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The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative diseases (ND). In vivo measurements of LC integrity and function are potentially important biomarkers for healthy ageing and early ND onset. In the present study, high-resolution functional MRI (fMRI), a reversal reinforcement learning task, and dedicated post-processing approaches were used to visualise age differences in LC function (N = 50). Increased LC responses were observed during emotionally and task-related salient events, with subsequent accelerations and decelerations in reaction times, respectively, indicating context-specific adaptive engagement of the LC. Moreover, older adults exhibited increased LC activation compared to younger adults, indicating possible compensatory overactivation of a structurally declining LC in ageing. Our study shows that assessment of LC function is a promising biomarker of cognitive aging.
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Envejecimiento , Locus Coeruleus , Imagen por Resonancia Magnética , Norepinefrina , Locus Coeruleus/diagnóstico por imagen , Locus Coeruleus/fisiología , Locus Coeruleus/metabolismo , Humanos , Masculino , Envejecimiento/fisiología , Imagen por Resonancia Magnética/métodos , Anciano , Femenino , Adulto , Norepinefrina/metabolismo , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Increased emphasis on workplace-based learning within pharmacy curricula has led to a focus on the quality of preceptors and the provision of preceptor training, with a diverse range of training programs for preceptors being developed across the globe. To ensure that preceptors are trained appropriately and deemed to be competent in their role, it is essential that all training programs are suitably evaluated. This research aimed to evaluate an online preceptor training program at a regional Australian University. METHODS: Kirkpatrick's four level model for assessment of training was used to evaluate this program. A multi method approach included a preceptor post training survey and interviews and a student survey evaluating the preceptor. Preceptor survey data were analysed using descriptive statistics and content analysis, while inductive thematic analysis was used to analyse the interviews. Student evaluations of trained and untrained preceptors were compared to determine whether training had impacted on student-rated preceptor effectiveness. RESULTS: Twenty-eight preceptor post-training surveys were received, ten preceptor post-training interviews were conducted, and 35 student surveys were completed. The program was rated positively overall, with notable mention by preceptors of the interactive networking session. Following their first post-training student placement, preceptors found that their overall confidence levels had improved, particularly in relation to student management, evaluating students and providing feedback. Student evaluations of preceptors revealed improved ratings of trained versus untrained preceptors, especially as effective communicators. CONCLUSIONS: This study demonstrated that training had a positive impact on preceptor attitudes, behaviour and confidence levels. From the perspective of the student, training was also found to improve preceptor performance. These results highlight the beneficial effects of training for preceptors, to optimize the student placement experience and their preparation for future practice.
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Farmacéuticos , Estudiantes , Humanos , Universidades , Australia , CurriculumRESUMEN
Biophysical diffusion-weighted imaging (DWI) models are increasingly used in neuroscience to estimate the axonal water fraction ( f AW ), which in turn is key for noninvasive estimation of the axonal volume fraction ( f A ). These models require thorough validation by comparison with a reference method, for example, electron microscopy (EM). While EM studies often neglect the unmyelinated axons and solely report the fraction of myelinated axons, in DWI both myelinated and unmyelinated axons contribute to the DWI signal. However, DWI models often include simplifications, for example, the neglect of differences in the compartmental relaxation times or fixed diffusivities, which in turn might affect the estimation of f AW . We investigate whether linear calibration parameters (scaling and offset) can improve the comparability between EM- and DWI-based metrics of f A . To this end, we (a) used six DWI models based on the so-called standard model of white matter (WM), including two models with fixed compartmental diffusivities (e.g., neurite orientation dispersion and density imaging, NODDI) and four models that fitted the compartmental diffusivities (e.g., white matter tract integrity, WMTI), and (b) used a multimodal data set including ex vivo diffusion DWI and EM data in mice with a broad dynamic range of fibre volume metrics. We demonstrated that the offset is associated with the volume fraction of unmyelinated axons and the scaling factor is associated with different compartmental T 2 and can substantially enhance the comparability between EM- and DWI-based metrics of f A . We found that DWI models that fitted compartmental diffusivities provided the most accurate estimates of the EM-based f A . Finally, we introduced a more efficient hybrid calibration approach, where only the offset is estimated but the scaling is fixed to a theoretically predicted value. Using this approach, a similar one-to-one correspondence to EM was achieved for WMTI. The method presented can pave the way for use of validated DWI-based models in clinical research and neuroscience.
