Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study.

INTRODUCTION: Neovascularization contributes to the development of sustained synovial inflammation in the early stages of Rheumatoid Arthritis. Ultrasound (US) provides an indirect method of assessing synovial blood flow and has been shown to correlate with clinical disease activity in patients with Rheumatoid Arthritis. This study examines the relationship of US determined synovitis with synovial vascularity, angiogenic/lymphangiogenic factors and cellular mediators of inflammation in a cohort of patients with early Rheumatoid Arthritis (RA) patients prior to therapeutic intervention with disease modifying therapy or corticosteroids. METHODS: An ultrasound guided synovial biopsy of the supra-patella pouch was performed in 12 patients with early RA prior to treatment. Clinical, US and biochemical assessments were undertaken prior to the procedure. Ultrasound images and histological samples were obtained from the supra-patella pouch. Histological samples were stained for Factor VIII and a-SMA (a-smooth muscle actin). Using digital imaging analysis a vascular area score was recorded. QT-PCR (quantitative-PCR) of samples provided quantification of angiogenic and lymphangiogenic gene expression and immunohistochemistry stained tissue was scored for macrophage, T cell and B cell infiltration using an existing semi-quantitative score. RESULTS: Power Doppler showed a good correlation with histological vascular area (Spearman r--0.73) and angiogenic factors such as vascular endothelial growth factor-A (VEGF-A), Angiopoietin 2 and Tie-2. In addition, lymphangiogenic factors such as VEGF-C and VEGF-R3 correlated well with US assessment of synovitis. A significant correlation was also found between power Doppler and synovial thickness, pro-inflammatory cytokines and sub-lining macrophage infiltrate. Within the supra-patella pouch there was no significant difference in US findings, gene expression or inflammatory cell infiltrate between any regions of synovium biopsied. CONCLUSION: Ultrasound assessment of synovial tissue faithfully reflects synovial vascularity. Both grey scale and power Doppler synovitis in early RA patients correlate with a pro-angiogenic and lymphangiogenic gene expression profile. In early RA both grey scale and power Doppler synovitis are associated with a pro-inflammatory cellular and cytokine profile providing considerable validity in its use as an objective assessment of synovial inflammation in clinical practice

PENGARUH PANDANGAN IKLAN, DIGITAL MARKETING, DAN CITRA MEREK TERHADAP KEPUASAN PENUMPANG PADA PT BIRO PERJALANAN WISATA NUSA INDAH

This study aims to examine the effect of advertising views, digital marketing, and brand image on passenger satisfaction at PT Nusa Indah Travel Bureau. This research uses a type of quantitative approach. The population of this study are all users or people who have used products and services from PT. Nusa Indah Travel Bureau with unknown population size. The research sample used the Cochran formula with a total of 100 respondents using the non-probability sampling method. The collected data will be analyzed using descriptive statistical tests, data quality tests, classical assumption tests, influence tests and hypothesis testing. The results of the multiple linear regression analysis show that advertising views have an effect of 20.5% on passenger satisfaction. Digital marketing has an influence of 33.5% on passenger satisfaction. Brand image has an influence of 31.7% on passenger satisfaction. Analysis of the coefficient of determination (R2) shows that the views of advertising, digital marketing and brand image have a strong influence on passenger satisfaction at PT. Nusa Indah Travel Bureau with a proportion of influence of 67.7% The results of the hypothesis test show that both partially and simultaneously views of advertising, digital marketing, and brand image have a positive and significant effect on passenger satisfaction at PT Nusa Indah Travel Bureau.Penelitian ini bertujuan untuk menguji pengaruh pandangan iklan, pemasaran digital, dan merekkepuasan penumpang di PT Nusa Indah Travel Bureau. Penelitian ini menggunakan ajenis pendekatan kuantitatif. Populasi dari penelitian ini adalah seluruh pengguna atau orang yangtelah menggunakan produk dan layanan dari PT. Biro Perjalanan Wisata Nusa Indah dengan tidak diketahuiukuran populasi. Sampel penelitian menggunakan rumus Cochran dengan jumlah 100responden dengan menggunakan metode non-probability sampling. Data yang dikumpulkan akandianalisis dengan menggunakan uji statistik deskriptif, uji kualitas data, uji asumsi klasik,uji pengaruh dan uji hipotesis. Hasil analisis regresi linier bergandamenunjukkan bahwa tampilan iklan berpengaruh sebesar 20,5% terhadap kepuasan penumpang. Digitalpemasaran memiliki pengaruh sebesar 33,5% terhadap kepuasan penumpang. Citra merek memilikipengaruh sebesar 31,7% terhadap kepuasan penumpang. Analisis koefisien determinasi(R2) menunjukkan bahwa dilihat dari advertising, digital marketing dan brand image memiliki pengaruh yang kuatpengaruh terhadap kepuasan penumpang di PT. Biro Perjalanan Wisata Nusa Indah dengan proporsi sebesarpengaruh sebesar 67,7% Hasil uji hipotesis menunjukkan bahwa baik secara parsial maupunsecara bersamaan dilihat dari advertising, digital marketing, dan brand image memiliki pengaruh yang positifdan berpengaruh signifikan terhadap kepuasan penumpang di PT Biro Perjalanan Wisata Nusa Inda

