The high comorbidity burden of the hepatitis C virus infected population in the United States

<p>Abstract</p> <p>Background</p> <p>Chronic hepatitis C (HCV) disease can be complicated with comorbid conditions that may impact treatment eligibility and outcomes. The aim of the study was to systematically review comorbidities and symptoms in an HCV infected population, specifically assessing comorbidities associated with HCV anti-viral treatment and disease, as well as comparing comorbidities between an HCV infected and uninfected control population.</p> <p>Methods</p> <p>This was a retrospective cohort study within a United States medical claims database among patients with chronic HCV designed to estimate the two-year period prevalence of comorbidities. Patients with two HCV diagnosis codes, 24 months of continuous health insurance coverage, and full medical and pharmacy benefits were included.</p> <p>Results</p> <p>Among a chronic HCV cohort of 7411 patients, at least one comorbid condition was seen in almost all patients (> 99%) during the study period. HCV-infected patients reported almost double the number of comorbidities compared to uninfected controls. Of the 25 most common comorbidities, the majority of the comorbidities (n = 22) were known to be associated with either HCV antiviral treatment or disease. The five most frequent comorbidities were liver disease [other] (37.5%), connective tissue disease (37.5%), abdominal pain (36.1%), upper respiratory infections (35.6%), and lower respiratory disease (33.7%). Three notable comorbidities not known to be associated with antiviral treatment or disease were benign neoplasms (24.3%), genitourinary symptoms & ill-defined conditions (14.8%), and viral infections (13.8%).</p> <p>Conclusions</p> <p>This US medically insured HCV population is highly comorbid. Effective strategies to manage these comorbidities are necessary to allow wider access to HCV treatment and reduce the future burden of HCV disease and its manifestations.</p

Temporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California

Abstract Background Hepatitis C virus (HCV) genotype (GT) has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S.) HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4). Results Overall, GT 1 was predominant (72.4%), however younger injection drug users (IDU) had a lower proportion of GT 1 infections (54.7%) compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively). Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34). African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99). Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level

DNA Barcode Sequence Identification Incorporating Taxonomic Hierarchy and within Taxon Variability

For DNA barcoding to succeed as a scientific endeavor an accurate and expeditious query sequence identification method is needed. Although a global multiple–sequence alignment can be generated for some barcoding markers (e.g. COI, rbcL), not all barcoding markers are as structurally conserved (e.g. matK). Thus, algorithms that depend on global multiple–sequence alignments are not universally applicable. Some sequence identification methods that use local pairwise alignments (e.g. BLAST) are unable to accurately differentiate between highly similar sequences and are not designed to cope with hierarchic phylogenetic relationships or within taxon variability. Here, I present a novel alignment–free sequence identification algorithm–BRONX–that accounts for observed within taxon variability and hierarchic relationships among taxa. BRONX identifies short variable segments and corresponding invariant flanking regions in reference sequences. These flanking regions are used to score variable regions in the query sequence without the production of a global multiple–sequence alignment. By incorporating observed within taxon variability into the scoring procedure, misidentifications arising from shared alleles/haplotypes are minimized. An explicit treatment of more inclusive terminals allows for separate identifications to be made for each taxonomic level and/or for user–defined terminals. BRONX performs better than all other methods when there is imperfect overlap between query and reference sequences (e.g. mini–barcode queries against a full–length barcode database). BRONX consistently produced better identifications at the genus–level for all query types

Identification of novel conserved peptide uORF homology groups in Arabidopsis and rice reveals ancient eukaryotic origin of select groups and preferential association with transcription factor-encoding genes

