Variability of extracorporeal cardiopulmonary resuscitation utilization for refractory adult out-of-hospital cardiac arrest: an international survey study.

Objective: A growing interest in extracorporeal cardiopulmonary resuscitation (ECPR) as a rescue strategy for refractory adult out-of-hospital cardiac arrest (OHCA) currently exists. This study aims to determine current standards of care and practice variation for ECPR patients in the USA and Korea. Methods: In December 2015, we surveyed centers from the Korean Hypothermia Network (KORHN) Investigators and the US National Post-Arrest Research Consortium (NPARC) on current targeted temperature management and ECPR practices. This project analyzes the subsection of questions addressing ECPR practices. We summarized survey. Results: Overall, 9 KORHN and 4 NPARC centers reported having ECPR programs and had complete survey data available. Two KORHN centers utilized extracorporeal membrane oxygenation only for postarrest circulatory support in patients with refractory shock and were excluded from further analysis. Centers with available ECPR generally saw a high volume of OHCA patients (10/11 centers care for \u3e75 OHCA a year). Location of, and providers trained for cannulation varied across centers. All centers in both countries (KORHN 7/7, NPARC 4/4) treated comatose ECPR patients with targeted temperature management. All NPARC centers and four of seven KORHN centers reported having a standardized hospital protocol for ECPR. Upper age cutoff for eligibility ranged from 60 to 75 years. No absolute contraindications were unanimous among centers. Conclusion: A wide variability in practice patterns exist between centers performing ECPR for refractory OHCA in the US and Korea. Standardized protocols and shared research databases might inform best practices, improve outcomes, and provide a foundation for prospective studies

Alpha-synuclein: a pathological factor with Aβ and tau and biomarker in Alzheimers disease

Abstract Background Alpha-synuclein (α-syn) is considered the main pathophysiological protein component of Lewy bodies in synucleinopathies. α-Syn is an intrinsically disordered protein (IDP), and several types of structural conformations have been reported, depending on environmental factors. Since IDPs may have distinctive functions depending on their structures, α-syn can play different roles and interact with several proteins, including amyloid-beta (Aβ) and tau, in Alzheimers disease (AD) and other neurodegenerative disorders. Main body In previous studies, α-syn aggregates in AD brains suggested a close relationship between AD and α-syn. In addition, α-syn directly interacts with Aβ and tau, promoting mutual aggregation and exacerbating the cognitive decline. The interaction of α-syn with Aβ and tau presented different consequences depending on the structural forms of the proteins. In AD, α-syn and tau levels in CSF were both elevated and revealed a high positive correlation. Especially, the CSF α-syn concentration was significantly elevated in the early stages of AD. Therefore, it could be a diagnostic marker of AD and help distinguish AD from other neurodegenerative disorders by incorporating other biomarkers. Conclusion The overall physiological and pathophysiological functions, structures, and genetics of α-syn in AD are reviewed and summarized. The numerous associations of α-syn with Aβ and tau suggested the significance of α-syn, as a partner of the pathophysiological roles in AD. Understanding the involvements of α-syn in the pathology of Aβ and tau could help address the unresolved issues of AD. In particular, the current status of the CSF α-syn in AD recommends it as an additional biomarker in the panel for AD diagnosis

Rapid exploration with multi-rotors: A frontier selection method for high speed flight

Exploring and mapping previously unknown environments while avoiding collisions with obstacles is a fundamental task for autonomous robots. In scenarios where this needs to be done rapidly, multi-rotors are a good choice for the task, as they can cover ground at potentially very high velocities. Flying at high velocities, however, implies the ability to rapidly plan trajectories and to react to new information quickly. In this paper, we propose an extension to classical frontier -based exploration that facilitates exploration at high speeds. The extension consists of a reactive mode in which the multi-rotor rapidly selects a goal frontier from its field of view. The goal frontier is selected in a way that minimizes the change in velocity necessary to reach it. While this approach can increase the total path length, it significantly reduces the exploration time, since the multi-rotor can fly at consistently higher speeds

The Effect of Direct Communication between Emergency Physicians and Interventional Cardiologists on Door to Balloon Times in STEMI

We developed an institutional protocol mandating emergency physicians to contact the interventional cardiologist directly in all cases of ST-segment elevation myocardial infarction (STEMI) and hypothesized that this would reduce door-to-balloon-times (DTBT). From January 2004 to July 2006, 208 patients with STEMI were treated with primary percutaneous coronary intervention (PCI). A total of 144 patients were treated before implementing the new protocol ("before") and 64 patients were treated after the implementation ("after"). The DTBT was significantly reduced from 148±101 min to 108±56 min (p<0.05). While only 25% of the "before" patients received PCI within 90 min after arrival, 50% of the "after" patients received PCI within 90 min (p<0.05). There were no significant differences between two groups in other outcomes (postprocedural TIMI flow, mortality, subsequent stroke, heart failure, shock, reinfarction, length of stay in intensive care unit, and the total hospital length of stay). In conclusion, mandating emergency physicians to directly notify interventional cardiologists of all STEMI patients reduces DTBT

