True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin α?

Background: The combination of methotrexate and the anti-tumour necrosis factor (TNF) antibody infliximab is a very effective treatment for rheumatoid arthritis (RA). However, a proportion of patients are not responsive to this treatment. Inefficacy may represent a TNF independent disease or insufficient drug at the site of action. Case report: A patient with RA resistant to repeated high dose infliximab infusions and intra-articular infliximab into an inflamed knee is described. No beneficial clinical effect was observed. Pre-injection arthroscopic biopsy of the study knee demonstrated TNF staining but also confirmed the presence of lymphotoxin (LT or TNFß) on immunohistochemistry. Subsequent treatment with etanercept (which blocks LT as well as TNF) resulted in clinical remission of disease. Conclusion: This case suggests that resistance to TNF blockade may occur when TNF is not the dominant inflammatory cytokine and suggests that LT may have a pathogenic role in RA

Development of the PsAQoL: a quality of life instrument specific to psoriatic arthritis

Background: Patient reported outcome measures used in studies of psoriatic arthritis (PsA) have been found to be inadequate for determining the impact of the disease from the patient’s perspective. Objective: To produce the PsAQoL, a PsA-specific quality of life (QoL) instrument, employing the needs based model of QoL that would be relevant and acceptable to respondents, valid, and reliable. Methods: Content was derived from qualitative interviews conducted with patients with PsA. Face and content validity were assessed by field test interviews with a new sample of patients with PsA. A postal survey was conducted to improve the scaling properties of the new measure. Finally, a test-retest postal survey was used to identify the final measure and to test its scaling properties, reliability, internal consistency, and validity. Results: Analysis of the qualitative interview transcripts identified a 51 item questionnaire. Field test interviews confirmed the acceptability and relevance of the measure. Analysis of data from the first postal survey (n = 94) reduced the questionnaire to 35 items. Rasch analysis of data from the test-retest survey (n = 286) identified a 20 item version of the PsAQoL with good item fit. This version had excellent internal consistency (a = 0.91), test-retest reliability (0.89), and validity. Conclusions: The PsAQoL is a valuable tool for assessing the impact of interventions for PsA in clinical studies and trials. It is well accepted by patients, taking about three minutes to complete, is easy to administer, and has excellent scaling and psychometric properties

Detecting Sarcasm in Multimodal Social Platforms

Sarcasm is a peculiar form of sentiment expression, where the surface sentiment differs from the implied sentiment. The detection of sarcasm in social media platforms has been applied in the past mainly to textual utterances where lexical indicators (such as interjections and intensifiers), linguistic markers, and contextual information (such as user profiles, or past conversations) were used to detect the sarcastic tone. However, modern social media platforms allow to create multimodal messages where audiovisual content is integrated with the text, making the analysis of a mode in isolation partial. In our work, we first study the relationship between the textual and visual aspects in multimodal posts from three major social media platforms, i.e., Instagram, Tumblr and Twitter, and we run a crowdsourcing task to quantify the extent to which images are perceived as necessary by human annotators. Moreover, we propose two different computational frameworks to detect sarcasm that integrate the textual and visual modalities. The first approach exploits visual semantics trained on an external dataset, and concatenates the semantics features with state-of-the-art textual features. The second method adapts a visual neural network initialized with parameters trained on ImageNet to multimodal sarcastic posts. Results show the positive effect of combining modalities for the detection of sarcasm across platforms and methods.Comment: 10 pages, 3 figures, final version published in the Proceedings of ACM Multimedia 201

The MASSIVE Survey - X. Misalignment between Kinematic and Photometric Axes and Intrinsic Shapes of Massive Early-Type Galaxies

We use spatially resolved two-dimensional stellar velocity maps over a $107"\times 107"$ field of view to investigate the kinematic features of 90 early-type galaxies above stellar mass $10^{11.5}M_\odot$ in the MASSIVE survey. We measure the misalignment angle $\Psi$ between the kinematic and photometric axes and identify local features such as velocity twists and kinematically distinct components. We find 46% of the sample to be well aligned ($\Psi < 15^{\circ}$), 33% misaligned, and 21% without detectable rotation (non-rotators). Only 24% of the sample are fast rotators, the majority of which (91%) are aligned, whereas 57% of the slow rotators are misaligned with a nearly flat distribution of $\Psi$ from $15^{\circ}$ to $90^{\circ}$. 11 galaxies have $\Psi \gtrsim 60^{\circ}$ and thus exhibit minor-axis ("prolate") rotation in which the rotation is preferentially around the photometric major axis. Kinematic misalignments occur more frequently for lower galaxy spin or denser galaxy environments. Using the observed misalignment and ellipticity distributions, we infer the intrinsic shape distribution of our sample and find that MASSIVE slow rotators are consistent with being mildly triaxial, with mean axis ratios of $b/a=0.88$ and $c/a=0.65$. In terms of local kinematic features, 51% of the sample exhibit kinematic twists of larger than $20^{\circ}$, and 2 galaxies have kinematically distinct components. The frequency of misalignment and the broad distribution of $\Psi$ reported here suggest that the most massive early-type galaxies are mildly triaxial, and that formation processes resulting in kinematically misaligned slow rotators such as gas-poor mergers occur frequently in this mass range.Comment: Accepted to MNRA

