Translational perspectives on perfusion-diffusion mismatch in ischemic stroke

Magnetic resonance imaging has tremendous potential to illuminate ischemic stroke pathophysiology and guide rational treatment decisions. Clinical applications to date have been largely limited to trials. However, recent analyses of the major clinical studies have led to refinements in selection criteria and improved understanding of the potential implications for the risk vs. benefit of thrombolytic therapy. In parallel, preclinical studies have provided complementary information on the evolution of stroke that is difficult to obtain in humans due to the requirement for continuous or repeated imaging and pathological verification. We review the clinical and preclinical advances that have led to perfusion–diffusion mismatch being applied in phase 3 randomized trials and, potentially, future routine clinical practice

Living clinical guidelines for stroke: Updates, challenges and opportunities

Continued growth in the number of published clinical studies has necessitated changes to the way evidence-based resources such as clinical guidelines are developed and updated. The Australian and New Zealand Clinical Guidelines for Stroke Management (https://informme.org.au/guidelines/clinical-guidelines-for-stroke-management) are based on continual evidence surveillance and timely updates to recommendations as new research is published. In this article, we outline the main updates to recommendations since the guidelines moved into a living mode in 2018, and discuss key challenges and benefits of living guidelines

Detection of Potential Transit Signals in Sixteen Quarters of Kepler Mission Data

We present the results of a search for potential transit signals in four years of photometry data acquired by the Kepler Mission. The targets of the search include 111,800 stars which were observed for the entire interval and 85,522 stars which were observed for a subset of the interval. We found that 9,743 targets contained at least one signal consistent with the signature of a transiting or eclipsing object, where the criteria for detection are periodicity of the detected transits, adequate signal-to-noise ratio, and acceptance by a number of tests which reject false positive detections. When targets that had produced a signal were searched repeatedly, an additional 6,542 signals were detected on 3,223 target stars, for a total of 16,285 potential detections. Comparison of the set of detected signals with a set of known and vetted transit events in the Kepler field of view shows that the recovery rate for these signals is 96.9%. The ensemble properties of the detected signals are reviewed.Comment: Accepted by ApJ Supplemen

Triplet energy differences and the low lying structure of Ga 62

Background: Triplet energy differences (TED) can be studied to yield information on isospin-non-conserving interactions in nuclei. Purpose: The systematic behavior of triplet energy differences (TED) of T=1, J\u3c0=2+ states is examined. The A=62 isobar is identified as having a TED value that deviates significantly from an otherwise very consistent trend. This deviation can be attributed to the tentative assignments of the pertinent states in Ga62 and Ge62. Methods: An in-beam \u3b3-ray spectroscopy experiment was performed to identify excited states in Ga62 using Gamma-Ray Energy Tracking In-Beam Nuclear Array with the S800 spectrometer at NSCL using a two-nucleon knockout approach. Cross-section calculations for the knockout process and shell-model calculations have been performed to interpret the population and decay properties observed. Results: Using the systematics as a guide, a candidate for the transition from the T=1, 2+ state is identified. However, previous work has identified similar states with different J\u3c0 assignments. Cross-section calculations indicate that the relevant T=1, 2+ state should be one of the states directly populated in this reaction. Conclusions: As spins and parities were not measurable, it is concluded that an unambiguous identification of the first T=1, 2+ state is required to reconcile our understanding of TED systematics

Community Consensus Guidelines to Support FAIR Data Standards in Clinical Research Studies in Primary Mitochondrial Disease

Primary mitochondrial diseases (PMD) are genetic disorders with extensive clinical and molecular heterogeneity where therapeutic development efforts have faced multiple challenges. Clinical trial design, outcome measure selection, lack of reliable biomarkers, and deficiencies in long-term natural history data sets remain substantial challenges in the increasingly active PMD therapeutic development space. Developing "FAIR" (findable, accessible, interoperable, reusable) data standards to make data sharable and building a more transparent community data sharing paradigm to access clinical research metadata are the first steps to address these challenges. This collaborative community effort describes the current landscape of PMD clinical research data resources available for sharing, obstacles, and opportunities, including ways to incentivize and encourage data sharing among diverse stakeholders. This work highlights the importance of, and challenges to, developing a unified system that enables clinical research structured data sharing and supports harmonized data deposition standards across clinical consortia and research groups. The goal of these efforts is to improve the efficiency and effectiveness of drug development and improve understanding of the natural history of PMD. This initiative aims to maximize the benefit for PMD patients, research, industry, and other stakeholders while acknowledging challenges related to differing needs and international policies on data privacy, security, management, and oversight

Face familiarity, distinctiveness, and categorical perception

Four experiments with faces support the original interpretation of categorical perception (CP) as only present for familiar categories. Unlike in the results of Levin and Beale (2000), no evidence is found for face identity CP with unfamiliar faces. Novel face identities were shown to be capable of encoding for immediate sorting purposes but the representations utilized do not have the format of perceptual categories. One possibility explored was that a choice of a distinctive face as an end-point in a morphed continuum can spuriously produce effects that resemble CP. Such morphed continua provided unequal psychological responses to equal physical steps though much more so in a better likeness paradigm than for forced-choice recognition. Thus, researchers doing almost the same experiments may produce very different results and come to radically different conclusions

