Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients

ObjectiveTo characterize, among European and Han Chinese populations, the genetic predictors ofmaculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepilepticdrugs.MethodsWe conducted a case-control genome-wide association study of autosomal genotypes, in-cluding Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent.Results from each cohort were meta-analyzed.ResultsWe report an association between a rare variant in the complement factor H–related 4(CFHR4) gene and phenytoin-induced MPE in Europeans (p= 4.5 × 10–11; odds ratio [95%confidence interval] 7 [3.2–16]). This variant is in complete linkage disequilibrium witha missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our resultsreinforce the association betweenHLA-A*31:01and carbamazepine hypersensitivity. We didnot identify significant genetic associations with MPE among Han Chinese patients.ConclusionsThe identification of genetic predictors of MPE in CFHR4 and CFH, members of thecomplement factor H–related protein family, suggest a new link between regulation of thecomplement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients

Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients

Objective To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. Methods We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. Results We report an association between a rare variant in the complement factor H–related 4 (CFHR4) gene and phenytoin-induced MPE in Europeans (p = 4.5 × 10–11; odds ratio [95% confidence interval] 7 [3.2–16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. Conclusions The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H–related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients

Cancer screening among migrants in an Australian cohort; cross-sectional analyses from the 45 and Up Study

<p>Abstract</p> <p>Background</p> <p>Limited evidence suggests that people from non-English speaking backgrounds in Australia have lower than average rates of participation in cancer screening programs. The objective of this study was to examine the distribution of bowel, breast and prostate cancer test use by place of birth and years since migration in a large population-based cohort study in Australia.</p> <p>Methods</p> <p>In 2006, screening status, country of birth and other demographic and health related factors were ascertained by self-completed questionnaire among 31,401 (16,126 women and 15,275 men) participants aged 50 or over from the 45 and Up Study in New South Wales.</p> <p>Results</p> <p>35% of women and 39% of men reported having a bowel cancer test and 57% of men reported having a prostate specific antigen (PSA) test, in the previous 5 years. 72% of women reported having screening mammography in the previous 2 years. Compared to Australian-born women, women from East Asia, Southeast Asia, Continental Western Europe, and North Africa/Middle East had significantly lower rates of bowel testing, with odds ratios (OR; 95%CI) ranging from 0.5 (0.4–0.7) to 0.7 (0.6–0.9); migrants from East Asia (0.5, 0.3–0.7) and North Africa/Middle East (0.5, 0.3–0.9) had significantly lower rates of mammography. Compared to Australian-born men, bowel cancer testing was significantly lower among men from all regions of Asia (OR, 95%CI ranging from 0.4, 0.3–0.6 to 0.6, 0.5–0.9) and Continental Europe (OR, 95%CI ranging from 0.4, 0.3–0.7 to 0.7, 0.6–0.9). Only men from East Asia had significantly lower PSA testing rates than Australian-born men (0.4, 0.3–0.6). As the number of years lived in Australia increased, cancer test use among migrants approached Australian-born rates.</p> <p>Conclusion</p> <p>Certain migrant groups within the population may require targeted intervention to improve their uptake of cancer screening, particularly screening for bowel cancer.</p

Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron

The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of $\sqrt s =1.96$ TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is $A_{\mathrm{FB}}^{t\bar{t}} = 0.128 \pm 0.025$. The combined inclusive and differential asymmetries are consistent with recent standard model predictions

TXS 0506+056 with Updated IceCube Data

Past results from the IceCube Collaboration have suggested that the blazar TXS 0506+056 is a potential source of astrophysical neutrinos. However, in the years since there have been numerous updates to event processing and reconstruction, as well as improvements to the statistical methods used to search for astrophysical neutrino sources. These improvements in combination with additional years of data have resulted in the identification of NGC 1068 as a second neutrino source candidate. This talk will re-examine time-dependent neutrino emission from TXS 0506+056 using the most recent northern-sky data sample that was used in the analysis of NGC 1068. The results of using this updated data sample to obtain a significance and flux fit for the 2014 TXS 0506+056 "untriggered" neutrino flare are reported

Galactic Core-Collapse Supernovae at IceCube: “Fire Drill” Data Challenges and follow-up

The next Galactic core-collapse supernova (CCSN) presents a once-in-a-lifetime opportunity to make astrophysical measurements using neutrinos, gravitational waves, and electromagnetic radiation. CCSNe local to the Milky Way are extremely rare, so it is paramount that detectors are prepared to observe the signal when it arrives. The IceCube Neutrino Observatory, a gigaton water Cherenkov detector below the South Pole, is sensitive to the burst of neutrinos released by a Galactic CCSN at a level >10σ. This burst of neutrinos precedes optical emission by hours to days, enabling neutrinos to serve as an early warning for follow-up observation. IceCube\u27s detection capabilities make it a cornerstone of the global network of neutrino detectors monitoring for Galactic CCSNe, the SuperNova Early Warning System (SNEWS 2.0). In this contribution, we describe IceCube\u27s sensitivity to Galactic CCSNe and strategies for operational readiness, including "fire drill" data challenges. We also discuss coordination with SNEWS 2.0

All-Energy Search for Solar Atmospheric Neutrinos with IceCube

The interaction of cosmic rays with the solar atmosphere generates a secondary flux of mesons that decay into photons and neutrinos – the so-called solar atmospheric flux. Although the gamma-ray component of this flux has been observed in Fermi-LAT and HAWC Observatory data, the neutrino component remains undetected. The energy distribution of those neutrinos follows a soft spectrum that extends from the GeV to the multi-TeV range, making large Cherenkov neutrino telescopes a suitable for probing this flux. In this contribution, we will discuss current progress of a search for the solar neutrino flux by the IceCube Neutrino Observatory using all available data since 2011. Compared to the previous analysis which considered only high-energy muon neutrino tracks, we will additionally consider events produced by all flavors of neutrinos down to GeV-scale energies. These new events should improve our analysis sensitivity since the flux falls quickly with energy. Determining the magnitude of the neutrino flux is essential, since it is an irreducible background to indirect solar dark matter searches