Optimizing ribavirin dose in HIV/hepatitis C (HCV) co-infected individuals treated for HCV

Hepatitis C (HCV) and HIV share common transmission pathways and the acquisition of both viruses are relatively common. Concurrent treatment for HCV with highly active anti-retroviral therapy (HAART) should be considered in HIV co-infected individuals to decrease the progression of liver damage. Adverse effects and less satisfactory treatment outcomes are often concerns when treating co-infected individuals. Although, direct acting antivirals (DAAs) may increase SVR, they may not be possible because of drug-drug interactions. he objective of this study is to investigate the difference in response rates of HCV treatment in HIV co-infected inmates with varying doses of ribavirin. Retrospective medical chart reviews of 52 HCV/HIV co-infected inmates who underwent HCV therapy between 2003 and 2010. All received standard doses of pegylated interferon alpha 2a or 2b and 800–1600 mg of ribavirin depending on weight. The recommended dosage for genotypes 2 and 3 is 800 mg/day. For other genotypes, if weight is<75 kg, the recommended ribavirin dose is 1000 mg/day or 1200 mg/day if>75 kg. Efficacy was defined as attaining sustained virological response (SVR) six months post treatment. Univariate analyses was performed using SPSS-18; Chi-square test with p-value<0.05 was defined significant. 52 co-infected (3 females & 49 males) were identified. Mean age was 40±7 years. Caucasians accounted for 84.6%; First Nations for 13.5% and Asians 1.9%. 36 were concurrently on HAART. The genotype distribution was: geno 1, 66.0%; geno 2, 7.5%; geno 3, 26.4%. SVR by ribavirin dosage ratio (actual dosage/recommended dosage):=1.0; 41.2% (14/34),>1.0; 58.8% (20/34). Doses greater than 1.5 times were associated with higher adverse events and lower SVR. Suboptimal doses of weight-based ribavirin may be contributing to a lower treatment response in HCV/HIV co-infectants. In our experience, the optimal dose of ribavirin is between 1 and 1.2 times the current recommended dose. We recommend that ribavirin dose be individualized in co-infected in order to enhance the likelihood of achieving SVR. Dual therapy is more practical in many of our population because of chaotic lifestyle. Therefore optimizing the ribavirin dose should be initially undertaken

OpenLearn Research Report 2006-2008

This report takes the experience of OpenLearn over its two-years of operation to reflect on what it means to offer free resources and the issues that we have been able to explore and learn from. The structure of the document is: (1) The OpenLearn initiative - an overview (2) OpenLearn research methods (3) Designing for Open Content (4) Types of user of OpenLearn (5) OpenLearn modes of us

DNA metabarcoding of trawling bycatch reveals diversity and distribution patterns of sharks and rays in the central Tyrrhenian Sea

Conservation and management of chondrichthyans are becoming increasingly important, as many species are particularly vulnerable to fishing activities, primarily as bycatch, which leads to incomplete catch reporting, potentially hiding the impact on these organisms. Here, we aimed at implementing an eDNA metabarcoding approach to reconstruct shark and ray bycatch composition from 24 hauls of a bottom trawl fishing vessel in the central Mediterranean. eDNA samples were collected through the passive filtration of seawater by simple gauze rolls encapsulated in a probe (the "metaprobe"), which already showed great efficiency in detecting marine species from trace DNA in the environment. To improve molecular taxonomic detection, we enhanced the 12S target marker reference library by generating sequences for 14 Mediterranean chondrichthyans previously unrepresented in public repositories. DNA metabarcoding data correctly identifies almost all bycaught species and detected five additional species not present in the net, highlighting the potential of this method to detect rare species. Chondrichthyan diversity showed significant association with some key environmental variables (depth and distance from the coast) and the fishing effort, which are known to influence demersal communities. As DNA metabarcoding progressively positions itself as a staple tool for biodiversity monitoring, we expect that its melding with opportunistic, fishery-dependent surveys could reveal additional distribution features of threatened and elusive megafauna

Social determinants of content selection in the age of (mis)information

Despite the enthusiastic rhetoric about the so called \emph{collective intelligence}, conspiracy theories -- e.g. global warming induced by chemtrails or the link between vaccines and autism -- find on the Web a natural medium for their dissemination. Users preferentially consume information according to their system of beliefs and the strife within users of opposite narratives may result in heated debates. In this work we provide a genuine example of information consumption from a sample of 1.2 million of Facebook Italian users. We show by means of a thorough quantitative analysis that information supporting different worldviews -- i.e. scientific and conspiracist news -- are consumed in a comparable way by their respective users. Moreover, we measure the effect of the exposure to 4709 evidently false information (satirical version of conspiracy theses) and to 4502 debunking memes (information aiming at contrasting unsubstantiated rumors) of the most polarized users of conspiracy claims. We find that either contrasting or teasing consumers of conspiracy narratives increases their probability to interact again with unsubstantiated rumors.Comment: misinformation, collective narratives, crowd dynamics, information spreadin

The impact of smoke exposure on the clinical phenotype of alpha-1 antitrypsin deficiency in Ireland: exploiting a national registry to understand a rare disease.

