207 research outputs found

    Developing music teacher identities: an international multi-site study

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    This study investigates pre-service music teacher’s (PSMT) perceptions of their professional identities. University-level education students in the United States America (USA), Spain and Australia were all asked interview questions based on general themes relevant to teacher identity development, and their responses were subjected to content analysis. Similarities were found in their perceptions of the role of ‘music teacher’ and their pre-university experiences/influences. Across the sites it seems that there was a dynamic and shifting relationship between PSMTs’ understandings of themselves as ‘musicians’ or as ‘teachers’ during their university years. This study confirms previous research in the area and contributes to the field in its discovery that these themes are found across three international sites. Implications of the findings are discussed and recommendations made for future research and practice

    Vertebral Artery Injury: Case Report and Review of Operative Approaches

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    Traumatic injury to the upper third of the neck, cephalad to the angle of the mandible, distorts the complexity of normal anatomy and underscores the importance of preoperative arteriography when possible. This report describes the case of a young man who was brought to the Emergency Room of our hospital suffering from a severe gunshot wound to the cervical spine, vertebral artery, and maxillofacial skeleton. His injury was successfully managed by combining a standard arterolateral incision with a procedure that has been described for exposing retro maxillary tumors. This operative technique provided the surgeon with direct access to the injury, controlled the loss of blood, and permitted repair of accompanying pharyngeal and facial injuries. Our report also reviews the technical considerations and pertinent surgical anatomy of this rare combination of Injuries

    Triple sign reversal of Hall effect in HgBa_{2}CaCu_{2}O_{6} thin films after heavy-ion irradiations

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    Triple sign reversal in the mixed-state Hall effect has been observed for the first time in ion-irradiated HgBa_{2}CaCu_{2}O_{6} thin films. The negative dip at the third sign reversal is more pronounced for higher fields, which is opposite to the case of the first sign reversal near T_c in most high-T_c superconductors. These observations can be explained by a recent prediction in which the third sign reversal is attributed to the energy derivative of the density of states and to a temperature-dependent function related to the superconducting energy gap. These contributions prominently appear in cases where the mean free path is significantly decreased, such as our case of ion-irradiated thin films.Comment: 4 pages, 3 eps figures, submitted Phys. Rev. Let

    Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson\u27s disease

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    \ua9 The Author(s) 2024. Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson’s disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression. Prasinezumab’s potential effects on disease progression were assessed in four prespecified and six exploratory subpopulations of PASADENA: use of monoamine oxidase B inhibitors at baseline (yes versus no); Hoehn and Yahr stage (2 versus 1); rapid eye movement sleep behavior disorder (yes versus no); data-driven subphenotypes (diffuse malignant versus nondiffuse malignant); age at baseline (≥60 years versus <60 years); sex (male versus female); disease duration (>12 months versus <12 months); age at diagnosis (≥60 years versus <60 years); motor subphenotypes (akinetic–rigid versus tremor-dominant); and motor subphenotypes (postural instability gait dysfunction versus tremor-dominant). In these subpopulations, the effect of prasinezumab on slowing motor signs progression (MDS-UPDRS Part III) was greater in the rapidly progressing subpopulations (for example, participants who were diffuse malignant or taking monoamine oxidase B inhibitors at baseline). This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson’s disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings

    Dynamics of the magnetic flux trapped in fractal clusters of normal phase in a superconductor

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    The influence of geometry and morphology of superconducting structure on critical currents and magnetic flux trapping in percolative type-II superconductor is considered. The superconductor contains the clusters of a normal phase, which act as pinning centers. It is found that such clusters have significant fractal properties. The main features of these clusters are studied in detail: the cluster statistics is analyzed; the fractal dimension of their boundary is estimated; the distribution of critical currents is obtained, and its peculiarities are explored. It is examined thoroughly how the finite resolution capacity of the cluster geometrical size measurement affects the estimated value of fractal dimension. The effect of fractal properties of the normal phase clusters on the electric field arising from magnetic flux motion is investigated in the case of an exponential distribution of cluster areas. The voltage-current characteristics of superconductors in the resistive state for an arbitrary fractal dimension are obtained. It is revealed that the fractality of the boundaries of the normal phase clusters intensifies the magnetic flux trapping and thereby raises the critical current of a superconductor.Comment: revtex, 16 pages with 1 table and 5 figures; text and figures are improved; more detailed version with geometric probability analisys of the distribution of entry points into weak links over the perimeter of a normal phase clusters and one additional figure is published in Phys.Rev.B; alternative e-mail of author is [email protected]

    Evaluation of dose-dependent treatment effects after mid-trial dose escalation in biomarker, clinical, and cognitive outcomes for gantenerumab or solanezumab in dominantly inherited Alzheimer's disease

