Pain patterns in early rheumatoid arthritis

Study I: Widespread non-joint pain in early rheumatoid arthritis. Objective: The aim of the study was to assess the development of widespread non-joint pain (WNP) in a cohort of patients with early rheumatoid arthritis (RA), the associated health-related quality of life (HRQoL), and clinical and demographical risk factors for WNP. Methods: Incident cases with RA, from the Swedish population-based study Epidemiological Investigation of Rheumatoid Arthritis (EIRA), with a follow-up of at least 3 years, constituted the study population. WNP was defined as pain outside the joints in all four body quadrants and was assessed at the 3-year follow-up. Patients who reported WNP were compared to patients without WNP regarding HRQoL, measured by the Short Form-36, at 3 years, and clinical and demographical characteristics at the time of RA diagnosis. Results: A total of 749 patients constituted the study sample, of whom 25 were excluded after reporting having severe pain already before RA diagnosis. At the 3-year follow-up, 8% of the patients reported having WNP as well as statistically significant worse HRQoL. At the time of RA diagnosis, the patients with WNP had worse pain and pain-related features, while no difference was seen in the inflammatory parameters. Conclusion: WNP occurs in a substantial subset of patients with RA, also early in the course of the disease, and the HRQoL for these patients is significantly reduced. Patients who develop WNP at 3 years are distinguishable already at the time of diagnosis by displaying more pronounced pain ratings together with an average level of inflammatory disease activity. Study II: Unmet needs in rheumatoid arthritis: A subgroup of patients with high levels of pain, fatigue, and psychosocial distress 3 years after diagnosis. Objective: The study objective was to identify subgroups of patients with rheumatoid arthritis (RA) based on their health status 3 years after diagnosis and to assess potential associations to clinical presentation at diagnosis. Methods: This observational study included patients with RA with 3-year follow-up data from the Swedish Epidemiological Investigation of RA (EIRA) study, collected from 2011 to 2018. Hierarchical agglomerative cluster analysis, based on symptoms of pain, fatigue, sleep quality, mood disturbances, and overall health-related quality of life (HRQoL), was used to identify subgroups 3 years after diagnosis. Modified Poisson regression was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for the associations between the subgroups and patient characteristics at diagnosis. Results: A total of 1055 individuals constituted the study population, of whom 1011 had complete data on the clustering variables and were thereby eligible for analysis (73% women, median age 58 years). The following three clusters were identified: Cluster 1 (466 patients with good health status), Cluster 2 (398 patients in an intermediate group) and Cluster 3 (147 patients with high levels of pain and fatigue together with markedly impaired HRQoL). Cluster 3 was associated to higher baseline pain (RR: 3.71 [95% CI: 2.14-6.41]), global health (RR: 6.60 [95% CI: 3.53-12.33]) and Stanford Health Assessment Questionnaire (RR: 4.40 [95% CI: 2.46-7.87]), compared with cluster 1 (highest compared to lowest quartiles). An inverse association was seen for baseline swollen joint count (RR: 0.51 [95% CI: 0.34-0.85]). Conclusion: A subgroup of patients with RA experience high levels of pain, fatigue, and psychosocial distress 3 years after diagnosis. This subgroup displayed pronounced pain and functional disabilities already at diagnosis. Study III: Failure to reach treatment targets despite being in inflammatory remission among patients with early rheumatoid arthritis: Associations to the use of disease-modifying antirheumatic drugs. Objective: The study objective was to assess the proportion of patients with early rheumatoid arthritis (RA) who fail to reach formal treatment targets despite being in inflammatory remission, and to assess patterns of use of disease-modifying antirheumatic drugs (DMARD’s), in comparison with patients who are likewise in inflammatory remission but who reach the formal treatment targets. Methods: Patients newly diagnosed with RA were identified in the Swedish Rheumatology Quality Register (SRQ) (n = 11,784). Disease activity score based on 28 joints (DAS28) and DMARD-treatment were assessed at RA diagnosis and at 3-, 6-, 12-, and 24 months thereafter. Inflammatory remission was defined as: swollen joint count (0-28) = 0 and C-reactive protein <10 mg/L and normal erythrocyte sedimentation rate. Primary treatment targets were DAS28 remission (<2.6) and DAS28 low disease activity (LDA) (≤3.2). The proportion of patients in inflammatory remission who failed to reach the DAS28 targets was assessed at each follow-up visit. Patients who failed to reach DAS28 targets despite being in inflammatory remission were compared with patients in inflammatory remission who reached treatment targets, in terms of new DMARD starts during follow-up. Risk ratios (RR) and 95% confidence intervals (CI) for DMARD starts were estimated with Poisson regression. Results: Overall, 34%, 39%, 44%, and 47%, respectively, were in inflammatory remission at 3, 6, 12, and 24 months. Among these, 20%, 22%, 20%, and 19%, respectively, failed to reach DAS28 remission, and 8%, 9%, 7%, and 8%, respectively, failed to reach DAS28 LDA. Patients who failed to reach DAS28 targets despite being in inflammatory remission at the same visit were more likely to start a new DMARD treatment (RR (95% CI) at 6 months = 1.59 (1.29-1.96), 12 months = 1.52 (1.23-1.87)), and 24 months = 1.47 (1.20-1.80) when DAS28 remission was the target, and at 3 months = 1.35 (1.06-1.71), 6 months = 1.84 (1.42-2.39), 12 months = 1.71 (1.29-2.27), and 24 months = 1.78 (1.39-2.27) when DAS28 LDA was the target. The start of a new DMARD did not affect the likelihood of reaching the treatment target at the subsequent visit for these patients. Conclusion: A substantial proportion of patients with early RA who are in inflammatory remission fail to reach formal treatment targets. These patients might be at risk of overtreatment with DMARD’s

Violent victimisation of psychiatric patients: a Swedish case–control study

The intriguing question of how mental disorder and violence relate to each other has become an epic academic debate. During the last decades, there has been a change in direction of the debate on individuals with mental disorder, with a greater focus on violent victimization than violent behaviour towards others. Up until now, no Swedish study has investigated the frequency of violent behaviour among general psychiatric patients undergoing psychiatric treatment. Moreover, no Swedish study so far has investigated the relative risk of victimization in general psychiatric patients, in comparison to the general population. The aim of this dissertation was to investigate these issues and to validate the risk assessment method Classification of Violence Risk (COVR)™. Method: In study I, general psychiatric patients were recruited from two public psychiatric hospitals in Stockholm County (n=390). The control group consisted of gender- and age-matched subjects recruited from an annual national survey of living conditions, (conducted by Statistics Sweden) (n=1170). Studies II-IV consisted of prospective follow-ups on 331 patients. At baseline, clinical and socio-demographic variables were collected and a COVR assessment was conducted. Follow-up included telephone interviews with the patients and collaterals 10 and 20 weeks after baseline. Violent behaviour was self-reported and in addition, data was collected from a national criminal register. Results: Twenty percent of the patients had been victimised during the year preceding inclusion. The relative rate of victimization was six times higher in patients compared to controls. Women appeared to be most vulnerable with a 10-fold risk increase (Study I). The base rate of violent behaviour was 5.7% and a receiver operating curve analysis (ROC) showed that the area under the curve (AUC) for COVR was 0.77. The gender gap concerning violent behaviour among the general population was not replicated, since there was no significant gender difference with respect to violent acts 20 weeks after discharge. The predictive validity of the COVR software was comparable between females and males. There was an overlap between offenders and victims among psychiatric patients (Studies II-IV). Conclusions: The risk of being subjected to violence is high among Swedish psychiatric patients. The findings are most pronounced for female patients. Research, clinicians and social policy should target the problem of victimization. The base rate of violent behaviour towards others is relatively low among general psychiatric patients in Sweden. Therefore, prediction is difficult. Violent behaviour was uncommon in female as well as male patients and there were no gender differences. The COVR software could significantly predict violent behaviour and its validity was comparable to other risk assessment tools. COVR predicted violent behaviour with the same precision in both genders. The overlap between offenders and victims should be taken into account in both research and clinical settings

Systematic Review of Intelligent Tutoring Systems for Hard Skills Training in Virtual Reality Environments

Advances in immersive virtual reality (I-VR) technology have allowed for the development of I-VR learning environments (I-VRLEs) with increasing fidelity. When coupled with a sufficiently advanced computer tutor agent, such environments can facilitate asynchronous and self-regulated approaches to learning procedural skills in industrial settings. In this study, we performed a systematic review of published solutions involving the use of an intelligent tutoring system (ITS) to support hard skills training in an I-VRLE. For the seven solutions that qualified for the final analysis, we identified the learning context, the implemented system, as well as the perceptual, cognitive, and guidance features of the utilized tutoring agent. Generally, the I-VRLEs emulated realistic work environments or equipment. The solutions featured either embodied or embedded tutor agents. The agents’ perception was primarily based on either learner actions or learner progress. The agents’ guidance actions varied among the solutions, ranging from simple procedural hints to event interjections. Several agents were capable of answering certain specific questions. The cognition of the majority of agents represented variations on branched programming. A central limitation of all the solutions was that none of the reports detailed empirical studies conducted to compare the effectiveness of the developed training and tutoring solutions.Peer reviewe

Transmission of Stress-Induced Learning Impairment and Associated Brain Gene Expression from Parents to Offspring in Chickens

BACKGROUND: Stress influences many aspects of animal behaviour and is a major factor driving populations to adapt to changing living conditions, such as during domestication. Stress can affect offspring through non-genetic mechanisms, but recent research indicates that inherited epigenetic modifications of the genome could possibly also be involved. METHODOLOGY/PRINCIPAL FINDINGS: Red junglefowl (RJF, ancestors of modern chickens) and domesticated White Leghorn (WL) chickens were raised in a stressful environment (unpredictable light-dark rhythm) and control animals in similar pens, but on a 12/12 h light-dark rhythm. WL in both treatments had poorer spatial learning ability than RJF, and in both populations, stress caused a reduced ability to solve a spatial learning task. Offspring of stressed WL, but not RJF, raised without parental contact, had a reduced spatial learning ability compared to offspring of non-stressed animals in a similar test as that used for their parents. Offspring of stressed WL were also more competitive and grew faster than offspring of non-stressed parents. Using a whole-genome cDNA microarray, we found that in WL, the same changes in hypothalamic gene expression profile caused by stress in the parents were also found in the offspring. In offspring of stressed WL, at least 31 genes were up- or down-regulated in the hypothalamus and pituitary compared to offspring of non-stressed parents. CONCLUSIONS/SIGNIFICANCE: Our results suggest that, in WL the gene expression response to stress, as well as some behavioural stress responses, were transmitted across generations. The ability to transmit epigenetic information and behaviour modifications between generations may therefore have been favoured by domestication. The mechanisms involved remain to be investigated; epigenetic modifications could either have been inherited or acquired de novo in the specific egg environment. In both cases, this would offer a novel explanation to rapid evolutionary adaptation of a population

Inheritance of Acquired Behaviour Adaptations and Brain Gene Expression in Chickens

Background: Environmental challenges may affect both the exposed individuals and their offspring. We investigated possible adaptive aspects of such cross-generation transmissions, and hypothesized that chronic unpredictable food access would cause chickens to show a more conservative feeding strategy and to be more dominant, and that these adaptations would be transmitted to the offspring. Methodology/Principal Findings: Parents were raised in an unpredictable (UL) or in predictable diurnal light rhythm (PL, 12:12 h light:dark). In a foraging test, UL birds pecked more at freely available, rather than at hidden and more attractive food, compared to birds from the PL group. Female offspring of UL birds, raised in predictable light conditions without parental contact, showed a similar foraging behavior, differing from offspring of PL birds. Furthermore, adult offspring of UL birds performed more food pecks in a dominance test, showed a higher preference for high energy food, survived better, and were heavier than offspring of PL parents. Using cDNA microarrays, we found that the differential brain gene expression caused by the challenge was mirrored in the offspring. In particular, several immunoglobulin genes seemed to be affected similarly in both UL parents and their offspring. Estradiol levels were significantly higher in egg yolk from UL birds, suggesting one possible mechanism for these effects. Conclusions/Significance: Our findings suggest that unpredictable food access caused seemingly adaptive responses in feeding behavior, which may have been transmitted to the offspring by means of epigenetic mechanisms, including regulation of immune genes. This may have prepared the offspring for coping with an unpredictable environment. Citation: Nätt D, Lindqvist N, Stranneheim H, Lundeberg J, Torjesen PA, et al. (2009) Inheritance of Acquired Behaviour Adaptations and Brain Gene Expression in Chickens. PLoS ONE 4(7): e6405. doi:10.1371/journal.pone.0006405 Editor: Tom Pizzari, University of Oxford, United Kingdom Received: March 26, 2009; Accepted: June 30, 2009; Published: July 28, 2009 Copyright: © 2009 Nätt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This project was funded by the Swedish Research Council (VR; www.vr.se; grant nrs 50280101 and 50280102) and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas; www.formas.se; grant no 221-2005-270). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the mauscript. Competing interests: The authors have declared that no competing interests exist.  Original Publication:Daniel Nätt, Niclas Lindqvist, Henrik Stranneheim, Joakim Lundeberg, Peter A. Torjesen and Per Jensen, Inheritance of Acquired Behaviour Adaptions and Brain Gene Expression in Chickens, 2009, PLoS ONE, (4), 7, e6405.http://dx.doi.org/10.1371/journal.pone.0006405Copyright: Author

Struggling for recognition and inclusion—parents' and pupils' experiences of special support measures in school

During the last decade an increasing use of differentiated support measures for pupils with special educational needs, indicative of a discrepancy between educational policies and practices, has been witnessed in Sweden. Another trend has been the increased use of medical diagnoses in school. The aim of this study was to explore the main concern of support given to pupils with special educational needs and how pupils and parents experience and handle this. Interviews were conducted with eight pupils in Grades 7–9—and their parents—at two compulsory schools in a city in northern Sweden. A grounded theory approach was used for analyzing the interview data. A conceptual model was generated illuminating the main concern of special support measures for pupils and parents. The core category of the model, struggling for recognition and inclusion, was related to two categories, which further described how this process was experienced and handled by the participants. These categories were labeled negotiating expertise knowledge within a fragmented support structure and coping with stigma, ambivalence, and special support measures. The developed conceptual model provides a deeper understanding of an ongoing process of struggle for recognition and inclusion in school as described by the pupils and parents

Implementing a Physician Roster Using Constraint Programming

A successful rostering of physicians to different activities demands satisfying the minimal allocation of physicians to each activity, following regulations and hospital guidelines in regard to workload, and adhering to the preferences of the physicians. Keeping track of all of the constraints, ensuring that they are not violated, is a complicated task, which is still often done manually. This thesis uses constraint programming to propose a general model to the problem, with which a solution can be found by incrementally tighten the constraints through an iterative interaction with a user. An implementation of the model was, to a great extent, successful in handling generated instances of these iterations

Implementing a Physician Roster Using Constraint Programming

A successful rostering of physicians to different activities demands satisfying the minimal allocation of physicians to each activity, following regulations and hospital guidelines in regard to workload, and adhering to the preferences of the physicians. Keeping track of all of the constraints, ensuring that they are not violated, is a complicated task, which is still often done manually. This thesis uses constraint programming to propose a general model to the problem, with which a solution can be found by incrementally tighten the constraints through an iterative interaction with a user. An implementation of the model was, to a great extent, successful in handling generated instances of these iterations

Performance Comparisons of IP Problem Formulation

When solving optimization problems, the importance of speed can not be emphasized enough for many organizations. One company encountered a major performance difference when solving a problem with the same integer programming solver, in two different locations. The difference was shown not to be caused by the environment of the solver, but rather a reformulation of the problem. However, the reformulation did not improve the performance of an expanded version of the problem. By analyzing and comparing the two versions one might be able to find the properties  of a problem which enables the reformulation to reduce the solving time. This in turn can be used to identify for which problems the reformulation should be applied to increase the speed at which they are solved

Implicit procedural textures as a means of saving texture memory

This thesis explores the possibility of exchanging regular textures with procedural textures. It focuses on classic procedural textures like different types of rock and sand. Most time is spent on implicit textures generation on a GPU, this means a limit to the types of algorithms that can be used. As such, much of the work focuses on noise implementations. The goal is to lower texture memory usage by changing regular sampled textures with procedural ones. In the end a few ways of creating textures with a satisfactory level of detail is suggested using a blend of regular textures and procedural ones.Validerat; 20101217 (root