Cardiovascular comorbidity in rheumatoid arthritis

This thesis is based on four different studies, all focusing on co-morbidities in rheumatoid arthritis. Diabetes mellitus is assessed as a risk factor for rheumatoid arthritis, the temporal relationship between ischemic heart disease and rheumatoid arthritis, and the extent of coronary stenosis in rheumatoid arthritis, is studied. The rationale for this is that patients with rheumatoid arthritis suffer an increased risk of ischemic heart disease that cannot be explained by traditional risk factors for cardiovascular disease but is hypothesized to be related to rheumatoid arthritis specific factors, that patients with rheumatoid arthritis have been reported to have a more severe atherosclerosis and that autoimmunity seem to aggregate. First, we studied diabetes mellitus and its relationship to rheumatoid arthritis using a population-based case-control study of rheumatoid arthritis. 1,419 patients with newly diagnosed rheumatoid arthritis and 1,674 age-, sex-, and residential area- matched controls were compared with respect to having diabetes mellitus prior to study inclusion. After validating self-reported information, 20 cases and 5 controls were classified as having type 1 diabetes mellitus and 42 cases and 46 controls as having type 2 diabetes mellitus. This study demonstrated that having type 1 diabetes mellitus conferred a seven-fold increased risk of developing a specific subset of rheumatoid arthritis defined by the presence of anti-citrullinated protein antibodies. This association depended to some extent on a genetic variant known to be involved in the pathogenesis of both type 1 diabetes and rheumatoid arthritis. We then studied the temporal relationship between ischemic heart disease and rheumatoid arthritis in two population-based cohorts of patients with rheumatoid arthritis and age-, sex-, and residential area-matched controls from the general population. The occurrence of ischemic heart disease before first symptom of rheumatoid arthritis (controls were given the same date as their matched case) in two population-based cohorts of rheumatoid arthritis (ncohort 1= 8,454, ncohort2=2,025) was compared to the occurrence of ischemic heart disease among controls (ncohort 1=42,267, ncohort2=2,760) and revealed that having a history of ischemic heart disease before onset of first symptom of rheumatoid arthritis was as common among cases as controls; approximately 6% of cases and 6% of controls in cohort 1 had experienced an ischemic heart disease before first symptom of rheumatoid arthritis. After excluding those who had had any ischemic heart disease at diagnosis of rheumatoid arthritis, we followed cohort 1 over time and found that there indeed was an increased risk of ischemic heart disease in patients with rheumatoid arthritis (n=7,469) compared with the general population (n=37,024) and that this increased risk was apparent and manifest already within a few years following rheumatoid arthritis diagnosis. Among individuals included in cohort 1 who underwent angiography with indication acute coronary syndrome (nrheumatoid arthritis=168, ncomparators=534) we found that although the development of ischemic heart disease was much more rapid in patients with rheumatoid arthritis, the extent of coronary stenosis was not related to rheumatoid arthritis. In summary, these results indicate that type 1 diabetes mellitus increases the risk of developing a specific type of rheumatoid arthritis defined by a specific auto-antibody, that the risk of ischemic heart disease in rheumatoid arthritis goes from not being elevated to 60% increased compared to the general population within a few years following diagnosis of rheumatoid arthritis, and that the extent of coronary stenosis in rheumatoid arthritis with acute coronary syndromes is very similar to that in controls with the same clinical symptoms of acute coronary syndrome. The rapid increase in risk of ischemic heart disease could be related to factors associated with rheumatoid arthritis

Design and development of a low-cost mask-type eye tracker to collect quality fixation measurements in the sport domain

The aim of the study was to build a low-cost mask-type eye tracker with accuracy and precision levels similar to those reported for commercial eye tracking devices. To this end, head-mounted hardware was designed and developed, while open-source software was modified for digital image capture, manipulation, and fixation analysis. An image recognition application was also included with different lighting scenarios. Moreover, parallax and viewing perspective errors were controlled to ensure the quality of data collection. The device was wireless and lightweight (99 g) to allow for natural movement and avoid participant discomfort. After calibration of a 9-target monocular grid, spatial accuracy and precision of the eye tracker was evaluated by 30 participants, at four different lighting setups, both before and after a climbing task. Validity tests showed high levels of accuracy in all conditions as evidenced by a systematic error for a 13-target grid of <0.5°. The reliability tests also showed consistent measurements with no differences in accuracy recorded between participants, lighting conditions, and visual behaviors for the pre- versus post-climbing task. These results suggest that the present eye tracker reports spatial accuracy similar to other commercial systems with levels of high quality. Altogether, this innovative user interface is suitable for research purposes and/or performance analysis in physical activity and sport-related activities. Also, features of this mask-type eye tracking system make it a suitable perceptual user interface to investigate human–computer interactions in a large number of other research fields including psychology, education, marketing, transportation, and medicine

Does Social Presence or the Potential for Interaction reduce Social Gaze in Online Social Scenarios? Introducing the "Live Lab" paradigm.

Research has shown that people’s gaze is biased away from faces in the real-world but towards them when they are viewed onscreen. Non-equivalent stimulus conditions may have represented a confound in this research however, as participants viewed onscreen stimuli as pre-recordings where interaction was not possible, compared to real-world stimuli which were viewed in real-time where interaction was possible. We assessed the independent contributions of online social presence and ability for interaction on social gaze by developing the “live lab” paradigm. Participants in three groups (N = 132) viewed a confederate either as a) a live webcam stream where interaction was not possible (one-way), b) a live webcam stream where an interaction was possible (two-way) or c) as a prerecording. Potential for interaction, rather than online social presence, was the primary influence on gaze behaviour: Participants in the pre-recorded and one-way conditions looked more to the face than those in the two-way condition, particularly when the confederate made “eye contact”. Fixation durations to the face were shorter when the scene was viewed live, particularly during a bid for eye contact Our findings support the dual function of gaze, but suggest that online social presence alone is not sufficient to activate social norms of civil inattention. Implications for the reinterpretation of previous research are discussed

Grad-seq guides the discovery of ProQ as a major small RNA-binding protein

The functional annotation of transcriptomes and identification of noncoding RNA (ncRNA) classes has been greatly facilitated by the advent of next-generation RNA sequencing which, by reading the nucleotide order of transcripts, theoretically allows the rapid profiling of all transcripts in a cell. However, primary sequence per se is a poor predictor of function, as ncRNAs dramatically vary in length and structure and often lack identifiable motifs. Therefore, to visualize an informative RNA landscape of organisms with potentially new RNA biology that are emerging from microbiome and environmental studies requires the use of more functionally relevant criteria. One such criterion is the association of RNAs with functionally important cognate RNA-binding proteins. Here we analyze the full ensemble of cellular RNAs using gradient profiling by sequencing (Grad-seq) in the bacterial pathogen Salmonella enterica, partitioning its coding and noncoding transcripts based on their network of RNA–protein interactions. In addition to capturing established RNA classes based on their biochemical profiles, the Grad-seq approach enabled the discovery of an overlooked large collective of structured small RNAs that form stable complexes with the conserved protein ProQ. We show that ProQ is an abundant RNA-binding protein with a wide range of ligands and a global influence on Salmonella gene expression. Given its generic ability to chart a functional RNA landscape irrespective of transcript length and sequence diversity, Grad-seq promises to define functional RNA classes and major RNA-binding proteins in both model species and genetically intractable organisms

Neolithic land use in the northern Boreal zone: high-resolution multiproxy analyses from Lake Huhdasjarvi, south-eastern Finland

Two high-resolution pollen and charcoal analyses were constructed from sediments obtained from a small bay in eastern Finland in order to gain information on human activity during the Neolithic Stone Age, 5200-1800 BC. We used measurements of loss on ignition (LOI), magnetic susceptibility and geochemical analyses to describe the sedimentological characteristics. Palaeomagnetic dating and measurements of Cs-137-activity were supported by C-14-datings. The analyses revealed human activity between 4400 and 3200 BC, which is synchronous with archaeological cultures defined through different stages of Comb Ware pottery types and Middle Neolithic pottery types with asbestos as a primary temper. Direct evidence of Hordeum cultivation was dated to 4040-3930 cal BC. According to the pollen data, more significant effort was put into the production of fibres from hemp and lime than the actual cultivation of food

Pupil dilation as an implicit measure of appetitive Pavlovian learning

Appetitive Pavlovian conditioning is a learning mechanism of fundamental biological and pathophysiological significance. Nonetheless, its exploration in humans remains sparse, which is partly attributed to the lack of an established psychophysiological parameter that aptly represents conditioned responding. This study evaluated pupil diameter and other ocular response measures (gaze dwelling time, blink duration and count) as indices of conditioning. Additionally, a learning model was used to infer participants' learning progress on the basis of their pupil dilation. Twenty-nine healthy volunteers completed an appetitive differential delay conditioning paradigm with a primary reward, while the ocular response measures along with other psychophysiological (heart rate, electrodermal activity, postauricular and eyeblink reflex) and behavioral (ratings, contingency awareness) parameters were obtained to examine the relation among different measures. A significantly stronger increase in pupil diameter, longer gaze duration and shorter eyeblink duration was observed in response to the reward-predicting cue compared to the control cue. The Pearce-Hall attention model best predicted the trial-by-trial pupil diameter. This conditioned response was corroborated by a pronounced heart rate deceleration to the reward-predicting cue, while no conditioning effect was observed in the electrodermal activity or startle responses. There was no discernible correlation between the psychophysiological response measures. These results highlight the potential value of ocular response measures as sensitive indices for representing appetitive conditioning

Re-analysis of the Levanluhta skeletal material : Sex and stature estimation of individuals in an Iron Age water burial in Finland

Levanluhta, an Iron Age water burial site in Finland, and its material consisting of commingled skeletal remains and artifacts, has been studied by several researchers over the past 100 years, resulting in multiple interpretations of the people and the site. Previous skeletal analyses have concluded that the majority of the individuals represented in the remains were females and children and were of relatively short stature, so possibly nutritionally deprived. This study re-analyzed the commingled adult human remains with updated methods. The methods applied in this study to estimate sex and stature were based on more representative European reference samples than the previously applied methods. The methods included morphology, osteometrics, and computed tomography (CT) scans. Our results indicated that depending on the reference data, the majority of the individual adult bones including os coxae (73%, n = 45) and long bones (humerus 83%-89%, n = 52; radius 72%-89%, n = 47; ulna 50%-65%, n = 58; femur 92%-100%, n = 25; tibia 77%-85%, n = 26) were classified as females based on their size and morphology. The cross-sectional bone properties of humerii, femora, and tibiae visualized using CT scanning also supported these findings. However, the cranial morphology did not show as clear female-biased sex ratio as other methods (42% females, 33% males, 24% undetermined, n = 33). In females, the mean stature based on the tibia (155.3 cm, n = 10) was within the range of the coeval European females and did not necessarily indicate nutritional deprivation, which is in line with previously published stable isotope findings from the site. The mean stature based on the tibia suggested that the Levanluhta males were short (164.0 cm, n = 3), but final interpretations were limited due to the small number of male individuals. The current study affirmed that the Levanluhta skeletal assemblage was female biased and gave new insights into interpretation of the stature.Peer reviewe

Substance abusers' personality disorders and staff members' emotional reactions

<p>Abstract</p> <p>Background</p> <p>Previous research has indicated that aggressive behaviour and DSM-IV cluster B personality disorders (PD) may be associated with professionals' emotional reactions to clients, and that cluster C PD may be associated with positive emotional reactions.</p> <p>Methods</p> <p>Staff members recruited from workshops completed a self-report inventory of emotional reactions to patients, the Feeling Word Checklist-58, and substance abusers completed a self-report of DSM-IV personality disorder, the DSM-IV and ICD-10 Personality Disorder Questionnaire. Correlational analysis and multiple regression analysis was used to assess the associations between personality disorders and emotional reations.</p> <p>Results</p> <p>Cluster B disorder features were associated with feeling distance to patients, and cluster C disorder features were associated with feeling helpful towards patients. Cluster A disorders had no significant impact on emotional reactions.</p> <p>Conclusion</p> <p>The findings confirm clinical experiences that personality disorder features in patients with substance abuse have an impact on staff members reactions to them. These reactions should be considered in supervision of staff, and in treatment models for patients with co-morbid personality disorders and substance abuse.</p

A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression

Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis