Long term cognitive outcomes of early term (37-38 weeks) and late preterm (34-36 weeks) births: a systematic review

Background: There is a paucity of evidence regarding long-term outcomes of late preterm (34-36 weeks) and early term (37-38 weeks) delivery.  The objective of this systematic review was to assess long-term cognitive outcomes of children born at these gestations. Methods: Four electronic databases (Medline, Embase, clinicaltrials.gov and PsycINFO) were searched.  Last search was 5 th August 2016.  Studies were included if they reported gestational age, IQ measure and the ages assessed.  The protocol was registered with the International prospective register of systematic reviews (PROSPERO Record CRD42015015472).  Two independent reviewers assessed the studies.  Data were abstracted and critical appraisal performed of eligible papers. Results: Of 11,905 potential articles, seven studies reporting on 41,344 children were included.  For early term births, four studies (n = 35,711) consistently showed an increase in cognitive scores for infants born at full term (39-41 weeks) compared to those born at early term (37-38 weeks) with increases for each week of term (difference between 37 and 40 weeks of around 3 IQ points), despite differences in age of testing and method of IQ/cognitive testing.  Four studies (n = 5644) reporting childhood cognitive outcomes of late preterm births (34 - 36 weeks) also differed in study design (cohort and case control); age of testing; and method of IQ testing, and found no differences in outcomes between late preterm and term births, although risk of bias was high in included studies. Conclusion:  Children born at 39-41 weeks have higher cognitive outcome scores compared to those born at early term (37-38 weeks).  This should be considered when discussing timing of delivery.  For children born late preterm, the data is scarce and when compared to full term (37-42 weeks) did not show any difference in IQ scores

The Lantern Vol. 17, No. 3, Summer 1949

• All the Silver in Taxco • The Fall • Parlor Games • Something There Is • Friday Night • Evening • Checker-Board Country • A Noise • Expected Up In Heaven Today • When Time Has Torn My Youth • Impression of Deathhttps://digitalcommons.ursinus.edu/lantern/1048/thumbnail.jp

Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER statement

Measurements of health indicators are rarely available for every population and period of interest, and available data may not be comparable. The Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) define best reporting practices for studies that calculate health estimates for multiple populations (in time or space) using multiple information sources. Health estimates that fall within the scope of GATHER include all quantitative population-level estimates (including global, regional, national, or subnational estimates) of health indicators, including indicators of health status, incidence and prevalence of diseases, injuries, and disability and functioning; and indicators of health determinants, including health behaviours and health exposures. GATHER comprises a checklist of 18 items that are essential for best reporting practice. A more detailed explanation and elaboration document, describing the interpretation and rationale of each reporting item along with examples of good reporting, is available on the GATHER website

A grounded theory of Internet and social media use by young people who use augmentative and alternative communication (AAC).

PURPOSE: This paper presents a conceptual grounded theory for how young people with a diagnosis of cerebral palsy who use augmentative and alternative communication (AAC), perceive using the Internet and social media. The aims of the research were to understand and contextualise their perceptions of access and use and explore implications for self-representation and social participation; to date literature on this topic is limited. METHOD: A constructivist grounded theory research approach concurrently collected and analysed interview data from 25 participants (aged 14-24 years) who use AAC and additional sources. RESULTS: A conceptual grounded theory was developed around an emergent core category that showed young people who use AAC have a clear desire to use the Internet and social media. This was underpinned by eight supporting categories: reported use, described support, online challenges, access technology, speech generating device (SGD) issues, self-determination, self-representation and online social ties. CONCLUSION: The conceptual grounded theory supports understanding of facilitators and challenges to use of the Internet and social media by young people with a diagnosis of cerebral palsy who use AAC. The grounded theory illustrates how the desire to use the Internet and social media is based upon perceived benefits for enriching social relationships and enhancing opportunities for self-representation and self-determination that are synonymous with identified antecedents for community-based social inclusion. Some of the participants are engaging with the Internet and social media through collaborative practice and the implications for how this phenomenon may impact on orthographic literacy and the personal care workforce are raised

Evaluating the role of pathogenic dementia variants in posterior cortical atrophy

Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to “posterior Alzheimer's disease (AD)” pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against ∼4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE ε4 association, and demonstrate the utility of NeuroX

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Rare coding variants and X-linked loci associated with age at menarche.

More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.UK sponsors (see article for overseas ones): This work made use of data and samples generated by the 1958 Birth Cohort (NCDS). Access to these resources was enabled via the 58READIE Project funded by Wellcome Trust and Medical Research Council (grant numbers WT095219MA and G1001799). A full list of the financial, institutional and personal contributions to the development of the 1958 Birth Cohort Biomedical resource is available at http://www2.le.ac.uk/projects/birthcohort. Genotyping was undertaken as part of the Wellcome Trust Case-Control Consortium (WTCCC) under Wellcome Trust award 076113, and a full list of the investigators who contributed to the generation of the data is available at www.wtccc.org.uk ... The Fenland Study is funded by the Wellcome Trust and the Medical Research Council, as well as by the Support for Science Funding programme and CamStrad. ... SIBS - CRUK ref: C1287/A8459 SEARCH - CRUK ref: A490/A10124 EMBRACE is supported by Cancer Research UK Grants C1287/A10118, C1287/A16563 and C1287/A17523. Genotyping was supported by Cancer Research - UK grant C12292/A11174D and C8197/A16565. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. ... Generation Scotland - Scottish Executive Health Department, Chief Scientist Office, grant number CZD/16/6. Exome array genotyping for GS:SFHS was funded by the Medical Research Council UK. 23andMe - This work was supported in part by NIH Award 2R44HG006981-02 from the National Human Genome Research Institute.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/ncomms875

Discovery of Pulsations from the Pulsar J0205+6449 in SNR 3C 58 with the Fermi Gamma-Ray Space Telescope

We report the discovery of gamma-ray pulsations (> 0.1 GeV) from the young radio and X-ray pulsar PSR J0205+6449 located in the Galactic supernova remnant 3C 58. Data in the gamma-ray band were acquired by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope (formerly GLAST), while the radio rotational ephemeris used to fold gamma-rays was obtained using both the Green Bank Telescope and the Lovell telescope at Jodrell Bank. The light curve consists of two peaks separated by 0.49 +/- 0.01 +/- 0.01 cycles which are aligned with the X-ray peaks. The first gamma-ray peak trails the radio pulse by 0.08 +/- 0.01 +/- 0.01, while its amplitude decreases with increasing energy as for the other gamma-ray pulsars. Spectral analysis of the pulsed gamma-ray emission suggests a simple power law of index -2.1 +/- 0.1 +/- 0.2 with an exponential cut-off at 3.0 +1.1 -0.7 +/- 0.4 GeV. The first uncertainty is statistical and the second is systematic. The integral gamma-ray photon flux above 0.1 GeV is (13.7 +/- 1.4 +/- 3.0) x 10^(-8) /cm2/s, which implies for a distance of 3.2 kpc and assuming a broad fan-like beam a luminosity of 8.3 x 10^(34) ergs/s and an efficiency eta of 0.3%. Finally, we report a 95% upper limit on the flux of 1.7 x 10^(-8) /cm2/s for off-pulse emission from the object.Comment: 7 pages, 1 figure, accepted for publication in Astrophysical Journal Letters, contact author: Damien Paren

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4