Prevalence of chronic respiratory diseases in Aboriginal children: A whole population study

Background The burden of bronchiectasis is disproportionately high in Aboriginal adults, with early mortality. Bronchiectasis precursors, that is, protracted bacterial bronchitis (PBB) and chronic suppurative lung disease (CSLD), often commence in early childhood. We previously reported a 10% prevalence of PBB in Aboriginal children aged 0 to 7 years, however there are no data on prevalence of chronic lung diseases in older children. Our study aimed to determine the prevalence of PBB, CSLD, bronchiectasis, and asthma in Aboriginal children living in four communities. Methods A whole-population cross-sectional community co-designed study of Aboriginal children aged <18-years in four remote communities in Western Australia across two-time points, a month apart. Children were assessed by pediatric respiratory clinicians with spirometry undertaken (when possible) between March–September 2021. Children with respiratory symptoms were followed up via medical record audit from either the local medical clinic or via a respiratory specialist clinic through to March 2022 to establish a final diagnosis. Findings We recruited 392 (91.6%) of those in the selected communities; median age = 8.4 years (interquartile range [IQR] 5.1–11.5). Seventy children (17.9%) had a chronic respiratory pathology or abnormal spirometry results. PBB was confirmed in 30 (7.7%), CSLD = 13 (3.3%), bronchiectasis = 5 (1.3%) and asthma = 17 (4.3%). The prevalence of chronic wet cough significantly increased with increasing age. Interpretation The prevalence of PBB, CSLD and bronchiectasis is high in Aboriginal children and chronic wet cough increases with age. This study highlights the high disease burden in Aboriginal children and the urgent need for strategies to address these conditions

CANDELS : constraining the AGN-merger connection with host morphologies at z ~ 2

Using Hubble Space Telescope/WFC3 imaging taken as part of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey, we examine the role that major galaxy mergers play in triggering active galactic nucleus (AGN) activity at z ~ 2. Our sample consists of 72 moderate-luminosity (L X ~ 1042-44 erg s-1) AGNs at 1.5 < z < 2.5 that are selected using the 4 Ms Chandra observations in the Chandra Deep Field South, the deepest X-ray observations to date. Employing visual classifications, we have analyzed the rest-frame optical morphologies of the AGN host galaxies and compared them to a mass-matched control sample of 216 non-active galaxies at the same redshift. We find that most of the AGNs reside in disk galaxies (51.4+5.8 - 5.9%), while a smaller percentage are found in spheroids (27.8+5.8 - 4.6%). Roughly 16.7+5.3 - 3.5% of the AGN hosts have highly disturbed morphologies and appear to be involved in a major merger or interaction, while most of the hosts (55.6+5.6 - 5.9%) appear relatively relaxed and undisturbed. These fractions are statistically consistent with the fraction of control galaxies that show similar morphological disturbances. These results suggest that the hosts of moderate-luminosity AGNs are no more likely to be involved in an ongoing merger or interaction relative to non-active galaxies of similar mass at z ~ 2. The high disk fraction observed among the AGN hosts also appears to be at odds with predictions that merger-driven accretion should be the dominant AGN fueling mode at z ~ 2, even at moderate X-ray luminosities. Although we cannot rule out that minor mergers are responsible for triggering these systems, the presence of a large population of relatively undisturbed disk-like hosts suggests that the stochastic accretion of gas plays a greater role in fueling AGN activity at z ~ 2 than previously thought

Random effects diagonal metric multidimensional scaling models

By assuming a distribution for the subject weights in a diagonal metric (INDSCAL) multidimensional scaling model, the subject weights become random effects. Including random effects in multidimensional scaling models offers several advantages over traditional diagonal metric models such as those fitted by the INDSCAL, ALSCAL, and other multidimensional scaling programs. Unlike traditional models, the number of parameters does not increase with the number of subjects, and, because the distribution of the subject weights is modeled, the construction of linear models of the subject weights and the testing of those models is immediate. Here we define a random effects diagonal metric multidimensional scaling model, give computational algorithms, describe our experiences with these algorithms, and provide an example illustrating the use of the model and algorithms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45758/1/11336_2005_Article_BF02295730.pd

Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment

A small fraction of cancer patients with advanced disease survive significantly longer than patients with clinically comparable tumors. Molecular mechanisms for exceptional responses to therapy have been identified by genomic analysis of tumor biopsies from individual patients. Here, we analyzed tumor biopsies from an unbiased cohort of 111 exceptional responder patients using multiple platforms to profile genetic and epigenetic aberrations as well as the tumor microenvironment. Integrative analysis uncovered plausible mechanisms for the therapeutic response in nearly a quarter of the patients. The mechanisms were assigned to four broad categories—DNA damage response, intracellular signaling, immune engagement, and genetic alterations characteristic of favorable prognosis—with many tumors falling into multiple categories. These analyses revealed synthetic lethal relationships that may be exploited therapeutically and rare genetic lesions that favor therapeutic success, while also providing a wealth of testable hypotheses regarding oncogenic mechanisms that may influence the response to cancer therapy. Profiling multi-platform genomics of 110 cancer patients with an exceptional therapeutic response, Wheeler et al. identify putative molecular mechanisms explaining this survival phenotype in ∼23% of cases. Therapeutic success is related to rare molecular features of responding tumors, exploiting synthetic lethality and oncogene addiction

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries