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Contains fulltext : 252186.pdf (Publisher’s version ) (Open Access), BACKGROUND AND AIMS: Detection of autoantibodies is a mainstay of diagnosing autoimmune hepatitis (AIH). However, conventional autoantibodies for the workup of AIH lack either sensitivity or specificity, leading to substantial diagnostic uncertainty. We aimed to identify more accurate serological markers of AIH with a protein macroarray. APPROACH AND RESULTS: During the search for more-precise autoantibodies to distinguish AIH from non-AIH liver diseases (non-AIH-LD), IgG antibodies with binding capacities to many human and foreign proteins were identified with a protein macroarray and confirmed with solid-phase ELISAs in AIH patients. Subsequently, polyreactive IgG (pIgG) was exemplarily quantified by reactivity against human huntingtin-interacting protein 1-related protein in bovine serum albumin blocked ELISA (HIP1R/BSA). The diagnostic fidelity of HIP1R/BSA binding pIgG to diagnose AIH was assessed in a retrospective training, a retrospective multicenter validation, and a prospective validation cohort in cryoconserved samples from 1,568 adults from 10 centers from eight countries. Reactivity against HIP1R/BSA had a 25% and 14% higher specificity to diagnose AIH than conventional antinuclear and antismooth muscle antibodies, a significantly higher sensitivity than liver kidney microsomal antibodies and antisoluble liver antigen/liver pancreas antigen, and a 12%-20% higher accuracy than conventional autoantibodies. Importantly, HIP1R/BSA reactivity was present in up to 88% of patients with seronegative AIH and in up to 71% of AIH patients with normal IgG levels. Under therapy, pIgG returns to background levels of non-AIH-LD. CONCLUSIONS: pIgG could be used as a promising marker to improve the diagnostic workup of liver diseases with a higher specificity for AIH compared to conventional autoantibodies and a utility in autoantibody-negative AIH. Likewise, pIgG could be a major source of assay interference in untreated AIH.

Contains fulltext : 252186.pdf (Publisher’s version ) (Open Access), BACKGROUND AND AIMS: Detection of autoantibodies is a mainstay of diagnosing autoimmune hepatitis (AIH). However, conventional autoantibodies for the workup of AIH lack either sensitivity or specificity, leading to substantial diagnostic uncertainty. We aimed to identify more accurate serological markers of AIH with a protein macroarray. APPROACH AND RESULTS: During the search for more-precise autoantibodies to distinguish AIH from non-AIH liver diseases (non-AIH-LD), IgG antibodies with binding capacities to many human and foreign proteins were identified with a protein macroarray and confirmed with solid-phase ELISAs in AIH patients. Subsequently, polyreactive IgG (pIgG) was exemplarily quantified by reactivity against human huntingtin-interacting protein 1-related protein in bovine serum albumin blocked ELISA (HIP1R/BSA). The diagnostic fidelity of HIP1R/BSA binding pIgG to diagnose AIH was assessed in a retrospective training, a retrospective multicenter validation, and a prospective validation cohort in cryoconserved samples from 1,568 adults from 10 centers from eight countries. Reactivity against HIP1R/BSA had a 25% and 14% higher specificity to diagnose AIH than conventional antinuclear and antismooth muscle antibodies, a significantly higher sensitivity than liver kidney microsomal antibodies and antisoluble liver antigen/liver pancreas antigen, and a 12%-20% higher accuracy than conventional autoantibodies. Importantly, HIP1R/BSA reactivity was present in up to 88% of patients with seronegative AIH and in up to 71% of AIH patients with normal IgG levels. Under therapy, pIgG returns to background levels of non-AIH-LD. CONCLUSIONS: pIgG could be used as a promising marker to improve the diagnostic workup of liver diseases with a higher specificity for AIH compared to conventional autoantibodies and a utility in autoantibody-negative AIH. Likewise, pIgG could be a major source of assay interference in untreated AIH.

