Serum cartilage oligomeric matrix protein and clinical signs and symptoms of potential pre-radiographic hip and knee pathology

OBJECTIVE: To examine the cross-sectional relationship between serum cartilage oligomeric matrix protein (COMP) and hip and knee clinical signs and symptoms in a sample of adults without radiographic hip or knee osteoarthritis (OA). DESIGN: A total of 145 persons with available sera and no evidence of radiographic hip or knee OA (Kellgren-Lawrence grade 0) were randomly selected from the Caucasian participants of the Johnston County Osteoarthritis Project. COMP was quantified by a competitive ELISA assay with a monoclonal antibody 17-C10. Hip and knee clinical signs and symptoms were assessed by physical examination and interview, and their associations with Ln COMP analysed with general linear models. RESULTS: After adjustment for age, gender, body mass index (BMI), and other symptomatic joints, mean Ln COMP was statistically significantly higher among persons with hip-related clinical signs (P=0.018), among those with hip-related symptoms (P=0.046), and among individuals meeting American College of Rheumatology clinical criteria for hip OA (P=0.021). There were no statistically significant associations between any of the knee-related clinical signs and symptoms and Ln COMP. CONCLUSION: Serum COMP may be useful as a biomarker of pre-radiographic hip joint pathology; its utility as a biomarker of pre-radiographic knee joint pathology is unclear

Current and Emerging Pharmacotherapies for the Treatment of Relapsed Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a very aggressive cancer with poor outcome if left untreated, but it is also one of the most chemotherapy responsive cancers. Overall it has a very poor prognosis especially if it is chemotherapy resistant to first line treatment. Second line chemotherapy has not been very beneficial in SCLC as opposed to breast cancer and lymphoma. In the last few years topotecan is the only drug that has been approved by the food and drug administration (FDA) for the second line treatment of SCLC but in Japan another drug, amrubicin is approved. There are many combinations of different chemotherapies available in moderate to high intensity, in this difficult to treat patient to overcome the chemo resistance, but many of these studies are small or phase II trials. In this article we have reviewed single agent and multidrug regimens that were studied in both chemo sensitive and refractory setting, including the most recent clinical trials

NGO Legitimacy: Four Models

The aim of this paper is to examine NGOs’ legitimacy in the context of global politics. In order to yield a better understanding of NGOs’ legitimacy at the international level it is important to examine how their legitimacy claims are evaluated. This paper proposes dividing the literature into four models based on the theoretical and analytical approaches to their legitimacy claims: the market model, social change model, new institutionalism model and the critical model. The legitimacy criteria generated by the models are significantly different in their analytical scope of how one is to assess the role of NGOs operating as political actors contributing to democracy. The paper argues that the models present incomplete, and sometimes conflicting, views of NGOs’ legitimacy and that this poses a legitimacy dilemma for those assessing the political agency of NGOs in world politics. The paper concludes that only by approaching their legitimacy holistically can the democratic role of NGOs be explored and analysed in the context of world politics

Multiple Front Propagation Into Unstable States

The dynamics of transient patterns formed by front propagation in extended nonequilibrium systems is considered. Under certain circumstances, the state left behind a front propagating into an unstable homogeneous state can be an unstable periodic pattern. It is found by a numerical solution of a model of the Fr\'eedericksz transition in nematic liquid crystals that the mechanism of decay of such periodic unstable states is the propagation of a second front which replaces the unstable pattern by a another unstable periodic state with larger wavelength. The speed of this second front and the periodicity of the new state are analytically calculated with a generalization of the marginal stability formalism suited to the study of front propagation into periodic unstable states. PACS: 47.20.Ky, 03.40.Kf, 47.54.+rComment: 12 page

Super-Hubbard models and applications

We construct XX- and Hubbard- like models based on unitary superalgebras gl(N|M) generalising Shastry's and Maassarani's approach of the algebraic case. We introduce the R-matrix of the gl(N|M) XX model and that of the Hubbard model defined by coupling two independent XX models. In both cases, we show that the R-matrices satisfy the Yang--Baxter equation, we derive the corresponding local Hamiltonian in the transfer matrix formalism and we determine the symmetry of the Hamiltonian. Explicit examples are worked out. In the cases of the gl(1|2) and gl(2|2) Hubbard models, a perturbative calculation at two loops a la Klein and Seitz is performed.Comment: 26 page

Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians

Background: Hallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome-wide association study (GWAS) conducted in 4409 Caucasians did not identify genome-wide significant associations with hallux valgus in both gender-specific and sex-combined GWAS meta-analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus. Methods: A total of 5925 individuals of European Ancestry were categorized into two groups: 'hallux valgus present' (n = 2314) or 'no deformity' (n = 3611) as determined by trained examiners or using the Manchester grading scale. Genotyping was performed using commercially available arrays followed by imputation to the Haplotype Reference Consortium (HRC) reference panel version 1.1. We conducted both sex-specific and sex-combined association analyses using logistic regression and generalized estimating equations as appropriate in each cohort. Results were then combined in a fixed-effects inverse-variance meta-analyses. Functional Mapping and Annotation web-based platform (FUMA) was used for positional mapping, gene and gene-set analyses. Results: We identified a novel locus in the intronic region of CLCA2 on chromosome 1, rs55807512 (OR = 0.48, p = 2.96E-09), an expression quantitative trait locus for COL24A1, a member of the collagen gene family. Conclusion: In this report of the largest GWAS of hallux valgus to date, we identified a novel genome-wide significant locus for hallux valgus. Additional replication and functional follow-up will be needed to determine the functional role of this locus in hallux valgus biology

Concerted loop motion triggers induced fit of FepA to ferric enterobactin

Spectroscopic analyses of fluorophore-labeled Escherichia coli FepA described dynamic actions of its surface loops during binding and transport of ferric enterobactin (FeEnt). When FeEnt bound to fluoresceinated FepA, in living cells or outer membrane fragments, quenching of fluorophore emissions reflected conformational motion of the external vestibular loops. We reacted Cys sulfhydryls in seven surface loops (L2, L3, L4, L5, L7 L8, and L11) with fluorophore maleimides. The target residues had different accessibilities, and the labeled loops themselves showed variable extents of quenching and rates of motion during ligand binding. The vestibular loops closed around FeEnt in about a second, in the order L3 > L11 > L7 > L2 > L5 > L8 > L4. This sequence suggested that the loops bind the metal complex like the fingers of two hands closing on an object, by individually adsorbing to the iron chelate. Fluorescence from L3 followed a biphasic exponential decay as FeEnt bound, but fluorescence from all the other loops followed single exponential decay processes. After binding, the restoration of fluorescence intensity (from any of the labeled loops) mirrored cellular uptake that depleted FeEnt from solution. Fluorescence microscopic images also showed FeEnt transport, and demonstrated that ferric siderophore uptake uniformly occurs throughout outer membrane, including at the poles of the cells, despite the fact that TonB, its inner membrane transport partner, was not detectable at the poles

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs49654

Hamburg's Spaces of Danger: Race, Violence and Memory in a Contemporary Global City

Germany today is experiencing the strongest upsurge of right-wing populism since the second world war, most notably with the rise of Pegida and Alternative für Deutschland. Yet wealthy global cities like Hamburg continue to present themselves as the gatekeepers of liberal progress and cosmopolitan openness. This article argues that Hamburg’s urban boosterism relies on, while simultaneously obscuring, the same structures of racial violence that embolden reactionary movements. Drawing on the work of Walter Benjamin and Allan Pred, we present an archaeology of Hamburg’s landscape, uncovering some of its ‘spaces of danger’––sites layered with histories of violence, many of which lie buried and forgotten. We find that these spaces, when they become visible, threaten to undermine Hamburg’s cosmopolitan narrative. They must, as a result, be continually erased or downplayed in order to secure the city as an attractive site for capital investment. To illustrate this argument, we give three historical examples: Hamburg’s role in the Hanseatic League during the medieval and early modern period; the city under the Nazi regime; and the recent treatment of Black African refugees. The article’s main contribution is to better situate issues of historical landscape, collective memory and racialized violence within the political economy of today’s global city