and maternity (Scottish Morbidity Record 02) databases for 801,592 singleton children attending Scottish schools in 2006-2011. We modeled monthly rates using principal sine and cosine transformations of the month number and demonstrated cyclicity in the percentage of children with special educational needs. Rates were highest among children conceived in the first quarter of the year (January-March) and lowest among those conceived in the third (July-September) (8.9% vs 7.6%; P < 0.001). Seasonal variations were specific to autistic spectrum disorder, intellectual disabilities, and learning difficulties (e.g., dyslexia) and were absent for sensory or motor/physical impairments and mental, physical, or communication problems. Seasonality accounted for 11.4% (95% confidence interval: 9.0, 13.7) of all cases. Some biologically plausible causes of this variation, such as infection and maternal vitamin D levels, are potentially amendable to intervention.Scottish Collaboration for Public Health Research & PolicyThis is the author accepted manuscript. The final version is available from Oxford University Press via http://dx.doi.org/10.1093/aje/kww09

Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren : A population-based record linkage cohort study

Data Availability: All health data are owned by the Information Services Division of NHS National Services Scotland (https://www.isdscotland.org), and all education data are owned by the ScotXed Unit, which is part of the Educational Analytical Services Division within the Learning and Justice Directorate of the Scottish Government (www2.gov.scot/Topics/Statistics/ScotXed). Interested researchers may apply at these sites for data access. Funding: The study was sponsored by Health Data Research UK (www.hdruk.ac.uk) (grant reference number MR/S003800/1) (MF) which is a joint investment led by the Medical Research Council, together with the National Institute for Health Research (England), the Chief Scientist Office (Scotland), Health and Care Research Wales, Health and Social Care Research and Development Division (Public Health Agency, Northern Ireland), the Engineering and Physical Sciences Research Council, the Economic and Social Research Council, the British Heart Foundation and Wellcome. There was additional funding from the Carnegie Trust for the Universities of Scotland (grant reference VAC007974) (EES) and an MRC Mental Health Data Pathfinder grant (grant reference MC_PC_17217) (MF, JPP, DK, SC).Peer reviewedPublisher PD

Age-Associated mRNA and miRNA Expression Changes in the Blood-Brain Barrier

Functional and structural age-associated changes in the blood-brain barrier (BBB) may affect the neurovascular unit and contribute to the onset and progression of age-associated neurodegenerative pathologies, including Alzheimer’s disease. The current study interrogated the RNA profile of the BBB in an ageing human autopsy brain cohort and an ageing mouse model using combined laser capture microdissection and expression profiling. Only 12 overlapping genes were altered in the same direction in the BBB of both ageing human and mouse cohorts. These included genes with roles in regulating vascular tone, tight junction protein expression and cell adhesion, all processes prone to dysregulation with advancing age. Integrated mRNA and miRNA network and pathway enrichment analysis of the datasets identified 15 overlapping miRNAs that showed altered expression. In addition to targeting genes related to DNA binding and/or autophagy, many of the miRNAs identified play a role in age-relevant processes, including BBB dysfunction and regulating the neuroinflammatory response. Future studies have the potential to develop targeted therapeutic approaches against these candidates to prevent vascular dysfunction in the ageing brain

The prevalence and incidence of mental ill-health in adults with autism and intellectual disabilities

The prevalence, and incidence, of mental ill-health in adults with intellectual disabilities and autism were compared with the whole population with intellectual disabilities, and with controls, matched individually for age, gender, ability-level, and Down syndrome. Although the adults with autism had a higher point prevalence of problem behaviours compared with the whole adult population with intellectual disabilities, compared with individually matched controls there was no difference in prevalence, or incidence of either problem behaviours or other mental ill-health. Adults with autism who had problem behaviours were less likely to recover over a two-year period than were their matched controls. Apparent differences in rates of mental ill-health are accounted for by factors other than autism, including Down syndrome and ability level

Inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 2 perturbs 26S proteasome-addicted neoplastic progression

Dependence on the 26S proteasome is an Achilles' heel for triple-negative breast cancer (TNBC) and multiple myeloma (MM). The therapeutic proteasome inhibitor, bortezomib, successfully targets MM but often leads to drug-resistant disease relapse and fails in breast cancer. Here we show that a 26S proteasome-regulating kinase, DYRK2, is a therapeutic target for both MM and TNBC. Genome editing or small-molecule mediated inhibition of DYRK2 significantly reduces 26S proteasome activity, bypasses bortezomib resistance, and dramatically delays in vivo tumor growth in MM and TNBC thereby promoting survival. We further characterized the ability of LDN192960, a potent and selective DYRK2-inhibitor, to alleviate tumor burden in vivo. The drug docks into the active site of DYRK2 and partially inhibits all 3 core peptidase activities of the proteasome. Our results suggest that targeting 26S proteasome regulators will pave the way for therapeutic strategies in MM and TNBC

Archive of Darkness:William Kentridge's Black Box/Chambre Noire

Situating itself in histories of cinema and installation art, William Kentridge's Black Box/Chambre Noire (2005) raises questions about screens, exhibition space, site-specificity and spectatorship. Through his timely intervention in a debate on Germany’s colonial past, Kentridge’s postcolonial art has contributed to the recognition and remembrance of a forgotten, colonial genocide. This article argues that, by transposing his signature technique of drawings for projection onto a new set of media, Kentridge explores how and what we can know through cinematic projection in the white cube. In particular, his metaphor of the illuminated shadow enables him to animate archival fragments as shadows and silhouettes. By creating a multi-directional archive, Black Box enables an affective engagement with the spectres of colonialism and provides a forum for the calibration of moral questions around reparation, reconciliation and forgiveness