Which children and young people are excluded from school? Findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) - poster abstract

Poster abstract presented at Spring Meeting for Clinician Scientists in Training 2015BACKGROUND: School exclusion is a disciplinary method used to remove a child from the school environment. It is known to affect certain groups disproportionately, including boys, some ethnic minorities, children in care, children in poverty, and children with special educational needs. Population-based studies on wider characteristics of excluded pupils are scarce. The aim of this study was to describe factors associated with school exclusion in the Avon Longitudinal Study of Parents and Children (ALSPAC), focussing on neurodevelopment and mental health. METHODS: ALSPAC is a prospective population-based British birth cohort study, with the initial sample consisting of 14 541 pregnancies. The study has data for whether a child has been permanently excluded from school up to the age of 8 years as reported by parents and also permanent and fixed period exclusions in the preceding 12 months as reported by parents and young people at age 16 years. Upstream risk factors were assessed for associations with exclusion on univariable analysis. The association with social communication difficulties was investigated with multivariable logistic regression. FINDINGS: Data for exclusions up to the age of 8 years were available for 8245 ALSPAC participants and 4482 participants for exclusion at age 16 years. 53 pupils (0·6%) were excluded from school by age 8 years, and 390 (8·7%) at age 16 years. The odds of exclusion by 8 years and at 16 years were increased with male sex (p=0·001 and p<0·0001, respectively), low family income (p=0·014 and p<0·0001), family adversity (p<0·0001 for both), maternal psychopathology (p=0·013 and p=0·004), low intelligence quotient (p=0·041 and p<0·0001), mental health difficulties (p<0·0001 for both), psychiatric disorder (p<0·0001 for both), social communication difficulties (p<0·0001 for both), antisocial activities (p=0·004 and p<0·0001), bullying or being bullied (p=0·005 and p<0·0001), low educational attainment (p<0·0001 for both), and increased special educational needs (p<0·0001 for both). On multivariable analysis, having social communication difficulties above a clinical threshold on the Social Communication Disorders Checklist was strongly associated with exclusion by 8 years (odds ratio 7·4, 95% CI 3·6-15·4) and at 16 years (2·3, 1·5-3·5), after adjustment for relevant confounders. INTERPRETATION: Although cohort attrition and small numbers of exclusions at 8 years are limitations, this study suggests that school exclusion is associated with numerous risk factors identifiable at or before primary school entry. Child health professionals have an important role in the holistic assessment of children who are excluded, or who are at risk of school exclusion. There is particular need to ensure that mental health and neurodevelopmental difficulties are appropriately recognised and supported. FUNDING: National Institute for Health Research Academic Clinical Fellowship

In situ studies of algal biomass in relation to physicochemical characteristics of the Salt Plains National Wildlife Refuge, Oklahoma, USA

This is the first in a series of experiments designed to characterize the Salt Plains National Wildlife Refuge (SPNWR) ecosystem in northwestern Oklahoma and to catalogue its microbial inhabitants. The SPNWR is the remnant of an ancient ocean, encompassing ~65 km(2 )of variably hypersaline flat land, fed by tributaries of the Arkansas River. Relative algal biomass (i.e., chlorophyll concentrations attributed to Chlorophyll-a-containing oxygenic phototrophs) and physical and chemical parameters were monitored at three permanent stations for a one-year period (July 2000 to July 2001) using a nested block design. Salient features of the flats include annual air temperatures that ranged from -10 to 40°C, and similar to other arid/semi-arid environments, 15–20-degree daily swings were common. Shade is absent from the flats system; intense irradiance and high temperatures (air and sediment surface) resulted in low water availability across the SPNWR, with levels of only ca. 15 % at the sediment surface. Moreover, moderate daily winds were constant (ca. 8–12 km h(-1)), sometimes achieving maximum speeds of up to 137 km h(-1). Typical of freshwater systems, orthophosphate (PO(4)(3-)) concentrations were low, ranging from 0.04 to <1 μM; dissolved inorganic nitrogen levels were high, but spatially variable, ranging from ca. 250–600 μM (NO(3)(- )+ NO(2)(-)) and 4–166 μM (NH(4)(+)). Phototroph abundance was likely tied to nutrient availability, with high-nutrient sites exhibiting high Chl-a levels (ca. 1.46 mg m(-2)). Despite these harsh conditions, the phototrophic microbial community was unexpectedly diverse. Preliminary attempts to isolate and identify oxygenic phototrophs from SPNWR water and soil samples yielded 47 species from 20 taxa and 3 divisions. Our data indicate that highly variable, extreme environments might support phototrophic microbial communities characterized by higher species diversity than previously assumed