Background: Progress in the field of evolutionary forest ecology has been hampered by the huge challenge of phenotyping trees across their ranges in their natural environments, and the limitation in high-resolution environmental information. Findings: The GenTree Platform contains phenotypic and environmental data from 4,959 trees from 12 ecologically and economically important European forest tree species: Abies alba Mill. (silver fir), Betula pendula Roth. (silver birch), Fagus sylvatica L. (European beech), Picea abies (L.) H. Karst (Norway spruce), Pinus cembra L. (Swiss stone pine), Pinus halepensis Mill. (Aleppo pine), Pinus nigra Arnold (European black pine), Pinus pinaster Aiton (maritime pine), Pinus sylvestris L. (Scots pine), Populus nigra L. (European black poplar), Taxus baccata L. (English yew), and Quercus petraea (Matt.) Liebl. (sessile oak). Phenotypic (height, diameter at breast height, crown size, bark thickness, biomass, straightness, forking, branch angle, fructification), regeneration, environmental in situ measurements (soil depth, vegetation cover, competition indices), and environmental modeling data extracted by using bilinear interpolation accounting for surrounding conditions of each tree (precipitation, temperature, insolation, drought indices) were obtained from trees in 194 sites covering the species’ geographic ranges and reflecting local environmental gradients. Conclusions: The GenTree Platform is a new resource for investigating ecological and evolutionary processes in forest trees. The coherent phenotyping and environmental characterization across 12 species in their European ranges allow for a wide range of analyses from forest ecologists, conservationists, and macro-ecologists. Also, the data here presented can be linked to the GenTree Dendroecological collection, the GenTree Leaf Trait collection, and the GenTree Genomic collection presented elsewhere, which together build the largest evolutionary forest ecology data c

Motivation: Trait variation within species can reveal plastic and/or genetic responses to environmental gradients, and may indicate where local adaptation has occurred. Here, we present a dataset of rangewide variation in leaf traits from seven of the most ecologically and economically important tree species in Europe. Sample collection and trait assessment are embedded in the GenTree project (EU‐Horizon 2020), which aims at characterizing the genetic and phenotypic variability of forest tree species to optimize the management and sustainable use of forest genetic resources. Our dataset captures substantial intra‐ and interspecific leaf phenotypic variability, and provides valuable information for studying the relationship between ecosystem functioning and trait variability of individuals, and the response and resilience of species to environmental changes. Main types of variable contained: We chose morphological and chemical characters linked to trade‐offs between acquisition and conservation of resources and water use, namely specific leaf area, leaf size, carbon and nitrogen content and their ratio, and the isotopic signature of stable isotope ¹³C and ¹⁵N in leaves. Spatial location and grain: We surveyed between 18 and 22 populations per species, 141 in total, across Europe. Time period: Leaf sampling took place between 2016 and 2017. Major taxa and level of measurement: We sampled at least 25 individuals in each population, 3,569 trees in total, and measured traits in 35,755 leaves from seven European tree species, i.e. the conifers Picea abies, Pinus pinaster and Pinus sylvestris, and the broadleaves Betula pendula, Fagus sylvatica, Populus nigra and Quercus petraea. Software format: The data files are in ASCII text, tab delimited, not compressed.

Oaks are an important part of our natural and cultural heritage. Not only are they ubiquitous in our most common landscapes1 but they have also supplied human societies with invaluable services, including food and shelter, since prehistoric times2. With 450 species spread throughout Asia, Europe and America3, oaks constitute a critical global renewable resource. The longevity of oaks (several hundred years) probably underlies their emblematic cultural and historical importance. Such long-lived sessile organisms must persist in the face of a wide range of abiotic and biotic threats over their lifespans. We investigated the genomic features associated with such a long lifespan by sequencing, assembling and annotating the oak genome. We then used the growing number of whole-genome sequences for plants (including tree and herbaceous species) to investigate the parallel evolution of genomic characteristics potentially underpinning tree longevity. A further consequence of the long lifespan of trees is their accumulation of somatic mutations during mitotic divisions of stem cells present in the shoot apical meristems. Empirical4 and modelling5 approaches have shown that intra-organismal genetic heterogeneity can be selected for6 and provides direct fitness benefits in the arms race with short-lived pests and pathogens through a patchwork of intra-organismal phenotypes7. However, there is no clear proof that large-statured trees consist of a genetic mosaic of clonally distinct cell lineages within and between branches. Through this case study of oak, we demonstrate the accumulation and transmission of somatic mutations and the expansion of disease-resistance gene families in trees.

