Headache in people with epilepsy

Epidemiological estimates indicate that individuals with epilepsy are more likely to experience headaches, including migraine, than individuals without epilepsy. Headaches can be temporally unrelated to seizures, or can occur before, during or after an episode; seizures and migraine attacks are mostly not temporally linked. The pathophysiological links between headaches (including migraine) and epilepsy are complex and have not yet been fully elucidated. Correct diagnoses and appropriate treatment of headaches in individuals with epilepsy is essential, as headaches can contribute substantially to disease burden. Here, we review the insights that have been made into the associations between headache and epilepsy over the past 5 years, including information on the pathophysiological mechanisms and genetic variants that link the two disorders. We also discuss the current best practice for the management of headaches co-occurring with epilepsy and highlight future challenges for this area of research.Paroxysmal Cerebral Disorder

Radiation-induced oscillatory magnetoresistance as a sensitive probe of the zero-field spin splitting in high mobility GaAs/AlGaAs devices

We suggest an approach for characterizing the zero-field spin splitting of high mobility two-dimensional electron systems, when beats are not readily observable in the Shubnikov-de Haas effect. The zero-field spin splitting and the effective magnetic field seen in the reference frame of the electron is evaluated from a quantitative study of beats observed in radiation-induced magnetoresistance oscillations.Comment: 4 pages, 4 color figure

DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia (DECONNECT):research protocol for a cross-sectional pilot study

Introduction Pre-eclampsia is a hypertensive disorder affecting up to 8% of pregnancies. After pre-eclampsia, women are at increased risk of cognitive problems, and cerebrovascular and cardiovascular disorders. These sequelae could result from microvascular dysfunction persisting after pre-eclampsia. This study will explore differences in cerebral and myocardial microvascular function between women after pre-eclampsia and women after normotensive gestation. We hypothesise that pre-eclampsia alters cerebral and myocardial microvascular functions, which in turn are related to diminished cognitive and cardiac performance. Methods and analysis The cross-sectional € DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia' (DECONNECT) pilot study includes women after pre-eclampsia and controls after normotensive pregnancy between 6 months and 20 years after gestation. We recruit women from the Queen of Hearts study, a study investigating subclinical heart failure after pre-eclampsia. Neuropsychological tests are employed to assess different cognitive domains, including attention, processing speed, and cognitive control. Cerebral images are recorded using a 7 Tesla MRI to assess blood-brain barrier integrity, perfusion, blood flow, functional and structural networks, and anatomical dimensions. Cardiac images are recorded using a 3 Tesla MRI to assess cardiac perfusion, strain, dimensions, mass, and degree of fibrosis. We assess the effect of a history of pre-eclampsia using multivariable regression analyses. Ethics and dissemination This study is approved by the Ethics Committee of Maastricht University Medical Centre (METC azM/UM, NL47252.068.14). Knowledge dissemination will include scientific publications, presentations at conferences and public forums, and social media. Trial registration number NCT02347540.</p

Granzyme B is correlated with clinical outcome after PD-1 blockade in patients with stage IV non-small-cell lung cancer

BACKGROUND: A minority of patients with advanced non-small-cell lung cancer (NSCLC) benefit from treatment with immune checkpoint inhibitors (ICIs). Ineffective effector function of activated T and NK cells may lead to reduced tumor cell death, even when these activated effector cells are released from their immune checkpoint brake. Hence, in this study we aimed to assess the association of baseline serum granzyme B, as well as germline variation of the GZMB gene, with clinical outcome to programmed cell death protein 1 (PD-1) blockade. METHODS: A total of 347 patients with stage IV NSCLC who started nivolumab treatment between June 2013 and June 2017 were prospectively included. Baseline serum and whole blood was available, allowing for protein quantification and targeted DNA sequencing. Clinical outcome was based on best overall response (BOR) according to Response Evaluation Criteria in Solid Tumors, V.1.1, progression-free survival (PFS), and overall survival (OS). RESULTS: Patients with low serum levels of granzyme B had worse PFS (HR: 1.96; 95% CI: 1.12 to 3.43; p=0.018) and worse OS (HR: 2.08; 95% CI: 1.12 to 3.87; p=0.021) than patients with high baseline serum levels. To validate the findings, germline variation of GZMB rs8192917 was assessed. Patients with homozygous and heterozygous variants of GZMB rs8192917 had worse BOR (OR: 1.60; 95% CI: 1.01 to 2.52; p=0.044) and worse PFS (HR: 1.38; 95% CI:1.02 to 1.87; p=0.036) than wild types. CONCLUSIONS: A low baseline serum level of granzyme B and germline variation of GZMB was associated with worse clinical outcome in NSCLC, emphasizing the relevance and additional value of monitoring germline genetic variations which mirror cytotoxic functions of T cells in ICI therapy. TRAIL REGISTRATION NUMBER: Dutch Trial Registry (NL6828)

Exclusion limits on the WIMP-nucleon cross-section from the Cryogenic Dark Matter Search

The Cryogenic Dark Matter Search (CDMS) employs low-temperature Ge and Si detectors to search for Weakly Interacting Massive Particles (WIMPs) via their elastic-scattering interactions with nuclei while discriminating against interactions of background particles. For recoil energies above 10 keV, events due to background photons are rejected with >99.9% efficiency, and surface events are rejected with >95% efficiency. The estimate of the background due to neutrons is based primarily on the observation of multiple-scatter events that should all be neutrons. Data selection is determined primarily by examining calibration data and vetoed events. Resulting efficiencies should be accurate to about 10%. Results of CDMS data from 1998 and 1999 with a relaxed fiducial-volume cut (resulting in 15.8 kg-days exposure on Ge) are consistent with an earlier analysis with a more restrictive fiducial-volume cut. Twenty-three WIMP candidate events are observed, but these events are consistent with a background from neutrons in all ways tested. Resulting limits on the spin-independent WIMP-nucleon elastic-scattering cross-section exclude unexplored parameter space for WIMPs with masses between 10-70 GeV c^{-2}. These limits border, but do not exclude, parameter space allowed by supersymmetry models and accelerator constraints. Results are compatible with some regions reported as allowed at 3-sigma by the annual-modulation measurement of the DAMA collaboration. However, under the assumptions of standard WIMP interactions and a standard halo, the results are incompatible with the DAMA most likely value at >99.9% CL, and are incompatible with the model-independent annual-modulation signal of DAMA at 99.99% CL in the asymptotic limit.Comment: 40 pages, 49 figures (4 in color), submitted to Phys. Rev. D; v.2:clarified conclusions, added content and references based on referee's and readers' comments; v.3: clarified introductory sections, added figure based on referee's comment

An improved method for measuring muon energy using the truncated mean of dE/dx

The measurement of muon energy is critical for many analyses in large Cherenkov detectors, particularly those that involve separating extraterrestrial neutrinos from the atmospheric neutrino background. Muon energy has traditionally been determined by measuring the specific energy loss (dE/dx) along the muon's path and relating the dE/dx to the muon energy. Because high-energy muons (E_mu > 1 TeV) lose energy randomly, the spread in dE/dx values is quite large, leading to a typical energy resolution of 0.29 in log10(E_mu) for a muon observed over a 1 km path length in the IceCube detector. In this paper, we present an improved method that uses a truncated mean and other techniques to determine the muon energy. The muon track is divided into separate segments with individual dE/dx values. The elimination of segments with the highest dE/dx results in an overall dE/dx that is more closely correlated to the muon energy. This method results in an energy resolution of 0.22 in log10(E_mu), which gives a 26% improvement. This technique is applicable to any large water or ice detector and potentially to large scintillator or liquid argon detectors.Comment: 12 pages, 16 figure

All-particle cosmic ray energy spectrum measured with 26 IceTop stations

We report on a measurement of the cosmic ray energy spectrum with the IceTop air shower array, the surface component of the IceCube Neutrino Observatory at the South Pole. The data used in this analysis were taken between June and October, 2007, with 26 surface stations operational at that time, corresponding to about one third of the final array. The fiducial area used in this analysis was 0.122 km^2. The analysis investigated the energy spectrum from 1 to 100 PeV measured for three different zenith angle ranges between 0{\deg} and 46{\deg}. Because of the isotropy of cosmic rays in this energy range the spectra from all zenith angle intervals have to agree. The cosmic-ray energy spectrum was determined under different assumptions on the primary mass composition. Good agreement of spectra in the three zenith angle ranges was found for the assumption of pure proton and a simple two-component model. For zenith angles {\theta} < 30{\deg}, where the mass dependence is smallest, the knee in the cosmic ray energy spectrum was observed between 3.5 and 4.32 PeV, depending on composition assumption. Spectral indices above the knee range from -3.08 to -3.11 depending on primary mass composition assumption. Moreover, an indication of a flattening of the spectrum above 22 PeV were observed.Comment: 38 pages, 17 figure

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe