Views of healthcare professionals to linkage of routinely collected healthcare data : a systematic review

Peer reviewedPublisher PD

Linked health data for pharmacovigilance in children : Perceived legal and ethical issues for stakeholders and data guardians

Peer reviewedPublisher PD

Separable mechanisms underlying global feature-based attention

Feature-based attention is known to operate in a spatially global manner, in that the selection of attended features is not bound to the spatial focus of attention. Here we used electromagnetic recordings in human observers to characterize the spatiotemporal signature of such global selection of an orientation feature. Observers performed a simple orientation-discrimination task while ignoring task-irrelevant orientation probes outside the focus of attention. We observed that global feature-based selection, indexed by the brain response to unattended orientation probes, is composed of separable functional components. One such component reflects global selection based on the similarity of the probe with task-relevant orientation values ("template matching"), which is followed by a component reflecting selection based on the similarity of the probe with the orientation value under discrimination in the focus of attention ("discrimination matching"). Importantly, template matching occurs at similar to 150 ms after stimulus onset, similar to 80 ms before the onset of discrimination matching. Moreover, source activity underlying template matching and discrimination matching was found to originate from ventral extrastriate cortex, with the former being generated in more anterolateral and the latter in more posteromedial parts, suggesting template matching to occur in visual cortex higher up in the visual processing hierarchy than discrimination matching. We take these observations to indicate that the population-level signature of global feature-based selection reflects a sequence of hierarchically ordered operations in extrastriate visual cortex, in which the selection based on task relevance has temporal priority over the selection based on the sensory similarity between input representations

Chern numbers for two families of noncommutative Hopf fibrations

We consider noncommutative line bundles associated with the Hopf fibrations of SUq(2) over all Podles spheres and with a locally trivial Hopf fibration of S^3_{pq}. These bundles are given as finitely generated projective modules associated via 1-dimensional representations of U(1) with Galois-type extensions encoding the principal fibrations of SUq(2) and S^3_{pq}. We show that the Chern numbers of these modules coincide with the winding numbers of representations defining them.Comment: 6 page

Task-load-dependent activation of dopaminergic midbrain areas in the absence of reward

Dopamine release in cortical and subcortical structures plays a central role in reward-related neural processes. Within this context, dopaminergic inputs are commonly assumed to play an activating role, facilitating behavioral and cognitive operations necessary to obtain a prospective reward. Here, we provide evidence from human fMRI that this activating role can also be mediated by task-demand-related processes and thus extendsbeyondsituationsthatonlyentailextrinsicmotivatingfactors. Using a visual discrimination task in which varying levels of task demands were precued, we found enhanced hemodynamic activity in the substantia nigra (SN) for high task demands in the absence of reward or similar extrinsic motivating factors. This observation thus indicates that the SN can also be activated in an endogenous fashion. In parallel to its role in reward-related processes, reward-independent activation likely serves to recruit the processing resources needed to meet enhanced task demands. Simultaneously, activity in a wide network of cortical and subcortical control regions was enhanced in response to high task demands, whereas areas of the default-mode network were deactivated more strongly. The present observations suggest that the SN represents a core node within a broader neural network that adjusts the amount of available neural and behavioral resources to changing situational opportunities and task requirements, which is often driven by extrinsic factors but can also be controlled endogenously

Retreatment with interferon-alpha and ribavirin in primary interferon-alpha non-responders with chronic hepatitis C

Background/Aims: Combination therapy with interferon-alpha (IFN-alpha) plus ribavirin is more efficacious than IFN-alpha monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-alpha relapse. Only limited data are available in IFN-alpha non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-alpha-resistant chronic hepatitis C. Methods: Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-alpha-2a (3 x 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-alpha dose of 3 x 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period. Results: After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-a dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001). Conclusions: Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-alpha non-responders. Higher IFN-alpha induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1

Cohomogeneity one manifolds and selfmaps of nontrivial degree

We construct natural selfmaps of compact cohomgeneity one manifolds with finite Weyl group and compute their degrees and Lefschetz numbers. On manifolds with simple cohomology rings this yields in certain cases relations between the order of the Weyl group and the Euler characteristic of a principal orbit. We apply our construction to the compact Lie group SU(3) where we extend identity and transposition to an infinite family of selfmaps of every odd degree. The compositions of these selfmaps with the power maps realize all possible degrees of selfmaps of SU(3).Comment: v2, v3: minor improvement

Historical reconstruction of polychlorinated biphenyl (PCB) exposures for workers in a capacitor manufacturing plant

We developed a semiquantitative job exposure matrix (JEM) for workers exposed to polychlorinated biphenyls (PCBs) at a capacitor manufacturing plant from 1946 to 1977. In a recently updated mortality study, mortality of prostate and stomach cancer increased with increasing levels of cumulative exposure estimated with this JEM (trend p values = 0.003 and 0.04, respectively). Capacitor manufacturing began with winding bales of foil and paper film, which were placed in a metal capacitor box (pre-assembly), and placed in a vacuum chamber for flood-filling (impregnation) with dielectric fluid (PCBs). Capacitors dripping with PCB residues were then transported to sealing stations where ports were soldered shut before degreasing, leak testing, and painting. Using a systematic approach, all 509 unique jobs identified in the work histories were rated by predetermined process- and plant-specific exposure determinants; then categorized based on the jobs' similarities (combination of exposure determinants) into 35 job exposure categories. The job exposure categories were ranked followed by a qualitative PCB exposure rating (baseline, low, medium, and high) for inhalation and dermal intensity. Category differences in other chemical exposures (solvents, etc.) prevented further combining of categories. The mean of all available PCB concentrations (1975 and 1977) for jobs within each intensity rating was regarded as a representative value for that intensity level. Inhalation (in microgram per cubic milligram) and dermal (unitless) exposures were regarded as equally important. Intensity was frequency adjusted for jobs with continuous or intermittent PCB exposures. Era-modifying factors were applied to the earlier time periods (1946-1974) because exposures were considered to have been greater than in later eras (1975-1977). Such interpolations, extrapolations, and modifying factors may introduce non-differential misclassification; however, we do believe our rigorous method minimized misclassification, as shown by the significant exposure-response trends in the epidemiologic analysis