139 research outputs found

    Aircraft design at the Naval Postgraduate School - Tactical waverider/long-range cargo aircraft

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    Aircraft Design, Systems, and Operations Meeting, 09 August 1993 - 11 August 1993The article of record as published may be located at https://doi.org/10.2514/6.1993-4007The graduate program of the Department of Aeronautics and Astronautics at the Naval Postgraduate School uniquely supports a comprehensive design program in aircraft, spacecraft, missile, helicopter, and engine design. This paper is focused on four aircraft configuration designs proposed by AA 4273 Military Aircraft Design course team members. The AA 4273 course is, in turn, supported by a growing research program to enhance and further develop the methodology of aircraft design. This design effort has received considerable support from the NASA/USRA Advanced Design Program in Aeronautics. Specifically, two design solutions for a long-range,carrier based, tactical, wave-rider configured fighter/interceptor aircraft are reviewed herein, as are two solutions for a global range military transport. Both types of aircraft were developed as a graduate student team response to specific design RFPs

    “Like works of our hands are giving testimony!” A qualitative study on kangaroo mother care and health worker empowerment in southern Malawi

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    The purpose of this paper is to explore health worker perspectives of empowerment associated with kangaroo mother care in southern Malawi. We conducted a secondary analysis of 27 in-depth interviews collected between May-Aug 2019 at a large Malawian tertiary hospital and three rural referral hospitals. Data was analyzed using a thematic approach with NVivo 12 software (QSR International, Melbourne, Australia). Health workers reported positive perceptions of kangaroo mother care because it helped save the lives of preterm and low birthweight infants who previously did not frequently survive. This gave them hope due to increased capacity to care for low birthweight infants and subsequently increased job satisfaction. Experiences of success supported workplace morale and strengthened commitment to their clinical roles. This study suggests that kangaroo mother care may support health worker empowerment and resilience in their work.   Cet article-ci se prend pour son objectif d'explorer les perspectives de l'autonomie associée avec les soins maternels kangourous implémentés aux cliniques médicales dans le sud du Malawi. Les perspectives de l'autonomie dont on parle ici appartiennent aux travailleurs de la santé. Nous avons effectué une analyse secondaire de vingt-sept entrevues collectionnées entre les mois mai et août en 2019 au Malawi à une hôpital de soins tertiaires et aux trois hôpitaux d'aiguillage ruraux. Les données ont été analysées en utilisant l'approche thématique avec le logiciel NVivo 12 (QSR International, Melbourne, Australia). Les travailleurs de la santé ont communiqué les perceptions positives des soins maternels kangourous parce que ceux-ci les ont aidé à sauver les vies des nourrissons prématurés et de faible poids de naissance qui autrefois souvent n'avaient pas survécu. Ceci leur a donné de l'espoir parce que leur capacité de prendre soin des nourrissons de faible poids de naissance est accrue et ensuite leur satisfaction au travail a augmenté aussi. Ces expériences de succès ont soutenu leur morale au travail et ont renforcé leur engagement envers leur rôles cliniques. Cette étude-ci suggère que les soins maternels kangourou peuvent promouvoir l'autonomie des travailleurs de la santé et leur résilience dans leur travail. &nbsp

    Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

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    © The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A)+ forkhead box P3 (FOXP3)+ CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.This work was supported by the Leona M. and Harry B. Helmsley Charitable trust (SHARE), the Digestive Diseases Research Core Center C-IID P30 DK42086 at the University of Chicago, the PSC Partners Seeking a Cure Canada and the Sczholtz Family Foundation. K.R.M. is supported by grant no. NS124187. S.C.S. is supported by an American Gastroenterological Association Research Scholar Award, Veterans Affairs Career Development Award (no. ICX002027A01) and the San Diego Digestive Diseases Research Center (no. P30 DK120515). C.Q. is supported by the BBSRC Core Strategic Programme Grant (BB/CSP1720/1, BBS/E/T/000PR9818 and BBS/E/T/000PR9817). I.H.J. is supported by a Rosalind Franklin Fellowship from the University of Groningen and a Netherlands Organization for Scientific Research VIDI grant no. 016.171.047. D.G.S. is supported by grant no. F30DK121470.info:eu-repo/semantics/publishedVersio

    "So sometimes, it looks like it's a neglected ward": Health worker perspectives on implementing kangaroo mother care in southern Malawi

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    IntroductionKangaroo mother care (KMC) involves continuous skin-to-skin contact of baby on mother's chest to provide warmth, frequent breastfeeding, recognizing danger signs of illness, and early discharge. Though KMC is safe, effective and recommended by the World Health Organization, implementation remains limited in practice. The objective of this study is to understand barriers and facilitators to KMC practice at tertiary and secondary health facilities in southern Malawi from the perspective of health workers.MethodsThis study is part of the "Integrating a neonatal healthcare package for Malawi" project in the Innovating for Maternal and Child Health in Africa initiative. In-depth interviews were conducted between May-Aug 2019 with a purposively drawn sample of service providers and supervisors working in newborn health at a large tertiary hospital and three district-level hospitals in southern Malawi. Data were analyzed using a thematic approach using NVivo 12 software (QSR International, Melbourne, Australia).FindingsA total of 27 nurses, clinical officers, paediatricians and district health management officials were interviewed. Staff attitudes, inadequate resources and reliance on families emerged as key themes. Health workers from Malawi described KMC practice positively as a low-cost, low-technology solution appropriate for resource-constrained health settings. However, staff perceptions that KMC babies were clinically stable was associated with lower prioritization in care and poor monitoring practices. Neglect of the KMC ward by medical staff, inadequate staffing and reliance on caregivers for supplies were associated with women self-discharging early.ConclusionThough routine uptake of KMC was policy for stable low birthweight and preterm infants in the four hospitals, there were gaps in monitoring and maintenance of practice. While conceptualized as a low-cost intervention, sustainable implementation requires investments in technologies, staffing and hospital provisioning of basic supplies such as food, bedding, and KMC wraps. Strengthening hospital capacities to support KMC is needed as part of a continuum of care for premature infants

    Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles

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    Background and Aims We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors. Approach and Results We analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6, and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A. Conclusions Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.National Institutes of Health (R01DK123763, R01DK119437, HL151328, P30DK52574, P30DK56341, and UL1TR002345); Ministerio de Economía y Competitividad de España (SAF2017-88041-R); Ministerio de Economía y Competitividad de España for the Severo Ochoa Excellence Accreditation (SEV-2016-0644); CIBERehd (Biomedical Research Center in Hepatic and Digestive Diseases) and Netherlands Organization for Applied Scientific Research Program (PMC13 and PMC15); Spanish Carlos III Health Institute (PI15/01132 and PI18/01075); Miguel Servet Program (CON14/00129 and CPII19/00008); Fondo Europeo de Desarrollo Regional, CIBERehd, Department of Industry of the Basque Country (Elkartek: KK-2020/00008); La Caixa Scientific Foundation (HR17-00601); Liver Investigation: Testing Marker Utility in Steatohepatitis consortium funded by the Innovative Medicines Initiative Program of the European Union (777377), which receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA; Newcastle NIHR Biomedical Research Center; Czech Ministry of Health (RVO-VFN64165/2020); Fondo Nacional De Ciencia y Tecnología de Chile (1191145); and the Comisión Nacional de Investigación, Ciencia y Tecnología (AFB170005, CARE Chile UC); Agencia Nacional de Investigación y Desarrollo (ANID ACE 210009); European Union's Horizon 2020 Research and Innovation Program (825510)

    Barriers and enablers of implementing bubble continuous positive airway pressure (CPAP) : perspectives of health professionals in Malawi

