35 research outputs found
PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer : rationale and design
Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, 0.2ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.Peer reviewe
Design and Synthesis of 11C-Labelled Compound Libraries for the Molecular Imaging of EGFr, VEGFr-2, AT1 and AT2 Receptors : Transition-Metal Mediated Carbonylations Using [11C]Carbon Monoxide
This work deals with radiochemistry and new approaches to develop novel PET tracers labelled with the radionuclide 11C. Two methods for the synthesis of 11C-labelled acrylamides have been explored. First, [1-11C]-acrylic acid was obtained from a palladium(0)-mediated 11C-carboxylation of acetylene with [11C]carbon monoxide; this could be converted to the corresponding acyl chloride and then combined with benzylamine to form N-benzyl[carbonyl-11C]acrylamide. In the second method, the palladium(0)-mediated carbonylation of vinyl halides with [11C]carbon monoxide was explored. This latter method, yielded labelled acrylamides in a single step with retention of configuration at the C=C double bond, and required less amine compared to the acetylene method. The vinyl halide method was used to synthesize a library of 11C-labelled EGFr-inhibitors in 7-61% decay corrected radiochemical yield via a combinatorial approach. The compounds were designed to target either the active or the inactive form of EGFr, following computational docking studies. The rhodium(I)-mediated carbonylative cross-coupling of an azide and an amine was shown to be a very general reaction and was used to synthesize a library of dual VEGFr-2/PDGFrÎČ inhibitors that were 11C-labelled at the urea position in 38-78% dc rcy. The angiotensin II AT1 receptor antagonist eprosartan was 11C-labelled at one of the carboxyl groups in one step using a palladium(0)-mediated carboxylation. Autoradiography shows specific binding in rat kidney, lung and adrenal cortex, and organ distribution shows a high accumulation in the intestines, kidneys and liver. Specific binding in frozen sections of human adrenal incidentalomas warrants further investigations of this tracer. Three angiotensin II AT2 ligands were 11C-labelled at the amide group in a palladium(0)-mediated aminocarbonylation in 16-36% dc rcy. One of the compounds was evaluated using in vitro using autoradiography, and in vivo using organ distribution and animal PET. The compound was metabolized fast and excreted via urine. High radioactivity was also found in the liver, meaning that more metabolically stable compounds are desirable for future development.
Bra verksamheter ska bada i barns hundra sprÄk
NyanlĂ€nda barns mottagande i skolan framhĂ„lls som ett bristfĂ€lligt forskningsomrĂ„de (Bunar, 2015). Ămnet Ă€r av högaktuell relevans för att alla barn i svensk skola och fritidshem ska ha likvĂ€rdiga förutsĂ€ttningar. Mot bakgrund av ett bristfĂ€lligt forskningsomrĂ„de och barns likvĂ€rdighet, har vi motiverats till att undersöka hur det arbetas med nyanlĂ€nda barn pĂ„ fritidshemmet. Vi vill undersöka arbetet bĂ„de ur skolledares och pedagogers perspektiv samt hur svenska som andrasprĂ„kslĂ€rares kompetens kan anvĂ€ndas pĂ„ fritidshemmet. Vi har vidare haft som syfte att undersöka nyanlĂ€nda barns egna uppfattningar av fritidshemmet, samt hur makt och hierarkier framtrĂ€der i barn och vuxnas samspel pĂ„ fritidshemmet.Studiens teoretiska angreppssĂ€tt innefattar ett sociokulturellt och interkulturellt perspektiv, men ocksĂ„ teorier om maktordningar, hierarkier samt sociala fĂ€lt och sociala band. Studien utgick ifrĂ„n en kombination av strukturerade och semistrukturerade intervjumetoder.Sammantaget visar studien att skolledares och pedagogers idĂ©er mĂ„nga gĂ„nger tenderar att stanna som tankar och inte etableras i verksamheten. Dock framhĂ„lls vĂ€lutvecklad kartlĂ€ggning av det nyanlĂ€nda barnets kunskaper, kulturell mix bland personalen och erfarenhetsutbyten som möjliga metoder för integrering. Pedagoger i studien lyfter fram praktisk-estetiska verktyg och aktiviteter som möjliga metoder för att gynna relationsskapande och sprĂ„kutveckling. Huruvida makt och hierarkier blir pĂ„tagligt mellan nyanlĂ€nda barn och andra barn, kan delvis bero pĂ„ pedagogers instĂ€llning till barnen, men ocksĂ„ deras erfarenheter av nyanlĂ€nda. De nyanlĂ€nda barnen framhĂ„ller trivsel, kamratskap och god variation av aktiviteter pĂ„ fritidshemmet
Bra verksamheter ska bada i barns hundra sprÄk
NyanlĂ€nda barns mottagande i skolan framhĂ„lls som ett bristfĂ€lligt forskningsomrĂ„de (Bunar, 2015). Ămnet Ă€r av högaktuell relevans för att alla barn i svensk skola och fritidshem ska ha likvĂ€rdiga förutsĂ€ttningar. Mot bakgrund av ett bristfĂ€lligt forskningsomrĂ„de och barns likvĂ€rdighet, har vi motiverats till att undersöka hur det arbetas med nyanlĂ€nda barn pĂ„ fritidshemmet. Vi vill undersöka arbetet bĂ„de ur skolledares och pedagogers perspektiv samt hur svenska som andrasprĂ„kslĂ€rares kompetens kan anvĂ€ndas pĂ„ fritidshemmet. Vi har vidare haft som syfte att undersöka nyanlĂ€nda barns egna uppfattningar av fritidshemmet, samt hur makt och hierarkier framtrĂ€der i barn och vuxnas samspel pĂ„ fritidshemmet.Studiens teoretiska angreppssĂ€tt innefattar ett sociokulturellt och interkulturellt perspektiv, men ocksĂ„ teorier om maktordningar, hierarkier samt sociala fĂ€lt och sociala band. Studien utgick ifrĂ„n en kombination av strukturerade och semistrukturerade intervjumetoder.Sammantaget visar studien att skolledares och pedagogers idĂ©er mĂ„nga gĂ„nger tenderar att stanna som tankar och inte etableras i verksamheten. Dock framhĂ„lls vĂ€lutvecklad kartlĂ€ggning av det nyanlĂ€nda barnets kunskaper, kulturell mix bland personalen och erfarenhetsutbyten som möjliga metoder för integrering. Pedagoger i studien lyfter fram praktisk-estetiska verktyg och aktiviteter som möjliga metoder för att gynna relationsskapande och sprĂ„kutveckling. Huruvida makt och hierarkier blir pĂ„tagligt mellan nyanlĂ€nda barn och andra barn, kan delvis bero pĂ„ pedagogers instĂ€llning till barnen, men ocksĂ„ deras erfarenheter av nyanlĂ€nda. De nyanlĂ€nda barnen framhĂ„ller trivsel, kamratskap och god variation av aktiviteter pĂ„ fritidshemmet
