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Background Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-β), bone morphogenic proteins (BMPs) and connective tissue growth factor (CTGF) are key mediators in the pathogenesis of fibrotic disorders. The aim of this systematic review was to investigate the evidence for the expression of TGF-β, BMPs and CTGF along tendon disease progression and the response of tendon cells to these growth factors accordingly. Method We conducted a systematic screen of the scientific literature using the Medline database. The search terms used were “tendon AND TGF-β,” “tendon AND BMP” or “tendon AND CTGF.” Studies of human samples, animal tendon injury and overuse models were included. Results Thirty-three studies were included. In eight studies the expression of TGF-β, BMPs or CTGF was dysregulated in chronic tendinopathy and tendon tear patient tissues in comparison with healthy control tissues. The expression of TGF-β, BMPs and CTGF was increased and showed temporal changes in expression in tendon tissues from animal injury or overuse models compared with the healthy control (23 studies), but the pattern of upregulation was inconsistent between growth factors and also the type of animal model. No study investigated the differences in the effect of TGF-β, BMPs or CTGF treatment between patient-derived cells from healthy and diseased tendon tissues. Tendon cells derived from animal models of tendon injury showed increased expression of extracellular matrix protein genes and increased cell signaling response to TGF-β and BMP treatments compared with the control cells (two studies). Conclusion The expression of TGF-β, BMPs and CTGF in tendon tissues is altered temporally during healing in animal models of tendon injury or overuse, but the transition during the development of human tendon disease is currently unknown. Findings from this systematic review suggest a potential and compelling role for TGF-β, BMPs and CTGF in tendon disease; however, there is a paucity of studies analyzing their expression and stimulated cellular response in well-phenotyped human samples. Future work should investigate the dynamic expression of these fibrotic growth factors and their interaction with tendon cells using patient samples at different stages of human tendon disease.

Recent outbreaks traced to contaminated flour have created a need in the milling industry for a process that reduces pathogens in wheat while maintaining its functional properties. Vacuum steam treatment is a promising technology for treatment of low-moisture foods. Traditional thermal treatment methods can compromise wheat functionality due to high temperatures; thus, maintaining the functional quality of the wheat protein was critical for this research. The objective of this study was to evaluate the effect of vacuum steam treatment of hard red spring (HRS) wheat kernels on final flour quality and the overall efficacy of vacuum stream treatment for reducing pathogens on HRS wheat kernels. HRS wheat samples were treated with steam under vacuum at 65, 70, 75, and 85°C for 4 and 8 min. Significant changes in dough and baked product functionality were observed for treatments at ≥70°C. Treatment time had no significant effect on the qualities evaluated. After determining that vacuum steam treatment at 65°C best preserved product quality, HRS wheat was inoculated with Escherichia coli O121 and Salmonella Enteritidis PT 30 and processed at 65°C for 0, 2, 4, 6, or 8 min. The treatments achieved a maximum average reduction of 3.57 ± 0.33 log CFU/g for E. coli O121 and 3.21 ± 0.27 log CFU/g for Salmonella. Vacuum steam treatment could be an effective pathogen inactivation method for the flour milling industry.

Vacuum steam pasteurization (VSP) is a promising technology for pasteurization of low moisture foods. Recent outbreaks traced to wheat flour, a low moisture food, have created demand in the milling industry for a process that reduces pathogens in wheat while maintaining its functional properties. The objective of this study was to evaluate the efficacy of VSP on Hard Red Spring (HRS) wheat. First, HRS wheat samples were pasteurized at 65, 70, 75, and 85°C for 4 and 8 minutes. Significant changes in dough and baked product functionality were observed in treatments ≥70°C suggesting gluten denaturation occurred. After determining that 65°C processing conditions best preserved functionality, HRS wheat was inoculated with Escherichia coli O121, and processed at 65°C for 0, 2, 4, 6, and 8 min periods. The treatments achieved a maximum microbial reduction of ~3.5 log CFU/g. VSP shows potential as an effective pasteurization method for the flour milling industry.