Sustaining a new model of acute stroke care : A mixed-method process evaluation of the Melbourne Mobile Stroke Unit

Background Internationally, Mobile Stroke Unit (MSU) ambulances have changed pre-hospital acute stroke care delivery. MSU clinical and cost-effectiveness studies are emerging, but little is known about important factors for achieving sustainability of this innovative model of care. Methods Mixed-methods study from the Melbourne MSU (operational since November 2017) process evaluation. Participant purposive sampling included clinical, operational and executive/management representatives from Ambulance Victoria (AV) (emergency medical service provider), the MSU clinical team, and receiving hospitals. Sustainability was defined as ongoing MSU operations, including MSU workforce and future model considerations. Theoretically-based on-line survey with Unified Theory of Acceptance and Use of Technology (UTAUT), Self Determination Theory (SDT, Intrinsic Motivation), and open-text questions targeting barriers and benefits was administered (June-September 2019). Individual/group interviews were conducted, eliciting improvement suggestions and requirements for ongoing use. Descriptive and regression analyses (quantitative data) and directed content and thematic analysis (open text and interview data) were conducted. Results There were 135 surveys completed. Identifying that the MSU was beneficial to daily work (β = 0.61), not experiencing pressure/tension about working on the MSU (β = 0.17) and thinking they did well working within the team model (β = 0.17) were significantly associated with wanting to continue working within the MSU model [R2 = 0.76; F(15, 60) = 12.76, P < .001]. Experiences varied between those on the MSU team and those working with the MSU. Advantages were identified for patients (better, faster care) and clinicians (interdisciplinary learning). Disadvantages included challenges integrating into established systems, and establishing working relationships. Themes identified from 35 interviews were MSU team composition, MSU vehicle design and layout, personnel recruitment and rostering, communication improvements between organisations, telemedicine options, MSU operations and dispatch specificity. Conclusion Important factors affecting the sustainability of the MSU model of stroke care emerged. A cohesive team approach, with identifiable benefits and good communication between participating organisations is important for clinical and operational sustainability

Planetary Candidates Observed by Kepler. VIII. A Fully Automated Catalog With Measured Completeness and Reliability Based on Data Release 25

We present the Kepler Object of Interest (KOI) catalog of transiting exoplanets based on searching four years of Kepler time series photometry (Data Release 25, Q1-Q17). The catalog contains 8054 KOIs of which 4034 are planet candidates with periods between 0.25 and 632 days. Of these candidates, 219 are new and include two in multi-planet systems (KOI-82.06 and KOI-2926.05), and ten high-reliability, terrestrial-size, habitable zone candidates. This catalog was created using a tool called the Robovetter which automatically vets the DR25 Threshold Crossing Events (TCEs, Twicken et al. 2016). The Robovetter also vetted simulated data sets and measured how well it was able to separate TCEs caused by noise from those caused by low signal-to-noise transits. We discusses the Robovetter and the metrics it uses to sort TCEs. For orbital periods less than 100 days the Robovetter completeness (the fraction of simulated transits that are determined to be planet candidates) across all observed stars is greater than 85%. For the same period range, the catalog reliability (the fraction of candidates that are not due to instrumental or stellar noise) is greater than 98%. However, for low signal-to-noise candidates between 200 and 500 days around FGK dwarf stars, the Robovetter is 76.7% complete and the catalog is 50.5% reliable. The KOI catalog, the transit fits and all of the simulated data used to characterize this catalog are available at the NASA Exoplanet Archive.Comment: 61 pages, 23 Figures, 9 Tables, Accepted to The Astrophysical Journal Supplement Serie

Phenomenology and Cosmology of an Electroweak Pseudo-Dilaton and Electroweak Baryons

In many strongly-interacting models of electroweak symmetry breaking the lowest-lying observable particle is a pseudo-Goldstone boson of approximate scale symmetry, the pseudo-dilaton. Its interactions with Standard Model particles can be described using a low-energy effective nonlinear chiral Lagrangian supplemented by terms that restore approximate scale symmetry, yielding couplings of the pseudo-dilaton that differ from those of a Standard Model Higgs boson by fixed factors. We review the experimental constraints on such a pseudo-dilaton in light of new data from the LHC and elsewhere. The effective nonlinear chiral Lagrangian has Skyrmion solutions that may be identified with the `electroweak baryons' of the underlying strongly-interacting theory, whose nature may be revealed by the properties of the Skyrmions. We discuss the finite-temperature electroweak phase transition in the low-energy effective theory, finding that the possibility of a first-order electroweak phase transition is resurrected. We discuss the evolution of the Universe during this transition and derive an order-of-magnitude lower limit on the abundance of electroweak baryons in the absence of a cosmological asymmetry, which suggests that such an asymmetry would be necessary if the electroweak baryons are to provide the cosmological density of dark matter. We revisit estimates of the corresponding spin-independent dark matter scattering cross section, with a view to direct detection experiments.Comment: 34 pages, 4 figures, additional references adde