Experimental evaluation of an advanced Space Shuttle main engine hot-gas manifold design concept

This study, using an extensively modified, full-scale space shuttle main engine (SSME) hot-gas manifold (HGM), established a detailed aerodynamic data base to support development of an advanced, three-dimensional, fluid-dynamic analysis computer model. In addition, the advanced SSME hot-gas manifold design used in this study demonstrated improved flow environment (uniformity) in the fuel side turbine exit and transfer duct exit regions. Major modifications were incorporated in the full-scale HGM flow test article model using two large transfer ducts on the fuel turbine side of the HGM in place of the three small transfer ducts in the present design. Other model features included an increases in the flow areas downstream of the 180-degree turn and in the fishbowl regions

An acetylcholinesterase biosensor for determination of low concentrations of Paraoxon and Dichlorvos

The characterization of an economic and ease-to-use carbon paste acetylcholinesterase (AChE) based biosensor to determine the concentration of pesticides Paraoxon and Dichlorvos is discussed. AChE hydrolyses acetylthiocholine (ATCh) in thiocoline (TC) and acetic acid (AA). When AChE is immobilized into a paste carbon working electrode kept at +410mV vs. Ag/AgCl electrode, the enzyme reaction rate using acetylthiocholine chloride (ATCl) as substrate is monitored as a current intensity. Because Paraoxon and Dichlorvos inhibit the AChE reaction, the decrease of the current intensity, at fixed ATCl concentration, is a measure of their concentration. Linear calibration curves for Paraoxon and Dichlorvos determination have been obtained. The detection limits resulted to be 0.86ppb and 4.2ppb for Paraoxon and Dichlorvos, respectively, while the extension of the linear range was up 23ppb for the former pesticide and up to 33ppb for the latter. Because the inhibited enzyme can be reactivated when immediately treated with an oxime, the biosensor reactivation has been studied when 1,1'-trimethylene bis 4-formylpyridinium bromide dioxime (TMB-4) and pyridine 2-aldoxime methiodide (2-PAM) were used. TMB-4 resulted more effective. The comparison with the behavior of similar AChE based biosensors is also presented

The effects of the spontaneous presence of a spouse/partner and others on cardiovascular reactions to an acute psychological challenge

The presence of supportive others has been associated with attenuated cardiovascular reactivity in the laboratory. The effects of the presence of a spouse and others in a more naturalistic setting have received little attention. Blood pressure and heart rate reactions to mental stress were recorded at home in 1028 married/partnered individuals. For 112 participants, their spouse/partner was present; for 78, at least one other person was present. Women tested with a spouse/partner present showed lower magnitude systolic blood pressure and heart rate reactivity than those tested without. Individuals tested with at least one nonspousal other present also displayed attenuated reactivity. This extends the results of laboratory studies and indicates that the spontaneous presence of others is associated with a reduction in cardiovascular reactivity in an everyday environment; spouse/partner presence would appear to be especially effective for women.\ud \u

Realistic constraints on the doubly charged bilepton couplings from Bhabha scattering with LEP data

Upper limits on doubly charged bilepton couplings and masses are extracted from LEP data for Bhabha scattering at energy range $\sqrt{s}=183-202$ GeV using standard model program ZFITTER which calculates radiative corrections. We find that $g_{L}^{2}/M_{L}^{2}<O(10^{-5})GeV^{-2}$ at 95% C.L. for scalar and vector bileptons.Comment: 5 pages, 1 EPS figur

Toward Common Data Elements for International Research in Long-term Care Homes: Advancing Person-Centered Care

To support person-centered, residential long-term care internationally, a consortium of researchers in medicine, nursing, behavioral, and social sciences from 21 geographically and economically diverse countries have launched the WE-THRIVE consortium to develop a common data infrastructure. WE-THRIVE aims to identify measurement domains that are internationally relevant, including in low-, middle-, and high-income countries, prioritize concepts to operationalize domains, and specify a set of data elements to measure concepts that can be used across studies for data sharing and comparisons. This article reports findings from consortium meetings at the 2016 meeting of the Gerontological Society of America and the 2017 meeting of the International Association of Gerontology and Geriatrics, to identify domains and prioritize concepts, following best practices to identify common data elements (CDEs) that were developed through the US National Institutes of Health/National Institute of Nursing Research's CDEs initiative. Four domains were identified, including organizational context, workforce and staffing, person-centered care, and care outcomes. Using a nominal group process, WE-THRIVE prioritized 21 concepts across the 4 domains. Several concepts showed similarity to existing measurement structures, whereas others differed. Conceptual similarity (convergence; eg, concepts in the care outcomes domain of functional level and harm-free care) provides further support of the critical foundational work in LTC measurement endorsed and implemented by regulatory bodies. Different concepts (divergence; eg, concepts in the person-centered care domain of knowing the person and what matters most to the person) highlights current gaps in measurement efforts and is consistent with WE-THRIVE's focus on supporting resilience and thriving for residents, family, and staff. In alignment with the World Health Organization's call for comparative measurement work for health systems change, WE-THRIVE's work to date highlights the benefits of engaging with diverse LTC researchers, including those in low-, middle-, and high-income countries, to develop a measurement infrastructure that integrates the aspirations of person-centered LTC

