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Hearing loss (HL) affects over 460 million people worldwide, significantly affecting quality of life. Genetic analysis has identified more than 150 causative monogenic genes for non-syndromic sensorineural hearing loss, presenting attractive targets for gene therapy interventions. These approaches also have the potential to enhance conventional treatment strategies. Particularly interesting in this regard are cochlear implants (CI), used for severe to profound HL. However, their efficacy is believed to depend on spiral ganglion neuron (SGN) survival. Recognizing the potential of neurotrophins to enhance SGN survival and improve CI outcomes, we here report on the development of a novel adeno-associated virus (AAV) vector optimized for transducing SGN, even in adult mice and at low vector doses. For this purpose, the capsid was engineered to display a heptamer peptide, which was previously derived from a phage library screen. Structure-focused modeling of our novel vector Var9 indicated a clear change in cell attachment receptor binding due to peptide insertion compared to its parental serotype AAV2. Predictions were confirmed using affinity chromatography and competition assays. Interestingly, Var9 demonstrated faster transgene expression in HEI-OC1 cells, a murine otic progenitor cell line, despite significantly lower entry efficiency, indicating enhanced intracellular processing of the vector. Subsequent IF-FISH analysis at single-cell level as well as our indirect uncoating assay revealed that Var9 vectors clearly outperform AAV2 vectors regarding kinetics and level of uncoating (3-fold), i.e. release of their genome from the capsid, a prerequisite for transgene transcription. Finally, in a neurotrophic gene therapy approach, Var9 effectively prevented SGN degeneration by overexpressing BDNF in SGN of deafened mice. Histological analysis of the cochlea revealed remarkable protective effects of SGN comparable to untreated control levels in all cochlear turns of mice treated with Var9-BDNF. In conclusion, our novel AAV vector demonstrated superior properties crucial for efficient SGN transduction and will be further refined for clinical applications, aiming to enhance neural survival and improve outcomes for cochlear gene therapy in CI recipients. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is increasingly prevalent worldwide, and disease‐modifying treatments may soon be at hand; hence, now, more than ever, there is a need to develop techniques that allow earlier and more secure diagnosis. Current biomarker‐based guidelines for AD diagnosis, which have replaced the historical symptom‐based guidelines, rely heavily on neuroimaging and cerebrospinal fluid (CSF) sampling. While these have greatly improved the diagnostic accuracy of AD pathophysiology, they are less practical for application in primary care, population‐based and epidemiological settings, or where resources are limited. In contrast, blood is a more accessible and cost‐effective source of biomarkers in AD. In this review paper, using the recently proposed amyloid, tau and neurodegeneration [AT(N)] criteria as a framework towards a biological definition of AD, we discuss recent advances in biofluid‐based biomarkers, with a particular emphasis on those with potential to be translated into blood‐based biomarkers. We provide an overview of the research conducted both in CSF and in blood to draw conclusions on biomarkers that show promise. Given the evidence collated in this review, plasma neurofilament light chain (N) and phosphorylated tau (p‐tau; T) show particular potential for translation into clinical practice. However, p‐tau requires more comparisons to be conducted between its various epitopes before conclusions can be made as to which one most robustly differentiates AD from non‐AD dementias. Plasma amyloid beta (A) would prove invaluable as an early screening modality, but it requires very precise tests and robust pre‐analytical protocols. [ABSTRACT FROM AUTHOR]

Projections of future conditions within the critical zone—earthcasts—can be used to understand the potential effects of changes in climate on processes affecting landscapes. We are developing an approach to earthcast how weathering will change in the future using scenarios of climate change. As a first step here, we use the earthcasting approach to model aspect‐related effects on soil water chemistry and weathering on hillsides in a well‐studied east‐west trending watershed (Shale Hills, Pennsylvania, USA). We completed model simulations of solute chemistry in soil water with and without the effect of aspect for comparison to catchment observations. With aspect included, aqueous weathering fluxes were higher on the sunny side of the catchment. But the effect of aspect on temperature (0.8 °C warmer soil on sunny side) and recharge (100 mm/year larger on shaded side) alone did not explain the magnitude of the observed higher weathering fluxes on the sunny side. Modeled aspect‐related differences in weathering fluxes only approach field observations when we incorporated the measured differences in clay content observed in augered soils on the two hillslopes. We also had to include a biolifting module to accurately describe cation concentrations in soil water versus depth. Biolifting lowered some mineral dissolution rates while accelerating kaolinite precipitation. These short‐duration simulations also highlighted that the inherited differences in particle size on the two sides of the catchment might in themselves be explained by weathering under different microclimates caused by aspect—over longer durations than simulated with our models. Key Points: Aspect‐related differences in solar radiation in watersheds affect both the fluxes and extents of weathering from short to long timescalesReactive transport models of weathering suggest biolifting by vegetation slows mineral dissolution rates during weathering of shaleEarthcasts of weathering fluxes must model not only geochemical processes but also erosion and biotic cycling rates [ABSTRACT FROM AUTHOR]

Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. In this review, current understanding of the epidemiology, genetics, pathology and pathogenesis of Alzheimer's disease is outlined, before its clinical presentation and current treatment strategies are discussed. Finally, the review discusses how our enhanced understanding of Alzheimer pathogenesis, including the recognition of a protracted preclinical phase, is informing new therapeutic strategies with the aim of moving from treatment to prevention. [ABSTRACT FROM AUTHOR]

We present new unit operations for valving and switching in centrifugal microfluidics that are actuated by a temperature change rate (TCR) and controlled by the rotational frequency. Implementation is realized simply by introducing a comparatively large fluidic resistance to an air vent of a fluidic structure downstream of a siphon channel. During temperature decrease at a given TCR, the air pressure inside the downstream structure decreases and the fluidic resistance of the air vent slows down air pressure compensation allowing a thermally induced underpressure to build up temporarily. Thereby the rate of temperature change determines the time course of the underpressure for a given geometry. The thermally induced underpressure pulls the liquid against a centrifugal counterpressure above a siphon crest, which triggers the valve or switch. The centrifugal counterpressure (adjusted by rotation) serves as an independent control parameter to allow or prevent valving or switching at any TCR. The unit operations are thus compatible with any temperature or centrifugation protocol prior to valving or switching. In contrast to existing methods, this compatibility is achieved at no additional costs: neither additional fabrication steps nor additional disk space or external means are required besides global temperature control, which is needed for the assay. For the layout, an analytical model is provided and verified. The TCR actuated unit operations are demonstrated, first, by a stand-alone switch that routes the liquid to either one of the two collection chambers (n = 6) and, second, by studying the robustness of TCR actuated valving within a microfluidic cartridge for highly integrated nucleic acid testing. Valving could safely be prevented during PCR by compensating the thermally induced underpressure of 3.52 kPa with a centrifugal counterpressure at a rotational frequency of 30 Hz with a minimum safety range to valving of 2.03 kPa. Subsequently, a thermally induced underpressure of 2.55 kPa was utilized for robust siphon valving at 3 Hz with a minimum safety range of 2.32 kPa. [ABSTRACT FROM AUTHOR]

Examines the current-voltage characteristics of zinc oxide varistors prior to and after exposure to gamma radiation. Description of zinc oxide varistors; Analysis of leakage current associated with the exposure; Influence of ionizing radiation on the breakover voltages of the avalanche diodes.

Background: Patients presenting with parkinsonian syndromes share many clinical features, which can make diagnosis difficult. This is important as atypical parkinsonian syndromes (APSs) such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS) carry a poor prognosis, compared with patients with Parkinson's disease (PD). In addition, there is overlap between APS and dementia diseases, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD).Objective: To use a panel of cerebrospinal fluid (CSF) biomarkers to differentiate patients with APS from PD and dementia.Methods: A prospective cohort of 160 patients and 30 control participants were recruited from a single specialist centre. Patients were clinically diagnosed according to current consensus criteria. CSF samples were obtained from patients with clinical diagnoses of PD (n=31), PSP (n=33), CBS (n=14), MSA (n=31), AD (n=26) and FTD (n=16). Healthy, elderly participants (n=30) were included as controls. Total τ (t-τ), phosphorylated τ (p-τ), β-amyloid 1-42 (Aβ42), neurofilament light chain (NFL), α-synuclein (α-syn), amyloid precursor protein soluble metabolites α and β (soluble amyloid precursor protein (sAPP)α, sAPPβ) and two neuroinflammatory markers (monocyte chemoattractant protein-1 and YKL-40) were measured in CSF. A reverse stepwise regression analysis and the false discovery rate procedure were used.Results: CSF NFL (p<0.001), sAPPα (p<0.001) and a-syn (p=0.003) independently predicted diagnosis of PD versus APS. Together, these nine biomarkers could differentiate patients with PD from APS with an area under the curve of 0.95 and subtypes of APS from one another. There was good discriminatory power between parkinsonian groups, dementia disorders and healthy controls.Conclusions: A panel of nine CSF biomarkers was able to differentiate APS from patients with PD and dementia. This may have important clinical utility in improving diagnostic accuracy, allowing better prognostication and earlier access to potential disease-modifying therapies. [ABSTRACT FROM AUTHOR]

