17 research outputs found

    Comparative performance of the new Aptima HIV-1 Quant Dx assay with three commercial PCR-based HIV-1 RNA quantitation assays

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    Background: Quantitative measurement of HIV-1 RNA levels in plasma ('viral load') plays a central role in clinical management. The choice of assay platform can influence results and treatment decisions. Objective: To compare the analytical performance of the new TMA-based Hologic Aptima® HIV-1 Quant Dx assay with that of three PCR-based assays: Abbott RealTime HIV-1, Qiagen Artus® HI Virus-1 QS-RGQ, and Roche CAP/CTM HIV-1 Test v2. Study design: Assay performance was evaluated using Acrometrix HIV-1 RNA Standard panels; the 3rd WHO HIV-1 RNA International Standard (12-500. copies/ml; 6 dilutions; 9 replicates); and plasma samples from 191 HIV-positive patients. Results: Aptima showed high (>0.99) precision, accuracy and concordance with the Acrometrix Standards across a wide dynamic range (2.0-6.7 log10copies/ml). Variance caused up to 2.1 (Aptima), 1.7 (RealTime), 7.5 (Artus), and 1.9 (CAP/CTM) fold changes in the International Standard quantifications at 50-500copies/ml. HIV-1 RNA detection rates in plasma samples were 141/191 (74%), 119/191 (62%), 108/191 (57%), and 145/191 (76%) for Aptima, RealTime, Artus and CAP/CTM, respectively. For categorising samples either side of 50 copies/ml, Aptima had excellent agreement with RealTime (kappa 0.92; 95% CI 0.87-0.98); lowest agreement was with Artus (kappa 0.79; 95%CI 0.70-0.88). Aptima quantifications were mean 0.12 and 0.06 log10copies/ml higher compared with RealTime and CAP/CTM, respectively, and 0.05 log10copies/ml lower compared with Artus. Limits of agreement were narrowest when comparing Aptima to RealTime. Conclusions: The new Aptima HIV assay is sensitive, precise, and accurate. HIV assays exhibit discordance at low HIV-1 RNA copy numbers

    HIV gp120 in Lungs of ART-treated Individuals Impairs Alveolar Macrophage Responses To Pneumococci

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    Rationale People living with HIV (PLWH) are at significantly increased risk of invasive pneumococcal disease, despite long-term antiretroviral therapy (ART). The mechanism explaining this observation remains undefined. Objectives We hypothesized apoptosis-associated microbicidal mechanisms, required to clear intracellular pneumococci that survive initial phagolysosomal killing, are perturbed. Methods Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from healthy donors or HIV-1-seropositive donors on long-term ART with undetectable plasma viral load. Monocyte-derived macrophages (MDM) were obtained from healthy donors and infected with HIV-1BaL or treated with gp120. Macrophages were challenged with opsonized serotype 2 Streptococcus pneumoniae and assessed for apoptosis, bactericidal activity, protein expression and mitochondrial reactive oxygen species (mROS). AM phenotyping, ultra-sensitive HIV-1 RNA quantification and gp120 measurement were also performed in BAL. Measurements and Main Results HIV-1BaL infection impaired apoptosis, induction of mROS and pneumococcal killing by MDM. Apoptosis-associated pneumococcal killing was also reduced in AM from ART treated HIV-1-seropositive donors. BAL fluid from these individuals demonstrated persistent lung CD8+ T-cell lymphocytosis, and gp120 or HIV-1 RNA was also detected. Despite this, transcriptional activity in AM freshly isolated from PLWH was broadly similar to healthy volunteers. Instead, gp120 phenocopied the defect in pneumococcal killing in healthy MDM through post-translational modification of Mcl-1, preventing apoptosis induction, caspase activation and increased mROS generation. Moreover gp120 also inhibited mROS dependent pneumococcal killing in MDM. Conclusions. Despite ART, HIV-1, via gp120, drives persisting innate immune defects in AM microbicidal mechanisms, enhancing susceptibility to pneumococcal disease

    Watershed-BIM Integration for Urban Flood Resilience: A Framework for Simulation, Assessment, and Planning

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    Urban flooding represents a growing global concern, especially in areas with rapid urbanization, unregulated urban sprawl and climate change conditions. Conventional flood modeling approaches do not effectively capture the complex dynamics between natural watershed behavior and urban infrastructure; they typically simulate these domains in isolation. This study introduces the Watershed-BIM methodology, a three-dimensional simulation framework that integrates Building and City Information Modeling (BIM/CIM), Geographic Information Systems (GIS), Flood Risk Assessment (FRA), and Flood Risk Management (FRM) into a single framework. Autodesk InfraWorks 2024, Civil 3D 2024, and RiverFlow2D v8.14 software are incorporated in the development. The methodology enhances interoperability and prediction accuracy by bridging hydrological processes with detailed urban-scale data. The framework was tested on a real-world flash flood event in Mandra, Greece, an area frequently exposed to extreme rainfall and runoff events. A specific comparison with observed flood characteristics indicates improved accuracy in comparison to other hydrological analyses (e.g., by HEC-RAS simulation). Beyond flood depth, the model offers additional insights into flow direction, duration, and localized water accumulation around buildings and infrastructure. In this context, integrated tools such as Watershed-BIM stand out as essential instruments for translating complex flood dynamics into actionable, city-scale resilience planning

    Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis

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    Background Hepatitis D virus (also known as hepatitis delta virus) can establish a persistent infection in people with chronic hepatitis B, leading to accelerated progression of liver disease. In sub-Saharan Africa, where HBsAg prevalence is higher than 8%, hepatitis D virus might represent an important additive cause of chronic liver disease. We aimed to establish the prevalence of hepatitis D virus among HBsAg-positive populations in sub-Saharan Africa. Methods We systematically reviewed studies of hepatitis D virus prevalence among HBsAg-positive populations in sub-Saharan Africa. We searched PubMed, Embase, and Scopus for papers published between Jan 1, 1995, and Aug 30, 2016, in which patient selection criteria and geographical setting were described. Search strings included sub-Saharan Africa, the countries therein, and permutations of hepatitis D virus. Cohort data were also added from HIV-positive populations in Malawi and Ghana. Populations undergoing assessment in liver disease clinics and those sampled from other populations (defined as general populations) were analysed. We did a meta-analysis with a DerSimonian-Laird random-effects model to calculate a pooled estimate of hepatitis D virus seroprevalence. Findings Of 374 studies identified by our search, 30 were included in our study, only eight of which included detection of hepatitis D virus RNA among anti-hepatitis D virus seropositive participants. In west Africa, the pooled seroprevalence of hepatitis D virus was 7·33% (95% CI 3·55–12·20) in general populations and 9·57% (2·31–20·43) in liver-disease populations. In central Africa, seroprevalence was 25·64% (12·09–42·00) in general populations and 37·77% (12·13–67·54) in liver-disease populations. In east and southern Africa, seroprevalence was 0·05% (0·00–1·78) in general populations. The odds ratio for anti-hepatitis D virus detection among HBsAg-positive patients with liver fibrosis or hepatocellular carcinoma was 5·24 (95% CI 2·74–10·01; p<0·0001) relative to asymptomatic controls. Interpretation Findings suggest localised clusters of hepatitis D virus endemicity across sub-Saharan Africa. Epidemiological data are needed from southern and east Africa, and from patients with established liver disease. Further studies should aim to define the reliability of hepatitis D virus testing methods, identify risk factors for transmission, and characterise the natural history of the infection in the region. Funding Wellcome Trust, Royal Society

    The Commons

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    "This book explores the potential creation of a broader collaborative economy through commons-based peer production (P2P) and the emergent role of information and communication technologies (ICTs). The book seeks to critically engage in the political discussion of commons-based peer production, which can be classified into three basic arguments: the liberal, the reformist and the anti-capitalist. This book categorises the liberal argument as being in favour of the coexistence of the commons with the market and the state. Reformists, on the other hand, advocate for the gradual adjustment of the state and of capitalism to the commons, while anti-capitalists situate the commons against capitalism and the state. By discussing these three viewpoints, the book contributes to contemporary debates concerning the future of commons-based peer production. Further, the author argues that for the commons to become a fully operational mode of peer production, it needs to reach critical mass arguing that the liberal argument underestimates the reformist insight that technology has the potential to decentralise production, thereby forcing capitalism to transition to post-capitalism. Surveying the three main strands of commons-based peer production, this book makes the case for a post-capitalist commons-orientated transition that moves beyond neoliberalism.

    BIM-Based Machine Learning Application for Parametric Assessment of Building Energy Performance

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    The energy performance of buildings has become a main concern globally in response to increased energy demand, the environmental impacts of energy production, and the reality of energy poverty. To improve energy efficiency, proper building design should be secured at the early design phase. Digital tools are currently available for performing energy assessment analyses and can efficiently handle complex and technically demanding buildings. However, alternative designs should be checked individually, and this makes the process time-consuming and prone to errors. Machine learning techniques can provide valuable assistance in developing decision support tools. In this paper, typical residential buildings are considered along with eleven factors that highly affect energy performance. A dataset of 337 instances of such parameters is developed. For each dataset, the building energy performance is estimated based on BIM analysis. Next, statistical and machine learning techniques are implemented to provide artificial models of energy performance. They include statistical regression modeling (SRM), decision trees (DTs), random forests (RFs), and artificial neural networks (ANNs). The analysis reveals the contribution of each factor and highlights the ANN as the best performing model. An easy-to-use interface tool has been developed for the instantaneous calculation of the energy performance based on the independent parameter values

    Seismic damage assessment of highway bridges by means of soft computing techniques

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    Seismic risk assessment in bridge networks is of great interest in reducing earthquake adverse effects in structures and the society. Among existing methods for risk and loss assessment, Hazus methodology is widely accepted and used. The method includes several steps and calculations, being thus rather complex and time-consuming, especially if several bridges with diverse characteristics are to be examined. The present study investigates the potential of using soft computing techniques for determining the seismic hazard and expected losses as an alternative to the Hazus methodology. In particular, a number of representative datasets have been developed on the basis of Hazus and a number of methods have been formulated and tested regarding their capacity to effectively simulate the process. The methods that are examined range from regression curve-fitting to artificial neural networks of different size and characteristics. Alternative statistical tests have been used to evaluate the developed model capabilities. Evaluation results indicate that appropriately designed ANN methods can attain high accuracy and stable results among different datasets (training, testing, and validation). The analysis indicates the potential of using similar techniques to simulate seismic risk assessment based on actual data from earthquake events that have taken place in the past.</p

    Protection or paternalism: A critical evaluation of Australian legislation relating to sexual acts involving persons with intellectual disability

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    As a result of the development and recognition of human rights and of the principle of normalisation, in recent decades sweeping changes have occurred in the living conditions of many people with intellectual disability. The United Nations Declaration on the Rights of Mentally Retarded Persons (1971)contains statements to the effect that, as far as possible, the lives of disabled persons should resemble those of their non-disabled peers, and this presumably extends to sexual expression. However, the words “as far as possible” imply that in some circumstances, limitations on a right may be justifiable. One such circumstance is where a competing right exists, for example, the right to sexual expression has to be balanced against a right to protection. Under some conditions, the provision of protective measures may fall to the criminal justice system, which may be used to afford protection to persons with intellectual disability. Australian jurisdictions have used three different approaches in current legislation: to set a minimum standard of sexual knowledge that must be present before the person is deemed capable of consent to sexual activities; to prohibit sexual relations with persons holding power or authority over the person; and to proscribe all sexual exploitation. This thesis contains proposals for reforms to each category of legislative provisions. First, it is suggested that the standard of knowledge required to support consent should more closely resemble the knowledge required for informed consent to medical procedures. Second, restrictions on sexual activity with persons with intellectual disability based on employment status should be relaxed where the role of the staff member does not confer power to coerce people with intellectual disability. Third, with regard to the prosecution of offences against incapable persons with mental impairment, it is proposed that the charge should be sex without consent. On the other hand, it is argued that prosecution under criminal law is inappropriate where a vulnerable but capable person is deemed to have been exploited. The thesis contains a number of further recommendations for the reform of anomalies which exist between the general law of sexual offences and those committed specifically against persons with mental impairment. It is suggested that marriage be abolished as a defence to sexual acts with an incapable person and that offences against persons with mental impairment carry equivalent penalties to general sexual offences. On the basis of literature reviewed in this thesis, two additional proposals have been made. First, that education in the sexual rights of persons with intellectual impairment should be given to carers so that they do not unduly inhibit the development of sexual relationships by that person. The second proposal is that reform should be accompanied by the provision of repeated, appropriate, detailed and specific sex education of all persons with intellectual impairment and that this education should be based on needs identified in the aforementioned research. The tentative outcome of proposals contained in this thesis is that persons capable of consent would enjoy enhanced freedom to exercise their right to sexual expression, and those incapable of consent would be afforded more certain protection
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