Life events and hemodynamic stress reactivity in the middle-aged and elderly

Recent versions of the reactivity hypothesis, which consider it to be the product of stress exposure and exaggerated haemodynamic reactions to stress that confers cardiovascular disease risk, assume that reactivity is independent of the experience of stressful life events. This assumption was tested in two substantial cohorts, one middle-aged and one elderly. Participants had to indicate from a list of major stressful life events up to six they had experienced in the previous two years. They were also asked to rate how disruptive and stressful they were, at the time of occurrence and now. Blood pressure and pulse rate were measured at rest and in response to acute mental stress. Those who rated the events as highly disruptive at the time of exposure and currently exhibited blunted systolic blood pressure reactions to acute stress. The present results suggest that acute stress reactivity may not be independent of stressful life events experience

Impact of therapeutic choices on outcome of osteomyelitis caused by MRSA

Fifty-four patients with chronic osteomyelitis sustained by methicillin-resistant staphylococcus were treated with daptomycin, linezolid, or teicoplanin and observed over time. Median time to CRP normalization was 7 weeks for daptomycin, 8 weeks for linezolid, and 12 weeks for teicoplanin (X2 =14.1; p < 0.001). Cure rate (intention to treat analysis) was 83% for the cases receiving teicoplanin, 77% for those receiving linezolid and 92% for those receiving daptomycin. We conclude that daptomycin and linezolid have to be considered at least equivalent to teicoplanin for the treatment of MRSA osteomyelitis

Ranibizumab population pharmacokinetics and free vegf pharmacodynamics in preterm infants with retinopathy of prematurity in the rainbow trial

Purpose: To develop a population pharmacokinetic (PK) model for intravitreal ranibizumab in infants with retinopathy of prematurity (ROP) and assess plasma free vascular endothelial growth factor (VEGF) pharmacodynamics (PD). Methods: The RAnibizumab compared with laser therapy for the treatment of INfants BOrn prematurely With retinopathy of prematurity (RAINBOW) trial enrolled 225 infants to receive a bilateral intravitreal injection of ranibizumab 0.1 mg, ranibizumab 0.2 mg, or laser in a 1:1:1 ratio and included sparse sampling of blood for population PK and PD analysis. An adult PK model using infant body weight as a fixed allometric covariate was re-estimated using the ranibizumab concentrations in the preterm population. Different variability, assumptions, and covariate relationships were explored. Model-based individual predicted concentrations of ranibizumab were plotted against observed free VEGF concentrations. Results: Elimination of ranibizumab had a median half-life of 5.6 days from the eye and 0.3 days from serum, resulting in an apparent serum half-life of 5.6 days. Time to reach maximum concentration was rapid (median: 1.3 days). Maximum concentration (median 24.3 ng/mL with ranibizumab 0.2 mg) was higher than that reported in adults. No differences in plasma free VEGF concentrations were apparent between the groups or over time. Plotted individual predicted concentrations of ranibizumab against observed free VEGF concentrations showed no relationship. Conclusions: In preterm infants with ROP, elimination of ranibizumab from the eye was the rate-limiting step and was faster compared with adults. No reduction in plasma free VEGF was observed. The five-year clinical safety follow-up from RAINBOW is ongoing. Translational Relevance: Our population PK and VEGF PD findings suggest a favorable ocular efficacy: systemic safety profile for ranibizumab in preterm infants

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity Two-Year Efficacy and Safety Outcomes in the Nonrandomized Controlled Trial FIREFLEYE next

IMPORTANCE Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti–vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. OBJECTIVE To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). DESIGN, SETTING, AND PARTICIPANTS This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. INTERVENTIONS Complications of ROP treated at investigator discretion (no study treatment). MAIN OUTCOMES AND MEASURES Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. RESULTS Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. CONCLUSIONS AND RELEVANCE In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP