Estimating HIV incidence from multiple sources of data

This thesis develops novel statistical methodology for estimating the incidence and the prevalence of Human Immunodeficiency Virus (HIV) using routinely collected surveillance data. The robust estimation of HIV incidence and prevalence is crucial to correctly evaluate the effectiveness of targeted public health interventions and to accurately predict the HIV- related burden imposed on healthcare services. Bayesian CD4-based multi-state back-calculation methods are a key tool for monitoring the HIV epidemic, providing estimates of HIV incidence and diagnosis rates by disentangling their competing contribution to the observed surveillance data. Improving the effectiveness of public health interventions, requires targeting specific age-groups at high risk of infection; however, existing methods are limited in that they do not allow for such subgroups to be identified. Therefore the methodological focus of this thesis lies in developing a rigorous statistical framework for age-dependent back-calculation in order to achieve the joint estimation of age-and-time dependent HIV incidence and diagnosis rates. Key challenges we specifically addressed include ensuring the computational feasibility of proposed methods, an issue that has previously hindered extensions of back-calculation, and achieving the joint modelling of time-and-age specific incidence. The suitability of non-parametric bivariate smoothing methods for modelling the age-and-time specific incidence has been investigated in detail within comprehensive simulation studies. Furthermore, in order to enhance the generalisability of the proposed model, we developed back-calculation that can admit surveillance data less rich in detail; these handle surveillance data collected from an intermediate point of the epidemic, or only available on a coarse scale, and concern both age-dependent and age-independent back-calculation. The applicability of the proposed methods is illustrated using routinely collected surveillance data from England and Wales, for the HIV epidemic among men who have sex with men (MSM).MRC BS

Breast Cancer Preoperative Staging: Does Contrast-Enhanced Magnetic Resonance Mammography Modify Surgery?

Women with newly diagnosed breast cancer may have lesions undetected by conventional imaging. Recently contrast-enhanced magnetic resonance mammography (CE-MRM) showed higher sensitivity in breast lesions detection. The present analysis was aimed at evaluating the benefit of preoperative CE-MRM in the surgical planning. From 2005 to 2009, 525 consecutive women (25–75 years) with breast cancer, newly diagnosed by mammography, ultrasound, and needle-biopsy, underwent CE-MRM. The median invasive tumour size was 19 mm. In 144 patients, CE-MRM identified additional lesions. After secondlook, 119 patients underwent additional biopsy. CE-MRM altered surgery in 118 patients: 57 received double lumpectomy or wider excision (41 beneficial), 41 required mastectomy (40 beneficial), and 20 underwent contra lateral surgery (18 beneficial). The overall false-positive rate was 27.1% (39/144). CE-MRM contributed significantly to the management of breast cancer, suggesting more extensive disease in 144/525 (27.4%) patients and changing the surgical plan in 118/525 (22.5%) patients (99/525, 18.8% beneficial)

Thermo-Structural Analysis Of Steam Tracing Arrangements Applied To Pump Barrels

LecturePumps steam tracing is widely used in Oil&Gas industry for critical services in which the process fluid requires a minimum temperature to avoid its crystallization during stand-by. This paper describes the process of utilizing Computational Fluid Dynamics to perform a thermo-structural analysis of a barrel pump to determine the optimal steam tracing arrangement to maintain a minimum internal temperature. The most critical part of the analysis was to define the Heat Transfer Coefficient of the entire system. The computations consisted in conjugate Computational Fluid Dynamics solutions involving the ambient temperature and wind distribution, the skid dimensions and arrangement (barrels materials), the tracing system (carbon steel piping), the insulation (Mineral Wool) and the fluid compartments, both steam inside the piping and air in the gaps. The steam was modelled as a single-phase fluid with properties defined to consider the latent heat of condensatio

Vibration and NPSHr (NPSH₃), improvement of BB1 two stage pump reliability

Case StudyThis case study discusses the impeller redesign of 10 8x15 BB1 two stages Amine pump in a Gas Sweeting Plant in Malaysia. The original pump was supplied in 1996 and after some design changes it had an history of recurring high vibration and impeller damages such as a cavitation erosion on inlet suction side and disk break at impeller outlet. Pump performance analysis revealed a service operative point close to Minimum Continuous Stable Flow showing vibration peak both on synchronous frequency and VPF (vane passing frequency) typical of secondary flow effect. After a FMEA analysis it was decided to redesign the impeller.CFD simulation and Static structural with pressure load profiles have been performed and a model test bench has been set up to compare new and old impeller design focusing on NPSHr curve and on interaction forces between impeller blades and volute lip. Currently the 10 pumps are operating without showing any vibration problem

Extending Bayesian back-calculation to estimate age and time specific HIV incidence.

CD4-based multi-state back-calculation methods are key for monitoring the HIV epidemic, providing estimates of HIV incidence and diagnosis rates by disentangling their inter-related contribution to the observed surveillance data. This paper, extends existing approaches to age-specific settings, permitting the joint estimation of age- and time-specific incidence and diagnosis rates and the derivation of other epidemiological quantities of interest. This allows the identification of specific age-groups at higher risk of infection, which is crucial in directing public health interventions. We investigate, through simulation studies, the suitability of various bivariate splines for the non-parametric modelling of the latent age- and time-specific incidence and illustrate our method on routinely collected data from the HIV epidemic among gay and bisexual men in England and Wales

The Inflammatory Cytokine IL-3 Hampers Cardioprotection Mediated by Endothelial Cell-Derived Extracellular Vesicles Possibly via Their Protein Cargo

The biological relevance of extracellular vesicles (EV) released in an ischemia/reperfusion setting is still unclear. We hypothesized that the inflammatory microenvironment prevents cardioprotection mediated by endothelial cell (EC)-derived extracellular vesicles. The effects of naïve EC-derived EV (eEV) or eEV released in response to interleukin-3 (IL-3) (eEV-IL-3) were evaluated in cardiomyoblasts (H9c2) and rat hearts. In transwell assay, eEV protected the H9c2 exposed to hypoxia/reoxygenation (H/R) more efficiently than eEV-IL-3. Conversely, only eEV directly protected H9c2 cells to H/R-induced damage. Consistent with this latter observation, eEV, but not eEV-IL-3, exerted beneficial effects in the whole heart. Protein profiles of eEV and eEV-IL-3, established using label-free mass spectrometry, demonstrated that IL-3 drives changes in eEV-IL-3 protein cargo. Gene ontology analysis revealed that both eEV and eEV-IL-3 were equipped with full cardioprotective machinery, including the Nitric Oxide Signaling in the Cardiovascular System. eEV-IL-3 were also enriched in the endothelial-nitric oxide-synthase (eNOS)-antagonist caveolin-1 and proteins related to the inflammatory response. In vitro and ex vivo experiments demonstrated that a functional Mitogen-Activated Protein Kinase Kinase (MEK1/2)/eNOS/guanylyl-cyclase (GC) pathway is required for eEV-mediated cardioprotection. Consistently, eEV were found enriched in MEK1/2 and able to induce the expression of B-cell-lymphoma-2 (Bcl-2) and the phosphorylation of eNOS in vitro. We conclude that an inflammatory microenvironment containing IL-3 changes the eEV cargo and impairs eEV cardioprotective action

Percutaneous Coronary Intervention (PCI) Reprograms Circulating Extracellular Vesicles from ACS Patients Impairing Their Cardio-Protective Properties

Extracellular vesicles (EVs) are promising therapeutic tools in the treatment of cardiovascular disorders. We have recently shown that EVs from patients with Acute Coronary Syndrome (ACS) undergoing sham pre-conditioning, before percutaneous coronary intervention (PCI) were cardio-protective, while EVs from patients experiencing remote ischemic pre-conditioning (RIPC) failed to induce protection against ischemia/reperfusion Injury (IRI). No data on EVs from ACS patients recovered after PCI are currently available. Therefore, we herein investigated the cardio-protective properties of EVs, collected after PCI from the same patients. EVs recovered from 30 patients randomly assigned (1:1) to RIPC (EV-RIPC) or sham procedures (EV-naive) (NCT02195726) were characterized by TEM, FACS and Western blot analysis and evaluated for their mRNA content. The impact of EVs on hypoxia/reoxygenation damage and IRI, as well as the cardio-protective signaling pathways, were investigated in vitro (HMEC-1 + H9c2 co-culture) and ex vivo (isolated rat heart). Both EV-naive and EV-RIPC failed to drive cardio-protection both in vitro and ex vivo. Consistently, EV treatment failed to activate the canonical cardio-protective pathways. Specifically, PCI reduced the EV-naive Dusp6 mRNA content, found to be crucial for their cardio-protective action, and upregulated some stress- and cell-cycle-related genes in EV-RIPC. We provide the first evidence that in ACS patients, PCI reprograms the EV cargo, impairing EV-naive cardio-protective properties without improving EV-RIPC functional capability