Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children.

BACKGROUND: Autism spectrum conditions have a strong genetic component. Atypical sensory sensitivities are one of the core but neglected features of autism spectrum conditions. GABRB3 is a well-characterised candidate gene for autism spectrum conditions. In mice, heterozygous Gabrb3 deletion is associated with increased tactile sensitivity. However, no study has examined if tactile sensitivity is associated with GABRB3 genetic variation in humans. To test this, we conducted two pilot genetic association studies in the general population, analysing two phenotypic measures of tactile sensitivity (a parent-report and a behavioural measure) for association with 43 SNPs in GABRB3. FINDINGS: Across both tactile sensitivity measures, three SNPs (rs11636966, rs8023959 and rs2162241) were nominally associated with both phenotypes, providing a measure of internal validation. Parent-report scores were nominally associated with six SNPs (P <0.05). Behaviourally measured tactile sensitivity was nominally associated with 10 SNPs (three after Bonferroni correction). CONCLUSIONS: This is the first human study to show an association between GABRB3 variation and tactile sensitivity. This provides support for the evidence from animal models implicating the role of GABRB3 variation in the atypical sensory sensitivity in autism spectrum conditions. Future research is underway to directly test this association in cases of autism spectrum conditions.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Development and Evaluation of an Undergraduate Science Communication Module

This paper describes the design and evaluation of an undergraduate final year science communication module for the Science Faculty at the University of East Anglia. The module focuses specifically on science communication and aims to bring an understanding of how science is disseminated to the public. Students on the module are made aware of the models surrounding science communication and investigate how the science culture interfaces with the public. During the module they learn how to adapt science concepts for different audiences and how to talk confidently about science to a lay-audience. Student motivation for module choice centres on the acquisition of transferable skills and students develop these skills through designing, running and evaluating a public outreach event at a school or in a public area. These transferable skills acquired include communication, interaction with different organisations such as museums and science centres, developing understanding of both the needs of different audiences and the importance of time management. They also develop skills relating to self-reflection and how to use this as a tool for future self development. The majority of students completing the module go on to further study, either a PhD, MSc or teacher training. The module can be sustained in its present formed if capped at 40 students, however it is recognised that to increase cohort size, further investment of faculty time and resources would be required

Reconstruction of the repetitive antifreeze glycoprotein genomic loci in the cold-water gadids Boreogadus saida and Microgadus tomcod.

Abstract Antifreeze glycoproteins (AFGPs) are a novel evolutionary innovation in members of the northern cod fish family (Gadidae), crucial in preventing death from inoculative freezing by environmental ice in their frigid Arctic and sub-Arctic habitats. However, the genomic origin and molecular mechanism of evolution of this novel life-saving adaptive genetic trait remained to be definitively determined. To this end, we constructed large insert genomic DNA BAC (bacterial artificial chromosome) libraries for two AFGP-bearing gadids, the high-Arctic polar cod Boreogadus saida and the cold-temperate Atlantic tomcod Microgadus tomcod, to isolate and sequence their AFGP genomic regions for fine resolution evolutionary analyses. The BAC library construction encountered poor cloning efficiency initially, which we resolved by pretreating the agarose-embedded erythrocyte DNA with a cationic detergent, a method that may be of general use to BAC cloning for teleost species and/or where erythrocytes are the source of input DNA. The polar cod BAC library encompassed 92,160 clones with an average insert size of 94.7 kbp, and the Atlantic tomcod library contained 73,728 clones with an average insert size of 89.6 kbp. The genome sizes of B. saida and M. tomcod were estimated by cell flow cytometry to be 836 Mbp and 645 Mbp respectively, thus their BAC libraries have approximately 10- and 9.7-fold genome coverage respectively. The inclusiveness and depth of coverage were empirically confirmed by screening the libraries with three housekeeping genes. The BAC clones that mapped to the AFGP genomic loci of the two gadids were then isolated by screening the BAC libraries with gadid AFGP gene probes. Eight minimal tiling path (MTP) clones were identified for B. saida, sequenced, and assembled. The B. saida AFGP locus reconstruction produced both haplotypes, and the locus comprises three distinct AFGP gene clusters, containing a total of 16 AFGP genes and spanning a combined distance of 512 kbp. The M. tomcod AFGP locus is much smaller at approximately 80 kbp, and contains only three AFGP genes. Fluorescent in situ hybridization with an AFGP gene probe showed the AFGP locus in both species occupies a single chromosomal location. The large AFGP locus with its high gene dosage in B. saida is consistent with its chronically freezing high Arctic habitats, while the small gene family in M. tomcod correlates with its milder habitats in lower latitudes. The results from this study provided the data for fine resolution sequence analyses that would yield insight into the molecular mechanisms and history of gadid AFGP gene evolution driven by northern hemisphere glaciation

The potential for utilising in-hospital glucose measurements to detect individuals at high risk of previously undiagnosed diabetes: retrospective cohort study

Background Many people with undiagnosed diabetes have hyperglycaemia when admitted to hospital. Inpatient hyperglycaemia can be an indication of diabetes mellitus but can also indicate a stress response. This study reports the extent to which an in-hospital maximum observed random glucose measurement is an indicator of the need for in-hospital (or subsequent) HbA1c measurement to look for undiagnosed diabetes. Methods Blood glucose, HbA1c, age and sex were collected for all adults following admission to a UK NHS trust hospital from 1 January 2019 to 31 December 2020. We restricted the analysis to those participants who were registered with a GP practice that uses the trust laboratory and who had at least some tests requested by those practices since 2008. We stratified individuals according to their maximum in-hospital glucose measurement and report the number of these with HbA1c measurement ≥48 mmol/mol (6.5%) prior to the index admission, and during and after admission. We calculated an estimated proportion of individuals in each blood glucose stratum without a follow-up HbA1c who could have undiagnosed diabetes. Results In toal, 764,241 glucose measurements were recorded for 81,763 individuals who were admitted to the Oxford University Hospitals Trust. The median (Q1, Q3) age was 70 (56, 81) years, and 53% were males. Of the population, 70.7% of individuals declared themselves to be of White ethnicity, 3.1% of Asian background, and 1.1% of Black background, with 23.1% unstated. Of those individuals, 22,375 (27.4%) had no previous HbA1c measurement recorded. A total of 1689 individuals had a diabetes-range HbA1c during or after their hospital admission (2.5%) while we estimate an additional 1496 (2.2%) may have undiagnosed diabetes, with the greatest proportion of these having an in-hospital glucose of ≥15 mmol/L. We estimate that the number needed to detect a possible new case of diabetes falls from 16 (in-hospital glucose 8 mmol/L to <9 mmol/L) to 4 (14 mmol/L to <15 mmol/L). Conclusion The number of people who need to be tested to identify an individual who may have diabetes decreases as a testing threshold based on maximum in-hospital glucose concentration increases. Among those with hyperglycaemia and no previous HbA1c measurement in the diabetes range, there appears to be a lack of subsequent HbA1c measurement. This work identifies the potential for integrating the testing and follow-up of people, with apparently unrecognised hospital hyperglycaemia across primary and secondary care

Removing prophylactic antibiotics from pig feed: how does it affect their performance and health?

