SHERPA-LEAP: a consortial model for the creation and support of academic institutional repositories

Purpose: To introduce SHERPA-LEAP, a model for the consortial development, population and support of eprints repositories. Design/methodology/approach: The organisational and technical structures of the consortium are described, including a brief summary of central and local resource responsibilities. Some positive and negative aspects of a consortial approach to institutional repository development, and of the SHERPA-LEAP model in particular, are identified. Outstanding issues and future plans for the consortium are outlined. Findings: SHERPA-LEAP is found to be succeeding in its aims of developing and supporting eprints repositories within the federal University of London. Some lessons learned from the SHERPA-LEAP approach are identified, but the SHERPA-LEAP consortial model is found to have been mostly beneficial to the participating institutions. In particular, the networking and experience-sharing opportunities which any consortial solution will facilitate are highly valued by the SHERPA-LEAP partners. Value: The case study is intended to help to inform the decision-making of institutions and consortia which are considering consortial solutions to the establishment and maintenance of institutional repositories

Analysis of the complete genome sequence of Cucumber mosaic virus strain K

The complete genome sequence of Cucumber mosaic virus strain K was determined by deep RNA sequencing. The tripartite genome consists of a 3,382-nucleotide (nt) RNA1, a 3,050-nt RNA2, and a 2,218-nt RNA3 segment. Phylogenetic analysis placed RNA1 and RNA2 in subgroup IB. However, RNA3 grouped with subgroup IA isolates, indicating a likely recombination event. © 2018 Moyle et al

In vivo passage of Salmonella Typhimurium results in minor mutations in the bacterial genome and increases in vitro invasiveness

International audienceAbstractEggs and raw or undercooked egg-containing food items are frequently identified as the bacterial source during epidemiolocal investigation of Salmonella outbreaks. Multi-locus variable number of tandem repeats analysis (MLVA) is a widely used Salmonella typing method enabling the study of diversity within populations of the same serotype. In vivo passage, however, has been linked with changes in MLVA type and more broadly the Salmonella genome. We sought to investigate whether in vivo passage through layer hens had an effect on MLVA type as well as the bacterial genome and whether any mutations affected bacterial virulence. Layer hens were infected with either Salmonella Typhimurium DT9 (03-24-11-11-523) as part of a single infection or were co-infected with an equal amount of Salmonella Mbandaka. Salmonella shedding in both single and co-infected birds was variable over the course of the 16-week experiment. Salmonella Typhimurium and Salmonella Mbandaka were identified in feces of co-infected birds. Salmonella colonies isolated from fecal samples were subtyped using MLVA. A single change in SSTR-6 was observed in Salmonella Typhimurium strains isolated from co-infected birds. Isolates of Salmonella Typhimurium of both the parent (03-24-11-11-523) and modified (03-24-12-11-523) MLVA type were sequenced and compared with the genome of the parent strain. Sequence analysis revealed that in vivo passaging resulted in minor mutation events. Passaged isolates exhibited significantly higher invasiveness in cultured human intestinal epithelial cells than the parent strain. The microevolution observed in this study suggests that changes in MLVA may arise more commonly and may have clinical significance

Assimilation to the Unmarked

Steel, JC ORCiD: 0000-0003-3608-7542Intravitreal injection of recombinant adeno-associated virus (AAV) might be an alternative approach for retinal gene therapy for certain applications. Although the jelly-like substance consists mainly of water, anti-viral antibodies against various viruses such as HIV or HSV have been observed in the human vitreous and anti-AAV neutralising antibodies (NAbs) in rhesus macaque vitreous have also been detected. In this study, the human vitreous humour was obtained from 70 post mortem unpaired eye cups and 10 paired eye cups from the Queensland Eye Bank. The transduction efficiency of 1-3 · 108 vcg of recombinant AAV-2, -5, -6 and -8 expressing secreted nanoluciferase was measured following transduction of ARPE-19 and Cos-7 cells at vitreous humour dilutions from 1:2 to 1:10 000. At vitreous humour dilution of 1:2, a reduction in transduction of over 50% was observed for AAV2 in 50.5% of samples and for AAV6 in 66.2% of samples. Only 23.2% of tested samples showed similar reduction in transduction efficiency for AAV5, and for AAV8 only 2.5% of samples inhibited transduction by 50% at 1:2 dilution. Differences in serum antibody levels have been previously observed in a similar Australian population, but low transduction inhibition at vitreous humour dilutions of 1:100 suggests that the concentration of NAbs within the vitreous humour is lower than in human serum. In addition, this study also reported an increase in transduction efficiency for AAV8 at highest vitreous humour concentrations, supporting previous reports that human albumin can increase AAV transduction but only in some serotypes

Developing a dementia-specific health state classification system for a new preference-based instrument AD-5D

© 2017 The Author(s). Background: With an ageing population, the number of people with dementia is rising. The economic impact on the health care system is considerable and new treatment methods and approaches to dementia care must be cost effective. Economic evaluation requires valid patient reported outcome measures, and this study aims to develop a dementia-specific health state classification system based on the Quality of Life for Alzheimer's disease (QOL-AD) instrument (nursing home version). This classification system will subsequently be valued to generate a preference-based measure for use in the economic evaluation of interventions for people with dementia. Methods: We assessed the dimensionality of the QOL-AD to develop a new classification system. This was done using exploratory and confirmatory factor analysis and further assessment of the structure of the measure to ensure coverage of the key areas of quality of life. Secondly, we used Rasch analysis to test the psychometric performance of the items, and select item(s) to describe each dimension. This was done on 13 items of the QOL-AD (excluding two general health items) using a sample of 284 residents living in long-term care facilities in Australia who had a diagnosis of dementia. Results: A five dimension classification system is proposed resulting from the three factor structure (defined as 'interpersonal environment', 'physical health' and 'self-functioning') derived from the factor analysis and two factors ('memory' and 'mood') from the accompanying review. For the first three dimensions, Rasch analysis selected three questions of the QOL-AD ('living situation', 'physical health', and 'do fun things') with memory and mood questions representing their own dimensions. The resulting classification system (AD-5D) includes many of the health-related quality of life dimensions considered important to people with dementia, including mood, global function and skill in daily living. Conclusions: The development of the AD-5D classification system is an important step in the future application of the widely used QOL-AD in economic evaluations. Future valuation studies will enable this tool to be used to calculate quality adjusted life years to evaluate treatments and interventions for people diagnosed with mild to moderate dementia

Deep subcutaneous application of poly-L-lactic acid as a filler for facial lipoatrophy in HIV-infected patients

Introduction: Facial lipoatrophy is a crucial problem of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Poly-L-lactic acid (PLA), provided as New-Fill(R)/Sculptra(TM), is known as one possible treatment option. In 2004 PLA was approved by the FDA as Sculptra(TM) for the treatment of lipoatrophy of the face in HIV-infected patients. While the first trials demonstrated relevant efficacy, this was to some extent linked to unwanted effects. As the depth of injection was considered relevant in this context, the application modalities of the preparation were changed. The preparation was to be injected more deeply into subcutaneous tissue, after increased dilution. Material and Methods: To test this approach we performed a pilot study following the new recommendations in 14 patients. Results: While the efficacy turned out to be about the same, tolerability was markedly improved. The increase in facial dermal thickness was particularly obvious in those patients who had suffered from lipoatrophy for a comparatively small period of time. Conclusion: With the new recommendations to dilute PLA powder and to inject it into the deeper subcutaneous tissue nodule formation is a minor problem. However, good treatment results can only be achieved if lipoatrophy is not too intense; treatment intervals should be about 2 - 3 weeks. Copyright (C) 2005 S. Karger AG, Basel

CCR5 antagonism impacts vaccination response and immune profile in HIV-1 infection.

Maraviroc (MVC) is the first licensed antiretroviral therapeutic agent to target a host cell surface molecule, and successful HIV-1 entry blockade by this C-C chemokine receptor type 5 (CCR5)-antagonist potentiates immunomodulation. We hypothesized that MVC intensification impacts immunization responses, T-cell phenotype, function and delayed type hypersensitivity (DTH) in HIV-1+ subjects. A 24-wk, double-blinded, placebo-controlled study of the addition of MVC to suppressive antiretroviral therapy in HIV-1+ persons was performed. Subjects received DTH tests, intramuscular tetanus, meningococcal and oral cholera immunizations. Antibody titers, T-cell function and phenotype were assessed. Of 157 patients referred, 47 were randomized 1:1; MVC:placebo. MVC enhanced meningococcal neo-immunization, blunted cholera response and expedited lymphoproliferation to tetanus boost, without affecting recall humoral response. Anti-HIV-1 group-specific antigen (Gag) and tetanus toxoid (TTox) function improved significantly, HIV-1-associated CD8 T-cell skewing normalized, and the percentage of late-stage and major histocompatibility complex (MHC) class II expressing CD4 T-cells increased. Activated CD4+ CD38+ human leukocyte antigen (HLA)-DR+ T-cells declined, and costimulation shifted to coinhibition. DTH was unchanged. Maraviroc intensification, through antagonism of the cell surface molecule CCR5, favorably influences immune profiles of HIV-1+ patients, supporting its immunomodulatory use in HIV-1 infection and potentially in other immunologically relevant settings

Covariation Among Vowel Height Effects on Acoustic Measures

Covariation among vowel height effects on vowel intrinsic fundamental frequency (IF0), voice onset time (VOT), and voiceless interval duration (VID) is analyzed to assess the plausibility of a common physiological mechanism underlying variation in these measures. Phrases spoken by 20 young adults, containing words composed of initial voiceless stops or /s/ and high or low vowels, were produced in habitual and voluntarily increased F0 conditions. High vowels were associated with increased IF0 and longer VIDs. VOT and VID exhibited significant covariation with IF0 only for males at habitua

Effects of recombinant human growth hormone on HIV-1-specific T-cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up

Background: Efficacious immune-based therapy in treated chronic HIV-1 infection requires the induction of virus-specific CD4+ T cells and subsequent maturation and maintenance of specific memory CD8+ T cells. Concomitant daily administration of recombinant human growth hormone (rhGH) with highly active antiretroviral therapy (HAART) was used in chronically infected patients with lipodystrophy in an attempt to reconstitute these virus-specific T-cell responses. Methods: Individuals with chronic HIV-1 infection on HAART were enrolled on a randomized, double-blinded, placebo-controlled study to receive rhGH therapy. We assessed HIV-1-specific proliferative CD4+ and interferon-gamma (IFN-γ)-producing CD8+ T-cell responses, quantified thymic output and proviral HIV-1 DNA at the following time points: baseline; after 12 weeks of rhGH therapy; at 24 weeks, after randomization into three groups [placebo weeks 12-24 (Group A), alternate-day dosing weeks 12-24 (Group B), and twice-per-week dosing weeks 12-24 (Group C)]; and at 48 weeks after all patients had received HAART alone for the final 24 weeks. Results: We found significant increases in both proliferative CD4+ and IFN-γ-producing CD8+ HIV-1-specific T-cell responses after daily administration of rhGH. This increase was focused on HIV-1 Gag-specific T-cell responses. Following subsequent randomisation into different dosing regimens, HIV-1-specific proliferative CD4+ T-cell responses declined in patients receiving less frequent dosing of rhGH, while virus-specific IFN-γ-producing CD8+ T-cell responses were maintained for longer periods of time. There was no significant change in thymic output and the cell-associated HIV-1 DNA remained stable in most patients. An increased anti-HIV-1 Nef-specific CD4+ T-cell proliferative response was correlated to a decrease in proviral load, and an increased HIV-1 Gag-specific IFN-γ-producing CD8+ T-cell response correlated with an increase in proviral load. Conclusion: The implication of these data is that daily dosing of rhGH with HAART, in addition to improving HIV-1-associated lipodystrophy, may reverse some of the T-lymphocyte dysfunction seen in most treated HIV-1-positive patients, in a dose-dependent manner. Such immune-based therapeutic strategies used in treated, chronic HIV-1 infection may enable the induction of virus-specific CD4+ T cells essential for the subsequent kick-start and expansion of virus-specific CD8+ T cells. © 2008 Herasimtschuk et al; licensee BioMed Central Ltd