U.S. Billion-ton Update: Biomass Supply for a Bioenergy and Bioproducts Industry

The Report, Biomass as Feedstock for a Bioenergy and Bioproducts Industry: The Technical Feasibility of a Billion-Ton Annual Supply (generally referred to as the Billion-Ton Study or 2005 BTS), was an estimate of “potential” biomass within the contiguous United States based on numerous assumptions about current and future inventory and production capacity, availability, and technology. In the 2005 BTS, a strategic analysis was undertaken to determine if U.S. agriculture and forest resources have the capability to potentially produce at least one billion dry tons of biomass annually, in a sustainable manner—enough to displace approximately 30% of the country’s present petroleum consumption. To ensure reasonable confidence in the study results, an effort was made to use relatively conservative assumptions. However, for both agriculture and forestry, the resource potential was not restricted by price. That is, all identified biomass was potentially available, even though some potential feedstock would more than likely be too expensive to actually be economically available. In addition to updating the 2005 study, this report attempts to address a number of its shortcoming

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Comments on “A Shorter Door-In-Door-Out Time Is Associated with Improved Outcome in Large Vessel Occlusion Stroke”

Door-in-door-out (DIDO) time has been considered an important factor for prognostication in large vessel occlusion stroke (LVOS) patients. Recently, Sigal et al. have concluded in their paper, “A Shorter Door-In-Door-Out Time Is Associated with Improved Outcome in Large Vessel Occlusion Stroke,” that DIDO was not an independent risk factor for worse outcomes following LVOS. In this letter to the editor, we argue that DIDO time should still be considered an important prognosticator for outcomes in LVOS, despite not being found to be significant in their multivariable analysis. Despite our concerns, we wholeheartedly agree with the authors that clinicians should still need to expedite patients who have LVOS to undergo thrombectomy, regardless of where they are during the critical period of time

Role of the Critical Care Resuscitation Unit in a Comprehensive Stroke Center: Operations for Mechanical Thrombectomy During the Pandemic

Introduction: Standard of care for patients with acute ischemic stroke from large vessel occlusion (AISLVO) includes prompt evaluation for urgent mechanical thrombectomy (MT) at a comprehensive stroke center (CSC). During the start of the coronavirus 2019 pandemic (COVID-19), there were reports about disruption to emergency department (ED) operations and delays in management of patients with AIS-LVO. In this study we investigate the outcome and operations for patients who were transferred from different EDs to an academic CSC’s critical care resuscitation unit (CCRU), which specializes in expeditious transfer of time-sensitive disease. Methods: This was a pre-post retrospective study using prospectively collected clinical data from our CSC’s stroke registry. Adult patientswho were transferred fromany ED to the CCRUand underwent MT were eligible. We compared time intervals in the pre-pandemic (PP) period between January 2018– February 2020, such as ED in-out and CCRU arrival-angiography, to those during the pandemic (DP) between March 2020–May 31, 2021. We used classification and regression tree (CART) analysis to identify which time intervals, besides clinical factors, were associated with good neurological outcome (90-day modified Rankin scale 0–2). Results: We analyzed 203 patients: 135 (66.5%) in the PP group and 68 (33.5%) in the DP group. Time from ED triage to computed tomography (difference 7 minutes, 95% confidence interval [CI] −12 to −1, P < 0.01) for the DP group was statistically longer, but ED in-out was similar for both groups. Time from CCRU arrival to angiography (difference 9 minutes, 95% CI 4–13, P < 0.01) for the DP group was shorter. Forty-nine percent of the DP group achieved mRS ≤ 2 vs 32% for the PP group (difference −17%, 95% CI −0.32 to −0.03, P < 0.01). The CART identified initial National Institutes of Health Stroke Scale, age, ED in-and-out time, and CCRU arrival-to-angiography time as important predictors of good outcome. Conclusion: Overall, the care process in EDs and at this single CSC for patients requiring MT were not heavily affected by the pandemic, as certain time metrics during the pandemic were statistically shorter than pre-pandemic intervals. Time intervals such as ED in-and-out and CCRU arrival-to-angiography were important factors in achieving good neurologic outcomes. Further study is necessary to confirm our observation and improve operational efficiency in the future

Acquisition Of Cocaine Self-Administration With Unsignaled Delayed Reinforcement In Rhesus Monkeys

Six experimentally naive rhesus monkeys produced 0.01 mg/kg/infusion cocaine by lever pressing under a tandem fixed-ratio 1 differential-reinforcement-of-other-behavior schedule. One lever press initiated an unsignaled 15- or 30-s delay culminating in cocaine delivery. Each press made during the delay reset the delay interval. With two exceptions, responding was acquired and maintained at higher rates than responding on a second (inoperative) lever. For the exceptions, a cancellation contingency was arranged in which each formerly inoperative-lever response reset the tandem schedule. This manipulation reduced presses on the inoperative lever. Subsequently, the consequences of responding on the two levers were reversed, and the monkeys again responded at higher rates on the operative lever. As a comparison, 3 additional experimentally naive monkeys received response-independent cocaine deliveries. Although lever pressing was observed, it extinguished and was subsequently reestablished under the tandem schedule. The results suggest that although response-reinforcer contiguity is not required for cocaine to acquire reinforcing functions, a response-reinforcer relation appears necessary

Acute worsening of CADASIL in a patient with COVID-19 infection: illustrative case

BACKGROUND: Reports of cerebrovascular ischemia and stroke occurring as predominant neurological sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), are increasingly evident within the literature. While various pathophysiological mechanisms have been postulated, including hypercoagulability, endothelial invasion, and systemic inflammation, discrete mechanisms for viral neurotropism remain unclear and controversial. OBSERVATIONS: The authors present a unique case study of a 64-year-old male with acute COVID-19 infection and acute worsening of previously stable cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare heritable arteriopathy due to mutation in the Notch3 gene, which is critical for vascular development and tone. Delayed cranial neuropathies, brainstem fluid-attenuated inversion recovery signal, and enhancement of olfactory and vagus nerves on magnetic resonance neurography in this patient further support viral neurotropism via cranial nerves in addition to cerebral vasculature. LESSONS: To the authors\u27 knowledge, this is the first case in the literature that not only demonstrates the consequences of COVID-19 infection in a patient with altered cerebrovascular autoregulation such as CADASIL but also highlights the tropism of SARS-CoV-2 for (1) cranial nerves as a mode of entry to the central nervous system and (2) vessels as a cause of cerebrovascular ischemia

U.S. Billion-ton Update: Biomass Supply for a Bioenergy and Bioproducts Industry

The Report, Biomass as Feedstock for a Bioenergy and Bioproducts Industry: The Technical Feasibility of a Billion-Ton Annual Supply (generally referred to as the Billion-Ton Study or 2005 BTS), was an estimate of “potential” biomass within the contiguous United States based on numerous assumptions about current and future inventory and production capacity, availability, and technology. In the 2005 BTS, a strategic analysis was undertaken to determine if U.S. agriculture and forest resources have the capability to potentially produce at least one billion dry tons of biomass annually, in a sustainable manner—enough to displace approximately 30% of the country’s present petroleum consumption. To ensure reasonable confidence in the study results, an effort was made to use relatively conservative assumptions. However, for both agriculture and forestry, the resource potential was not restricted by price. That is, all identified biomass was potentially available, even though some potential feedstock would more than likely be too expensive to actually be economically available. In addition to updating the 2005 study, this report attempts to address a number of its shortcomings</p