Secukinumab demonstrated sustained retention, effectiveness and safety in a real-world setting in patients with moderate-to-severe plaque psoriasis: long-term results from an interim analysis of the SERENA study.

Randomized controlled trials of secukinumab have shown sustained efficacy and a favourable safety profile in multiple manifestations of psoriatic disease. To assess the long-term, real-world retention, effectiveness and safety of secukinumab in routine clinical practice for the treatment of moderate-to-severe plaque-type psoriasis (PsO). SERENA (CAIN457A3403) is a large, ongoing, longitudinal, observational study conducted at 438 sites and 19 countries for an expected duration of up to 5 years in adult patients with moderate-to-severe PsO, psoriatic arthritis and ankylosing spondylitis. Patients received ≥16 weeks of secukinumab treatment before enrolment. This interim analysis presents data from PsO patients, who were enrolled in the study between October-2016 and October-2018 and were observed for ≥2 years. In total, 1756 patients (67.3% male) with a mean age of 48.4 years and body mass index of 28.8 kg/m <sup>2</sup> were included in the analysis. The secukinumab treatment retention rates after 1, 2 and 3 years in the study were 88.0%, 76.4% and 60.5%, respectively. Of the 648 patients who discontinued the study, the most common reasons included lack of efficacy (42.6%), adverse event (17.4%), physician decision (12.2%) and subject decision (11.6%). Mean ± SD absolute PASI was 21.0 ± 13.0 at the start of treatment (n = 1,564). At baseline, the mean ± SD PASI score reduced to 2.6 ± 4.8 and remained low at Year 1 (2.3 ± 4.3), Year 2 (1.9 ± 3.6) and Year 3 (1.9 ± 3.5). The safety profile of secukinumab during the SERENA study was consistent with its known safety profile, with no new safety signals reported. Particularly, low rates of inflammatory bowel disease (0.3%; Incidence Rate [IR]:0.15), candida infections (3.1%; IR:1.43) and MACE (0.9%; IR:0.37) were observed. Secukinumab showed high treatment persistence, sustained effectiveness and a favourable safety profile up to 3 years of follow-up in the real-world population of PsO patients observed in SERENA

Emergent variant modeling of the serological repertoire to norovirus in young children

Human norovirus is the leading cause of acute gastroenteritis. Young children and the elderly bear the greatest burden of disease, representing more than 200,000 deaths annually. Infection prevalence peaks at younger than 2 years and is driven by novel GII.4 variants that emerge and spread globally. Using a surrogate neutralization assay, we characterize the evolution of the serological neutralizing antibody (nAb) landscape in young children as they transition between sequential GII.4 pandemic variants. Following upsurge of the replacement variant, antigenic cartography illustrates remodeling of the nAb landscape to the new variant accompanied by improved nAb titer. However, nAb relative avidity remains focused on the preceding variant. These data support immune imprinting as a mechanism of immune evasion and GII.4 virus persistence across a population. Understanding the complexities of immunity to rapidly evolving and co-circulating viral variants, like those of norovirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), and dengue viruses, will fundamentally inform vaccine design for emerging pathogens

First Observation of Coherent π0\pi^0 Production in Neutrino Nucleus Interactions with Eν<E_{\nu}< 2 GeV

The MiniBooNE experiment at Fermilab has amassed the largest sample to date of $\pi^0$s produced in neutral current (NC) neutrino-nucleus interactions at low energy. This paper reports a measurement of the momentum distribution of $\pi^0$s produced in mineral oil (CH$_2$) and the first observation of coherent $\pi^0$ production below 2 GeV. In the forward direction, the yield of events observed above the expectation for resonant production is attributed primarily to coherent production off carbon, but may also include a small contribution from diffractive production on hydrogen. Integrated over the MiniBooNE neutrino flux, the sum of the NC coherent and diffractive modes is found to be (19.5 $\pm$1.1 (stat) $\pm$2.5 (sys))% of all exclusive NC $\pi^0$ production at MiniBooNE. These measurements are of immediate utility because they quantify an important background to MiniBooNE's search for $\nu_{\mu} \to \nu_e$ oscillations.Comment: Submitted to Phys. Lett.

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

The Future of Psychopharmacological Enhancements: Expectations and Policies

The hopes and fears expressed in the debate on human enhancement are not always based on a realistic assessment of the expected possibilities. Discussions about extreme scenarios may at times obscure the ethical and policy issues that are relevant today. This paper aims to contribute to an adequate and ethically sound societal response to actual current developments. After a brief outline of the ethical debate concerning neuro-enhancement, it describes the current state of the art in psychopharmacological science and current uses of psychopharmacological enhancement, as well as the prospects for the near future. It then identifies ethical issues regarding psychopharmacological enhancements that require attention from policymakers, both on the professional and on the governmental level. These concern enhancement research, the gradual expansion of medical categories, off-label prescription and responsibility of doctors, and accessibility of enhancers on the Internet. It is concluded that further discussion on the advantages and drawbacks of enhancers on a collective social level is still needed

Test of Lorentz and CPT violation with Short Baseline Neutrino Oscillation Excesses

The sidereal time dependence of MiniBooNE electron neutrino and anti-electron neutrino appearance data are analyzed to search for evidence of Lorentz and CPT violation. An unbinned Kolmogorov-Smirnov test shows both the electron neutrino and anti-electron neutrino appearance data are compatible with the null sidereal variation hypothesis to more than 5%. Using an unbinned likelihood fit with a Lorentz-violating oscillation model derived from the Standard Model Extension (SME) to describe any excess events over background, we find that the electron neutrino appearance data prefer a sidereal time-independent solution, and the anti-electron neutrino appearance data slightly prefer a sidereal time-dependent solution. Limits of order 10E-20 GeV are placed on combinations of SME coefficients. These limits give the best limits on certain SME coefficients for muon neutrino to electron neutrino and anti-muon neutrino to anti-electron neutrino oscillations. The fit values and limits of combinations of SME coefficients are provided.Comment: 14 pages, 3 figures, and 2 tables, submitted to Physics Letters

An Empirical Comparison of Consumer Innovation Adoption Models: Implications for Subsistence Marketplaces

So called “pro-poor” innovations may improve consumer wellbeing in subsistence marketplaces. However, there is little research that integrates the area with the vast literature on innovation adoption. Using a questionnaire where respondents were asked to provide their evaluations about a mobile banking innovation, this research fills this gap by providing empirical evidence of the applicability of existing innovation adoption models in subsistence marketplaces. The study was conducted in Bangladesh among a geographically dispersed sample. The data collected allowed an empirical comparison of models in a subsistence context. The research reveals the most useful models in this context to be the Value Based Adoption Model and the Consumer Acceptance of Technology model. In light of these findings and further examination of the model comparison results the research also shows that consumers in subsistence marketplaces are not just motivated by functionality and economic needs. If organizations cannot enhance the hedonic attributes of a pro-poor innovation, and reduce the internal/external constraints related to adoption of that pro-poor innovation, then adoption intention by consumers will be lower

The On-orbit Calibrations for the Fermi Large Area Telescope

The Large Area Telescope (LAT) on--board the Fermi Gamma ray Space Telescope began its on--orbit operations on June 23, 2008. Calibrations, defined in a generic sense, correspond to synchronization of trigger signals, optimization of delays for latching data, determination of detector thresholds, gains and responses, evaluation of the perimeter of the South Atlantic Anomaly (SAA), measurements of live time, of absolute time, and internal and spacecraft boresight alignments. Here we describe on orbit calibration results obtained using known astrophysical sources, galactic cosmic rays, and charge injection into the front-end electronics of each detector. Instrument response functions will be described in a separate publication. This paper demonstrates the stability of calibrations and describes minor changes observed since launch. These results have been used to calibrate the LAT datasets to be publicly released in August 2009.Comment: 60 pages, 34 figures, submitted to Astroparticle Physic