The lived experience of juvenile idiopathic arthritis in young people receiving etanercept

BACKGROUND: This study explores young people's daily experiences of living with Juvenile Idiopathic Arthritis (JIA) and their thoughts, beliefs and feelings related to the biological drug Etanercept, prescribed as part of their treatment. METHODS: An Interpretive Phenomenological approach was used to allow in-depth examinations of the young people's personal accounts of their lived experiences. Data were obtained from 6 young people between the ages of 10-13 years, from one tertiary institution's Paediatric Rheumatology department using audio-taped open-ended interviews. RESULTS: The transcripts yielded seven thousand words of data and two hundred significant statements, which were reduced to five themes; 1) Who understands me, 2) Medicines and injections, 3) Challenges of schooling and friendships, 4) Being different, and 5) Exclusion from sports. There were marked similarities between the young people's statements; however, there were also some striking differences. The theme 'Who understands me' yielded the biggest section of data, but also produced the biggest disparity between the young people. Two patients were very clear that they thought everyone 'understands', whilst two other patients held the belief that 'no one understood'. This paper explores these statements in further detail. CONCLUSIONS: The findings from this study can give healthcare professionals novel insight into the likely reactions to treatment for JIA and, through this, enable them to offer improved support, education and early intervention before these issues become a concern. This study also provides insight into the emotional resilience of young people with JIA

International Labor Standards, Soft Regulation, and National Government Roles

[Excerpt] In this article, we briefly describe the different approaches to the regulation of international labor standards, and then argue for a new role for national governments based on soft rather than hard regulation approaches. We argue that this new role shows potential for significantly enhancing progress in international labor standards, since it enables governments to articulate a position without having to deal with the enforcement issues that hard regulation mandates. We justify this new role for governments based on the increasing use of soft regulation in the international arena. Of course, this approach is not without its own problems, but given that existing approaches have all provided imperfect solutions to the problem of improving labor standards globally, re-visiting the role of national governments is in our view, highly important

Comparison of some Reduced Representation Approximations

In the field of numerical approximation, specialists considering highly complex problems have recently proposed various ways to simplify their underlying problems. In this field, depending on the problem they were tackling and the community that are at work, different approaches have been developed with some success and have even gained some maturity, the applications can now be applied to information analysis or for numerical simulation of PDE's. At this point, a crossed analysis and effort for understanding the similarities and the differences between these approaches that found their starting points in different backgrounds is of interest. It is the purpose of this paper to contribute to this effort by comparing some constructive reduced representations of complex functions. We present here in full details the Adaptive Cross Approximation (ACA) and the Empirical Interpolation Method (EIM) together with other approaches that enter in the same category

Cyclists in shared bus lanes: could there be unrecognised impacts on bus journey times?

This paper contributes to debates around improving the modelling of cycles, through an exploratory case study of bus–cycle interactions in London. This case study examines undocumented delays to buses caused by high volumes of cyclists in bus lanes. It has generally been assumed that cyclists do not noticeably delay buses in shared lanes. However, in many contexts where cyclists routinely share bus lanes, cyclist numbers have historically been low. In some such places, bus lanes are now seeing very high volumes of cyclists, far above those previously studied. This may have implications for bus – and cycle – journey times, but traditionally traffic modelling has not represented the effects of such interactions well. With some manipulation of parameters taken from models of other cities, the model described here demonstrates that cycles can cause significant delays to buses in shared lanes, at high cycling volumes. These delays are likely to become substantially larger if London's cycling demographic becomes more diverse, because cyclist speeds will decline. Hence bus journey time benefits may derive from separating cycles from buses, where cycle flows are high. The project also suggests that microsimulation modelling software, as typically used, remains problematic for representing cyclists

Open Problems on Central Simple Algebras

We provide a survey of past research and a list of open problems regarding central simple algebras and the Brauer group over a field, intended both for experts and for beginners.Comment: v2 has some small revisions to the text. Some items are re-numbered, compared to v

Maternal Serum Macrophage Inhibitory Cytokine-1 as a Biomarker for Ectopic Pregnancy in Women with a Pregnancy of Unknown Location

Ectopic pregnancy (EP) occurs in 1-2% of pregnancies, but is over-represented as a leading cause of maternal death in early pregnancy. It remains a challenge to diagnose early and accurately. Women often present in early pregnancy with a 'pregnancy of unknown location' (PUL) and the diagnosis and exclusion of EP is difficult due to a lack of reliable biomarkers. A serum biomarker able to clearly distinguish between EP and other pregnancy outcomes would greatly assist clinicians in diagnosing and safely managing PULs. This study evaluates the ability of maternal serum macrophage inhibitory cytokine-1 (MIC-1) levels to differentiate between EP and other pregnancy outcomes in women with a PUL.Sera were collected from 120 women with a PUL at first clinical presentation and assayed for MIC-1 by ELISA. Results were classified according to ultimate pregnancy outcome and the discriminatory ability of MIC-1 to diagnose EP was assessed.Serum MIC-1 levels were lower in women with histologically confirmed (definite) EP (dEP) (median 552 ng/mL; interquartile range (IQR) 414-693 ng/mL) compared to women with definite viable intra-uterine pregnancies (dVIUPs) (722 ng/mL; IQR 412-1122 ng/mL), and higher when compared to women with definite non-viable intra-uterine pregnancies (dNVIUPs) (465 ng/mL; IQR 341-675 ng/mL). MIC-1 levels were significantly higher in women with dEP compared to women whose PULs resolved without medical intervention (srPUL) (401 ng/mL; IQR 315-475 ng/mL) (p<0.003). There were no women with an ectopic pregnancy where serum MIC-1>1000 ng/mL.Serum MIC-1 levels in PUL were not able to categorically diagnose EP, however, MIC-1 could distinguish women with an EP that required medical intervention and those women whose PULs spontaneously resolved. A single serum MIC-1 measurement also excluded EP at levels above 1000 ng/mL. MIC-1 may play a role in the development of a combined assay of biomarkers for the diagnosis of EP

Shotgun Proteomics Identifies Serum Fibronectin as a Candidate Diagnostic Biomarker for Inclusion in Future Multiplex Tests for Ectopic Pregnancy

Ectopic pregnancy (EP) is difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a 'pregnancy of unknown location' (PUL), and diagnosis and exclusion of EP is challenging due to a lack of reliable biomarkers. The objective of this study was to identify novel diagnostic biomarkers for EP. Shotgun proteomics, incorporating combinatorial-ligand library pre-fractionation, was used to interrogate pooled sera (n = 40) from women undergoing surgery for EP, termination of viable intrauterine pregnancy and management of non-viable intrauterine pregnancy. Western blot was used to validate results in individual sera. ELISAs were developed to interrogate sera from women with PUL (n = 120). Sera were collected at time of first symptomatic presentation and categorized according to pregnancy outcome. The main outcome measures were differences between groups and area under the receiver operating curve (ROC). Proteomics identified six biomarker candidates. Western blot detected significant differences in levels of two of these candidates. ELISA of sera from second cohort revealed that these differences were only significant for one of these candidates, fibronectin. ROC analysis of ability of fibronectin to discriminate EP from other pregnancy outcomes suggested that fibronectin has diagnostic potential (ROC 0.6439; 95% CI 0.5090 to 0.7788; P>0.05), becoming significant when 'ambiguous' medically managed PUL excluded from analysis (ROC 0.6538; 95% CI 0.5158 to 0.7918; P<0.05). Fibronectin may make a useful adjunct to future multiplex EP diagnostic tests

Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum

Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology

Feedback Stabilization of a Class of Diagonal Infinite-Dimensional Systems with Delay Boundary Control

This paper studies the boundary feedback stabilization of a class of diagonal infinite-dimensional boundary control systems. In the studied setting, the boundary control input is subject to a constant delay while the open loop system might exhibit a finite number of unstable modes. The proposed control design strategy consists in two main steps. First, a finite-dimensional subsystem is obtained by truncation of the original Infinite-Dimensional System (IDS) via modal decomposition. It includes the unstable components of the infinite-dimensional system and allows the design of a finite-dimensional delay controller by means of the Artstein transformation and the pole-shifting theorem. Second, it is shown via the selection of an adequate Lyapunov function that 1) the finite-dimensional delay controller successfully stabilizes the original infinite-dimensional system; 2) the closed-loop system is exponentially Input-to-State Stable (ISS) with respect to distributed disturbances. Finally, the obtained ISS property is used to derive a small gain condition ensuring the stability of an IDS-ODE interconnection.Comment: Preprin

Similarities and Differences Between Juvenile and Adult Spondyloarthropathies

Spondyloarthritis (SpA) encompasses a broad spectrum of conditions occurring from childhood to middle age. Key features of SpA include axial and peripheral arthritis, enthesitis, extra-articular manifestations, and a strong association with HLA-B27. These features are common across the ages but there are important differences between juvenile and adult onset disease. Juvenile SpA predominantly affects the peripheral joints and the incidence of axial arthritis increases with age. Enthesitis is important in early disease. This review article highlights the similarities and differences between juvenile and adult SpA including classification, pathogenesis, clinical features, imaging, therapeutic strategies, and disease outcomes. In addition, the impact of the biological transition from childhood to adulthood is explored including the importance of musculoskeletal and immunological maturation. We discuss how the changes associated with adolescence may be important in explaining age-related differences in the clinical phenotype between juvenile and adult SpA and their implications for the treatment of juvenile SpA