Autoimmune Hepatitis (AIH) can present under clinical profile as acute hepatitis of unexplained cause. We analyzed clinical, therapeutical and prognostic implications of AIH presenting as acute hepatitis in a cohort of patients admitted to 3 referral Centres in Italy. AIH onset was considered acute when transaminases were higher than 10 times the normal limit and/or bilirubin higher than 5 mg/ml (irrespectively from the histology, available only in 62% of cases). Among 479 patients diagnosed as AIH, 202 (43%) met the criteria of acute onset. This former group of patients on the basis of the histology has been subdivided in the “genuine” acute onset (83 pts) and acute “on chronic” onset (45 pts) At onset, clinical acute AIH showed significantly higher ALT, bilirubin and INR levels (p < 0.001 for all), lower albumin values (p = 0.001), similar IgG levels; Response to treatment was similar between the two groups. The progression to liver cirrhosis or its complications was significantly less frequent in acute onset AIH (13% vs. 22%, p = 0.02). The “genuine” acute patients showed a higher albumin serum levels (40 vs. 36, p = 0.001), lower INR levels (1.12 vs. 1.26, p = 0.002) and less tendency to the progression of liver disease (7% vs. 12%, p = NS) with respect to acute “on chronic” onset patients. Clinical acute hepatitis represents a common presentation of AIH, responds to standard immunosuppression regimen and would seem to be correlated with a better long-term prognosis.

Objectives The aim of the study was to assess user acceptability in patients and caregivers with an electronic application designed to input patient reported outcome (ePRO) data, in this instance, the health-related quality of life instrument PROQOL-HIV, prior to clinical consultation. A feature of the application will enable the transfer of ePRO data into clinical software and the patient’s medical record. The aim being to systematically collect ePRO data that can be referenced during a clinical consultation. Methods Thirty-six semi-directive interviews were conducted in several hospitals in France and a private clinic in Australia to determine the initial user acceptability of such an application. In the first part of the interviews researchers described the purpose of the application and questioned patients (n=25) and doctors (n=11) about their computer usage habits and capabilities, their views on envisaged benefits or harms. Results The patients’ showed interest in using electronic health applications in general and in the potential capabilities of the prototype that was demonstrated. Patients envisaged an ‘efficiency gain’ for themselves and for the doctor if the volume of data transmitted was not ‘overwhelming’. Many of the doctors were already using eHealth applications. The application was perceived as potentially time saving during medical consultations but on the other hand could be time consuming if data was voluminous. Doctors asked for a clear presentation of meaningful scores. Confidentiality was a major concern for French patients, particularly migrants; and doctors, but was less striking among Australian interviewees who had confidence in data protection processes. Conclusions The qualitative study was an important part of the app development. Integration of user’s opinions on different aspects of the app such as confidentiality and the result presentation should make the development more efficient.

Background Hepatitis C virus (HCV) compromises Health-related Quality of Life (HRQL) with detriments to Physical, Mental and Social health domains. Treatment with interferon and ribavirin is associated with side effects which further impair HRQL. New treatments appear potent, effective and tolerable. However, Patient Reported Outcomes instruments that capture the impact on HRQL for people with hepatitis C are largely non-specific and will be needed in the new treatment era. Therefore, we developed a conceptually valid multidimensional model of HCV-specific quality of life and pilot survey instrument, the Patient Reported Outcome Quality of Life survey for HCV (PROQOL-HCV). Methods HCV patients from France (n = 30), Brazil (n = 20) and Australia (n = 20) were interviewed to investigate HCV-HRQL issues raised in the scientific literature and by treatment specialists. Interviews were recorded, transcribed and translated into English and French. Results Fifteen content dimensions were derived from the qualitative analysis, refined and fitted to four domains: (1) Physical Health included: fatigue, pain, sleep, sexual impairment and physical activity; (2) Mental Health: psychological distress, psychosocial impact, and cognition; (3) Social Health: support, stigma, social activity, substance use; (4) Treatment: management, side effects, and fear of treatment failure. The impact of some dimensions extended beyond their primary domain including: physical activity, cognition, sleep, sexual impairment, and the three treatment dimensions. A bank of 300 items was constructed to reflect patient reports and, following expert review, reduced to a 72-item pilot questionnaire. Conclusion We present a conceptually valid multidimensional model of HCV-specific quality of life and the pilot survey instrument, PROQOL-HCV. The model is widely inclusive of the experience of hepatitis C and the first to include the treatment dimension.