Educational challenges for teaching nanotechnology : Part 2. Pedagogic content development for teaching nanotechnology in life sciences
The present work aims to provide a framework for teaching nanotechnology for life sciences applications, with special focus on nanotechnology-enabled treatments based on advanced physical and biological principles. By expanding and adapting the so-called âBig Ideasâ of NSE to further include core elements of cell and molecular biology, an eight-level learning progression is suggested. The challenges of teaching nanotechnology are further addressed in different learning contexts to highlight the importance of size-dependent physical and biological interactions. A number of core nanomedicine concepts are discussed, including, e.g., directed self-assembly, enhance permeability and retention effect, protein corona, size-dependent cellular uptake, disease-specific environment, and theranostics. The outcome of this work will be useful for educators designing curriculum with specialization in nanomedicine
Educational challenges for teaching nanotechnology : Part 2. Pedagogic content development for teaching nanotechnology in life sciences
The present work aims to provide a framework for teaching nanotechnology for life sciences applications, with special focus on nanotechnology-enabled treatments based on advanced physical and biological principles. By expanding and adapting the so-called âBig Ideasâ of NSE to further include core elements of cell and molecular biology, an eight-level learning progression is suggested. The challenges of teaching nanotechnology are further addressed in different learning contexts to highlight the importance of size-dependent physical and biological interactions. A number of core nanomedicine concepts are discussed, including, e.g., directed self-assembly, enhance permeability and retention effect, protein corona, size-dependent cellular uptake, disease-specific environment, and theranostics. The outcome of this work will be useful for educators designing curriculum with specialization in nanomedicine
No zero burden assumption in a circular economy
A majority of previous studies on environmental problems caused by waste generation have focused on waste disposal issues without fully highlighting the primary reasons behind the problems. As a consequence, efforts to reduce these problems are usually directed towards the stakeholders that provide waste treatment and disposal instead of the stakeholders that contribute to waste generation. In order to detect connections between different problems of sustainability and to suggest measures which may contribute to their solutions, this study provides a simplified overview of the mechanisms behind waste generation and management. The results from the study show that the only way to eliminate problems of sustainability is to apply an upstream approach by dealing with the primary problems which occur in the early stages of the system (e.g. overconsumption of products, as well as use of finite resources, toxic materials, and non-recyclable materials). By dealing with these problems, the emergence of secondary problems would be prevented. Thereby, stakeholders who have the highest possibility to contribute to the sustainable development of the waste generation and management are the stakeholders from the origin of the products life cycles, such as product developers, manufacturing companies, product users and policy makers. Different trade-off situations such as contradictions between economics, recyclability, energy efficiency, make it even harder to deal with issues of sustainability related to the system and to detect the stakeholders who may contribute to the development. One of the main conclusions from this study is that when transforming society towards a circular economy, the traditional view of separate systems for production and waste management must be changed. In order to refer to all problems of sustainability and also cover the top steps of the waste hierarchy, life cycle assessment of waste management should include manufacture and use of products ending up as waste. Waste entering the waste management system with "zero burden", by releasing the previous actors of the waste life cycle from any responsibility related to the environment (i.e. by shifting the total environmental burden into the waste management system), does not capture the problems with waste generation. (C) 2018 Elsevier Ltd. All rights reserved.Funding Agencies|Swedish Energy Company: Tekniska Verken; Swedish Energy Company: Goteborg Energi</p
Educational challenges for teaching nanotechnology : Part 1. Global and local perspectives for teaching nanotechnology