Background and purpose Previous studies have indicated clinical benefits of a combination of cholinesterase inhibitors (Ch EI) and memantine over Ch EI monotherapy in Alzheimer's disease ( AD). Our objective was the development of guidelines on the question of whether combined Ch EI/memantine treatment rather than Ch EI alone should be used in patients with moderate to severe AD to improve global clinical impression ( GCI), cognition, behaviour and activities of daily living ( ADL). Methods A systematic review and meta-analysis of randomized controlled trials based on a literature search in ALOIS, the register of the Cochrane Dementia and Cognitive Improvement Group, was carried out with subsequent guideline development according to the Grading of Recommendations Assessment, Development and Evaluation ( GRADE) system. Results Pooled data from four trials including 1549 AD patients in the moderate to severe disease stage demonstrated significant beneficial effects of combination therapy compared to Ch EI monotherapy for GCI [standardized mean difference ( SMD) −0.20; 95% confidence interval ( CI) −0.31; −0.09], cognitive functioning ( SMD −0.27, 95% CI −0.37; −0.17) and behaviour ( SMD −0.19; 95% CI −0.31; −0.07). The quality of evidence was high for behaviour, moderate for cognitive function and GCI and low for ADL. Agreement of panellists was reached after the second round of the consensus finding procedure. The desirable effects of combined Ch EI and memantine treatment were considered to outweigh undesirable effects. The evidence was weak for cognition, GCI and ADL so that the general recommendation for using combination therapy was weak. Conclusions We suggest the use of a combination of Ch EI plus memantine rather than Ch EI alone in patients with moderate to severe AD. The strength of this recommendation is weak. [ABSTRACT FROM AUTHOR]

In its recent guidance document on tiered risk assessment for plant protection products for aquatic organisms, the European Food Safety Authority (EFSA) proposed to use Glyceria maxima as monocotyledonous grass species for the testing of special herbicide groups. However, published toxicity data for this species is very limited and there is no test guideline for Glyceria sp. For this reason a microcosm study was conducted in order to gain experience on the degree of sensitivity of G. maxima to the herbicidal substances clodinafop-propargyl (grass herbicide) and fluroxypyr (auxin) in comparison to the already established test organism water milfoil Myriophyllum spicatum and the duckweed species Landoltia punctata. Five concentrations without replicates were tested for each test substance using 10 microcosms and three microcosms served as controls. The experiment was run for 8 weeks. Morphological endpoints were used to determine growth and EC values. The results show that M. spicatum was most sensitive to fluroxypyr (37 days EC for roots: 62 µg/L) and G. maxima most sensitive to clodinafop-propargyl (22 days EC for total shoot length: 48 µg/L) whereas the duckweed species was considerable less sensitive. Hence, G. maxima turns out to be a good candidate for testing grass specific herbicides, supporting its inclusion as an additional macrophyte test for the risk assessment of herbicides as proposed by the EFSA. [ABSTRACT FROM AUTHOR]

Oculoleptomeningeal amyloidosis is a rare manifestation of hereditary transthyretin (TTR) amyloidosis. Here, we present the first case of leptomeningeal amyloidosis associated with the TTR variant Leu12Pro mutation in an African patient. A 43-year-old right-handed Nigerian man was referred to our centre with rapidly progressive neurological decline. He presented initially with weight loss, confusion, fatigue, and urinary and erectile dysfunction. He then suffered recurrent episodes of slurred speech with right-sided weakness. He went on to develop hearing difficulties and painless paraesthesia. Neurological examination revealed horizontal gaze-evoked nystagmus, brisk jaw jerk, increased tone, brisk reflexes throughout and bilateral heel-shin ataxia. Magnetic resonance imaging showed extensive leptomeningeal enhancement. Cerebrospinal fluid analysis showed a raised protein of 6.4 g/dl. Nerve conduction studies showed an axonal neuropathy. Echocardiography was characteristic of cardiac amyloid. TTR gene sequencing showed that he was heterozygous for the leucine 12 proline mutation. Meningeal and brain biopsy confirmed widespread amyloid angiopathy. TTR amyloidosis is a rare cause of leptomeningeal enhancement, but should be considered if there is evidence of peripheral or autonomic neuropathy with cardiac or ocular involvement. The relationship between different TTR mutations and clinical phenotype, disease course, and response to treatment remains unclear. [ABSTRACT FROM AUTHOR]

