Tumor necrosis factor inhibitor therapy but not standard therapy is associated with resolution of erosion in the sacroiliac joints of patients with axial spondyloarthritis

INTRODUCTION: Radiography is an unreliable and insensitive tool for the assessment of structural lesions in the sacroiliac joints (SIJ). Magnetic resonance imaging (MRI) detects a wider spectrum of structural lesions but has undergone minimal validation in prospective studies. The Spondyloarthritis Research Consortium of Canada (SPARCC) MRI Sacroiliac Joint (SIJ) Structural Score (SSS) assesses a spectrum of structural lesions (erosion, fat metaplasia, backfill, ankylosis) and its potential to discriminate between therapies requires evaluation. METHODS: The SSS score assesses five consecutive coronal slices through the cartilaginous portion of the joint on T1-weighted sequences starting from the transitional slice between cartilaginous and ligamentous portions of the joint. Lesions are scored dichotomously (present/absent) in SIJ quadrants (fat metaplasia, erosion) or halves (backfill, ankylosis). Two readers independently scored 147 pairs (baseline, 2 years) of scans from a prospective cohort of patients with SpA who received either standard (n = 69) or tumor necrosis factor alpha (TNFα) inhibitor (n = 78) therapy. Smallest detectable change (SDC) was calculated using analysis of variance (ANOVA), discrimination was assessed using Guyatt’s effect size, and treatment group differences were assessed using t-tests and the Mann–Whitney test. We identified baseline demographic and structural damage variables associated with change in SSS score by univariate analysis and analyzed the effect of treatment by multivariate stepwise regression adjusted for severity of baseline structural damage and demographic variables. RESULTS: A significant increase in mean SSS score for fat metaplasia (P = 0.017) and decrease in mean SSS score for erosion (P = 0.017) was noted in anti-TNFα treated patients compared to those on standard therapy. Effect size for this change in SSS fat metaplasia and erosion score was moderate (0.5 and 0.6, respectively). Treatment and baseline SSS score for erosion were independently associated with change in SSS erosion score (β = 1.75, P = 0.003 and β = 0.40, P < 0.0001, respectively). Change in ASDAS (β = −0.46, P = 0.006), SPARCC MRI SIJ inflammation (β = −0.077, P = 0.019), and baseline SSS score for fat metaplasia (β = 0.085, P = 0.034) were independently associated with new fat metaplasia. CONCLUSION: The SPARCC SSS method for assessment of structural lesions has discriminative capacity in demonstrating significantly greater reduction in erosion and new fat metaplasia in patients receiving anti-TNFα therapy

Gamifying Navigation in Location-Based Applications

Location-based games entertain players usually by interactions at points of interest (POIs). Navigation between POIs often involve the use of either a physical or digital map, not taking advantage of the opportunity available to engage users in activities between POIs. The paper presents riddle solving as a navigational method for a location-based game. 10 families with 2-6 persons and at least one child in the age range 9- 11 years old participated in the evaluation. Results show that riddle solving as a navigational method is more enjoyable than a 2D digital map. Additional findings from video recordings, field notes, questionnaires, logging and semi-structured interviews revealed that riddle solving has potential for engaging users in learning activities

Activin/nodal signaling and NANOG orchestrate human embryonic stem cell fate decisions by controlling the H3K4me3 chromatin mark.