Objectives The aim of the study was to assess user acceptability in patients and caregivers with an electronic application designed to input patient reported outcome (ePRO) data, in this instance, the health-related quality of life instrument PROQOL-HIV, prior to clinical consultation. A feature of the application will enable the transfer of ePRO data into clinical software and the patient’s medical record. The aim being to systematically collect ePRO data that can be referenced during a clinical consultation. Methods Thirty-six semi-directive interviews were conducted in several hospitals in France and a private clinic in Australia to determine the initial user acceptability of such an application. In the first part of the interviews researchers described the purpose of the application and questioned patients (n=25) and doctors (n=11) about their computer usage habits and capabilities, their views on envisaged benefits or harms. Results The patients’ showed interest in using electronic health applications in general and in the potential capabilities of the prototype that was demonstrated. Patients envisaged an ‘efficiency gain’ for themselves and for the doctor if the volume of data transmitted was not ‘overwhelming’. Many of the doctors were already using eHealth applications. The application was perceived as potentially time saving during medical consultations but on the other hand could be time consuming if data was voluminous. Doctors asked for a clear presentation of meaningful scores. Confidentiality was a major concern for French patients, particularly migrants; and doctors, but was less striking among Australian interviewees who had confidence in data protection processes. Conclusions The qualitative study was an important part of the app development. Integration of user’s opinions on different aspects of the app such as confidentiality and the result presentation should make the development more efficient.

Background Hepatitis C virus (HCV) compromises Health-related Quality of Life (HRQL) with detriments to Physical, Mental and Social health domains. Treatment with interferon and ribavirin is associated with side effects which further impair HRQL. New treatments appear potent, effective and tolerable. However, Patient Reported Outcomes instruments that capture the impact on HRQL for people with hepatitis C are largely non-specific and will be needed in the new treatment era. Therefore, we developed a conceptually valid multidimensional model of HCV-specific quality of life and pilot survey instrument, the Patient Reported Outcome Quality of Life survey for HCV (PROQOL-HCV). Methods HCV patients from France (n = 30), Brazil (n = 20) and Australia (n = 20) were interviewed to investigate HCV-HRQL issues raised in the scientific literature and by treatment specialists. Interviews were recorded, transcribed and translated into English and French. Results Fifteen content dimensions were derived from the qualitative analysis, refined and fitted to four domains: (1) Physical Health included: fatigue, pain, sleep, sexual impairment and physical activity; (2) Mental Health: psychological distress, psychosocial impact, and cognition; (3) Social Health: support, stigma, social activity, substance use; (4) Treatment: management, side effects, and fear of treatment failure. The impact of some dimensions extended beyond their primary domain including: physical activity, cognition, sleep, sexual impairment, and the three treatment dimensions. A bank of 300 items was constructed to reflect patient reports and, following expert review, reduced to a 72-item pilot questionnaire. Conclusion We present a conceptually valid multidimensional model of HCV-specific quality of life and the pilot survey instrument, PROQOL-HCV. The model is widely inclusive of the experience of hepatitis C and the first to include the treatment dimension.

Objectives To validate a new international questionnaire to assess Health-Related Quality of Life (HRQL) in patients living with HCV. Existing tools used in HCV were mostly generic and missing important concepts such as impact of the treatment. Methods 660 HCV mono-infected or HIV co-infected patients included in a cross-sectional survey in 3 countries (France [59%], Brazil [30%], and Australia [11%]) completed paper- or internet-based version of 3 HRQL questionnaires and symptom, sociodemographic and biomedical checklist. Psychometric item analysis and factor analysis were used to reduce the original 72-item PROQOL-HVC questionnaire. Reliability (Cronbach’s alpha), convergent validity (EQ-5D, SF-12, symptoms), and clinical validity (biological markers) were assessed on the final version using correlation and two-group comparison at a fixed 5% level. Results Sample characteristics: 57% men, 52 years, 80% vocational level and higher, 35% living alone. Regarding comorbidities and treatment status: 35% co-infected with VIH (95% under ART), 15% not treated, 25% undergoing interferon, 35% ribavirine, 43% Direct-Acting Antivirals (35% without associated interferon); 27% depressive (71% treated). The PROQOL-HCV questionnaire was reduced to 38 items spanning 7 dimensions scored on a 100-point scale: Physical Health (PH, 6 items, α=0.90), Emotional Health (EH, 9 items, α=0.93), Future Uncertainty (FU, 6 items, α=0.79), Intimate Relationships (IR, 3 items, α=0.86), Social Health (SH, 3 items, α=0.47), Cognitive Functioning (CF, 3 items, α=0.80), and Treatment Impact (TI, 8 items, α=0.61). Pearson correlations of PROQOL-HCV dimension with the EQ5-D (general health) and SF-12 mental and physical composites were in the acceptable range. The PH dimension was negatively correlated to the number of bothersome symptoms (p<0.001). Lower HRQL (PH, EH, CF) was reported in women (p<0.01), depressive patients (p<0.001), patients under interferon (p<0.01, except CF), patients without trea

Background Many northern-hemisphere forests are dominated by oaks. These species extend over diverse environmental conditions and are thus interesting models for studies of plant adaptation and speciation. The genomic toolbox is an important asset for exploring the functional variation associated with natural selection. Results The assembly of previously available and newly developed long and short sequence reads for two sympatric oak species, Quercus robur and Quercus petraea, generated a comprehensive catalog of transcripts for oak. The functional annotation of 91 k contigs demonstrated the presence of a large proportion of plant genes in this unigene set. Comparisons with SwissProt accessions and five plant gene models revealed orthologous relationships, making it possible to decipher the evolution of the oak genome. In particular, it was possible to align 9.5 thousand oak coding sequences with the equivalent sequences on peach chromosomes. Finally, RNA-seq data shed new light on the gene networks underlying vegetative bud dormancy release, a key stage in development allowing plants to adapt their phenology to the environment. Conclusion In addition to providing a vast array of expressed genes, this study generated essential information about oak genome evolution and the regulation of genes associated with vegetative bud phenology, an important adaptive traits in trees. This resource contributes to the annotation of the oak genome sequence and will provide support for forward genetics approaches aiming to link genotypes with adaptive phenotypes.

Purpose Symptoms which are found to cluster consistently can have synergistic effects on patient outcomes and therefore may serve to predict morbidity or disentangle disease progression from comorbid conditions. Self-report HIV-specific symptom and HRQL measures were jointly analyzed in HIV-positive patients under different antiretroviral treatment regimens. Methods The responses of N=365 patients from four countries to the 9-item Physical Health and Symptom dimension of the PROOQL-HIV questionnaire and an HIV Symptom checklist were analyzed. Item response modeling and multidimensional scaling were used to derive HRQL scores free of any differential item functioning related to gender and target language and to summarize symptom co-expression in patients under protease inhibitor treatment (PI, N=164 , 45 %) versus other medication (Non-PI). Results Women reported poorer HRQL ( p=0.037 ), and HRQL did not differ between the target languages of French, English, and Thai. Fatigue, muscular pain, or difficulties falling asleep was the most frequently reported symptoms >35 %). PI versus Non-PI patients exhibited different pattern of symptoms with lipodystrophy-related and gastrointestinal symptoms forming well-separated clusters in the PI group. A higher number of symptoms were associated with lower HRQL ( p<0.001 ), and patients taking PIs reported lower HRQL ( p=0.003 ). Patients in both groups who reported fatigue, sexual dysfunction, or several lipodystrophy-related symptoms had poorer quality of life. Conclusion The co-expression of symptoms and their relation to HRQL are important aspects for the monitoring of HIV treatments.

Electronic patient-reported outcomes (PRO) provide quick and usually reliable assessments of patients' health-related quality of life (HRQL). Objective: An electronic version of the Patient-Reported Outcomes Quality of Life-human immunodeficiency virus (PROQOL-HIV) questionnaire was developed, and its face validity and reliability were assessed using standard psychometric methods. Methods: A sample of 80 French outpatients (66% male, 52/79; mean age 46.7 years, SD 10.9) were recruited. Paper-based and electronic questionnaires were completed in a randomized crossover design (2-7 day interval). Biomedical data were collected. Questionnaire version and order effects were tested on full-scale scores in a 2-way ANOVA with patients as random effects. Test-retest reliability was evaluated using Pearson and intraclass correlation coefficients (ICC, with 95% confidence interval) for each dimension. Usability testing was carried out from patients' survey reports, specifically, general satisfaction, ease of completion, quality and clarity of user interface, and motivation to participate in follow-up PROQOL-HIV electronic assessments. Results: Questionnaire version and administration order effects (N=59 complete cases) were not significant at the 5% level, and no interaction was found between these 2 factors (P=.94). Reliability indexes were acceptable, with Pearson correlations greater than .7 and ICCs ranging from .708 to .939; scores were not statistically different between the two versions. A total of 63 (79%) complete patients' survey reports were available, and 55% of patients (30/55) reported being satisfied and interested in electronic assessment of their HRQL in clinical follow-up. Individual ratings of PROQOL-HIV user interface (85%-100% of positive responses) confirmed user interface clarity and usability. Conclusions: The electronic PROQOL-HIV introduces minor modifications to the original paper-based version, following International Society for Pharmacoeconomics a

No abstract available

Purpose Symptoms which are found to cluster consistently can have synergistic effects on patient outcomes and therefore may serve to predict morbidity or disentangle disease progression from comorbid conditions. Self-report HIV-specific symptom and HRQL measures were jointly analyzed in HIV-positive patients under different antiretroviral treatment regimens. Methods The responses of N=365 patients from four countries to the 9-item Physical Health and Symptom dimension of the PROOQL-HIV questionnaire and an HIV Symptom checklist were analyzed. Item response modeling and multidimensional scaling were used to derive HRQL scores free of any differential item functioning related to gender and target language and to summarize symptom co-expression in patients under protease inhibitor treatment (PI, N=164 , 45 %) versus other medication (Non-PI). Results Women reported poorer HRQL ( p=0.037 ), and HRQL did not differ between the target languages of French, English, and Thai. Fatigue, muscular pain, or difficulties falling asleep was the most frequently reported symptoms >35 %). PI versus Non-PI patients exhibited different pattern of symptoms with lipodystrophy-related and gastrointestinal symptoms forming well-separated clusters in the PI group. A higher number of symptoms were associated with lower HRQL ( p<0.001 ), and patients taking PIs reported lower HRQL ( p=0.003 ). Patients in both groups who reported fatigue, sexual dysfunction, or several lipodystrophy-related symptoms had poorer quality of life. Conclusion The co-expression of symptoms and their relation to HRQL are important aspects for the monitoring of HIV treatments.

Electronic patient-reported outcomes (PRO) provide quick and usually reliable assessments of patients' health-related quality of life (HRQL). Objective: An electronic version of the Patient-Reported Outcomes Quality of Life-human immunodeficiency virus (PROQOL-HIV) questionnaire was developed, and its face validity and reliability were assessed using standard psychometric methods. Methods: A sample of 80 French outpatients (66% male, 52/79; mean age 46.7 years, SD 10.9) were recruited. Paper-based and electronic questionnaires were completed in a randomized crossover design (2-7 day interval). Biomedical data were collected. Questionnaire version and order effects were tested on full-scale scores in a 2-way ANOVA with patients as random effects. Test-retest reliability was evaluated using Pearson and intraclass correlation coefficients (ICC, with 95% confidence interval) for each dimension. Usability testing was carried out from patients' survey reports, specifically, general satisfaction, ease of completion, quality and clarity of user interface, and motivation to participate in follow-up PROQOL-HIV electronic assessments. Results: Questionnaire version and administration order effects (N=59 complete cases) were not significant at the 5% level, and no interaction was found between these 2 factors (P=.94). Reliability indexes were acceptable, with Pearson correlations greater than .7 and ICCs ranging from .708 to .939; scores were not statistically different between the two versions. A total of 63 (79%) complete patients' survey reports were available, and 55% of patients (30/55) reported being satisfied and interested in electronic assessment of their HRQL in clinical follow-up. Individual ratings of PROQOL-HIV user interface (85%-100% of positive responses) confirmed user interface clarity and usability. Conclusions: The electronic PROQOL-HIV introduces minor modifications to the original paper-based version, following International Society for Pharmacoeconomics a

