Examining sex differences in knee pain: the Multicenter Osteoarthritis Study

SummaryObjectiveTo determine whether women experience greater knee pain severity than men at equivalent levels of radiographic knee osteoarthritis (OA).Design and methodsA cross-sectional analysis of 2712 individuals (60% women) without knee replacement or a recent steroid injection. Sex differences in pain severity at each Kellgren–Lawrence (KL) grade were assessed by knee using visual analog scale (VAS) scale and Western Ontario and McMaster Universities Arthritis Index (WOMAC) with and without adjustment for age, analgesic use, Body mass index (BMI), clinic site, comorbid conditions, depression score, education, race, and widespread pain (WSP) using generalized estimating equations. Effect sizes (Cohen's d) were also calculated. Analyses were repeated in those with and without patellofemoral OA (PFOA).ResultsWomen reported higher VAS pain at all KL grades in unadjusted analyses (d = 0.21–0.31, P < 0.0001–0.0038) and in analyses adjusted for all covariates except WSP (d = 0.16–0.22, P < 0.0001–0.0472). Pain severity differences further decreased with adjustment for WSP (d = 0.10–0.18) and were significant for KL grade ≤2 (P = 0.0015) and 2 (P = 0.0200). Presence compared with absence of WSP was associated with significantly greater knee pain at all KL grades (d = 0.32–0.52, P < 0.0001–0.0008). In knees with PFOA, VAS pain severity sex differences were greater at each KL grade (d = 0.45–0.62, P = 0.0006–0.0030) and remained significant for all KL grades in adjusted analyses (d = 0.31–0.57, P = 0.0013–0.0361). Results using WOMAC were similar.ConclusionsWomen reported greater knee pain than men regardless of KL grade, though effect sizes were generally small. These differences increased in the presence of PFOA. The strong contribution of WSP to sex differences in knee pain suggests that central sensitivity plays a role in these differences

Reconstruction of the palaeo‐sea level of Britain and Ireland arising from empirical constraints of ice extent: implications for regional sea level forecasts and North American ice sheet volume

Reconstructions of palaeo-sea level are vital for predicting future sea level change and constraining palaeo-ice sheet reconstructions, as well as being useful for a wide array of applications across Quaternary Science. Previous reconstructions of the palaeo-sea level of Britain and Ireland relied on a circular tuning of glacio-isostatic models: input ice sheet thicknesses and extents were iteratively altered to fit relative sea level data. Here we break that circularity by utilizing new data from the BRITICE-CHRONO project, which constrains the position of the British–Irish ice sheet margin through time, and we compare derived glacio-isostatic modelling to the rich relative sea level record. We test a combination of plausible ice thickness scenarios which account for the uncertainty of ice margin position over the North Sea, demonstrating the region where regional sea level data could distinguish between different glaciation scenarios. Our optimal reconstruction is then combined with several global-scale reconstructions. As the signal of the British–Irish Ice Sheet is constrained, we demonstrate how the relative sea level record of Britain and Ireland can be used to test reconstructions of far-field ice sheets (e.g. Antarctica, Eurasia and the Laurentide). The derived palaeo-topography data are likely to be useful for multiple disciplines. Finally, our improved method of sea level reconstruction impacts predictions of contemporary vertical land motion

ICER is requisite for Th17 differentiation.

Inducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6-STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORγt. In vitro differentiation from naive ICER/CREM-deficient CD4(+) T cells to Th17 cells is impaired but can be rescued by forced overexpression of ICER. Consistent with a role of Th17 cells in autoimmune and inflammatory diseases, ICER/CREM-deficient B6.lpr mice are protected from developing autoimmunity. Similarly, both anti-glomerular basement membrane-induced glomerulonephritis and experimental encephalomyelitis are attenuated in ICER/CREM-deficient mice compared with their ICER/CREM-sufficient littermates. Importantly, we find ICER overexpressed in CD4(+) T cells from patients with systemic lupus erythematosus. Collectively, our findings identify a unique role for ICER, which affects both organ-specific and systemic autoimmunity in a Th17-dependent manner