Serum leptin and risk of cognitive decline in elderly italians.

Background: US studies suggest that leptin, a fat-derived hormone, may be protective against the development of dementia. Objective: To investigate the complex relationship between leptin levels and cognitive decline in elderly Italians. Methods: We studied circulating fasting leptin levels in 809 elderly adults free from dementia who participated in the prospective Italian population-based InCHIANTI study between 1998 and 2009 (mean follow-up of 8.0 years). Global cognitive decline was defined as a reduction of ≥5 points on the Mini-Mental State Examination (MMSE). Trail-Making Tests A and B were also incorporated, with cognitive decline defined as discontinued testing or the worst 10% of change from baseline. We also investigated whether any association could be explained by midlife weight and whether cognitive decline was associated with changing leptin levels. Results: The multivariate adjusted relative risk ([RR]; 95% confidence interval [CI]) of cognitive decline on the MMSE was 0.84 (95% CI 0.73–0.97) in relation to baseline sex-standardized log-leptin levels. High leptin levels showed a non-significant trend toward a reduced risk of decline on the Trail-Making Tests A (RR = 0.85, 95% CI 0.71–1.02) and B (RR = 0.90, 0.79–1.02). Adjusting for midlife weight or change in weight did not alter the pattern of results, and cognitive decline was not associated with changing leptin levels. Conclusions: High leptin levels were independently associated with a reduced risk of cognitive decline in elderly Italians.Italian Ministry of HealthU.S. National Institute on AgingAlzheimer’s AssociationNational Institute for Health Research (NIHR)National Institute of Health (Baltimore)National Institute of Health (Maryland)Mary Kinross Charitable TrustJames Tudor FoundationHalpin TrustSir Halley Stewart TrustAge Related Diseases and Health TrustNorman Family Charitable Trus

Impact of influenza vaccination on amoxicillin prescriptions in older adults: A retrospective cohort study using primary care data

Background: Bacterial infections of the upper and lower respiratory tract are a frequent complication of influenza and contribute to the widespread use of antibiotics. Influenza vaccination may help reduce both appropriate and inappropriate prescribing of antibiotics. Electronic health records provide a rich source of information for assessing secondary effects of influenza vaccination. Methods: We conducted a retrospective study to estimate effects of influenza vaccine on antibiotic (amoxicillin) prescription in the elderly based on data from the Clinical Practice Research Datalink. The introduction of UK policy to recommend the influenza vaccine to older adults in 2000 led to a substantial increase in uptake, creating a natural experiment. Of 259,753 eligible patients that were unvaccinated in 1999 and aged≥65y by January 2000, 88,519 patients received influenza vaccination in 2000. These were propensity score matched 1:1 to unvaccinated patients. Time-to-amoxicillin was analysed using the Prior Event Rate Ratio (PERR) Pairwise method to address bias from time-invariant measured and unmeasured confounders. A simulation study and negative control outcome were used to help strengthen the validity of results. Results: Compared to unvaccinated patients, those from the vaccinated group were more likely to be prescribed amoxicillin in the year prior to vaccination: hazard ratio (HR) 1.90 (95% confidence interval 1.83, 1.98). Following vaccination, the vaccinated group were again more likely to be prescribed amoxicillin, HR 1.64 (1.58,1.71). After adjusting for prior differences between the two groups using PERR Pairwise, overall vaccine effectiveness was 0.86 (0.81, 0.92). Additional analyses suggested that provided data meet the PERR assumptions, these estimates were robust. Conclusions: Once differences between groups were taken into account, influenza vaccine had a beneficial effect, lowering the frequency of amoxicillin prescribing in the vaccinated group. Ensuring successful implementation of national programmes of vaccinating older adults against influenza may help contribute to reducing antibiotic resistance

