Degenerate flag varieties: moment graphs and Schr\"oder numbers

We study geometric and combinatorial properties of the degenerate flag varieties of type A. These varieties are acted upon by the automorphism group of a certain representation of a type A quiver, containing a maximal torus T. Using the group action, we describe the moment graphs, encoding the zero- and one-dimensional T-orbits. We also study the smooth and singular loci of the degenerate flag varieties. We show that the Euler characteristic of the smooth locus is equal to the large Schr\"oder number and the Poincar\'e polynomial is given by a natural statistics counting the number of diagonal steps in a Schr\"oder path. As an application we obtain a new combinatorial description of the large and small Schr\"oder numbers and their q-analogues.Comment: 25 page

Will We Do If We Can? Habitual Qualitative and Quantitative Physical Activity in Multi-Morbid, Older Persons with Cognitive Impairment

This study aimed to identify determinants of quantitative dimensions of physical activity (PA; duration, frequency, and intensity) in community-dwelling, multi-morbid, older persons with cognitive impairment (CI). In addition, qualitative and quantitative aspects of habitual PA have been described. Quantitative PA and qualitative gait characteristics while walking straight and while walking turns were documented by a validated, sensor-based activity monitor. Univariate and multiple linear regression analyses were performed to delineate associations of quantitative PA dimensions with qualitative characteristics of gait performance and further potential influencing factors (motor capacity measures, demographic, and health-related parameters). In 94 multi-morbid, older adults (82.3 ± 5.9 years) with CI (Mini-Mental State Examination score: 23.3 ± 2.4), analyses of quantitative and qualitative PA documented highly inactive behavior (89.6% inactivity) and a high incidence of gait deficits, respectively. The multiple regression models (adjusted R$^{2}$ = 0.395–0.679, all p < 0.001) identified specific qualitative gait characteristics as independent determinants for all quantitative PA dimensions, whereas motor capacity was an independent determinant only for the PA dimension duration. Demographic and health-related parameters were not identified as independent determinants. High associations between innovative, qualitative, and established, quantitative PA performances may suggest gait quality as a potential target to increase quantity of PA in multi-morbid, older persons

An Assessment of Computer Use, Knowledge, and Attitudes of Diabetes Educators

A questionnaire to survey attitudes, use, and knowledge of computers was sent to 816 randomly selected members of AADE to determine the degree to which currently available computer resources are used in diabetes education and to investigate the need for future computing resources designed to support diabetes education. Analysis of the data showed that even diabetes educators who use computers infrequently have a generally favorable attitude toward them. Highest use of computers is in noneducational applications, mostly for word processing and record keeping. Most respondents believe that computers have yet to make a major contribution to the teaching and learning process in diabetes education, and few felt adequately prepared for creative use or development of computer applications. Increasing the role of computers in support of patient education will require encouragement and demonstrations of computer efficacy from health care institutions and professional organizations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68469/2/10.1177_014572179201800107.pd

Aromatase inhibitors, estrogens and musculoskeletal pain: estrogen-dependent T-cell leukemia 1A (TCL1A) gene-mediated regulation of cytokine expression

