'New ordinary' of 'winners' : South Africa as part of BRICS

ASC – Publicaties niet-programma gebonde

Износ кругов из СТМ при зубошлифовании

The problems of increasing the efficiency of grinding highly precision gearwheels of the 3–4 degree of precision using superhard material tools are discussed. The efficiency of cubic boron nitride dish grinding wheels in various bonds has been studied. Recommendations how to use cubic boron nitride wheels in gear grinding are given

Routine outcome monitoring en benchmarking: hoe kunnen we behandelresultaten op een zorgvuldige manier vergelijken?

Contains fulltext : 157216.pdf (publisher's version ) (Open Access)Achtergrond: Het structureel meten van de resultaten van een behandeling in de geestelijke gezondheidszorg en het vergelijken daarvan tussen instellingen helpen om inzicht te krijgen in het effect van behandelingen in de reguliere praktijk. Doel: Geven van een overzicht van de kwesties die van belang zijn bij het vergelijken van instellingen. Methode: Analyseren van documentatie en beleidsinformatie over en praktijkervaring met routine outcome monitoring (rom). Resultaten: We beschrijven knelpunten die kunnen ontstaan bij het vergelijken van instellingen en formuleren oplossingsrichtingen voor deze knelpunten. Daarbij staat centraal dat het werken met rom een groeiproces is, waarbij men experimenteert met verschillende oplossingsrichtingen en op basis van ervaringen definitieve keuzes maakt. Conclusie: Het is leerzaam om instellingen te vergelijken, zowel onderling als met 'best practices' (benchmarking). Instellingen verschillen echter in cliëntenpopulaties, meetprocedures en instrumentarium. Een zinvolle vergelijking is op termijn toch mogelijk.5 p

Rapid and Sustained Effect of Dupilumab on Work Productivity in Patients with Difficult-to-treat Atopic Dermatitis:Results from the Dutch BioDay Registry

Dupilumab treatment improves signs, symptoms, and quality of life in patients with moderate-to-severe atopic dermatitis. This study evaluated the impact of dupilumab treatment on absenteeism, presenteeism, and related costs in a large multi-centre cohort of adult patients with difficult-to-treat atopic dermatitis in daily practice. Patients treated with dupilumab participating in the Dutch BioDay Registry reporting employment were included. Absenteeism, presenteeism, and related costs at baseline and during follow-up were calculated using the Work Productivity and Activity Impairment questionnaire. A total of 218 adult patients with moderate-to-severe atopic dermatitis were included. Total work impairment reduced significantly from baseline (35.5%) to week 52 (11.5%), p &lt; 0.001. Median weekly productivity losses reduced significantly from baseline (€379.8 (140.7-780.8)) to week 52 (€0.0 (0.0-211.0), p &lt; 0.001). In this study, dupilumab treatment demonstrated a significant improvement in work productivity and reduction in associated costs in a large cohort of patients with difficult-to-treat atopic dermatitis in daily practice.</p

Dupilumab is very effective in a large cohort of difficult-to-treat adult atopic dermatitis patients:First clinical and biomarker results from the BioDay registry

Introduction: Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab treatment are scarce. Objective: To study the effect of 16-week treatment with dupilumab on clinical response and serum biomarkers in adult patients with moderate-severe AD in daily practice. Methods: Data were extracted from the BioDay registry, a prospective multicenter registry. Sixteen-week clinical effectiveness of dupilumab was expressed as number of patients achieving EASI-50 (Eczema Area and Severity Index) or EASI-75, as well as patient-reported outcomes measures (Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Numeric Rating Scale pruritus). Twenty-one biomarkers were measured in patients treated with dupilumab without concomitant use of oral immunosuppressive drugs at five different time points (baseline, 4, 8, 12, and 16 weeks). Results: In total, 138 patients treated with dupilumab in daily practice were included. This cohort consisted of patients with very difficult-to-treat AD, including 84 (61%) patients who failed treatment on ≥2 immunosuppressive drugs. At week 16, the mean percent change in EASI score was 73%. The EASI-50 and EASI-75 were achieved by 114 (86%) and 82 (62%) patients after 16 weeks of treatment. The most reported side effect was conjunctivitis, occurring in 47 (34%) patients. During dupilumab treatment, disease severity-related serum biomarkers (TARC, PARC, periostin, and IL-22), eotaxin-1, and eotaxin-3 significantly decreased. Conclusion: Treatment with dupilumab significantly improved disease severity and decreased severity-related serum biomarkers in patients with very difficult-to-treat AD in a daily practice setting

Sensitivity to situated positionings: Generating insight into organizational change

Within ethnographic forms of organisational research, sensitivity to context is generally acknowledged as a critical ingredient for analysing processes and practices. When conducting such research, however, researchers typically privilege one particular research context for generating knowledge: although some ethnographic scholars underscore the importance of adopting a diversity of both insider and outsider roles, ethnographic research is usually equated with gaining a deep familiarity with the field of study through immersion. First, we argue that, although immersion elicits valuable knowledge ‘from within’, its prioritisation inevitably blinds the researcher’s eye to equally interesting insights stemming from alternative – and often unintended – positionings. Testifying to the significance of researchers’ relational reflexivity for data interpretation, we show how a variety of researcher’ positionings vis-à-vis the researched generated a variety of insights. Critical sensitivity to fieldworker identities in an ethnographic study of planned organisational change within a police organisation allowed us, second, to criticise the change management literature for routinely building on a fixed dichotomy between ‘change agents’ and ‘change recipients’ and to empirically demonstrate a wider variety of police officers’ positionings in relation to change initiatives (i.e. countering, complying with and co-opting) and its initiators (i.e. engaging in other-depreciating, self-questioning or self-affirming identity work)

Genetically Programmed Differences in Epidermal Host Defense between Psoriasis and Atopic Dermatitis Patients

In the past decades, chronic inflammatory diseases such as psoriasis, atopic dermatitis, asthma, Crohn’s disease and celiac disease were generally regarded as immune-mediated conditions involving activated T-cells and proinflammatory cytokines produced by these cells. This paradigm has recently been challenged by the finding that mutations and polymorphisms in epithelium-expressed genes involved in physical barrier function or innate immunity, are risk factors of these conditions. We used a functional genomics approach to analyze cultured keratinocytes from patients with psoriasis or atopic dermatitis and healthy controls. First passage primary cells derived from non-lesional skin were stimulated with pro-inflammatory cytokines, and expression of a panel of 55 genes associated with epidermal differentiation and cutaneous inflammation was measured by quantitative PCR. A subset of these genes was analyzed at the protein level. Using cluster analysis and multivariate analysis of variance we identified groups of genes that were differentially expressed, and could, depending on the stimulus, provide a disease-specific gene expression signature. We found particularly large differences in expression levels of innate immunity genes between keratinocytes from psoriasis patients and atopic dermatitis patients. Our findings indicate that cell-autonomous differences exist between cultured keratinocytes of psoriasis and atopic dermatitis patients, which we interpret to be genetically determined. We hypothesize that polymorphisms of innate immunity genes both with signaling and effector functions are coadapted, each with balancing advantages and disadvantages. In the case of psoriasis, high expression levels of antimicrobial proteins genes putatively confer increased protection against microbial infection, but the biological cost could be a beneficial system gone awry, leading to overt inflammatory disease

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer

Background: Phenoxodiol is a novel isoflavone currently being studied in clinical trials for the treatment of cancer. This study reports the pharmacokinetics of phenoxodiol in patients with cancer.Methods: The pharmacokinetics of phenoxodiol was studied following a single intravenous (iv) bolus dose and during a continuous intravenous infusion. Three men with prostate cancer and 3 women with breast cancer received IV bolus phenoxodiol (5 mg/kg) and plasma was sampled for free and total phenoxodiol levels. On a separate occasion 5 of the same patients received a continuous intravenous infusion of phenoxodiol (2 mg/kg/h) and plasma was again sampled for free and total phenoxodiol levels. Phenoxodiol was measured using gradient HPLC with ultraviolet detection.Results: Following bolus injection, free and total phenoxodiol appeared to follow first order pharmacokinetics. The elimination half-lives for free and total phenoxodiol were 0.67 ± 0.53 h and 3.19 ± 1.93 h, respectively, while the total plasma clearance rates were 2.48 ± 2.33 L/h and 0.15 ± 0.08 L/h, respectively. The respective apparent volumes of distribution were 1.55 ± 0.69 L/kg and 0.64 ± 0.51 L/kg. During continuous intravenous infusion, free phenoxodiol accumulated rapidly to reach a mean concentration at steady state of 0.79 ± 0.14 μg/ml after 0.87 ± 0.18 h. The apparent accumulation half-life of free phenoxodiol was 0.17 ± 0.04 h while the plasma clearance during continuous infusion was 1.29 ± 0.23 L/h.Conclusions: Phenoxodiol has a short plasma half-life, particularly in the free form, leading to a rapid attainment of steady state levels during continuous intravenous infusion.Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000334000