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Imagen de Difusión por Resonancia Magnética , Sustancia Blanca , Ratones , Animales , Axones , Sustancia Blanca/diagnóstico por imagen , Vaina de Mielina , Microscopía Electrónica , Encéfalo/diagnóstico por imagenRESUMEN
BACKGROUND: Emotional reactivity is an important construct to consider when studying mental disorders. This study was conducted to translate and assess the factor structure, construct validity and internal consistency of a German version of the Emotion Reactivity Scale (ERS), which is an originally English questionnaire assessing three components of emotional reactivity: sensitivity, intensity and persistence of emotions. METHODS: The German ERS and a range of questionnaires used to assess convergent and discriminant validity were completed by 334 German speaking Swiss participants. RESULTS: Confirmatory factor analysis showed strong support for a bi-factor model, with evaluation indices pointing to a unidimensional construct rather than to domain specific factors. The questionnaire showed good reliability and the factor structure was similar across gender. The ERS showed convergent validity with general psychopathology, behavioral inhibition, negative affect, orienting sensitivity, depressive symptoms and symptoms of disordered eating, and discriminant validity with behavioral activation and alcohol consumption. CONCLUSIONS: Findings support the construct validity of the German ERS and suggest that it assesses a unidimensional construct with high internal consistency. Accounting for the unidimensional nature of the scale and aiming for efficient assessment tools, future research could, based on these findings, develop and evaluate the psychometric properties of a short version of the ERS.
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Emociones , Inhibición Psicológica , Humanos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Psicometría/métodosRESUMEN
Perception has been proposed to result from the integration of feedforward sensory signals with internally generated feedback signals. Feedback signals are believed to play an important role in driving false percepts, that is, seeing things that are not actually there. Feedforward and feedback influences on perception can be studied using layer-specific fMRI, which we used here to interrogate neural activity underlying high-confidence false percepts while healthy human participants (N = 25, male and female) performed a perceptual orientation discrimination task. Auditory cues implicitly signaled the most likely upcoming orientation (referred to here as expectations). These expectations induced orientation-specific templates in the deep and superficial layers of V2, without affecting perception. In contrast, the orientation of falsely perceived stimuli with high confidence was reflected in the middle input layers of V2, suggesting a feedforward signal contributing to false percepts. The prevalence of high-confidence false percepts was related to everyday hallucination severity in a separate online sample (N = 100), suggesting a possible link with abnormal perceptual experiences. These results reveal a potential feedforward mechanism underlying false percepts, reflected by spontaneous stimulus-like activity in the input layers of the visual cortex, independent of top-down signals reflecting cued orientations.SIGNIFICANCE STATEMENT False percepts have been suggested to arise through excessive feedback signals. However, feedforward contributions to false percepts have remained largely understudied. Laminar fMRI has been shown to be useful in distinguishing feedforward from feedback activity as it allows the imaging of different cortical layers. In the present study we demonstrate that although cued orientations are encoded in the feedback layers of the visual cortex, the content of the false percepts are encoded in the feedforward layers and did not rely on these cued orientations. This shows that false percepts can in principle emerge from random feedforward signals in the visual cortex, with possible implications for disorders hallmarked by hallucinations like schizophrenia and Parkinson's disease.
