Measuring the health impact of human rights violations related to Australian asylum policies and practices: A mixed methods study

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Johnston et al.BACKGROUND: Human rights violations have adverse consequences for health. However, to date, there remains little empirical evidence documenting this association, beyond the obvious physical and psychological effects of torture. The primary aim of this study was to investigate whether Australian asylum policies and practices, which arguably violate human rights, are associated with adverse health outcomes. METHODS: We designed a mixed methods study to address the study aim. A cross-sectional survey was conducted with 71 Iraqi Temporary Protection Visa (TPV) refugees and 60 Iraqi Permanent Humanitarian Visa (PHV) refugees, residing in Melbourne, Australia. Prior to a recent policy amendment, TPV refugees were only given temporary residency status and had restricted access to a range of government funded benefits and services that permanent refugees are automatically entitled to. The quantitative results were triangulated with semi-structured interviews with TPV refugees and service providers. The main outcome measures were self-reported physical and psychological health. Standardised self-report instruments, validated in an Arabic population, were used to measure health and wellbeing outcomes. RESULTS: Forty-six percent of TPV refugees compared with 25% of PHV refugees reported symptoms consistent with a diagnosis of clinical depression (p = 0.003). After controlling for the effects of age, gender and marital status, TPV status made a statistically significant contribution to psychological distress (B = 0.5, 95% CI 0.3 to 0.71, p </= 0.001) amongst Iraqi refugees. Qualitative data revealed that TPV refugees generally felt socially isolated and lacking in control over their life circumstances, because of their experiences in detention and on a temporary visa. This sense of powerlessness and, for some, an implicit awareness they were being denied basic human rights, culminated in a strong sense of injustice. CONCLUSION: Government asylum policies and practices violating human rights norms are associated with demonstrable psychological health impacts. This link between policy, rights violations and health outcomes offers a framework for addressing the impact of socio-political structures on health.This research was supported by an Australian National and Medical Research Council PhD Scholarship (N. 251782) and a Victorian Health Promotion Foundation research grant (No. 2002-0280)

Assessment of treatment burden and its impact on quality of life in dialysis-dependent and pre-dialysis chronic kidney disease patients

Background The management of chronic kidney disease (CKD) and its complications places a significant burden on patients, resulting in impairment of their health-related quality of life (HR-QOL). Little is known about treatment-related burden in pre-dialysis and hemodialysis (HD) CKD patients. Objective This study aimed to investigate the magnitude of treatment-related burden and its impact on HR-QOL among patients with CKD. Methods This was a prospective, cross-sectional study to assess treatment-related burden and HR-QOL among patients with CKD in Qatar. Treatment-related burden and HR-QOL were assessed quantitatively using the Treatment Burden Questionnaire (TBQ) and the Kidney Disease Quality of Life (KDQOL™) questionnaire, respectively. The total TBQ score ranges from 0 to 150, with a higher score indicating higher treatment burden, while the range of total possible scores for the KDQOL™ are from 0 to 3600 with higher transformed score indicating better QOL. Pre-dialysis and hemodialysis (HD) CKD patients who had regular follow-up appointments at Fahad Bin Jassim Kidney Center in Qatar were enrolled. Data were analyzed descriptively and inferentially using SPSS version-24. Results Two hundred-eighty CKD patients (HD = 223 and pre-dialysis = 57) were included in the analyses (response rate 60.9%). Approximately 35% of the participants reported moderate to high treatment-related burden (TBQ global score 51–150). HD patients experienced significantly higher treatment burden compared to pre-dialysis patients with a median (IQR) score of 45 (36) versus 25 (33), respectively (p < 0.001). Medication burden and lifestyle changes burden were the highest perceived treatment-related burden. Overall, the perceived median (IQR) HR-QOL measured using the KDQOL-36™ among the participants was 2280.6 (1096.2) compared to the maximum global score of 3600. Similarly, the HD patients demonstrated significantly lower HR-QOL compared to the pre-dialysis patients [median (IQR) score of 2140 (1100) vs. 2930 (995), respectively; p < 0.001). There was a strong negative correlation between TBQ score and KDQOL-36™ score [rs (251) = −0.616, p < 0.001], signifying that HR-QOL decreases as treatment burden increases. Conclusions This study suggests that a considerable proportion of CKD patients suffered from treatment-related burden and deterioration in HR-QOL at a varying degree of seriousness. HD patients experienced significantly higher burden of treatment and lower HR-QOL compared to pre-dialysis patients and that HR-QOL declines as treatment burden increases. Therefore, treatment-related burden should be considered in CKD management and factors that increase it should be considered when designing healthcare interventions directed to CKD patients.This research was funded by Qatar University under Student Grant number QUST-CPH-SPR/2017-19 [Approved amount QAR 20,000.00 (~US$ 5,480)]. The funders had no role in the design, planning, and implementation of the study. The content is the sole responsibility of the authors.Scopu

The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin

Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition

Therapeutic effect of combination vitamin D3 and siponimod on remyelination and modulate microglia activation in cuprizone mouse model of multiple sclerosis

Stimulation of remyelination is critical for the treatment of multiple sclerosis (MS) to alleviate symptoms and protect the myelin sheath from further damage. The current study aimed to investigate the possible therapeutic effects of combining vitamin D3 (Vit D3) and siponimod (Sipo) on enhancing remyelination and modulating microglia phenotypes in the cuprizone (CPZ) demyelination mouse model. The study was divided into two stages; demyelination (first 5 weeks) and remyelination (last 4 weeks). In the first 5 weeks, 85 mice were randomly divided into two groups, control (n = 20, standard rodent chow) and CPZ (n = 65, 0.3% CPZ mixed with chow for 6 weeks, followed by 3 weeks of standard rodent chow). At week 5, the CPZ group was re-divided into four groups (n = 14) for remyelination stages; untreated CPZ (0.2 ml of CMC orally), CPZ+Vit D3 (800 IU/kg Vit D3 orally), CPZ+Sipo (1.5 mg/kg Sipo orally), and CPZ+Vit D3 (800 IU/kg Vit D3) + Sipo (1.5 mg/kg Sipo orally). Various behavioral tasks were performed to evaluate motor performance. Luxol Fast Blue (LFB) staining, the expression level of myelin basic protein (MBP), and M1/M2 microglia phenotype genes were assessed in the corpus callosum (CC). The results showed that the combination of Vit D3 and Sipo improved behavioral deficits, significantly promoted remyelination, and modulated expression levels of microglia phenotype genes in the CC at early and late remyelination stages. These results demonstrate for the first time that a combination of Vit D3 and Sipo can improve the remyelination process in the cuprizone (CPZ) mouse model by attenuating the M1 microglia phenotype. This may help to improve the treatment of MS patients

Search based software engineering: Trends, techniques and applications

© ACM, 2012. This is the author's version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version is available from the link below.In the past five years there has been a dramatic increase in work on Search-Based Software Engineering (SBSE), an approach to Software Engineering (SE) in which Search-Based Optimization (SBO) algorithms are used to address problems in SE. SBSE has been applied to problems throughout the SE lifecycle, from requirements and project planning to maintenance and reengineering. The approach is attractive because it offers a suite of adaptive automated and semiautomated solutions in situations typified by large complex problem spaces with multiple competing and conflicting objectives. This article provides a review and classification of literature on SBSE. The work identifies research trends and relationships between the techniques applied and the applications to which they have been applied and highlights gaps in the literature and avenues for further research.EPSRC and E

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Cloning and Characterization of the Antiviral Activity of Feline Tetherin/BST-2

Human Tetherin/BST-2 has recently been identified as a cellular antiviral factor that blocks the release of various enveloped viruses. In this study, we cloned a cDNA fragment encoding a feline homolog of Tetherin/BST-2 and characterized the protein product. The degree of amino acid sequence identity between human Tetherin/BST-2 and the feline homolog was 44.4%. Similar to human Tetherin/BST-2, the expression of feline Tetherin/BST-2 mRNA was inducible by type I interferon (IFN). Exogenous expression of feline Tetherin/BST-2 efficiently inhibited the release of feline endogenous retrovirus RD-114. The extracellular domain of feline Tetherin/BST-2 has two putative N-linked glycosylation sites, N79 and N119. Complete loss of N-linked glycosylation by introduction of mutations into both sites resulted in almost complete abolition of its antiviral activity. In addition, feline Tetherin/BST-2 was insensitive to antagonism by HIV-1 Vpu, although the antiviral activity of human Tetherin/BST-2 was antagonized by HIV-1 Vpu. Our data suggest that feline Tetherin/BST-2 functions as a part of IFN-induced innate immunity against virus infection and that the induction of feline Tetherin/BST-2 in vivo may be effective as a novel antiviral strategy for viral infection

BST2/Tetherin Enhances Entry of Human Cytomegalovirus

Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV