36 research outputs found
Atazanavir/ritonavir monotherapy: 96 week efficacy, safety and bone mineral density from the MODAt randomized trial
No full textTo report the 96 week results on efficacy, safety and bone mineral density (BMD) in subjects with HIV-1 that were virologically suppressed and treated with atazanavir/ritonavir monotherapy versus atazanavir/ritonavir triple therapy
Immune activation, inflammation and HIV DNA after 96-weeks of ATV/r monotherapy : a MODAt substudy
No full textImage computing tools for the investigation of the neurological effects of preterm birth and corticosteroid administration
Get PDFIn this thesis we present a range of computational tools for medical imaging purposes within two main research projects. The first one is a methodological project oriented towards the improvement of the performance of a numerical computation utilised in diffeomorphic image registration. The second research project is a pre-clinical study aimed at the investigation of the effects of antenatal corticosteroids in a preterm rabbit animal model. In the first part we addressed the problem of integrating stationary velocity fields. This mathematical challenge had originated with early studies in fluid dynamics and had been subsequently mathematically formalised in the Lie group theory. Given a tangent velocity field defined in the tridimensional space as in input, the goal is to compute the position of the particles to which the velocity field is applied. This computation, also called numerical Lie exponential, is a fundamental component of several medical image registration algorithm based on diffeomorphisms, i.e. bijective differentiable maps with differentiable inverse. It is as well a widely utilised tool in computational anatomy to quantify the differences between two anatomical shapes measuring the parameters of the transformation that belongs to a metric vector space. The resulting new class of algorithms introduced in this thesis was created combining the known scaling and squaring algorithm with a class of numerical integrators aimed to solve systems of ordinary differential equations called exponential integrators. The introduced scaling and squaring based approximated exponential integrator algorithm have improved the computational time and accuracy respect to the state- of-the-art methods. The second part of the research is a pre-clinical trial carried forward in collab- oration with the Department of Development and Regeneration, Woman and Child Cluster at the KU Leuven University. The clinical research question is related to the understanding of the possible negative effects of administering antenatal cor- ticosteroids for preterm birth. To tackle this problem we designed and started a pre-clinical study using a New Zealand perinatal rabbit model. In this part of the research I was involved in the research team to provide the tools to automatise the data analysis and to eliminate the time consuming and non reproducible manual segmentation step. The main result of this collaboration is the creation of the first multi-modal multi-atlas for the newborn rabbit brain. This is embedded in a segmentation propagation and label fusion algorithm at the core of the proposed open-sourced automatic pipeline, having as input the native scanner format and as output the main MRI readouts, such as volume, fractional anisotropy and mean diffusivity
The Importance of Group-Wise Registration in Tract Based Spatial Statistics Study of Neurodegeneration: A Simulation Study in Alzheimer's Disease
Get PDFTract-based spatial statistics (TBSS) is a popular method for the analysis of diffusion tensor imaging data. TBSS focuses on differences in white matter voxels with high fractional anisotropy (FA), representing the major fibre tracts, through registering all subjects to a common reference and the creation of a FA skeleton. This work considers the effect of choice of reference in the TBSS pipeline, which can be a standard template, an individual subject from the study, a study-specific template or a group-wise average. While TBSS attempts to overcome registration error by searching the neighbourhood perpendicular to the FA skeleton for the voxel with maximum FA, this projection step may not compensate for large registration errors that might occur in the presence of pathology such as atrophy in neurodegenerative diseases. This makes registration performance and choice of reference an important issue. Substantial work in the field of computational anatomy has shown the use of group-wise averages to reduce biases while avoiding the arbitrary selection of a single individual. Here, we demonstrate the impact of the choice of reference on: (a) specificity (b) sensitivity in a simulation study and (c) a real-world comparison of Alzheimer's disease patients to controls. In (a) and (b), simulated deformations and decreases in FA were applied to control subjects to simulate changes of shape and WM integrity similar to what would be seen in AD patients, in order to provide a "ground truth" for evaluating the various methods of TBSS reference. Using a group-wise average atlas as the reference outperformed other references in the TBSS pipeline in all evaluations
Summary of the results obtained with different TBSS pipelines in the literature and specificity evaluation study on FA.