peer-reviewedBackground Antibiotics (AB) are an important tool to tackle infectious disease in pig farms; however some research indicates that their frequent mis/over-use may contribute to the development of antibiotic resistance and the WHO has declared that this issue should be addressed. Little is known about the long term consequences of withdrawing prophylactic AB from pig feed; hence we aimed to assess its effects on performance and health of pigs from weaning to slaughter. Six batches of 140 pigs each were monitored on a commercial farm through the weaner and finisher stages to slaughter. In-feed antibiotics were not added to the feed for half of the pigs (NOI) and were added in the other half (ABI) within each batch for the whole weaner stage. Individual pigs in both treatments were treated with parenteral administrations if and when detected as ill or lame. Productive performance, parenteral treatments and mortality were recorded on farm and the presence of respiratory disease was recorded at slaughter. Pen was considered the experimental unit. Results ABI pigs showed higher growth (P = 0.018) and feed intake (P = 0.048) than NOI pigs in the first weaner stage but feed efficiency was not affected (NOI = 1.48 vs. ABI = 1.52). Despite an initial reduction in performance, NOI pigs had similar performance in finisher stage (ADG: NOI = 865.4 vs. ABI = 882.2) and minimal effects on health compared to ABI pigs. No difference between treatments was found at the abattoir for the percentage of pigs affected by pneumonia, pleurisy, pleuropneumonia and abscesses (P > 0.05). Mortality rate was not affected by treatment during the weaner stage (P = 0.806) although it tended to be slightly higher in NOI than ABI pigs during the finisher stage (P = 0.099). Parenteral treatments were more frequent in NOI pigs during the weaner stage (P <  0.001) while no difference was recorded during the finisher stage (P = 0.406). Conclusions These data suggest that the removal of prophylactic in-feed antibiotics is possible with only minor reductions in productive performance and health which can be addressed by improved husbandry and use of parenteral antibiotics

Effect of osteoarthritis on the repeatability of patella tendon angle measurement in dogs

Objective: To evaluate the influence of osteoarthritis on the measurement of patella tendon angle (PTA) and determine intraobserver and interobserver variability. Study design: Retrospective clinical study. Sample population: Eighty‐seven mediolateral radiographs that were obtained prior to tibial tuberosity advancement. Methods: Radiographic osteoarthritis was scored by 2 observers using guidelines derived from the International Elbow Working Group Protocol. Patella tendon angle was measured by 3 observers on 3 occasions, with at least 7 days between measurements. The data were statistically analyzed via weighted κ and Kruskal‐Wallis testing. Results: A fair strength of agreement was found among observers scoring osteoarthritis, with the same grades in 48% of radiographs. The intraobserver average bias between PTA measurements 1 and 3 ranged from −0.38° to −0.94°. Interobserver bias in angle measurement ranged from −0.92° to −2.00°. Observer 1 had the narrowest range of PTA differences (12.1°), and observer 3 had the highest range of PTA differences (23.5°). Observer 2 had the lowest mean bias (−0.38°). The mean bias was lowest between observers 1 and 2 (−0.92°) and highest between observers 1 and 3 (−2.0°). The mean intraobserver standard deviation of the PTA measurement differences was 2.90°, and interobserver standard deviation of the PTA measurement differences was 2.26°. The degree of osteoarthritis did not influence PTA measurements or their variability. Conclusion: The current study did not find evidence of an influence of osteoarthritis on PTA or on the repeatability of measurements. Clinical significance: Our findings suggest that osteoarthritis should not affect the radiographic planning for tibial tuberosity advancement surgery. The high variances in PTA measurement in less experienced observers may influence the clinical outcome of surgery

A Randomized, Double-Blinded, Phase II Trial of Gemcitabine and Nab-Paclitaxel Plus Apatorsen or Placebo in Patients with Metastatic Pancreatic Cancer: The RAINIER Trial.

Lessons learnedThe addition of the heat shock protein 27 (Hsp27)-targeting antisense oligonucleotide, apatorsen, to a standard first-line chemotherapy regimen did not result in improved survival in unselected patients with metastatic pancreatic cancer.Findings from this trial hint at the possible prognostic and predictive value of serum Hsp27 that may warrant further investigation.BackgroundThis randomized, double-blinded, phase II trial evaluated the efficacy of gemcitabine/nab-paclitaxel plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 (Hsp27) mRNA, or placebo in patients with metastatic pancreatic cancer.MethodsPatients were randomized 1:1 to Arm A (gemcitabine/nab-paclitaxel plus apatorsen) or Arm B (gemcitabine/nab-paclitaxel plus placebo). Treatment was administered in 28-day cycles, with restaging every 2 cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and on treatment. The primary endpoint was overall survival (OS).ResultsOne hundred thirty-two patients were enrolled, 66 per arm. Cytopenias and fatigue were the most frequent grade 3/4 treatment-related adverse events for both arms. Median progression-free survival (PFS) and OS were 2.7 and 5.3 months, respectively, for arm A, and 3.8 and 6.9 months, respectively, for arm B. Objective response rate was 18% for both arms. Patients with high serum level of Hsp27 represented a poor-prognosis subgroup who may have derived modest benefit from addition of apatorsen.ConclusionAddition of apatorsen to chemotherapy does not improve outcomes in unselected patients with metastatic pancreatic cancer in the first-line setting, although a trend toward prolonged PFS and OS in patients with high baseline serum Hsp27 suggests this therapy may warrant further evaluation in this subgroup

Which growth standards should be used to identify large- and small-for-gestational age infants of mothers with type 1 diabetes? A pre-specified analysis of the CONCEPTT trial.

BACKGROUND: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT). METHODS: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres ( ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome. RESULTS: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes. CONCLUSIONS: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov . number NCT01788527 . Trial registered 11/2/2013

A Community-Based Social Networking Intervention to Increase Walking in Dog Owners

Roughly 40% of U.S. households own a dog and while dog ownership is associated with greater engagement in physical activity, up to 60% of dog owners do not achieve the recommended 150 minutes of weekly physical activity. The present study aims to develop and test a dog walking intervention addressing individual, interpersonal, and community factors. The study represents collaboration between UMass Medical School, UMass Lowell and their community partners, Common Pathways and the Greater Lowell Health Alliance. The developmental phase uses a community-based participatory research approach by creating community advisory boards and conducting focus groups with residents to ensure community perspectives are represented throughout intervention development. Information gathered from the developmental phase will inform the intervention. The intervention phase will determine the feasibility and efficacy of a multi-component dog walking intervention using a group randomized controlled trial. The intervention uses a social networking website, newsletters, pedometers, neighborhood walks, and community events to educate owners on the benefits of walking, create a supportive environment, and increase the “dog friendliness” of a community. Communities in Worcester and Lowell will be randomized to the intervention or control condition. Outcome measures include pedometer steps, time spent walking the dog, social support for exercise, and sense of community. This study is one of the first studies to test whether increasing dog walking in dog owners can increase owner physical activity via a social networking website. If successful, we will assess the extent to which the community can sustain the intervention

Dietary Intervention in Pregnant Women with Gestational Diabetes; Protocol for the DiGest Randomised Controlled Trial.

Funder: Wellcome TrustGestational diabetes mellitus (GDM) annually affects 35,000 pregnancies in the United Kingdom, causing suboptimal health outcomes to the mother and child. Obesity and excessive gestational weight gain are risk factors for GDM. The Institute of Medicine recommends weight targets for women that are overweight and obese, however, there are no clear guidelines for women with GDM. Observational data suggest that modest weight loss (0.6-2 kg) after 28 weeks may reduce risk of caesarean section, large-for-gestational-age (LGA), and maternal postnatal glycaemia. This protocol for a multicentre randomised double-blind controlled trial aims to identify if a fully controlled reduced energy diet in GDM pregnancy improves infant birthweight and reduces maternal weight gain (primary outcomes). A total of 500 women with GDM (National Institute of Health and Care Excellence (NICE) 2015 criteria) and body mass index (BMI) ≥25 kg/m2 will be randomised to receive a standard (2000 kcal/day) or reduced energy (1200 kcal/day) diet box containing all meals and snacks from 28 weeks to delivery. Women and caregivers will be blinded to the allocations. Food diaries, continuous glucose monitoring, and anthropometry will measure dietary compliance, glucose levels, and weight changes. Women will receive standard antenatal GDM management (insulin/metformin) according to NICE guidelines. The secondary endpoints include caesarean section rates, LGA, and maternal postnatal glucose concentrations