Statistical estimation of trailing edge noise from finite wall-mounted airfoils

The 2016 Joint Conference of The Australian Acoustical Society and The Acoustical Society of New Zealand. Acoustics2016 - The Second Australasian Acoustical Societies ConferenceIt is important to be able to accurately model the flow and noise generated by finite wall-mounted airfoil flows because of the many engineering applications in which these flows occur. One method for predicting turbulent trailing edge noise is the Reynolds-averaged Navier-Stokes based statistical noise model (RSNM) of Doolan et al. (Proceedings of 20th International Congress on Acoustics, ICA 2010). The RSNM method has previously been used successfully on a range of two-dimensional geometry-flow cases. In this paper a new turbulent velocity cross-spectrum model and improved implementation are proposed to allow the RSNM method to be used to effectively and efficiently predict turbulent trailing edge noise from more complex three-dimensional cases. Reynolds-averaged Navier-Stokes (RANS) simulations of a series of wing-in-junction cases are used in combination with the developed acoustic model to predict the far-field noise and compared against experimental noise measurements.Jesse Coombs, Con Doolan, Anthony Zander, Danielle Moreau and Laura Brook

Bacterial Antigen Expression Is an Important Component in Inducing an Immune Response to Orally Administered Salmonella-Delivered DNA Vaccines

BACKGROUND: The use of Salmonella to deliver heterologous antigens from DNA vaccines is a well-accepted extension of the success of oral Salmonella vaccines in animal models. Attenuated S. typhimurium and S. typhi strains are safe and efficacious, and their use to deliver DNA vaccines combines the advantages of both vaccine approaches, while complementing the limitations of each technology. An important aspect of the basic biology of the Salmonella/DNA vaccine platform is the relative contributions of prokaryotic and eukaryotic expression in production of the vaccine antigen. Gene expression in DNA vaccines is commonly under the control of the eukaryotic cytomegalovirus (CMV) promoter. The aim of this study was to identify and disable putative bacterial promoters within the CMV promoter and evaluate the immunogenicity of the resulting DNA vaccine delivered orally by S. typhimurium. METHODOLOGY/PRINCIPAL FINDINGS: The results reported here clearly demonstrate the presence of bacterial promoters within the CMV promoter. These promoters have homology to the bacterial consensus sequence and functional activity. To disable prokaryotic expression from the CMV promoter a series of genetic manipulations were performed to remove the two major bacterial promoters and add a bacteria transcription terminator downstream of the CMV promoter. S. typhimurium was used to immunise BALB/c mice orally with a DNA vaccine encoding the C-fragment of tetanus toxin (TT) under control of the original or the modified CMV promoter. Although both promoters functioned equally well in eukaryotic cells, as indicated by equivalent immune responses following intramuscular delivery, only the original CMV promoter was able to induce an anti-TT specific response following oral delivery by S. typhimurium. CONCLUSIONS: These findings suggest that prokaryotic expression of the antigen and co-delivery of this protein by Salmonella are at least partially responsible for the successful oral delivery of C-fragment DNA vaccines containing the CMV promoter by S. typhimurium

Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia

Nucleophosmin is commonly both over-expressed and mutated in acute myeloid leukemia (AML). NPM1 mutations are always heterozygous. In addition, NPM1 has a number of different splice variants with the major variant encoded by exons 1–9 and 11–12 (NPM1.1). Further variants include NPM1.2 which lacks exons 8 and 10 and NPM1.3 which comprises exons 1–10 (and so lacks the region of sequence mutated in AML). In this study we quantified the expression of these three variants in 108 AML patient samples with and without NPM1 mutations and also assessed the level of expression from the wild-type and mutant alleles in variants NPM1.1 and NPM1.2. The results show that NPM1.1 is the most commonly expressed variant, however transcripts from wild-type and mutated alleles do not occur at equal levels, with a significant bias toward the mutated allele. Considering the involvement of mutant nucleophosmin in the progression and maintenance of AML, a bias towards mutated transcripts could have a significant impact on disease maintenance

Men’s Health Research in New Zealand: A Scoping Review

Background: Globally, there has been a growing awareness of the health challenges faced by men. The current public health agenda in Aotearoa New Zealand (NZ) does not specifically address the needs of men. The aim of this scoping review was to capture the major health issues facing men in NZ and particularly to identify the knowledge gaps in the understanding of men’s health within the NZ context. This was achieved by presenting key data on their health status and systematically mapping research in NZ related to men’s health; international data are also referenced for context as relevant. Method: A search and screening of the literature were conducted using Ovid, Web of Science and Scopus databases from January 1996 to July 2021, with advice from a medical librarian. Search terms included “men’s/male’s health” and “men’s/male’s health NZ.” An environmental scan of international literature was also carried out and information from the Ministry of Health and Statistics NZ was obtained to provide context of the status of research on men’s health in NZ. Main Findings: In keeping with international literature, the major health issues for men in NZ are life-limiting diseases including cancer and cardiovascular disease, the spread of overweight and obesity, issues with masculinity and help-seeking behaviours, unhealthy lifestyles, mental health issues and poor health literacy. The main areas of research related to men’s health from the NZ literature were highlighted. Discussion: Men’s health remains an under-recognised issue in NZ. If we are to address current inequities in health for men, clinicians, researchers and relevant agencies need to pay more attention to men’s health issues and take up the challenge to highlight and promote men’s health status in NZ

Ageing well in older men in Otago and Southland of New Zealand: a focus group study protocol

Background: Men in New Zealand (NZ) do not enjoy the same level of health and wellbeing as women. Men generally experience a higher incidence of, and mortality from, major diseases; most importantly, life expectancies for men in NZ are approximately four years less than for women. Such disparities vary across rural and urban communities, and across ethnic sub-groups. In particular, Māori men live some seven years less than other NZ men. Despite such inequalities, men’s health is not recognised as a priority by healthcare providers, government, or at the wider societal level. This qualitative study seeks to address this, by contributing to our understanding of factors associated with health and wellbeing for men in the ageing process. Study findings will also inform the development of a national survey of older men. Method: Focus groups will be used to explore the expectations and experiences of health and wellbeing in a cohort of older men (≥45 years) in the Otago and Southland regions. Topics to be explored will include gender role conflict, health service help-seeking, lifestyle behaviours, social engagement, and self-identified health risks. In total, five groups are planned (6-10 men per group) and will be conducted in urban, rural, and urban-rural adjunct areas. Focus groups will be recorded, and transcribed verbatim. Transcriptions will be coded for themes using the abductive thematic analysis approach. Results: This paper presents a protocol of a study in progress, and results are not yet known. Discussion: This is the first qualitative study focussing on ageing well in men in NZ. It will contribute to our understanding of this aspect of men’s health, and–ultimately–help to inform interventions and policies to better support men to age positively

Novel high-throughput fluorescence-based assay for the identification of nematocidal compounds that target the blood-feeding pathway

Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model Nippostrongylus brasiliensis (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms

Probing of a human proteome microarray with a recombinant pathogen protein reveals a novel mechanism by which hookworms suppress B-cell receptor signaling.

Na-ASP-2 is an efficacious hookworm vaccine antigen. However, despite elucidation of its crystal structure and studies addressing its immunobiology, the function of Na-ASP-2 has remained elusive. We probed a 9000-protein human proteome microarray with Na-ASP-2 and showed binding to CD79A, a component of the B-cell antigen receptor complex. Na-ASP-2 bound to human B lymphocytes ex vivo and downregulated the transcription of approximately 1000 B-cell messenger RNAs (mRNAs), while only approximately 100 mRNAs were upregulated, compared with control-treated cells. The expression of a range of molecules was affected by Na-ASP-2, including factors involved in leukocyte transendothelial migration pathways and the B-cell signaling receptor pathway. Of note was the downregulated transcription of lyn and pi3k, molecules that are known to interact with CD79A and control B-cell receptor signaling processes. Together, these results highlight a previously unknown interaction between a hookworm-secreted protein and B cells, which has implications for helminth-driven immunomodulation and vaccine development. Further, the novel use of human protein microarrays to identify host-pathogen interactions, coupled with ex vivo binding studies and subsequent analyses of global gene expression in human host cells, demonstrates a new pipeline by which to explore the molecular basis of infectious diseases.This is the author accepted version. The final version is available at http://dx.doi.org/10.1093/infdis/jiu451

Interactions and potential implications of Plasmodium falciparum-hookworm coinfection in different age groups in south-central Côte d'Ivoire

BACKGROUND: Given the widespread distribution of Plasmodium and helminth infections, and similarities of ecological requirements for disease transmission, coinfection is a common phenomenon in sub-Saharan Africa and elsewhere in the tropics. Interactions of Plasmodium falciparum and soil-transmitted helminths, including immunological responses and clinical outcomes of the host, need further scientific inquiry. Understanding the complex interactions between these parasitic infections is of public health relevance considering that control measures targeting malaria and helminthiases are going to scale.METHODOLOGY: A cross-sectional survey was carried out in April 2010 in infants, young school-aged children, and young non-pregnant women in south-central Côte d'Ivoire. Stool, urine, and blood samples were collected and subjected to standardized, quality-controlled methods. Soil-transmitted helminth infections were identified and quantified in stool. Finger-prick blood samples were used to determine Plasmodium spp. infection, parasitemia, and hemoglobin concentrations. Iron, vitamin A, riboflavin, and inflammation status were measured in venous blood samples.PRINCIPAL FINDINGS: Multivariate regression analysis revealed specific association between infection and demographic, socioeconomic, host inflammatory and nutritional factors. Non-pregnant women infected with P. falciparum had significantly lower odds of hookworm infection, whilst a significant positive association was found between both parasitic infections in 6- to 8-year-old children. Coinfected children had lower odds of anemia and iron deficiency than their counterparts infected with P. falciparum alone.CONCLUSIONS/SIGNIFICANCE: Our findings suggest that interaction between P. falciparum and light-intensity hookworm infections vary with age and, in school-aged children, may benefit the host through preventing iron deficiency anemia. This observation warrants additional investigation to elucidate the mechanisms and consequences of coinfections, as this information could have important implications when implementing integrated control measures against malaria and helminthiases