NGS-pipe: a flexible, easily extendable, and highly configurable framework for NGS analysis

Next-generation sequencing is now an established method in genomics, and massive amounts of sequencing data are being generated on a regular basis. Analysis of the sequencing data is typically performed by lab-specific in-house solutions, but the agreement of results from different facilities is often small. General standards for quality control, reproducibility, and documentation are missing.; We developed NGS-pipe, a flexible, transparent, and easy-to-use framework for the design of pipelines to analyze whole-exome, whole-genome, and transcriptome sequencing data. NGS-pipe facilitates the harmonization of genomic data analysis by supporting quality control, documentation, reproducibility, parallelization, and easy adaptation to other NGS experiments. https://github.com/cbg-ethz/NGS-pipe [email protected]

Retrospective comparison of the distribution and abundance of breeding Prairie Warbler (Setophaga discolor) along eastern Georgian Bay, Ontario, Canada

Species inhabiting rare habitats or unique geographic regions may be underrepresented in standard surveys. More intensive, periodic surveys may be required to improve data quality, especially for species of conservation concern. Prairie Warbler (Setophaga discolor) has experienced range-wide declines of >50% in recent decades and is a species of conservation concern in Canada. The largest continually occupied breeding population of this species in Canada occurs along the shoreline of eastern Georgian Bay, Ontario, where annual Breeding Bird Survey and eBird coverage is generally poor. In 2015, we replicated a spatially intensive 1997 survey of this species along the eastern shore of Georgian Bay, visiting the same sites and using comparable methods. We detected more male birds at the survey sites in 2015 (estimated >350 breeding pairs) than in 1997 (estimated 265 breeding pairs). We also surveyed sites farther north than those covered in 1997, but the breeding range appears not to have moved substantially northward. We also conducted additional surveys and canoe transects in the core range in southern Georgian Bay to ensure that breeding birds were not being missed. Combining data from all our surveys in 2015, we estimated a total of 427 singing males in eastern Georgian Bay. Although overall numbers here appear to have increased in recent decades, localized declines in some areas warrant further investigation. The population appears to be stable or increasing in this region, but we recommend intensively re-surveying this population on at least a 20-year basis

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD

Some aspects of the quark-antiquark Wilson loop formalism in the NRQCD framework

Starting from the NRQCD Lagrangian the heavy quark-antiquark potential is written in terms of field strength insertions on a static Wilson loop. The relevant matching coefficients are given at the present status of knowledge. The short-range, perturbatively dominated, behaviour of the spin-dependent terms is discussed.Comment: 4 pages, Latex (espcrc2.sty), 2 figures. Talk presented at the Euroconference QCD'98, Montpellier, July 2-8, 1998; to appear in Nucl. Phys. B (Proc. Suppl.

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loc

Correlations of differentially expressed gap junction connexins cx26, cx30, cx32, cx43 and cx46 with breast cancer progression and prognosis.

BACKGROUND AND AIMS: Connexins and their cell membrane channels contribute to the control of cell proliferation and compartmental functions in breast glands and their deregulation is linked to breast carcinogenesis. Our aim was to correlate connexin expression with tumor progression and prognosis in primary breast cancers. MATERIALS AND METHODS: Meta-analysis of connexin isotype expression data of 1809 and 1899 breast cancers from the Affymetrix and Illumina array platforms, respectively, was performed. Expressed connexins were also monitored at the protein level in tissue microarrays of 127 patients equally representing all tumor grades, using immunofluorescence and multilayer, multichannel digital microscopy. Prognostic correlations were plotted in Kaplan-Meier curves and tested using the log-rank test and cox-regression analysis in univariate and multivariate models. RESULTS: The expression of GJA1/Cx43, GJA3/Cx46 and GJB2/Cx26 and, for the first time, GJA6/Cx30 and GJB1/Cx32 was revealed both in normal human mammary glands and breast carcinomas. Within their subfamilies these connexins can form homo- and heterocellular epithelial channels. In cancer, the array datasets cross-validated each other's prognostic results. In line with the significant correlations found at mRNA level, elevated Cx43 protein levels were linked with significantly improved breast cancer outcome, offering Cx43 protein detection as an independent prognostic marker stronger than vascular invasion or necrosis. As a contrary, elevated Cx30 mRNA and protein levels were associated with a reduced disease outcome offering Cx30 protein detection as an independent prognostic marker outperforming mitotic index and necrosis. Elevated versus low Cx43 protein levels allowed the stratification of grade 2 tumors into good and poor relapse free survival subgroups, respectively. Also, elevated versus low Cx30 levels stratified grade 3 patients into poor and good overall survival subgroups, respectively. CONCLUSION: Differential expression of Cx43 and Cx30 may serve as potential positive and negative prognostic markers, respectively, for a clinically relevant stratification of breast cancers

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes