Technology facilitates advances in learning and drives learning paradigms. One recent innovation is Twitch™, an online streaming platform often used for video game tutorials but also enables amateur ...online instruction (Hamilton, Garretson, & Kerne, 2014)). Twitch represents a unique learning paradigm that is not perfectly represented in previous technologies because of its “ground-up” evolution and the opportunity for novice instructors to educate mass audiences in real-time over the Internet while enabling interaction between teachers and learners and among learners. The purpose of this research is to empirically examine the efficacy of Twitch as a learning platform by manipulating each of the key characteristics of Twitch and to understand the conditions in which novice instructors may be beneficial. Drawing from Cognitive Load Theory, we demonstrate the worked-example effect in the Twitch environment by manipulating teacher-learner-learner interactions, live versus recorded streaming, and expert-versus novice-based instruction. Based on a laboratory experiment involving 350 participants, we found that learning performance under novice instructors was at least as good as that of experts. However, an exploratory analysis of learner personalities revealed that extroverts benefit only when learner-learner interaction is enabled. Surprisingly, those who are highly agreeable and less neurotic benefited more from novice instructors.
•Using Cognitive Load Theory, we demonstrate the worked-example effect with Twitch.tv.•Learning performance under novice instructors was as good as that of experts.•Extroverts benefit only when learner-learner interaction is enabled.•Highly agreeable and less neurotic people benefited more from novice instructors.
Health policy in the UK and elsewhere is prioritising patient empowerment and patient evaluations of healthcare. Patient reported outcome measures now take centre-stage in implementing strategies to ...increase patient empowerment. This article argues for consideration of patient empowerment itself as a directly measurable patient reported outcome for chronic conditions, highlights some issues in adopting this approach, and outlines a research agenda to enable healthcare evaluation on the basis of patient empowerment.
Patient empowerment is not a well-defined construct. A range of condition-specific and generic patient empowerment questionnaires have been developed; each captures a different construct e.g. personal control, self-efficacy/self-mastery, and each is informed by a different implicit or explicit theoretical framework. This makes it currently problematic to conduct comparative evaluations of healthcare services on the basis of patient empowerment. A case study (clinical genetics) is used to (1) illustrate that patient empowerment can be a valued healthcare outcome, even if patients do not obtain health status benefits, (2) provide a rationale for conducting work necessary to tighten up the patient empowerment construct (3) provide an exemplar to inform design of interventions to increase patient empowerment in chronic disease. Such initiatives could be evaluated on the basis of measurable changes in patient empowerment, if the construct were properly operationalised as a patient reported outcome measure. To facilitate this, research is needed to develop an appropriate and widely applicable generic theoretical framework of patient empowerment to inform (re)development of a generic measure. This research should include developing consensus between patients, clinicians and policymakers about the content and boundaries of the construct before operationalisation. This article also considers a number of issues for society and for healthcare providers raised by adopting the patient empowerment paradigm.
Healthcare policy is driving the need to consider patient empowerment as a measurable patient outcome from healthcare services. Research is needed to (1) tighten up the construct (2) develop consensus about what is important to include (3) (re)develop a generic measure of patient empowerment for use in evaluating healthcare (4) understand if/how people make trade-offs between empowerment and gain in health status.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Versican (VCAN) proteolysis and the accumulation of VCAN fragments occur in many developmental and disease processes, affecting extracellular matrix (ECM) structure and cell phenotype. Little is ...known about the significance of proteolysis and the roles of fragments, or how this ECM remodeling affects the microenvironment and phenotype of diseased cells. G1-DPEAAE fragments promote aspects of epithelial-mesenchymal transitioning in developing and diseased cells, resulting in cell migration. Enhanced proliferation and invasion of tumor and endothelial cells is directly associated with G1 domain deposition and G1-DPEAAE localization respectively. These tumorigenic and angiogenic roles could explain the disease exacerbating effect often associated with G1-containing fragments, however, the pathogenicity of G1 fragments depends entirely upon the context. Overall, VCAN fragments promote tumorigenesis and inflammation; however, the specific cleavage site, the extent of cleavage activity and the microenvironment in which cleavage occurs collectively determine how this pleiotropic molecule and its fragments influence cells.