In this study, systematic analysis of nanotechnology education programmes was carried out from a global and local perspective. Although several universities offer 3-4 year nanotechnology-centred educational programmes, in general the most common modes for nanotechnology education include either modular courses integrated in traditional scientific disciplines or 2-year specialised MSc programmes. Nanotechnology education has a number of peculiarities. For example, it is common to include ânanoâ-labelling of education for marketing purposes to attract students to study traditional disciplines. Another conclusion of the analysis is that specialised nanotechnology programmes require access to advanced characterisation equipment, which can be limiting for programmes with small number of students. The nanotechnology education in Sweden does not differ much from other countries in its structure. MSc programmes or modular courses in nanotechnology are offered by major universities. Lund University and KTH offer 2-year MSc programmes with specialisation in nanoscience, having strong focus on nanoelectronics and nanophysics, whereas Chalmers is offering nanoelectronics as a part of international 2-year Erasmus Mundus MSc programme in nanoscience and nanotechnology- EMMNano. The nanotechnology education at Uppsala University is conducted mainly through modular courses, with significantly higher number of courses specialised in life sciences applications than that at other major Swedish universities. At this time, it appears that no 2-year MSc programme is offered by major Swedish universities with specialisation in nanomedicine. Finally, extensive analysis of nanotechnology for life science education is conducted to highlight core concepts in the field
Educational challenges for teaching nanotechnology : Part 1. Global and local perspectives for teaching nanotechnology
In this study, systematic analysis of nanotechnology education programmes was carried out from a global and local perspective. Although several universities offer 3-4 year nanotechnology-centred educational programmes, in general the most common modes for nanotechnology education include either modular courses integrated in traditional scientific disciplines or 2-year specialised MSc programmes. Nanotechnology education has a number of peculiarities. For example, it is common to include ânanoâ-labelling of education for marketing purposes to attract students to study traditional disciplines. Another conclusion of the analysis is that specialised nanotechnology programmes require access to advanced characterisation equipment, which can be limiting for programmes with small number of students. The nanotechnology education in Sweden does not differ much from other countries in its structure. MSc programmes or modular courses in nanotechnology are offered by major universities. Lund University and KTH offer 2-year MSc programmes with specialisation in nanoscience, having strong focus on nanoelectronics and nanophysics, whereas Chalmers is offering nanoelectronics as a part of international 2-year Erasmus Mundus MSc programme in nanoscience and nanotechnology- EMMNano. The nanotechnology education at Uppsala University is conducted mainly through modular courses, with significantly higher number of courses specialised in life sciences applications than that at other major Swedish universities. At this time, it appears that no 2-year MSc programme is offered by major Swedish universities with specialisation in nanomedicine. Finally, extensive analysis of nanotechnology for life science education is conducted to highlight core concepts in the field
Levels of mannose-binding lectin (MBL) associates with sepsis-related in-hospital mortality in women
Background: Mannose-binding lectin (MBL) mediates the innate immune response either through direct opsonisation of microorganisms or through activation of the complement system. There are conflicting data whether MBL deficiency leads to increased susceptibility to infections or not. The aim of this study was to determine if low levels of mannose-binding lectin (MBL) predict sepsis development, sepsis severity and outcome from severe sepsis or septic shock. Method: Patients aged 18âyears or more with documented sepsis within 24âh after admission to the intensive care unit were included if they had participated in a health survey and donated blood samples prior to the sepsis event. A subset of these patients had stored plasma also from the acute phase. Two matched referents free of known sepsis were selected for each case. Plasma levels MBL were determined in stored samples from health surveys (baseline) and from ICU admission (acute phase). The association between MBL and sepsis, sepsis severity and in-hospital mortality were determined with 1300âng/mL as cut-off for low levels. Results: We identified 148 patients (61.5% women) with a first-time sepsis event 6.5âyears (median with IQR 7.7) after participation in a health survey, of which 122 also had samples from the acute septic phase. Both high MBL levels in the acute phase (odds ratio [95% confidence interval]) (2.84 [1.20-6.26]), and an increase in MBL levels from baseline to the acute phase (3.76 [1.21-11.72]) were associated with increased risk for in-hospital death in women, but not in men (0.47 [0.11-2.06]). Baseline MBL levels did not predict future sepsis, sepsis severity or in-hospital mortality. Conclusions: An increase from baseline to the acute phase as well as high levels in the acute phase associated with an unfavourable outcome in women