Does frequent residential mobility in early years affect the uptake and timeliness of routine immunisations? An anonymised cohort study

Background: There are conflicting findings regarding the impact of residential mobility on immunisationstatus. Our aim was to determine whether there was any association between residential mobility andtake up of immunisations and whether they were delayed in administration. Methods: We carried out a cohort analysis of children born in Wales, UK. Uptake and time of immunisationwere collected electronically. We defined frequent movers as those who had moved: 2 or more times inthe period prior to the final scheduled on-time date (4 months) for 5 in 1 vaccinations; and 3 or moretimes in the period prior to the final scheduled on-time date (12 months) for MMR, pneumococcal andmeningitis C vaccinations. We defined immunisations due at 2–4 months delayed if they had not beengiven by age 1; and those due at 12–13 months as delayed if they had not been given by age 2. Results: Uptake rates of routine immunisations and whether they were given within the specified time-frame were high for both groups. There was no increased risk (odds ratios (95% confidence intervals)between frequent movers compared to non-movers for the uptake of: primary MMR 1.08 (0.88–1.32);booster Meningitis C 1.65 (0.93–2.92); booster pneumococcal 1.60 (0.59–4.31); primary 5 in 1 1.28(0.92–1.78); and timeliness: primary MMR 0.92 (0.79–1.07); booster Meningitis C 1.26 (0.77–2.07);booster pneumococcal 1.69 (0.23–12.14); and primary 5 in 1 1.04 (0.88–1.23). Discussion: Findings suggest that children who move home frequently are not adversely affected in termsof the uptake of immunisations and whether they were given within a specified timeframe. Both werehigh and may reflect proactive behaviour in the primary healthcare setting to meet Government coveragerates for immunisation

Residential Moving and Preventable Hospitalizations

OBJECTIVES: To investigate the association between moving home in the first year of life and subsequent emergency admissions for potentially preventable hospitalizations. METHODS: We undertook a cohort analysis of linked anonymized data on 237 842 children in the Welsh Electronic Cohort for Children. We included children born in Wales between April 1, 1999 and December 31, 2008. The exposure was the number of residential moves from birth up to 1 year. The main outcome was emergency admissions for potentially preventable hospitalizations (PPH) between the age of 1 and 5 years. RESULTS: After adjustment for confounders, we identified that moving home frequently in the first year of life was associated with an increased risk of emergency PPH between the ages of 1 and 5 when compared with not moving. We found significant differences associated with ≥2 moves for the following: ear, nose, and throat infections (incidence risk ratio [IRR], 1.44; 95% confidence interval [CI], 1.29–1.61); convulsions/epilepsy (IRR, 1.58; 95% CI, 1.23–2.04); injuries (IRR, 1.33; 95% CI, 1.18–1.51); dehydration/gastroenteritis (IRR, 1.51; 95% CI, 1.21–1.88); asthma (IRR, 1.61; 95% CI, 1.19–2.16); influenza/pneumonia (IRR, 1.15; 95% CI, 1.00–1.32); and dental conditions (IRR, 1.30; 95% CI, 1.03–1.64) for ≥1 moves. CONCLUSIONS: Children who move home in the first year of life are at substantially increased risk of emergency admissions for PPH in early childhood. Additional research that focuses on enhancing health and social support services for highly mobile families, educating parents about safety risks, and improving housing quality is warranted

Do Children Who Move Home and School Frequently Have Poorer Educational Outcomes in Their Early Years at School? An Anonymised Cohort Study

Frequent mobility has been linked to poorer educational attainment. We investigated the association between moving home and moving school frequently and the early childhood formal educational achievement. We carried out a cohort analysis of 121,422 children with anonymised linked records. Our exposure measures were: 1) the number of residential moves registered with a health care provider, and 2) number of school moves. Our outcome was the formal educational assessment at age 6–7. Binary regression modeling was used to examine residential moves within the three time periods: 0 – ,1 year; 1 – ,4 years and 4 – ,6 years. School moves were examined from age 4 to age 6. We adjusted for demographics, residential moves at different times, school moves and birth related variables. Children who moved home frequently were more likely not to achieve in formal assessments compared with children not moving. Adjusted odds ratios were significant for 3 or more moves within the time period 1 –,4 years and for any number of residential moves within the time period 4– ,6 years. There was a dose response relationship, with increased odds ratios with increased frequency of residential moves (2 or more moves at 4–,6 years, adjusted odds ratio 1.16 (1.03, 1.29). The most marked effect was seen with frequent school moves where 2 or more moves resulted in an adjusted odds ratio of 2.33 (1.82, 2.98). This is the first study to examine the relationship between residential and school moves in early childhood and the effect on educational attainment. Children experiencing frequent mobility may be disadvantaged and should be closely monitored. Additional educational support services should be afforded to children, particularly those who frequently change school, in order to help them achieve the expected educational standards

Lung Megakaryocytes are Immune Modulatory Cells that Present Antigen to CD4+ T cells.

Although platelets are the cellular mediators of thrombosis, they are also immune cells. Platelets interact both directly and indirectly with immune cells, impacting their activation and differentiation, as well as all phases of the immune response. Megakaryocytes (Mks) are the cell source of circulating platelets, and until recently Mks were typically only considered bone marrow–resident (BM-resident) cells. However, platelet-producing Mks also reside in the lung, and lung Mks express greater levels of immune molecules compared with BM Mks. We therefore sought to define the immune functions of lung Mks. Using single-cell RNA sequencing of BM and lung myeloid-enriched cells, we found that lung Mks, which we term MkL, had gene expression patterns that are similar to antigen-presenting cells. This was confirmed using imaging and conventional flow cytometry. The immune phenotype of Mks was plastic and driven by the tissue immune environment, as evidenced by BM Mks having an MkL-like phenotype under the influence of pathogen receptor challenge and lung-associated immune molecules, such as IL-33. Our in vitro and in vivo assays demonstrated that MkL internalized and processed both antigenic proteins and bacterial pathogens. Furthermore, MkL induced CD4+ T cell activation in an MHC II–dependent manner both in vitro and in vivo. These data indicated that MkL had key immune regulatory roles dictated in part by the tissue environment.pre-print236 K

Future research directions on the "elusive" white shark

White sharks, Carcharodon carcharias, are often described as elusive, with little information available due to the logistical difficulties of studying large marine predators that make long-distance migrations across ocean basins. Increased understanding of aggregation patterns, combined with recent advances in technology have, however, facilitated a new breadth of studies revealing fresh insights into the biology and ecology of white sharks. Although we may no longer be able to refer to the white shark as a little-known, elusive species, there remain numerous key questions that warrant investigation and research focus. Although white sharks have separate populations, they seemingly share similar biological and ecological traits across their global distribution. Yet, white shark’s behavior and migratory patterns can widely differ, which makes formalizing similarities across its distribution challenging. Prioritization of research questions is important to maximize limited resources because white sharks are naturally low in abundance and play important regulatory roles in the ecosystem. Here, we consulted 43 white shark experts to identify these issues. The questions listed and developed here provide a global road map for future research on white sharks to advance progress toward key goals that are informed by the needs of the research community and resource managers

Just do it? Investigating the gap between prediction and action in toddlers' causal inferences

Adults’ causal representations integrate information about predictive relations and the possibility of effective intervention; if one event reliably predicts another, adults can represent the possibility that acting to bring about the first event might generate the second. Here we show that although toddlers (mean age: 24 months) readily learn predictive relationships between physically connected events, they do not spontaneously initiate one event to try to generate the second (although older children, mean age: 47 months, do; Experiments 1 and 2). Toddlers succeed only when the events are initiated by a dispositional agent (Experiment 3), when the events involve direct contact between objects (Experiment 4), or when the events are described using causal language (Experiment 5). This suggests that causal language may help children extend their initial causal representations beyond agent-initiated and direct contact events.James S. McDonnell Foundation (Causal Learning Collaborative)American Psychological FoundationTempleton Foundatio

Measurement of the charge asymmetry in dileptonic Decays of top quark pairs in pp collisions at √ s = 7 TeV using the ATLAS detector

A measurement of the top-antitop (tt) charge asymmetry is presented using data corresponding to an integrated luminosity of 4.6 fb −1 of LHC pp collisions at a centre- of-mass energy of 7 TeV collected by the ATLAS detector. Events with two charged leptons, at least two jets and large missing transverse momentum are selected. Two observables are studied: A tt/C, based on the reconstructed tt final state. The asymmetries are measured to be A ll/C = 0.024 +/- 0.015 (stat.) +/- 0.009 (syst.) Att/C = 0.021 +/- 0.025 (stat.) +/- 0.017 (syst.) The measured values are in agreement with the Standard Model predictions

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum

Circulating adipokines are associated with pre-eclampsia in women with type 1 diabetes