Substituent effects on energetics and crystal morphology modulate singlet fission in 9,10-bis(phenylethynyl)anthracenes

Singlet fission (SF) converts a singlet exciton into two triplet excitons in two or more electronically coupled organic chromophores, which may then be used to increase solar cell efficiency. Many known SF chromophores are unsuitable for device applications due to chemical instability or low triplet state energies. The results described here show that efficient SF occurs in derivatives of 9,10-bis(phenylethynyl)anthracene (BPEA), which is a highly robust and tunable chromophore. Fluoro and methoxy substituents at the 4- and 4′-positions of the BPEA phenyl groups control the intermolecular packing in the crystal structure, which alters the interchromophore electronic coupling, while also changing the SF energetics. The lowest excited singlet state (S1) energy of 4,4′-difluoro-BPEA is higher than that of BPEA so that the increased thermodynamic favorability of SF results in a (16 ± 2 ps)−1 SF rate and a 180% ± 16% triplet yield, which is about an order of magnitude faster than BPEA with a comparable triplet yield. By contrast, 4-fluoro-4′-methoxy-BPEA and 4,4′-dimethoxy-BPEA have slower SF rates, (90 ± 20 ps)−1 and (120 ± 10 ps)−1, and lower triplet yields, (110 ± 4)% and (168 ± 7)%, respectively, than 4,4′-difluoro-BPEA. These differences are attributed to changes in the crystal structure controlling interchromophore electronic coupling as well as SF energetics in these polycrystalline solids

Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation

Background: Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients. Methods and Findings: Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6–15.8, p = 1×10−7) and ME ARDS (OR 8.4, 95% CI 2.9–24.2, p = 9×10−5) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10−4) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers. Conclusions: Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients. Please see later in the article for the Editors' Summar

Blood amyloid-β oligomerization associated with neurodegeneration of Alzheimers disease

Introduction Oligomeric amyloid-ß is a major toxic species associated with Alzheimers disease pathogenesis. Methods used to measure oligomeric amyloid-β in the blood have increased in number in recent years. The Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) is a specific method to measure oligomerization tendencies in the blood. The objective of this study was to determine the association between amyloid-ß oligomerization in the plasma and structural changes of the brain. Methods We studied 162 subjects composed of 92 community-based normal healthy subjects, 17 with subjective cognitive decline, 14 with mild cognitive impairment and 39 with Alzheimers disease dementia. All subjects underwent MDS-OAβ and three-dimensional T1 magnetic resonance imaging. To determine the structural changes of the brain that are statistically correlated with MDS-OAβ level, we used voxel-based morphometry with corrections for age and total intracranial volume covariates. Results We found brain volume reduction in the bilateral temporal, amygdala, parahippocampal and lower parietal lobe and left cingulate and precuneus regions (family-wise error, p < 0.05). Reduction was also found in white matter in proximity to the left temporal and bilateral lower parietal lobes and posterior corpus callosum (family-wise error, p < 0.05). Brain volume increment was not observed in any regions within grey or white matter. Discussion Findings suggest that substantial correlation exists between amyloid ß oligomerization in the blood and brain volume reduction in the form of Alzheimers disease despite of uncertainty in the casual relationship.This work was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C1251)

Global patterns in genomic diversity underpinning the evolution of insecticide resistance in the aphid crop pest Myzus persicae

Abstract: The aphid Myzus persicae is a destructive agricultural pest that displays an exceptional ability to develop resistance to both natural and synthetic insecticides. To investigate the evolution of resistance in this species we generated a chromosome-scale genome assembly and living panel of >110 fully sequenced globally sampled clonal lines. Our analyses reveal a remarkable diversity of resistance mutations segregating in global populations of M. persicae. We show that the emergence and spread of these mechanisms is influenced by host–plant associations, uncovering the widespread co‐option of a host-plant adaptation that also offers resistance against synthetic insecticides. We identify both the repeated evolution of independent resistance mutations at the same locus, and multiple instances of the evolution of novel resistance mechanisms against key insecticides. Our findings provide fundamental insights into the genomic responses of global insect populations to strong selective forces, and hold practical relevance for the control of pests and parasites.Peer reviewedFinal Published versio