Themes Underlying Australian General Practitioner Views towards Chiropractic and Osteopathy: An Assessment of Free Text Data from a Cross-Sectional Survey

The Australian chiropractic and osteopathic professions underwent a period of significant transformation between 1960 and 2000. This resulted in an improvement in the views held by the medical profession towards the two professions. However, a recent survey of Australian general practitioners (GPs) reported that a number of GPs still hold negative views towards chiropractors and osteopaths. This paper examines these views from the perspective of critical realism and explores the generative mechanisms that can influence the willingness of health practitioners to collaborate over patient care. A qualitative analysis of open-ended responses to a survey of 630 Australian GPs was conducted. Unfavourable attitudes of GPs towards chiropractors and osteopaths included perceived lack of safety, efficacy, and inadequacy of training, despite chiropractic’s and osteopathy’s reliance on the same evidence base and similar training to those of other manual therapy professions such as physiotherapy. These attitudes may be underpinned by the professional biases against chiropractic and osteopathy that continue to marginalise the professions within the Australian healthcare system. Continued investment in the research base for chiropractic and osteopathic practice is required, along with raising the awareness of GPs about the education and skills of chiropractors and osteopaths

Coadministration of a 9-Valent Human Papillomavirus Vaccine With Meningococcal and Tdap Vaccines

BACKGROUND: This study in 11- to 15-year-old boys and girls compared the immunogenicity and safety of GARDASIL 9 (9-valent human papillomavirus [9vHPV] vaccine) administered either concomitantly or nonconcomitantly with 2 vaccines routinely administered in this age group (Menactra [MCV4; Neisseria meningitidis serotypes A/C/Y/W-135] or Adacel [Tdap; diphtheria/tetanus/acellular pertussis]). METHODS: Participants received 9vHPV vaccine at day 1 and months 2 and 6; the concomitant group (n = 621) received MCV4/Tdap concomitantly with 9vHPV vaccine at day 1; the nonconcomitant group (n = 620) received MCV4/Tdap at month 1. Antibodies to HPV-, MCV4-, and Tdap-relevant antigens were determined. Injection-site and systemic adverse events (AEs) were monitored for 15 days after any vaccination; serious AEs were monitored throughout the study. RESULTS: The geometric mean titers for all HPV types in 9vHPV vaccine 4 weeks after dose 3, proportion of subjects with a fourfold rise or greater in titers for 4 N meningitidis serotypes 4 weeks after injection with MCV4, proportion of subjects with antibody titers to diphtheria and tetanus ≥0.1 IU/mL, and geometric mean titers for pertussis antigens 4 weeks after injection with Tdap were all noninferior in the concomitant group compared with the nonconcomitant group. Injection-site swelling occurred more frequently in the concomitant group. There were no vaccine-related serious AEs. CONCLUSIONS: Concomitant administration of 9vHPV vaccine with MCV4/Tdap was generally well tolerated and did not interfere with the antibody response to any of these vaccines. This strategy would minimize the number of visits required to deliver each vaccine individually

An automated deep learning pipeline based on advanced optimisations for leveraging spectral classification modelling

Na modelagem de deep learning (DL) para dados espectrais, um grande desafio está relacionado à escolha da arquitetura de rede DL e à seleção dos melhores hiperparmetros. Muitas vezes, pequenas mudanças na arquitetura neural ou seu hiperparômetro podem ter uma influência direta no desempenho do modelo, tornando sua robustez questionável. Para lidar com isso, este estudo apresenta uma modelagem automatizada de aprendizagem profunda baseada em técnicas avançadas de otimização envolvendo hyperband e otimização bayesiana, para encontrar automaticamente a arquitetura neural ideal e seus hiperparmetros para alcançar modelos robustos de DL. A otimização requer uma arquitetura neural base para ser inicializada, no entanto, mais tarde, ajusta automaticamente a arquitetura neural e os hiperparmetros para alcançar o modelo ideal. Além disso, para apoiar a interpretação dos modelos DL, foi implementado um esquema de pesagem de comprimento de onda baseado no mapeamento de ativação de classe ponderada por gradiente (Grad-CAM). O potencial da abordagem foi mostrado em um caso real de classificação da variedade de trigo com dados espectrais quase infravermelhos. O desempenho da classificação foi comparado com o relatado anteriormente no mesmo conjunto de dados com diferentes abordagens DL e quimiométrica. Os resultados mostraram que, com a abordagem proposta, foi alcançada uma precisão de classificação de 94,9%, melhor do que a melhor precisão relatada no mesmo conjunto de dados, ou seja, 93%. Além disso, o melhor desempenho foi obtido com uma arquitetura neural mais simples em comparação com o que foi usado em estudos anteriores. O deep learning automatizado baseado na otimização avançada pode suportar a modelagem DL de dados espectrais.info:eu-repo/semantics/publishedVersio

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Pseudomonas aeruginosa Pili and Flagella Mediate Distinct Binding and Signaling Events at the Apical and Basolateral Surface of Airway Epithelium

Pseudomonas aeruginosa, an important opportunistic pathogen of man, exploits numerous factors for initial attachment to the host, an event required to establish bacterial infection. In this paper, we rigorously explore the role of two major bacterial adhesins, type IV pili (Tfp) and flagella, in bacterial adherence to distinct host receptors at the apical (AP) and basolateral (BL) surfaces of polarized lung epithelial cells and induction of subsequent host signaling and pathogenic events. Using an isogenic mutant of P. aeruginosa that lacks flagella or utilizing beads coated with purified Tfp, we establish that Tfp are necessary and sufficient for maximal binding to host N-glycans at the AP surface of polarized epithelium. In contrast, experiments utilizing a P. aeruginosa isogenic mutant that lacks Tfp or using beads coated with purified flagella demonstrate that flagella are necessary and sufficient for maximal binding to heparan sulfate (HS) chains of heparan sulfate proteoglycans (HSPGs) at the BL surface of polarized epithelium. Using two different cell-free systems, we demonstrate that Tfp-coated beads show highest binding affinity to complex N-glycan chains coated onto plastic plates and preferentially aggregate with beads coated with N-glycans, but not with single sugars or HS. In contrast, flagella-coated beads bind to or aggregate preferentially with HS or HSPGs, but demonstrate little binding to N-glycans. We further show that Tfp-mediated binding to host N-glycans results in activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway and bacterial entry at the AP surface. At the BL surface, flagella-mediated binding to HS activates the epidermal growth factor receptor (EGFR), adaptor protein Shc, and PI3K/Akt, and induces bacterial entry. Remarkably, flagella-coated beads alone can activate EGFR and Shc. Together, this work provides new insights into the intricate interactions between P. aeruginosa and lung epithelium that may be potentially useful in the development of novel treatments for P. aeruginosa infections

MOPED: Model Organism Protein Expression Database

Large numbers of mass spectrometry proteomics studies are being conducted to understand all types of biological processes. The size and complexity of proteomics data hinders efforts to easily share, integrate, query and compare the studies. The Model Organism Protein Expression Database (MOPED, htttp://moped.proteinspire.org) is a new and expanding proteomics resource that enables rapid browsing of protein expression information from publicly available studies on humans and model organisms. MOPED is designed to simplify the comparison and sharing of proteomics data for the greater research community. MOPED uniquely provides protein level expression data, meta-analysis capabilities and quantitative data from standardized analysis. Data can be queried for specific proteins, browsed based on organism, tissue, localization and condition and sorted by false discovery rate and expression. MOPED empowers users to visualize their own expression data and compare it with existing studies. Further, MOPED links to various protein and pathway databases, including GeneCards, Entrez, UniProt, KEGG and Reactome. The current version of MOPED contains over 43 000 proteins with at least one spectral match and more than 11 million high certainty spectra

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO