Long-term persistence and adherence on urate-lowering treatment can be maintained in primary care-5-year follow-up of a proof-of-concept study

Objectives: To evaluate the persistence and adherence on urate-lowering treatment (ULT) in primary care 5 years after an initial nurse-led treatment of gout. Methods: One hundred gout patients initiated on up-titrated ULT between March and July 2010 were sent a questionnaire that elicited information on current ULT, reasons for discontinuation of ULT if applicable, medication adherence and generic and disease-specific quality-of-life measures in 2015. They were invited for one visit at which height and weight were measured and blood was collected for serum uric acid measurement. Results: Seventy-five patients, mean age 68.13 years ( s . d . 10.07) and disease duration 19.44 years ( s . d . 13), returned completed questionnaires. The 5-year persistence on ULT was 90.7% (95% CI 81.4, 91.6) and 85.3% of responders self-reported taking ULT ⩾6 days/week. Of the 65 patients who attended the study visit, the mean serum uric acid was 292.8 μmol/l ( s . d . 97.2). Conclusion: An initial treatment that includes individualized patient education and involvement in treatment decisions results in excellent adherence and persistence on ULT >4 years after the responsibility of treatment is taken over by the patient's general practitioner, suggesting that this model of gout management should be widely adopted

Changes in received quality of care for knee osteoarthritis after a multicomponent intervention in a general practice in Denmark.

Objective: First-line treatment for patients with knee osteoarthritis should ideally prescribe patient education, exercise, and if needed, weight loss. In practice, however, adjunctive treatments, including painkillers and referrals to specialists, are typically introduced before these measures. This study evaluated interventions to sustainably improve general practitioner delivered care for patients with knee osteoarthritis. Design: Comparison of impacts of knee osteoarthritis care during four half-year periods: before, 6, 12, and 18 months after primary intervention based on electronic medical records (EMR) and patient questionnaires. Setting: Danish general practitioners (GPs) treating 6240 patients. Participants: Four GPs, two GP trainees, and six staff members. Interventions: Six pre-planned primary interventions: patient leaflet, GP and staff educational session, knee osteoarthritis consultation, two functional tests monitoring patient function, EMR phrase aiding consultation, and waiting room advertisement and three supportive follow-up interventions. Main outcome measures: Usage of first-line and adjunctive treatment elements, the functional tests, and the EMR phrase. Results: Approximately 50 knee osteoarthritis cases participated in each of the four half-year periods. Primary interventions had only transient effects lasting <12 months on the knee osteoarthritis care. Functional tests and EMR phrases were used predominantly during the first 6 months, where a transient drop in the referral rate to orthopedics was observed. Use of educational elements was moderate and without significant change during follow-up. Conclusion: More routine use of the primary or inclusion of novel increased-adherence interventions is needed to sustainably improve care for knee osteoarthritis patients in Danish general practice

Composing individuals: ethnographic reflections on success and prestige in the British New Music Network

In contrast to established musicians, lesser-known composers have received scant attention in art music scholarship. This article, based on an ethnographic study, considers how a group of British composers construed ideas of success and prestige, which I analyse in terms of anthropological writings on exchange, Bourdieusian symbolic economies, and Foucauldian notions of disciplinary power. Prestige was ascribed to composers who created ‘interesting’ music, a category that eclipsed novelty as an aim. Individuality, enacted within a context of individualism, was key to assessing whether music was interesting. This individuality had to be tempered, structured, and embedded in the social norms of this and related ‘art worlds’. The article examines the social processes involved in creating this individuality, musical personality, and music considered interesting

Corporate ownership and control in Victorian Britain

© Economic History Society 2014. Using ownership and control data for 890 firm-years, this article examines the concentration of capital and voting rights in British companies in the second half of the nineteenth century. We find that both capital and voting rights were diffuse by modern-day standards. However, this does not necessarily mean that there was a modern-style separation of ownership from control in Victorian Britain. One major implication of our findings is that diffuse ownership was present in the UK much earlier than previously thought, and given that it occurred in an era with weak shareholder protection law, it somewhat undermines the influential law and finance hypothesis. We also find that diffuse ownership is correlated with large boards, a London head office, non-linear voting rights, and shares traded on multiple markets

Antibodies from rabbits immunized with HIV-1 clade B SOSIP trimers can neutralize multiple clade B viruses by destabilizing the envelope glycoprotein

The high HIV-1 viral diversity is a formidable hurdle for the development of an HIV-1 vaccine. Elicitation of broadly neutralizing antibodies (bNAbs) would offer a solution, but so far immunization strategies have failed to elicit bNAbs efficiently. To overcome the obstacles, it is important to understand the immune responses elicited by current HIV-1 envelope glycoprotein (Env) immunogens. To gain more insight, we characterized monoclonal antibodies (mAbs) isolated from rabbits immunized with Env SOSIP trimers based on the clade B isolate AMC008. Four rabbits that were immunized three times with AMC008 trimer developed robust autologous and sporadic low-titer heterologous neutralizing responses. Seventeen AMC008 trimer-reactive mAbs were isolated using antigen-specific single B cell sorting. Four of these mAbs neutralized the autologous AMC008 virus and several other clade B viruses. When visualized by electron microscopy, the complex of the neutralizing mAbs with the AMC008 trimer showed binding to the gp41 subunit with unusual approach angles and we observed that their neutralization ability depended on their capacity to induce Env trimer dissociation. Thus, AMC008 SOSIP trimer immunization induced clade B neutralizing mAbs with unusual approach angles with neutralizing effects that involve trimer destabilization. Optimizing these responses might provide an avenue to the induction of trimer dissociating bNAbs. IMPORTANCE Roughly 32 million people have died as a consequence of HIV-1 infection since the start of the epidemic and still 1.7 million people get infected with HIV-1 annually. Therefore, a vaccine to prevent HIV-1 infection is urgently needed. Current HIV-1 immunogens are not able to elicit the broad immune responses needed to provide protection against the large variation of HIV-1 strains circulating globally. A better understanding of the humoral immune responses elicited by immunization with state-of-the-art HIV-1 immunogens should facilitate the design of improved HIV-1 vaccine candidates. We identified antibodies with the ability to neutralize multiple HIV-1 viruses by destabilization of the envelope glycoprotein. Their weak but consistent cross-neutralization ability indicates the potential of this epitope to elicit broad responses. The trimer-destabilizing effect of the neutralizing mAbs combined with detailed characterization of the neutralization epitope can be used to shape the next generation of HIV-1 immunogens to elicit improved humoral responses after vaccination

Life-Cycle and Genome of OtV5, a Large DNA Virus of the Pelagic Marine Unicellular Green Alga Ostreococcus tauri

Large DNA viruses are ubiquitous, infecting diverse organisms ranging from algae to man, and have probably evolved from an ancient common ancestor. In aquatic environments, such algal viruses control blooms and shape the evolution of biodiversity in phytoplankton, but little is known about their biological functions. We show that Ostreococcus tauri, the smallest known marine photosynthetic eukaryote, whose genome is completely characterized, is a host for large DNA viruses, and present an analysis of the life-cycle and 186,234 bp long linear genome of OtV5. OtV5 is a lytic phycodnavirus which unexpectedly does not degrade its host chromosomes before the host cell bursts. Analysis of its complete genome sequence confirmed that it lacks expected site-specific endonucleases, and revealed the presence of 16 genes whose predicted functions are novel to this group of viruses. OtV5 carries at least one predicted gene whose protein closely resembles its host counterpart and several other host-like sequences, suggesting that horizontal gene transfers between host and viral genomes may occur frequently on an evolutionary scale. Fifty seven percent of the 268 predicted proteins present no similarities with any known protein in Genbank, underlining the wealth of undiscovered biological diversity present in oceanic viruses, which are estimated to harbour 200Mt of carbon

Role of the gap junctions in the contractile response to agonists in pulmonary artery from two rat models of pulmonary hypertension

International audienceBackground: Pulmonary hypertension (PH) is characterized by arterial vascular remodelling and alteration in vascular reactivity. Since gap junctions are formed with proteins named connexins (Cx) and contribute to vasoreactivity, we investigated both expression and role of Cx in the pulmonary arterial vasoreactivity in two rat models of PH. Methods: Intrapulmonary arteries (IPA) were isolated from normoxic rats (N), rats exposed to chronic hypoxia (CH) or treated with monocrotaline (MCT). RT-PCR, Western Blot and immunofluorescent labelling were used to study the Cx expression. The role of Cx in arterial reactivity was assessed by using isometric contraction and specific gap junction blockers. Contractile responses were induced by agonists already known to be involved in PH, namely serotonin, endothelin-1 and phenylephrine. Results: Cx 37, 40 and 43 were expressed in all rat models and Cx43 was increased in CH rats. In IPA from N rats only, the contraction to serotonin was decreased after treatment with 37-43Gap27, a specific Cx-mimetic peptide blocker of Cx 37 and 43. The contraction to endothelin-1 was unchanged after incubation with 40Gap27 (a specific blocker of Cx 40) or 37-43Gap27 in N, CH and MCT rats. In contrast, the contraction to phenylephrine was decreased by 40Gap27 or 37-43Gap27 in CH and MCT rats. Moreover, the contractile sensitivity to high potassium solutions was increased in CH rats and this hypersensitivity was reversed following 37-43Gap27 incubation. Conclusion: Altogether, Cx 37, 40 and 43 are differently expressed and involved in the vasoreactivity to various stimuli in IPA from different rat models. These data may help to understand alterations of pulmonary arterial reactivity observed in PH and to improve the development of innovative therapies according to PH aetiology