This thesis extends our understanding of a ‘puzzle of participation’ (Brody 1978). Across established Western democracies, turnout in elections has been steadily falling - at the same time, society is modernising. Central to this latter phenomenon is educational expansion, a process in which there is increased higher education (HE) enrolment, rising attainment levels, and even wider citizenship education. Under classic civic education hypotheses, such factors are anticipated to increase political literacy, raise electoral interest, and provide encouraging environments for political participation. Hence, the patterns we observe in turnout present as paradoxical. This is especially evident among the very youngest electors, who comprise arguably the most educated generation yet but are also the least likely to vote. The thesis thus poses the question: Why is the comparatively higher level of education enjoyed by young people today not associated with a higher level of voter turnout? My response takes inspiration from Norris’s ‘critical citizens’ (1999, 2011) and combines this with repertoire replacement (Dalton 2008; Norris 2003) and sorting model (Nie et al 1996) theories to develop an argument based on a multiplicity of education effects on turnout. Specifically, I present a thesis which contends that higher levels of education today encourage the emergence of a non-voting disaffected citizenry, characterised by two distinct dimensions. The first, a dissatisfied-disaffection is thought to be present among growing student populations. It is this demographic group which, in response to its members’ HE experiences, is challenging established political processes, becoming more demanding of an active role in politics, and turning to alternative participation activities when opportunities arise. Within this I posit two non-voter types: (a) frustrated electors, committed to voting yet exasperated by the responsiveness of political actors and their policy offers at elections, and (b) engaged activists, pointedly rejecting voting in favour of more direct and ongoing influencing activities. The second dimension reflects alienated-disaffection. Here, individuals who lack HE experience are seeing their status and position decline in line with educational inflation, and, as a consequence, experience limited political network mobilisation, find their confidence for participation falling, and so withdraw from politics altogether. They are marginalised citizens. Meanwhile, a number of young people will continue to vote, receiving encouragement from their social networks and partisan attachments; mobilised voters. This thesis makes its contributions in testing and refining these propositions in the case of the British electorate using data from the British Election Study, British Participation Survey, and the Citizens in Transition Survey. Through a range of statistical techniques (including logistic regression, latent class analysis, and structural equation modelling) I devise new ways of operationalising disaffection, and assess its varied impact on turnout. This thesis progresses to explore typologies of participation repertoires, within which combinations of disaffection attitudes and turnout behaviours exist. It then examines in more detail the educational mechanisms through which these occur.

Palmer and Snelling discusses Design Museum courses for student teachers. The Design Museum is launching a program to provide additional practical support and subject knowledge in design and technology for post-graduate teacher trainees.

In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation.

In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation. ClinicalTrials.gov NCT01735084 and NCT01174849.

Background Untreated hepatitis C virus (HCV) infection can result in cirrhosis and hepatocellular cancer. Direct-acting antiviral (DAA) therapies are highly effective and have few side effects compared to older interferon-based therapy. Despite the Australian government providing subsidised and unrestricted access to DAA therapy for chronic HCV infection, uptake has not been sufficient to meet the global target of eliminating HCV as a public health threat by 2030. This study will offer people with HCV financial incentives of varying values in order to evaluate its effect on initiation of DAA therapy in primary care. Methods Australian adults (18 years or older) who self-report as having current untreated HCV infection can register to participate via an automated SMS-based system. Following self-screening for eligibility, registrants are offered a financial incentive of randomised value (AUD 0 to 1000) to initiate DAA therapy. Study treatment navigators contact registrants who have consented to be contacted, to complete eligibility assessment, outline the study procedures (including the requirement for participants to consult a primary care provider), obtain consent, and finalise enrolment. Enrolled participants receive their offered incentive on provision of evidence of DAA therapy initiation within 12 weeks of registration (primary endpoint). Balanced randomisation is used across the incentive range until the first analysis, after which response-adaptive randomisation will be used to update the assignment probabilities. For the primary analysis, a Bayesian 4-parameter EMAX model will be used to estimate the dose–response curve and contrast treatment initiation at each incentive value against the control arm (AUD 0). Specified secondary statistical and economic analyses will evaluate the effect of incentives on adherence to DAA therapy, virological response, and cost-effectiveness. Discussion This project seeks to gain an understanding of the dose–response relationship between incentive value and DAA treatment initiation, while maximising the number of people treated for HCV within fixed budget and time constraints. In doing so, we hope to offer policy-relevant recommendation(s) for the use of financial incentives as a pragmatic, efficient, and cost-effective approach to achieving elimination of HCV from Australia. Trial registration ANZCTR (anzctr.org.au), Identifier ACTRN12623000024640, Registered 11 January 2023 ( https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384923&isReview=true ).