AIMS/HYPOTHESIS: The incidence of pre-eclampsia, a multisystem disorder of pregnancy, is fourfold higher in type 1 diabetic than non-diabetic women; it is also increased in women with features of the metabolic syndrome and insulin resistance. In a prospective study of pregnant women with type 1 diabetes, we measured plasma levels of adipokines known to be associated with insulin resistance: leptin, fatty acid binding protein 4 (FABP4), adiponectin (total and high molecular weight [HMW]; also known as high molecular mass), retinol binding protein 4 (RBP4) and resistin and evaluated associations with the subsequent development of pre-eclampsia. METHODS: From an established prospective cohort of pregnant type 1 diabetic women, we studied 23 who developed pre-eclampsia and 24 who remained normotensive; for reference values we included 19 healthy non-diabetic normotensive pregnant women. Plasma adipokines were measured (by ELISA) in stored samples from three study visits (Visit 1 – Visit 3) at different gestational ages (mean ± SD): Visit 1, 12.4 ± 1.8 weeks; Visit 2, 21.7 ± 1.4 weeks; and Visit 3, 31.4 ± 1.5 weeks. All the women were free of microalbuminuria and hypertension at enrolment. All study visits preceded the clinical onset of pre-eclampsia. RESULTS: In all groups, leptin, the ratio of leptin to total or HMW adiponectin, FABP4 concentration, ratio of FABP4 to total or HMW adiponectin and resistin level increased, while total and HMW adiponectin decreased, with gestational age. At Visit 1, (1) in diabetic women with vs without subsequent pre-eclampsia, leptin, ratio of leptin to total or HMW adiponectin, and ratio of FABP4 to total or HMW adiponectin, were increased (p<0.05), while total adiponectin was decreased (p<0.05); and (2) in normotensive diabetic vs non-diabetic women, total adiponectin was elevated (p<0.05). At Visits 2 and 3, (1) the primary findings in the two diabetic groups persisted, and FABP4 also increased in women with subsequent pre-eclampsia (p<0.05); and (2) there were no differences between the two normotensive groups. By logistic regression analyses after covariate adjustment (HbA(1c), insulin kg(−1) day(−1) and gestational age), the best predictive models for pre-eclampsia were as follows: Visit 1, doubling of leptin, OR 9.0 (p<0.01); Visit 2, doubling of the leptin:total adiponectin ratio, OR 3.7 (p<0.05); and Visit 3, doubling of FABP4 concentration, OR 25.1 (p<0.01). The associations were independent of BMI. CONCLUSIONS/INTERPRETATION: As early as the first trimester in type 1 diabetic women, adipokine profiles that suggest insulin resistance are associated with subsequent pre-eclampsia, possibly reflecting maternal characteristics that precede pregnancy. These associations persist in the second and third trimesters, and are independent of BMI. Insulin resistance may predispose women with type 1 diabetes to pre-eclampsia

SRSF1 Haploinsufficiency Is Responsible for a Syndromic Developmental Disorder Associated with Intellectual Disability

SRSF1 (also known as ASF/SF2) is a non-small nuclear ribonucleoprotein (non-snRNP) that belongs to the arginine/serine (R/S) domain family. It recognizes and binds to mRNA, regulating both constitutive and alternative splicing. The complete loss of this proto-oncogene in mice is embryonically lethal. Through international data sharing, we identified 17 individuals (10 females and 7 males) with a neurodevelopmental disorder (NDD) with heterozygous germline SRSF1 variants, mostly de novo, including three frameshift variants, three nonsense variants, seven missense variants, and two microdeletions within region 17q22 encompassing SRSF1. Only in one family, the de novo origin could not be established. All individuals featured a recurrent phenotype including developmental delay and intellectual disability (DD/ID), hypotonia, neurobehavioral problems, with variable skeletal (66.7%) and cardiac (46%) anomalies. To investigate the functional consequences of SRSF1 variants, we performed in silico structural modeling, developed an in vivo splicing assay in Drosophila, and carried out episignature analysis in blood-derived DNA from affected individuals. We found that all loss-of-function and 5 out of 7 missense variants were pathogenic, leading to a loss of SRSF1 splicing activity in Drosophila, correlating with a detectable and specific DNA methylation episignature. In addition, our orthogonal in silico, in vivo, and epigenetics analyses enabled the separation of clearly pathogenic missense variants from those with uncertain significance. Overall, these results indicated that haploinsufficiency of SRSF1 is responsible for a syndromic NDD with ID due to a partial loss of SRSF1-mediated splicing activity