A new class of ratiometric small molecule intracellular pH sensors for Raman microscopy

Intracellular pH (pHi) homeostasis is intertwined with a myriad of normal cellular behaviors as well as pathological processes. As such, small molecule probes for the measurement of pHi are invaluable tools for chemical biology, facilitating the study of the role of pH in cellular function and disease. The field of small molecule pHi sensors has traditionally been dominated with probes based on fluorescent scaffolds. In this study, a series of low molecular weight (<260) oligoyne compounds have been developed which exhibit pH sensitive alkyne stretching frequencies (νalkyne) in Raman spectroscopy. The modular design of the compounds enabled tuneability of their pKa(H) through simple structural modification, such that continuous pH sensitivity is achieved over the range 2-10. Alkyne stretching bands reside in the 'cell-silent' region of the Raman spectrum (1800-2600 cm-1) and are readily detectable in a cellular environment with subcellular spatial resolution. This enabled the application of a pH sensitive oligoyne compound to the ratiometric sensing of pHi in prostate cancer (PC3) cells in response to drug treatment. We propose that probes based on Alkyne Tag Raman Imaging offer an entirely new platform for the sensing of pHi, complementary to fluorescence microscopy

Garcinolic Acid Distinguishes Between GACKIX Domains and Modulates Interaction Networks

Natural products are often uniquely suited to modulate protein-protein interactions (PPIs) due to their architectural and functional group complexity relative to synthetic molecules. Here we demonstrate that the natural product garcinolic acid allosterically blocks the CBP/p300 KIX PPI network and displays excellent selectivity over related GACKIX motifs. It does so via a strong interaction (KD 1 μM) with a non-canonical binding site containing a structurally dynamic loop in CBP/p300 KIX. Garcinolic acid engages full-length CBP in the context of the proteome and in doing so effectively inhibits KIX-dependent transcription in a leukemia model. As the most potent small-molecule KIX inhibitor yet reported, garcinolic acid represents an important step forward in the therapeutic targeting of CBP/p300

Association between Serum Perfluorooctanoic Acid (PFOA) and Thyroid Disease in the U.S. National Health and Nutrition Examination Survey

addresses: Epidemiology and Public Health Group, eninsula Medical School, Exeter, United Kingdom.notes: PMCID: PMC2866686types: Journal Article'Reproduced with permission from Environmental Health Perspectives'Copyright © 2010 National Institute of Environmental Health SciencesPerfluorooctanoic acid (PFOA, also known as C8) and perfluorooctane sulfonate (PFOS) are stable compounds with many industrial and consumer uses. Their persistence in the environment plus toxicity in animal models has raised concern over low-level chronic exposure effects on human health

O2‐03‐02: Vitamin D and the risk of developing neuroimaging abnormalities

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152624/1/alzjjalz201507143.pd

Time trends in prescribing of type 2 diabetes drugs, glycaemic response and risk factors:a retrospective analysis of primary care data, 2010-2017

This is the author accepted manuscript. The final version is available on open access from Wiley via the DOI in this recordAim: Prescribing in type 2 diabetes has changed markedly in recent years, with increasing use of newer, more expensive glucose-lowering drugs. We aimed to describe population-level time trends in both prescribing patterns and short-term patient outcomes (HbA1c, weight, blood pressure, hypoglycemia and treatment discontinuation) after initiating new therapy. Materials and methods: We studied 81,532 UK patients with type 2 diabetes initiating a first to fourth line drug in primary care between 2010-2017 inclusive (Clinical Practice Research Datalink). Trends in new prescriptions and subsequent six and twelve-month adjusted changes in glycemic response (reduction in HbA1c), weight, blood pressure, and rates of hypoglycemia and treatment discontinuation were examined. Results: DPP4-inhibitor use second-line near doubled (41% of new prescriptions in 2017 vs. 22% 2010), replacing sulfonylureas as the most common second-line drug (29% 2017 vs. 53% 2010). SGLT2-inhibitors, introduced in 2013, comprised 17% of new first-fourth line prescriptions by 2017. First-line use of metformin remained stable (91% of new prescriptions in 2017 vs. 91% 2010). Over the study period there was little change in average glycemic response and treatment discontinuation. There was a modest reduction in weight second and third-line (second line 2017 vs. 2010: -1.5 kg (95%CI -1.9;-1.1), p<0.001), and a slight reduction in systolic blood pressure first to third-line (2017 vs. 2010 difference range -1.7 to -2.1 mmHg, all p<0.001). Hypoglycemia rates decreased second-line (incidence rate ratio 0.94 per-year (95%CI 0.88;1.00, p=0.04)), mirroring the decline in use of sulfonylureas. 4 Conclusions: Recent changes in prescribing of therapy in type 2 diabetes have not led to a change in glycemic response and have resulted in modest improvements in other population-level short-term patient outcomes.Medical Research Council (MRC)National Institute for Health Research (NIHR)Wellcome Trus

Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes:the TriMaster study

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData availability: To minimize the risk of patient re-identification, de-identified individual patient-level clinical data are available under restricted access. Requests for access to anonymized individual participant data and study documents should be made to the corresponding author and will be reviewed by the Peninsula Research Bank Steering Committee. Access to data through the Peninsula Research Bank will be granted for requests with scientifically valid questions by academic teams with the necessary skills appropriate for the research. Data that can be shared will be released with the relevant transfer agreement.Code availability: Requests for access to code should be made to the corresponding author and will be reviewed by the Peninsula Research Bank Steering Committee. Access to code through the Peninsula Research Bank will be granted for requests with scientifically valid questions by academic teams with the necessary skills appropriate for the research. Code will be released by the lead statistician.Precision medicine aims to treat an individual based on their clinical characteristics. A differential drug response, critical to using these features for therapy selection, has never been examined directly in type 2 diabetes. In this study, we tested two hypotheses: (1) individuals with body mass index (BMI) > 30 kg/m2, compared to BMI ≤ 30 kg/m2, have greater glucose lowering with thiazolidinediones than with DPP4 inhibitors, and (2) individuals with estimated glomerular filtration rate (eGFR) 60-90 ml/min/1.73 m2, compared to eGFR >90 ml/min/1.73 m2, have greater glucose lowering with DPP4 inhibitors than with SGLT2 inhibitors. The primary endpoint for both hypotheses was the achieved HbA1c difference between strata for the two drugs. In total, 525 people with type 2 diabetes participated in this UK-based randomized, double-blind, three-way crossover trial of 16 weeks of treatment with each of sitagliptin 100 mg once daily, canagliflozin 100 mg once daily and pioglitazone 30 mg once daily added to metformin alone or metformin plus sulfonylurea. Overall, the achieved HbA1c was similar for the three drugs: pioglitazone 59.6 mmol/mol, sitagliptin 60.0 mmol/mol and canagliflozin 60.6 mmol/mol (P = 0.2). Participants with BMI > 30 kg/m2, compared to BMI ≤ 30 kg/m2, had a 2.88 mmol/mol (95% confidence interval (CI): 0.98, 4.79) lower HbA1c on pioglitazone than on sitagliptin (n = 356, P = 0.003). Participants with eGFR 60-90 ml/min/1.73 m2, compared to eGFR >90 ml/min/1.73 m2, had a 2.90 mmol/mol (95% CI: 1.19, 4.61) lower HbA1c on sitagliptin than on canagliflozin (n = 342, P = 0.001). There were 2,201 adverse events reported, and 447/525 (85%) randomized participants experienced an adverse event on at least one of the study drugs. In this precision medicine trial in type 2 diabetes, our findings support the use of simple, routinely available clinical measures to identify the drug class most likely to deliver the greatest glycemic reduction for a given patient. (ClinicalTrials.gov registration: NCT02653209 ; ISRCTN registration: 12039221 .).Medical Research Council (MRC)National Institute for Health and Care Research (NIHR