No full text<p> significant reduction in FA (); no significant results; n = number of studies.</p><p>CC: Corpus callosum; ST-TBSS: Standard; RS-TBSS: Most-Representative-Subject TBSS; SS-TBSS: Study-Specific-Template; GW-TBSS: Group-wise TBSS; Results of the specificity evaluation study is reported bilaterally and in the case of asymmetry they are reported for the right hemisphere. 1: Left with only significant difference in ; 2: Left with no significant difference; 3: Left with significant difference at .</p
Post-vaccination infection rates and modification of COVID-19 symptoms in vaccinated UK school-aged children and adolescents: A prospective longitudinal cohort study
No full text\ua9 2022 The Author(s). Background: We aimed to explore the effectiveness of one-dose BNT162b2 vaccination upon SARS-CoV-2 infection, its effect on COVID-19 presentation, and post-vaccination symptoms in children and adolescents (CA) in the UK during periods of Delta and Omicron variant predominance. Methods: In this prospective longitudinal cohort study, we analysed data from 115,775 CA aged 12-17 years, proxy-reported through the Covid Symptom Study (CSS) smartphone application. We calculated post-vaccination infection risk after one dose of BNT162b2, and described the illness profile of CA with post-vaccination SARS-CoV-2 infection, compared to unvaccinated CA, and post-vaccination side-effects. Findings: Between August 5, 2021 and February 14, 2022, 25,971 UK CA aged 12-17 years received one dose of BNT162b2 vaccine. The probability of testing positive for infection diverged soon after vaccination, and was lower in CA with prior SARS-CoV-2 infection. Vaccination reduced proxy-reported infection risk (-80\ub74% (95% CI -0\ub782 -0\ub778) and -53\ub77% (95% CI -0\ub762 -0\ub743) at 14–30 days with Delta and Omicron variants respectively, and -61\ub75% (95% CI -0\ub774 -0\ub744) and -63\ub77% (95% CI -0\ub768 -0.59) after 61–90 days). Vaccinated CA who contracted SARS-CoV-2 during the Delta period had milder disease than unvaccinated CA; during the Omicron period this was only evident in children aged 12-15 years. Overall disease profile was similar in both vaccinated and unvaccinated CA. Post-vaccination local side-effects were common, systemic side-effects were uncommon, and both resolved within few days (3 days in most cases). Interpretation: One dose of BNT162b2 vaccine reduced risk of SARS-CoV-2 infection for at least 90 days in CA aged 12-17 years. Vaccine protection varied for SARS-CoV-2 variant type (lower for Omicron than Delta variant), and was enhanced by pre-vaccination SARS-CoV-2 infection. Severity of COVID-19 presentation after vaccination was generally milder, although unvaccinated CA also had generally mild disease. Overall, vaccination was well-tolerated. Funding: UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation and Alzheimer\u27s Society, and ZOE Limited
Most-Representative-Subject TBSS (RS-TBSS) and Study-Specific-Template TBSS (SS-TBS) pipeline.
No full text<p>The remainder of this paper is organised as follows: In Section, different registration approaches for the TBSS pipeline are reviewed and a modification to the pipeline is introduced to incorporate a group-wise atlas. In Section, a misalignment between two groups (patients and controls) is modelled using a simulation study. In Section, results are presented on the simulation study and on a dataset of AD (n = 20) and age-matched controls (n = 21).</p
Results obtained with Group-wise TBSS on sensitivity evaluation study when reducing FA virtually.
No full text<p>Corrected p-value at ; 10% (20–40%) FA reduction; significant reduction in FA at ; no significant results.</p><p>ST-TBSS: Standard; RS-TBSS: Most-Representative-Subject TBSS; SS-TBSS: Study-Specific-Template.</p
Anatomical locations reported to show reduced FA in AD patients in the literature using TBSS to date.
No full text<p>In some, a mild cognitive impairment (MCI) group was studied alongside the AD and control groups. For simplicity we summarise the FA findings of the AD versus control group comparison only. ST-TBSS: Standard; RS-TBSS: Most-Representative-Subject TBSS; SS-TBSS: Study-Specific-Template.</p
aMAP is a validated pipeline for registration and segmentation of high-resolution mouse brain data
Get PDFThe validation of automated image registration and segmentation is crucial for accurate and reliable mapping of brain connectivity and function in three-dimensional (3D) data sets. While validation standards are necessarily high and routinely met in the clinical arena, they have to date been lacking for high-resolution microscopy data sets obtained from the rodent brain. Here we present a tool for optimized automated mouse atlas propagation (aMAP) based on clinical registration software (NiftyReg) for anatomical segmentation of high-resolution 3D fluorescence images of the adult mouse brain. We empirically evaluate aMAP as a method for registration and subsequent segmentation by validating it against the performance of expert human raters. This study therefore establishes a benchmark standard for mapping the molecular function and cellular connectivity of the rodent brain
