The uniting of Europe and the foundation of EU studies: revisiting the neofunctionalism of Ernst B. Haas

This article suggests that the neofunctionalist theoretical legacy left by Ernst B. Haas is somewhat richer and more prescient than many contemporary discussants allow. The article develops an argument for routine and detailed re-reading of the corpus of neofunctionalist work (and that of Haas in particular), not only to disabuse contemporary students and scholars of the normally static and stylized reading that discussion of the theory provokes, but also to suggest that the conceptual repertoire of neofunctionalism is able to speak directly to current EU studies and comparative regionalism. Neofunctionalism is situated in its social scientific context before the theory's supposed erroneous reliance on the concept of 'spillover' is discussed critically. A case is then made for viewing Haas's neofunctionalism as a dynamic theory that not only corresponded to established social scientific norms, but did so in ways that were consistent with disciplinary openness and pluralism

Is there evidence for accelerated polyethylene wear in uncemented compared to cemented acetabular components? A systematic review of the literature

Joint arthroplasty registries show an increased rate of aseptic loosening in uncemented acetabular components as compared to cemented acetabular components. Since loosening is associated with particulate wear debris, we postulated that uncemented acetabular components demonstrate a higher polyethylene wear rate than cemented acetabular components in total hip arthroplasty. We performed a systematic review of the peer-reviewed literature, comparing the wear rate in uncemented and cemented acetabular components in total hip arthroplasty. Studies were identified using MEDLINE (PubMed), EMBASE and the Cochrane Central Register of Controlled Trials. Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The search resulted in 425 papers. After excluding duplicates and selection based on title and abstracts, nine studies were found eligible for further analysis: two randomised controlled trials, and seven observational studies. One randomised controlled trial found a higher polyethylene wear rate in uncemented acetabular components, while the other found no differences. Three out of seven observational studies showed a higher polyethylene wear in uncemented acetabular component fixation; the other four studies did not show any differences in wear rates. The available evidence suggests that a higher annual wear rate may be encountered in uncemented acetabular components as compared to cemented components

Child resilience: Relationships between stress, adaptation and family functioning

Not availabl

The state of play: securities of childhood - insecurities of children

This article is broadly concerned with the positioning of children, both within and outside the subject area of International Relations. It considers the costs of an adult- 5 centric standpoint in security studies and contrasts this with investments made seemingly on behalf of children and their security. It begins by looking at how children and childhoods are constructed and contained - yet also defy categorization - at some cost to their protection. The many competing children and childhoods that are invoked in security discourses and partially sustain their victimcy are then illustrated. It is 10 argued that at their entry point into academia they are essentialized and sentimentalized. Power relations which subvert, yet also rely on children and childhoods can only be disrupted through a reconfiguration of politics and agency which includes an engagement with political literacy on a societal level and acknowledgement of the ubiquitous presence of war in all our live

Genotipagem do vírus da hepatite B de pacientes crônicos com resistência ao tratamento com lamivudina na Cidade de Ribeirão Preto, Estado de São Paulo

INTRODUCTION: Lamivudine is a nucleoside analogue that is used clinically for treating chronic hepatitis B infection. However, the main problem with prolonged use of lamivudine is the development of viral resistance to the treatment. Mutations in the YMDD motif of the hepatitis B virus DNA polymerase gene have been associated with resistance to drug therapy. So far, there have not been many studies in Brazil reporting on genotype-dependent development of resistance to lamivudine. Thus, the aim of the present study was to determine the possible correlation between a certain genotype and increased development of resistance to lamivudine among chronic hepatitis B patients. METHODS: HBV DNA in samples from 50 patients under lamivudine treatment was amplified by means of conventional PCR. Samples were collected at Hospital das Clínicas, FMRP-USP. The products were then sequenced and phylogenetic analysis was performed. RESULTS: Phylogenetic analysis revealed that 29 (58%) patients were infected with genotype D, 20 (40%) with genotype A and one (2%) with genotype F. Mutations in the YMDD motif occurred in 20% of the patients with genotype A and 27.6% of the patients with genotype D. CONCLUSIONS: Despite the small number of samples, our results indicated that mutations in the YMDD motif were 1.38 times more frequent in genotype D than in genotype A.INTRODUÇÃO: Lamivudina é um análogo de nucleosídeo clinicamente utilizado para o tratamento da infecção crônica pela hepatite B. Entretanto, o principal problema do uso prolongado da lamivudina é o desenvolvimento de resistência viral ao tratamento. Mutações no motivo YMDD no gene da DNA polimerase do vírus da hepatite B estão associados com a resistência a terapia medicamentosa. Até o presente momento, não há muitos estudos no Brasil que descrevem o desenvolvimento genótipo-dependente da resistência à lamivudina. Assim, o intuito do trabalho aqui descrito foi determinar a possível correlação entre um determinado genótipo e o desenvolvimento aumentado da resistência à lamivudina em pacientes com hepatite B crônica. MÉTODOS: O HBV DNA foi amplificado por PCR convencional a partir de 50 amostras coletadas de pacientes submetidos ao tratamento com lamivudina no Hospital das Clínicas- FMRP- USP. Posteriormente, os produtos foram seqüenciados e a análise filogenética foi realizada. RESULTADOS: A análise filogenética mostrou que 29 (58%) pacientes foram infectados com o genótipo D, 20 (40%) com o genótipo A e 1 (2%) com o genótipo F. Mutações no motivo YMDD ocorreu em 20% dos pacientes com genótipo A e 27,6% em pacientes do genótipo D. CONCLUSÕES: Apesar do baixo número de amostras, nossos resultados indicaram que mutações no motivo YMDD são 1,38 X mais frequentes no genótipo D em relação ao genótipo A.Universidade de São Paulo USP - FCFR

Measurements of in vivo intra-articular gentamicin levels from antibiotic loaded articulating spacers in revision total knee replacement

a b s t r a c t a r t i c l e i n f o Previous in vitro studies have found high levels of antibiotic release in the days immediately following implantation of antibiotic loaded articulating spacers. However there are relatively few data describing the elution profile beyond this immediate period. This study was designed to measure if gentamicin levels continue to be clinically therapeutic after an extended period following in vivo implantation. Twelve patients received a gentamicin loaded articulating spacer between a 1st and 2nd stage revision total knee arthroplasty. At the 2nd stage procedure synovial fluid and blood samples were collected and assayed for the presence of gentamicin. The second stage revision occurred at a median of 99 days following spacer insertion. The median intraarticular gentamicin levels were 0.46 mg/L (0.24 to 2.36 mg/L) which would be considered therapeutic. There were no cases of reinfection. In this study, preformed articulating spacers containing gentamicin provided therapeutic concentrations in the synovial fluid surrounding the joint throughout the period of implantation. These data confirm the observations from in vitro studies, where a prolonged elution profile was observed for such spacers

Outcomes after successful direct acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis

Abstract Direct-acting antivirals have become widely used for patients with chronic hepatitis C virus infection with decompensated cirrhosis. Virological responses are excellent and early improvements in liver function, at least in a proportion of patients, have been observed but the longer term impact of viral clearance on end-stage liver disease complications is unclear. Methods Prospective study of patients with decompensated cirrhosis who received 12 weeks of all-oral direct-acting antivirals through the English Expanded Access Programme. Endpoints were deaths, liver transplantation, hepatocellular carcinoma, serious decompensation events, sepsis or hospitalisations, and MELD scores between start of therapy to 15 months post treatment start. An untreated cohort of patients was retrospectively studied over 6 months for comparison. Results Amongst 317/406 patients who achieved sustained virological response at 24 weeks post-treatment, there were 9 deaths (3%), 17 new liver cancers (5%), 39 transplantations (12%) and 52 with serious decompensations (16%), over 15 months. When compared to the first six months from treatment start and to untreated patients, there was a reduction in incidence of decompensations [30/406 (7%) in months 6-15 and 72/406 (18%) in months 0-6 for treated patients vs 73/261 (28%) in untreated patients). There was no significant difference in liver cancer incidence (10/406 (2.5%) in months 6-15 and 17/406 (4%) in months 0-6 for treated patients vs 11/261 (4%) in untreated patients). Conclusions This study suggests that antiviral therapy in patients with decompensated cirrhosis led to prolonged improvement in liver function, with no evidence of paradoxical adverse impact nor increase in liver malignancy. Lay summary This is a report of a large group of patients in England who have hepatitis C virus (HCV) infection with advanced liver disease. They have been treated with new anti-HCV drugs, which cured the infection in the majority. This study looks at their outcomes a year following treatment, in terms of deaths, cancers and other complications of advanced liver disease. We conclude that in most patients anti-HCV treatment is beneficial even in advanced liver disease

Development of Cytomegalovirus (CMV) Immune Recovery Uveitis Is Associated with Th17 Cell Depletion and Poor Systemic CMV-Specific T Cell Responses

We tested whether impaired systemic immunoregulation and hyperactive immune responses are associated with an immune reconstitution inflammatory syndrome, CMV IRU. We found instead that T-regs in CMV IRU patients are functionally intact, while virus-specific immune responses and Th17 cells are compromise

Effect of scavenger receptor BI antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation

Hepatitis C virus (HCV) entry inhibitors have been hypothesized to prevent infection of the liver after transplantation. ITX5061 is a Scavenger Receptor B-I (SR-BI) antagonist that blocks HCV entry and infection in vitro. We assessed the safety and efficacy of ITX5061 to limit HCV infection of the graft. The study included 23 HCV infected patients undergoing liver transplantation. The first 13 "control" patients did not receive drug. The subsequent 10 patients received ITX5061 150 mg immediately pre- and post-transplant, and daily for 1 week thereafter. ITX5061 pharmacokinetics and plasma HCV RNA were quantified. Viral genetic diversity was measured by ultradeep pyrosequencing. ITX5061 was well tolerated with measurable plasma concentrations during therapy. Whilst the median HCV RNA reduction was greater in ITX treated patients at all time points in the first week after transplantation there was no difference in the overall change in the area over the HCV RNA curve in the 7-day treatment period. However, in genotype 1 infected patients treatment was associated with a sustained reduction in HCV RNA levels compared to the control group (area over the HCV RNA curve analysis, p=0.004). Ultradeep pyrosequencing revealed a complex and evolving pattern of HCV variants infecting the graft during the first week. ITX5061 significantly limited viral evolution where the median divergence between day 0 and day 7 was 3.5% in the control group compared to 0.1% in the treated group.CONCLUSIONS: ITX5061 reduces plasma HCV RNA post transplant notably in genotype 1 infected patients and slows viral evolution. Following liver transplantation the likely contribution of extrahepatic reservoirs of HCV necessitates combining entry inhibitors such as ITX5061 with inhibitors of replication in future studies. Clinicaltrials.gov NCT01292824. This article is protected by copyright. All rights reserved.</p

High Sustained Virologic Response Rates of Glecaprevir/Pibrentasvir in Patients With Dosing Interruption or Suboptimal Adherence

INTRODUCTION: Pangenotypic, all-oral direct-acting antivirals, such as glecaprevir/pibrentasvir (G/P), are recommended for treatment of hepatitis C virus (HCV) infection. Concerns exist about the impact on efficacy in patients with suboptimal adherence, particularly with shorter treatment durations. These post hoc analyses evaluated adherence (based on pill count) in patients prescribed 8- or 12-week G/P, the impact of nonadherence on sustained virologic response at post-treatment week 12 (SVR12), factors associated with nonadherence, and efficacy in patients interrupting G/P treatment. METHODS: Data were pooled from 10 phase 3 clinical trials of treatment-naive patients with HCV genotype 1-6 without cirrhosis/with compensated cirrhosis (treatment adherence analysis) and 13 phase 3 clinical trials of all patients with HCV (interruption analysis). RESULTS: Among 2,149 patients included, overall mean adherence was 99.4%. Over the treatment duration, adherence decreased (weeks 0-4: 100%; weeks 5-8: 98.3%; and weeks 9-12: 97.1%) and the percentage of patients with ≥80% or ≥90% adherence declined. SVR12 rate in the intention-to-treat (ITT) population was 97.7% (modified ITT SVR12 99.3%) and remained high in nonadherent patients in the modified ITT population (<90%: 94.4%-100%; <80%: 83.3%-100%). Psychiatric disorders were associated with <80% adherence, and shorter treatment duration was associated with ≥80% adherence. Among 2,902 patients in the interruption analysis, 33 (1.1%) had a G/P treatment interruption of ≥1 day, with an SVR12 rate of 93.9% (31/33). No virologic failures occurred. DISCUSSION: These findings support the impact of treatment duration on adherence rates and further reinforce the concept of "treatment forgiveness" with direct-acting antivirals.SCOPUS: ar.jinfo:eu-repo/semantics/publishe