143 research outputs found

    GP trainees’ perceptions on learning EBM using conversations in the workplace : a video-stimulated interview study

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    Background To be able to practice evidence-based medicine (EBM) when making decisions for individual patients, it is important to learn how to combine the best available evidence with the patient's preferences and the physician's clinical expertise. In general practice training, these skills can be learned at the workplace using learning conversations: meetings between the supervising general practitioner (GP) and GP trainee to discuss medical practice, selected topics or professional performance. This study aimed to give insight into the perceptions of GP trainees on their EBM learning processes during learning conversations. Methods We held semi-structured video-stimulated elicitation interviews (n = 22) with GP trainees affiliated to GP training institutes in the Netherlands and Belgium. GP trainees were shown fragments of their learning conversations, enabling reflection during the interview. Taking an inductive approach, interview recordings were transcribed verbatim and analysed with NVivo software. Results GP trainees perceived learning conversations as useful for learning and discussing EBM. Multiple EBM learning activities were identified, such as discussing evidence together, relating evidence to cases in daily practice and discussing the supervisor's experience and the specific local context in the light of what the evidence recommends. However, for learning to occur, trainees need and expect specific behaviour, both from their supervisors and themselves. Supervisors should supply well-substantiated answers that are applicable in practice and give the trainee confirmation. In turn, the trainee needs to prepare well in order to ask focused, in-depth questions. A safe space allowing equal and open discussion between trainee and supervisor is perceived as an essential context for optimal EBM learning. Conclusions Our findings show that trainees find learning conversations useful for EBM learning in general practice. To bring EBM learning to its full potential, attention should be paid to optimising the behavioural and contextual factors found relevant to enhancing EBM learning

    Enzyme Mechanisms: Fast Reaction and Computational Approaches Ultrafast catalytic processes and conformational changes in the light-driven enzyme protochlorophyllide oxidoreductase (POR)

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    Abstract The enzyme POR (protochlorophyllide oxidoreductase), from the family of alcohol dehydrogenases, reduces protochlorophyllide into chlorophyllide on the absorption of light. The reduction involves the transfer of two protons and two electrons and is an important regulatory step in the biosynthesis of chlorophyll. In recent years, due to the availability of large quantities of the pure enzyme, much of the catalytic reaction has been unravelled by using a variety of spectroscopic methods, including ultrafast initial events in catalysis. In addition, it has been demonstrated that a light-activated conformational change of the protein is necessary to activate catalysis. This makes POR a very important model system to study the relationship between structural changes of enzymes and functionality

    Learning conversations with trainees : an undervalued but useful EBM learning opportunity for clinical supervisors

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    Phenomenon: Supervisors and trainees can learn skills related to evidence-based medicine from each other in the workplace by collaborating and interacting, in this way benefiting from each other's strengths. This study explores supervisors' perceptions of how they currently learn evidence-based medicine by engaging in learning conversations with their trainee. Approach: Semi-structured, video-stimulated elicitation interviews were held with twenty-two Dutch and Belgian supervisors in general practice. Supervisors were shown fragments of their video-recorded learning conversations, allowing them to reflect. Recorded interviews were analyzed using a grounded theory-based approach.Findings: Supervisors did not immediately perceive workplace learning conversations as an opportunity to learn evidence-based medicine from their trainee. They mostly saw these conversations as a learning opportunity for trainees and a chance to maintain the quality of care within their practice. Nevertheless, during the interviews, supervisors did acknowledge that learning conversations help them to gain up-to-date knowledge and search skills or more awareness of their own knowledge or gaps in their knowledge. Not identified as a learning outcome was how to apply evidence-based medicine within a clinical practice by combining evidence with clinical expertise and the patient's preferences. Insights: Supervisors acknowledge that they learn elements of the three aspects of evidence-based medicine by having learning conversations with their trainee, but they currently see this as secondary to the trainee's learning process. Emphasizing opportunities for bidirectional learning could improve learning of evidence-based medicine during workplace learning conversations