Sigurðar saga fóts (The Saga of Sigurðr Foot): A Translation

This is the first English translation of the short Icelandic romance Sigurðar saga fóts, with an introduction presenting the evidence for its dating and immediate literary context. Like most Icelandic romances, Sigurðar saga is a bridal-quest story; the support of a foster-brother is key to the hero winning the bride; and the foster-brothers start out as opponents before recognising their mutual excellence and swearing foster-brotherhood. Uniquely, however, the men who become foster-brothers begin by competing for the same bride (Signý): the eponymous Sigurðr fótr wins Signý only because Ásmundr gives her to him in exchange for foster-brotherhood. Ásmundr’s decision can be read as demonstrating with unusual starkness the superior importance in much Icelandic romance of homosocial relationships over heterosexual ones, giving the saga a certain paradigmatic status. Translating the saga in an open-access forum and reconstructing its literary context will, we hope, encourage further analyses

Long-Term Outcomes of Cognitive-Behavioral Therapy for Adolescent Body Dysmorphic Disorder

Emerging evidence suggests that cognitive-behavioral therapy (CBT) is an efficacious treatment for adolescent body dysmorphic disorder (BDD) in the short term, but longer-term outcomes remain unknown. The current study aimed to follow up a group of adolescents who had originally participated in a randomized controlled trial of CBT for BDD to determine whether treatment gains were maintained. Twenty-six adolescents (mean age = 16.2, SD = 1.6) with a primary diagnosis of BDD received a course of developmentally tailored CBT and were followed up over 12 months. Participants were assessed at baseline, midtreatment, posttreatment, 2-, 6-, and 12-month follow-up. The primary outcome measure was the clinician-rated Yale-Brown Obsessive-Compulsive Scale Modified for BDD. Secondary outcomes included measures of insight, depression, quality of life, and global functioning. BDD symptoms decreased significantly from pre- to posttreatment and remained stable over the 12-month follow-up. At this time point, 50% of participants were classified as responders and 23% as remitters. Participants remained significantly improved on all secondary outcomes at 12-month follow-up. Neither baseline insight nor baseline depression predicted long-term outcomes. The positive effects of CBT appear to be durable up to 12-month follow-up. However, the majority of patients remained symptomatic and vulnerable to a range of risks at 12-month follow-up, indicating that longer-term monitoring is advisable in this population. Future research should focus on enhancing the efficacy of CBT in order to improve long-term outcomes.Full Tex

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3–4 months. Both cohorts produced naïve T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort

Advances in Ambulatory Oxygen workshop and Longterm Oxygen therapy in real-life practice.

The practical workshop presented recent advances in the field of ambulatory oxygen (AO), with experts discussing identification of patients who would benefit from AO, as well as current trials to measure specific benefits of AO in chronic patients. In particular, AO prescription in clinical practice and developments in pulsed-dose delivery of AO as a more efficient method of oxygen delivery were extensively discussed. After audience questions, the attendees had the opportunity to handle the AO systems on display in order to gain greater insight into their functionality and wearability, which should assist them in providing the most appropriate device for each patient. The symposium addressed considerations required when prescribing long-term oxygen therapy (LTOT). Dr Kampelmacher reviewed current indications for LTOT, emphasising the importance of accurate assessment of patients for LTOT, optimisation of oxygen dose, and patient education. Dr Vivodtzev discussed the evidence for LTOT in patients with exercise-induced desaturation, the role of portable oxygen concentrators, and the optimisation necessary to benefit from their use. The symposium concluded with a health economic study presented by Dr Little, demonstrating the cost benefits of a reform of the Scottish healthcare oxygen supply service

An empirical investigation of dance addiction

Although recreational dancing is associated with increased physical and psychological well-being, little is known about the harmful effects of excessive dancing. The aim of the present study was to explore the psychopathological factors associated with dance addiction. The sample comprised 447 salsa and ballroom dancers (68% female, mean age: 32.8 years) who danced recreationally at least once a week. The Exercise Addiction Inventory (Terry, Szabo, & Griffiths, 2004) was adapted for dance (Dance Addiction Inventory, DAI). Motivation, general mental health (BSI-GSI, and Mental Health Continuum), borderline personality disorder, eating disorder symptoms, and dance motives were also assessed. Five latent classes were explored based on addiction symptoms with 11% of participants belonging to the most problematic class. DAI was positively associated with psychiatric distress, borderline personality and eating disorder symptoms. Hierarchical linear regression model indicated that Intensity (ß=0.22), borderline (ß=0.08), eating disorder (ß=0.11) symptoms, as well as Escapism (ß=0.47) and Mood Enhancement (ß=0.15) (as motivational factors) together explained 42% of DAI scores. Dance addiction as assessed with the Dance Addiction Inventory is associated with indicators of mild psychopathology and therefore warrants further research

Sigurðar saga fóts (The Saga of Sigurðr Foot): A Translation

This is the first English translation of the short Icelandic romance Sigurðar saga fóts, with an introduction presenting the evidence for its dating and immediate literary context. Like most Icelandic romances, Sigurðar saga is a bridal-quest story; the support of a foster-brother is key to the hero winning the bride; and the foster-brothers start out as opponents before recognising their mutual excellence and swearing foster-brotherhood. Uniquely, however, the men who become foster-brothers begin by competing for the same bride (Signý): the eponymous Sigurðr fótr wins Signý only because Ásmundr gives her to him in exchange for foster-brotherhood. Ásmundr’s decision can be read as demonstrating with unusual starkness the superior importance in much Icelandic romance of homosocial relationships over heterosexual ones, giving the saga a certain paradigmatic status. Translating the saga in an open-access forum and reconstructing its literary context will, we hope, encourage further analyses