Colonialism and Male Domestic Service Across the Asia Pacific

Examining the role of Asian and indigenous male servants across the Asia Pacific from the late-19th century to the 1930s, this study shows how their ubiquitous presence in these purportedly \u27humble\u27 jobs gave them a degree of cultural influence that has been largely overlooked in the literature on labour mobility in the age of empire. With case studies from British Hong Kong, Singapore, Northern Australia, Fiji and British Columbia, French Indochina, the American Philippines and the Dutch East Indies, the book delves into the intimate and often conflicted relationships between European and American colonists and their servants. It explores the lives of \u27houseboys\u27, cooks and gardeners in the colonial home, considers the bell-boys and waiters in the grand colonial hotels, and follows the stewards and cabin-boys on steamships travelling across the Indian and Pacific Oceans. This broad conception of service allows Colonialism and Male Domestic Service across Asia and the Pacific to illuminate trans-colonial or cross-border influences through the mobility of servants and their employers. This path-breaking study is an important book for students and scholars of colonialism, labour history and the Asia Pacific region

Cost Analysis of Adjuvant Whole‑Brain Radiotherapy Treatment Versus No Whole‑Brain Radiotherapy After Stereotactic Radiosurgery and/or Surgery Among Adults with One to Three Melanoma Brain Metastases: Results from a Randomized Trial

Purpose We aimed to compare Australian health system costs at 12 months for adjuvant whole-brain radiotherapy (WBRT) treatment after stereotactic radiosurgery (SRS) and/or surgery versus observation among adults with one to three melanoma brain metastases. We hypothesized that treatment with adjuvant WBRT and subsequent healthcare would be more expensive than SRS/surgery alone. Methods The analysis was conducted alongside a multicentre, randomized phase III trial. A bespoke cost questionnaire was used to measure healthcare use, including hospitalizations, specialist and primary care visits, imaging, and medicines over 12 months. Mean per-patient costs were calculated based on the quantity of resources used and unit costs, reported in Australian dollars ($AU), year 2018 values. Skewness of cost data was determined using normality tests and censor-adjusted costs reported using the Kaplan–Meier sample average method. The analysis of diference in mean costs at each 2-month time point and at 12 months was performed and checked using Kruskal–Wallis, generalized linear models with gamma distribution and log link, modifed Park test, ordinary least squares, and non-parametric bootstrapping. Results In total, 89 patients with similar characteristics at baseline were included in the cost analysis (n = 43 WBRT; n = 46 observation). Hospitalization cost was the main cost, ranging from 63 to 8912-monthly cost for WBRT was$AU71,138 ± standard deviation 41,475 and for observation $AU69,848 ± 33,233; p = 0.7426. The censor-adjusted 12-monthly cost for WBRT was$AU90,277 ± 36,274 and $AU82,080 ± 34,411 for observation. There was no signifcant diference in 2-monthly costs between groups (p > 0.30 for all models). Conclusions Most costs were related to inpatient hospitalizations associated with disease recurrence. Adding WBRT after local SRS/surgery for patients with one to three melanoma brain metastases did not signifcantly increase health system costs during the frst 12 months. Trial Registration ACTRN12607000512426, prospectively registered 14 September 200

Mouse screen reveals multiple new genes underlying mouse and human hearing loss.

Adult-onset hearing loss is very common, but we know little about the underlying molecular pathogenesis impeding the development of therapies. We took a genetic approach to identify new molecules involved in hearing loss by screening a large cohort of newly generated mouse mutants using a sensitive electrophysiological test, the auditory brainstem response (ABR). We review here the findings from this screen. Thirty-eight unexpected genes associated with raised thresholds were detected from our unbiased sample of 1,211 genes tested, suggesting extreme genetic heterogeneity. A wide range of auditory pathophysiologies was found, and some mutant lines showed normal development followed by deterioration of responses, revealing new molecular pathways involved in progressive hearing loss. Several of the genes were associated with the range of hearing thresholds in the human population and one, SPNS2, was involved in childhood deafness. The new pathways required for maintenance of hearing discovered by this screen present new therapeutic opportunities

Whole brain radiotherapy (WBRT) after local treatment of brain metastases in melanoma patients: Statistical Analysis Plan

