A qualitative study of Internet use comparing the experiences of people with physical disabilities and early onset dementia

People living with Early Onset Dementia and/or physical disabilities face distinct challenges in accessing increasingly digitised services and information. Relatively little is known about how either of these groups access and use the internet on a day-to-day basis, or their plans to negotiate changes in access. Early Onset Dementia, also called young onset or working age dementia, refers to a diagnosis of dementia given before the age of 65. People in this group usually have considerably different lifestyles and responsibilities compared to people who are diagnosed in their 80s. For example, people with Early Onset Dementia are likely to have more experience of computers and working online. Even so, they and their families may have difficulties in accessing appropriate information and services. Another sizeable group for whom assistive online access may be highly relevant is people living with physical disabilities. People in this group may be dependent on assistive technologies and interventions to access technology and the internet. However, despite the difficulties that both of these groups are likely to face, relatively little research has been done about any of their day-to-day activities’. This thesis collects and compares the experiences of two groups of participants through both the literature and qualitative research: Group 1, people living with physical disabilities; and Group 2, people living with Early Onset Dementia and their family members. A comprehensive literature search was conducted into internet use and service access by members of these two groups, and data were collected in semi-structured interviews and online questionnaires. Group 1 comprised of 15 interviews with people living with physical disabilities across Nottinghamshire who were recruited with the assistance of Nottinghamshire County Council (NCC). In addition to the interviews, 29 online questionnaires were completed by people with physical disabilities living across the UK. The data were analysed using an iterative coding approach to draw out the main themes and inform the approach used with Group 2. Group 2 also used an online questionnaire, which had 19 participants, and semi-structured interviews to collect data. The interviews used a number of different online recruitment methods to recruit 10 people living with Early Onset Dementia and eight family members from across England. The data were also analysed using an iterative coding approach, followed by thematic analysis informed by the analysis and results of Group 1. These themes were then compared to posts from the Alzheimer’s Society Talking Point forum by using word frequency analysis and word searches within the dataset. The experiences of the two groups were then compared to draw out the similarities and differences between the two, with the main combined themes centring on online access, support, online information, and digital legacies. All these themes indicated similarities in how people with Early Onset Dementia, their family members, and people living with physical disabilities use the internet and online resources to find information and support. There were also differences between the groups, especially between the group of people diagnosed with Early Onset Dementia and people with physical disabilities. The former group had far more limited involvement in searching for health-related information than the people with physical disabilities, or indeed their family members The themes also highlight the need for further research on both of these groups regarding the appropriateness of a ‘digital first’ approach to local authority services and the nature of support needed by these groups to retain online independence. As online access is not yet universal, it is premature for local authorities to plan a programme of digitisation and assume that service users will be in a position to cope with this change. These themes also underline the need for more up-to-date and appropriate post-diagnostic information, and guidance on which sites or services are safe or trustworthy. Significantly, the findings also draw attention to the need to prompt conversations about changing access needs and the nature of digital legacy, both between family members and between service users and professionals. This includes not just what people think a digital legacy is, but also plans they may want to put in place for online accounts and digital assets, and when this should occur. Further research is needed with larger cohorts of both people with Early Onset Dementia and people with physical disabilities who are active online to understand the changing patterns of internet use and dependence. This will help to ensure that people with Early Onset Dementia or physical disabilities can receive appropriate and accessible online services and support

A Chondritic Solar Neighborhood

A persistent question in exoplanet demographics is whether exoplanetary systems form from similar compositional building blocks to our own. Polluted white dwarf stars offer a unique way to address this question as they provide measurements of the bulk compositions of exoplanetary material. We present a statistical analysis of the rocks polluting oxygen-bearing white dwarfs and compare their compositions to rocks in the Solar System. We find that the majority of the extrasolar rocks are consistent with the composition of typical chondrites. Measurement uncertainties prevent distinguishing between chondrites and bulk Earth, but do permit detecting the differences between chondritic compositions and basaltic or continental crust. We find no evidence of crust amongst the polluted white dwarfs. We show that the chondritic nature of extrasolar rocks is also supported by the compositions of local stars. While galactic chemical evolution results in variations in the relative abundances of rock-forming elements spatially and temporally on galaxy-wide scales, the current sample of polluted white dwarfs are sufficiently young and close to Earth that they are not affected by this process. We conclude that exotic compositions are not required to explain the majority of observed rock types around polluted white dwarfs, and that variations between exoplanetary compositions in the stellar neighborhood are generally not due to significant differences in the initial composition of protoplanetary disks. Nonetheless, there is evidence from stellar observations that planets formed in the first several billion years in the Galaxy have lower metal core fractions compared with Earth on average.Comment: Accepted to PS

The Effects of Modulating Endothelial Nitric Oxide Synthese (eNOS) Activity and Coupling in Extracorporeal Shock Wave Lithotripsy (ESWL)

Introduction: ESWL is a clinical therapy to break down kidney and uretal stones into smaller fragments that are more easily eliminated through the urinary tract. High-energy shock waves are focused on the stone to cause shear stress and cavitation bubbles which synergistically ablate the stones. While ESWL is the preferred treatment for kidney stones over invasive surgeries, the repetitive shock waves necessary to break up the stones may also cause damage to the renal vasculature endothelium and that can lead to chronic hypertension [1]. Previous studies have found that ESWL can cause endothelial dysfunction which is characterized decreased nitric oxide (NO) bioavailability and increased production of reactive oxygen species (ROS) such as superoxide (O2-) [2]. Normally, endothelial nitric oxide synthase (eNOS) is in a coupled state which forms NO in the presence of essential cofactor tetrahydrobiopterin (BH4) and molecular oxygen. Oxidative stress, such as that caused by ESWL-induced ROS, can cause BH4 to be oxidized to dihydrobiopterin (BH2). When the BH2:BH4 ratio is increased, eNOS becomes uncoupled and produces O2- instead of NO [2, 3] (Figure 1). O2- is short-lived and converted to hydrogen peroxide (H2O2) in blood by superoxide dismutase. Protein kinase C epsilon (PKCε) has previously been found to regulate eNOS activity via phosphorylation at serine-1177. Cell-permeable PKCε peptide activator (PKCε+) increases eNOS activity while PKCε inhibitor (PKCε-) reduces eNOS activity [2]. Using a combination of eNOS cofactors BH4 or BH2 with eNOS activity regulators PKCε+ or PKCε-, we can explore the role of modulating eNOS to reduce oxidative stress and endothelial dysfunction caused by ESWL

Evaluating the Consistency of Gene Sets Used in the Analysis of Bacterial Gene Expression Data

Background Statistical analyses of whole genome expression data require functional information about genes in order to yield meaningful biological conclusions. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) are common sources of functionally grouped gene sets. For bacteria, the SEED and MicrobesOnline provide alternative, complementary sources of gene sets. To date, no comprehensive evaluation of the data obtained from these resources has been performed. Results We define a series of gene set consistency metrics directly related to the most common classes of statistical analyses for gene expression data, and then perform a comprehensive analysis of 3581 Affymetrix gene expression arrays across 17 diverse bacteria. We find that gene sets obtained from GO and KEGG demonstrate lower consistency than those obtained from the SEED and MicrobesOnline, regardless of gene set size. Conclusions Despite the widespread use of GO and KEGG gene sets in bacterial gene expression data analysis, the SEED and MicrobesOnline provide more consistent sets for a wide variety of statistical analyses such data. Increased use of the SEED and MicrobesOnline gene sets in the analysis of bacterial gene expression data may improve statistical power and utility of expression data

Disease Knowledge Transfer across Neurodegenerative Diseases

We introduce Disease Knowledge Transfer (DKT), a novel technique for transferring biomarker information between related neurodegenerative diseases. DKT infers robust multimodal biomarker trajectories in rare neurodegenerative diseases even when only limited, unimodal data is available, by transferring information from larger multimodal datasets from common neurodegenerative diseases. DKT is a joint-disease generative model of biomarker progressions, which exploits biomarker relationships that are shared across diseases. Our proposed method allows, for the first time, the estimation of plausible, multimodal biomarker trajectories in Posterior Cortical Atrophy (PCA), a rare neurodegenerative disease where only unimodal MRI data is available. For this we train DKT on a combined dataset containing subjects with two distinct diseases and sizes of data available: 1) a larger, multimodal typical AD (tAD) dataset from the TADPOLE Challenge, and 2) a smaller unimodal Posterior Cortical Atrophy (PCA) dataset from the Dementia Research Centre (DRC), for which only a limited number of Magnetic Resonance Imaging (MRI) scans are available. Although validation is challenging due to lack of data in PCA, we validate DKT on synthetic data and two patient datasets (TADPOLE and PCA cohorts), showing it can estimate the ground truth parameters in the simulation and predict unseen biomarkers on the two patient datasets. While we demonstrated DKT on Alzheimer's variants, we note DKT is generalisable to other forms of related neurodegenerative diseases. Source code for DKT is available online: https://github.com/mrazvan22/dkt.Comment: accepted at MICCAI 2019, 13 pages, 5 figures, 2 table

Hydraulic permeability and compressive properties of porcine and human synovium

The synovium is a multilayer connective tissue separating the intra-articular spaces of the diarthrodial joint from the extra-synovial vascular and lymphatic supply. Synovium regulates drug transport into and out of the joint, yet its material properties remain poorly characterized. Here, we measured the compressive properties (aggregate modulus, Young\u27s modulus, and Poisson\u27s ratio) and hydraulic permeability of synovium with a combined experimental-computational approach. A compressive aggregate modulus and Young\u27s modulus for the solid phase of synovium were quantified from linear regression of the equilibrium confined and unconfined compressive stress upon strain, respectively (

New chondritic bodies identified in eight oxygen-bearing white dwarfs

We present observations and analyses of eight white dwarf stars that have accreted rocky material from their surrounding planetary systems. The spectra of these helium-atmosphere white dwarfs contain detectable optical lines of all four major rock-forming elements (O, Mg, Si, Fe). This work increases the sample of oxygen-bearing white dwarfs with parent body composition analyses by roughly thirty-three percent. To first order, the parent bodies that have been accreted by the eight white dwarfs are similar to those of chondritic meteorites in relative elemental abundances and oxidation states. Seventy-five percent of the white dwarfs in this study have observed oxygen excesses implying volatiles in the parent bodies with abundances similar to those of chondritic meteorites. Three white dwarfs have oxidation states that imply more reduced material than found in CI chondrites, indicating the possible detection of Mercury-like parent bodies, but are less constrained. These results contribute to the recurring conclusion that extrasolar rocky bodies closely resemble those in our solar system, and do not, as a whole, yield unusual or unique compositions.Comment: Accepted for publication in ApJ. 7 Figures, 7 Table

Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals.

After several years of steady decline, syphilis is reemerging globally as a public health hazard, especially among people living with human immunodeficiency virus (HIV). Syphilis resurgence is observed mainly in men who have sex with men (MSM), yet other transmission groups are affected too. In this manuscript, we study the factors associated with syphilis incidence in the Swiss HIV cohort study in the era of highly effective antiretrovirals. Using parametric interval censored models with fixed and time-varying covariates, we studied the immunological, behavioral, and treatment-related elements associated with syphilis incidence in 3 transmission groups: MSM, heterosexuals, and intravenous drug users. Syphilis incidence has been increasing annually since 2005, with up to 74 incident cases per 1000 person-years in 2013, with MSM being the population with the highest burden (92% of cases). While antiretroviral treatment (ART) in general did not affect syphilis incidence, nevirapine (NVP) was associated with a lower hazard of syphilis incidence (multivariable hazard ratio 0.5, 95% confidence interval 0.2-1.0). We observed that condomless sex and younger age were associated with higher syphilis incidence. Moreover, time-updated CD4, nadir CD4, and CD8 cell counts were not associated with syphilis incidence. Finally, testing frequency higher than the recommended once a year routine testing was associated with a 2-fold higher risk of acquiring syphilis. Condomless sex is the main driver of syphilis resurgence in the Swiss HIV Cohort study; ART and immune reconstitution provide no protection against syphilis. This entails targeted interventions and frequent screening of high-risk populations. There is no known effect of NVP on syphilis; therefore, further clinical, epidemiological, and microbiological investigation is necessary to validate our observation