Design of Non-Uniformly Excited Linear Slot Arrays Fed by Coplanar Waveguide

Non

Psychological factors associated with response to treatment in rheumatoid arthritis

This paper presents a comprehensive review of research relating psychological domains with response to therapy in patients with rheumatoid arthritis. A holistic approach to the disease was adopted by incorporating not only disease activity but also dimensions of the impact of disease on patients' lives. Psychological distress, including depression and anxiety, is common among patients with rheumatoid arthritis and has a significant negative impact on response to therapy and on patients' abilities to cope with chronic illness. Evidence regarding the influence of positive psychological dimensions such as acceptance, optimism, and adaptive coping strategies is scarce. The mechanisms involved in these interactions are incompletely understood, although changes in neuro-endocrine-immune pathways, which are common to depression and rheumatoid arthritis, seem to play a central role. Indirect psychological influences on therapeutic efficacy and long-term effectiveness include a myriad of factors such as adherence, placebo effects, cognition, coping strategies, and family and social support. Data suggest that recognition and appropriate management of psychological distress may improve response to treatment and significantly reduce disease burden

Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data

Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo

Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes

<p>Background: Resistance to ESAs (erythropoietin stimulating agents) is highly prevalent in hemodialysis patients with diabetes and associated with an increased mortality. The aim of this study was to identify predictors for ESA resistance and to develop a prediction model for the risk stratification in these patients.</p> <p>Methods: A post-hoc analysis was conducted of the 4D study, including 1015 patients with type 2 diabetes undergoing hemodialysis. Determinants of ESA resistance were identified by univariate logistic regression analyses. Subsequently, multivariate models were performed with stepwise inclusion of significant predictors from clinical parameters, routine laboratory and specific biomarkers.</p> <p>Results: In the model restricted to clinical parameters, male sex, shorter dialysis vintage, lower BMI, history of CHF, use of ACE-inhibitors and a higher heart rate were identified as independent predictors of ESA resistance. In regard to routine laboratory markers, lower albumin, lower iron saturation, higher creatinine and higher potassium levels were independently associated with ESA resistance. With respect to specific biomarkers, higher ADMA and CRP levels as well as lower Osteocalcin levels were predictors of ESA resistance.</p> <p>Conclusions: Easily obtainable clinical parameters and routine laboratory parameters can predict ESA resistance in diabetic hemodialysis patients with good discrimination. Specific biomarkers did not meaningfully further improve the risk prediction of ESA resistance. Routinely assessed data can be used in clinical practice to stratify patients according to the risk of ESA resistance, which may help to assign appropriate treatment strategies.</p&gt

Cancer associated auto-antibodies to MUC1 and MUC4 - A blinded case control study of colorectal cancer in UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Recent reports suggest that autoantibodies directed to aberrantly glycosylated mucins, in particular MUC1 and MUC4, are found in patients with colorectal cancer. There is, however, limited information on the autoantibody levels prior to clinical diagnosis, and their utility in cancer screening in the general population. In this study, we have generated O-glycosylated synthetic MUC1 and MUC4 peptides in vitro, to mimic cancer associated glycoforms, and displayed these on microarrays. The assay's performance was tested through an initial screening of serum samples taken from patients at the time of colorectal cancer diagnosis and healthy controls. Subsequently the selected biomarkers were evaluated in a blinded nested case control study, using stored serum samples from among the 50,640 women randomised to the multimodal arm of the UKCTOCS, where women gave annual blood samples for several years. Cases were 97 postmenopausal women who developed colorectal cancer following recruitment, and were age-matched to 97 women without any history of cancer. MUC1-STn and MUC1-Core3 IgG autoantibodies identified cases with 8.2% and 13.4% sensitivity, respectively, at 95% specificity. IgA to MUC4-glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity to 32.0% at 95% specificity in the UKCTOCS set. These findings suggest that a combination of antibody signatures may have a role as part of a biomarker panel for the early detection of colorectal cancer

‘Warrant’ revisited: Integrating mathematics teachers’ pedagogical and epistemological considerations into Toulmin’s model for argumentation