Introduction: Arthralgias and myalgias are major side effects associated with aromatase inhibitor (AI) therapy of breast cancer. In a recent genome-wide association study, we identified SNPs - including one that created an estrogen response element near the 3' end of the T-cell leukemia 1A (TCL1A) gene - that were associated with musculoskeletal pain in women on adjuvant AI therapy for breast cancer. We also showed estrogen-dependent, SNP-modulated variation in TCL1A expression and, in preliminary experiments, showed that TCL1A could induce IL-17RA expression. In the present study, we set out to determine whether these SNPs might influence cytokine expression and effect more widely, and, if so, to explore the mechanism of TCL1A-related AI-induced side effects. Methods: The functional genomic experiments performed included determinations of TCL1A, cytokine and cytokine receptor expression in response to estrogen treatment of U2OS cells and lymphoblastoid cell lines that had been stably transfected with estrogen receptor alpha. Changes in mRNA and protein expression after gene knockdown and overexpression were also determined, as was NF-κB transcriptional activity. Results: Estradiol (E2) increased TCL1A expression and, in a TCL1A SNP-dependent fashion, also altered the expression of IL-17, IL-17RA, IL-12, IL-12RB2 and IL-1R2. TCL1A expression was higher in E2-treated lymphoblastoid cell lines with variant SNP genotypes, and induction of the expression of cytokine and cytokine receptor genes was mediated by TCL1A. Finally, estrogen receptor alpha blockade with ICI-182,780 in the presence of E2 resulted in greatly increased NF-κB transcriptional activity, but only in cells that carried variant SNP genotypes. These results linked variant TCL1A SNP sequences that are associated with AI-dependent musculoskeletal pain with increased E2-dependent TCL1A expression and with downstream alterations in cytokine and cytokine receptor expression as well as NF-κB transcriptional activity. Conclusions: SNPs near the 3' terminus of TCL1A were associated with AI-dependent musculoskeletal pain. E2 induced SNP-dependent TCL1A expression, which in turn altered IL-17, IL-17RA, IL-12, IL-12RB2, and IL-1R2 expression as well as NF-κB transcriptional activity. These results provide a pharmacogenomic explanation for a clinically important adverse drug reaction as well as insights into a novel estrogen-dependent mechanism for the modulation of cytokine and cytokine receptor expression

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases - a longitudinal study.

INTRODUCTION: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects. METHODS: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients. RESULTS: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p &lt; 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections. CONCLUSIONS: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections

Sensory marketing for the organic market : key insights from the EU funded project ECROPOLIS

none13The organic food sector in Europe is growing since several years. However the development of the organic food market varies across European countries. High developed markets (e.g. Germany and Switzerland) coexist with markets in the introduction stage (e.g. Poland). Sensory marketing strategies are not well implemented in the organic sector although this market segment is built on consumers with clear preferences for differentiated sensory properties. Sensory attributes are an important element of organic marketing and a possible tool to create a unique value proposition. The EC funded project Ecropolis investigated the organic market in six European countries (Germany, Poland, The Netherlands, Italy, France and Switzerland). Based on its results the OSIS database was developed and made available on the website. The main results of Ecropolis are summarized for different target groups on different levels: On level 1 a short summary addressed to consumers, retailers and SMEs in English, German, Italian, French, Dutch and Polish is available for different product groups. A concise overview about specific sensory characteristics for the chosen product groups in the six countries is provided, together with information about consumer habits and sensory marketing for those product groups. OSIS offers a sensory journey through the participating countries to learn about country specific preferences. On level 2 more specific guidance for the practical implementation of sensory marketing and sensory analyses in the companies is worked out in form of fact sheets addressed to retailers, SME and SME associations also available in 6 languages. On level 3 all public research reports are available for the interested audience. OSIS is a unique tool that provides support with ready to use information for various questions that occur in organic food production, marketing and communication. Next to OSIS all the Ecropolis project results and dissemination activities are available on the website www.ecropolis.org.mixedM.-L. Cezanne; L. Baumgart; A. Bongartz; K. Buchecker; M. Canavari; T. Gallina Toschi; A. Kole; E. Kostyra; S. Kremer; P. Reichl; A. Spiller; S. Zakowska-Biemans; U. Kretzschmar-Rüger et al.M.-L. Cezanne; L. Baumgart; A. Bongartz; K. Buchecker; M. Canavari; T. Gallina Toschi; A. Kole; E. Kostyra; S. Kremer; P. Reichl; A. Spiller; S. Zakowska-Biemans; U. Kretzschmar-Rüger et al

Imaging in the time of NFD/NSF: do we have to change our routines concerning renal insufficiency?

