Direct-acting antivirals are effective and safe in HCV/HIV-coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study.

Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/µL. HIV-RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV-RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon-free regimens with DAAs for post-LT recurrence of HCV infection in HIV-infected individuals were highly effective and well tolerated, with results comparable to those of HCV-monoinfected patients

Single-Image Depth Prediction Makes Feature Matching Easier

Good local features improve the robustness of many 3D re-localization and multi-view reconstruction pipelines. The problem is that viewing angle and distance severely impact the recognizability of a local feature. Attempts to improve appearance invariance by choosing better local feature points or by leveraging outside information, have come with pre-requisites that made some of them impractical. In this paper, we propose a surprisingly effective enhancement to local feature extraction, which improves matching. We show that CNN-based depths inferred from single RGB images are quite helpful, despite their flaws. They allow us to pre-warp images and rectify perspective distortions, to significantly enhance SIFT and BRISK features, enabling more good matches, even when cameras are looking at the same scene but in opposite directions.Comment: 14 pages, 7 figures, accepted for publication at the European conference on computer vision (ECCV) 202

A Ks-band-selected catalogue of objects in the ALHAMBRA survey

The original ALHAMBRA catalogue contained over 400,000 galaxies selected using a synthetic F814W image, to the magnitude limit AB(F814W)$\approx$24.5. Given the photometric redshift depth of the ALHAMBRA multiband data (=0.86) and the approximately $I$-band selection, there is a noticeable bias against red objects at moderate redshift. We avoid this bias by creating a new catalogue selected in the $K_s$ band. This newly obtained catalogue is certainly shallower in terms of apparent magnitude, but deeper in terms of redshift, with a significant population of red objects at $z>1$. We select objects using the $K_s$ band images, which reach an approximate AB magnitude limit $K_s \approx 22$. We generate masks and derive completeness functions to characterize the sample. We have tested the quality of the photometry and photometric redshifts using both internal and external checks. Our final catalogue includes $\approx 95,000$ sources down to $K_s \approx 22$, with a significant tail towards high redshift. We have checked that there is a large sample of objects with spectral energy distributions that correspond to that of massive, passively evolving galaxies at $z > 1$, reaching as far as $z \approx 2.5$. We have tested the possibility of combining our data with deep infrared observations at longer wavelengths, particularly Spitzer IRAC data

An analysis of ophthalmology services in Finland - has the time come for a Public-Private Partnership?

<p>Abstract</p> <p>Background</p> <p>We studied the prerequisites for Public-Private Partnership (PPP) in the context of the Finnish health care system and more specifically in the field of ophthalmology. PPP can be defined as a more or less permanent cooperation between public and private actors, through which the joint products or services are developed and in which the risks, costs and profits are shared.</p> <p>The Finnish eye care services system is heterogeneous with several different providers and can be regarded as sub-optimal in terms of overall resource use. What is more, the public sector is suffering from a shortage of ophthalmologists, which further decreases its possibilities to meet the present needs. As ophthalmology has traditionally been a medical specialty with a substantial private sector involvement in service provision, PPP could be a feasible policy to be used in the field. We thus ask the following research question: Is there, and to what extent, an open window of opportunity for PPP?</p> <p>Methods</p> <p>In addition to the previously published literature, the research data consisted of 17 thematic interviews with public and private experts in the field of ophthalmology. The analysis was conducted in two stages. First, a literature-based content analysis was used to explore the prerequisites for PPP. Second, Kingdon's (1995) multiple streams theory was used to study the opening of the window of opportunity for PPP.</p> <p>Results</p> <p>Public and private parties reported similar problems in the current situation but defined them differently. Also, there is no consensus on policy alternatives. Public opinion seems to be somewhat uncertain as to the attitudes towards private service providers. The analysis thus showed that although there are prerequisites for PPP, the time has not yet come for a Public-Private Partnership.</p> <p>Conclusion</p> <p>Should the window open fully, the emergence of policy entrepreneurs and an opportunity for a win-win situation between public and private organizations are required.</p

Manipulation of Plant Defense Responses by the Tomato Psyllid (Bactericerca cockerelli) and Its Associated Endosymbiont Candidatus Liberibacter Psyllaurous

Some plant pathogens form obligate relationships with their insect vector and are vertically transmitted via eggs analogous to insect endosymbionts. Whether insect endosymbionts manipulate plant defenses to benefit their insect host remains unclear. The tomato psyllid, Bactericerca cockerelli (Sulc), vectors the endosymbiont “Candidatus Liberibacter psyllaurous” (Lps) during feeding on tomato (Solanum lycopersicum L.). Lps titer in psyllids varied relative to the psyllid developmental stage with younger psyllids harboring smaller Lps populations compared to older psyllids. In the present study, feeding by different life stages of B. cockerelli infected with Lps, resulted in distinct tomato transcript profiles. Feeding by young psyllid nymphs, with lower Lps levels, induced tomato genes regulated by jasmonic acid (JA) and salicylic acid (SA) (Allene oxide synthase, Proteinase inhibitor 2, Phenylalanine ammonia-lyase 5, Pathogenesis-related protein 1) compared to feeding by older nymphs and adults, where higher Lps titers were found. In addition, inoculation of Lps without insect hosts suppressed accumulation of these defense transcripts. Collectively, these data suggest that the endosymbiont-like pathogen Lps manipulates plant signaling and defensive responses to benefit themselves and the success of their obligate insect vector on their host plant

Interacción entre clima y ocupación humana en la configuración del paisaje vegetal del Parque Nacional de Aigüestortes i Estany de Sant Maurici a lo largo de los últimos 15.000 años

The vegetation of the National Park of Aigüestortes i Estany de St Maurici is the result of an interaction between climate, plant community dynamics and the human occupation of the territory. The OCUPAproject aimed to reconstruct this interaction across the last millennia combining methods from palaeoecology and archaeology. The study focused primarily on the Sant Nicolau valley and built on the multidisciplinary analysis of the sedimentary archive of two lakes (Llebreta and Redó) and a number of archaeological sites located in shelters and outdoors. There is archaeological evidence of human presencesince 9000 yr cal BP, and a continuous record since 7500 yr cal BP. At early stages, humans transformed the surroundings of the shelters occupied and lithic tools indicate contacts with locations far away (i.e.,the Ebro plains). Since more than 3000 years ago, there has been human impact on the vegetation withoutinterruption until present. Initially, the impacts were mostly related to livestock: use of fire to open grazing lands, soil erosion and, during the medieval period, forestry and eutrophication of lakes. The agriculture impact in the lower part of the valley (e.g., Llebreta) occurred about 2100 yr ago, although some cereal grains and tools for harvesting have been found for the Neolithic. In the medieval period, the impact was higher than during the last centuries. In general, the changes in the human land use approximately follow the major changes in climate, but the specific causal link is likely related to the social and cultural dynamics of a broader territory since the Neolithic

Inducible liver-specific knockdown of protein tyrosine phosphatase 1B improves glucose and lipid homeostasis in adult mice.

AIMS/HYPOTHESIS Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signalling. Hepatic PTP1B deficiency, using the Alb-Cre promoter to drive Ptp1b deletion from birth in mice, improves glucose homeostasis, insulin sensitivity and lipid metabolism. The aim of this study was to investigate the therapeutic potential of decreasing liver PTP1B levels in obese and insulin-resistant adult mice. METHODS Inducible Ptp1b liver-specific knockout mice were generated using SA-Cre-ER(T2) mice crossed with Ptp1b floxed (Ptp1b(fl/fl)) mice. Mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity and insulin resistance. Tamoxifen was administered in the HFD to induce liver-specific deletion of Ptp1b (SA-Ptp1b(-/-) mice). Body weight, glucose homeostasis, lipid homeostasis, serum adipokines, insulin signalling and endoplasmic reticulum (ER) stress were examined. RESULTS Despite no significant change in body weight relative to HFD-fed Ptp1b(fl/fl) control mice, HFD-fed SA-Ptp1b(-/-) mice exhibited a reversal of glucose intolerance as determined by improved glucose and pyruvate tolerance tests, decreased fed and fasting blood glucose and insulin levels, lower HOMA of insulin resistance, circulating leptin, serum and liver triacylglycerols, serum NEFA and decreased HFD-induced ER stress. This was associated with decreased glycogen synthase, eukaryotic translation initiation factor-2α kinase 3, eukaryotic initiation factor 2α and c-Jun NH2-terminal kinase 2 phosphorylation, and decreased expression of Pepck. CONCLUSIONS/INTERPRETATION Inducible liver-specific PTP1B knockdown reverses glucose intolerance and improves lipid homeostasis in HFD-fed obese and insulin-resistant adult mice. This suggests that knockdown of liver PTP1B in individuals who are already obese/insulin resistant may have relatively rapid, beneficial therapeutic effects

Nitric oxide production and antioxidant function during viral infection of the coccolithophore Emiliania huxleyi

Emiliania huxleyi is a globally important marine phytoplankton that is routinely infected by viruses. Understanding the controls on the growth and demise of E. huxleyi blooms is essential for predicting the biogeochemical fate of their organic carbon and nutrients. In this study, we show that the production of nitric oxide (NO), a gaseous, membrane-permeable free radical, is a hallmark of early-stage lytic infection in E. huxleyi by Coccolithoviruses, both in culture and in natural populations in the North Atlantic. Enhanced NO production was detected both intra- and extra-cellularly in laboratory cultures, and treatment of cells with an NO scavenger significantly reduced viral production. Pre-treatment of exponentially growing E. huxleyi cultures with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) prior to challenge with hydrogen peroxide (H2O2) led to greater cell survival, suggesting that NO may have a cellular antioxidant function. Indeed, cell lysates generated from cultures treated with SNAP and undergoing infection displayed enhanced ability to detoxify H2O2. Lastly, we show that fluorescent indicators of cellular ROS, NO, and death, in combination with classic DNA- and lipid-based biomarkers of infection, can function as real-time diagnostic tools to identify and contextualize viral infection in natural E. huxleyi blooms

DNA methylation patterns of Brachypodium distachyon chromosomes and their alteration by 5-azacytidine treatment

Sequential immunolocalisation of 5-methylcytosine (5-MeC) and fluorescence in situ hybridisation with chromosome-specific BAC clones were performed on Brachypodium distachyon mitotic metaphase chromosomes to determine specific DNA methylation patterns of each chromosome in the complement. In the majority of cells examined, chromosomes Bd4 and Bd5, which bear the loci of 5S and 35S ribosomal DNA, respectively, had characteristic 5-MeC patterns. In contrast, the distribution of 5-MeC along the metacentric chromosome pairs Bd1, Bd2 and Bd3 was more variable. There were numerous differences in distribution of methylated sites between homologous chromosomes as well as between chromosome arms. Some chromosome sites, such as pericentromeric regions, were highly methylated in all chromosomes. Additionally, the influence of a hypomethylating agent, 5-azacytidine, on B. distachyon chromosome methylation patterns was confirmed. It was found that some chromosome pairs underwent demethylation more easily than others, but there was no apparent regularity in demethylation of particular chromosome segments

Practice change in chronic conditions care: an appraisal of theories

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Management of chronic conditions can be complex and burdensome for patients and complex and costly for health systems. Outcomes could be improved and costs reduced if proven clinical interventions were better implemented, but the complexity of chronic care services appears to make clinical change particularly challenging. Explicit use of theories may improve the success of clinical change in this area of care provision. Whilst theories to support implementation of practice change are apparent in the broad healthcare arena, the most applicable theories for the complexities of practice change in chronic care have not yet been identified. Methods We developed criteria to review the usefulness of change implementation theories for informing chronic care management and applied them to an existing list of theories used more widely in healthcare. Results Criteria related to the following characteristics of chronic care: breadth of the field; multi-disciplinarity; micro, meso and macro program levels; need for field-specific research on implementation requirements; and need for measurement. Six theories met the criteria to the greatest extent: the Consolidate Framework for Implementation Research; Normalization Process Theory and its extension General Theory of Implementation; two versions of the Promoting Action on Research Implementation in Health Services framework and Sticky Knowledge. None fully met all criteria. Involvement of several care provision organizations and groups, involvement of patients and carers, and policy level change are not well covered by most theories. However, adaptation may be possible to include multiple groups including patients and carers, and separate theories may be needed on policy change. Ways of qualitatively assessing theory constructs are available but quantitative measures are currently partial and under development for all theories. Conclusions Theoretical bases are available to structure clinical change research in chronic condition care. Theories will however need to be adapted and supplemented to account for the particular features of care in this field, particularly in relation to involvement of multiple organizations and groups, including patients, and in relation to policy influence. Quantitative measurement of theory constructs may present difficulties