Diffusion on random site percolation clusters. Theory and NMR microscopy experiments with model objects

Quasi two-dimensional random site percolation model objects were fabricate based on computer generated templates. Samples consisting of two compartments, a reservoir of H$_2$O gel attached to a percolation model object which was initially filled with D$_2$O, were examined with NMR (nuclear magnetic resonance) microscopy for rendering proton spin density maps. The propagating proton/deuteron inter-diffusion profiles were recorded and evaluated with respect to anomalous diffusion parameters. The deviation of the concentration profiles from those expected for unobstructed diffusion directly reflects the anomaly of the propagator for diffusion on a percolation cluster. The fractal dimension of the random walk, $d_w$, evaluated from the diffusion measurements on the one hand and the fractal dimension, $d_f$, deduced from the spin density map of the percolation object on the other permits one to experimentally compare dynamical and static exponents. Approximate calculations of the propagator are given on the basis of the fractional diffusion equation. Furthermore, the ordinary diffusion equation was solved numerically for the corresponding initial and boundary conditions for comparison. The anomalous diffusion constant was evaluated and is compared to the Brownian case. Some ad hoc correction of the propagator is shown to pay tribute to the finiteness of the system. In this way, anomalous solutions of the fractional diffusion equation could experimentally be verified for the first time.Comment: REVTeX, 12 figures in GIF forma

Epidemiological, clinical and genetic aspects of adult onset isolated focal dystonia in Ireland

Background: Adult onset idiopathic isolated focal dystonia presents with a number of phenotypes. Reported prevalence rates vary considerably; well-characterized cohorts are important to our understanding of this disorder. Aim: To perform a nationwide epidemiological study of adult onset idiopathic isolated focal dystonia in the Republic of Ireland. Methods: Patients with adult onset idiopathic isolated focal dystonia were recruited from multiple sources. Diagnosis was based on assessment by a neurologist with an expertise in movement disorders. When consent was obtained, a number of clinical features including family history were assessed. Results: On the prevalence date there were 592 individuals in Ireland with adult onset idiopathic isolated focal dystonia, a point prevalence of 17.8 per 100 000 (95% confidence interval 16.4-19.2). Phenotype numbers were cervical dystonia 410 (69.2%), blepharospasm 102 (17.2%), focal hand dystonia 39 (6.6%), spasmodic dysphonia 18 (3.0%), musician\u27s dystonia 17 (2.9%) and oromandibular dystonia six (1.0%). Sixty-two (16.5%) of 375 consenting index cases had a relative with clinically confirmed adult onset idiopathic isolated focal dystonia (18 multiplex and 24 duplex families). Marked variations in the proportions of patients with tremor, segmental spread, sensory tricks, pain and psychiatric symptoms by phenotype were documented. Conclusions: The prevalence of adult onset idiopathic isolated focal dystonia in Ireland is higher than that recorded in many similar service-based epidemiological studies but is still likely to be an underestimate. The low proportion of individuals with blepharospasm may reflect reduced environmental exposure to sunlight in Ireland. This study will serve as a resource for international comparative studies of environmental and genetic factors in the pathogenesis of the disorder

Lenalidomide/melphalan/dexamethasone in newly diagnosed patients with immunoglobulin light chain amyloidosis: results of a prospective phase 2 study with long-term follow up

Chemotherapy in light chain amyloidosis aims to normalize the involved free light chain in serum, which leads to an improvement, or at least stabilization of organ function in most responding patients. We performed a prospective single center phase 2 trial with 50 untreated patients not eligible for high-dose treatment. The treatment schedule comprised 6 cycles of oral lenalidomide, melphalan and dexamethasone every 4 weeks. After 6 months, complete remission was achieved in 9 patients (18%), very good partial remission in 16 (32%) and partial response in 9 (18%). Overall, organ response was observed in 24 patients (48%). Hematologic and cardiac toxicities were predominant adverse events. Mortality at 3 months was low at 4% (n=2) despite the inclusion of 36% of patients (n=18) with cardiac stage Mayo 3. After a median follow-up of 50 months, median overall and event-free survival were 67.5 months and 25.1 months, respectively. We conclude that the treatment of lenalidomide, melphalan and dexamethasone is very effective in achieving a hematologic remission, organ response and, consecutively, a long survival in transplant ineligible patients with light chain amyloidosis. However, as toxicity and tolerability are the major problems of a 3-drug regimen, a strict surveillance program is necessary and sufficient to avoid severe toxicities. clinicaltrials.gov Identifier: 00883623 (Eudract2008-001405-41)

Gaussian Process-based prediction of memory performance and biomarker status in ageing and Alzheimer's disease-A systematic model evaluation

Neuroimaging markers based on Magnetic Resonance Imaging (MRI) combined with various other measures (such as genetic covariates, biomarkers, vascular risk factors, neuropsychological tests etc.) might provide useful predictions of clinical outcomes during the progression towards Alzheimer's disease (AD). The use of multiple features in predictive frameworks for clinical outcomes has become increasingly prevalent in AD research. However, many studies do not focus on systematically and accurately evaluating combinations of multiple input features. Hence, the aim of the present work is to explore and assess optimal combinations of various features for MR-based prediction of (1) cognitive status and (2) biomarker positivity with a multi kernel learning Gaussian process framework. The explored features and parameters included (A) combinations of brain tissues, modulation, smoothing, and image resolution;(B) incorporating demographics & clinical covariates;(C) the impact of the size of the training data set;(D) the influence of dimensionality reduction and the choice of kernel types. The approach was tested in a large German cohort including 959 subjects from the multicentric longitudinal study of cognitive impairment and dementia (DELCODE). Our evaluation suggests the best prediction of memory performance was obtained for a combination of neuroimaging markers, demographics, genetic information (ApoE4) and CSF biomarkers explaining 57% of outcome variance in out-of sample predictions. The highest performance for A 42/40 status classification was achieved for a combination of demographics, ApoE4, and a memory score while usage of structural MRI further improved the classification of individual patient's pTau status

Gaussian Process-based prediction of memory performance and biomarker status in ageing and Alzheimer's disease-A systematic model evaluation

Neuroimaging markers based on Magnetic Resonance Imaging (MRI) combined with various other measures (such as genetic covariates, biomarkers, vascular risk factors, neuropsychological tests etc.) might provide useful predictions of clinical outcomes during the progression towards Alzheimer's disease (AD). The use of multiple features in predictive frameworks for clinical outcomes has become increasingly prevalent in AD research. However, many studies do not focus on systematically and accurately evaluating combinations of multiple input features. Hence, the aim of the present work is to explore and assess optimal combinations of various features for MR-based prediction of (1) cognitive status and (2) biomarker positivity with a multi kernel learning Gaussian process framework. The explored features and parameters included (A) combinations of brain tissues, modulation, smoothing, and image resolution;(B) incorporating demographics & clinical covariates;(C) the impact of the size of the training data set;(D) the influence of dimensionality reduction and the choice of kernel types. The approach was tested in a large German cohort including 959 subjects from the multicentric longitudinal study of cognitive impairment and dementia (DELCODE). Our evaluation suggests the best prediction of memory performance was obtained for a combination of neuroimaging markers, demographics, genetic information (ApoE4) and CSF biomarkers explaining 57% of outcome variance in out-of sample predictions. The highest performance for A 42/40 status classification was achieved for a combination of demographics, ApoE4, and a memory score while usage of structural MRI further improved the classification of individual patient's pTau status

The comorbidity and co-medication profile of patients with progressive supranuclear palsy

Background: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. Objectives: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. Methods: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug–drug interactions were evaluated using AiDKlinik®. Results: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug–drug interactions was higher in PSP patients, especially severe and moderate interactions. Conclusions: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients

Wear and corrosion interactions on titanium in oral environment : literature review

The oral cavity is a complex environment where corrosive substances from dietary, human saliva, and oral biofilms may accumulate in retentive areas of dental implant systems and prostheses promoting corrosion at their surfaces. Additionally, during mastication, micromovements may occur between prosthetic joints causing a relative motion between contacting surfaces, leading to wear. Both processes (wear and corrosion) result in a bio-tribocorrosion system once that occurs in contact with biological tissues and fluids. This review paper is focused on the aspects related to the corrosion and wear behavior of titanium-based structures in the oral environment. Furthermore, the clinical relevance of the oral environment is focused on the harmful effect that acidic substances and biofilms, formed in human saliva, may have on titanium surfaces. In fact, a progressive degradation of titanium by wear and corrosion (tribocorrosion) mechanisms can take place affecting the performance of titanium-based implant and prostheses. Also, the formation of wear debris and metallic ions due to the tribocorrosion phenomena can become toxic for human tissues. This review gathers knowledge from areas like materials sciences, microbiology, and dentistry contributing to a better understanding of bio-tribocorrosion processes in the oral environment.(undefined

Intramolecular and Intermolecular Contributions to the Barriers for Rotation of Methyl Groups in Crystalline Solids: Electronic Structure Calculations and Solid-State NMR Relaxation Measurements

The rotation barriers for 10 different methyl groups in five methyl-substituted phenanthrenes and three methyl-substituted naphthalenes were determined by ab initio electronic structure calculations, both for the isolated molecules and for the central molecules in clusters containing 8–13 molecules. These clusters were constructed computationally using the carbon positions obtained from the crystal structures of the eight compounds and the hydrogen positions obtained from electronic structure calculations. The calculated methyl rotation barriers in the clusters (Eclust) range from 0.6 to 3.4 kcal/mol. Solid-state 1H NMR spin–lattice relaxation rate measurements on the polycrystalline solids gave experimental activation energies (ENMR) for methyl rotation in the range from 0.4 to 3.2 kcal/mol. The energy differences Eclust – ENMR for each of the ten methyl groups range from −0.2 kcal/mol to +0.7 kcal/mol, with a mean value of +0.2 kcal/mol and a standard deviation of 0.3 kcal/mol. The differences between each of the computed barriers in the clusters (Eclust) and the corresponding computed barriers in the isolated molecules (Eisol) provide an estimate of the intermolecular contributions to the rotation barriers in the clusters. The values of Eclust – Eisol range from 0.0 to 1.0 kcal/mol

Accumulation of calcium and phosphate stimulated by carboxylic antibiotics into mitochondria

Carboxylic ionophores such as nigericin, dianemycin, the monensins and compounds Lilly A 217 or X-537 A, stimulate an electron-transport dependent accumulation of Ca 2+ and phosphate into mitochondria. Ion accumulation is stimulated under conditions of limited Ca 2+ loading imposed by phosphate in the presence of β-hydroxybutyrate. Carboxylic ionophores do not affect divalent ion uptake when β-hydroxybutyrate is replaced for by succinate. They block Ca 2+ and phosphate accumulation when energy is provided from the hydrolysis of ATP, or from the oxidation of glutamate, α-ketoglutarate, pyruvate or glutamate+malate. Nigericin-like antibiotics also transform the indefinite prolongation of state 3 respiration induced by Ca 2+ and phosphate on β-hydroxybutyrate oxidation, into tightly coupled state 3 to 4 transitions. Evidence suggests that electrophoretic Ca 2+ transport occurs in parallel with proton or K + carriers. The anion movements associated to Ca 2+ uptake are most probably driven by the existent ΔpH across the mitochondrial membrane.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44799/1/10863_2005_Article_BF01516075.pd