On the large-Q^2 behavior of the pion transition form factor

We study the transition of non-perturbative to perturbative QCD in situations with possible violations of scaling limits. To this end we consider the singly- and doubly-virtual pion transition form factor $\pi^0\to\gamma\gamma$ at all momentum scales of symmetric and asymmetric photon momenta within the Dyson-Schwinger/Bethe-Salpeter approach. For the doubly virtual form factor we find good agreement with perturbative asymptotic scaling laws. For the singly-virtual form factor our results agree with the Belle data. At very large off-shell photon momenta we identify a mechanism that introduces quantitative modifications to Efremov-Radyushkin-Brodsky-Lepage scaling.Comment: 5 pages, 7 figures, v3:contents revised, version published in PL

Spread of a highly mucoid Streptococcus pyogenes emm3/ST15 clone

<p>Abstract</p> <p>Background</p> <p>Hyaluronic acid capsule plays a key role in <it>Streptococcus pyogenes </it>virulence. Circulation of mucoid or highly encapsulated strains has been related to rheumatic fever epidemics and invasive disease in several countries. In 2009, an outbreak of mucoid <it>S. pyogenes </it>isolates was detected in northern Spain. The aim of the study was to describe clinical and molecular characteristics of mucoid strains causing this outbreak and to compare them with a sample of non-mucoid <it>S. pyogenes </it>isolates obtained during the same period of time.</p> <p>Methods</p> <p>All <it>S. pyogenes </it>isolates with a mucoid colony morphology (n = 132), 10% of non-mucoid (n = 144) and all invasive <it>S. pyogenes </it>isolates (n = 7) obtained in 2009 were included. Characterization was performed by T-agglutination, <it>emm </it>typing, pulsed field gel electrophoresis and multilocus sequence typing.</p> <p>Results</p> <p>One clone characterized as <it>emm</it>3.1/ST15 comprised 98.5% (n = 130) of all mucoid isolates. Subjects of all ages were affected. Main clinical manifestations were pharyngitis and scarlet fever, but this clone also caused invasive disease: two cases of streptococcal toxic shock syndrome, one arthritis, and one celullitis with a fatal outcome. Mucoid isolates were more prone to cause invasive disease than non-mucoid isolates (p = 0.001).</p> <p>Conclusions</p> <p>Although no acute rheumatic fever cases were detected, the most worrisome characteristics of this clone were the success for causing invasive disease and the merge of two virulent features: the serotype, <it>emm</it>3, and capsule hyper-production, expressed as a mucoid morphology.</p

Outcome Measures for Disease-Modifying Trials in Parkinson's Disease:Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative

BACKGROUND: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach.OBJECTIVE: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials.METHODS: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory.RESULTS: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages.CONCLUSION: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges.</p

Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson’s disease

An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson’s disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson’s disease, a multiarm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson’s disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of predefined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of Parkinson’s disease patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson’s disease.</p

Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson’s disease

An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson’s disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson’s disease, a multiarm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson’s disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of predefined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of Parkinson’s disease patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson’s disease.</p

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations