T-cell responses against rhinovirus species A and C in asthmatic and healthy children

Background Infections by rhinovirus (RV) species A and C are the most common causes of exacerbations of asthma and a major cause of exacerbations of other acute and chronic respiratory diseases. Infections by both species are prevalent in pre-school and school-aged children and, particularly for RV-C, can cause severe symptoms and a need for hospitalization. While associations between RV infection and asthma are well established, the adaptive immune-mechanisms by which RV infections influence asthma exacerbations are yet to be defined. Objective The aim of this study was to characterize and compare T-cell responses between RV-A and RV-C and to test the hypothesis that T-cell responses would differ between asthmatic children and healthy controls. Methods A multi-parameter flow cytometry assay was used to characterize the in vitro recall T-cell response against RV-A and RV-C in PBMCs from children with acute asthma (n = 22) and controls (n = 26). The responses were induced by pools of peptides containing species-specific VP1 epitopes of RV-A and RV-C. Results Regardless of children's clinical status, all children that responded to the in vitro stimulation (>90%) had a similar magnitude of CD4+ T-cell responses to RV-A and RV-C. However, asthmatic children had a significantly lower number of circulating regulatory T cells (Tregs), and healthy controls had significantly more Tregs induced by RV-A than RV-C. Conclusions and Clinical Relevance The comparable recall memory T-cell responses in asthmatic and control children to both RV-A and RV-C show that differences in the antibody and inflammatory responses previously described are likely to be due to regulation, with a demonstrated candidate being reduced regulatory T-cells. The reduced Treg numbers demonstrated here could explain the asthmatic's inability to appropriately control immunopathological responses to RV infections

Key lessons from the COVID-19 public health response in Australia

Australia avoided the worst effects of the COVID-19 pandemic, but still experienced many negative impacts. Reflecting on lessons from Australia's public health response, an Australian expert panel composed of relevant discipline experts identified the following key lessons: 1) movement restrictions were effective, but their implementation requires careful consideration of adverse impacts, 2) disease modelling was valuable, but its limitations should be acknowledged, 3) the absence of timely national data requires re-assessment of national surveillance structures, 4) the utility of advanced pathogen genomics and novel vaccine technology was clearly demonstrated, 5) decision-making that is evidence informed and consultative is essential to maintain trust, 6) major system weaknesses in the residential aged-care sector require fixing, 7) adequate infection prevention and control frameworks are critically important, 8) the interests and needs of young people should not be compromised, 9) epidemics should be recognised as a ‘standing threat’, 10) regional and global solidarity is important. It should be acknowledged that we were unable to capture all relevant nuances and context specific differences. However, the intent of this review of Australia's public health response is to critically reflect on key lessons learnt and to encourage constructive national discussion in countries across the Western Pacific Region

Diagnostic accuracy of CT pulmonary angiography in suspected pulmonary hypertension

Objectives Computed tomography (CT) pulmonary angiography is widely used in patients with suspected pulmonary hypertension (PH). However, the diagnostic and prognostic significance remains unclear. The aim of this study was to (a) build a diagnostic CT model and (b) test its prognostic significance. Methods Consecutive patients with suspected PH undergoing routine CT pulmonary angiography and right heart catheterisation (RHC) were identified. Axial and reconstructed images were used to derive CT metrics. Multivariate regression analysis was performed in the derivation cohort to identify a diagnostic CT model to predict mPAP ≥ 25 mmHg (the existing ESC guideline definition of PH) and > 20 mmHg (the new threshold proposed at the 6th World Symposium on PH). In the validation cohort, sensitivity, specificity and compromise CT thresholds were identified with receiver operating characteristic (ROC) analysis. The prognostic value of the CT model was assessed using Kaplan-Meier analysis. Results Between 2012 and 2016, 491 patients were identified. In the derivation cohort (n = 247), a CT model was identified including pulmonary artery diameter, right ventricular outflow tract thickness, septal angle and left ventricular area. In the validation cohort (n = 244), the model was diagnostic, with an area under the ROC curve of 0.94/0.91 for mPAP ≥ 25/> 20 mmHg respectively. In the validation cohort, 93 patients died; mean follow-up was 42 months. The diagnostic thresholds for the CT model were prognostic, log rank, all p < 0.01. Discussion In suspected PH, a diagnostic CT model had diagnostic and prognostic utility

A reassessment of Kelmayisaurus petrolicus, a large theropod dinosaur from the Early Cretaceous of China

The Early Cretaceous fossil record of large−bodied theropods from Asia is poor, hindering comparison of Asian predatory dinosaur faunas with those from other continents. One of the few large Asian theropod specimens from this interval is a partial skull (maxilla and dentary) from the Lianmugin Formation (?Valanginian–Albian), the holotype of Kelmayisaurus petrolicus. Most authors have either considered this specimen as an indeterminate basal tetanuran or a nomen dubium. Weredescribe K. petrolicus and note that it possesses a single autapomorphy (a deep accessory groove on the lateral surface of the anterior dentary), as well as a unique combination of characters that differentiates it from other theropods, affirming its validity. A phylogenetic analysis recovers K. petrolicus as a basal carcharodontosaurid, which is supported by various features: very deep interdental plates (a carcharodontosaurid synapomorphy), fused interdental plates (present in carchardontosaurids and a limited number of other theropods), and the absence of diagnostic features of other clades of large−bodied theropods such as abelisaurids, megalosauroids, and coelurosaurs. As such, Kelmayisaurus is the second known carcharodontosaurid from Asia, and further evidence that this clade represented a global radiation of large−bodied predators during the Early–mid Cretaceous

Projected WIMP sensitivity of the LUX-ZEPLIN dark matter experiment

LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4 × 10-48cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3 × 10−43 cm2 (7.1 × 10−42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020

Inhaled treatment for chronic obstructive pulmonary disease:what’s new and how does it fit?

Since chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction, inhaled bronchodilators form the mainstay of treatment. A variety of new inhaled drugs and inhaler devices have recently been licensed and approved for prescribing to patients with COPD; many such drugs have been formulated in devices to deliver two different drugs at the same time. The evidence based review article highlights all of the drugs now licensed, describes some of the evidence surrounding their use and highlights practical steps in helping decide when these drugs should be considered in the context of guidelines

Melioidosis in a rural community of Western Province, Papua New Guinea

A prospective study was conducted to determine the significance of melioidosis in the Balimo district of Western Province, Papua New Guinea. During 1998, after the establishment of laboratory procedures and increasing local clinical awareness, the disease was found in 1.8% (95% CI 0.37–5.1%) of individuals presenting with fever refractory to standard treatment. The clinical incidence was 20.0 per 100 000 population (95% CI 12.2–30.9). The median age of culture-confirmed cases was 9.5 years (interquartile range 8.3–14.8 years). The seroprevalence of 747 community children in the region tested was 8.2% (95% CI 6.2–10.4%). Most individuals presented during the rainy season with a febrile disease refractory to standard treatment, sometimes mimicking tuberculosis. Some family clustering was apparent. All patients with bacteraemic melioidosis died, but treatment with the available conventional therapies of chloramphenicol, co-trimoxazole or doxycycline resulted in survival and cure in six patients with subacute/localised melioidosis. Further studies are needed to ascertain the local epidemiology and why children appear particularly at risk, as well as to establish the true extent of melioidosis in Papua New Guinea