Symptomatic intracranial hemorrhage (sICH) is the most feared complication of intravenous thrombolytic therapy in acute ischemic stroke. Treatment of sICH is based on expert opinion and small case ...series, with the efficacy of such treatments not well established. This document aims to provide an overview of sICH with a focus on pathophysiology and treatment.
A literature review was performed for randomized trials, prospective and retrospective studies, opinion papers, case series, and case reports on the definitions, epidemiology, risk factors, pathophysiology, treatment, and outcome of sICH. The document sections were divided among writing group members who performed the literature review, summarized the literature, and provided suggestions on the diagnosis and treatment of patients with sICH caused by systemic thrombolysis with alteplase. Several drafts were circulated among writing group members until a consensus was achieved.
sICH is an uncommon but severe complication of systemic thrombolysis in acute ischemic stroke. Prompt diagnosis and early correction of the coagulopathy after alteplase have remained the mainstay of treatment. Further research is required to establish treatments aimed at maintaining integrity of the blood-brain barrier in acute ischemic stroke based on inhibition of the underlying biochemical processes.
Small pulmonary nodules are often difficult to identify during thoracoscopic resection, and preoperative CT-guided localization performed using either hookwire placement or methylene blue injection ...can be helpful. The purpose of this study is to compare the localization success and complication rates of these two techniques.
One hundred two consecutive patients who underwent a total of 109 localization procedures performed with CT fluoroscopic guidance were analyzed. The procedures included 52 hookwire insertions and 57 methylene blue injections. The localization success and complication rates associated with the two groups were compared.
All nodules in both groups were identified intraoperatively, except for those in two patients in the hookwire group who did not proceed to undergo same-day surgery, including one with a massive systemic air embolus that resulted in death. Hookwires were dislodged in seven of 52 cases (13%), but the surgeons were still able to locate the nodules through visualization of the parenchymal puncture sites. The total number of complications was higher in the hookwire insertion group than in the methylene blue injection group, but this trend was not statistically significant, with all types of complications occurring in 28 cases (54%) versus 26 cases (46%) (p = 0.45), major complications noted in four cases (8%) versus one case (2%) (p = 0.19), pneumothorax observed in 20 cases (38%) versus 14 cases (25%) (p = 0.15), and perilesional hemorrhage occurring in six cases (12%) versus two cases (4%) (p = 0.15), respectively.
The present study suggests that methylene blue injection and hookwire insertion are statistically equivalent for preoperative pulmonary nodule localization; however, seven of 52 hookwires dislodged, and trends toward more frequent and severe complications were noted in the hookwire insertion group.
While the focus of earth system governance is on the human-social aspects of Earth system changes, law has played a peripheral part in the earth system governance scientific agenda. Earth system ...governance perspectives have also not significantly infiltrated the juridical domain. In this paper we seek to initiate a debate on the juridical dimensions of earth system governance. We make out a case in support of developing a new overarching legal phenomenon that, more than environmental law (among others) comprehensively accommodates and encapsulates the juridical aspects of earth system governance, including a new accompanying research agenda. We call this new legal phenomenon ‘earth system law’. Earth system law, as we aim to show, could introduce a new era in legal scholarship, while seeking to comprehensively respond to the regulatory challenges presented by a changing Earth system in the Anthropocene. For illustrative purposes, we provide a conceptual framework of earth system law by focusing on international environmental law. We show how core considerations of earth system law might set in motion some of the conceptual and regulatory changes required to eventually progress from international environmental law to a mature form of earth system law.
Commensal bacteria are believed to have important roles in human health. The mechanisms by which they affect mammalian physiology remain poorly understood, but bacterial metabolites are likely to be ...key components of host interactions. Here we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids that they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, although future studies are needed to define their potential physiological role in humans. Our results suggest that chemical mimicry of eukaryotic signalling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a possible small-molecule therapeutic modality (microbiome-biosynthetic gene therapy).
