New insights into atypical Alzheimer's disease in the era of biomarkers

Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease

Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy

OBJECTIVE: To provide an overview of the phenotype of 2 clinically, radiologically, and pathologically similar leukodystrophies, adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and alanyl-transfer RNA synthetase 2 mutation-related leukodystrophy (AARS2-L), and highlight key differentiating features. METHODS: ALSP and AARS2-L cases were identified from the adult-onset leukodystrophy database at our institution. In addition, cases with imaging findings were identified from a literature review. The phenotypic features were determined by combining published cases with those from our database. RESULTS: A combined total of 74 cases of ALSP and 10 cases of AARS2-L with neuroimaging data were identified. The mean age at onset was 42 years in ALSP and 26 years in AARS2-L. Cognitive and motor symptoms were the most common symptoms overall in both. Ovarian failure was exclusive to AARS2-L, present in all known female cases. Both ALSP and AARS2-L showed a confluent, asymmetric, predominantly frontoparietal, periventricular pattern of white matter disease with subcortical U-fiber sparing; pyramidal tract and corpus callosum involvement; and diffusion changes in the white matter which we have termed "deep white matter diffusion dots." Central atrophy and corpus callosal thinning were prominent in ALSP and disproportionately mild in AARS2-L when present. ALSP also occasionally showed ventricular abnormalities and calcifications in the frontal periventricular white matter, features not seen in AARS2-L. AARS2-L demonstrates white matter rarefaction which suppresses on fluid-attenuated inversion recovery MRI sequences, a feature not seen in ALSP. CONCLUSIONS: ALSP and AARS2-L share similar clinical, imaging, and pathologic characteristics with key differentiating features that we have highlighted

Does household access to improved water and sanitation in infancy and childhood predict better vocabulary test performance in Ethiopian, Indian, Peruvian and Vietnamese cohort studies?

Abstract Objective Test associations between household water and sanitation (W&S) and children's concurrent and subsequent Peabody Picture Vocabulary Test (PPVT) scores. Design Prospective cohort study. Setting Ethiopia, India, Peru, Vietnam. Participants 7269 children. Primary outcome measures PPVT scores at 5 and 8 years. Key exposure variables were related to W&S, and collected at 1, 5 and 8 years, including ‘improved’ water (eg, piped, public tap or standpipe) and ‘improved’ toilets (eg, collection, storage, treatment and recycling of human excreta). Results Access to improved water at 1 year was associated with higher language scores at 5 years (3/4 unadjusted associations) and 8 years (4/4 unadjusted associations). Ethiopian children with access to improved water at 1 year had test scores that were 0.26 SD (95% CI 0.17 to 0.36) higher at 5 years than children without access. Access to improved water at 5 years was associated with higher concurrent PPVT scores (in 3/4 unadjusted associations), but not later scores (in 1/4 unadjusted associations). 5-year-old Peruvian children with access to improved water had better concurrent performance on the PPVT (0.44 SD, 95% CI 0.30 to 0.59) than children without access to improved water. Toilet access at 1 year was also associated with better PPVT scores at 5 years (3/4 unadjusted associations) and sometimes associated with test results at 8 years (2/4 unadjusted associations). Toilet access at 5 years was associated with concurrent PPVT scores (3/4 unadjusted associations). More than half of all associations in unadjusted models (water and toilets) persisted in adjusted models, particularly for toilets in India, Peru and Vietnam. Conclusions Access to ‘improved’ water and toilets had independent associations with children's PPVT scores that often persisted with adjustment for covariates. Our findings suggest that effects of W&S may go beyond subacute and acute infections and physical growth to include children's language performance, a critical component of cognitive development

Children with access to improved sanitation but not improved water are at lower risk of stunting compared to children without access: a cohort study in Ethiopia, India, Peru, and Vietnam

Background This study’s purpose was to understand associations between water, sanitation, and child growth. Methods We estimated stunting (height-for-age Z score <−2 SD) and thinness (BMI-Z <−2 SD) risk ratios using data from 7,715 Ethiopian, Indian, Peruvian, and Vietnamese children from the Young Lives study. Results In unadjusted models, household access to improved water and toilets was often associated with reduced stunting risk. After adjusting for child, household, parent, and community variables, access to improved water was usually not associated with stunting nor thinness except in Ethiopia where access to improved water was associated with reduced stunting and thinness at 1y and 5y. In contrast, in both unadjusted and adjusted models, stunting at 1y was less common among children with good toilet access than among those without access and this difference persisted when children were 5y and 8y. For example, in adjusted estimates, Vietnamese 5y olds with access to improved toilets had relative stunting risk at 8y 0.62-0.68 that of 5y olds with no access to improved toilets. Water and toilets were rarely associated with thinness. Conclusions Results from our study indicate that access to improved sanitation is more frequently associated with reduced stunting risk than access to improved water. However, additional studies are needed before drawing definitive conclusions about the impact of toilets relative to water. This study is the first to our knowledge to demonstrate the robust and persistent importance of access to improved toilets in infancy, not only during the first year but continuing into childhood. Additional longitudinal investigations are needed to determine concurrent and long-term associations of WASH with stunting and thinness

Differential cross sections and spin density matrix elements for the reaction gamma p -> p omega

High-statistics differential cross sections and spin density matrix elements for the reaction gamma p -> p omega have been measured using the CLAS at Jefferson Lab for center-of-mass (CM) energies from threshold up to 2.84 GeV. Results are reported in 112 10-MeV wide CM energy bins, each subdivided into cos(theta_CM) bins of width 0.1. These are the most precise and extensive omega photoproduction measurements to date. A number of prominent structures are clearly present in the data. Many of these have not previously been observed due to limited statistics in earlier measurements

Practical approach to the diagnosis of adult-onset leukodystrophies: an updated guide in the genomic era

Adult-onset leukodystrophies and genetic leukoencephalopathies comprise a diverse group of neurodegenerative disorders of white matter with a wide age of onset and phenotypic spectrum. Patients with white matter abnormalities detected on MRI often present a diagnostic challenge to both general and specialist neurologists. Patients typically present with a progressive syndrome including various combinations of cognitive impairment, movement disorders, ataxia and upper motor neuron signs. There are a number of important and treatable acquired causes for this imaging and clinical presentation. There are also a very large number of genetic causes which due to their relative rarity and sometimes variable and overlapping presentations can be difficult to diagnose. In this review, we provide a structured approach to the diagnosis of inherited disorders of white matter in adults. We describe clinical and radiological clues to aid diagnosis, and we present an overview of both common and rare genetic white matter disorders. We provide advice on testing for acquired causes, on excluding small vessel disease mimics, and detailed advice on metabolic and genetic testing available to the practising neurologist. Common genetic leukoencephalopathies discussed in detail include CSF1R, AARS2, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and mitochondrial and metabolic disorders

Common Variation in ISL1 Confers Genetic Susceptibility for Human Congenital Heart Disease

Congenital heart disease (CHD) is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1) is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variant–common disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations

Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse

Association of physical exercise and calcium intake with bone mass measured by quantitative ultrasound

<p>Abstract</p> <p>Background</p> <p>Interventions other than medications in the management of osteoporosis are often overlooked. The purpose of this study was to investigate the association of physical activity and calcium intake with bone parameters.</p> <p>Methods</p> <p>We measured the heel T-score and stiffness index (SI) in 1890 pre- and postmenopausal women by quantitative ultrasound (QUS) and assessed physical activity and dietary calcium intake by questionnaire. Participants were divided according to their weekly physical activity (sedentary, moderately active, systematically active) and daily calcium consumption (greater than or less than 800 mg/day).</p> <p>Results</p> <p>SI values were significantly different among premenopausal groups (p = 0.016) and between sedentary and systematically active postmenopausal women (p = 0.039). QUS T-scores in systematically active premenopausal women with daily calcium intake > 800 mg/day were significantly higher than those in all other activity groups (p < 0.05) independent of calcium consumption.</p> <p>Conclusions</p> <p>Systematic physical activity and adequate dietary calcium intake are indicated for women as a means to maximize bone status benefits.</p

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO