Heat shock protein 60 reactive T cells in juvenile idiopathic arthritis: what is new?

Juvenile idiopathic arthritis (JIA) is a disease characterized by chronic joint inflammation, caused by a deregulated immune response. In patients with JIA, heat shock proteins (HSPs) are highly expressed in the synovial lining tissues of inflamed joints. HSPs are endogenous proteins that are expressed upon cellular stress and are able to modulate immune responses. In this review, we concentrate on the role of HSPs, especially HSP60, in modulating immune responses in both experimental and human arthritis, with a focus on JIA. We will mainly discuss the tolerogenic immune responses induced by HSPs, which could have a beneficial effect in JIA. Overall, we will discuss the immune modulatory capacity of HSPs, and the underlying mechanisms of HSP60-mediated immune regulation in JIA, and how this can be translated into therapy

Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument

Contains fulltext : 80284.pdf (publisher's version ) (Closed access)PURPOSE: To compose a battery of instruments that provides a detailed assessment of health status (HS) in COPD but that is applicable and clinically meaningful in routine care. METHODS: In a previous study, we developed the Nijmegen Integral Assessment Framework (NIAF) that organizes existing tests and instruments by the sub-domains of HS they measure. Based on clinical and statistical criteria (correlation coefficients and Cronbach alpha's) we selected for each sub-domain instruments from the NIAF. A COPD-study group was used to determine c-scores, and two control groups were used to determine the score ranges indicating normal functioning versus clinically relevant problems for each sub-domain. Existing questionnaire completion software (TestOrganiser) was adapted to enhance clinical applicability. RESULTS: The NCSI measures eleven sub-domains of physiological functioning, symptoms, functional impairment, and quality of life. The TestOrganiser automatically processes the data and produces the graphical PatientProfileChart, which helps to easily interpret results. This envisages the problem areas and discrepancies between the different sub-domains. CONCLUSION: The NCSI provides a valid and detailed picture of a patient's HS within 15-25 min. In combination with the PatientProfileChart, the NCSI can be used perfectly in routine care as screening instrument and as a guide in patient-tailored treatment

Comprehensive self management and routine monitoring in chronic obstructive pulmonary disease patients in general practice: randomised controlled trial

OBJECTIVE To assess the long term effects of two different modes of disease management (comprehensive self management and routine monitoring) on quality of life (primary objective), frequency and patients' management of exacerbations, and self efficacy (secondary objectives) in patients with chronic obstructive pulmonary disease (COPD) in general practice. DESIGN 24 month, multicentre, investigator blinded, three arm, pragmatic, randomised controlled trial. SETTING 15 general practices in the eastern part of the Netherlands. PARTICIPANTS Patients with COPD confirmed by spirometry and treated in general practice. Patients with very severe COPD or treated by a respiratory physician were excluded. INTERVENTIONS A comprehensive self management programme as an adjunct to usual care, consisting of four tailored sessions with ongoing telephone support by a practice nurse; routine monitoring as an adjunct to usual care, consisting of 2-4 structured consultations a year with a practice nurse; or usual care alone (contacts with the general practitioner at the patients' own initiative). OUTCOME MEASURES The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory questionnaire total score. Secondary outcomes were chronic respiratory questionnaire domain scores, frequency and patients' management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system, and self efficacy measured with the COPD self-efficacy scale. RESULTS 165 patients were allocated to self management (n=55), routine monitoring (n=55), or usual care alone (n=55). At 24 months, adjusted treatment differences between the three groups in mean chronic respiratory questionnaire total score were not significant. Secondary outcomes did not differ, except for exacerbation management. Compared with usual care, more exacerbations in the self management group were managed with bronchodilators (odds ratio 2.81, 95% confidence interval 1.16 to 6.82) and with prednisolone, antibiotics, or both (3.98, 1.10 to 15.58). CONCLUSIONS Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice. Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group. TRIAL REGISTRATION Clinical trials NCT00128765.This study was funded by the Netherlands Organisation for Health Research and Development (ZonMw) and Partners in Care Solutions for COPD (PICASSO). The funding sources had no role in the design, conduct, or reporting of the stud

'Exacerbation-free time' to assess the impact of exacerbations in patients with chronic obstructive pulmonary disease (COPD):a prospective observational study

COPD exacerbations are commonly quantified as rate per year. However, the total amount of time a patient suffers from exacerbations may be stronger related to his or her disease burden than just counting exacerbation episodes. In this study, we examined the relationship between exacerbation frequency and exacerbation-free time, and their associations with baseline characteristics and health-related quality of life. A total of 166 COPD patients reported symptom changes during 12 months. Symptom-defined exacerbation episodes were correlated to the number of exacerbation-free weeks per year. Analysis of covariance was used to examine the effects of baseline characteristics on annual exacerbation frequency and exacerbation-free weeks, Spearman's rank correlations to examine associations between the two methods to express exacerbations and the Chronic Respiratory Questionnaire (CRQ). The correlation between exacerbation frequency and exacerbation-free weeks was -0.71 (p < 0.001). However, among frequent exacerbators (i.e., ≥3 exacerbations/year, n = 113) the correlation was weak (r = -0.25; p < 0.01). Smokers had less exacerbation-free weeks than non-smokers (β = -5.709, p < 0.05). More exacerbation-free weeks were related to better CRQ Total (r = 0.22, p < 0.05), Mastery (r = 0.22, p < 0.05), and Fatigue (r = 0.23, p < 0.05) scores, whereas no significant associations were found between exacerbation frequency and CRQ scores. In COPD patients with frequent exacerbations, there is substantial variation in exacerbation-free time. Exacerbation-free time may better reflect the burden of exacerbations in patients with COPD than exacerbation frequency does

Health status in COPD cannot be measured by the St George's Respiratory Questionnaire alone: an evaluation of the underlying concepts of this questionnaire

Contains fulltext : 88421.pdf (publisher's version ) (Open Access)BACKGROUND: Improving patients' health status is one of the major goals in COPD treatment. Questionnaires could facilitate the guidance of patient-tailored disease management by exploring which aspects of health status are problematic, and which aspects are not. Health status consists of four main domains (physiological functioning, symptoms, functional impairment, and quality of life), and at least sixteen sub-domains. A prerequisite for patient-tailored treatment is a detailed assessment of all these sub-domains. Most questionnaires developed to measure health status consist of one or a few subscales and measure merely some aspects of health status. The question then rises which aspects of health status are measured by these instruments, and which aspects are not covered. As it is one of the most frequently used questionnaires in COPD, we evaluated which aspects of health status are measured and which aspects are not measured by the St George's Respiratory Questionnaire (SGRQ). METHODS: One hundred and forty-six outpatients with COPD participated. Correlations were calculated between the three sections of the SGRQ and ten sub-domains of the Nijmegen Integral Assessment Framework, covering Symptoms, Functional Impairment, and Quality of Life. As the SGRQ was not expected to measure physiological functioning, we did not include this main domain in the statistical analyses. Pearson's r > or = 0.70 was used as criterion for conceptual similarity. RESULTS: The SGRQ sections Symptoms and Total showed conceptual similarity with the sub-domain Subjective Symptoms (main domain Symptoms). The sections Activity, Impacts and Total were conceptual similar to Subjective Impairment (main domain Functional Impairment). The SGRQ sections were not conceptual similar to other sub-domains of Symptoms, Functional Impairment, nor to any sub-domain of Quality of Life. CONCLUSIONS: The SGRQ could facilitate the guidance of disease management in COPD only partially. The SGRQ is appropriately only for measuring problems in the sub-domains Subjective Symptoms and Subjective Impairment, and not for measuring problems in other sub-domains of health status, such as Quality of Life

Lifting the Shroud: Government, Investment Banks and Power in Post Financial Crisis United Kingdom - A critical deconstruction of the relationship between government and investment banks in the United Kingdom post global financial crisis (2007 – 2011)

The late 2000s Global Financial Crisis swept the advanced world and spilled into the developing, creating chaos in its wake. At the crux of the crisis were the high-risk activities of investment banks in the developed world – and especially United Kingdom. Since then, academic and public discussion has revolved around the questionable relationship between investment banks and government that resulted in subpar regulation and the costly bank ‘bailouts’ of 2008 and 2009. What this thesis will to do is holistically assess how the power relationship between British investment banks and the United Kingdom government has evolved since the crisis, utilising Doris Fuchs’ Three Dimensional Approach to Business Power and Governance and a wide array of research to address those structural, instrumental and discursive elements of business power

Differences in the experience of fatigue in patients and healthy controls: patients' descriptions

Contains fulltext : 51764.pdf ( ) (Open Access)BACKGROUND: The primary objective was to develop an adjective checklist, the Fatigue Quality List (FQL), aimed at assessing different perceptions of fatigue. METHODS: 961 participants filled out the FQL (28 adjectives). A component and confirmatory factor analyses were performed and psychometric properties were evaluated. Differences on factor scores between different patients' groups were investigated and pre- and post treatment scores were compared in demonstrating change of perceptions after treatment of fatigue. RESULTS: Four independent factors were found with adequate psychometric properties. Different perceptions were found between the patients' groups. Patients who were recovered after treatment for fatigue showed similar scores on the factors as healthy controls. CONCLUSION: The FQL appears to be a promising tool in measuring different perceptions of fatigue, which can be especially interesting for clinical practice

Carbon-neutral steel production and its impact on the economies of China, Japan, and Korea: A simulation with E3ME-FTT:steel

This is the final version. Available from MDPI via the DOI in this record. Data Availability Statement: Historical macro-economic data and exogenous projections used to develop econometric relationships in E3ME originate from various sources. See the Technical Manual for an overview [23]. The datasets behind FTT:Steel were compiled from various sources. Historical production mostly relies on the Steel Statistical Yearbooks published by the World Steel Association, available at https://worldsteel.org/steel-topics/statistics/steel-statistical-yearbook/, accessed on 2 February 2023. The technology cost dataset was compiled from various sources and the compiled dataset can be made available upon reasonable request. An overview is provided at https://www.researchgate.net/publication/348845183_Decarbonising_The_East_Asian_ Iron_and_Steel_Sector_In_2050_An_Analysis_Performed_By_E3ME-FTTSteel, accessed on 23 August 2022. The models (E3ME and FTT:Steel) used in this study are operated and owned by Cambridge Econometrics and therefore not publicly available. However, the code base of FTT:Steel will be made available as a stand-alone model in the near future.The iron and steel industry is a large emitter of CO2 globally. This is especially true for the iron and steel industries in China, Japan, and Korea due to their production volumes and the prevalence of carbon-based steel production. With few low-carbon and commercially available alternatives, the iron and steel industry is truly a hard-to-abate sector. Each of the countries of interest have committed to a net-zero future involving the mitigation of emissions from steel production. However, few studies have investigated the means by which to achieve decarbonization beyond the inclusion of price signalling policies (e.g., carbon tax or emission trading schemes). Here, we use E3ME-FTT:Steel to simulate technology diffusion in the ISI under several policy environments and we investigate the likely impacts on the wider economy. The results show that penalizing carbon intensive processes can incentivize a transition towards scrap recycling, but it is relatively unsuccessful in aiding the uptake of low carbon primary steelmaking. A combination of support and penalizing policies can achieve deep decarbonisation (>80% emission reduction compared with the baseline). Mitigating the emissions in the iron and steel industry can lead to economic benefits in terms of GDP (China: +0.8%; Japan: +1.3%; Korea: +0.1%), and employment (Japan: +0.7%; Korea: +0.3%) with China, where job losses in the coal sector would negate job gains elsewhere, as the exception.Asia Research Project of Meijo Universit

Is a solar future inevitable?

This is the final version. Available from the Global Systems Institute, University of Exeter via the link in this recordDecarboni sation plans across the globe require zerocarbon energy sources to be widely deployed by 2050 or 2060. Solar energy is the most widely available energy resource on Earth, and its economic attractiveness is improving fast in a cycle of increasing investmen ts. Here we use datadriven conditional technology and economic forecasting modelling to determine which zero carbon power sources could become dominant worldwide. We find that, due to technological trajectories set in motion by past policy, a global solar tipping point may have passed where solar energy gradually comes to dominate global electricity markets, even without additional climate policies. Uncertainties arise, however, over grid stability in a renewables dominated power system, the availability o f sufficient finance in the Global South, the capacity of supply chains and political resistance from regions that lose employment. Policies resolving these barriers may be more effective than price instruments to accelerate the transition to clean energy. 3European Union Horizon 2020UK Department for Business, Energy and Industrial Strategy (BEIS

Effects of training and albuterol on pain and fatigue in facioscapulohumeral muscular dystrophy

Contains fulltext : 51802.pdf (publisher's version ) (Closed access)BACKGROUND : We recently reported a randomised controlled trial on the efficacy of strength training and the beta2-adrenergic agonist albuterol in patients with facioscapulohumeral muscular dystrophy (FSHD). Strength training and albuterol appeared safe interventions with limited positive effect on muscle strength and volume. We concurrently explored the prevalence and the characteristics of pain and fatigue in the participating FSHD patients, because these are probably underreported but clinically relevant symptoms in this disorder. Next, we studied the effects of albuterol and strength training on pain, experienced fatigue, health-related functional status and psychological distress. METHODS : Sixty-five patients were randomised to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks, albuterol (sustained-release, 8 mg bid) was added in a randomised, double-blind, placebo-controlled design. Outcomes comprised self-reported pain, experienced fatigue, functional status and psychological distress obtained with validated questionnaires at 52 weeks. RESULTS : Eighty percent of patients reported chronic persistent or periodic, multifocal pains. Thirty-four percent of the participants were severely fatigued. Strength training and albuterol failed to have a significant effect on all outcomes. CONCLUSIONS : Pain and fatigue are important features in FSHD. Strength training and albuterol do not have a positive or negative effect on pain, experienced fatigue, functional status and psychological distress