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Señales (Psicología) , Corteza Visual , Humanos , Masculino , Femenino , Motivación , Imagen por Resonancia Magnética , Retroalimentación , Percepción VisualRESUMEN
The effective transverse relaxation rate (R2*) is sensitive to the microstructure of the human brain like the g-ratio which characterises the relative myelination of axons. However, the fibre-orientation dependence of R2* degrades its reproducibility and any microstructural derivative measure. To estimate its orientation-independent part (R2,iso*) from single multi-echo gradient-recalled-echo (meGRE) measurements at arbitrary orientations, a second-order polynomial in time model (hereafter M2) can be used. Its linear time-dependent parameter, ß1, can be biophysically related to R2,iso* when neglecting the myelin water (MW) signal in the hollow cylinder fibre model (HCFM). Here, we examined the performance of M2 using experimental and simulated data with variable g-ratio and fibre dispersion. We found that the fitted ß1 can estimate R2,iso* using meGRE with long maximum-echo time (TEmax ≈ 54 ms), but not accurately captures its microscopic dependence on the g-ratio (error 84%). We proposed a new heuristic expression for ß1 that reduced the error to 12% for ex vivo compartmental R2 values. Using the new expression, we could estimate an MW fraction of 0.14 for fibres with negligible dispersion in a fixed human optic chiasm for the ex vivo compartmental R2 values but not for the in vivo values. M2 and the HCFM-based simulations failed to explain the measured R2*-orientation-dependence around the magic angle for a typical in vivo meGRE protocol (with TEmax ≈ 18 ms). In conclusion, further validation and the development of movement-robust in vivo meGRE protocols with TEmax ≈ 54 ms are required before M2 can be used to estimate R2,iso* in subjects.
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Increased experiential learning within pharmacy education has highlighted the need for quality preceptors, leading to a recent focus on their development and training. This study describes the design, development and implementation of a pharmacist preceptor training program in a regional Australian University. The design of this program utilized the results of a previously conducted scoping review of preceptor training programs and a comprehensive preceptor training needs analysis. In addition, participation was sought from an expert advisory group, comprising preceptors and pharmacy professional organizations. Program materials were developed and transferred onto a suitable online learning platform for implementation. Post-training program evaluation will follow Kirkpatrick's model of training evaluation criteria, gaining feedback from both preceptors and students. The four flexible online modules that were designed are aligned with the main preceptor roles: role model, educator, mentor and assessor. The program also included a small-group online interactive networking session and an online discussion forum. Following implementation, 28 pharmacist preceptors completed the training. Preliminary feedback on the training program was extremely positive, particularly to the interactive networking activity. Future programs will continue to be adapted to reflect stakeholder feedback and optimize student placement experiences.
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BACKGROUND: Meeting the needs of users when it comes to accessing prosthetic limbs is an important factor in the acceptance and use of a prosthesis; the cost of such prosthetics also constitutes a potential financial challenge. OBJECTIVES: The aim of this study was to investigate potential hurdles to accessing limb prosthetics in the German health care system, including organizational, social, economic, and regulatory issues, and to provide food for thought about ethical implications. METHODS: Sixteen German users of limb prosthetics with upper-limb and/or lower-limb amputation were recruited by means of purposive sampling. Semistructured interviews were performed, with the guiding question being as follows: "What were your experiences with the German prosthetic care and reimbursement system?" Ten stakeholders (insurance representatives, prosthetic technicians, medical service representatives, a law expert, and a lawyer) were asked about the issues they encounter in their work related to prosthetic care and reimbursement, and about ways to ameliorate these issues. A qualitative content analysis method was used to analyze the data. RESULTS: Half of the interviewed service users experienced hurdles to gaining a suitable prosthetic device, such as waiting times and pressure to negotiate their need for a certain prosthesis. Some of the views expressed about the issues relating to prosthetic reimbursement in Germany were common to all stakeholders, whereas some conflicted with the views of others. CONCLUSIONS: Equitable access to prostheses and the efficient distribution of prosthetic innovations could be improved by organizational and regulatory measures. Furthermore, a user-centered design of prostheses, a health technology assessment, monitoring of prosthetic care pathways, and a societal discussion about rationing in health care should be considered as parts of a broader approach to tackle this issue.