Imaging, cerebrospinal fluid (CSF) and blood-based biomarkers have the potential to improve the accuracy by which specific causes of dementia can be diagnosed in vivo, provide insights into the underlying pathophysiology, and may be used as inclusion criteria and outcome measures for clinical trials. While a number of imaging and CSF biomarkers are currently used for each of these purposes, this is an evolving field, with numerous potential biomarkers in varying stages of research and development. We review the currently available biomarkers for the three most common forms of neurodegenerative dementia, and give an overview of research techniques that may in due course make their way into the clinic. [ABSTRACT FROM AUTHOR]

The Landsat archive of thermal data (Landsats 4, 5 and 7) has gone through a rigorous calibration assessment and update. However, in order to be useful to most users the calibrated sensor reaching radiance must be corrected to surface temperatures by first compensating for atmospheric effects and then emissivity variations. The USGS is exploring the possibility of producing a LST product through a joint program with RIT (the atmospheric compensation component) and JPL (the emissivity compensation component). This paper addresses the atmospheric compensation component for an initial North American pilot study. In particular, the results of a comparison of retrieved water surface temperature (where emissivity is well known) and truth temperatures for over 800 sites are presented. The errors are broken down by cloud conditions with extremely good results for cloud-free conditions (errors less than 1K). The results of the error assessment for North America by cloud class are presented along with a discussion of potential quality data for a LST product. An initial assessment of the LST errors observed for Landsat 8 bands 10 and 11 are also presented. The next steps on this effort include testing of a global atmospheric compensation approach and full integration of the atmospheric and emissivity compensation tools into an operational LST product. [ABSTRACT FROM AUTHOR]

Retroviral vectors are versatile gene transfer vehicles widely used in basic research and gene therapy. Mutation of retroviral integrase converts these vectors into transient, integration-deficient gene delivery vehicles associated with a high degree of biosafety. We explored the option to use integration-deficient retroviral vectors to achieve transient ectopic expression of transcription factors, which is considered an important tool for induced cell fate conversion. Stepwise optimization of the retroviral episome transfer as exemplified for the transcription factor Oct4 enabled to improve both expression magnitude and endurance. Long terminal repeat-driven γ-retroviral vectors were identified as the most suitable vector architecture. Episomal expression was enhanced by epigenetic modifiers, and Oct4 activity was increased following fusion to a minimal transactivation motif of herpes simplex virus VP16. Based on kinetic analyses, we identified optimal time intervals for repeated vector administration and established prolonged expression windows of choice. Providing proof-of-concept, episomal transfer of Oct4 was potent to mediate conversion of human fibroblasts stably expressing Klf4, Sox2 and c-Myc into induced pluripotent stem cells, which were mainly free of residual Oct4 vector integration. This study provides evidence for suitability of retroviral episome transfer of transcription factors for cell fate conversion, allowing the generation of distinct patient- or disease-specific cell types. [ABSTRACT FROM AUTHOR]

Due to their use in the fields of sensors, energy harvesting, capacitors and FeRAMs the fabrication of microstructured ferroelectric thin films is an important research field. Therefore a modified sol-gel process chain has been developed to produce fine patterned ferroelectric PZT (PbZrTiO) thin films by direct UV-lithography. A sol based on methacrylic acid was developed to provide a photosensitive metal organic PZT precursor. The sol was used to obtain photosensitive xerogel films by spin-coating, which were patterned using conventional UV-photolithography equipment. After development the patterned xerogel films were pyrolized and crystallized in air via rapid thermal annealing in order to obtain crystalline PZT thin films. The patterned PZT films were investigated by XRD technique and SEM-micrographs. Finely patterned, crack free, crystalline PZT thin films were obtained. [ABSTRACT FROM AUTHOR]

The article focuses on the diagnosis of adult-onset leukodystrophies, and mentions that the term leukodystrophy refers to a group of conditions that are inherited and involve the destruction or loss of previously acquired myelin. It presents a case study of middle aged patient with history of progressive gait and cognitive difficulties, whose frontal and parietal lobe functions were found impaired. Topics discussed include differential diagnosis, family history of patients and Krabbe disease.

