Replacement of Hydrochlorofluorocarbon (HCFC) -225 Solvent for Cleaning and Verification Sampling of NASA Propulsion Oxygen Systems Hardware, Ground Support Equipment, and Associated Test Systems

Since the 1990's, NASA's rocket propulsion test facilities at Marshall Space Flight Center (MSFC) and Stennis Space Center (SSC) have used hydrochlorofluorocarbon-225 (HCFC-225), a Class II ozone-depleting substance, to safety clean and verify the cleanliness of large scale propulsion oxygen systems and associated test facilities. In 2012 through 2014, test laboratories at MSFC, SSC, and Johnson Space Center-White Sands Test Facility collaborated to seek out, test, and qualify an environmentally preferred replacement for HCFC-225. Candidate solvents were selected, a test plan was developed, and the products were tested for materials compatibility, oxygen compatibility, cleaning effectiveness, and suitability for use in cleanliness verification and field cleaning operations. Honewell Soltice (TradeMark) Performance Fluid (trans-1-chloro-3,3, 3-trifluoropropene) was selected to replace HCFC-225 at NASA's MSFC and SSC rocket propulsion test facilities

Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: A randomised, double-blind, multicentre, placebo-controlled, phase 2b trial

Background: Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury.Methods: This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18-70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1-C8) within 4-28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate-buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was change in UEMS at 6 months, analysed alongside safety in the full analysis set. The completed trial was registered at ClinicalTrials.gov, NCT03935321.Findings: From May 20, 2019, to July 20, 2022, 463 patients with acute traumatic cervical spinal cord injury were screened, 334 were deemed ineligible and excluded, and 129 were randomly assigned to an intervention (80 patients in the NG101 group and 49 in the placebo group). The full analysis set comprised 78 patients from the NG101 group and 48 patients from the placebo group. 107 (85%) patients were male and 19 (15%) patients were female, with a median age of 51·5 years (IQR 30·0-60·0). Across all patients, the primary endpoint showed no significant difference between groups (with UEMS change at 6 months 1·37 [95% CI -1·44 to 4·18]; placebo group mean 19·20 [SD 11·78] at baseline and 30·91 [SD 15·49] at day 168; NG101 group mean 18·23 [SD 15·14] at baseline and 31·31 [19·54] at day 168). Treatment-related adverse events were similar between groups (nine in the NG101 group and six in the placebo group). 25 severe adverse events were reported: 18 in 11 (14%) patients in the NG101 group and seven in six (13%) patients in the placebo group. Although no treatment-related fatalities were reported in the NG101 group, one fatality not related to treatment occurred in the placebo group. Infections were the most common adverse event affecting 44 (92%) patients in the placebo group and 65 (83%) patients in the NG101 group.Interpretation: NG101 did not improve UEMS in patients with acute spinal cord injury. Post-hoc subgroup analyses assessing UEMS and Spinal Cord Independence Measure of self-care in patients with motor-incomplete injury indicated potential beneficial effects that require investigation in future studies

Interconnecting global threats: climate change, biodiversity loss, and infectious diseases

The concurrent pressures of rising global temperatures, rates and incidence of species decline, and emergence of infectious diseases represent an unprecedented planetary crisis. Intergovernmental reports have drawn focus to the escalating climate and biodiversity crises and the connections between them, but interactions among all three pressures have been largely overlooked. Non-linearities and dampening and reinforcing interactions among pressures make considering interconnections essential to anticipating planetary challenges. In this Review, we define and exemplify the causal pathways that link the three global pressures of climate change, biodiversity loss, and infectious disease. A literature assessment and case studies show that the mechanisms between certain pairs of pressures are better understood than others and that the full triad of interactions is rarely considered. Although challenges to evaluating these interactions—including a mismatch in scales, data availability, and methods—are substantial, current approaches would benefit from expanding scientific cultures to embrace interdisciplinarity and from integrating animal, human, and environmental perspectives. Considering the full suite of connections would be transformative for planetary health by identifying potential for co-benefits and mutually beneficial scenarios, and highlighting where a narrow focus on solutions to one pressure might aggravate another

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection

IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: PASC and 44 participant-reported symptoms (with severity thresholds). RESULTS: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. CONCLUSIONS AND RELEVANCE: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC