An analytical approach to the multiply scattered light in the optical images of the extensive air showers of ultra-high energies

One of the methods for studying the highest energy cosmic rays is to measure the fluorescence light emitted by the extensive air showers induced by them. To reconstruct a shower cascade curve from measurements of the number of photons arriving from the subsequent shower track elements it is necessary to take into account the multiple scatterings that photons undergo on their way from the shower to the detector. In contrast to the earlier Monte-Carlo work, we present here an analytical method to treat the Rayleigh and Mie scatterings in the atmosphere. The method consists in considering separately the consecutive 'generations' of the scattered light. Starting with a point light source in a uniform medium, we then examine a source in a real atmosphere and finally - a moving source (shower) in it. We calculate the angular distributions of the scattered light superimposed on the not scattered light registered from a shower at a given time. The analytical solutions (although approximate) show how the exact numerical results should be parametrised what we do for the first two generations (the contribution of the higher ones being small). Not allowing for the considered effect may lead to an overestimation of shower primary energy by ~15% and to an underestimation of the primary particle mass.Comment: 23 pages, 18 figures, submited to Astroparticle Physic

Atmospheric multiple scattering of fluorescence and Cherenkov light emitted by extensive air showers

Atmospheric scattering of light emitted by an air shower not only attenuates direct fluorescence light from the shower, but also contributes to the observed shower light. So far only direct and singly-scattered Cherenkov photons have been taken into account in routine analyses of the observed optical image of air showers. In this paper a Monte Carlo method of evaluating the contribution of multiply scattered light to the optical air shower image is presented, as well as results of simulations and a parameterization of scattered light contribution to measured shower signal.Comment: 27 pages, 18 figures, accepted for publication in NIM

Characteristics of geomagnetic cascading of ultra-high energy photons at the southern and northern sites of the Pierre Auger Observatory

Cosmic-ray photons above 10^19 eV can convert in the geomagnetic field and initiate a preshower, i.e. a particle cascade before entering the atmosphere. We compare the preshower characteristics at the southern and northern sites of the Pierre Auger Observatory. In addition to a shift of the preshower patterns on the sky due to the different pointing of the local magnetic field vectors, the fact that the northern Auger site is closer to the geomagnetic pole results in a different energy dependence of the preshower effect: photon conversion can start at smaller energies, but large conversion probabilitites (>90%) are reached for the whole sky at higher energies compared to the southern Auger site. We show how the complementary preshower features at the two sites can be used to search for ultra-high energy photons among cosmic rays. In particular, the different preshower characteristics at the northern Auger site may provide an elegant and unambiguous confirmation if a photon signal is detected at the southern site.Comment: 25 pages, 14 figures, minor changes, conclusions unchanged, Appendix A replaced, accepted by Astroparticle Physic

Universal lateral distribution of energy deposit in air showers and its application to shower reconstruction

The light intensity distribution in a shower image and its implications to the primary energy reconstructed by the fluorescence technique are studied. Based on detailed CORSIKA energy deposit simulations, a universal analytical formula is derived for the lateral distribution of light in the shower image and a correction factor is obtained to account for the fraction of shower light falling into outlying pixels in the detector. The expected light profiles and the corresponding correction of the primary shower energy are illustrated for several typical event geometries. This correction of the shower energy can exceed 10%, depending on shower geometry.Comment: 21 pages, 9 figure

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

Successful reduction of intraventricular asynchrony is associated with superior response to cardiac resynchronization therapy

<p>Abstract</p> <p>Background</p> <p>Cardiac resynchronization therapy (CRT) is generally associated with a low to moderate increase of the left ventricular ejection fraction (LVEF). In some patients, however, LVEF improves remarkably and reaches near-normal values. The aim of the present study was to further characterize these so called 'super-responders' with a special focus on the extent of intra- and interventricular asynchrony before and after device implantation compared to average responders.</p> <p>Methods</p> <p>37 consecutive patients who underwent CRT device implantation according to current guidelines were included in the study. Patients were examined by echocardiography before, one day after and six months after device implantation. Pre-defined criterion for superior response to CRT was an LVEF increase > 15% after six months.</p> <p>Results</p> <p>At follow-up, eight patients (21.6%) were identified as super-responders. There were no significant differences regarding age, gender, prevalence of ischemic heart disease and LVEF between average and super-responders at baseline. After six months, LVEF had significantly increased from 26.7% ± 5.7% to 33.1% ± 7.9% (<it>p </it>< 0.001) in average and from 24.0% ± 6.7% to 50.3% ± 7.4% (<it>p </it>< 0.001) in super-responders. Both groups showed a significant reduction of QRS duration as well as LV end-diastolic and -systolic volumes under CRT. At baseline, the interventricular mechanical delay (IVMD) was 53.7 ± 20.9 ms in average and 56.9 ± 22.4 ms in super-responders - representing a similar extent of interventricular asynchrony in both groups (<it>p </it>= 0.713). CRT significantly reduced the IVMD to 20.3 ± 15.7 (<it>p </it>< 0.001) in average and to 19.8 ± 15.9 ms (<it>p </it>= 0.013) in super-responders with no difference between both groups (<it>p </it>= 0.858). As a marker for intraventricular asynchrony, we assessed the longest intraventricular delay between six basal LV segments. At baseline, there was no difference between average (86.2 ± 30.5 ms) and super-responders (78.8 ± 23.6 ms, <it>p </it>= 0.528). CRT significantly reduced the longest intraventricular delay in both groups - with a significant difference between average (66.2 ± 36.2 ms) and super-responders (32.5 ± 18.3 ms, <it>p </it>= 0.022). Multivariate logistic regression analysis identified the longest intraventricular delay one day after device implantation as an independent predictor of superior response to CRT (<it>p </it>= 0.038).</p> <p>Conclusions</p> <p>A significant reduction of the longest intraventricular delay correlates with superior response to CRT.</p

Limited polymorphism in Plasmodium falciparum ookinete surface antigen, von Willebrand factor A domain-related protein from clinical isolates

BACKGROUND: As malaria becomes increasingly drug resistant and more costly to treat, there is increasing urgency to develop effective vaccines. In comparison to other stages of the malaria lifecycle, sexual stage antigens are under less immune selection pressure and hence are likely to have limited antigenic diversity. METHODS: Clinical isolates from a wide range of geographical regions were collected. Direct sequencing of PCR products was then used to determine the extent of polymorphisms for the novel Plasmodium falciparum sexual stage antigen von Willebrand Factor A domain-related Protein (PfWARP). These isolates were also used to confirm the extent of diversity of sexual stage antigen Pfs28. RESULTS: PfWARP was shown to have non-synonymous substitutions at 3 positions and Pfs28 was confirmed to have a single non-synonymous substitution as previously described. CONCLUSION: This study demonstrates the limited antigenic diversity of two prospective P. falciparum sexual stage antigens, PfWARP and Pfs28. This provides further encouragement for the proceeding with vaccine trials based on these antigens

Genome-wide association study of Alzheimer's disease

In addition to apolipoprotein E (APOE), recent large genome-wide association studies (GWASs) have identified nine other genes/loci (CR1, BIN1, CLU, PICALM, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7) for late-onset Alzheimer's disease (LOAD). However, the genetic effect attributable to known loci is about 50%, indicating that additional risk genes for LOAD remain to be identified. In this study, we have used a new GWAS data set from the University of Pittsburgh (1291 cases and 938 controls) to examine in detail the recently implicated nine new regions with Alzheimer's disease (AD) risk, and also performed a meta-analysis utilizing the top 1% GWAS single-nucleotide polymorphisms (SNPs) with P<0.01 along with four independent data sets (2727 cases and 3336 controls) for these SNPs in an effort to identify new AD loci. The new GWAS data were generated on the Illumina Omni1-Quad chip and imputed at ∼2.5 million markers. As expected, several markers in the APOE regions showed genome-wide significant associations in the Pittsburg sample. While we observed nominal significant associations (P<0.05) either within or adjacent to five genes (PICALM, BIN1, ABCA7, MS4A4/MS4A6E and EPHA1), significant signals were observed 69–180 kb outside of the remaining four genes (CD33, CLU, CD2AP and CR1). Meta-analysis on the top 1% SNPs revealed a suggestive novel association in the PPP1R3B gene (top SNP rs3848140 with P=3.05E–07). The association of this SNP with AD risk was consistent in all five samples with a meta-analysis odds ratio of 2.43. This is a potential candidate gene for AD as this is expressed in the brain and is involved in lipid metabolism. These findings need to be confirmed in additional samples

Differential overexpression of SERPINA3 in human prion diseases

Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans