EELV Secondary Payload Adapter (ESPA)

Despite growing worldwide interest in small satellites, launch costs continue to hinder the full exploitation of small satellite technology. In the United States, the Department of Defense (DoD), NASA, other government agencies, commercial companies, and many universities use small satellites to perform space experiments, demonstrate new technology, and test operational prototype hardware. In addition, the DoD continues to study the role of small satellites in fulfilling operational mission requirements. However, US government agencies are restricted to the use of US launch vehicles, which eliminates many affordable launch opportunities. Additionally, many small satellite users are faced with shrinking budgets, which limits the scope of what can be considered an affordable launch opportunity. In order to increase the number of space experiments that can be flown with a small, fixed budget, the Space Test Program (STP) has teamed with the Air Force Research Laboratory Space Vehicles Directorate (AFRLNSD) to develop a low-cost solution for the small satellite launch problem. Our solution, which will be implemented on Evolved Expendable Launch Vehicle-Medium (EEL V -M) boosters, is called the EEL V Secondary Pay load Adapter (ESPA). ESP A can potentially shrink the cost of launching a 180kg (or smaller) satellite to under $500,000, less than 5% of the cost of a dedicated launch vehicle

The Vehicle, Spring 1983

Vol. 24, No. 2 Table of Contents A-B-C-D-E-F-G-H....Beth Kennypage 1 Contemporary IssuesBrook Wilsonpage 1 BlackJohn Stockmanpage 2 BeatGraham Lewispage 2 Catholic DazeSuzanne Hornpage 4 AfricaGraham Lewispage 5 The Friendly SkiesRajendra Sinhanpage 5 BreadKen Kempckepage 7 PhotographLinda Fraembspage 8 SnapshotMaggie Kennedypage 9 PoemAnne Smithpage 9 Activities on IceKerri Mahatpage 11 Beecham\u27s Orchard And VineyardBecky Lawsonpage 11 PoemKarri Mahatpage 12 Sneak PreviewsMaggie Kennedypage 12 ZooKen Kempckepage 12 PhotographNick Haskettpage 13 The Slave HouseCraig Barnespage 13 The Nomad Preacher\u27s SermonStacey Flanniganpage 16 Owl Creek RevisitedScott Graypage 16 Thought On CopperGraham Lewispage 20 OutfielderKen Kempckepage 20 HoneymoonJohn Stockmanpage 21 Candy Wrapper Dream GirlStacey Flanniganpage 21 PhotographLinda Fraembspage 22 October DreamMarlene Weekspage 23 IndistinctionStacey Flanniganpage 24 Taking InventorySara Farrispage 24 Flying In From K-Mart, NebraskaMichelle Mitchellpage 25 PhotographNick Haskettpage 26 Bone ChinaMichelle Mitchellpage 27 She Was A DollNick Haskettpage 30 The Seventh DayGeoffrey Andrespage 31 Blade Of Grass (On A Golf Course)Ken Kempckepage 31 PoemKen Kempckepage 32 Cigarette SmokeJean M. Davispage 33 Future LoveR. Lawsonpage 34 PhotographNick Haskettpage 35 Dancing In The StreetBetsy Acklinpage 35 PhotographLinda Fraembspage 38 CleoMarlene Weekspage 39 Teddy BearKen Kempckepage 39 PreludeBecky Lawsonpage 40https://thekeep.eiu.edu/vehicle/1043/thumbnail.jp

The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: an evidence synthesis.

BACKGROUND: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. OBJECTIVES: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. STUDY DESIGN: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. PARTICIPANTS: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. INTERVENTIONS: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. MAIN OUTCOME MEASURES: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. METHODS: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. RESULTS: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive-behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) -0.44 (95% CI -4.43 to -1.53)], depression [mean difference -2.83 (95% CI -4.53 to -1.13)] and anxiety [SMD -0.23 (95% CI -0.03 to -0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist-child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. CONCLUSIONS: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. LIMITATIONS: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. FUTURE WORK: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003889. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Peptide-MHC-I from Endogenous Antigen Outnumber Those from Exogenous Antigen, Irrespective of APC Phenotype or Activation