Stem cells can self-renew and differentiate into multiple cell types. These characteristics are maintained by the combination of specific signaling pathways and transcription factors that cooperate to establish a unique epigenetic state. Despite the broad interest of these mechanisms, the precise molecular controls by which extracellular signals organize epigenetic marks to confer multipotency remain to be uncovered. Here, we use human embryonic stem cells (hESCs) to show that the Activin-SMAD2/3 signaling pathway cooperates with the core pluripotency factor NANOG to recruit the DPY30-COMPASS histone modifiers onto key developmental genes. Functional studies demonstrate the importance of these interactions for correct histone 3 Lys4 trimethylation and also self-renewal and differentiation. Finally, genetic studies in mice show that Dpy30 is also necessary to maintain pluripotency in the pregastrulation embryo, thereby confirming the existence of similar regulations in vivo during early embryonic development. Our results reveal the mechanisms by which extracellular factors coordinate chromatin status and cell fate decisions in hESCs.We thank Andrew Knights for the technical support and helpful discussion, and the Wellcome-Trust Sanger Institute Microarray and Next-Generation Sequencing facilities for the technical support. We also thank the Sanger Institute Mouse Genetics Projects for mouse production and genotyping. This work was supported by the European Research Council starting grant Relieve-IMDs and the Cambridge Hospitals National Institute for Health Research Biomedical Research Centre (L.V.), a British Heart Foundation Ph.D. Studentship (A.B.), a Federation of European Biochemical Societies (FEBS) long-term fellowship and EU Fp7 grant InnovaLIV (S.P.), EU Fp7 grant TissuGEN (S.M.), and Wellcome Trust grant 098051 (D.G.). A.B. conceived the research, performed and analyzed the experiments, and wrote the manuscript. P.M. computationally analyzed ChIP-seq data sets and performed statistical analyses. N.C.H., S.B., and R.A.P. provided technical support. A.G. performed embryo dissections and dysmorphology assessments. I.M. and D.B. performed teratoma assays. D.G. supervised the bioinformatics data analysis. S.P., S.M., and L.V. conceived the research and wrote the manuscript.This is the final published version. It first appeared at http://genesdev.cshlp.org/content/29/7/702.full

The impact of hypoglycaemia on quality of life among adults with type 1 diabetes:Results from “YourSAY: Hypoglycaemia”

Aims Research on hypoglycaemia and quality of life (QoL) has focused mostly on severe hypoglycaemia and psychological outcomes, with less known about other aspects of hypoglycaemia (e.g., self-treated episodes) and impacts on other QoL domains (e.g., relationships). Therefore, we examined the impact of all aspects of hypoglycaemia on QoL in adults with type 1 diabetes (T1DM). Methods Participants completed an online survey, including assessment of hypoglycaemia-specific QoL (using the 12-item Hypoglycaemia Impact Profile). Mann-Whitney U tests examined differences in hypoglycaemia-specific QoL by hypoglycaemia frequency, severity, and awareness. Hierarchical linear regression examined associations with QoL. Results Participants were 1028 adults with T1DM (M ± SD age: 47 ± 15 years; diabetes duration: 27 ± 16 years). Severe and self-treated hypoglycaemia and impaired awareness negatively impacted on overall QoL and several QoL domains, including leisure activities, physical health, ability to keep fit/be active, sleep, emotional well-being, spontaneity, independence, work/studies, and dietary freedom. Diabetes distress was most strongly associated with hypoglycaemia-specific QoL, followed by generic emotional well-being, fear of hypoglycaemia, and confidence in managing hypoglycaemia. Hypoglycaemia frequency and awareness were no longer significantly associated with QoL once psychological factors were considered. Conclusions Hypoglycaemia negatively impacts on several QoL domains. Psychological factors supersede the effect of hypoglycaemia frequency and awareness in accounting for this negative impact

Export Production in the Subarctic North Pacific over the Last 800 kyrs: No Evidence for Iron Fertilization?

The subarctic North Pacific is a high nitrate-low chlorophyll (HNLC) region, where phytoplankton growth rates, especially those of diatoms, are enhanced when micronutrient Fe is added. Accordingly, it has been suggested that glacial Fe-laden dust might have increased primary production in this region. This paper reviews published palaeoceanographic records of export production over the last 800 kyrs from the open North Pacific (north of ∼35°N). We find different patterns of export production change over time in the various domains of the North Pacific (NW and NE subarctic gyres, the marginal seas and the transition zone). However, there is no compelling evidence for an overall increase in productivity during glacials in the subarctic region, challenging the paradigm that dust-born Fe fertilization of this region has contributed to the glacial draw down of atmospheric CO 2 . Potential reasons for the lack of increased glacial export production include the possibility that Fe-fertilization rapidly drives the ecosystem towards limitation by another nutrient. This effect would have been exacerbated by an even more stable mixed layer compared to today.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41539/1/10872_2004_Article_5383267.pd

Automated detection and quantification of contact behaviour in pigs using deep learning