Atenolol versus losartan in children and young adults with Marfan's syndrome

BACKGROUND : Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS : We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS : From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [+/- SD] age, 11.5 +/- 6.5 years in the atenolol group and 11.0 +/- 6.2 years in the losartan group), who had an aorticroot z score greater than 3.0. The baseline-adjusted rate of change (+/- SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139 +/- 0.013 and -0.107 +/- 0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS : Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aorticroot dilatation between the two treatment groups over a 3-year period

Photon-axion conversion in intergalactic magnetic fields and cosmological consequences

Photon-axion conversion induced by intergalactic magnetic fields causes an apparent dimming of distant sources, notably of cosmic standard candles such as supernovae of type Ia (SNe Ia). We review the impact of this mechanism on the luminosity-redshift relation of SNe Ia, on the dispersion of quasar spectra, and on the spectrum of the cosmic microwave background. The original idea of explaining the apparent dimming of distant SNe Ia without cosmic acceleration is strongly constrained by these arguments. However, the cosmic equation of state extracted from the SN Ia luminosity-redshift relation remains sensitive to this mechanism. For example, it can mimic phantom energy.Comment: (14 pages, 9 eps figures) Contribution to appear in a volume of Lecture Notes in Physics (Springer-Verlag) on Axion

A Greenland-wide empirical reconstruction of paleo ice sheet retreat informed by ice extent markers: PaleoGrIS version 1.0

The Greenland Ice Sheet is a large contributor to global sea level rise, and current mass losses are projected to accelerate. However, model projections of future ice sheet evolution are limited by the fact that the ice sheet is not in equilibrium with present-day climate but is still adjusting to past changes that occurred over thousands of years. While the influence of such committed adjustments on future ice sheet evolution remains unquantified, it could be addressed by calibrating numerical ice sheet models over larger timescales and, importantly, against empirical data on ice margin positions. To enable such paleo data–model interactions, we need Greenland-wide empirical reconstructions of past ice sheet extent that combine geomorphological and geochronological evidence. Despite an increasing number of field studies producing new chronologies, such a reconstruction is currently lacking in Greenland. Furthermore, a time slice reconstruction can help to (i) answer open questions regarding the rate and pattern of ice margin evolution in Greenland since the glacial maximum, (ii) develop a standardised record of empirical data, and (iii) identify new sites for future field campaigns. Based on these motivations, we here present PaleoGrIS 1.0, a new Greenland-wide isochrone reconstruction of ice sheet extent evolution through the Late Glacial and early- to mid-Holocene informed by both geomorphological and geochronological markers. Our isochrones have a temporal resolution of 500 years and span ∼ 7.5 kyr from approximately 14 to 6.5 kyr BP. We describe the resulting reconstruction of the shrinking ice sheet and conduct a series of ice-sheet-wide and regional analyses to quantify retreat rates, areal extent change, and their variability across space and time. During the Late Glacial and early- to mid-Holocene, we find the Greenland Ice Sheet has lost about one-third of its areal extent (0.89 million km2). Between ∼ 14 and ∼ 8.5 kyr BP, it experienced a near-constant rate of areal extent loss of 170 ± 27 km2 yr−1. We find that the ice-sheet-scale pattern of margin retreat is well correlated to atmospheric and oceanic temperature variations, which implies a high sensitivity of the ice sheet to deglacial warming. However, during the Holocene, we observe inertia in the ice sheet system that likely caused a centennial- to millennial-scale time lag in ice extent response. At the regional scale, we observe highly heterogeneous deglacial responses in ice extent evident in both the magnitude and rate of retreat. We hypothesise that non-climatic factors, such as the asymmetrical nature of continental shelves and onshore bed topographies, play important roles in determining the regional- to valley-scale dynamics. PaleoGrIS 1.0 is an open-access database designed to be used by both the empirical and numerical modelling communities. It should prove a useful basis for improved future versions of the reconstruction when new geomorphological and geochronological data become available