Background: The WBRTMel trial is a multinational, open-label, phase III randomised controlled trial comparing whole brain radiotherapy (WBRT) to observation following local treatment of one to three melanoma brain metastases with surgery and/or stereotactic irradiation. The primary trial endpoint was to determine the effect of adding WBRT to local treatment on distant intracranial control, and the secondary endpoints were neurocognitive function, quality of life (QoL), performance status, overall survival, death from intracranial causes, death from melanoma and cost-effectiveness. Objective: The objective of this update is to outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis. Methods: The SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical and QoL outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data. Results: The resulting SAP is consistent with best practice and will allow open and transparent reporting. Conclusion: We have developed a SAP for the WBRTMel trial which will be followed to ensure high-quality standards of internal validity to minimise analysis bias

Depression in multicultural Australia: Policies, research and services

BACKGROUND: Depression is one of the leading causes of disability in Australia. The cultural and linguistic diversity of the Australian population poses a significant challenge to health policy development, service provision, professional education, and research. The purpose of this study is to explore the extent to which the fact of cultural and linguistic diversity has influenced the formulation of mental health policy, the conduct of mental health research and the development of mental health services for people with depression from ethnic minority communities. METHODS: The methods used for the different components of the study included surveys and document-based content and thematic analyses. RESULTS: Policy is comprehensive but its translation into programs is inadequate. Across Australia, there were few specific programs on depression in ethnic minority communities and they are confronted with a variety of implementation difficulties. The scope and scale of research on depression in Ethnic minority communities is extremely limited. CONCLUSION: A key problem is that the research that is necessary to provide evidence for policy and service delivery is lacking. If depression in Ethnic minority communities is to be addressed effectively the gaps between policy intentions and policy implementation, and between information needs for policies and practice and the actual research that is being done, have to be narrowed

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila. We found that fly dTnpo (orthologous to TNPO2) is expressed in a subset of neurons. dTnpo is critical for neuronal maintenance and function as downregulating dTnpo in mature neurons using RNAi disrupts neuronal activity and survival. Altering the activity and expression of dTnpo using mutant alleles or RNAi causes developmental defects, including eye and wing deformities and lethality. These effects are dosage dependent as more severe phenotypes are associated with stronger dTnpo loss. Interestingly, similar phenotypes are observed with dTnpo upregulation and ectopic expression of TNPO2, showing that loss and gain of Transportin activity causes developmental defects. Further, proband-associated variants can cause more or less severe developmental abnormalities compared to wild-type TNPO2 when ectopically expressed. The impact of the variants tested seems to correlate with their position within the protein. Specifically, those that fall within the RAN binding domain cause more severe toxicity and those in the acidic loop are less toxic. Variants within the cargo binding domain show tissue-dependent effects. In summary, dTnpo is an essential gene in flies during development and in neurons. Further, proband-associated de novo variants within TNPO2 disrupt the function of the encoded protein. Hence, TNPO2 variants are causative for neurodevelopmental abnormalities

Dual bronchodilators in Bronchiectasis study (DIBS): protocol for a pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial studying bronchodilators in preventing exacerbations of bronchiectasis

Introduction: Bronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung disease, further exacerbations, hospitalisations, reduced quality of life and increased risk of death. Despite an increasing prevalence of bronchiectasis, there is a critical lack of high-quality studies into the disease and no treatments specifically approved for its treatment. This trial aims to establish whether inhaled dual bronchodilators (long acting beta agonist (LABA) and long acting muscarinic antagonist (LAMA)) taken as either a stand-alone therapy or in combination with inhaled corticosteroid (ICS) reduce the number of exacerbations of bronchiectasis requiring treatment with antibiotics during a 12 month treatment period. Methods: This is a multicentre, pragmatic, double-blind, randomised controlled trial, incorporating an internal pilot and embedded economic evaluation. 600 adult patients (≥18 years) with CT confirmed bronchiectasis will be recruited and randomised to either inhaled dual therapy (LABA+LAMA), triple therapy (LABA+LAMA+ICS) or matched placebo, in a 2:2:1 ratio (respectively). The primary outcome is the number of protocol defined exacerbations requiring treatment with antibiotics during the 12 month treatment period. Ethics and dissemination: Favourable ethical opinion was received from the North East—Newcastle and North Tyneside 2 Research Ethics Committee (reference: 21/NE/0020). Results will be disseminated in peer-reviewed publications, at national and international conferences, in the NIHR Health Technology Assessments journal and to participants and the public (using lay language). Trial registration number: ISRCTN15988757