Structural Design of Ares V Interstage Composite Structure

Preliminary and detailed design studies were performed to mature composite structural design concepts for the Ares V Interstage structure as a part of NASA s Advanced Composite Technologies Project. Aluminum honeycomb sandwich and hat-stiffened composite panel structural concepts were considered. The structural design and analysis studies were performed using HyperSizer design sizing software and MSC Nastran finite element analysis software. System-level design trade studies were carried out to predict weight and margins of safety for composite honeycomb-core sandwich and composite hat-stiffened skin design concepts. Details of both preliminary and detailed design studies are presented in the paper. For the range of loads and geometry considered in this work, the hat-stiffened designs were found to be approximately 11-16 percent lighter than the sandwich designs. A down-select process was used to choose the most favorable structural concept based on a set of figures of merit, and the honeycomb sandwich design was selected as the best concept based on advantages in manufacturing cost

Tuberculosis patients' knowledge and beliefs about tuberculosis: a mixed methods study from the Pacific Island nation of Vanuatu

Background: The setting for this study was the Pacific island nation of Vanuatu, an archipelago of 82 islands, located in the South Pacific Ocean. Our objective was to assess the knowledge, attitudes and practices of tuberculosis (TB) patients towards TB. Methods. This was a descriptive study using qualitative and quantitative methods. Quantitative analysis was based on the responses provided to closed questions, and we present frequencies to describe the TB patients' knowledge, attitudes and practice relating to TB. Qualitative analysis was based on open questions permitting fuller explanations. We used thematic analysis and developed a posteriori inductive categories to draw conclusions. Results: Thirty five TB patients were interviewed; 22 (63%) were male. They attributed TB to cigarettes, kava, alcohol, contaminated food, sharing eating utensils and "kastom" (the local term for the traditional way of life, but also for sorcery). Most (94%) did not attribute TB to a bacterial cause. However, almost all TB patients (89%) thought that TB was best treated at a hospital with antibiotics. Three quarters (74%) experienced stigma after their TB diagnosis.Seeking health care from a traditional healer was common; 54% of TB patients stated that they would first consult a traditional healer for any illness. When seeking a diagnosis for signs and symptoms of TB, 34% first consulted a traditional healer. Patients cited cost, distance and beliefs about TB causation as reasons for first consulting a traditional healer or going to the hospital. Of the TB patients who consulted a traditional healer first, there was an average of two weeks delay before they consulted the health service. In some cases, however, the delay was up to six years. Conclusion: The majority of the TB patients interviewed did not attribute TB to a bacterial cause. Consulting a traditional healer for health care, including while seeking a diagnosis for TB symptoms, was common and may have delayed diagnosis. People require better information about TB to correct commonly held misperceptions about the disease. Traditional healers could also be engaged with the national TB programme, in order to refer people with signs and symptoms of TB to the nearest health service

Comparative proteomic profiling reveals mechanisms for early spinal cord vulnerability in CLN1 disease

CLN1 disease is a fatal inherited neurodegenerative lysosomal storage disease of early childhood, caused by mutations in the CLN1 gene, which encodes the enzyme Palmitoyl protein thioesterase-1 (PPT-1). We recently found significant spinal pathology in Ppt1-deficient (Ppt1−/−) mice and human CLN1 disease that contributes to clinical outcome and precedes the onset of brain pathology. Here, we quantified this spinal pathology at 3 and 7 months of age revealing significant and progressive glial activation and vulnerability of spinal interneurons. Tandem mass tagged proteomic analysis of the spinal cord of Ppt1−/−and control mice at these timepoints revealed a significant neuroimmune response and changes in mitochondrial function, cell-signalling pathways and developmental processes. Comparing proteomic changes in the spinal cord and cortex at 3 months revealed many similarly affected processes, except the inflammatory response. These proteomic and pathological data from this largely unexplored region of the CNS may help explain the limited success of previous brain-directed therapies. These data also fundamentally change our understanding of the progressive, site-specific nature of CLN1 disease pathogenesis, and highlight the importance of the neuroimmune response. This should greatly impact our approach to the timing and targeting of future therapeutic trials for this and similar disorders

Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNA7 mouse model of SMA

Spinal muscular atrophy (SMA) is a severe motor neuron (MN) disease caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene, which results in reduced levels of the SMN protein and the selective degeneration of lower MNs. The best-known function of SMN is the biogenesis of spliceosomal snRNPs, the major components of the pre-mRNA splicing machinery. Therefore, SMN deficiency in SMA leads to widespread splicing abnormalities. We used the SMN?7 mouse model of SMA to investigate the cellular reorganization of polyadenylated mRNAs associated with the splicing dysfunction in MNs. We demonstrate that SMN deficiency induced the abnormal nuclear accumulation in euchromatin domains of poly(A) RNA granules (PARGs) enriched in the splicing regulator Sam68. However, these granules lacked other RNA-binding proteins, such as TDP43, PABPN1, hnRNPA12B, REF and Y14, which are essential for mRNA processing and nuclear export. These effects were accompanied by changes in the alternative splicing of the Sam68-dependent Bcl-x and Nrnx1 genes, as well as changes in the relative accumulation of the intron-containing Chat, Chodl, Myh9 and Myh14 mRNAs, which are all important for MN functions. PARG-containing MNs were observed at presymptomatic SMA stage, increasing their number during the symptomatic stage. Moreover, the massive accumulations of poly(A) RNA granules in MNs was accompanied by the cytoplasmic depletion of polyadenylated mRNAs for their translation. We suggest that the SMN-dependent abnormal accumulation of polyadenylated mRNAs and Sam68 in PARGs reflects a severe dysfunction of both mRNA processing and translation, which could contribute to SMA pathogenesis.This work was supported by grants from: “Dirección General de Investigación” of Spain (BFU2014-54754-P and SAF2015-70801-R, cofinanced by FEDER) and “Instituto de Investigación Marqués de Valdecilla-IDIVAL (NVAL17/22). Dr. Tapia is the recipient of a grant from SMA Europe and FundAME (Spain)

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Traditional healers and the potential for collaboration with the national tuberculosis programme in Vanuatu: results from a mixed methods study

Background: This study was conducted in the Pacific island nation of Vanuatu. Our objective was to assess knowledge, attitudes and practice of traditional healers who treat lung diseases and tuberculosis (TB), including their willingness to collaborate with the national TB programme. Methods. This was a descriptive study using both qualitative and quantitative methods. Quantitative analysis was based on the responses provided to closed-ended questions, and we used descriptive analysis (frequencies) to describe the knowledge, attitudes and practice of the traditional healers towards TB. Qualitative analysis was based on open-ended questions permitting fuller explanations. We used thematic analysis and developed a posteriori inductive categories to draw original and unbiased conclusions. Results: Nineteen traditional healers were interviewed; 18 were male. Fifteen of the healers reported treating short wind (a local term to describe lung, chest or breathing illnesses) which they attributed to food, alcohol, smoking or pollution from contact with menstrual blood, and a range of other physical and spiritual causes. Ten said that they would treat TB with leaf medicine. Four traditional healers said that they would not treat TB. Twelve of the healers had referred someone to a hospital for a strong wet-cough and just over half of the healers (9) reported a previous collaboration with the Government health care system. Eighteen of the traditional healers would be willing to collaborate with the national TB programme, with or without compensation. Conclusions: Traditional healers in Vanuatu treat lung diseases including TB. Many have previously collaborated with the Government funded health care system, and almost all of them indicated a willingness to collaborate with the national TB programme. The engagement of traditional healers in TB management should be considered, using an evidence based and culturally sensitive approach