Experimental and theoretical investigation of fatigue life in reusable rocket thrust chambers

During a test program to investigate low-cycle thermal fatigue, 13 rocket combustion chambers were fabricated and cyclically test fired to failure. Six oxygen-free, high-conductivity (OFHC) copper and seven Amzirc chambers were tested. The failures in the OFHC copper chambers were not typical fatigue failures but are described as creep rupture enhanced by ratcheting. The coolant channels bulged toward the chamber centerline, resulting in progressive thinning of the wall during each cycle. The failures in the Amzirc alloy chambers were caused by low-cycle thermal fatigue. The zirconium in this alloy was not evenly distributed in the chamber materials. The life that was achieved was nominally the same as would have been predicted from OFHC copper isothermal test data

Australia IBD Microbiome (AIM) Study: protocol for a multicentre longitudinal prospective cohort study.

INTRODUCTION: Crohn's disease and ulcerative colitis are common chronic idiopathic inflammatory bowel diseases (IBD), which cause considerable morbidity. Although the precise mechanisms of disease remain unclear, evidence implicates a strong multidirectional interplay between diet, environmental factors, genetic determinants/immune perturbations and the gut microbiota. IBD can be brought into remission using a number of medications, which act by suppressing the immune response. However, none of the available medications address any of the underlying potential mechanisms. As we understand more about how the microbiota drives inflammation, much interest has focused on identifying microbial signals/triggers in the search for effective therapeutic targets. We describe the establishment of the Australian IBD Microbiota (AIM) Study, Australia's first longitudinal IBD bioresource, which will identify and correlate longitudinal microbial and metagenomics signals to disease activity as evaluated by validated clinical instruments, patient-reported surveys, as well as biomarkers. The AIM Study will also gather extensive demographic, clinical, lifestyle and dietary data known to influence microbial composition in order to generate a more complete understanding of the interplay between patients with IBD and their microbiota. METHODS: The AIM Study is an Australian multicentre longitudinal prospective cohort study, which will enrol 1000 participants; 500 patients with IBD and 500 healthy controls over a 5-year period. Assessment occurs at 3 monthly intervals over a 24-month period. At each assessment oral and faecal samples are self-collected along with patient-reported outcome measures, with clinical data also collected at baseline, 12 and 24 months. Intestinal tissue will be sampled whenever a colonoscopy is performed. Dietary intake, general health and psychological state will be assessed using validated self-report questionnaires. Samples will undergo metagenomic, transcriptomic, proteomic, metabolomic and culturomic analyses. Omics data will be integrated with clinical data to identify predictive biomarkers of response to therapy, disease behaviour and environmental factors in patients with IBD. ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the South Eastern Sydney Local Health District Research Ethics Committee (HREC 2019/ETH11443). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12619000911190

FeMn and FeMnAg biodegradable alloys : an in vitro and in vivo investigation

Iron-based biodegradable metal bone graft substitutes are in their infancy but promise to fill bone defects that arise after incidents such as trauma and revision arthroplasty surgery. Before clinical use however, a better understanding of their in vivo biodegradability, potential cytotoxicity and biocompatibility is required. In addition, these implants must ideally be able to resist infection, a complication of any implant surgery. In this study there was significant in vitro cytotoxicity caused by pure Fe, FeMn, FeMn1Ag and FeMn5Ag on both human foetal osteoblast (hFOB) and mouse pre-osteoblast (MC3T3-E1) cell lines. In vivo experiments on the other hand showed no signs of ill-effect on GAERS rats with the implanted FeMn, FeMn1Ag and FeMn5Ag pins being removed largely uncorroded. All Fe-alloys showed anti-bacterial performance but most markedly so in the Ag-containing alloys, there is significant bacterial resistance in vitro.peer-reviewe

Sero-prevalence and risk factors for hepatitis B virus infection among health care workers in a tertiary hospital in Uganda

BACKGROUND: Hepatitis B virus (HBV) infection is a global public health challenge. Prevalence of current hepatitis B virus infection in the general population in Uganda is about 10%. Health care workers (HCW) have an extra risk of getting infected from their workplace and yet they are not routinely vaccinated against HBV infection. This study aimed at estimating prevalence of hepatitis B virus infection and associated risk factors among health care workers in a tertiary hospital in Uganda. METHODS: Data were obtained from a cross sectional survey conducted in Mulago, a national referral and teaching hospital in Uganda among health care workers in 2003. A proportionate to size random sample was drawn per health care worker category. A structured questionnaire was used to collect data on socio-demographic characteristics and risk factors. ELISA was used to test sera for HBsAg, anti-HBs and total anti-HBc. Descriptive and logistic regression models were used for analysis. RESULTS: Among the 370 participants, the sero-prevalence of current hepatitis B virus infection was 8.1%; while prevalence of life time exposure to hepatitis B virus infection was 48.1%. Prevalence of needle stick injuries and exposure to mucous membranes was 67.8% and 41.0% respectively. Cuts were also common with 31.7% of doctors reporting a cut in a period of one year preceding the survey. Consistent use of gloves was reported by 55.4% of respondents. The laboratory technicians (18.0% of respondents) were the least likely to consistently use gloves. Only 6.2% of respondents were vaccinated against hepatitis B virus infection and 48.9% were susceptible and could potentially be protected through vaccination. Longer duration in service was associated with a lower risk of current infection (OR = 0.13; p value = 0.048). Being a nursing assistant (OR = 17.78; p value = 0.007) or a laboratory technician (OR = 12.23; p value = 0.009) were associated with a higher risk of current hepatitis B virus infection. Laboratory technicians (OR = 3.99; p value = 0.023) and individuals with no training in infection prevention in last five years (OR = 1.85; p value = 0.015) were more likely to have been exposed to hepatitis B virus infection before. CONCLUSIONS: The prevalence of current and life time exposure to hepatitis B virus infection was high. Exposure to potentially infectious body fluids was high and yet only a small percentage of HCW were vaccinated. There is need to vaccinate all health care workers as a matter of policy and ensure a safer work environment

Active Whey Protein Edible Films and Coatings Incorporating Lactobacillus buchneri for Penicillium nordicum Control in Cheese

Fungal contamination of food is responsible for health issues and food waste. In this work, the incorporation of a lactic acid bacteria (LAB) with antifungal properties (Lactobacillus buchneri UTAD104) into whey protein-based films and coatings was tested for the control of an ochratoxigenic fungi (Penicillium nordicum) in a cheese matrix. The incorporation of L. buchneri cells resulted in thicker films with less luminosity than control films and colour alteration. Nevertheless, cells inclusion did not alter moisture content, water vapour permeability, mechanical properties, hydrophobicity and chemical structure of the films. Whey protein films were able to maintain the viability of L. buchneri UTAD104 cells in 105 CFU/mL after 30 days of storage at 25 \textdegreeC. When applied in cheese, films and coatings containing L. buchneri cells prevented fungal contamination for at least 30 days, while control cheeses with films and coatings either without LAB or with Lactobacillus casei UM3 (a strain without antifungal ability) showed fungal contamination during that period. Ochratoxin A was not found in cheeses treated with films and coatings containing L. buchneri UTAD104. Results showed that the inclusion of a LAB with antifungal properties in edible films and coatings can help to reduce or eliminate P. nordicum contamination in cheeses.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Ana Guimarães received support through grant SFRH/BD/103245/2014 from the Portuguese FCT.info:eu-repo/semantics/publishedVersio

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease

The FANTOM5 consortium utilised cap analysis of gene expression (CAGE) to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived macrophages grown in macrophage colony-stimulating factor (CSF1) to bacterial lipopolysaccharide (LPS). We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria. The response to LPS is shown to be a cascade of successive waves of transient gene expression extending over at least 48 hours, with hundreds of positive and negative regulatory loops. Promoter analysis using motif activity response analysis (MARA) identified some of the transcription factors likely to be responsible for the temporal profile of transcriptional activation. Each LPS-inducible locus was associated with multiple inducible enhancers, and in each case, transient eRNA transcription at multiple sites detected by CAGE preceded the appearance of promoter-associated transcripts. LPS-inducible long non-coding RNAs were commonly associated with clusters of inducible enhancers. We used these data to re-examine the hundreds of loci associated with susceptibility to inflammatory bowel disease (IBD) in genome-wide association studies. Loci associated with IBD were strongly and specifically (relative to rheumatoid arthritis and unrelated traits) enriched for promoters that were regulated in monocyte differentiation or activation. Amongst previously-identified IBD susceptibility loci, the vast majority contained at least one promoter that was regulated in CSF1-dependent monocyte-macrophage transitions and/or in response to LPS. On this basis, we concluded that IBD loci are strongly-enriched for monocyte-specific genes, and identified at least 134 additional candidate genes associated with IBD susceptibility from reanalysis of published GWA studies. We propose that dysregulation of monocyte adaptation to the environment of the gastrointestinal mucosa is the key process leading to inflammatory bowel disease