The Regenerative Lens: A conceptual framework for regenerative social-ecological systems

Societies must transform their dynamics to support the flourishing of life. There is increasing interest in regeneration and regenerative practice as a solution, but also limited cohered understanding of what constitutes regenerative systems at social-ecological scales. In this perspective we present a conceptual, cross-disciplinary, and action-oriented regenerative systems framework, the Regenerative Lens, informed by a wide literature review. The framework emphasizes that regenerative systems maintain positive reinforcing cycles of wellbeing within and beyond themselves, especially between humans and wider nature, such that “life begets life.” We identify five key qualities needed in systems to encourage such dynamics: an ecological worldview embodied in human action; mutualism; high diversity; agency for humans and non-humans to act regeneratively; and continuous reflexivity. We apply the Lens to an envisioned future food system to illustrate its utility as a reflexive tool and for stretching ambition. We hope that the conceptual clarity provided here will aid the necessary acceleration of learning and action toward regenerative systems

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

ADVANCED HOT GAS FILTER DEVELOPMENT

Advanced, coal-based power plants will require durable and reliable hot gas filtration systems to remove particulate contaminants from the gas streams to protect downstream components such as turbine blades from erosion damage. It is expected that the filter elements in these systems will have to be made of ceramic materials to withstand goal service temperatures of 1600 F or higher. Recent demonstration projects and pilot plant tests have indicated that the current generation of ceramic hot gas filters (cross-flow and candle configurations) are failing prematurely. Two of the most promising materials that have been extensively evaluated are clay-bonded silicon carbide and alumina-mullite porous monoliths. These candidates, however, have been found to suffer progressive thermal shock fatigue damage, as a result of rapid cooling/heating cycles. Such temperature changes occur when the hot filters are back-pulsed with cooler gas to clean them, or in process upset conditions, where even larger gas temperature changes may occur quickly and unpredictably. In addition, the clay-bonded silicon carbide materials are susceptible to chemical attack of the glassy binder phase that holds the SiC particles together, resulting in softening, strength loss, creep, and eventual failure

PRD-66 Gas Filter Development

The PRD-66 manufacturing process offers a unique approach to the production of hot gas candle filters for application in Pressurized Fluidized Bed Combustors (PFBC) and Integrated Gas Combined Cycle (IGCC) power systems. Fabricated from readily available and inexpensive raw materials, the PRD-66 process uses an admixture of textile and ceramic concepts to produce an all-oxide filter element containing no refractor ceramic fiber (RCF) residues in the finished products. The use demonstration of textile grade glass yarn as a consumable reactant gives the advantages of fabrication versatility and shape control and a unique micro-layered phase structure in the fired product, resulting in unsurpassed thermal shock resistance and operating temperature capability of greater than 1200{degrees}C in a low-cost package. This high throughput, adaptable process allows tailoring of filter element dimensions and operating properties to specific system needs with short lead times and low cost penalties

Shunt failure in idiopathic intracranial hypertension presenting with spontaneous cerebrospinal fluid leak

A case of spontaneous cerebrospinal (CSF) fluid leak after ventriculoperitoneal shunt (VPS) failure in a patient with idiopathic intracranial hypertension (IIH) is reported. This is the first report of spontaneous CSF leak in an IIH patient without a history of trauma, sinus surgery, or intracranial surgery. The diagnosis was confirmed using thin-sliced post-contrast computed tomography, which revealed a micro-dehiscence of the cribiform plate at the superior aspect of the ethmoid sinus. The patient underwent VPS revision without complication, resulting in complete amelioration of symptoms and cessation of CSF rhinorrhoea at 1 year follow up

Management of ruptured brain arteriovenous malformations

Item does not contain fulltextIntracranial arteriovenous malformations (AVMs) are a common cause of stroke in younger patients, and often present as intracerebral hemorrhages (ICH), associated with 10 % to 30 % mortality. Patients who present with a hemorrhage from an AVM should be initially stabilized according to acute management guidelines for ICH. The characteristics of a lesion including its size, location in eloquent tissue, and high-risk features will influence risk of rupture, prognosis, as well as help guide management decisions. Given that rupture is associated with an increased risk of 6 % re-rupture in the year following the initial hemorrhage, versus 1 % to 3 % predicted annual risk in non-ruptured lesions only, definitive treatment is encouraged after ICH stabilization. A rest period of 2 to 6 weeks after hemorrhage is recommended before definitive treatment to avoid disrupting friable parenchyma and the hematoma. Treatment may consist of endovascular embolization, surgical resection, radiosurgery, or a combination of these three interventions based on the lesion

Transcranial Doppler for predicting delayed cerebral ischemia after subarachnoid hemorrhage.

OBJECTIVE: Transcranial Doppler (TCD) is widely used to monitor the temporal course of vasospasm after subarachnoid hemorrhage (SAH), but its ability to predict clinical deterioration or infarction from delayed cerebral ischemia (DCI) remains controversial. We sought to determine the prognostic utility of serial TCD examination after SAH. METHODS: We analyzed 1877 TCD examinations in 441 aneurysmal SAH patients within 14 days of onset. The highest mean blood flow velocity (mBFV) value in any vessel before DCI onset was recorded. DCI was defined as clinical deterioration or computed tomographic evidence of infarction caused by vasospasm, with adjudication by consensus of the study team. Logistic regression was used to calculate adjusted odds ratios for DCI risk after controlling for other risk factors. RESULTS: DCI occurred in 21% of patients (n = 92). Multivariate predictors of DCI included modified Fisher computed tomographic score (P = 0.001), poor clinical grade (P = 0.04), and female sex (P = 0.008). After controlling for these variables, all TCD mBFV thresholds between 120 and 180 cm/s added a modest degree of incremental predictive value for DCI at nearly all time points, with maximal sensitivity by SAH day 8. However, the sensitivity of any mBFV more than 120 cm/s for subsequent DCI was only 63%, with a positive predictive value of 22% among patients with Hunt and Hess grades I to III and 36% in patients with Hunt and Hess grades IV and V. Positive predictive value was only slightly higher if mBFV exceeded 180 cm/s. CONCLUSION: Increased TCD flow velocities imply only a mild incremental risk of DCI after SAH, with maximal sensitivity by day 8. Nearly 40% of patients with DCI never attained an mBFV more than 120 cm/s during the course of monitoring. Given the poor overall sensitivity of TCD, improved methods for identifying patients at high risk for DCI after SAH are needed

Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study.

OBJECTIVES: To analyze the effect of tight glycemic control with the use of intensive insulin therapy on cerebral glucose metabolism in patients with severe brain injury. DESIGN: Retrospective analysis of a prospective observational cohort. SETTING: University hospital neurologic intensive care unit. PATIENTS: Twenty patients (median age 59 yrs) monitored with cerebral microdialysis as part of their clinical care. INTERVENTIONS: Intensive insulin therapy (systemic glucose target: 4.4-6.7 mmol/L [80-120 mg/dL]). MEASUREMENTS AND MAIN RESULTS: Brain tissue markers of glucose metabolism (cerebral microdialysis glucose and lactate/pyruvate ratio) and systemic glucose were collected hourly. Systemic glucose levels were categorized as within the target "tight" (4.4-6.7 mmol/L [80-120 mg/dL]) vs. "intermediate" (6.8-10.0 mmol/L [121-180 mg/dL]) range. Brain energy crisis was defined as a cerebral microdialysis glucose &lt;0.7 mmol/L with a lactate/pyruvate ratio &gt;40. We analyzed 2131 cerebral microdialysis samples: tight systemic glucose levels were associated with a greater prevalence of low cerebral microdialysis glucose (65% vs. 36%, p &lt; 0.01) and brain energy crisis (25% vs.17%, p &lt; 0.01) than intermediate levels. Using multivariable analysis, and adjusting for intracranial pressure and cerebral perfusion pressure, systemic glucose concentration (adjusted odds ratio 1.23, 95% confidence interval [CI] 1.10-1.37, for each 1 mmol/L decrease, p &lt; 0.001) and insulin dose (adjusted odds ratio 1.10, 95% CI 1.04-1.17, for each 1 U/hr increase, p = 0.02) independently predicted brain energy crisis. Cerebral microdialysis glucose was lower in nonsurvivors than in survivors (0.46 +/- 0.23 vs. 1.04 +/- 0.56 mmol/L, p &lt; 0.05). Brain energy crisis was associated with increased mortality at hospital discharge (adjusted odds ratio 7.36, 95% CI 1.37-39.51, p = 0.02). CONCLUSIONS: In patients with severe brain injury, tight systemic glucose control is associated with reduced cerebral extracellular glucose availability and increased prevalence of brain energy crisis, which in turn correlates with increased mortality. Intensive insulin therapy may impair cerebral glucose metabolism after severe brain injury