In this paper, we propose an approach to analysing teacher arguments that takes into account field dependence—namely, in Toulmin’s sense, the dependence of warrants deployed in an argument on the field of activity to which the argument relates. Freeman, to circumvent issues that emerge when we attempt to determine the field(s) that an argument relates to, proposed a classification of warrants (a priori, empirical, institutional and evaluative). Our approach to analysing teacher arguments proposes an adaptation of Freeman’s classification that distinguishes between: epistemological and pedagogical a priori warrants, professional and personal empirical warrants, epistemological and curricular institutional warrants, and evaluative warrants. Our proposition emerged from analyses conducted in the course of a written response and interview study that engages secondary mathematics teachers with classroom scenarios from the mathematical areas of analysis and algebra. The scenarios are hypothetical, grounded on seminal learning and teaching issues, and likely to occur in actual practice. To illustrate our proposed approach to analysing teacher arguments here, we draw on the data we collected through the use of one such scenario, the Tangent Task. We demonstrate how teacher arguments, not analysed for their mathematical accuracy only, can be reconsidered, arguably more productively, in the light of other teacher considerations and priorities: pedagogical, curricular, professional and personal

Screening chimeric GAA variants in preclinicalstudy results in hematopoietic stem cell genetherapy candidate vectors for Pompe disease

Pompe disease is a rare genetic neuromuscular disorder caused by acid α-glucosidase (GAA) deficiency resulting in lysosomal glycogen accumulation and progressive myopathy. Enzyme replacement therapy, the current standard of care, penetrates poorly into the skeletal muscles and the peripheral and central nervous system (CNS), risks recombinant enzyme immunogenicity, and requires high doses and frequent infusions. Lentiviral vector-mediated hematopoietic stem and progenitor cell (HSPC) gene therapy was investigated in a Pompe mouse model using a clinically relevant promoter driving nine engineered GAA coding sequences incorporating distinct peptide tags and codon optimizations. Vectors solely including glycosylation-independent lysosomal targeting tags enhanced secretion and improved reduction of glycogen, myofiber, and CNS vacuolation in key tissues, although GAA enzyme activity and protein was consistently lower compared with native GAA. Genetically modified microglial cells in brains were detected at low levels but provided robust phenotypic correction. Furthermore, an amino acid substitution introduced in the tag reduced insulin receptor-mediated signaling with no evidence of an effect on blood glucose levels in Pompe mice. This study demonstrated the therapeutic potential of lentiviral HSPC gene therapy exploiting optimized GAA tagged coding sequences to reverse Pompe disease pathology in a preclinical mouse model, providing promising vector candidates for further investigation

Age-dependent prevalence of 14 high-risk HPV types in the Netherlands: implications for prophylactic vaccination and screening

We determined the prevalence of type-specific hrHPV infections in the Netherlands on cervical scrapes of 45 362 women aged 18–65 years. The overall hrHPV prevalence peaked at the age of 22 with peak prevalence of 24%. Each of the 14 hrHPV types decreased significantly with age (P-values between 0.0009 and 0.03). The proportion of HPV16 in hrHPV-positive infections also decreased with age (OR=0.76 (10-year scale), 95% CI=0.67–0.85), and a similar trend was observed for HPV16 when selecting hrHPV-positive women with cervical intraepithelial neoplasia grade 2 or worse (CIN2+) (OR=0.76, 95% CI=0.56–1.01). In women eligible for routine screening (age 29–61 years) with confirmed CIN2+, 65% was infected with HPV16 and/or HPV18. When HPV16/18-positive infections in women eligible for routine screening were discarded, the positive predictive value of cytology for the detection of CIN2+ decreased from 27 to 15%, the positive predictive value of hrHPV testing decreased from 26 to 15%, and the predictive value of a double-positive test (positive HPV test and a positive cytology) decreased from 54 to 41%. In women vaccinated against HPV16/18, screening remains important to detect cervical lesions caused by non-HPV16/18 types. To maintain a high-positive predictive value, screening algorithms must be carefully re-evaluated with regard to the screening modalities and length of the screening interval