The prevalence of Rhizoctonia spp. in European soils was determined by analysing soil samples from 282 locations. Rhizoctonia spp. were found in 68% of these samples from France, Germany, the UK, Poland, Italy, Spain, Hungary and the Czech Republic. Samples from 136 locations were further analysed by pyrosequencing. Seventy-six percent of the isolates were Rhizoctonia solani and 24% binucleate Rhizoctonia spp. Rhizoctonia solani anastomosis group ( AG) 5 was detected most frequently (25%), followed by AG 9 (16%) and AG 4 (13%). For the binucleate Rhizoctonia spp., AG E was most prevalent (13%). Rhizoctonia cerealis was not detected in soil samples. Soil type or cropping history had no effect on the type of Rhizoctonia observed. Rhizoctonia solani AG 5 was the most frequently detected AG irrespective of the previous crop. The spectrum of AGs detected was similar for France, Germany and Poland but was significantly different for the UK ( P = 0·0016). Finally, the baseline sensitivity towards sedaxane, a new active ingredient for seed treatment, was analysed for all isolates. The results indicate a low baseline sensitivity (average EC50 of 0·028 p.p.m.) for all Rhizoctonia AGs. No difference in sensitivity was observed with the isolates obtained from different countries. [ABSTRACT FROM AUTHOR]

Quantifying how C fluxes will change in the future is a complex task for models because of the coupling between climate, hydrology, and biogeochemical reactions. Here we investigate how pedogenesis of the Peoria loess, which has been weathering for the last 13 kyr, will respond over the next 100 yr of climate change. Using a cascade of numerical models for climate (ARPEGE), vegetation (CARAIB) and weathering (WITCH), we explore the effect of an increase in CO2 of 315 ppmv (1950) to 700 ppmv (2100 projection). The increasing CO2 results in an increase in temperature along the entire transect. In contrast, drainage increases slightly for a focus pedon in the south but decreases strongly in the north. These two variables largely determine the behavior of weathering. In addition, although CO2 production rate increases in the soils in response to global warming, the rate of diffusion back to the atmosphere also increases, maintaining a roughly constant or even decreasing CO2 concentration in the soil gas phase. Our simulations predict that temperature increasing in the next 100 yr causes the weathering rates of the silicates to increase into the future. In contrast, the weathering rate of dolomite -- which consumes most of the CO2 -- decreases in both end members (south and north) of the transect due to its retrograde solubility. We thus infer slower rates of advance of the dolomite reaction front into the subsurface, and faster rates of advance of the silicate reaction front. However, additional simulations for 9 pedons located along the north--south transect show that the dolomite weathering advance rate will increase in the central part of the Mississippi Valley, owing to a maximum in the response of vertical drainage to the ongoing climate change. The carbonate reaction front can be likened to a terrestrial lysocline because it represents a depth interval over which carbonate dissolution rates increase drastically. However, in contrast to the lower pH and shallower lysocline expected in the oceans with increasing atmospheric CO2, we predict a deeper lysocline in future soils. Furthermore, in the central Mississippi Valley, soil lysocline deepening accelerates but in the south and north the deepening rate slows. This result illustrates the complex behavior of carbonate weathering facing short term global climate change. Predicting the global response of terrestrial weathering to increased atmospheric CO2 and temperature in the future will mostly depend upon our ability to make precise assessments of which areas of the globe increase or decrease in precipitation and soil drainage. [ABSTRACT FROM AUTHOR]

CO2 exchange between terrestrial ecosystems and the atmosphere is key to understanding the feedbacks between climate change and the land surface. In regions with carbonaceous parent material, CO2 exchange patterns occur that cannot be explained by biological processes, such as disproportionate outgassing during daytime or nighttime CO2 uptake during periods when all vegetation is senescent. Neither of these phenomena can be attributed to carbonate weathering reactions, since their CO2 exchange rates are too small. Soil ventilation induced by high atmospheric turbulence is found to explain atypical CO2 exchange between carbonaceous systems and the atmosphere. However, by strongly altering subsurface CO2 concentrations, ventilation can be expected to influence carbonate weathering rates. By imposing ventilation-driven CO2 outgassing in a carbonate weathering model, we show here that carbonate geochemistry is accelerated and does play a surprisingly large role in the observed CO2 exchange patterns. We found that by rapidly depleting soil CO2 during daytime, ventilation disturbs soil carbonate equilibria and therefore strongly magnifies daytime carbonate precipitation and associated CO2 production. At night, ventilation ceases and the depleted CO2 concentrations increase steadily. Dissolution of carbonate is now enhanced, which consumes CO2 and largely compensates for the enhanced daytime carbonate precipitation. This is why only a relatively small effect on global carbonate weathering rates is to be expected. On the short term, however, ventilation has a drastic effect on synoptic carbonate weathering rates, resulting in a pronounced diel pattern that exacerbates the non-biological behavior of soil-atmosphere CO2 exchanges in dry regions with carbonate soils. [ABSTRACT FROM AUTHOR]

