743 research outputs found

    Exploring the interplay between Buddhism and career development : a study of highly skilled women workers in Sri Lanka

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    This article adopts a socio cultural lens to examine the role of Buddhism in highly skilled women workers’ careers in Sri Lanka. While Buddhism enabled women’s career development by giving them strength to cope with difficult situations in work, it also seemed to restrict their agency and constrain their career advancement. Based on our findings, we argue that being perceived as a good Buddhist woman worked as a powerful form of career capital for the respondents in our sample, who used their faith to combat gender disadvantage in their work settings

    Reduced LRRK2 in association with retromer dysfunction in post-mortem brain tissue from LRRK2 mutation carriers

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    Missense mutations in leucine-rich repeat kinase 2 (LRRK2) are pathogenic for familial Parkinson's disease. However, it is unknown whether levels of LRRK2 protein in the brain are altered in patients with LRRK2-associated Parkinson's disease. Because LRRK2 mutations are relatively rare, accounting for approximately 1% of all Parkinson's disease, we accessioned cases from five international brain banks to investigate levels of the LRRK2 protein, and other genetically associated Parkinson's disease proteins. Brain tissue was obtained from 17 LRRK2 mutation carriers (12 with the G2019S mutation and five with the I2020T mutation) and assayed by immunoblot. Compared to matched controls and idiopathic Parkinson's disease cases, we found levels of LRRK2 protein were reduced in the LRRK2 mutation cases. We also measured a decrease in two other proteins genetically implicated in Parkinson's disease, the core retromer component, vacuolar protein sorting associated protein 35 (VPS35), and the lysosomal hydrolase, glucocerebrosidase (GBA). Moreover, the classical retromer cargo protein, cation-independent mannose-6-phosphate receptor (MPR300, encoded by IGF2R), was also reduced in the LRRK2 mutation cohort and protein levels of the receptor were correlated to levels of LRRK2. These results provide new data on LRRK2 protein expression in brain tissue from LRRK2 mutation carriers and support a relationship between LRRK2 and retromer dysfunction in LRRK2-associated Parkinson's disease brain

    Regulation of Dense-Core Granule Replenishment by Autocrine BMP Signalling in Drosophila Secondary Cells

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    Regulated secretion by glands and neurons involves release of signalling molecules and enzymes selectively concentrated in dense-core granules (DCGs). Although we understand how many secretagogues stimulate DCG release, how DCG biogenesis is then accelerated to replenish the DCG pool remains poorly characterised. Here we demonstrate that each prostate-like secondary cell (SC) in the paired adult Drosophila melanogaster male accessory glands contains approximately ten large DCGs, which are loaded with the Bone Morphogenetic Protein (BMP) ligand Decapentaplegic (Dpp). These DCGs can be marked in living tissue by a glycophosphatidylinositol (GPI) lipid-anchored form of GFP. In virgin males, BMP signalling is sporadically activated by constitutive DCG secretion. Upon mating, approximately four DCGs are typically released immediately, increasing BMP signalling, primarily via an autocrine mechanism. Using inducible knockdown specifically in adult SCs, we show that secretion requires the Soluble NSF Attachment Protein, SNAP24. Furthermore, mating-dependent BMP signalling not only promotes cell growth, but is also necessary to accelerate biogenesis of new DCGs, restoring DCG number within 24 h. Our analysis therefore reveals an autocrine BMP-mediated feedback mechanism for matching DCG release to replenishment as secretion rates fluctuate, and might explain why in other disease-relevant systems, like pancreatic β-cells, BMP signalling is also implicated in the control of secretion

    Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

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    Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

    Agenda setting and framing of gender-based violence in Nepal: how it became a health issue.

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    : Gender-based violence (GBV) has been addressed as a policy issue in Nepal since the mid 1990s, yet it was only in 2010 that Nepal developed a legal and policy framework to combat GBV. This article draws on the concepts of agenda setting and framing to analyse the historical processes by which GBV became legitimized as a health policy issue in Nepal and explored factors that facilitated and constrained the opening and closing of windows of opportunity. The results presented are based on a document analysis of the policy and regulatory framework around GBV in Nepal. A content analysis was undertaken. Agenda setting for GBV policies in Nepal evolved over many years and was characterized by the interplay of political context factors, actors and multiple frames. The way the issue was depicted at different times and by different actors played a key role in the delay in bringing health onto the policy agenda. Women's groups and less powerful Ministries developed gender equity and development frames, but it was only when the more powerful human rights frame was promoted by the country's new Constitution and the Office of the Prime Minister that legislation on GBV was achieved and a domestic violence bill was adopted, followed by a National Plan of Action. This eventually enabled the health frame to converge around the development of implementation policies that incorporated health service responses. Our explicit incorporation of framing within the Kindgon model has illustrated how important it is for understanding the emergence of policy issues, and the subsequent debates about their resolution. The framing of a policy problem by certain policy actors, affects the development of each of the three policy streams, and may facilitate or constrain their convergence. The concept of framing therefore lends an additional depth of understanding to the Kindgon agenda setting model.<br/

    Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages.

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    Tuned and distinct responses of macrophages and dendritic cells to Toll-like receptor 4 (TLR4) activation induced by lipopolysaccharide (LPS) underpin the balance between innate and adaptive immunity. However, the molecule(s) that confer these cell-type-specific LPS-induced effects remain poorly understood. Here we report that the integrin α(M) (CD11b) positively regulates LPS-induced signalling pathways selectively in myeloid dendritic cells but not in macrophages. In dendritic cells, which express lower levels of CD14 and TLR4 than macrophages, CD11b promotes MyD88-dependent and MyD88-independent signalling pathways. In particular, in dendritic cells CD11b facilitates LPS-induced TLR4 endocytosis and is required for the subsequent signalling in the endosomes. Consistent with this, CD11b deficiency dampens dendritic cell-mediated TLR4-triggered responses in vivo leading to impaired T-cell activation. Thus, by modulating the trafficking and signalling functions of TLR4 in a cell-type-specific manner CD11b fine tunes the balance between adaptive and innate immune responses initiated by LPS

    Monitoring of water quality in a shrimp farm using a FANET

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    This paper develops an architecture for flying ad-hoc networks (FANETs) to enable monitoring of water quality in a shrimp farm. Firstly, the key monitoring parameters for the characterization of water quality are highlighted and their desired operational ranges are summarized. These parameters directly influence shrimp survival and healthy growth. Based on the considered sensing modality, a reference architecture for implementing a cost-effective FANET based mobile sensing platform is developed. The controlled mobility of the platform is harnessed to increase the spatial monitoring resolution without the need for extensive infrastructure deployment. The proposed solution will be offered to shrimp farmers in the Mexican state of Colima once the laboratory trials are concluded

    Work related complaints of neck, shoulder and arm among computer office workers: a cross-sectional evaluation of prevalence and risk factors in a developing country

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    <p>Abstract</p> <p>Background</p> <p>Complaints of arms, neck and shoulders (CANS) is common among computer office workers. We evaluated an aetiological model with physical/psychosocial risk-factors.</p> <p>Methods</p> <p>We invited 2,500 computer office workers for the study. Data on prevalence and risk-factors of CANS were collected by validated Maastricht-Upper-extremity-Questionnaire. Workstations were evaluated by Occupational Safety and Health Administration (OSHA) Visual-Display-Terminal workstation-checklist. Participants' knowledge and awareness was evaluated by a set of expert-validated questions. A binary logistic regression analysis investigated relationships/correlations between risk-factors and symptoms.</p> <p>Results</p> <p>Sample size was 2,210. Mean age 30.8 ± 8.1 years, 50.8% were males. The 1-year prevalence of CANS was 56.9%, commonest region of complaint was forearm/hand (42.6%), followed by neck (36.7%) and shoulder/arm (32.0%). In those with CANS, 22.7% had taken treatment from a health care professional, only in 1.1% seeking medical advice an occupation-related injury had been suspected/diagnosed. In addition 9.3% reported CANS-related absenteeism from work, while 15.4% reported CANS causing disruption of normal activities. A majority of evaluated workstations in all participants (88.4%,) and in those with CANS (91.9%) had OSHA non-compliant workstations. In the binary logistic regression analyses female gender, daily computer usage, incorrect body posture, bad work-habits, work overload, poor social support and poor ergonomic knowledge were associated with CANS and its' severity In a multiple logistic regression analysis controlling for age, gender and duration of occupation, incorrect body posture, bad work-habits and daily computer usage were significant independent predictors of CANS</p> <p>Conclusions</p> <p>The prevalence of work-related CANS among computer office workers in Sri Lanka, a developing, South Asian country is high and comparable to prevalence in developed countries. Work-related physical factors, psychosocial factors and lack of awareness were all important associations of CANS and effective preventive strategies need to address all three areas.</p

    Limited Value of Staging Squamous Cell Carcinoma of the Anal Margin and Canal Using the Sentinel Lymph Node Procedure: A Prospective Study with Long-Term Follow-Up

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    Background. Selection of patients with anal cancer for groin irradiation is based on tumor size, palpation, ultrasound, and fine needle cytology. Current staging of anal cancer may result in undertreatment in small tumors and overtreatment of large tumors. This study reports the feasibility of the sentinel lymph node biopsy (SLNB) in patients with anal cancer and whether this improves the selection for inguinal radiotherapy. Methods. A total of 50 patients with squamous anal cancer were evaluated prospectively. Patients without a SLNB (n = 29) received irradiation of the inguinal lymph nodes based on lymph node status, tumor size, and location of the primary tumor. Inguinal irradiation treatment in patients with a SLNB was based on the presence of metastases in the SLN. Results. SLNs were found in all 21 patients who underwent a SLNB. There were 5 patients (24%) who had complications after SLNB and 7 patients (33%) who had a positive SLN and received inguinal irradiation. However, 2 patients with a tumor-free SLN and no inguinal irradiation developed lymph node metastases after 12 and 24 months, respectively. Conclusions. We conclude that SLNB in anal cancer is technically feasible. SLNB can identify those patients who would benefit from refrain of inguinal irradiation treatment and thereby reducing the incidence of unnecessary inguinal radiotherapy. However, because of the occurrence of inguinal lymph node metastases after a tumor-negative SLNB, introduction of this procedure as standard of care in all patients with anal carcinoma should be done with caution to avoid undertreatment of patient who otherwise would benefit from inguinal radiotherapy
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