Moving instead of asking? performance-based tests and BASFI-questionnaire measure different aspects of physical function in ankylosing spondylitis

INTRODUCTION: Ankylosing Spondylitis (AS) is characterised by limitations in physical function. The Bath Ankylosing Spondylitis Functional Index (BASFI) is considered to be the gold-standard to assess physical function in AS patients. However, the BASFI questionnaire is a self-reported outcome measure and susceptible to subjective interpretation (under- or over-estimation). More objective outcome measures, like performance-based tests, could provide an objective outcome measurement for the evaluation of limitations in physical function. Therefore, the primary aim of this study was to determine the association between performance-based measures and the BASFI questionnaire. METHODS: In this cross-sectional study 126 AS patients completed the BASFI questionnaire and eight performance-based tests based on BASFI-items. Each test received three scores: one for performance (time or points) and a score for exertion and pain experienced during performance (using modified Borg-scale and VAS 0-100 mm, respectively). Linear regression analyses were used to assess the associations between the BASFI questionnaire and performance-based tests. RESULTS: The univariable association between performance and BASFI-score was moderate with a R-square of 0.31 and Beta of 0.56 (p's < 0.05). In a multivariable analysis, the association between performance, exertion and pain on the one hand and BASFI-score on the other was assessed; R-square increased to 0.54: the Beta's for exertion and pain during performance were 0.38 and 0.26, respectively; the Beta for performance decreased to 0.19 (p's < 0.05). CONCLUSIONS: This study demonstrates that alongside actual performance, patients seem to incorporate exertion and pain in their assessment of perceived physical function on the BASFI questionnaire. Performance-based tests could provide an objective outcome measurement for the evaluation of physical function and give relevant new information in addition to the BASFI questionnaire

Dimerization and nuclear entry of mPER proteins in mammalian cells

Nuclear entry of circadian oscillatory gene products is a key step for the generation of a 24-hr cycle of the biological clock. We have examined nuclear import of clock proteins of the mammalian period gene family and the effect of serum shock, which induces a synchronous clock in cultured cells. Previously, mCRY1 and mCRY2 have been found to complex with PER proteins leading to nuclear import. Here we report that nuclear translocation of mPER1 and mPER2 (1) involves physical interactions with mPER3, (2) is accelerated by serum treatment, and (3) still occurs in mCry1/mCry2 double-deficient cells lacking a functional biological clock. Moreover, nuclear localization of endogenous mPER1 was observed in cultured mCry1/mCry2 double-deficient cells as well as in the liver and the suprachiasmatic nuclei (SCN) of mCry1/mCry2 double-mutant mice. This indicates that nuclear translocation of at least mPER1 also can occur under physiological conditions (i.e., in the intact mouse) in the absence of any CRY protein. The mPER3 amino acid sequence predicts the presence of a cytoplasmic localization domain (CLD) and a nuclear localization signal (NLS). Deletion analysis suggests that the interplay of the CLD and NLS proposed to regulate nuclear entry of PER in Drosophila is conserved in mammals, but with the novel twist that mPER3 can act as the dimerizing partner

PTF11iqb: cool supergiant mass-loss that bridges the gap between Type IIn and normal supernovae

The supernova (SN) PTF11iqb was initially classified as a Type IIn event caught very early after explosion. It showed narrow Wolf–Rayet (WR) spectral features on day 2 (as in SN 1998S and SN 2013cu), but the narrow emission weakened quickly and the spectrum morphed to resemble Types II-L and II-P. At late times, H? exhibited a complex, multipeaked profile reminiscent of SN 1998S. In terms of spectroscopic evolution, we find that PTF11iqb was a near twin of SN 1998S, although with somewhat weaker interaction with circumstellar material (CSM) at early times, and stronger interaction at late times. We interpret the spectral changes as caused by early interaction with asymmetric CSM that is quickly (by day 20) enveloped by the expanding SN ejecta photosphere, but then revealed again after the end of the plateau when the photosphere recedes. The light curve can be matched with a simple model for CSM interaction (with a mass-loss rate of roughly 10?4 M? yr?1) added to the light curve of a normal SN II-P. The underlying plateau requires a progenitor with an extended hydrogen envelope like a red supergiant at the moment of explosion, consistent with the slow wind speed (&lt;80?km?s?1) inferred from narrow H? emission. The cool supergiant progenitor is significant because PTF11iqb showed WR features in its early spectrum – meaning that the presence of such WR features does not necessarily indicate a WR-like progenitor. Overall, PTF11iqb bridges SNe IIn with weaker pre-SN mass-loss seen in SNe II-L and II-P, implying a continuum between these types

PTF11iqb: cool supergiant mass-loss that bridges the gap between Type IIn and normal supernovae

The supernova (SN) PTF11iqb was initially classified as a Type IIn event caught very early after explosion. It showed narrow Wolf–Rayet (WR) spectral features on day 2 (as in SN 1998S and SN 2013cu), but the narrow emission weakened quickly and the spectrum morphed to resemble Types II-L and II-P. At late times, H? exhibited a complex, multipeaked profile reminiscent of SN 1998S. In terms of spectroscopic evolution, we find that PTF11iqb was a near twin of SN 1998S, although with somewhat weaker interaction with circumstellar material (CSM) at early times, and stronger interaction at late times. We interpret the spectral changes as caused by early interaction with asymmetric CSM that is quickly (by day 20) enveloped by the expanding SN ejecta photosphere, but then revealed again after the end of the plateau when the photosphere recedes. The light curve can be matched with a simple model for CSM interaction (with a mass-loss rate of roughly 10?4 M? yr?1) added to the light curve of a normal SN II-P. The underlying plateau requires a progenitor with an extended hydrogen envelope like a red supergiant at the moment of explosion, consistent with the slow wind speed (&lt;80?km?s?1) inferred from narrow H? emission. The cool supergiant progenitor is significant because PTF11iqb showed WR features in its early spectrum – meaning that the presence of such WR features does not necessarily indicate a WR-like progenitor. Overall, PTF11iqb bridges SNe IIn with weaker pre-SN mass-loss seen in SNe II-L and II-P, implying a continuum between these types

Bone formation rather than inflammation reflects Ankylosing Spondylitis activity on PET-CT: a pilot study

INTRODUCTION: Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [(18)F]FDG and [(11)C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [(18)F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference. METHODS: In a stepwise approach different PET tracers were investigated. First, whole body [(18)F]FDG and [(11)C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [(18)F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data. RESULTS: No increased [(18)F]FDG and [(11)C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [(18)F]Fluoride PET-CT, [(18)F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [(18)F]FDG depicted only three lesions, with an uptake of five times lower compared to [(18)F]Fluoride, and again no [(11)C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [(18)F]Fluoride uptake. Conventional radiographs showed structural bony changes in 11 out of 17 [(18)F]Fluoride PET positive lesions. CONCLUSIONS: Our PET-CT data suggest that AS activity is reflected by bone activity (formation) rather than inflammation. The results also show the potential value of PET-CT for imaging AS activity using the bone tracer [(18)F]Fluoride. In contrast to active RA, inflammation tracers [(18)F]FDG and [(11)C](R)PK11195 appeared to be less useful for AS imaging

Biplanar versus conventional two-dimensional ultrasound guidance for radial artery catheterisation

Background: Ultrasound guidance increases first-pass success rates and decreases the number of cannulation attempts and complications during radial artery catheterisation but it is debatable whether short-, long-, or oblique-axis imaging is superior for obtaining access. Three-dimensional (3D) biplanar ultrasound combines both short- and long-axis views with their respective benefits. This study aimed to determine whether biplanar imaging would improve the accuracy of radial artery catheterisation compared with conventional 2D imaging. Methods: This before-and-after trial included adult patients who required radial artery catheterisation for elective cardiothoracic surgery. The participating anaesthesiologists were experienced in 2D and biplanar ultrasound-guided vascular access. The primary endpoint was successful catheterisation in one skin break without withdrawals. Secondary endpoints were the numbers of punctures and withdrawals, scanning and procedure times, needle visibility, perceived mental effort of the operator, and posterior wall puncture or other mechanical complications. Results: From November 2021 until April 2022, 158 patients were included and analysed (2D=75, biplanar=83), with two failures to catheterise in each group. First-pass success without needle redirections was 58.7% in the 2D group and 60.2% in the biplanar group (difference=1.6%; 95% confidence interval [CI], –14.0%–17.1%; P=0.84), and first-pass success within one skin break was 77.3% in the 2D group vs 81.9% in the biplanar group (difference=4.6%; 95% CI, 8.1%–17.3%; P=0.473). None of the secondary endpoints differed significantly. Conclusions: Biplanar ultrasound guidance did not improve success rates nor other performance measures of radial artery catheterisation. The additional visual information acquired with biplanar imaging did not offer any benefit. Clinical trial registration: N9687 (Dutch Trial Register).</p

Does Reverse Causality Underlie the Temporal Relationship between Depression and Crohn's Disease?

Background: Studies suggest that there is a temporal relationship between depression and Crohn's disease (CD) activity. However, these studies assumed a unidirectional relationship and did not examine the possibility of reverse causality and the risk of a spurious association due to the overlap of symptoms underlying the depression-CD relationship. We evaluated the existence of reverse causality reflected in a possible bidirectional relationship between patient-reported CD activity and an affective-cognitive dimension of depression. Methods: We studied 3307 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, and an affective-cognitive index of depression. Crohn's disease status and the affective-cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We used structural equation models to evaluate whether the effect of depression on future CD activity is stronger than the effect of CD activity on future depression. We calculated the likelihood that each of these hypotheses is supported by the data and calculated the likelihood ratio to provide a relative measure of which hypothesis best accounts for the data. Results: The results of the informative hypothesis testing showed the most support for the hypothesis stating that an affective-cognitive dimension of depression is a stronger predictor of patient-reported CD activity than the converse. Conclusions: The hypothesis that an affective-cognitive dimension of depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse

Identifying patients with medically unexplained physical symptoms in electronic medical records in primary care: a validation study

Prevention, Population and Disease management (PrePoD

Oracle-based optimization applied to climate model calibration

In this paper, we show how oracle-based optimization can be effectively used for the calibration of an intermediate complexity climate model. In a fully developed example, we estimate the 12 principal parameters of the C-GOLDSTEIN climate model by using an oracle- based optimization tool, Proximal-ACCPM. The oracle is a procedure that finds, for each query point, a value for the goodness-of-fit function and an evaluation of its gradient. The difficulty in the model calibration problem stems from the need to undertake costly calculations for each simulation and also from the fact that the error function used to assess the goodness-of-fit is not convex. The method converges to a Fbest fit_ estimate over 10 times faster than a comparable test using the ensemble Kalman filter. The approach is simple to implement and potentially useful in calibrating computationally demanding models based on temporal integration (simulation), for which functional derivative information is not readily available