The bifunctional chelator S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-1,4,7,10-tetraacetate (IB-DOTA) is on paper the most attractive of the commercially available ...bifunctional chelators for magnetic resonance imaging (MRI) applications. The preserved DOTA scaffold is known to produce extremely kinetically and thermodynamically robust chelates with the Gd3+ ion. Also, ligation through four acetate pendant arms should ensure that the rapid water exchange kinetics so, crucial to the function of an MRI contrast agent are retained. However, upon ligation of the Gd3+ ion, IB-DOTA differentiates into two distinct isomers defined by the positions of the benzylic substituent (corner or side). A relaxometric analysis of these two isomers revealed marked differences in the property and behavior of the two chelates. Most notably the side isomer is found to be substantially more likely to aggregate in aqueous solution than its corner counterpart. This aggregation results in higher relaxivity for the side isomer versus the corner isomer, an observation that potentially obscures the impact of differences in water exchange kinetics between the two isomers. The side isomer is composed of a significant fraction of a twisted square antiprismatic coordination geometry that exchanges water more rapidly than optimal (τM = 7 ns) for maximizing relaxivity. The impact of this excessively fast exchange is not observed in the relaxivity of the side isomer only because in isolation this chelate tumbles much more slowly than the corner isomer. However, this situation is not expected to persist when the chelate is employed in a typical bioconjugate. These results imply that the corner isomer of IB-DOTA may represent a better choice of bifunctional chelator for bioconjugation applications in which a large macromolecule is to be tagged for MRI applications.
The bifunctional chelator IB-DOTA has found use in a range of biomedical applications given its ability to chelate many metal ions, but in particular the lanthanide(III) ions. Gd3+ in particular is ...of interest in the development of new molecular imaging agents for MRI and is highly suitable for chelation by IB-DOTA. Given the long-term instability of the aryl isothiocyanate functional group we have used the more stable nitro derivative (NB-DOTA) to conduct a follow-up study of some of our previous work on the coordination chemistry of chelates of these BFCs. Using a combination of NMR and HPLC to study the Eu3+ and Yb3+ chelates of NB-DOTA, we have demonstrated that this ligand will produce two discrete regioisomeric chelates at the point at which the metal ion is introduced into the BFC. These regioisomers are defined by the position of the benzylic substituent on the macrocyclic ring: adopting an equatorial position either at the corner or the side of the 3333 ring conformation. These regioisomers are incapable of interconversion and are distinct, separate structures with different SAP/TSAP ratios. The side isomer exhibits an increased population of the TSAP isomer, pointing to more rapid water exchange kinetics in this regioisomer. This has potential ramifications for the use of these two regioisomers of Gd3+-BFC chelates in MRI applications. We have also found that, remarkably, there is little or no freedom of rotation about the first single bond extending from the macrocyclic ring to the benzylic substituent. Since this is the linkage through which the chelate is conjugated to the remainder of the molecular imaging probe, this result implies that there may be reduced local rotation of the Gd3+ chelate within a molecular imaging probe. This implies that this type of BFC could exhibit higher relaxivities than other types of BFC.
Abstract There is a need for methodological scrutiny in the economic assessment of personalized medicine. In this article, we present a list of 10 specific issues that we argue pose specific ...methodological challenges that require careful consideration when designing and conducting robust model-based economic evaluations in the context of personalized medicine. Key issues are related to the correct framing of the research question, interpretation of test results, data collection of medical management options after obtaining test results, and expressing the value of tests. The need to formulate the research question clearly and be explicit and specific about the technology being evaluated is essential because various test kits can have the same purpose and yet differ in predictive value, costs, and relevance to practice and patient populations. The correct reporting of sensitivity/specificity, and especially the false negatives and false positives (which are population dependent), of the investigated tests is also considered as a key element. This requires additional structural complexity to establish the relationship between the test result and the consecutive treatment changes and outcomes. This process involves translating the test characteristics into clinical utility, and therefore outlining the clinical and economic consequences of true and false positives and true and false negatives. Information on treatment patterns and on their costs and outcomes, however, is often lacking, especially for false-positive and false-negative test results. The analysis can even become very complex if different tests are combined or sequentially used. This potential complexity can be handled by explicitly showing how these tests are going to be used in practice and then working with the combined sensitivities and specificities of the tests. Each of these issues leads to a higher degree of uncertainty in economic models designed to assess the added value of personalized medicine compared with their simple pharmaceutical counterparts. To some extent, these problems can be overcome by performing early population-level simulations, which can lead to the identification and collection of data on critical input parameters. Finally, it is important to understand that a test strategy does not necessarily lead to more quality-adjusted life-years (QALYs). It is possible that the test will lead to not only fewer QALYs but also fewer costs, which can be defined as “decremental” cost per QALYs. Different decision criteria are needed to interpret such results.
Relaxometric analyses and in particular the use of fast-field cycling techniques have become routine in the study of paramagnetic metal complexes. The field dependence of the solvent proton ...relaxation properties (nuclear magnetic relaxation dispersion, NMRD) can provide unparalleled insights into the chemistry of these complexes. However, analyzing NMRD data is a multiparametric problem, and some sets of variables are mutually compensatory. Specifically, when fitting NMRD profiles, the metal–proton distance and the rotational correlation time constant have a push–pull relationship in which a change to one causes a predictable compensation in the other. A relaxometric analysis of four isomeric chelates highlights the pitfalls that await when fitting the NMRD profiles of chelates for which dissociative water exchange is extremely rapid. In the absence of independently verified values for one of these parameters, NMRD profiles can be fitted to multiple parameter sets. This means that NMRD fitting can inadvertently be used to buttress a preconceived notion of how the complex should behave when a different parameter set may more accurately describe the actual behavior. These findings explain why the effect of very rapid dissociative exchange on the hydration state of Gd3+ has remained obscured until only recently.