•P3-MumBubVax is a multi-component intervention to support maternal vaccine delivery by Australian midwives.•The intervention targets all three levels of the healthcare encounter - the practice, provider and parent-levels (P3).•It includes midwife prompts and vaccine communication training, website, fact sheets, and parent SMS reminders.•Midwives and pregnant women reported that P3-MumBubVax was feasible and acceptable. Pregnancy is a critical time for vaccine decision-making, but coverage remains suboptimal for maternal influenza (45–60%) and pertussis vaccination (65–80%) in Australia. The multi-component P3-MumBubVax intervention has been designed for Australian midwives to optimise antenatal vaccine discussions and improve maternal and childhood vaccine uptake. A pilot study was conducted to assess intervention feasibility and acceptability. P3-MumBubVax includes components at three levels: 1. Practice ('vaccine champions'; stickers to prompt and record vaccine discussions/delivery); 2. Provider (website with vaccine communication training; learning exercise; fact sheets; links to child vaccination resources); 3. Parent (SMS reminders; website; fact sheets). Midwives and pregnant women 18–22 weeks gestation were recruited at the Royal Women's Hospital, Melbourne. Post-intervention online surveys assessed intervention feasibility, implementation, acceptability and impact on vaccine uptake. Twenty-five midwives and 62 pregnant women were recruited and 19/25 midwives completed training. Surveys were returned by 18/25 midwives and 56/62 women. 14/18 midwives reported using the sticker prompts, 10/18 reported using or referring to the website, and 11/18 reported using the fact sheets. 48/56 pregnant women (86%) reported discussing influenza and 46/56 (82%) discussed pertussis vaccines with their midwives. These conversations were reported to be short (1–3 min) for 48/56 women (87%). All midwives were satisfied with the intervention and 17/18 reported feeling more confident discussing vaccines following the intervention. Women were very satisfied with SMS content (50/56; 94%) and timing (49/55; 89%), and with their vaccine discussions in general (34/56; 63%). However, 16/54 (30%) wanted more discussion about childhood vaccines. Self-reported maternal vaccine uptake was 82% (45/55) and 93% (51/55) for influenza and pertussis (baseline 2017–2018: 43% influenza, 60% pertussis) and 96% (50/52) of infants were fully vaccinated at 12 weeks. The P3-MumBubVax intervention is feasible and acceptable in the Australian public antenatal setting. Further evaluation is required to determine effectiveness.

IntroductionRotavirus vaccines were introduced into the Australian National Immunisation Program in 2007. Despite this, Northern Territory Indigenous children continue to be hospitalised with rotavirus at a rate more than 20 times higher than non-Indigenous children in other Australian jurisdictions, with evidence of waning protection in the second year of life. We hypothesised that scheduling an additional (third) dose of oral human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to <12 months would improve protection against clinically significant all-cause gastroenteritis.Methods and analysisThis Bayesian adaptive clinical trial will investigate whether routinely scheduling an additional dose of Rotarix for Australian Indigenous children aged 6 to <12 months old confers significantly better protection against clinically important all-cause gastroenteritis than the current two-dose schedule at 2 and 4 months old. There are two coprimary endpoints: (1) seroconversion from baseline serum anti-rotavirus immunoglobulin A (IgA) titre <20 U/mL prior to an additional dose of Rotarix/placebo to serum anti-rotavirus IgA titre >20 U/mL following the administration of the additional dose of Rotarix/placebo and (2) time from randomisation to medical attendance (up to age 36 months old) for which the primary reason is acute gastroenteritis/diarrhoea. Secondary endpoints include the change in anti-rotavirus IgA log titre, time to hospitalisation for all-cause diarrhoea and for rotavirus-confirmed gastroenteritis/diarrhoea, and rotavirus notification. Analysis will be based on Bayesian inference with adaptive sample size.Ethics, registration and disseminationEthics approval has been granted by Central Australian Human Research Ethics Committee (HREC-16-426) and Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC-2016-2658). Study investigators will ensure the trial is conducted in accordance with the principles of the Declaration of Helsinki and with the ICH Guidelines for Good Clinical Practice. Individual participant consent will be obtained. Results will be disseminated via peer-reviewed publication. The trial is registered with Clinicaltrials.gov (NCT02941107) and important modifications to this protocol will be updated.Trial registration numberNCT02941107; Pre-results.