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    Introduction: While the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) was ongoing, external data suggested higher doses were needed to achieve targeted effects; therefore, doses of gantenerumab were increased 5-fold, and solanezumab was increased 4-fold. We evaluated to what extent mid-trial dose increases produced a dose-dependent treatment effect. Methods: Using generalized linear mixed effects (LME) models, we estimated the annual low- and high-dose treatment effects in clinical, cognitive, and biomarker outcomes. Results: Both gantenerumab and solanezumab demonstrated dose-dependent treatment effects (significant for gantenerumab, non-significant for solanezumab) in their respective target amyloid biomarkers (Pittsburgh compound B positron emission tomography standardized uptake value ratio and cerebrospinal fluid amyloid beta 42), with gantenerumab demonstrating additional treatment effects in some downstream biomarkers. No dose-dependent treatment effects were observed in clinical or cognitive outcomes. Conclusions: Mid-trial dose escalation can be implemented as a remedy for an insufficient initial dose and can be more cost effective and less burdensome to participants than starting a new trial with higher doses, especially in rare diseases. Highlights: We evaluated the dose-dependent treatment effect of two different amyloid-specific immunotherapies. Dose-dependent treatment effects were observed in some biomarkers. No dose-dependent treatment effects were observed in clinical/cognitive outcomes, potentially due to the fact that the modified study may not have been powered to detect such treatment effects in symptomatic subjects at a mild stage of disease exposed to high (or maximal) doses of medication for prolonged durations

    In vivo MRI signatures of hippocampal subfield pathology in intractable epilepsy.

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    OBJECTIVES: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo. EXPERIMENTAL DESIGN: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively assessed in CA1, CA2/3, and CA4/DG. PRINCIPAL OBSERVATIONS: MRI volumes across all subfields were positively correlated with neuronal density and size. Higher T2 intensity related to increased GFAP fraction in CA1, while quantitative T1 and diffusion MRI parameters showed negative correlations with neuronal density in CA4 and DG. Multiple linear regression analysis revealed that in vivo multiparametric MRI can predict neuronal loss in all the analyzed subfields with up to 90% accuracy. CONCLUSION: Our results, based on an accurate co-registration pipeline and a subfield-specific analysis of MRI and histology, demonstrate the potential of MRI volumetry, diffusion, and quantitative T1 as accurate in vivo biomarkers of hippocampal pathology

    Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopaty

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    The stratum lacunosum moleculare (SLM) is the connection hub between entorhinal cortex and hippocampus, two brain regions that are most vulnerable in Alzheimer’s disease. We recently identified a specific synaptic deficit of Nectin-3 in transgenic models for tauopathy. Here we defined cognitive impairment and electrophysiological problems in the SLM of Tau.P301L mice, which corroborated the structural defects in synapses and dendritic spines. Reduced diffusion of DiI from the ERC to the hippocampus indicated defective myelinated axonal pathways. Ultrastructurally, myelinated axons in the temporoammonic pathway (TA) that connects ERC to CA1 were damaged in Tau.P301L mice at young age. Unexpectedly, the myelin defects were even more severe in bigenic biGT mice that co-express GSK3β with Tau.P301L in neurons. Combined, our data demonstrate that neuronal expression of protein Tau profoundly affected the functional and structural organization of the entorhinal-hippocampal complex, in particular synapses and myelinated axons in the SLM. White matter pathology deserves further attention in patients suffering from tauopathy and Alzheimer’s disease

    A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci

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    Common variant genome-wide association studies (GWASs) have, to date, identified >24 risk loci for Parkinson's disease (PD). To discover additional loci, we carried out a GWAS comparing 6,476 PD cases with 302,042 controls, followed by a meta-analysis with a recent study of over 13,000 PD cases and 95,000 controls at 9,830 overlapping variants. We then tested 35 loci (P < 1 × 10−6) in a replication cohort of 5,851 cases and 5,866 controls. We identified 17 novel risk loci (P < 5 × 10−8) in a joint analysis of 26,035 cases and 403,190 controls. We used a neurocentric strategy to assign candidate risk genes to the loci. We identified protein-altering or cis–expression quantitative trait locus (cis-eQTL) variants in linkage disequilibrium with the index variant in 29 of the 41 PD loci. These results indicate a key role for autophagy and lysosomal biology in PD risk, and suggest potential new drug targets for PD

    Systematic review: conservative treatments for secondary lymphedema

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    <p>Abstract</p> <p>Background</p> <p>Several conservative (i.e., nonpharmacologic, nonsurgical) treatments exist for secondary lymphedema. The optimal treatment is unknown. We examined the effectiveness of conservative treatments for secondary lymphedema, as well as harms related to these treatments.</p> <p>Methods</p> <p>We searched MEDLINE<sup>®</sup>, EMBASE<sup>®</sup>, Cochrane Central Register of Controlled Trials<sup>®</sup>, AMED, and CINAHL from 1990 to January 19, 2010. We obtained English- and non-English-language randomized controlled trials or observational studies (with comparison groups) that reported primary effectiveness data on conservative treatments for secondary lymphedema. For English-language studies, we extracted data in tabular form and summarized the tables descriptively. For non-English-language studies, we summarized the results descriptively and discussed similarities with the English-language studies.</p> <p>Results</p> <p>Thirty-six English-language and eight non-English-language studies were included in the review. Most of these studies involved upper-limb lymphedema secondary to breast cancer. Despite lymphedema's chronicity, lengths of follow-up in most studies were under 6 months. Many trial reports contained inadequate descriptions of randomization, blinding, and methods to assess harms. Most observational studies did not control for confounding. Many studies showed that active treatments reduced the size of lymphatic limbs, although extensive between-study heterogeneity in areas such as treatment comparisons and protocols, and outcome measures, prevented us from assessing whether any one treatment was superior. This heterogeneity also precluded us from statistically pooling results. Harms were rare (< 1% incidence) and mostly minor (e.g., headache, arm pain).</p> <p>Conclusions</p> <p>The literature contains no evidence to suggest the most effective treatment for secondary lymphedema. Harms are few and unlikely to cause major clinical problems.</p
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