The crystal structures of chelates formed between each stable paramagnetic lanthanide ion and the octadentate polyamino carboxylate ligand DOTMA are described. A total of 23 individual chelates ...structures were obtained; in each chelate the coordination geometry around the metal ion is best described as a twisted square antiprism (torsion angle −25.0°–−31.4°). Despite the uniformity of the general coordination geometry provided by the DOTMA ligand, there is a considerable variation in the hydration state of each chelate. The early Ln3+ chelates are associated with a single inner sphere water molecule; the Ln‐OH2 interaction is remarkable for being very long. After a clear break at gadolinium, the number of chelates in the unit cell that have a water molecule interacting with the Ln3+ decreases linearly until at Tm3+ no water is found to interact with the metal ion. The Ln‐OH2 distance observed in the chelates of the later Ln3+ ions are also extremely long and increase as the ions contract (2.550–2.732 Å). No clear break between hydrated and dehydrated chelates is observed; rather this series of chelates appear to represent a continuum of hydration states in which the ligand gradually closes around the metal ion as its ionic radius decreases (with decreased hydration) and the metal drops down into the coordination cage.
Well‐coordinated: Loss of water from the inner coordination sphere of LnDOTMA chelates does not occur abruptly with decreasing Ln3+ size. Hydration decreases continuously from Tb3+ to Tm3+ until water is completely expelled from the metal.
One of the most persistent arguments against the segment as the minimal planning unit is that the seemingly ubiquitous, thus, presumed obligatory, nature of anticipatory coarticulation (AC) effects ...favors the syllable or a larger unit. By contrast, we present the results of 3 experiments showing that AC is not ubiquitous, but graded and variable based on (a) phonological availability and (b) the specific criterion to initiate articulation adopted by a speaker. We further argue that phonological encoding is parallel. These results point to (a) the segment, and not the syllable, as the minimal planning unit and (b) a flexible planning scope. Implications with respect to the current formulation of AC regarding phonological availability and the minimal unit of speech articulation are discussed.
Public Significance Statement
This article examines whether the next stage in the final stages in uttering a monosyllabic word can start before the current stage is complete. Many theories argue that because of anticipatory coarticulation (AC), where a sound like /s/ in still and stool sounds quite different depending on which sound follows it, the current stage must be finished before the next onestarts. This is important because if AC must always be produced, then all the sounds of a syllable must be known. We found that AC is optional by holding back some of the sounds of a syllable. That is, some speakers waited for the sounds to be available and produced AC while others that did not produced no AC. We conclude that whether the next stage begins before the current stage is completely up to the speaker. Implications regarding the coordination between phonological planning and articulation are discussed.
The experiments reported in this study provided a more comprehensive insight into the effect of chemical composition on the crystallization behavior of milk fat (MF). MF was fractionated between 20 ...and 40 °C into nine fractions with different melting points and was first subjected to the heating step (L20, L30, L40, and S40) followed by the cooling phase (SS40, SL40, SS30, SL30, and LL40). Furthermore, the species of fatty acids (FAs) and triglycerides (TAGs) of the MF fractions were identified. The thermodynamics, crystallization behavior, and polymorphs were determined using differential scanning calorimetry, pulsed nuclear magnetic resonance, and X‐ray diffraction, respectively. The results indicated that L40 yielded the highest percentage (∼35% of the total MF) of all the fractions. Enthalpies of the melting and crystallization processes of solid fat content in this study were related to the different FA and TAG compositions of MF and its fractions. High melting fractions (HMFs) were enriched with long‐chain saturated fatty acids and tri‐saturated (S3) TAGs, and low melting fractions (LMFs) were enriched with short‐chain unsaturated FAs and tri‐unsaturated (U3) TAGs. Moreover, the various nucleation mechanisms of MF fractions were identified according to the Avrami equation. The polymorphic transformation from a β’ form of double chain length structures to a β form of triple chain length occurred in the native MF and HMFs, whereas the LMFs displayed almost no crystals.
Practical Application
This study represented the first time that nine fractions were obtained using MF fractionation via a heating step, followed by a cooling phase. Furthermore, the chemical composition of MF fractions was investigated. The results obtained from this study might be of specific value in understanding the functional properties of fat‐based dairy food in both storage conditions and real‐time applications.
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