Відкритість економік: фактори, показники та переваги

In de 'Kennismontage Hitte en Klimaat in de Stad' is een overzicht gemaakt van de huidige kennis rond de thema’s ‘stedelijk hitte-eiland’ en ‘hittestress’ relevant voor de uitvoeringspraktijk. De kennismontage is uitgevoerd door het Climate Proof Cities consortium in opdracht van de Alliantie Klimaatbestendige Steden, een samenwerkingsverband tussen de vier grote steden (Amsterdam, Rotterdam, Den Haag en Utrecht) en het Ministerie van Infrastructuur en Milieu. De kennismontage dient als informatiebasis voor de gemeenteambtenaar die met het thema hitte in de stad aan de slag wil

The era of bioengineering: how will this affect the next generation of cancer immunotherapy?

Immunotherapy consists of activating the patient's immune system to fight cancer and has the great potential of preventing future relapses thanks to immunological memory. A great variety of strategies have emerged to harness the immune system against tumors, from the administration of immunomodulatory agents that activate immune cells, to therapeutic vaccines or infusion of previously activated cancer-specific T cells. However, despite great recent progress many difficulties still remain, which prevent the widespread use of immunotherapy. Some of these limitations include: systemic toxicity, weak immune cellular responses or persistence over time and most ultimately costly and time-consuming procedures. Synthetic and natural biomaterials hold great potential to address these hurdles providing biocompatible systems capable of targeted local delivery, co-delivery, and controlled and/or sustained release. In this review we discuss some of the bioengineered solutions and approaches developed so far and how biomaterials can be further implemented to help and shape the future of cancer immunotherapy. The bioengineering strategies here presented constitute a powerful toolkit to develop safe and successful novel cancer immunotherapies

Выявление резервов производства методами статистического моделирования по пассивным данным

Предложенные методы позволяют использовать цеховую контрольно-измерительную информацию для получения модели конкретного технологического процесса (операции)

Thermal tolerance, climatic variability and latitude

The greater latitudinal extents of occurrence of species towards higher latitudes has been attributed to the broadening of physiological tolerances with latitude as a result of increases in climatic variation. While there is some support for such patterns in climate, the physiological tolerances of species across large latitudinal gradients have seldom been assessed. Here we report findings for insects based on published upper and lower lethal temperature data. The upper thermal limits show little geographical variation. In contrast, the lower bounds of supercooling points and lower lethal temperatures do indeed decline with latitude. However, this is not the case for the upper bounds, leading to an increase in the variation in lower lethal limits with latitude. These results provide some support for the physiological tolerance assumption associated with Rapoport's rule, but highlight the need for coupled data on species tolerances and range size

General practitioners' prescribing behaviour as a determinant of poor persistence with inhaled corticosteroids in children with respiratory symptoms:Mixed methods study

OBJECTIVES: To evaluate general practitioners’ (GPs’) prescribing behaviour as a determinant of persistence with and adherence to inhaled corticosteroids (ICS) in children. DESIGN: Prospective observational study of persistence with and adherence to ICS followed by a focus group study of the GPs prescribing this treatment. SETTING: 7 primary care practices in the area of Zwolle, the Netherlands. PARTICIPANTS: 134 children aged 2–12 years had been prescribed ICS in the year before the study started by their 19 GPs. MAIN OUTCOME MEASURES: Patterns and motives of GPs’ prescribing behaviour and the relationship with persistence with and adherence to ICS. RESULTS: GPs’ prescribing behaviour was characterised by prescribing short courses of ICS to children with various respiratory symptoms without follow-up for making a diagnosis of asthma. This was driven by the GPs’ pragmatic approach to deal with the large number of children with respiratory symptoms, and by beliefs about ICS which differed from currently available evidence. This prescribing behaviour was the main reason why 68 (51%) children did not persist with the use of ICS. In children with persistent use of ICS and a GP's advice to use ICS on a daily basis, the median (IQR) adherence was 70% (41–84%), and was similar for patients with persistent asthma and children lacking a diagnosis or symptoms of asthma. CONCLUSIONS: Inappropriate prescription of ICS to children by GPs is common and drives the lack of persistence with ICS therapy in primary care. This finding should be taken into account when interpreting data from large prescription database studies. Improving primary healthcare providers’ knowledge and competence in diagnosing and managing asthma in children is needed

Immediate and late impact of reperfusion therapies in acute pulmonary embolism

Haemodynamic instability and right ventricular dysfunction are the key determinants of short-term prognosis in patients with acute pulmonary embolism (PE). Residual thrombi and persistent right ventricular dysfunction may contribute to post-PE functional impairment, and influence the risk of developing chronic thromboembolic pulmonary hypertension. Patients with haemodynamic instability at presentation (high-risk PE) require immediate primary reperfusion to relieve the obstruction in the pulmonary circulation and increase the chances of survival. Surgical removal of the thrombi or catheter-directed reperfusion strategies is alternatives in patients with contraindications to systemic thrombolysis. For haemodynamically stable patients with signs of right ventricular overload or dysfunction (intermediate-risk PE), systemic standard-dose thrombolysis is currently not recommended, because the risk of major bleeding associated with the treatment outweighs its benefits. In such cases, thrombolysis should be considered only as a rescue intervention if haemodynamic decompensation develops. Catheter-directed pharmaco-logical and pharmaco-mechanical techniques ensure swift recovery of echocardiographic and haemodynamic parameters and may be characterized by better safety profile than systemic thrombolysis. For survivors of acute PE, little is known on the effects of reperfusion therapies on the risk of chronic functional and haemodynamic impairment. In intermediate-risk PE patients, available data suggest that systemic thrombolysis may have little impact on long-term symptoms and functional limitation, echocardiographic parameters, and occurrence of chronic thromboembolic pulmonary hypertension. Ongoing and future interventional studies will clarify whether 'safer' reperfusion strategies may improve early clinical outcomes without increasing the risk of bleeding and contribute to reducing the burden of long-term complications after intermediate-risk PE

External validation of AF-BLEED for predicting major bleeding and for tailoring NOAC dose in AF patients: A post hoc analysis in the ENGAGE AF-TIMI 48

OBJECTIVE AF-BLEED, a simple bleeding risk classifier, was found to predict major bleeding (MB) in patients with atrial fibrillation (AF) and identify AF patients at high risk of MB who might potentially benefit from a lower direct oral anticoagulant dose. This post hoc study aimed to externally validate these findings in the ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor Xa next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction study 48) trial. METHODS The ENGAGE AF-TIMI 48 trial randomized AF patients to higher-dose edoxaban regimen (HDER 60/30 mg) versus lower-dose edoxaban regimen (LDER 30/15 mg), with prespecified dose reduction criteria. AF-BLEED was calculated in the modified intention-to-treat cohort (n = 21,026 patients) used for primary outcome analysis. Annualized event rates and hazard ratios (HRs) were obtained for the primary composite outcome (PCO) and its single components (MB, ischemic stroke/systemic embolism and death) to compare LDER 30 mg with HDER 60 mg in both AF-BLEED classes. RESULTS AF-BLEED classified 2882 patients (13.7 %) as high-risk, characterized by a two- to three-fold higher MB risk than AF-BLEED classified low-risk patients. AF-BLEED classified high-risk patients randomized to LDER 30 mg demonstrated a 3.3 % reduction in MB at the cost of a 0.5 % increase in ischemic stroke/systemic embolism. LDER 30 mg resulted in a 3.1 % reduction of PCO compared to HDER 60 mg (HR of 0.81; 95%CI 0.65-1.01). Additional to existing dose reduction criteria, another 6 % of patients could potentially benefit of this dose adjustment strategy. CONCLUSION AF-BLEED could identify AF patients to be at high risk of major bleeding. Our findings support the hypothesis that LDER 30 mg might provide a reasonable option in AF patients with legitimate bleeding concerns

Ecotoxicological models for Dutch environmental policy: Models to be addressed in the Stimulation Program Systems-Oriented Ecotoxicological Research (NWO/SSEO)

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