    Ultrafast mid-infrared spectroscopy by chirped pulse upconversion in 1800-1000cm(-1) region

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    Broadband femtosecond mid-infrared pulses can be converted into the visible spectral region by chirped pulse upconversion. We report here the upconversion of pump probe transient signals in the frequency region below 1800c

    Identification of the first steps in charge separation in bacterial photosynthetic reaction centers of Rhodobacter sphaeroides by ultrafast mid-infrared spectroscopy: Electron transfer and protein dynamics

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    AbstractTime-resolved visible pump/mid-infrared (mid-IR) probe spectroscopy in the region between 1600 and 1800cm−1 was used to investigate electron transfer, radical pair relaxation, and protein relaxation at room temperature in the Rhodobacter sphaeroides reaction center (RC). Wild-type RCs both with and without the quinone electron acceptor QA, were excited at 600nm (nonselective excitation), 800nm (direct excitation of the monomeric bacteriochlorophyll (BChl) cofactors), and 860nm (direct excitation of the dimer of primary donor (P) BChls (PL/PM)). The region between 1600 and 1800cm−1 encompasses absorption changes associated with carbonyl (CO) stretch vibrational modes of the cofactors and protein. After photoexcitation of the RC the primary electron donor P excited singlet state (P*) decayed on a timescale of 3.7ps to the state P+BL− (where BL is the accessory BChl electron acceptor). This is the first report of the mid-IR absorption spectrum of P+BL−; the difference spectrum indicates that the 9-keto CO stretch of BL is located around 1670–1680cm−1. After subsequent electron transfer to the bacteriopheophytin HL in ∌1ps, the state P+HL− was formed. A sequential analysis and simultaneous target analysis of the data showed a relaxation of the P+HL− radical pair on the ∌20ps timescale, accompanied by a change in the relative ratio of the PL+ and PM+ bands and by a minor change in the band amplitude at 1640cm−1 that may be tentatively ascribed to the response of an amide CO to the radical pair formation. We conclude that the drop in free energy associated with the relaxation of P+HL−, is due to an increased localization of the electron hole on the PL half of the dimer and a further consequence is a reduction in the electrical field causing the Stark shift of one or more amide CO oscillators

    Deliverable 3.6 zoning plan of case studies : evaluation of spatial management options for the case studies

