1,521 research outputs found

    Compulsory te reo Māori in Aotearoa New Zealand schools: A future-focused analysis

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    While support for compulsory te reo Māori in schools in Aoteaora New Zealand is growing, there is a risk that any future policy could fail, or be only poorly implemented, unless we understand more deeply the factors which shape effective language policy implementation in schools. In this paper we employ a ‘future policy analysis' to explore what it would take to effectively implement a compulsory te reo Māori policy in schools in the future. We report on interviews with twelve purposively selected stakeholders (including Māori, Pākehā, Chinese and Samoan teachers, principals and one Member of Parliament) to elicit from their experiences and reflections the key elements required to implement te reo Māori well in schools. Participants identified that prioritising and valuing te reo Maori was foundational and essential for any potential policy shift at both national and school level. In addition, participants elaborated on how teacher expertise, resourcing, time and leadership support through senior management was integral to successful adoption and implementation. The paper concludes by recommending urgent attention to a range of future-focused strategies that beginning right now could bring about transformational change in our schools and give te reo Māori the mana it deserves

    Prognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosis

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    BACKGROUND: Detection of the mycobacterial cell wall antigen lipoarabinomannan (LAM) in urine can be used to diagnose HIV-associated tuberculosis (TB) using a qualitative (positive/negative) read-out. However, it is not known whether the quantity of LAM present in urine provides additional prognostic information. Methods/FINDINGS: Consecutively recruited adult outpatients initiating antiretroviral therapy (ART) in South Africa were investigated for TB regardless of clinical symptoms using sputum smear microscopy and liquid culture (reference standard). Urine samples were tested using the Clearview TB-ELISA for LAM and the Xpert MTB/RIF assay. The ELISA optical densities (OD) were used as a quantitative assessment of urine LAM. Among 514 patients with complete sputum and urine LAM OD results, culture-confirmed TB was diagnosed in 84 patients. Twenty-three (27.3%) were LAM-positive with a median LAM OD of 0.68 (IQR 0.16-2.43; range, 0.10-3.29) and 61 (72.6%) were LAM negative (LAM OD <0.1 above background). Higher LAM ODs were associated with a range of prognostic indices, including lower CD4 cell counts, lower haemoglobin levels, higher blood neutrophil counts and higher mycobacterial load as assessed using both sputum and urine samples. The median LAM OD among patients who died was more than 6.8-fold higher than that of patients who remained alive at 3 months (P<0.001). The small number of deaths, however, precluded adequate assessment of mortality risk stratified according to urine LAM OD. CONCLUSIONS: In patients with HIV-associated TB, concentrations of LAM in urine were strongly associated with a range of poor prognostic characteristics known to be associated with mortality risk. Urine LAM assays with a semi-quantitative (negative vs. low-positive vs. high-positive) read-out may have improved clinical utility over assays with a simple binary result

    Plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) and early mortality risk among patients enrolling for antiretroviral treatment in South Africa

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    BACKGROUND: Serum concentrations of soluble urokinase-type plasminogen activator receptor (suPAR) have a strong independent association with HIV-1-related mortality. The practical utility of plasma suPAR in assessing short-term all-cause mortality risk was evaluated in patients with advanced immunodeficiency enrolling in an antiretroviral treatment (ART) programme in South Africa. METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma concentrations of suPAR in patients at the time of enrollment to the ART programme. The association between plasma suPAR concentrations, baseline patient characteristics and cohort outcomes after 4 months of ART were determined. RESULTS: Patients (n = 293, 70% female) had a median age of 33 years and were followed up for a median of 5 months from enrollment. The median CD4 cell count was 47 cells/mul (IQR = 22-72) and 38% of patients had WHO stage 4 disease. 218 (74%) patients remained alive after 4 months of ART; 39 (13%) died and 36 (12%) were lost to the programme for other reasons. Patients who died had significantly higher plasma suPAR concentrations compared to those who either survived (P < 0.01) or left the programme for other reasons (P < 0.043). In multivariate analysis, higher log10 suPAR concentrations were significantly associated with lower CD4 cell counts, WHO clinical stage 4 disease and male sex. In multivariate analysis to identify factors associated with death, log10 suPAR concentration was the most strongly associated variable (P < 0.001). However, examination of sensitivity and specificity characteristics using receiver operating characteristic (ROC) analysis revealed that results from this assay did not have a discriminatory cut-point to provide clinically useful information. CONCLUSION: Plasma suPAR concentration was the strongest independent predictor of short-term mortality risk among patients with advanced immunodeficiency enrolling in this ART programme. However, lack of a discriminatory threshold did not permit this marker to be used to triage patients according to short-term mortality risk

    Blood neutrophil counts in HIV-infected patients with pulmonary tuberculosis: association with sputum mycobacterial load.