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BACKGROUND: Consistent noise variance across data points (i.e. homoscedasticity) is required to ensure the validity of statistical analyses of MRI data conducted using linear regression methods. However, head motion leads to degradation of image quality, introducing noise heteroscedasticity into ordinary-least square analyses. NEW METHOD: The recently introduced QUIQI method restores noise homoscedasticity by means of weighted least square analyses in which the weights, specific for each dataset of an analysis, are computed from an index of motion-induced image quality degradation. QUIQI was first demonstrated in the context of brain maps of the MRI parameter R2 * , which were computed from a single set of images with variable echo time. Here, we extend this framework to quantitative maps of the MRI parameters R1, R2 * , and MTsat, computed from multiple sets of images. RESULTS: QUIQI restores homoscedasticity in analyses of quantitative MRI data computed from multiple scans. QUIQI allows for optimization of the noise model by using metrics quantifying heteroscedasticity and free energy. COMPARISON WITH EXISTING METHODS: QUIQI restores homoscedasticity more effectively than insertion of an image quality index in the analysis design and yields higher sensitivity than simply removing the datasets most corrupted by head motion from the analysis. CONCLUSION: QUIQI provides an optimal approach to group-wise analyses of a range of quantitative MRI parameter maps that is robust to inherent homoscedasticity.
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Algoritmos , Imagen por Resonancia Magnética , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Movimiento (Física)RESUMEN
Small molecule drugs known as modulators can treat ~90% of people with cystic fibrosis (CF), but do not work for premature termination codon variants such as W1282X (c.3846G>A). Here we evaluated two gene editing strategies, Adenine Base Editing (ABE) to correct W1282X, and Homology-Independent Targeted Integration (HITI) of a CFTR superexon comprising exons 23-27 (SE23-27) to enable expression of a CFTR mRNA without W1282X. In Flp-In-293 cells stably expressing a CFTR expression minigene bearing W1282X, ABE corrected 24% of W1282X alleles, rescued CFTR mRNA from nonsense mediated decay and restored protein expression. However, bystander editing at the adjacent adenine (c.3847A>G), caused an amino acid change (R1283G) that affects CFTR maturation and ablates ion channel activity. In primary human nasal epithelial cells homozygous for W1282X, ABE corrected 27% of alleles, but with a notably lower level of bystander editing, and CFTR channel function was restored to 16% of wild-type levels. Using the HITI approach, correct integration of a SE23-27 in intron 22 of the CFTR locus in 16HBEge W1282X cells was detected in 5.8% of alleles, resulting in 7.8% of CFTR transcripts containing the SE23-27 sequence. Analysis of a clonal line homozygous for the HITI-SE23-27 produced full-length mature protein and restored CFTR anion channel activity to 10% of wild-type levels, which could be increased three-fold upon treatment with the triple combination of CF modulators. Overall, these data demonstrate two different editing strategies can successfully correct W1282X, the second most common class I variant, with a concomitant restoration of CFTR function.
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Fibrosis Quística , Humanos , Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Edición Génica , Codón sin Sentido/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , MutaciónRESUMEN
Pharmacist preceptors are fundamental to experiential placements and their training is considered essential to provide a quality and consistent student placement experience. To optimise the impact of training, the views of key stakeholders are required to inform the design of a training program. This commentary aims to synthesise the perceptions of the stakeholders, including community pharmacy preceptors, academic staff and students on preceptor training requirements. Their opinions were sought to gain an understanding of preceptor roles and associated skills and attributes, training and support requirements, and barriers and enablers to training. Responses indicated a preference for a flexible online training program, with content including an overview of the university curriculum and expectations, teaching strategies, how to provide feedback and student management. A role was identified for the university to acknowledge the work of preceptors and ensure that they are included in their plans for future experiential placement activities and curriculum development. Several barriers were identified, which challenged precepting, providing the opportunity for this commentary to focus on preceptor training that will address these key challenges, in the context of a clinical teaching environment.