Publication history: Accepted - 5 October 2022; Published online - 22 October 2022Change in the frequency of contact between pigs within a group may be indicative of a change in the physiological or health status of one or more pigs within a group, or indicative of the occurrence of abnormal behaviour, e.g. tail-biting. Here, we developed a novel framework that detects and quantifies the frequency of interaction, i.e., a pig head to another pig rear, between pigs in groups. The method does not require individual pig tracking/identification and uses only inexpensive camera-based data capturing infrastructure. We modified the architecture of well-established deep learning models and further developed a lightweight processing stage that scans over pigs to score said interactions. This included the addition of a detection subnetwork to a selected layer of the base residual network. We first validated the automated system to score the interactions between individual pigs within a group, and determined an average accuracy of 92.65% ± 3.74%, under a variety of settings, e.g., management set-ups and data capturing. We then applied the method to a significant welfare challenge in pigs, that of the detection of tail-biting outbreaks in pigs and quantified the changes that happen in contact behaviour during such an outbreak. Our study shows that the system is able to accurately monitor pig interactions under challenging farming conditions, without the need for additional sensors or a pig tracking stage. The method has a number of potential applications to the field of precision livestock farming of pigs that may transform the industry.We are grateful to Dr Katarina Buckova, Melanie McAuley, Zoe Tey and Joy McMillen for help with the collection and annotation of the datasets. This research was part of the EU-China HealthyLivestock project https://healthylivestock.net/. The authors wish to acknowledge that HealthyLivestock is funded by the European Union H2020 research and innovation program under grant agreement number 773436. The European Commission’s support for the production of this publication does not constitute an endorsement of the contents, which reflect the views only of the authors, and the Commission cannot be held responsible for any use which may be made of the information contained therein. The automated detection work was supported in part by the UK Centre for Innovation Excellence in Livestock (CIEL) and Zoetis Inc. Zoetis did not influence the data selection, interpretation, conclusions drawn or the decision on how or what to publish. The study was made possible by a grant from the Green Development and Demonstration Programme under the Ministry of Food, Agriculture and Fisheries, Denmark (project IntactTails j. nr. 34,009-13-0743)

Association between recent exposure to continuous glucose monitoring-recorded hypoglycaemia and counterregulatory and symptom responses to subsequent controlled hypoglycaemia in people with type 1 diabetes

AimExperimental hypoglycaemia blunts the counterregulatory hormone and symptom responses to a subsequent episode of hypoglycaemia. In this study, we aimed to assess the associations between antecedent exposure and continuous glucose monitoring (CGM)-recorded hypoglycaemia during a 1-week period and the counterregulatory responses to subsequent experimental hypoglycaemia in people with type 1 diabetes.Materials and MethodsForty-two people with type 1 diabetes (20 females, mean ± SD glycated haemoglobin 7.8% ± 1.0%, diabetes duration median (interquartile range) 22.0 (10.5-34.9) years, 29 CGM users, and 19 with impaired awareness of hypoglycaemia) wore an open intermittently scanned CGM for 1 week to detect hypoglycaemic exposure before a standardized hyperinsulinaemic-hypoglycaemic [2.8 ± 0.1 mmol/L (50.2 ± 2.3 mg/dl)] glucose clamp. Symptom responses and counterregulatory hormones were measured during the clamp. The study is part of the HypoRESOLVE project.ResultsCGM-recorded hypoglycaemia in the week before the clamp was negatively associated with adrenaline response [β −0.09, 95% CI (−0.16, −0.02) nmol/L, p = .014], after adjusting for CGM use, awareness of hypoglycaemia, glycated haemoglobin and total daily insulin dose. This was driven by level 2 hypoglycaemia [&lt;3.0 mmol/L (54 mg/dl)] [β −0.21, 95% CI (−0.41, −0.01) nmol/L, p = .034]. CGM-recorded hypoglycaemia was negatively associated with total, autonomic, and neuroglycopenic symptom responses, but these associations were lost after adjusting for potential confounders.ConclusionsRecent exposure to CGM-detected hypoglycaemia was independently associated with an attenuated adrenaline response to experimental hypoglycaemia in people with type 1 diabetes