Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised c

BackgroundRecurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. MethodsA multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged ≥6 years; and vaccine safety. DiscussionAs H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis

The Relationship between 60-yard sprint, 30-yard sprint, Standardized Base Stealing Sprint, and Offensive Baseball Performance

Athletic performance testing protocols strive to accurately predicting or gain better understanding of an athlete’s performance within a particular sport or game. Regarding baseball, Wolfe and colleagues (2012) examined the predictive validity of the 60-yard shuttle run on pitching performance and concluded that strikeouts and innings pitched were significantly related to elevated kinetic energy factors of pitchers obtained from the shuttle run performance. Concerning for baseball position players, the 60-yard sprint (60YS) is traditionally utilized to showcase “baseball speed”, with minimal empirical evident supporting predictability to baseball specific performance outcomes. PURPOSE: The aim of the current investigation was to have examine the relationship between 60YS and offensive baseball performance outcomes, as well as the 30-yard sprint (30YS) test, and newly created standardized 1st to 2nd sprint (STS) test relationship to offensive baseball performance outcomes. METHODS: Division I baseball position players (n = 17; height: 180.92 ± 5.61 cm; weight: 82.1 ± 11.12 kg) performed three sprinting tests: 60YS, 30YS, and STS. Each test was recorded using the Brower Timing Gate System, with sprint time recorded in second. All testing was completed prior to the first game of the team’s college baseball season. Offensive baseball performance measures were recorded throughout 61 regular season games. The following baseball performance data was collected from the university’s official NCAA game performance website: total stolen bases (SB), stole base attempts (AT), stolen base percentage (SBP), at bats (AB), hits (H), doubles (DB), triples (TR), homeruns (HR), runs (R), base-on-balls (BB), hit by pitch (HBP), on base percentage (OBP), slugging percentage (SLP), touched bases (TB), runs batted in (RBI), and batting average (AVE). Pearson’s product-moment correlation (p \u3c .05) was employed to examine the correlation between sprint tests and offensive baseball performance. RESULTS: The statistical analysis revealed significant correlations between STS (p = .002, r = -.762), 30 yd sprint (p = .048, r = -.556), and 60 yd sprint (p = .038, r = -.578) and SB. Additionally, a significant correlation was identified between OBP and STS (p = .022, r = -.625), 30YS (p = .027, r = -.609), and 60YS (p = .020, r = -.633). Aside from these two baseball performance metrics, 30YS and 60YS had no significant correlation with baseball performance. However, STS, additionally, significantly (p \u3c .05) correlated with AT, AB, H, TR, HR, R, BB, SLP, TB, RBI, and AVE. CONCLUSION: The STS, 30YS, and 60YS had a significant relationship with offensive baseball performance. However, the results of 30YS and 60YS only correlated with two offensive measures, while STS had a significant correlation with all but 3 offensive performance metrics. These findings suggest STS may be a more relevant measure for predicting offensive baseball performance than the traditional 30YS and 60YS tests

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children

Understanding the aetiology and resolution of chronic otitis media from animal and human studies

Inflammation of the middle ear, known clinically as chronic otitis media, presents in different forms, such as chronic otitis media with effusion (COME; glue ear) and chronic suppurative otitis media (CSOM). These are highly prevalent diseases, especially in childhood, and lead to significant morbidity worldwide. However, much remains unclear about this disease, including its aetiology, initiation and perpetuation, and the relative roles of mucosal and leukocyte biology, pathogens, and Eustachian tube function. Chronic otitis media is commonly modelled in mice but most existing models only partially mimic human disease and many are syndromic. Nevertheless, these models have provided insights into potential disease mechanisms, and have implicated altered immune signalling, mucociliary function and Eustachian tube function as potential predisposing mechanisms. Clinical studies of chronic otitis media have yet to implicate a particular molecular pathway or mechanism, and current human genetic studies are underpowered. We also do not fully understand how existing interventions, such as tympanic membrane repair, work, nor how chronic otitis media spontaneously resolves. This Clinical Puzzle article describes our current knowledge of chronic otitis media and the existing research models for this condition. It also identifies unanswered questions about its pathogenesis and treatment, with the goal of advancing our understanding of this disease to aid the development of novel therapeutic interventions

Transit station or destination? Attendance patterns, movements, and abundance estimate of humpback whales off west South Africa from photographic and genotypic matching

Humpback whales found off west South Africa (WSA) are known to display an atypical migration that may include temporary residency and feeding during spring and summer. At a regional scale there is uncertainty about how these whales relate to the greater West African Breeding Stock B as a whole, with evidence both for and against its division into two sub-stocks. A database containing sighting information of humpback whales intercepted by boat in the WSA region from 1983 to 2008 was compiled. It included a total of 1,820 identification images of ventral tail flukes and lateral views of dorsal fins. After systematic within- and between-year matching of images of usable quality, it yielded 154 different individuals identified by tail flukes (TF), 230 by left dorsal fins (LDF), and 237 by right dorsal fins (RDF). Microsatellite (MS) matching of 216 skin biopsies yielded 156 individuals. By linking all possible sightings of the same individuals using all available identification features, the periodicity and seasonality of 281 individual whales were examined. Sixty whales were resighted on different days of which 44 were between different calendar years. The most resightings for one individual was 11 times, seen in six different years, while the longest interval between first and last sightings was about 18 years. A resighting rate of 15.6% of whales at intervals of a year or more indicates long-term fidelity to the region. Shorter intervals of 1 – 6 months between sequential sightings in the same year may suggest temporary residency. The TF image collection from WSA was compared to TF collections from four other regions, namely Gabon, Cabinda (Angola), Namibia and the Antarctic Humpback Whale Catalogue (AHWC). Three matches were detected were between WSA (in late spring or summer) and Gabon (in winter), confirming direct movement between these regions. The capture-recapture data of four different identification features (TF, RDF, LDF and MS) from six successive subsets of data from periods with the highest collection effort (2001 – 2007), were used to calculate the number of whales that utilise the region, using both closed and open-population models. Since dorsal fins have never been used to estimate abundance for humpback whales, the different identification features were evaluated for potential biases. This revealed 9 – 14% incidence of missed matches (false negatives) when using dorsal fins that will result in an overestimate, while variation in individual fluke-up behaviour may lower estimates due to heterogeneity of individual capture probability, by as much as 57-69%. Taking into consideration the small dataset and low number of recaptures, the most consistent and precise results were obtained from a fully time-dependent version of the Jolly-Seber open-population model, with annual survival fixed at 0.96, using the MS dataset. This suggests that the WSA feeding assemblage during the months of spring and summer of the study period numbered about 500. The relationship of these whales to those (perhaps strictly migratory) that may occur here in other seasons of the year, and their links to possible migratory routes and other feeding or breeding areas remain uncertain.National Research Foundation (NRF), South Africa, under Grant Number 2047517. Earthwatch Institute (funding), The Mazda Wildlife Fund (through the provision of a field vehicle), SASOL (through the donation of two four-stroke engines), PADI Project AWARE (UK) (funding), the South African Navy (access to the shore-based look-out), the Military Academy, University of Stellenbosch (accommodation) and Iziko South African Museum (office space and support). JB gratefully received financial support in the form of bursaries from the NRF, the Society for Marine Mammalogy, University of Pretoria, and the Wildlife Society of South Africa (Charles Astley Maberley Memorial bursary). The Namibian Dolphin Project is supported by NACOMA (Namibian Coastal Conservation and Management Project), the Nedbank Go Green Fund, Mohammed bin Zayed Species Conservation Fund, the British Ecological Society, the Rufford Small Grants Foundation and the Namibia Nature Foundation. JB and TJQC received funding from the International Whaling Commission (IWC) to conduct between-region matching.http://www.tandfonline.com/loi/tams20nf201

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Human gestation-associated tissues express functional cytosolic nucleic acid sensing pattern recognition receptors

The role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways, that yield a cytokine output in response to pathogenic stimuli, have been postulated to link infection at the maternal–fetal interface and adverse pregnancy outcomes. The objective of this study was to investigate the expression and functional response of nucleic acid ligand responsive Toll-like receptors (TLR-3, −7, −8 and −9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors [RIG-I, melanoma differentiation-associated protein 5 (MDA5) and Laboratory of Genetics and Physiology 2(LGP2)] in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model. Immunohistochemistry revealed that these PRRs were expressed by the term placenta, choriodecidua and amnion. A statistically significant increase in interleukin (IL)-6 and/or IL-8 production in response to specific agonists for TLR-3 (Poly(I:C); low and high molecular weight), TLR-7 (imiquimod), TLR-8 (ssRNA40) and RIG-I/MDA5 (Poly(I:C)LyoVec) was observed; there was no response to a TLR-9 (ODN21798) agonist. A hierarchical clustering approach was used to compare the response of each tissue type to the ligands studied and revealed that the placenta and choriodecidua generate a more similar IL-8 response, while the choriodecidua and amnion generate a more similar IL-6 response to nucleic acid ligands. These findings demonstrate that responsiveness via TLR-3, TLR-7, TLR-8 and RIG-1/MDA5 is a broad feature of human term gestation-associated tissues with differential responses by tissue that might underpin adverse obstetric outcomes

The contribution of geogenic particulate matter to lung disease in indigenous children

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Indigenous children have much higher rates of ear and lung disease than non-Indigenous children, which may be related to exposure to high levels of geogenic (earth-derived) particulate matter (PM). The aim of this study was to assess the relationship between dust levels and health in Indigenous children in Western Australia (W.A.). Data were from a population-based sample of 1077 Indigenous children living in 66 remote communities of W.A. (>2,000,000 km2), with information on health outcomes derived from carer reports and hospitalisation records. Associations between dust levels and health outcomes were assessed by multivariate logistic regression in a multi-level framework. We assessed the effect of exposure to community sampled PM on epithelial cell (NuLi-1) responses to non-typeable Haemophilus influenzae (NTHi) in vitro. High dust levels were associated with increased odds of hospitalisation for upper (OR 1.77 95% CI [1.02–3.06]) and lower (OR 1.99 95% CI [1.08–3.68]) respiratory tract infections and ear disease (OR 3.06 95% CI [1.20–7.80]). Exposure to PM enhanced NTHi adhesion and invasion of epithelial cells and impaired IL-8 production. Exposure to geogenic PM may be contributing to the poor respiratory health of disadvantaged communities in arid environments where geogenic PM levels are high

Institutional review board challenges related to community-based participatory research on human exposure to environmental toxins: A case study

<p>Abstract</p> <p>Background</p> <p>We report on the challenges of obtaining Institutional Review Board (IRB) coverage for a community-based participatory research (CBPR) environmental justice project, which involved reporting biomonitoring and household exposure results to participants, and included lay participation in research.</p> <p>Methods</p> <p>We draw on our experiences guiding a multi-partner CBPR project through university and state Institutional Review Board reviews, and other CBPR colleagues' written accounts and conference presentations and discussions. We also interviewed academics involved in CBPR to learn of their challenges with Institutional Review Boards.</p> <p>Results</p> <p>We found that Institutional Review Boards are generally unfamiliar with CBPR, reluctant to oversee community partners, and resistant to ongoing researcher-participant interaction. Institutional Review Boards sometimes unintentionally violate the very principles of beneficence and justice which they are supposed to uphold. For example, some Institutional Review Boards refuse to allow report-back of individual data to participants, which contradicts the CBPR principles that guide a growing number of projects. This causes significant delays and may divert research and dissemination efforts. Our extensive education of our university Institutional Review Board convinced them to provide human subjects protection coverage for two community-based organizations in our partnership.</p> <p>Conclusions</p> <p>IRBs and funders should develop clear, routine review guidelines that respect the unique qualities of CBPR, while researchers and community partners can educate IRB staff and board members about the objectives, ethical frameworks, and research methods of CBPR. These strategies can better protect research participants from the harm of unnecessary delays and exclusion from the research process, while facilitating the ethical communication of study results to participants and communities.</p