To date there are potential chronology-based but not conclusive reasons to believe that at least some of the gadolinium complexes play a causative role in the pathophysiology of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). Still, the exact pathogenesis and the risk for patients is unclear beside the obvious connection to moderate to severe renal insufficiency. So far, MR imaging with Gd-enhancement was regarded as the safest imaging modality in these patients—the recent development creates tremendous uncertainty in the MR-community. Nevertheless, one should remember that, despite the over 200 cases of NSF and about 100 with proven involvement of Gd3+, the vast majority of over 200 million patients exposed to gadolinium since the 1980s have tolerated these agents well. Importantly, NSF is a rare disease and does not appear to occur in patients without renal impairment. Many patients and researchers have undergone MR investigations with Gd exposure in the past. For those, it is essential to know about the safety of the agents at normal renal function. We can hope that pharmacoepidemiological and preclinical studies will allow us to better understand the pathophysiology and role of the various MR contrast agents in the near future

A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis

Rheumatoid arthritis (RA) is strongly associated with the human leukocyte antigen (HLA)- DRB1 locus that possesses the shared susceptibility epitope (SE) and the citrullination of self-antigens. We show how citrullinated aggrecan and vimentin epitopes bind to HLADRB1* 04:01/04. Citrulline was accommodated within the electropositive P4 pocket of HLA-DRB1*04:01/04, whereas the electronegative P4 pocket of the RA-resistant HLADRB1* 04:02 allomorph interacted with arginine or citrulline-containing epitopes. Peptide elution studies revealed P4 arginine-containing peptides from HLA-DRB1*04:02, but not from HLA-DRB1*04:01/04. Citrullination altered protease susceptibility of vimentin, thereby generating self-epitopes that are presented to T cells in HLA-DRB1*04:01+ individuals. Using HLA-II tetramers, we observed citrullinated vimentin- and aggrecan-specific CD4+ T cells in the peripheral blood of HLA-DRB1*04:01+ RA-affected and healthy individuals. In RA patients, autoreactive T cell numbers correlated with disease activity and were deficient in regulatory T cells relative to healthy individuals. These findings reshape our understanding of the association between citrullination, the HLA-DRB1 locus, and T cell autoreactivity in RA

Atherosclerotic renal artery stenosis is prevalent in cardiorenal patients but not associated with left ventricular function and myocardial fibrosis as assessed by cardiac magnetic resonance imaging

<p>Abstract</p> <p>Background</p> <p>Atherosclerotic renal artery stenosis (ARAS) is common in cardiovascular diseases and associated with hypertension, renal dysfunction and/or heart failure. There is a paucity of data about the prevalence and the role of ARAS in the pathophysiology of combined chronic heart failure (CHF) and chronic kidney disease (CKD). We investigated the prevalence in patients with combined CHF/CKD and its association with renal function, cardiac dysfunction and the presence and extent of myocardial fibrosis.</p> <p>Methods</p> <p>The EPOCARES study (ClinTrialsNCT00356733) investigates the role of erythropoietin in anaemic patients with combined CHF/CKD. Eligible subjects underwent combined cardiac magnetic resonance imaging (cMRI), including late gadolinium enhancement, with magnetic resonance angiography of the renal arteries (MRA).</p> <p>Results</p> <p>MR study was performed in 37 patients (median age 74 years, eGFR 37.4 ± 15.6 ml/min, left ventricular ejection fraction (LVEF) 43.3 ± 11.2%), of which 21 (56.8%) had ARAS (defined as stenosis >50%). Of these 21 subjects, 8 (21.6%) had more severe ARAS >70% and 8 (21.6%) had a bilateral ARAS >50% (or previous bilateral PTA). There were no differences in age, NT-proBNP levels and medication profile between patients with ARAS versus those without. Renal function declined with the severity of ARAS (p = 0.03), although this was not significantly different between patients with ARAS versus those without. Diabetes mellitus was more prevalent in patients without ARAS (56.3%) against those with ARAS (23.8%) (p = 0.04). The presence and extent of late gadolinium enhancement, depicting myocardial fibrosis, did not differ (p = 0.80), nor did end diastolic volume (p = 0.60), left ventricular mass index (p = 0.11) or LVEF (p = 0.15). Neither was there a difference in the presence of an ischemic pattern of late enhancement in patients with ARAS versus those without.</p> <p>Conclusions</p> <p>ARAS is prevalent in combined CHF/CKD and its severity is associated with a decline in renal function. However, its presence does not correlate with a worse LVEF, a higher left ventricular mass or with the presence and extent of myocardial fibrosis. Further research is required for the role of ARAS in the pathophysiology of combined chronic heart and renal failure.</p