Maritime pine (Pinus pinasterAit.) is a widely distributed conifer species in Southwestern Europe and one of the most advanced models for conifer research. In the current work, comprehensive characterization of the maritime pine transcriptome was performed using a combination of two different next-generation sequencing platforms, 454 and Illumina. De novo assembly of the transcriptome provided a catalogue of 26 020 unique transcripts in maritime pine trees and a collection of 9641 full-length cDNAs. Quality of the transcriptome assembly was validated by RT-PCR amplification of selected transcripts for structural and regulatory genes. Transcription factors and enzyme-encoding transcripts were annotated. Furthermore, the available sequencing data permitted the identification of polymorphisms and the establishment of robust single nucleotide polymorphism (SNP) and simple-sequence repeat (SSR) databases for genotyping applications and integration of translational genomics in maritime pine breeding programmes. All our data are freely available at SustainpineDB, the P. pinaster expressional database. Results reported here on the maritime pine transcriptome represent a valuable resource for future basic and applied studies on this ecological and economically important pine species. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Background The health-related quality of life (HRQL) of people living with HIV infection is an important consideration in HIV management. The PROQOL-HIV psychometric instrument was recently developed internationally as a contemporary, discriminating HIV-HRQL measure incorporating influential emotional dimensions such as stigma. Here we present the first within-country results of PROQOL-HIV using qualitative and quantitative data collected from a West Australian cohort who participated in the development and validation of PROQOL-HIV, and provide a comprehensive picture of HRQL in our setting. Methods We carried out a secondary analysis of data from Australian patients who participated in the international study: 15 in-depth interviews were conducted and 102 HRQL surveys using the PROQOL-HIV instrument and a symptom questionnaire were administered. We employed qualitative methods to extract description from the interview data and linear regression for exploration of the composite and sub-scale scores derived from the survey. Results Interviews revealed the long-standing difficulties of living with HIV, particularly in the domains of intimate relationships, perceived stigma, and chronic ill health. The novel PROQOL-HIV instrument discriminated impact of treatment via symptomatology, pill burden and treatment duration. Patients demonstrated lower HRQL if they were: newly diagnosed (p=0.001); naive to anti-retroviral treatment (p=0.009); reporting depression, unemployment or a high frequency of adverse symptoms, (all p<0.001). Total HRQL was notably reduced by perceived stigma with a third of surveyed patients reporting persistent fears of both disclosing their HIV status and infecting others. Conclusions The analysis showed that psychological distress was a major influence on HRQL in our cohort. This was compounded in people with poor physical health which in turn was associated with unemployment and depression. People with HIV infection are living longer and residual s

Background The health-related quality of life (HRQL) of people living with HIV infection is an important consideration in HIV management. The PROQOL-HIV psychometric instrument was recently developed internationally as a contemporary, discriminating HIV-HRQL measure incorporating influential emotional dimensions such as stigma. Here we present the first within-country results of PROQOL-HIV using qualitative and quantitative data collected from a West Australian cohort who participated in the development and validation of PROQOL-HIV, and provide a comprehensive picture of HRQL in our setting. Methods We carried out a secondary analysis of data from Australian patients who participated in the international study: 15 in-depth interviews were conducted and 102 HRQL surveys using the PROQOL-HIV instrument and a symptom questionnaire were administered. We employed qualitative methods to extract description from the interview data and linear regression for exploration of the composite and sub-scale scores derived from the survey. Results Interviews revealed the long-standing difficulties of living with HIV, particularly in the domains of intimate relationships, perceived stigma, and chronic ill health. The novel PROQOL-HIV instrument discriminated impact of treatment via symptomatology, pill burden and treatment duration. Patients demonstrated lower HRQL if they were: newly diagnosed (p=0.001); naive to anti-retroviral treatment (p=0.009); reporting depression, unemployment or a high frequency of adverse symptoms, (all p<0.001). Total HRQL was notably reduced by perceived stigma with a third of surveyed patients reporting persistent fears of both disclosing their HIV status and infecting others. Conclusions The analysis showed that psychological distress was a major influence on HRQL in our cohort. This was compounded in people with poor physical health which in turn was associated with unemployment and depression. People with HIV infection are living longer and residual s

Objectives: This study reports the psychometric validation of a new HIV/AIDS-specific health-related quality of life (HRQL) questionnaire, the Patient Reported Outcomes Quality of Life-HIV. The instrument was developed simultaneously across Europe, North and South America, Africa, Asia, and Australia to assess multidimensional quality of life impairments in the era of highly active antiretroviral therapy. Method: A cross-sectional study was performed in 8 countries. The pilot 70-item questionnaire was co-administered with the HIV symptoms index, the EQ-5D and Medical Outcomes Study-HIV questionnaires. Demographic and biomedical data were collected. After item analysis and reduction, convergent discriminant concurrent validity and known-group validity were examined. Internal consistency and reliability scores were assessed using Cronbach alpha and intraclass correlation. Results: The final sample of 791 patients was composed of 64% males (median age: 41 years, HIV diagnosis = 5 years), 13.8% were treatment naive. Item reduction yielded a 43-item form surveying 8 dimensions and 1 global health item that showed good convergent and discriminant validity and reliability (98% scaling success; Cronbach alphas 0.77-0.89). Correlations with EQ-5D and Medical Outcomes Study-HIV complied with concurrent validity expectations; likewise, correlations against the number of self-reported symptoms and depression showed good support for criterion validity. A test-retest study on French patients (n = 34) showed temporal stability (intraclass correlation coefficient = 0.86). Significant and meaningful differences of HRQL scores between countries were found. Conclusions: The Patient Reported Outcomes Quality of Life-HIV questionnaire is a valid and reliable instrument for assessing HRQL specific to HIV disease in different cultures and healthcare systems.

Objectives: This study reports the psychometric validation of a new HIV/AIDS-specific health-related quality of life (HRQL) questionnaire, the Patient Reported Outcomes Quality of Life-HIV. The instrument was developed simultaneously across Europe, North and South America, Africa, Asia, and Australia to assess multidimensional quality of life impairments in the era of highly active antiretroviral therapy. Method: A cross-sectional study was performed in 8 countries. The pilot 70-item questionnaire was co-administered with the HIV symptoms index, the EQ-5D and Medical Outcomes Study-HIV questionnaires. Demographic and biomedical data were collected. After item analysis and reduction, convergent discriminant concurrent validity and known-group validity were examined. Internal consistency and reliability scores were assessed using Cronbach alpha and intraclass correlation. Results: The final sample of 791 patients was composed of 64% males (median age: 41 years, HIV diagnosis = 5 years), 13.8% were treatment naive. Item reduction yielded a 43-item form surveying 8 dimensions and 1 global health item that showed good convergent and discriminant validity and reliability (98% scaling success; Cronbach alphas 0.77-0.89). Correlations with EQ-5D and Medical Outcomes Study-HIV complied with concurrent validity expectations; likewise, correlations against the number of self-reported symptoms and depression showed good support for criterion validity. A test-retest study on French patients (n = 34) showed temporal stability (intraclass correlation coefficient = 0.86). Significant and meaningful differences of HRQL scores between countries were found. Conclusions: The Patient Reported Outcomes Quality of Life-HIV questionnaire is a valid and reliable instrument for assessing HRQL specific to HIV disease in different cultures and healthcare systems.

To develop a conceptual framework demonstrating the impact of Hepatitis C (HCV) and treatment on health-related quality of life (HRQL).

Health-related quality of life (HRQL) is modulated by the type and frequency of symptoms experienced in daily life. Such a relationship is likely determined in part by treatment regimen and health care system. We studied how symptoms reported by HIV patients under PI- vs. NNTI-based HAART relate to different HRQL dimensions on the PROQOL-HIV questionnaire.

OBJECTIVES: The PROQOL-HIV questionnaire was developed to measure the health-related quality-of-life (HRQL) of People living with HIV/AIDS (PLWHA) in different cultures in the highly-active antiretroviral therapy era. This study presents the psychometric validation and the conceptual model: the psychosocial and clinical factors impacting on HRQL. METHODS: 830 patients were included in a cross-sectional survey in 8 countries: Australia, Brazil, Cambodia, China, France, Senegal, Thailand and USA. Item reduction was based on content, distribution of responses and factorial analysis. Reliability, construct and clinical validity with reference to biological markers and socio-demographic data were assessed. RESULTS: The 39-item questionnaire (and 4 individual items including Care Satisfaction and Financial Impact) demonstrates consistent psychometric properties (60% variance explained, Cronbach’s alpha above 0.8, intrascale correlations above 0.5). Concurrent validity was demonstrated (MOSHIV, EQ-5D). From 9 dimensions, 4 subscores were derived: Physical Health and Symptoms, Treatment Impact, Social and Intimate Relationships, Emotional Distress. Significant differences in HRQL scores according to symptoms, comorbidities, CD4 and CDC stage support our endpoint model. PROQOL-HIV dimensionality across countries is consistent with previous qualitative research. Western countries (early diagnosis and treatment, higher income) and emerging countries like Thailand and Brazil had better HRQL than China and Cambodia. Chinese and Khmer patients had lower HRQL scores (p < 0.001), particularly on physical health and symptoms, health concerns, and stigma dimension, which was highest in Senegal. Between-country differences are also reflected by significant correlations between PROQOL scores and external factors: frequency of symptoms (higher in Cambodia, China and Thailand), omorbidities (higher frequency of psychiatric disorders in Cambodia), and CD4 count (low in Chinese and Khmer p