Production optimization under geological uncertainty is computationally expensive, as a large number of well control schedules must be evaluated over multiple geological realizations. In this work, a ...convolutional-recurrent neural network (CNN-RNN) proxy model is developed to predict well-by-well oil and water rates, for given time-varying well bottom-hole pressure (BHP) schedules, for each realization in an ensemble. This capability enables the estimation of the objective function and nonlinear constraint values required for robust optimization. The proxy model represents an extension of a recently developed long short-term memory (LSTM) RNN proxy designed to predict well rates for a single geomodel. A CNN is introduced here to processes permeability realizations, and this provides the initial states for the RNN. The CNN-RNN proxy is trained using simulation results for 300 different sets of BHP schedules and permeability realizations. We demonstrate proxy accuracy for oil-water flow through multiple realizations of 3D multi-Gaussian permeability models. The proxy is then incorporated into a closed-loop reservoir management (CLRM) workflow, where it is used with particle swarm optimization and a filter-based method for nonlinear constraint satisfaction. History matching is achieved using an adjoint-gradient-based procedure. The proxy model is shown to perform well in this setting for five different (synthetic) ‘true’ models. Improved net present value along with constraint satisfaction and uncertainty reduction are observed with CLRM. For the robust production optimization steps, the proxy provides
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(100) runtime speedup over simulation-based optimization.
The purpose of this study was to investigate the prevalence of hepatic steatosis in an asymptomatic U.S. adult population using attenuation values at unenhanced CT as the reference standard. We also ...assessed the utility of known clinical risk factors for diagnosis.
For 3,357 consecutive asymptomatic adults (1,865 women and 1,492 men; mean age, 57.0 years), hepatic and splenic CT attenuation values (Hounsfield units) were obtained by unenhanced CT using a low-dose colonography technique for colorectal cancer screening. Multiple attenuation criteria for steatosis were applied, including liver thresholds and comparison of liver and spleen attenuation. Relevant clinical risk factors were compared against a CT liver attenuation < or = 40 HU, which has been shown to exclude mild steatosis.
Mean liver attenuation was 58.8 +/- 10.8 (SD) HU. The prevalence of moderate-to-severe hepatic steatosis (defined by liver attenuation < or = 40 HU) was 6.2% (208/3,357). For CT attenuation criteria that include milder degrees of steatosis, prevalence increased to as high as 45.9% (1,542/3,357) for a liver-to-spleen attenuation ratio of < or = 1.1. Overweight status (body mass index > 25) was a sensitive indicator for moderate-to-severe steatosis (92.8%) but was highly nonspecific (37.5%). Other clinical risk factors, such as diabetes, dyslipidemia, hypertension, alcohol overuse, and hepatitis, were more specific (77.6-92.4%) but highly insensitive (1.9-37.5%). Combining clinical risk factors did not substantially increase the accuracy for screening.
Assessment of liver attenuation by use of unenhanced CT represents an objective and noninvasive means for detection of asymptomatic hepatic steatosis, whereas clinical risk factor assessment is unreliable. Further longitudinal investigation is needed to determine the most appropriate attenuation threshold and the risk for disease progression to steatohepatitis and cirrhosis.
First developed in Earth system science, the idea of planetary boundaries has gradually spilled over into social science research in the past decade. An interdisciplinary body of literature has ...emerged as a result at the intersection of Earth system science, law and governance. In this article, we provide a bird’s eye view of the state of the art, and examine how social scientists frame the planetary boundaries framework and what they identify as key regulatory challenges and implications. To that end, we conducted a systematic review of 80 peer‐reviewed articles identified through a keyword search. Our survey finds that social scientists have approached the planetary boundaries framework using four key problem framings, which revolve around the notion of planetary boundaries as embodying a set of interdependent and politically constructed environmental limits that are global in scale. We also identify four key clusters of governance solutions offered in the literature, which broadly relate to the ideas of institutionalizing, coordinating, downscaling and democratizing planetary boundaries. We then apply the foregoing insights to the legal domain and explore their implications for law. More specifically, we discuss how the recently proposed notion of Earth system law is related to these emerging problem framings and how it might contribute to these responses.
Nexus governance recognises that sustainability concerns such as water, energy, and food security are interlinked and provides an alternative to fragmented governance. Although it has been applied ...mostly in the domestic context, the need for nexus governance is also apparent at a planetary scale, as highlighted by interacting planetary boundaries, global telecoupling, and global tipping cascades. However, international environmental law is unable to facilitate what we call ‘planetary nexus governance’. This is mainly because international environmental law lacks an ecological Grundnorm and because its primary rules of conduct remain fragmented in the absence of effective secondary rules on how primary rules should relate to each other. Recognising this challenge, scholars have recently proposed earth system law as a new framework to rethink, in an integrated way, law in an Anthropocene context. Building on this framework, we suggest that international environmental law should adopt a unifying Grundnorm such as planetary integrity. We also suggest that international institutional law, as a body of secondary rules, has an important role to play in facilitating planetary nexus governance by bringing together fragmented bodies of international law. We briefly discuss ways in which international environmental law could reorientate itself to better facilitate planetary nexus governance.
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