Individuals with Alpha-1 antitrypsin deficiency (AATD) have mutations in the SERPINA1 gene causing genetic susceptibility to early onset lung and liver disease that may result in premature death. Environmental interactions have a significant impact in determining the disease phenotype and outcome in AATD. The aim of this study was to assess the impact of smoke exposure on the clinical phenotype of AATD in Ireland. Clinical demographics and available thoracic computerised tomography (CT) imaging were detected from 139 PiZZ individuals identified from the Irish National AATD Registry. Clinical information was collected by questionnaire. Data was analysed to assess AATD disease severity and evaluate predictors of clinical phenotype. Questionnaires were collected from 107/139 (77%) and thoracic CT evaluation was available in 72/107 (67.2%). 74% of respondents had severe Chronic Obstructive Pulmonary Disease (COPD) (GOLD stage C or D). Cigarette smoking was the greatest predictor of impairment in FEV1 and DLCO (%predicted) and the extent of emphysema correlated most significantly with DLCO. Interestingly the rate of FEV1 decline was similar in ex-smokers when compared to never-smokers. Passive smoke exposure in childhood resulted in a greater total pack-year smoking history. Radiological evidence of bronchiectasis was a common finding and associated with increasing age. The Irish National AATD Registry facilitates clinical and basic science research of this condition in Ireland. This study illustrates the detrimental effect of smoke exposure on the clinical phenotype of AATD in Ireland and the benefit of immediate smoking cessation at any stage of lung disease

Mechanical Control of Spin States in Spin-1 Molecules and the Underscreened Kondo Effect

The ability to make electrical contact to single molecules creates opportunities to examine fundamental processes governing electron flow on the smallest possible length scales. We report experiments in which we controllably stretch individual cobalt complexes having spin S = 1, while simultaneously measuring current flow through the molecule. The molecule's spin states and magnetic anisotropy were manipulated in the absence of a magnetic field by modification of the molecular symmetry. This control enabled quantitative studies of the underscreened Kondo effect, in which conduction electrons only partially compensate the molecular spin. Our findings demonstrate a mechanism of spin control in single-molecule devices and establish that they can serve as model systems for making precision tests of correlated-electron theories.Comment: main text: 5 pages, 4 figures; supporting information attached; to appear in Science

An experimental study investigating the effect of pain relief from oral analgesia on lumbar range of motion, velocity, acceleration and movement irregularity

Background Movement alterations are often reported in individuals with back pain. However the mechanisms behind these movement alterations are not well understood. A commonly cited mechanism is pain. The aim of this study was to investigate the effect of pain reduction, from oral analgesia, on lumbar kinematics in individuals with acute and chronic low back pain. Methods A prospective, cross-sectional, experimental repeated-measures design was used. Twenty acute and 20 chronic individuals with low back pain were recruited from General Practitioner and self-referrals to therapy departments for low back pain. Participants complained of movement evoked low back pain. Inertial sensors were attached to the sacrum and lumbar spine and used to measure kinematics. Kinematic variables measured were range of motion, angular velocity and angular acceleration as well as a determining movement irregularity (a measure of deviation from smooth motion). Kinematics were investigated before and after administration of oral analgesia to instigate pain reduction. Results Pain was significantly reduced following oral analgesia. There were no significant effects on the kinematic variables before and after pain reduction from oral analgesia. There was no interaction between the variables group (acute and chronic) and time (pre and post pain reduction). Conclusion The results demonstrate that pain reduction did not alter lumbar range of motion, angular velocity, angular acceleration or movement irregularity questioning the role of pain in lumbar kinematics

Survey propagation at finite temperature: application to a Sourlas code as a toy model

In this paper we investigate a finite temperature generalization of survey propagation, by applying it to the problem of finite temperature decoding of a biased finite connectivity Sourlas code for temperatures lower than the Nishimori temperature. We observe that the result is a shift of the location of the dynamical critical channel noise to larger values than the corresponding dynamical transition for belief propagation, as suggested recently by Migliorini and Saad for LDPC codes. We show how the finite temperature 1-RSB SP gives accurate results in the regime where competing approaches fail to converge or fail to recover the retrieval state

Evidence for directional selection at a novel major histocompatibility class I marker in wild common frogs (Rana temporaria) exposed to a viral pathogen (Ranavirus).

(c) 2009 Teacher et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Whilst the Major Histocompatibility Complex (MHC) is well characterized in the anuran Xenopus, this region has not previously been studied in another popular model species, the common frog (Rana temporaria). Nor, to date, have there been any studies of MHC in wild amphibian host-pathogen systems. We characterise an MHC class I locus in the common frog, and present primers to amplify both the whole region, and specifically the antigen binding region. As no more than two expressed haplotypes were found in over 400 clones from 66 individuals, it is likely that there is a single class I locus in this species. This finding is consistent with the single class I locus in Xenopus, but contrasts with the multiple loci identified in axolotls, providing evidence that the diversification of MHC class I into multiple loci likely occurred after the Caudata/Anura divergence (approximately 350 million years ago) but before the Ranidae/Pipidae divergence (approximately 230 mya). We use this locus to compare wild populations of common frogs that have been infected with a viral pathogen (Ranavirus) with those that have no history of infection. We demonstrate that certain MHC supertypes are associated with infection status (even after accounting for shared ancestry), and that the diseased populations have more similar supertype frequencies (lower F(ST)) than the uninfected. These patterns were not seen in a suite of putatively neutral microsatellite loci. We interpret this pattern at the MHC locus to indicate that the disease has imposed selection for particular haplotypes, and hence that common frogs may be adapting to the presence of Ranavirus, which currently kills tens of thousands of amphibians in the UK each year