Synovial membrane protein expression differs between juvenile idiopathic arthritis subtypes in early disease

Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood with a prevalence of around 1 in 1000. Without appropriate treatment it can have devastating consequences including permanent disability from joint destruction and growth deformities. Disease aetiology remains unknown. Investigation of disease pathology at the level of the synovial membrane is required if we want to begin to understand the disease at the molecular and biochemical level. The synovial membrane proteome from early disease-stage, treatment naive JIA patients was compared between polyarticular and oligoarticular subgroups.

Methods: Protein was extracted from 15 newly diagnosed, treatment naive JIA synovial membrane biopsies and separated by two dimensional fluorescent difference in-gel electrophoresis. Proteins displaying a two-fold or greater change in expression levels between the two subgroups were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry with expression further verified by Western blotting and immunohistochemistry.

Results: Analysis of variance analysis (P <= 0.05) revealed 25 protein spots with a two-fold or greater difference in expression levels between polyarticular and oligoarticular patients. Hierarchical cluster analysis with Pearson ranked correlation revealed two distinctive clusters of proteins. Some of the proteins that were differentially expressed included: integrin alpha 2b (P = 0.04); fibrinogen D fragment (P =0.005); collagen type VI (P = 0.03); fibrinogen gamma chain (P = 0.05) and peroxiredoxin 2 (P = 0.02). The identified proteins are involved in a number of different processes including platelet activation and the coagulation system.

Conclusions: The data indicates distinct synovial membrane proteome profiles between JIA subgroups at an early stage in the disease process. The identified proteins also provide insight into differentially perturbed pathways which could influence pathological events at the joint level.

New and Alternative Social Movements in Spain: The Left, Identity and Globalizing Processes

This collection offers a diachronic analytical study of new and alternative social movements in Spain from the democratic transition to the first decade of the 21st century, paying attention to anti-war mobilizations and the use of new technologies as a mobilizing resource. New and alternative social movements are studied through the prism of identified linkages among the left, movement identities and global processes in the Spanish context. Weight is given to certain important historical aspects, like Spain’s relatively recent authoritarian past, and certain value-added factors, such as the weak associationalism and materialism exhibited by the Spanish public. These are complemented by exploring insights offered by key theoretical approaches on social movements (political opportunities structures, resource mobilization). The volume covers established social movement cases (gender, peace, environmental movements) as well as those with a more explicit connection to the current context of global contestation (squatters’ and anti-globalization movements).

Identifying solutions to increase participation in physical activity interventions within a socio-economically disadvantaged community: a qualitative study

Background: There is an urgent need to increase population levels of physical activity, particularly amongst those who are socio-economically disadvantaged. Multiple factors influence physical activity behaviour but the generalisability of current evidence to such ‘hard-to-reach’ population subgroups is limited by difficulties in recruiting them into studies. Also, rigorous qualitative studies of lay perceptions and perceptions of community leaders about public health efforts to increase physical activity are sparse. We sought to explore, within a socio-economically disadvantaged community, residents’ and community leaders’ perceptions of physical activity (PA) interventions and issues regarding their implementation, in order to improve understanding of needs, expectations, and social/environmental factors relevant to future interventions.

Methods: Within an ongoing regeneration project (Connswater Community Greenway), in a socio-economically disadvantaged community in Belfast, we collaborated with a Community Development Agency to purposively sample leaders from public- and voluntary-sector community groups and residents. Individual semi-structured interviews were conducted with 12 leaders. Residents (n=113), of both genders and a range of ages (14 to 86 years) participated in focus groups (n=14) in local facilities. Interviews and focus groups were recorded, transcribed verbatim and analysed using a thematic framework.

Results: Three main themes were identified: awareness of PA interventions; factors contributing to intervention effectiveness; and barriers to participation in PA interventions. Participants reported awareness only of interventions in which they were involved directly, highlighting a need for better communications, both inter- and intra-sectoral, and with residents. Meaningful engagement of residents in planning/organisation, tailoring to local context, supporting volunteers, providing relevant resources and an ‘exit strategy’ were perceived as important factors related to intervention effectiveness. Negative attitudes such as apathy, disappointing experiences, information with no perceived personal relevance and limited access to facilities were barriers to people participating in interventions.

Conclusions: These findings illustrate the complexity of influences on a community’s participation in PA interventions and support a social-ecological approach to promoting PA. They highlight the need for cross-sector working, effective information exchange, involving residents in bottom-up planning and providing adequate financial and social support. An in-depth understanding of a target population’s perspectives is of key importance in translating PA behaviour change theories into practice.

Repackaging Prostate Cancer Support Group Research Findings: An e-KT Case Study

n the context of psychosocial oncology research, disseminating study findings to a range of knowledge “end-users” can advance the well-being of diverse patient subgroups and their families. This article details how findings drawn from a study of prostate cancer support groups were repackaged in a knowledge translation website—www.prostatecancerhelpyourself.ubc.ca—using Web 2.0 features. Detailed are five lessons learned from developing the website: the importance of pitching a winning but feasible idea, keeping a focus on interactivity and minimizing text, negotiating with the supplier, building in formal pretests or a pilot test with end-users, and completing formative evaluations based on data collected through Google™ and YouTube™ Analytics. The details are shared to guide the e-knowledge translation efforts of other psychosocial oncology researchers and clinicians.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Ecological impacts of invasive alien species along temperature gradients: testing the role of environmental matching

Invasive alien species (IAS) can cause substantive ecological impacts, and the role of temperature in mediating these impacts may become increasingly significant in a changing climate. Habitat conditions and physiological optima offer predictive information for IAS impacts in novel environments. Here, using meta-analysis and laboratory experiments, we tested the hypothesis that the impacts of IAS in the field are inversely correlated with the difference in their ambient and optimal temperatures. A meta-analysis of 29 studies of consumptive impacts of IAS in inland waters revealed that the impacts of fishes and crustaceans are higher at temperatures that more closely match their thermal growth optima. In particular, the maximum impact potential was constrained by increased differences between ambient and optimal temperatures, as indicated by the steeper slope of a quantile regression on the upper 25th percentile of impact data compared to that of a weighted linear regression on all data with measured variances. We complemented this study with an experimental analysis of the functional response - the relationship between predation rate and prey supply - of two invasive predators (freshwater mysid shrimp, Hemimysis anomala and Mysis diluviana) across relevant temperature gradients; both of these species have previously been found to exert strong community-level impacts that are corroborated by their functional responses to different prey items. The functional response experiments showed that maximum feeding rates of H. anomala and M. diluviana have distinct peaks near their respective thermal optima. Although variation in impacts may be caused by numerous abiotic or biotic habitat characteristics, both our analyses point to temperature as a key mediator of IAS impact levels in inland waters and suggest that IAS management should prioritize habitats in the invaded range that more closely match the thermal optima of targeted invaders.

Topology synthesis of three-legged spherical parallel manipulators employing Lie group theory

Driven by the requirements of the bionic joint or tracking equipment for the spherical parallel manipulators (SPMs) with three rotational degrees-of-freedom (DoFs), this paper carries out the topology synthesis of a class of three-legged SPMs employing Lie group theory. In order to achieve the intersection of the displacement subgroups, the subgroup characteristics and operation principles are defined in this paper. Mainly drawing on the Lie group theory, the topology synthesis procedure of three-legged SPMs including four stages and two functional blocks is proposed, in which the assembly principles of three legs are defined. By introducing the circular track, a novel class of three-legged SPMs is synthesized, which is the important complement to the existing SPMs. Finally, four typical examples are given to demonstrate the finite displacements of the synthesized three-legged SPMs.

Optical and magneto-optical properties of gold core cobalt shell magnetoplasmonic nanowire arrays

In this work we present core–shell nanowire arrays of gold coated with a nanometric layer of cobalt. Despite the extremely small Co volume, these core–shell nanowires display large magneto-optical activity and plasmonic resonance determined by the geometry of the structure. Therefore, we are able to tune both the plasmonic and magneto-optical response in the visible range. Through optical and ellipsometric measurements in transmission, and applying a magnetic field to the sample, it is possible to modulate the value of the phase angle (Del {Δ}) between the S and P polarised components. It was found that the core–shell sample produced an order of magnitude larger variation in Del with changing magnetic field direction, compared with hollow cobalt tubes. The enhancement of magneto optical properties through the plasmonic nature of the gold core is complemented with the ability to induce magnetic influence over optical properties via an externally applied field. Moreover, we demonstrate for the first time the ability to use the remanent magnetisation of the Co, in conjunction with the optical properties defined by the Au, to observe remanent optical states in this uniquely designed structure. This new class of magnetoplasmonic metamaterial has great potential in a wide range of applications, from bio-sensing to data storage due to the tuneable nature of multiple resonance modes and dual functionality.

PRECYSE: Cyber-attack Detection and Response for Industrial Control Systems

In this short paper, we present an integrated approach to detecting and mitigating cyber-attacks to modern interconnected industrial control systems. One of the primary goals of this approach is that it is cost effective, and thus whenever possible it builds on open-source security technologies and open standards, which are complemented with novel security solutions that address the specific challenges of securing critical infrastructures.

Dimensionality, Reliability and Validity of the InterRAI Depression Rating Scale in a Canadian Palliative Care Population

A reliable and valid instrument is needed to screen for depression in palliative patients. The interRAI Depression Rating Scale (DRS) is based on seven items in the interRAI Palliative Care instrument. This study is the first to explore the dimensionality, reliability and validity of the DRS in a palliative population. Palliative home care patients (n = 5,175) residing in Ontario (Canada) were assessed with the interRAI Palliative Care instrument. Exploratory factor analysis and Mokken scale analysis were used to identify candidate conceptual models and evaluate scale homogeneity/performance. Confirmatory factor analysis compared models using standard goodness-of-fit indices. Convergent and divergent validity were investigated by examining polychoric correlations between the DRS and other items. The “known groups” test determined if the DRS meaningfully distinguished among client subgroups. The non-hierarchical two factor model showed acceptable fit with the data, and ordinal alpha coefficients of 0.83 and 0.82 were observed for the two DRS subscales. Omega hierarchical (ωh) was 0.78 for the bifactor model, with the general factor explaining three quarters of the common variance. Despite the multidimensionality evident in the factor analyses, bifactor modelling and the Mokken homogeneity coefficient (0.34) suggest that the DRS is a coherent scale that captures important information on sub-constructs of depression (e.g., somatic symptoms). Higher correlations were seen between the DRS and mood and psychosocial well-being items, and lower correlations with functional status and demographic variables. The DRS distinguished in the expected manner for known risk factors (e.g., social support, pain). The results suggest that the DRS is primarily unidimensional and reliable for use in screening for depression in palliative care patients.

Phase Behavior of Reverse Poloxamers and Poloxamines in Water

The phase behavior of two types of poly(ethylene oxide)/poly(propylene oxide) (PEO/PPO) copolymers in aqueous solutions was studied by light scattering, viscometry, and infrared spectroscopy. Both the reverse poloxamer (Pluronic 10R5) and the star type poloxamine (Tetronic 90R4) have practically the same PEO/PPO ratio with their hydrophobic blocks (PPO) located in the outer part. The temperature-composition phase diagrams show that both 10R5 and 90R4 tend to form aggregates in water. Up to four different phases can be detected in the case of Tetronic 90R4 for each temperature: unimers, random networks, micellar networks, and macrophase separation. Viscometric and infrared measurements complemented the results obtained by light scattering and visual inspection.

Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: A prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial

Background: Primary results from the phase 3 ALSYMPCA trial showed that radium-223 dichloride (radium-223), a targeted α-emitter, improved overall survival compared with placebo and was well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases. We did a prespecified subgroup analysis from ALSYMPCA to assess the effect of previous docetaxel use on the efficacy and safety of radium-223. 

Methods: In the phase 3, randomised, double-blind ALSYMPCA trial, patients with symptomatic castration-resistant prostate cancer, at least two symptomatic bone metastases, no known visceral metastases, and who were receiving best standard of care were randomly assigned (2:1) via an interactive voice response system to receive six injections of radium-223 (50 kBq/kg intravenously) or matching placebo, with one injection given every 4 weeks. Patients had either received previous docetaxel treatment or were unsuitable for or declined docetaxel; previous docetaxel use (yes or no) was a trial stratification factor. We investigated the effect of previous docetaxel use on radium-223 treatment for the primary endpoint of overall survival, the main secondary efficacy endpoints, and safety. Efficacy analyses were done for the intention-to-treat population; safety analyses were done for the safety population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT00699751. 

Findings: Randomisation took place between June 12, 2008, and Feb 1, 2011. 526 (57%) of 921 randomly assigned patients had received previous docetaxel treatment (352 in the radium-223 group and 174 in the placebo group) and 395 (43%) had not (262 in the radium-223 group and 133 in the placebo group). Radium-223 prolonged median overall survival compared with placebo, irrespective of previous docetaxel use (previous docetaxel use, hazard ratio [HR] 0·70, 95% CI 0·56-0·88; p=0·002; no previous docetaxel use, HR 0·69, 0·52-0·92; p=0·01). The benefit of radium-223 compared with placebo was seen in both docetaxel subgroups for most main secondary efficacy endpoints; risk for time to time to first symptomatic skeletal event was reduced with radium-223 versus placebo in patients with previous docetaxel use, but the difference was not significant in those with no previous docetaxel use. 322 (62%) of 518 patients previously treated with docetaxel had grade 3-4 adverse events, compared with 205 (54%) of 383 patients without docetaxel. Patients who had previously been treated with docetaxel had a higher incidence of grade 3-4 thrombocytopenia with radium-223 than with placebo (31 [9%] of 347 patients vs five [3%] of 171 patients), whereas the incidence was similar between treatment groups among patients with no previous docetaxel use (seven [3%] of 253 patients vs one [1%] of 130 patients). The incidences of grade 3-4 anaemia and neutropenia were similar between the radium-223 and placebo groups within both docetaxel subgroups. 

Interpretation: Radium-223 is effective and well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases, irrespective of previous docetaxel use. 

Funding: Algeta ASA and Bayer HealthCare Pharmaceuticals.

A mixed methods study of the work patterns of full-time nurse practitioners in nursing homes

Aims and objectives: The aim of this study was to explore the integration of the nurse practitioner role in Canadian nursing homes to enable its full potential to be realised for resident and family care. The objective was to determine nurse practitioners' patterns of work activities. 

Background: Nurse practitioners were introduced in Canadian nursing homes a decade ago on a pilot basis. In recent years, government and nursing home sector interest in the role has grown along with the need for data to inform planning efforts. 

Design: The study used a sequential mixed methods design using a national survey followed by case studies. 

Methods: A national survey of nurse practitioners included demographic items and the EverCare Nurse Practitioner Role and Activity Scale. Following the survey, case studies were conducted in four nursing homes. Data were collected using individual and focus group interviews, document reviews and field notes. 

Results: Twenty-three of a target population of 26 nurse practitioners responded to the survey, two-thirds of whom provided services in nursing homes with one site and the remainder in nursing homes with as many as four sites. On average, nurse practitioners performed activities in communicator, clinician, care manager/coordinator and coach/educator subscales at least three to four times per week and activities in the collaborator subscale once a week. Of the 43 activities, nurse practitioners performed daily, most were in the clinician and communicator subscales. Case study interviews involved 150 participants. Findings complemented those of the survey and identified additional leadership activities. 

Conclusion: Nurse practitioners undertake a range of primary health care and advanced practice activities which they adapt to meet the unique needs of nursing homes. Relevance to clinical practice: Knowledge of work patterns enables nursing homes to implement the full range of nurse practitioner roles and activities to enhance resident and family care.

Addressing inequalities in physical activity participation: Implications for public health policy and practice

OBJECTIVE: To investigate the characteristics of those doing no moderate-vigorous physical activity (MVPA) (0days/week), some MVPA (1-4days/week) and sufficient MVPA (≥5days/week) to meet the guidelines in order to effectively develop and target PA interventions to address inequalities in participation.

METHOD: A population survey (2010/2011) of 4653 UK adults provided data on PA and socio-demographic characteristics. An ordered logit model investigated the covariates of 1) participating in no PA, 2) participating in some PA, and 3) meeting the PA guidelines. Model predictions were derived for stereotypical subgroups to highlight important policy and practice implications.

RESULTS: Mean age of participants was 45years old (95% CI 44.51, 45.58) and 42% were male. Probability forecasting showed that males older than 55years of age (probability=0.20; 95% CI 0.11, 0.28), and both males (probability=0.31; 95% CI 0.17, 0.45) and females (probability=0.38; 95% CI 0.27, 0.50) who report poor health are significantly more likely to do no PA.

CONCLUSIONS: Understanding the characteristics of those doing no MVPA and some MVPA could help develop population-level interventions targeting those most in need. Findings suggest that interventions are needed to target older adults, particularly males, and those who report poor health.

Large panel-survey data demonstrated country-level and ethnic minority variation in consent for health record linkage

Objectives
To investigate individual, household and country variation in consent to health record linkage.

Study Design and Setting
Data from 50,994 individuals aged 16-74 years recruited to wave 1 of a large UK general purpose household survey (January 2009 – December 2010) were analysed using multi-level logistic regression models.

Results
Overall, 70.7% of respondents consented to record linkage. Younger age, marriage, tenure, car ownership and education were all significantly associated with consent, though there was little deviation from 70% in subgroups defined by these variables. There were small increases in consent rates in individuals with poor health when defined by self-reported long term limiting illness (adjusted OR 1.11; 95%CIs 1.06, 1.16), less so when defined by General Health Questionnaire score (adjusted OR=1.05; 95%CIs 1.00, 1.10), but the range in absolute consent rates between categories was generally less than 10%. Larger differences were observed for those of non-white ethnicity who were 38% less likely to consent (adjusted OR 0.62; 95%CIs 0.59, 0.66). Consent was higher in Scotland than England (adjusted OR 1.17; 95%CIs 1.06, 1.29) but lower in Northern Ireland (adjusted OR 0.56; 95%CIs 0.50, 0.63).

Conclusion
The modest overall level of systematic bias in consent to record linkage provides reassurance for record linkage potential in general purpose household surveys. However, the low consent rates amongst non-white ethnic minority survey respondents will further compound their low survey participation rates. The reason for the country-level variation requires further study.