The effect of three years of TNF alpha blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study

INTRODUCTION: The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-alpha) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS). METHODS: This is a prospective cohort study of 111 consecutive AS outpatients who started TNF-alpha blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly. RESULTS: After three years, 72 patients (65%) were still using their first TNF-alpha blocking agent. In these patients, TNF-alpha blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician's global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life. CONCLUSIONS: Three years of TNF-alpha blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-alpha blocking therapy in AS, in addition to the currently used more subjective measures

Two-dimensional superconductivity at the (111)LaAlO3_3/SrTiO3_3 interface

We report on the discovery and transport study of the superconducting ground state present at the (111)LaAlO$_3$/SrTiO$_3$ interface. The superconducting transition is consistent with a Berezinskii-Kosterlitz-Thouless transition and its 2D nature is further corroborated by the anisotropy of the critical magnetic field, as calculated by Tinkham. The estimated superconducting layer thickness and coherence length are 10 nm and 60 nm, respectively. The results of this work provide a new platform to clarify the microscopic details of superconductivity at LaAlO$_3$/SrTiO$_3$ interfaces, in particular in what concerns the link with orbital symmetry.Comment: 4 pages, 4 figure

Etnički identitet i racionalnost

Ethnic identity is explained through the lens of collective action theory. Like other groups (Tribes, Feudal states, international organizations, nation states, etc.,) ethnic groups are a result of an individuals cost-benefit analysis that maximizes wealth and security. External variables associated with social relations determine the individual’s cost benefit analysis to choose ethnicity over other groups. However, collective action will not necessarily result just because the group provides benefits for its members. Individuals have incentive to consume and not produce collective goods. To overcome this problem, at least some individuals must have the incentive to produce collective goods that support ethnic groups. This paper illustrates how a rigorous cost benefit analysis explains when an individual will have the incentive to provide collective goods.U radu se fenomen etničkog identiteta promatra kroz optiku teorije kolektivne akcije. Poput ostalih društvenih skupina (plemena, feudalnih država, međunarodnih organizacija i si.) i etničke su grupe rezultat individualne analize troškova-i-koristi, čija je svrha maksimiziranje materijalnih sredstava i sigurnosti. Eksterne varijable, određene društvenim odnosima, determiniraju individualnu sklonost etnicitetu, to jesi nekom drugom principu združivanja. Kolektivna akcija nije neizbježna posljedica koristi koju grupe pribavljaju svojim članovima; pojedinci su motivirani da konzumiraju zajedničko dobro, ali ne i da ga ostvaruju. Rigorozna analiza troškova-i-koristi, prema autoru, pomaže u objašnjavanju individualnog doprinošenja zajedničkom dobru

Actions of metformin and statins on lipid and glucose metabolism and possible benefit of combination therapy

Patients with diabetes type 2 have an increased risk for cardiovascular disease and commonly use combination therapy consisting of the anti-diabetic drug metformin and a cholesterol-lowering statin. However, both drugs act on glucose and lipid metabolism which could lead to adverse effects when used in combination as compared to monotherapy. In this review, the proposed molecular mechanisms of action of statin and metformin therapy in patients with diabetes and dyslipidemia are critically assessed, and a hypothesis for mechanisms underlying interactions between these drugs in combination therapy is developed

Gidsen in de stadse jungle, biologentweeling wekt verwondering voor stadsecologie

Conservation Biolog

Exploring temporal relationships among worrying, anxiety, and somatic symptoms

OBJECTIVES: The role of anxiety symptoms in the development of functional somatic symptoms (FSS) is unknown. Somatic symptoms may be triggered by or give rise to anxiety symptoms. This study aimed to 1) explore interrelationships among within-day worrying, feeling anxious, and somatic symptoms, and 2) investigate the association between these interrelationships and overall level of FSS. METHODS: This study included 767 participants (83% females, mean age 39 years), who were recruited through an online crowdsourcing study in the Dutch general population. Somatic, and anxiety symptoms were reported thrice daily (6-h intervals) for 30 days using electronic diaries. FSS were assessed at baseline (PHQ-15). Temporal relationships among worrying, feeling anxious, and somatic symptoms were modeled using a multilevel vector autoregressive model. RESULTS: We observed large heterogeneity in the within-person interrelationships among worrying, feeling anxious and somatic symptoms. Averaged over participants, higher-than-usual somatic symptoms were associated with increases in levels of worrying six hours later (B = 0.017, 95% CI [0.006, 0.027]). At the between-person level, FSS levels predicted the persistence of feeling anxious (B = 0.230 95% CI [0.105, 0.350]) and the carry-over of worrying to feeling anxious over six-hours (B = 0.159, 95% CI [0.031, 0.283]). CONCLUSIONS: In contrast to what we expected, higher levels of somatic symptoms over multiple weeks were associated with the persistence and carry-over of within-day anxiety-related symptoms. One within-person association between psychological and somatic symptoms during the day was observed, suggesting that, over a time span of 6-h, anxiety symptoms relate to somatic symptoms only in a minority of people from the general population