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Educación en Farmacia , Servicios Farmacéuticos , Farmacias , Farmacia , Estudiantes de Farmacia , Humanos , Preceptoría , CurriculumRESUMEN
Geometric distortion is a major limiting factor for spatial specificity in high-resolution fMRI using EPI readouts and is exacerbated at higher field strengths due to increased B0 field inhomogeneity. Prominent correction schemes are based on B0 field-mapping or acquiring reverse phase-encoded (reversed-PE) data. However, to date, comparisons of these techniques in the context of fMRI have only been performed on 2DEPI data, either at lower field or lower resolution. In this study, we investigate distortion compensation in the context of sub-millimetre 3DEPI data at 7T. B0 field-mapping and reversed-PE distortion correction techniques were applied to both partial coverage BOLD-weighted and whole brain MT-weighted 3DEPI data with matched distortion. Qualitative assessment showed overall improvement in cortical alignment for both correction techniques in both 3DEPI fMRI and whole-brain MT-3DEPI datasets. The distortion-corrected MT-3DEPI images were quantitatively evaluated by comparing cortical alignment with an anatomical reference using dice coefficient (DC) and correlation ratio (CR) measures. These showed that B0 field-mapping and reversed-PE methods both improved correspondence between the MT-3DEPI and anatomical data, with more substantial improvements consistently obtained using the reversed-PE approach. Regional analyses demonstrated that the largest benefit of distortion correction, and in particular of the reversed-PE approach, occurred in frontal and temporal regions where susceptibility-induced distortions are known to be greatest, but had not led to complete signal dropout. In conclusion, distortion correction based on reversed-PE data has shown the greater capacity for achieving faithful alignment with anatomical data in the context of high-resolution fMRI at 7T using 3DEPI.
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Imagen Eco-Planar , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Imagen Eco-Planar/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , ArtefactosRESUMEN
Objective: The term consumer health technologies we use in this paper refers to fitness and health apps, wearables and other self-tracking devices that collect health-related data. Our paper aims to bridge the gap between the growing literature base of sociological research and ethical reflection on the (non-intended) effects of consumer health technology use on the psycho-social level, such as stress, responsibilization or a loss of intuitive sense for signs of health or illness. Special consideration should be given to vulnerable individuals, as the positive and negative effects of consumer health technology use may be unequally distributed. This perspective may help to guide policymaking and the responsible development of consumer health technologies. Methods: Using a narrative review approach, we refer to empirical and theoretical studies dealing with user types and effects related to the use of consumer health technologies. We provide an overview of consumer health technology user typologies and evidence of the unintended psycho-social effects of consumer health technology use. On this basis, we propose a user typology that may serve as a future tool for ethical reflection on negative side effects. Results: Evidence of the potential negative side effects of consumer health technology use, as presented in the literature, is inconclusive due to the high diversity of consumer health technology users and the way they use consumer health technologies. Our proposed user typology aims to more comprehensively document the diversity of users by incorporating the way in which users identify with and use their self-tracked data, attitudes towards the new technology and social interactions via consumer health technologies, and the purpose and self-determinedness of consumer health technology use. Conclusions: More systematic and quantitative empirical research on the effects of consumer health technology use in diverse settings and with diverse user types is necessary to inform public health policy. In addition to evidence-based certification of medical consumer health technologies, more practical and flexible ways to protect users from side effects may have to be developed and adopted, especially regarding the increasing number of non-medical consumer health technologies.
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Motor skill learning relies on neural plasticity in the motor and limbic systems. However, the spatial and temporal characteristics of these changes-and their microstructural underpinnings-remain unclear. Eighteen healthy males received 1 h of training in a computer-based motion game, 4 times a week, for 4 consecutive weeks, while 14 untrained participants underwent scanning only. Performance improvements were observed in all trained participants. Serial myelin- and iron-sensitive multiparametric mapping at 3T during this period of intensive motor skill acquisition revealed temporally and spatially distributed, performance-related microstructural changes in the grey and white matter across a corticospinal-cerebellar-hippocampal circuit. Analysis of the trajectory of these transient changes suggested time-shifted cascades of plasticity from the dominant sensorimotor system to the contralateral hippocampus. In the cranial corticospinal tracts, changes in myelin-sensitive metrics during training in the posterior limb of the internal capsule were of greater magnitude in those who trained their upper limbs vs. lower limb trainees. Motor skill learning is associated with waves of grey and white matter plasticity, across a broad sensorimotor network.
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Destreza Motora , Sustancia Blanca , Masculino , Humanos , Aprendizaje , Sustancia Blanca/diagnóstico por imagen , Extremidad Superior , Vaina de Mielina , Plasticidad NeuronalRESUMEN
The habenula is a small, epithalamic brain structure situated between the mediodorsal thalamus and the third ventricle. It plays an important role in the reward circuitry of the brain and is implicated in psychiatric conditions, such as depression. The importance of the habenula for human cognition and mental health make it a key structure of interest for neuroimaging studies. However, few studies have characterised the physical properties of the human habenula using magnetic resonance imaging because its challenging visualisation in vivo, primarily due to its subcortical location and small size. To date, microstructural characterization of the habenula has focused on quantitative susceptibility mapping. In this work, we complement this previous characterisation with measures of longitudinal and effective transverse relaxation rates, proton density and magnetisation transfer saturation using a high-resolution quantitative multi-parametric mapping protocol at 3T, in a cohort of 26 healthy participants. The habenula had consistent boundaries across the various parameter maps and was most clearly visualised on the longitudinal relaxation rate maps. We have provided a quantitative multi-parametric characterisation that may be useful for future sequence optimisation to enhance visualisation of the habenula, and additionally provides reference values for future studies investigating pathological differences in habenula microstructure.
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Habénula , Humanos , Cognición , Imagen por Resonancia Magnética , NeuroimagenRESUMEN
PURPOSE: The effective transverse relaxation rate ( R 2 * $$ {\mathrm{R}}_2^{\ast } $$ ) is influenced by biological features that make it a useful means of probing brain microstructure. However, confounding factors such as dependence on flip angle (α) and fiber orientation with respect to the main field ( θ $$ \uptheta $$ ) complicate interpretation. The α- and θ $$ \uptheta $$ -dependence stem from the existence of multiple sub-voxel micro-environments (e.g., myelin and non-myelin water compartments). Ordinarily, it is challenging to quantify these sub-compartments; therefore, neuroscientific studies commonly make the simplifying assumption of a mono-exponential decay obtaining a single R 2 * $$ {\mathrm{R}}_2^{\ast } $$ estimate per voxel. In this work, we investigated how the multi-compartment nature of tissue microstructure affects single compartment R 2 * $$ {\mathrm{R}}_2^{\ast } $$ estimates. METHODS: We used 2-pool (myelin and non-myelin water) simulations to characterize the bias in single compartment R 2 * $$ {\mathrm{R}}_2^{\ast } $$ estimates. Based on our numeric observations, we introduced a linear model that partitions R 2 * $$ {\mathrm{R}}_2^{\ast } $$ into α-dependent and α-independent components and validated this in vivo at 7T. We investigated the dependence of both components on the sub-compartment properties and assessed their robustness, orientation dependence, and reproducibility empirically. RESULTS: R 2 * $$ {\mathrm{R}}_2^{\ast } $$ increased with myelin water fraction and residency time leading to a linear dependence on α. We observed excellent agreement between our numeric and empirical results. Furthermore, the α-independent component of the proposed linear model was robust to the choice of α and reduced dependence on fiber orientation, although it suffered from marginally higher noise sensitivity. CONCLUSION: We have demonstrated and validated a simple approach that mitigates flip angle and orientation biases in single-compartment R 2 * $$ {\mathrm{R}}_2^{\ast } $$ estimates.
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Imagen por Resonancia Magnética , Vaina de Mielina , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Vaina de Mielina/química , Encéfalo/diagnóstico por imagen , Agua/análisisRESUMEN
The pharmacist preceptor is key to the success of pharmacy student experiential placements with a recent focus being placed on the quality of preceptors. This study sought to investigate student perceptions of the ideal roles and attributes of pharmacist preceptors to inform the development of a preceptor training program. This was a mixed methods study using an online survey of pharmacy students from levels two to four of an undergraduate pharmacy honours program at a regional Australian university followed by qualitative, semi-structured focus group interviews. Surveys were analysed using descriptive statistics and content analysis while interviews were thematically analysed. Thirty-seven complete survey responses were received, and three student focus groups were conducted. Students identified the key role of preceptors in linking theory to practice and felt that the role of the preceptor in student assessment should focus on practical skills, such as communication and professionalism. There was overall strong agreement between the quantitative and qualitative findings on the ideal preceptor attributes with good communication, enthusiasm for the profession and the provision of clear and honest student feedback thought to be most important. Students regarded these attributes as essential for a good preceptor-student relationship to promote learning in the practice environment.
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Leber Hereditary Optic Neuropathy (LHON) is an inherited mitochondrial retinal disease that causes the degeneration of retinal ganglion cells and leads to drastic loss of visual function. In the last decades, there has been a growing interest in using Magnetic Resonance Imaging (MRI) to better understand mechanisms of LHON beyond the retina. This is partially due to the emergence of gene-therapies for retinal diseases, and the accompanying expanded need for reliably quantifying and monitoring visual processing and treatment efficiency in patient populations. This paper aims to draw a current picture of key findings in this field so far, the challenges of using neuroimaging methods in patients with LHON, and important open questions that MRI can help address about LHON disease mechanisms and prognoses, including how downstream visual brain regions are affected by the disease and treatment and why, and how scope for neural plasticity in these pathways may limit or facilitate recovery.
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Enfermedades Mitocondriales , Atrofia Óptica Hereditaria de Leber , Humanos , Atrofia Óptica Hereditaria de Leber/diagnóstico por imagen , Atrofia Óptica Hereditaria de Leber/genética , Atrofia Óptica Hereditaria de Leber/metabolismo , Células Ganglionares de la Retina/metabolismo , Retina/diagnóstico por imagen , Retina/patología , Imagen por Resonancia MagnéticaRESUMEN
Conduction velocity is the speed at which electrical signals travel along axons and is a crucial determinant of neural communication. Inferences about conduction velocity can now be made in vivo in humans using a measure called the magnetic resonance (MR) g-ratio. This is the ratio of the inner axon diameter relative to that of the axon plus the myelin sheath that encases it. Here, in the first application to cognition, we found that variations in MR g-ratio, and by inference conduction velocity, of the parahippocampal cingulum bundle were associated with autobiographical memory recall ability in 217 healthy adults. This tract connects the hippocampus with a range of other brain areas. We further observed that the association seemed to be with inner axon diameter rather than myelin content. The extent to which neurites were coherently organised within the parahippocampal cingulum bundle was also linked with autobiographical memory recall ability. Moreover, these findings were specific to autobiographical memory recall and were not apparent for laboratory-based memory tests. Our results offer a new perspective on individual differences in autobiographical memory recall ability, highlighting the possible influence of specific white matter microstructure features on conduction velocity when recalling detailed memories of real-life past experiences.
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Memoria Episódica , Sustancia Blanca , Adulto , Encéfalo , Humanos , Imagen por Resonancia Magnética , Recuerdo Mental , Sustancia Blanca/diagnóstico por imagenRESUMEN
Silicification of DNA origami structures increases their stability and provides chemical protection. Yet, it is unclear whether the whole DNA framework is embedded or if silica just forms an outer shell and how silicification affects the origami's internal structure. Employing in situ small-angle X-ray scattering (SAXS), we show that addition of silica precursors induces substantial condensation of the DNA origami at early reaction times by almost 10 %. Subsequently, the overall size of the silicified DNA origami increases again due to increasing silica deposition. We further identify the SAXS Porod invariant as a reliable, model-free parameter for the evaluation of the amount of silica formation at a given time. Contrast matching of the DNA double helix Lorentzian peak reveals silica growth also inside the origami. The less polar silica forming within the origami structure, replacing more than 40 % of the internal hydration water, causes a hydrophobic effect: condensation. DNA origami objects with flat surfaces show a strong tendency towards aggregation during silicification, presumably driven by the same entropic forces causing condensation. Maximally condensed origami displayed thermal stability up to 60 °C. Our studies provide insights into the silicification reaction allowing for the formulation of optimized reaction protocols.