Quantifying how C fluxes will change in the future is a complex task for models because of the coupling between climate, hydrology, and biogeochemical reactions. Here we investigate how pedogenesis of the Peoria loess, which has been weathering for the last 13 kyr, will respond over the next 100 yr of climate change. Using a cascade of numerical models for climate (ARPEGE), vegetation (CARAIB) and weathering (WITCH) we explore the effect of an increase in CO2 of 315 ppmv (1950) to 700 ppmv (2100 projection). The increasing CO2 results in an increase in temperature along the entire transect. In contrast, drainage increases slightly for a focus pedon in the South but decreases strongly in the North. These two variables largely determine the behavior of weathering. In addition, although CO2 production rate increases in the soils in response to global warming, the rate of diffusion back to the atmosphere also increases, maintaining a roughly constant or even decreasing CO2 concentration in the soil gas phase. Our simulations predict that temperature increasing in the next 100 yr causes the weathering rates of the silicates to increase into the future. In contrast, the weathering rate of dolomite -- which consumes most of the CO2-decreases due to its retrograde solubility in both end members (South and North) of the transect. We thus infer slower rates of advance of the dolomite reaction front into the subsurface, and faster rates of advance of the silicate reaction front. However, additional simulations for 9 pedons located along the North--South transect show that dolomite weathering will increase in the central part of the Mississippi Valley, owing to a maximum in the response of vertical drainage to the ongoing climate change. The carbonate reaction front can be likened to a terrestrial lysocline because it represents a depth interval over which carbonate dissolution rates increase drastically. However, in contrast to the lower pH and shallower lysocline expected in the oceans with increasing atmospheric CO2, we predict an acceleration of the lysocline deepening in soils in the central area of the Mississippi Valley, but a slowdown of its deepening in the Southern and Northern section. This result illustrates the complex behavior of carbonate weathering facing short term global climate change. Predicting the global response of terrestrial weathering to increased atmospheric CO2 and temperature in the future will mostly depend upon our ability to make precise assessments of which areas of the globe increase or decrease in precipitation and soil drainage. [ABSTRACT FROM AUTHOR]

Cerebral atrophy calculated from serial MRI is a marker of Alzheimer’s disease (AD) progression, and a potential outcome measure for therapeutic trials. Reducing within-subject variability in cerebral atrophy rates by acquiring more than two serial scans could allow for shorter clinical trials requiring smaller patient numbers. Forty-six patients with AD and 23 controls each had up to 10 serial MR brain scans over two years. Whole brain atrophy was calculated for each subject from every scan-pair. 708 volumetric MRI scans were acquired: 2199 measures of atrophy were made for patients, and 1182 for controls. A linear mixed model was used to characterise between and within-individual variability. These results were used to investigate the power of combining multiple serial scans in treatment trials of varying lengths. In AD, the mean whole brain atrophy rate was 2.23%/year (95% CI: 1.90–2.56%/year). The linear mixed model was shown to fit the data well and led to a formula (0.992+(0.82/t)2) for the variance of atrophy rates calculated from two scans “t” years apart. Utilising five optimally timed scans with repeat scans at each visit reduced the component of atrophy rate variance attributable to within-subject variability by ~ 56%, equating to a ~ 40% sample size reduction (228 vs 387 patients per arm to detect 20% reduction in atrophy rate) in a six-month placebo-controlled trial. This benefit in terms of sample size is relatively reduced in longer trials, although adding extra scanning visits may have benefits when patient drop-outs are accounted for. We conclude that sample sizes required in short interval therapeutic trials using cerebral atrophy as an outcome measure may be reduced if multiple serial MRI is performed [ABSTRACT FROM AUTHOR]

Background: Frontotemporal lobar degeneration (FTLD) may be inherited as an autosomal dominant disease. Studying patients "at risk" for developing FTLD can provide insights into the earliest onset and evolution of the disease.Method: We carried out approximately annual clinical, MRI, and neuropsychological assessments on an asymptomatic 51 year old "at risk" family member from a family with FTLD associated with ubiquitin-positive and tau-negative inclusion bodies. We used non-linear (fluid) registration of serial MRI to determine areas undergoing significant regional atrophy at different stages of the disease.Results: Over the first 26 months of the study, the patient remained asymptomatic, but subsequently developed progressive speech production difficulties, and latterly severe orofacial dyspraxia, dyscalculia, frontal executive impairment, and limb dyspraxia. Regional atrophy was present prior to the onset of symptoms, and was initially centred on the left dorsolateral prefrontal cortex and the left middle frontal gyrus. Latterly, there was increasing asymmetric left frontal and parietal atrophy. Imaging revealed excess and increasing global atrophy throughout the study. Neuropsychological evaluation revealed mild intellectual impairment prior to the onset of these clinical symptoms; frontal executive and left parietal impairment subsequently emerged, culminating in widespread cognitive impairment. Fluid registered MRI allowed the emerging atrophy patterns to be delineated.Conclusion: We have demonstrated the onset and progressive pattern of in vivo atrophy in familial FTLD using fluid registered MRI and correlated this with the clinical features. Fluid registered MRI may be a useful technique in assessing patterns of focal atrophy in vivo and demonstrating the progression of degenerative diseases. [ABSTRACT FROM AUTHOR]

The geomagnetic field above the surface of the Earth in the current-free region may be expressed as the gradient of a scalar potential solving Laplace's equation. For regions with a fairly dense coverage of data at different altitudes, a regional model ought to offer a better spatial resolution of the regional field over the volume under study than a global field expanded in spherical harmonics (SH). The spherical cap harmonics analysis (SCHA) is an attractive regional modelling tool having close relationship with global SH. With the SCHA adopted so far, difficulties arise in upward continuation and in establishing a relationship between global and local Gauss coefficients. Such a relationship would be useful, for instance, for introducing prior constraint on an inverse problem dealing with the estimation of local Gauss coefficients based upon a local data set. In this paper, we show that these difficulties are overcome if the SCHA modelling is formulated as a boundary value (BV) problem in a cone bounded radially by the surface of the Earth and an upper surface suitable for satellite data, and bounded laterally in order to encompass a specific region of study. Although the example worked out here applies only to a limited class of fields, which verifies some special flux condition, the ideas behind this formalism are quite general and should offer a new way of processing data in a bounded region of space. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether patients presenting with a first transient ischaemic attack (TIA) subsequently show increased rates of brain atrophy compared with age matched controls; and to assess potential risk factors for brain atrophy in this group.Methods: 60 patients with a first, isolated TIA and 26 age and sex matched controls were recruited. None had evidence of cognitive impairment. Vascular risk factors were treated appropriately. All subjects had volumetric imaging at the start of the study and one year later, when they were clinically reassessed. TIA patients also had serial dual echo brain imaging. Rates of whole brain atrophy were calculated from the registered volumetric scans, as was the incidence of new ischaemic lesions. In the TIA group, the degree of white matter disease was assessed. Atrophy rates and blood pressure were compared between patients and controls.Results: 22 patients (37%) developed new "clinically silent" infarcts during follow up. The mean (SD) annualised percentage atrophy rate in the TIA group was significantly higher than in the controls, at 0.82 (0.39)% v 0.33 (0.3)% (p < 0.0001). In the TIA group, diastolic blood pressure (p = 0.004) and white matter disease severity (p < 0.001) were correlated with cerebral atrophy rate. Increased white matter disease was found in patients in whom new ischaemic lesions developed (p < 0.001).Conclusions: Patients presenting with a first TIA have excess global brain atrophy compared with age matched controls over the subsequent year. Increased atrophy rates following a TIA may be directly or indirectly related to increasing white matter disease and diastolic hypertension. Future studies should assess whether this atrophy inevitably leads to cognitive decline, and whether aggressive treatment of risk factors for cerebrovascular disease (particularly hypertension) after a TIA can influence outcome. [ABSTRACT FROM AUTHOR]

The article provides information on hereditary dementias including Alzheimer's disease, familial Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker syndrome. Other genetic diseases where dementia is a prominent if not sole criterion including Huntington's disease, familial British and Danish dementias, and familial encephalopathy with neuroserpin inclusion bodies are discussed. It is suggested that genetic testing should be accompanied by a detailed family history. INSETS: Abbreviations;UK associations and societies providing information for patients;Useful websites for health care professionals.

A remotely detectable signature for biomass burning that is specific to flaming combustion is found in the strong emission lines of potassium (K) at 766.5 nm and 769.9 nm. Ground level spectra of a test fire illustrate the high contrast signal provided by K emission. Image data collected at high altitude using the Airborne Visible Infrared Imaging Spectrometer (AVIRIS) sensor and analysed for K emission vividly displays the fire fronts of a 1995 fire in Brazil. Sensors for K emission can use silicon detector technology for advantages in high sensitivity, low cost, wide area coverage and fine spatial resolution. [ABSTRACT FROM AUTHOR]

Raman spectroscopic measurements were performed at ambient temperature onaqueous silica-bearing solutions (0.005 < mSi < 0.02; 0 < pH < 14). The spectraare consistent with the formation of monomeric Si(OH)o 4, SiO(OH)− 3 andSiO2(OH)2− 2 species at acid to neutral, basic, and strongly basic pH, respectively.Raman spectra of aqueous Al-bearing solutions at basic pH confirm thepredominance of the Al(OH)− 4 species in a wide concentration range (0.01 < mAl < 0.1).Raman spectra of basic solutions (12.4 < pH < 14.3), containing both Al andSi, exhibit a strong decrease in intensities of SiO(OH)− 3, SiO2(OH)2− 2, andAl(OH)− 4 bands in comparison with Al-free Si-bearing and Si-free Al-bearingsolutions of the same metal concentration and pH, suggesting the formation ofsoluble Al—Si complexes. The amounts of complexed Al and Si derived fromthe measurements of the Al and Si band intensities in strongly basic solutions(pH ∼ 14) are consistent with the formation, between Al(OH)− 4 andSiO2(OH)2− 2, of the single Al—Si dimer SiAlO3(OH)3− 4 according to the reactionSiO2(OH)2− 2 + Al(OH)− 4 ⇔ SiAlO3(OH)3− 4 + H2OAt lower pH (∼ 12.5) the changes in band intensities are consistent with theformation of several, likely more polymerized, Al—Si complexes. [ABSTRACT FROM AUTHOR]

The authors reflect on the clinical phenotype and underlying pathology of Alzheimer's disease. They talk about the different cognitive symptomatology and distinct disease variants of individual patients of Alzheimer's disease, which include patients with prominent dysexecutive or behavioural problems and those presenting with word-finding difficulties and pauses in speech. The mention the differences between the posterior cortical atrophy and amnestic forms of Alzheimer's disease.

Raman spectroscopic measurements were performed on aqueous acid to neutral silica-bearing solutions (0.005 ≤ mSi ≤ 0.02, 0 ≤ pH ≤ 8) and Al–silica solutions at temperature from 20 to 150°C. At 20°C, the spectrum of silica-bearing solutions exhibits only the bands of water and a completely polarized band at 785 cm−1. This band is attributed to the ν1 band of the tetrahedral Si(OH)4 molecule. In $${\text{Si(OH)}}_{\text{4}} {\kern 1pt} {\kern 1pt} - {\kern 1pt} {\text{AlCl}}_3 {\kern 1pt} - {\kern 1pt} {\text{HCl}}$$ solutions, the intensity of this band decreases with increasing Al concentration, temperature, and pH. This decrease can be explained by the formation of an inner sphere complex between Al3+ and Si(OH)4 according to the reaction: $${\text{Al}}^{{\text{3 + }}} {\text{ + H}}_{\text{4}} {\text{SiO}}_{\text{4}}^{\text{0}} ({\text{aq}}){\text{ }} \Leftrightarrow {\text{ AlH}}_{\text{3}} {\text{SiO}}_{\text{4}}^{{\text{2 + }}} {\text{ + H}}^{\text{ + }} $$ The fraction of complexed silica deduced from raman spectroscopic measurements is in good agreement with that calculated for the similar solution compositions and temperatures using the complexation constant generated by Pokrovski et al.(23) from potentiometric measurements. At ambient temperature, the formation of aluminum silicate complex is weak and does not account for more than ca. 5 % of the total Al in most natural waters. As temperature increases, this complex becomes more significant and can dominate Al speciation in acid (pH ≤ 2) hydrothermal solutions. [ABSTRACT FROM AUTHOR]

We examined oronasal flow partitioning in 27 volunteers with normal or slightly increased nasal resistance (mean ± SD, 0.24±0.19 kPa/l/s). Mean percentage of inspiratory nasal flow contribution was measured during spontaneous oronasal breathing. The averaged nasal admixture of airflow differed considerably within and between all subjects (mean ± SD, 20.9%±16.5%; range 1%-70%), showing no correlation to nasal resistance. Five of 27 subjects with a history of habitual mouth breathing had a significantly lower nasal admixture as compared with controls (2.5%±1.7% vs 25.1%±15.4%; P<0.005), but with no statistical difference in nasal resistance. To evaluate the hypothesis that velopharyngeal narrowing is due to an increased tone of the soft palate, measurements were also performed under positive nasal pressure, inspiratory resistive loading at the mouth, and during breath-holding. There was no significant difference of airflow distribution between these modifications and unloaded breathing in either group. These data suggest, therefore, that (a) oronasal flow distribution is due to active positioning of the soft palate, and that (b) habitual mouth breathing without any nasal obstruction may be associated with closure of the velopharyngeal isthmus as a consequence of disturbed neural control mechanisms. [ABSTRACT FROM AUTHOR]