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    The study explored the factors that influence the implementation of Continuous Positive Airway Pressure (bubble CPAP) among health care professionals in secondary and tertiary hospitals in Malawi. Influencing factors occurred in an interconnected manner and included: inadequate healthcare provider training; rigid division of roles and responsibilities among providers; lack of effective communication between providers and newborn’s caregivers; human resources constraints; and inadequate equipment and infrastructure. Complications of prematurity are the leading cause of neonatal deaths, an important consideration in Malawi, which has the highest rate of preterm births in the world, at 18% of live-births.Global Affairs Canada (GAC)Canadian Institutes for Health Research (CIHR

    Host Responses to Intestinal Microbial Antigens in Gluten-Sensitive Mice

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    BACKGROUND AND AIMS: Excessive uptake of commensal bacterial antigens through a permeable intestinal barrier may influence host responses to specific antigen in a genetically predisposed host. The aim of this study was to investigate whether intestinal barrier dysfunction induced by indomethacin treatment affects the host response to intestinal microbiota in gluten-sensitized HLA-DQ8/HCD4 mice. METHODOLOGY/PRINCIPAL FINDINGS: HLA-DQ8/HCD4 mice were sensitized with gluten, and gavaged with indomethacin plus gluten. Intestinal permeability was assessed by Ussing chamber; epithelial cell (EC) ultra-structure by electron microscopy; RNA expression of genes coding for junctional proteins by Q-real-time PCR; immune response by in-vitro antigen-specific T-cell proliferation and cytokine analysis by cytometric bead array; intestinal microbiota by fluorescence in situ hybridization and analysis of systemic antibodies against intestinal microbiota by surface staining of live bacteria with serum followed by FACS analysis. Indomethacin led to a more pronounced increase in intestinal permeability in gluten-sensitized mice. These changes were accompanied by severe EC damage, decreased E-cadherin RNA level, elevated IFN-gamma in splenocyte culture supernatant, and production of significant IgM antibody against intestinal microbiota. CONCLUSION: Indomethacin potentiates barrier dysfunction and EC injury induced by gluten, affects systemic IFN-gamma production and the host response to intestinal microbiota antigens in HLA-DQ8/HCD4 mice. The results suggest that environmental factors that alter the intestinal barrier may predispose individuals to an increased susceptibility to gluten through a bystander immune activation to intestinal microbiota

    Coupling remote sensing and eDNA to monitor environmental impact: A pilot to quantify the environmental benefits of sustainable agriculture in the Brazilian Amazon

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    Monitoring is essential to ensure that environmental goals are being achieved, including those of sustainable agriculture. Growing interest in environmental monitoring provides an opportunity to improve monitoring practices. Approaches that directly monitor land cover change and biodiversity annually by coupling the wall-to-wall coverage from remote sensing and the site-specific community composition from environmental DNA (eDNA) can provide timely, relevant results for parties interested in the success of sustainable agricultural practices. To ensure that the measured impacts are due to the environmental projects and not exogenous factors, sites where projects have been implemented should be benchmarked against counterfactuals (no project) and control (natural habitat) sites. Results can then be used to calculate diverse sets of indicators customized to monitor different projects. Here, we report on our experience developing and applying one such approach to assess the impact of shaded cocoa projects implemented by the Instituto de Manejo e Certificação Florestal e Agrícola (IMAFLORA) near São Félix do Xingu, in Pará, Brazil. We used the Continuous Degradation Detection (CODED) and LandTrendr algorithms to create a remote sensing-based assessment of forest disturbance and regeneration, estimate carbon sequestration, and changes in essential habitats. We coupled these remote sensing methods with eDNA analyses using arthropod-targeted primers by collecting soil samples from intervention and counterfactual pasture field sites and a control secondary forest. We used a custom set of indicators from the pilot application of a coupled monitoring framework called TerraBio. Our results suggest that, due to IMAFLORA’s shaded cocoa projects, over 400 acres were restored in the intervention area and the community composition of arthropods in shaded cocoa is closer to second-growth forests than that of pastures. In reviewing the coupled approach, we found multiple aspects worked well, and we conclude by presenting multiple lessons learned

    Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis

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    Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients’ BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process

    Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

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