<div><p>Naïve anti-viral CD8⁺ T cells (T_CD8+) are activated by the presence of peptide-MHC Class I complexes (pMHC-I) on the surface of professional antigen presenting cells (pAPC). Increasing the number of pMHC-I <i>in vivo</i> can increase the number of responding T_CD8+. Antigen can be presented directly or indirectly (cross presentation) from virus-infected and uninfected cells, respectively. Here we determined the relative importance of these two antigen presenting pathways in mousepox, a natural disease of the mouse caused by the poxvirus, ectromelia (ECTV). We demonstrated that ECTV infected several pAPC types (macrophages, B cells, and dendritic cells (DC), including DC subsets), which directly presented pMHC-I to naïve T_CD8+ with similar efficiencies <i>in vitro</i>. We also provided evidence that these same cell-types presented antigen <i>in vivo</i>, as they form contacts with antigen-specific T_CD8+. Importantly, the number of pMHC-I on infected pAPC (direct presentation) vastly outnumbered those on uninfected cells (cross presentation), where presentation only occurred in a specialized subset of DC. In addition, prior maturation of DC failed to enhance antigen presentation, but markedly inhibited ECTV infection of DC. These results suggest that direct antigen presentation is the dominant pathway in mice during mousepox. In a broader context, these findings indicate that if a virus infects a pAPC then the presentation by that cell is likely to dominate over cross presentation as the most effective mode of generating large quantities of pMHC-I is on the surface of pAPC that endogenously express antigens. Recent trends in vaccine design have focused upon the introduction of exogenous antigens into the MHC Class I processing pathway (cross presentation) in specific pAPC populations. However, use of a pantropic viral vector that targets pAPC to express antigen endogenously likely represents a more effective vaccine strategy than the targeting of exogenous antigen to a limiting pAPC subpopulation.</p></div

RNA-Seq and CyTOF immuno-profiling of regenerating lacrimal glands identifies a novel subset of cells expressing muscle-related proteins

<div><p>The purpose of the present studies was to use CyTOF and RNA-Seq technologies to identify cells and genes involved in lacrimal gland repair that could be targeted to treat diseases of lacrimal gland dysfunction. Lacrimal glands of female BALB/c mice were experimentally injured by intra-glandular injection of interleukin 1 alpha (IL-1α). The lacrimal glands were harvested at various time points following injury (1 to 14 days) and used to either prepare single cell suspensions for CyTOF immuno-phenotyping analyses or to extract RNA for gene expression studies using RNA-Seq. CyTOF immuno-phenotyping identified monocytes and neutrophils as the major infiltrating populations 1 and 2 days post injury. Clustering of significantly differentially expressed genes identified 13 distinct molecular signatures: 3 associated with immune/inflammatory processes included genes up-regulated at days 1–2 and 3 associated with reparative processes with genes up-regulated primarily between days 4 and 5. Finally, clustering identified 65 genes which were specifically up-regulated 2 days post injury which was enriched for muscle specific genes. The expression of select muscle-related proteins was confirmed by immunohistochemistry which identified a subset of cells expressing these proteins. Double staining experiments showed that these cells are distinct from the myoepithelial cells. We conclude that experimentally induced injury to the lacrimal gland leads to massive infiltration by neutrophils and monocytes which resolved after 3 days. RNAseq and immunohistochemistry identified a group of cells, other than myoepithelial cells, that express muscle-related proteins that could play an important role in lacrimal gland repair.</p></div

Histological analysis of IL-1α injected lacrimal glands.

<p>Lacrimal gland tissue was excised 1, 2, 3, 4, and 7 days post IL-1α or saline (vehicle) injection and processed for hematoxylin and eosin staining. Scale bar represents 50 μm for all panels.</p

Double-staining of β-taxilin and desmin proteins.

<p>Lacrimal gland tissue from IL-1α injected mice were double-stained for muscle related proteins desmin and β-taxilin. Panels represent staining from 2 days post IL-1α injected lacrimal glands which were counterstained with DAPI to visualize cell nuclei. Arrows represent cells expressing both proteins; arrowheads represent cells expressing β-taxilin only; stars represent cells expressing desmin only; BV represents a blood vessel. Scale bars represent 25 μm.</p

Antigen specific T cells relocate to the LN periphery where they interact with infected pAPC expressing antigen <i>in vivo</i>.

<p>(A and B) Localization of OT-I T_CD8+ following ECTV infection. Naïve OT-I T_CD8+ were labeled with cell tracker CMTMR dye (red) and adoptively transferred. Mice were injected with NP-S-EGFP or NP-EGFP i.d., and 12 h.p.i., D-LN were harvested and analyzed by fluorescence microscopy. (C, E, G, I) Mice were injected with NP-S-EGFP or NP-EGFP i.d., and 24 h.p.i. D-LN were harvested and stained for B220⁺ B cells, CD169⁺ macrophages, CD11c⁺ DC and CD103⁺ DC, and analyzed by fluorescence microscopy. (D, F, H, J) High power view of interaction of naïve OT-I T_CD8+ and ECTV-infected pAPC. The insets (D, F, H, and J) show 2-dimensional projections of one plane of the 3-dimensional datasets. Each image is representative of 3 experiments, with a minimum of 4 infected nodes per experiment.</p