Osteoarthritis: genetics and phenotypes in all their complexity

The genetic epidemiology of ostheoarthritis, using genome-wide association studies and other omics to elucidate teh pathology of this common joint disorder

Paleomagnetism and astronomically induced cyclicity of the Armantes section; a Miocene continental red sequence in the Calatayud-Daroca basin (Central Sapin)

The Armantes section is a red-bed sequence consisting of a regular altemation (10 m scale) of reddish silts and pink/white limestones.In between these limestones, a smaller-scale bedding (2-3 m scale) is intercalated, characterised by varying carbonate content and related differences in erosion resistance. An earlier correlation of the magnetic polarity sequence of the Armantes section to the geomagnetic polarity time scale (GPTS) suggested a periodicity of 111 kyr for the large-scale cyclicity (Krijgsman et al., 1994b). The carbonate, gamma-ray and susceptibility records indicate that 4 to 5 small-scale cycles are developed in one large-scale cycle, showing that the small-scale cyclicity is related to precession and thus caused by climate forcing. We suggest that the precipitation of the carbonates is most likely related to rising ground-water levels and an increase of evaporation. This implies that the thick limestone beds would correlate to eccentricity maxima and the smaller-scale limestone beds to precession minima. Rock magnetic experiments show that the NRM in the Armantes section results from the presence of hematite and magnetite/maghemite.The relative contribution of hematite is strongly related to the lithology. Hematite is the dominant carrier in the limestones, while in the silts magnetite/maghemite prevail

The gut microbiome: a new frontier in musculoskeletal research

Purpose of the review The human gut harbors a complex community of microbes that influence many processes regulating musculoskeletal development and homeostasis. This review gives an update on the current knowledge surrounding the impact of the gut microbiota on musculoskeletal health, with an emphasis on research conducted over the last three years. Recent findings The gut microbiota and their metabolites are associated with sarcopenia, osteoporosis, osteoarthritis, and rheumatoid arthritis. The field is moving fast from describing simple correlations to pursue establishing causation through clinical trials. The gut microbiota and their microbial-synthesized metabolites hold promise for offering new potential alternatives for the prevention and treatment of musculoskeletal diseases given its malleability and response to environmental stimuli.</p

Closed String Field Theory with Dynamical D-brane

We consider a closed string field theory with an arbitrary matter current as a source of the closed string field. We find that the source must satisfy a constraint equation as a consequence of the BRST invariance of the theory. We see that it corresponds to the covariant conservation law for the matter current, and the equation of motion together with this constraint equation determines the classical behavior of both the closed string field and the matter. We then consider the boundary state (D-brane) as an example of a source. We see that the ordinary boundary state cannot be a source of the closed string field when the string coupling g turns on. By perturbative expansion, we derive a recursion relation which represents the bulk backreaction and the D-brane recoil. We also make a comment on the rolling tachyon boundary state.Comment: 30 pages, LaTeX2e, no figures. Typos are correcte

Development of a prediction model for future risk of radiographic hip osteoarthritis

Objective: To develop and validate a prognostic model for incident radiologic hip osteoarthritis (HOA) and determine the value of previously identified predictive factors. Design: We first validated previously reported predictive factors for HOA by performing univariate and multivariate analyses for all predictors in three large prospective cohorts (total sample size of 4548 with 653 incident cases). The prognostic model was developed in 2327 individuals followed for 10 years from the Rotterdam Study-I (RS-I) cohort. External validation of the model was tested on discrimination in two other cohorts: RS-II (n = 1435) and the Cohort Hip and Cohort Knee (CHECK) study (n = 786). Results: From the total number of 28 previously reported predictive factors, we were able to replicate 13 factors, while 15 factors were not significantly predictive in a meta-analysis of the three cohorts. The basic model including the demographic, questionnaire, and clinical examination variables (area under the receiver-operating characteristic curve (AUC) = 0.67) or genetic markers (AUC = 0.55) or urinary C-terminal cross-linked telopeptide of type II collagen (uCTX-II) levels (AUC = 0.67) alone were poor predictors of HOA in all cohorts. Imaging factors showed the highest predictive value for the development of HOA (AUC = 0.74). Addition of imaging variables to the basic model led to substantial improvement in the discriminative ability of the model (AUC = 0.78) compared with uCTX-II (AUC = 0.74) or genetic markers (AUC = 0.68). Applying external validation, similar results were observed in the RS-II and the CHECK cohort. Conclusions: The developed prediction model included demographic, a limited number of questionnaire, and imaging risk factors seems promising for prediction of HOA

Azimuthal asymmetries in lepton-pair production at a fixed-target experiment using the LHC beams (AFTER)

A multi-purpose fixed-target experiment using the proton and lead-ion beams of the LHC was recently proposed by Brodsky, Fleuret, Hadjidakis and Lansberg, and here we concentrate our study on some issues related to the spin physics part of this project (referred to as AFTER). We study the nucleon spin structure through $pp$ and $pd$ processes with a fixed-target experiment using the LHC proton beams, for the kinematical region with 7 TeV proton beams at the energy in center-of-mass frame of two nucleons $\sqrt{s}=115$ GeV. We calculate and estimate the $\cos2\phi$ azimuthal asymmetries of unpolarized $pp$ and $pd$ dilepton production processes in the Drell--Yan continuum region and at the $Z$-pole. We also calculate the $\sin(2\phi-\phi_S)$, $\sin(2\phi+\phi_S)$ and $\sin2\phi$ azimuthal asymmetries of $pp$ and $pd$ dilepton production processes with the target proton and deuteron longitudinally or transversally polarized in the Drell--Yan continuum region and around $Z$ resonances region. We conclude that it is feasible to measure these azimuthal asymmetries, consequently the three-dimensional or transverse momentum dependent parton distribution functions (3dPDFs or TMDs), at this new AFTER facility.Comment: 15 pages, 40 figures. Version accepted for publication in EPJ

Endothelial dysfunction and low-grade inflammation are associated with greater arterial stiffness over a 6-year period

Endothelial dysfunction and low-grade inflammation are associated with cardiovascular disease. Arterial stiffening plays an important role in cardiovascular disease and, thus, may be a mechanism through which endothelial dysfunction and/or low-grade inflammation lead to cardiovascular disease. We investigated the associations between, on the one hand, biomarkers of endothelial dysfunction (soluble endothelial selectin, thrombomodulin, and both vascular and intercellular adhesion molecules 1 and von Willebrand factor) and of low-grade inflammation (C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumor necrosis factor-α and, soluble intercellular adhesion molecule 1) and, on the other hand, arterial stiffness over a 6-year period, in 293 healthy adults (155 women). Biomarkers were combined into mean z scores. Carotid, femoral, and brachial arterial stiffness and carotid-femoral pulse wave velocity were determined by ultrasonography. Measurements were obtained when individuals were 36 and 42 years of age. Associations were analyzed with generalized estimating equation and adjusted for sex, height, and mean arterial pressure. The endothelial dysfunction z score was inversely associated with femoral distensibility (β:-0.51 [95% CI:-0.95 to-0.06]) and compliance coefficients (β:-0.041 [95% CI:-0.076 to-0.006]) but not with carotid or brachial stiffness or carotid-femoral pulse wave velocity. The low-grade inflammation z score was inversely associated with femoral distensibility (β:-0.51 [95% CI:-0.95 to-0.07]) and compliance coefficients (β:-0.050 [95% CI:-0.084 to-0.016]) and with carotid distensibility coefficient (β:-0.910 [95% CI:-1.810 to-0.008]) but not with brachial stiffness or carotid-femoral pulse wave velocity. Biomarkers of endothelial dysfunction and low-grade inflammation are associated with greater arterial stiffness. This provides evidence that arterial stiffening may be a mechanism through which endothelial dysfunction and low-grade inflammation lead to cardiovascular disease

Flux Backgrounds in 2D String Theory

We study RR flux backgrounds in two dimensional type 0 string theories. In particular, we study the relation between the 0A matrix model and the extremal black hole in two dimensions. Using T-duality we find a dual flux background in type 0B theory and propose its matrix model description. When the Fermi level is set to zero this system remains weakly coupled and exhibits a larger symmetry related to the structure of flux vacua. Finally, we construct a two dimensional type IIB background as an orbifold of the 0B background.Comment: Harvmac, 40 pages, 6 figs, minor changes, references adde

Chopped or long roughage: what do calves prefer? Using cross point analysis of double demand functions

The present study aimed to quantify calves'(Bos taurus) preference for long versus chopped hay and straw, and hay versus straw, using cross point analysis of double demand functions, in a context where energy intake was not a limiting factor. Nine calves, fed milk replacer and concentrate, were trained to work for roughage rewards from two simultaneously available panels. The cost (number of muzzle presses) required on the panels varied in each session (left panel/right panel): 7/35, 14/28, 21/21, 28/14, 35/7. Demand functions were estimated from the proportion of rewards achieved on one panel relative to the total number of rewards achieved in one session. Cross points (cp) were calculated as the cost at which an equal number of rewards was achieved from both panels. The deviation of the cp from the midpoint (here 21) indicates the strength of the preference. Calves showed a preference for long versus chopped hay (cp ¿=¿14.5; P ¿=¿0.004), and for hay versus straw (cp ¿=¿38.9; P¿=¿0.004), both of which improve rumen function. Long hay may stimulate chewing more than chopped hay, and the preference for hay versus straw could be related to hedonic characteristics. No preference was found for chopped versus long straw (cp ¿=¿20.8; P¿=¿0.910). These results could be used to improve the welfare of calves in production systems; for example, in systems where calves are fed hay along with high energy concentrate, providing long hay instead of chopped could promote roughage intake, rumen development, and rumination