Abstract Background Upstream open reading frames (uORFs) can mediate translational control over the largest, or major ORF (mORF) in response to starvation, polyamine concentrations, and sucrose concentrations. One plant uORF with conserved peptide sequences has been shown to exert this control in an amino acid sequence-dependent manner but generally it is not clear what kinds of genes are regulated, or how extensively this mechanism is invoked in a given genome. Results By comparing full-length cDNA sequences from Arabidopsis and rice we identified 26 distinct homology groups of conserved peptide uORFs, only three of which have been reported previously. Pairwise Ka/Ks analysis showed that purifying selection had acted on nearly all conserved peptide uORFs and their associated mORFs. Functions of predicted mORF proteins could be inferred for 16 homology groups and many of these proteins appear to have a regulatory function, including 6 transcription factors, 5 signal transduction factors, 3 developmental signal molecules, a homolog of translation initiation factor eIF5, and a RING finger protein. Transcription factors are clearly overrepresented in this data set when compared to the frequency calculated for the entire genome (p = 1.2 × 10-7). Duplicate gene pairs arising from a whole genome duplication (ohnologs) with a conserved uORF are much more likely to have been retained in Arabidopsis (Arabidopsis thaliana) than are ohnologs of other genes (39% vs 14% of ancestral genes, p = 5 × 10-3). Two uORF groups were found in animals, indicating an ancient origin of these putative regulatory elements. Conclusion Conservation of uORF amino acid sequence, association with homologous mORFs over long evolutionary time periods, preferential retention after whole genome duplications, and preferential association with mORFs coding for transcription factors suggest that the conserved peptide uORFs identified in this study are strong candidates for translational controllers of regulatory genes.</p

'This is our Call of Duty': hegemony, history and resistant videogames in the Middle East

In recent years, non-state actors in the Middle East have engaged a new generation of activists through a variety of media strategies. Notable among these is a series of videogame interventions, which have appropriated Western game products to convey political and religious messages through the inversion or complication of the roles of hero and enemy. This article explores a selection of such media, produced by or in support of two non-state groups, Hezbollah and Islamic State (IS). The article takes a discourse theoretical approach to examine the ideologies presented in these media and reflects on the ways in which these game artefacts engage with, and reject, Western narratives of history and of US pre-eminence. It concludes that while these game interventions challenge existing hegemonic (re)presentations of the Middle East and the ‘War on Terror’, they remove or reduce agency to the extent that those who engage with them can only witness these challenges, rather than instigate their own. While we acknowledge that hegemony can always be challenged, we view this lack of agency as support for Mouffe’s proposition that the result of counter-hegemonic resistance is often to maintain and reproduce the hegemonic order

Measurements of atmospheric electricity aloft

Measurements of the electrical characteristics of the atmosphere above the surface have been made for over 200 years, from a variety of different platforms, including kites, balloons, rockets and aircraft. From these measurements, a great deal of information about the electrical characteristics of the atmosphere has been gained, assisting our understanding of the global atmospheric electric circuit, thunderstorm electrification and lightning generation mechanisms, discovery of transient luminous events above thunderstorms, and many other electrical phenomena. This paper surveys the history of atmospheric electrical measurements aloft, from the earliest manned balloon ascents to current day observations with free balloons and aircraft. Measurements of atmospheric electrical parameters in a range of meteorological conditions are described, including clear air conditions, polluted conditions, non-thunderstorm clouds, and thunderstorm clouds, spanning a range of atmospheric conditions, from fair weather, to the most electrically active

The impact of currently licensed therapies on viral and immune responses in Chronic Hepatitis B: considerations for future novel therapeutics.

Despite the availability of a preventative vaccine, chronic hepatitis B (CHB) remains a global healthcare challenge with the risk of disease progression due to cirrhosis and hepatocellular carcinoma. Although current treatment strategies, interferon and nucleos(t)ide analogues have contributed to reducing morbidity and mortality related to CHB, these therapies are limited in providing functional cure. The treatment paradigm in CHB is rapidly evolving with a number of new agents in the developmental pipeline. However, until novel agents with functional cure capability are available in the clinical setting, there is a pressing need to optimize currently licensed therapies. Here, we discuss current agents used alone and/or in combination strategies along with the impact of these therapies on viral and immune responses. Novel treatment strategies are outlined, and the potential role of current therapies in the employment of pipeline agents is discussedWellcome Trust Clinical Research Training Fellowship (107389/Z/15/Z)NIHR Academic Clinical LectureshipBarts Charity Project Grants (723/1795 and MGU/0406NIHR Research for patient benefit award (PB‐PG‐0614‐34087) to PTF