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    Within MESMA, nine case studies (CS) represent discrete marine European spatial entities, at different spatial scales, where a spatial marine management framework is in place, under development or considered. These CS (described in more details below) are chosen in such a way (MESMA D. 3.1 ) that they encompass the complexity of accommodating the various user functions of the marine landscape in various regions of the European marine waters. While human activities at sea are competing for space, there is also growing awareness of the possible negative effects of these human activities on the marine ecosystem. As such, system specific management options are required, satisfying current and future sectoral needs, while safeguarding the marine ecosystem from further detoriation. This integrated management approach is embedded in the concept of ecosystem based management (EBM). The goal of marine EBM is to maintain marine ecosystems in a healthy, productive and resilient condition, making it possible that they sustain human use and provide the goods and services required by society (McLeod et al. 2005). Therefore EBM is an environmental mangagement approach that recognises the interactions within a marine ecosystem, including humans. Hence, EBM does not consider single issues, species or ecosystems good and services in isolation. Operationalisation of EBM can be done through place-based or spatial management approaches (Lackey 1998), such as marine spatial planning (MSP). MSP is a public process of analysing and allocating the spatial and temporal distribution of human activities aiming at achieving ecological, economic and social objectives. These objectives are usually formulated through political processes (Douvere et al. 2007, Douvere 2008). Within MESMA, a spatially managed area (SMA) is then defined as “a geographical area within which marine spatial planning initiatives exist in the real world”. Marine spatial planning initiatives refer to existing management measures actually in place within a defined area, or in any stage of a process of putting management in place, e.g. plans or recommendations for a particular area. Management can include management for marine protection (e.g. in MPAs), or management for sectoral objectives (e.g. building a wind farm to meet renewable energy objectives). Within MESMA, SMAs can have different spatial scales. A SMA can be a small, specific area that is managed/planned to be managed for one specific purpose, but it can also be a larger area within which lots of plans or ‘usage zones’ exist. This definition is different from the definition mentioned in the DoW (page 60). The original definition was adapted during a CS leader workshop (2-4 May 2012 in Gent, Belgium) and formally accepted by the MESMA ExB during the ExB meeting in Cork (29-30 May 2012). MSP should result in a marine spatial management plan that will produce the desired future trough explicit decisions about the location and timing of human activities. Ehler & Douvere (2009) consider this spatial management as a beginning toward the the implementation of desired goals and objectives. They describe the spatial management plan as a comprehensive, strategic document that provides the framework and direction for marine spatial management decisions. The plan should identify when, where and how goals and objectives will be met. Zoning (the development of zoning plans) is often an important management measure to implement spatial management plans. The purpose of a zoning plan (Ehler & Douvere 2009) is: To provide protection for biologically and ecologically important habitats, ecosystems, and ecological processes. To seperate conflicting human activities, or to combine compatible activities. To protect the natural values of the marine management area (in MESMA terminology: the SMA) while allowing reasonable human uses of the area. To allocate areas for reasonable human uses while minimising the effects of these human uses on each other, and nature. To preserve some areas of the SMA in their natural state undisturbed by humans except for scientific and educational purposes.peer-reviewe

    On the involvement of Single-Bond Rotation in the Primary Photochemistry of Photoactive Yellow Protein

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    AbstractPrior experimental observations, as well as theoretical considerations, have led to the proposal that C4-C7 single-bond rotation may play an important role in the primary photochemistry of photoactive yellow protein (PYP). We therefore synthesized an analog of this protein's 4-hydroxy-cinnamic acid chromophore, (5-hydroxy indan-(1E)-ylidene)acetic acid, in which rotation across the C4-C7 single bond has been locked with an ethane bridge, and we reconstituted the apo form of the wild-type protein and its R52A derivative with this chromophore analog. In PYP reconstituted with the rotation-locked chromophore, 1), absorption spectra of ground and intermediate states are slightly blue-shifted; 2), the quantum yield of photochemistry is ∌60% reduced; 3), the excited-state dynamics of the chromophore are accelerated; and 4), dynamics of the thermal recovery reaction of the protein are accelerated. A significant finding was that the yield of the transient ground-state intermediate in the early phase of the photocycle was considerably higher in the rotation-locked samples than in the corresponding samples reconstituted with p-coumaric acid. In contrast to theoretical predictions, the initial photocycle dynamics of PYP were observed to be not affected by the charge of the amino acid residue at position 52, which was varied by 1), varying the pH of the sample between 5 and 10; and 2), site-directed mutagenesis to construct R52A. These results imply that C4-C7 single-bond rotation in PYP is not an alternative to C7=C8 double-bond rotation, in case the nearby positive charge of R52 is absent, but rather facilitates, presumably with a compensatory movement, the physiological Z/E isomerization of the blue-light-absorbing chromophore

    Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1:a multicentre, single-blind, randomised trial

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    Background: Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1. Methods: We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≄35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep–wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10–14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0–100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered with ClinicalTrials.gov, number NCT02118779. Findings: Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 to cognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1-Activ-c score increased from a mean (SD) of 61·22 (17·35) points at baseline to 63·92 (17·41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1·53, 95% CI −0·14 to 3·20), and decreased from 63·00 (17·35) to 60·79 (18·49) in the standard care group (−2·02, −4·02 to −0·01), with a mean difference between groups of 3·27 points (95% CI 0·93 to 5·62, p=0·007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac. Interpretation: Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1. Funding: The European Union Seventh Framework Programme
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