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    BACKGROUND: Increasing evidence suggests that neutrophils play a role in the host response to Mycobacterium tuberculosis. We determined whether neutrophil counts in peripheral blood are associated with tuberculosis (TB) and with mycobacterial load in sputum in HIV-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Adults enrolling in an antiretroviral treatment (ART) clinic in a Cape Town township were screened for TB regardless of symptoms. Paired sputum samples were examined using liquid culture, fluorescence microscopy, and the Xpert MTB/RIF assay. Absolute neutrophil counts (ANC) were measured in blood samples. Of 602 HIV-infected patients screened, 523 produced one or more sputum samples and had complete results available for analysis. Among these 523 patients, the median CD4 count was 169×10(9)/L (IQR, 96-232) and median ANC was 2.6×10(9)/L (IQR, 1.9-3.6). Culture-positive pulmonary tuberculosis was diagnosed in 89 patients. Patients with TB had a median ANC of 3.4×10(9)/L (IQR, 2.4-5.1) compared to 2.5×10(9)/L (IQR, 1.8-3.4) among those who were culture negative (p7.5×10(9)/L; p = 0.0005). Patients were then classified into four mutually exclusive groups with increasing sputum mycobacterial load as defined by the results of culture, Xpert MTB/RIF and sputum smear microscopy. Multivariable analyses demonstrated that increasing sputum mycobacterial load was positively associated with blood ANC ≥2.6×10(9)/L and with neutrophilia. CONCLUSIONS/SIGNIFICANCE: Increased blood neutrophil counts were independently associated with pulmonary TB and sputum mycobacterial burden in this HIV-infected patient group. This observation supports the growing body of literature regarding the potential role for neutrophils in the host response to TB

    Role of environment and sex differences in the development of autoimmune diseases: A roundtable meeting project

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    Autoimmune diseases (ADs) impose substantial health and financial burdens in the United States and in many parts of the world. Women are disproportionately affected by many of these disorders, which often contribute to lifelong disabilities. While the number of patients with some ADs appears to be rising, the complexities of conducting epidemiological studies prevent a thorough understanding of the prevalence and incidence of these various conditions. Research on environmental influences of these illnesses is limited, although they are generally hypothesized to result from the interaction of environmental agents in genetically susceptible individuals. Further, there is little known regarding the role of sex and gender in the environmentally influenced mechanisms leading to the development of AD. To address these issues, particularly the roles of environment and sex and gender in ADs and the factors that contribute to the rise in ADs, the Society for Women\u27s Health Research convened an interdisciplinary roundtable of experts from academia, medicine, and government agencies to share their expertise, address knowledge gaps in research, and propose future research recommendations

    HIV-associated tuberculosis: relationship between disease severity and the sensitivity of new sputum-based and urine-based diagnostic assays

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    BACKGROUND: Reducing mortality from HIV-associated tuberculosis (TB) requires diagnostic tools that are rapid and have high sensitivity among patients with poor prognosis. We determined the relationship between disease severity and the sensitivity of new sputum-based and urine-based diagnostic assays. METHODS: Consecutive ambulatory patients enrolling for antiretroviral treatment in South Africa were screened for TB regardless of symptoms using diagnostic assays prospectively applied to sputum (fluorescence smear microscopy, Xpert MTB/RIF and liquid culture (reference standard)) and retrospectively applied to stored urine samples (Determine TB-LAM and Xpert MTB/RIF). Assay sensitivities were calculated stratified according to pre-defined indices of disease severity: CD4 count, symptom intensity, serum C-reactive protein (CRP), hemoglobin concentration and vital status at 90 days. RESULTS: Sputum culture-positive TB was diagnosed in 15% (89/602) of patients screened and data from 86 patients were analyzed (median CD4 count, 131 cells/muL) including 6 (7%) who died. The sensitivity of sputum microscopy was 26.7% overall and varied relatively little with disease severity. In marked contrast, the sensitivities of urine-based and sputum-based diagnosis using Determine TB-LAM and Xpert MTB/RIF assays were substantially greater in sub-groups with poorer prognosis. Rapid diagnosis from sputum and/or urine samples was possible in >80% of patients in sub-groups with poor prognosis as defined by either CD4 counts 200 mg/L or hemoglobin <8.0 g/dl. Retrospective testing of urine samples with Determine TB-LAM correctly identified all those with TB who died. CONCLUSIONS: The sensitivities of Xpert MTB/RIF and Determine TB-LAM for HIV-associated TB were highest among HIV-infected patients with the most advanced disease and poorest prognostic characteristics. These data provide strong justification for large-scale intervention studies that assess the impact on survival of screening using these new sputum-based and urine-based diagnostic approaches

    Cyclooxygenase-2 expression in oligodendrocytes increases sensitivity to excitotoxic death

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    <p>Abstract</p> <p>Background</p> <p>We previously found that cyclooxygenase 2 (COX-2) was expressed in dying oligodendrocytes at the onset of demyelination in the Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model of multiple sclerosis (MS) (Carlson et al. J.Neuroimmunology 2006, 149:40). This suggests that COX-2 may contribute to death of oligodendrocytes.</p> <p>Objective</p> <p>The goal of this study was to examine whether COX-2 contributes to excitotoxic death of oligodendrocytes and potentially contributes to demyelination.</p> <p>Methods</p> <p>The potential link between COX-2 and oligodendrocyte death was approached using histopathology of MS lesions to examine whether COX-2 was expressed in dying oligodendrocytes. COX-2 inhibitors were examined for their ability to limit demyelination in the TMEV-IDD model of MS and to limit excitotoxic death of oligodendrocytes <it>in vitro</it>. Genetic manipulation of COX-2 expression was used to determine whether COX-2 contributes to excitotoxic death of oligodendrocytes. A transgenic mouse line was generated that overexpressed COX-2 in oligodendrocytes. Oligodendrocyte cultures derived from these transgenic mice were used to examine whether increased expression of COX-2 enhanced the vulnerability of oligodendrocytes to excitotoxic death. Oligodendrocytes derived from COX-2 knockout mice were evaluated to determine if decreased COX-2 expression promotes a greater resistance to excitotoxic death.</p> <p>Results</p> <p>COX-2 was expressed in dying oligodendrocytes in MS lesions. COX-2 inhibitors limited demyelination in the TMEV-IDD model of MS and protected oligodendrocytes against excitotoxic death <it>in vitro</it>. COX-2 expression was increased in wild-type oligodendrocytes following treatment with Kainic acid (KA). Overexpression of COX-2 in oligodendrocytes increased the sensitivity of oligodendrocytes to KA-induced excitotoxic death eight-fold compared to wild-type. Conversely, oligodendrocytes prepared from COX-2 knockout mice showed a significant decrease in sensitivity to KA induced death.</p> <p>Conclusions</p> <p>COX-2 expression was associated with dying oligodendrocytes in MS lesions and appeared to increase excitotoxic death of oligodendrocytes in culture. An understanding of how COX-2 expression influences oligodendrocyte death leading to demyelination may have important ramifications for future treatments for MS.</p

    Self-folding shape memory laminates for automated fabrication

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    Nature regularly uses self-folding as an efficient approach to automated fabrication. In engineered systems, however, the use of self-folding has been primarily restricted to the assembly of small structures using exotic materials and/or complex infrastructures. In this paper we present three approaches to the self-folding of structures using low-cost, rapid-prototyped shape memory laminates. These structures require minimal deployment infrastructure, and are activated by light, heat, or electricity. We compare the fabrication of a fundamental structure (a cube) using each approach, and test ways to control fold angles in each case. Finally, for each self-folding approach we present a unique structure that the approach is particularly suited to fold, and discuss the advantages and disadvantages of each approach.National Science Foundation (U.S.) (Award CCF-1138967)National Science Foundation (U.S.) (Award EFRI-1240383
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