Saccadic Eye Movement Abnormalities in Children with Epilepsy

Childhood onset epilepsy is associated with disrupted developmental integration of sensorimotor and cognitive functions that contribute to persistent neurobehavioural comorbidities. The role of epilepsy and its treatment on the development of functional integration of motor and cognitive domains is unclear. Oculomotor tasks can probe neurophysiological and neurocognitive mechanisms vulnerable to developmental disruptions by epilepsy-related factors. The study involved 26 patients and 48 typically developing children aged 8–18 years old who performed a prosaccade and an antisaccade task. Analyses compared medicated chronic epilepsy patients and unmedicated controlled epilepsy patients to healthy control children on saccade latency, accuracy and dynamics, errors and correction rate, and express saccades. Patients with medicated chronic epilepsy had impaired and more variable processing speed, reduced accuracy, increased peak velocity and a greater number of inhibitory errors, younger unmedicated patients also showed deficits in error monitoring. Deficits were related to reported behavioural problems in patients. Epilepsy factors were significant predictors of oculomotor functions. An earlier age at onset predicted reduced latency of prosaccades and increased express saccades, and the typical relationship between express saccades and inhibitory errors was absent in chronic patients, indicating a persistent reduction in tonic cortical inhibition and aberrant cortical connectivity. In contrast, onset in later childhood predicted altered antisaccade dynamics indicating disrupted neurotransmission in frontoparietal and oculomotor networks with greater demand on inhibitory control. The observed saccadic abnormalities are consistent with a dysmaturation of subcortical-cortical functional connectivity and aberrant neurotransmission. Eye movements could be used to monitor the impact of epilepsy on neurocognitive development and help assess the risk for poor neurobehavioural outcomes

Incorporating concepts of inequality and inequity into health benefits analysis

BACKGROUND: Although environmental policy decisions are often based in part on both risk assessment information and environmental justice concerns, formalized approaches for addressing inequality or inequity when estimating the health benefits of pollution control have been lacking. Inequality indicators that fulfill basic axioms and agree with relevant definitions and concepts in health benefits analysis and environmental justice analysis can allow for quantitative examination of efficiency-equality tradeoffs in pollution control policies. METHODS: To develop appropriate inequality indicators for health benefits analysis, we provide relevant definitions from the fields of risk assessment and environmental justice and consider the implications. We evaluate axioms proposed in past studies of inequality indicators and develop additional axioms relevant to this context. We survey the literature on previous applications of inequality indicators and evaluate five candidate indicators in reference to our proposed axioms. We present an illustrative pollution control example to determine whether our selected indicators provide interpretable information. RESULTS AND CONCLUSIONS: We conclude that an inequality indicator for health benefits analysis should not decrease when risk is transferred from a low-risk to high-risk person, and that it should decrease when risk is transferred from a high-risk to low-risk person (Pigou-Dalton transfer principle), and that it should be able to have total inequality divided into its constituent parts (subgroup decomposability). We additionally propose that an ideal indicator should avoid value judgments about the relative importance of transfers at different percentiles of the risk distribution, incorporate health risk with evidence about differential susceptibility, include baseline distributions of risk, use appropriate geographic resolution and scope, and consider multiple competing policy alternatives. Given these criteria, we select the Atkinson index as the single indicator most appropriate for health benefits analysis, with other indicators useful for sensitivity analysis. Our illustrative pollution control example demonstrates how these indices can help a policy maker determine control strategies that are dominated from an efficiency and equality standpoint, those that are dominated for some but not all societal viewpoints on inequality averseness, and those that are on the optimal efficiency-equality frontier, allowing for more informed pollution control policies

Genetic predisposition to mosaic Y chromosome loss in blood.

Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1-5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases.This research has been conducted using the UK Biobank Resource under application 9905 and 19808. This work was supported by the Medical Research Council [Unit Programme number MC_UU_12015/2]. Full study-specific and individual acknowledgements can be found in the supplementary information

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Search for light sterile neutrinos with the T2K far detector Super-Kamiokande at a baseline of 295 km

We perform a search for light sterile neutrinos using the data from the T2K far detector at a baseline of 295 km, with an exposure of 14.7ð7.6Þ × 1020 protons on target in neutrino (antineutrino) mode. A selection of neutral-current interaction samples is also used to enhance the sensitivity to sterile mixing. No evidence of sterile neutrino mixing in the 3 þ 1 model was found from a simultaneous fit to the charged-current muon, electron and neutral-current neutrino samples. We set the most stringent limit on the sterile oscillation amplitude sin2 θ24 for the sterile neutrino mass splitting Δm241 < 3 × 10−3 eV2=c4

Search for neutral-current induced single photon production at the ND280 near detector in T2K

Neutrino neutral-current (NC) induced single photon production is a sub-leading order process for accelerator-based neutrino beam experiments including T2K. It is, however, an important process to understand because it is a background for electron (anti)neutrino appearance oscillation experiments. Here, we performed the first search of this process below 1 GeV using the fine-grained detector at the T2K ND280 off-axis near detector. By reconstructing single photon kinematics from electron-positron pairs, we achieved 95% pure gamma ray sample from 5.738 x 10(20) protons-on-targets neutrino mode data. We do not find positive evidence of NC induced single photon production in this sample. We set the model-dependent upper limit on the cross-section for this process, at 0.114 x 10(-38) cm(2) (90% C.L.) per nucleon, using the J-PARC off-axis neutrino beam with an average energy of similar to 0.6 GeV. This is the first limit on this process below 1 GeV which is important for current and future oscillation experiments looking for electron neutrino appearance oscillation signals

Search for heavy neutrinos with the T2K near detector ND280

International audienceThis paper reports on the search for heavy neutrinos with masses in the range 140<MN<493  MeV/c2 using the off-axis near detector ND280 of the T2K experiment. These particles can be produced from kaon decays in the standard neutrino beam and then subsequently decay in ND280. The decay modes under consideration are N→ℓα±π∓ and N→ℓα+ℓβ-ν(−)(α,β=e,μ). A search for such events has been made using the Time Projection Chambers of ND280, where the background has been reduced to less than two events in the current dataset in all channels. No excess has been observed in the signal region. A combined Bayesian statistical approach has been applied to extract upper limits on the mixing elements of heavy neutrinos to electron-, muon- and tau- flavored currents (Ue2, Uμ2, Uτ2) as a function of the heavy neutrino mass, e.g., Ue2<10-9 at 90% C.L. for a mass of 390  MeV/c2. These constraints are competitive with previous experiments