Retinal thickness as a potential biomarker in patients with amyloid-proven early- and late-onset Alzheimer's disease

Introduction: Retinal thickness measured with optical coherence tomography has been proposed as a noninvasive biomarker for Alzheimer’s disease (AD). We therefore measured retinal thickness in well-characterized AD and control participants, considering ophthalmological confounders. Methods: We included 57 amyloid-proven AD cases and 85 cognitively normal, amyloid-negative controls. All subjects underwent retinal thickness measurements with spectral domain optical coherence tomography and an ophthalmological assessment to exclude ocular disease. Results: Retinal thickness did not discriminate cases from controls, including stratified analyses for early- versus late-onset AD. We found significant associations between macular thickness and global cortical atrophy [b 20.358; P 5 .01] and parietal cortical atrophy on magnetic resonance imaging [b 20.371; P , .01] in AD cases. Discussion: In this study, representing the largest optical coherence tomography cohort with amyloid-proven AD cases, we show that retinal thickness does not discriminate AD from controls, despite evident changes on clinical, neuroimaging, and CSF measures, querying the use of retinal thickness measurements as an AD biomarke

A cool dust factory in the Crab Nebula: a Herschel study of the filaments

Whether supernovae are major sources of dust in galaxies is a long-standing debate. We present infrared and submillimeter photometry and spectroscopy from the Herschel Space Observatory of the Crab Nebula between 51 and 670 μm as part of the Mass Loss from Evolved StarS program. We compare the emission detected with Herschel with multiwavelength data including millimeter, radio, mid-infrared, and archive optical images. We carefully remove the synchrotron component using the Herschel and Planck fluxes measured in the same epoch. The contribution from line emission is removed using Herschel spectroscopy combined with Infrared Space Observatory archive data. Several forbidden lines of carbon, oxygen, and nitrogen are detected where multiple velocity components are resolved, deduced to be from the nitrogen-depleted, carbon-rich ejecta. No spectral lines are detected in the SPIRE wavebands; in the PACS bands, the line contribution is 5% and 10% at 70 and 100 μm and negligible at 160 μm. After subtracting the synchrotron and line emission, the remaining far-infrared continuum can be fit with two dust components. Assuming standard interstellar silicates, the mass of the cooler component is 0.24+0.32 – 0.08 M ☉ for T = 28.1+5.5 – 3.2 K. Amorphous carbon grains require 0.11 ± 0.01 M ☉ of dust with T = 33.8+2.3 – 1.8 K. A single temperature modified blackbody with 0.14 M ☉ and 0.08 M ☉ for silicate and carbon dust, respectively, provides an adequate fit to the far-infrared region of the spectral energy distribution but is a poor fit at 24-500 μm. The Crab Nebula has condensed most of the relevant refractory elements into dust, suggesting the formation of dust in core-collapse supernova ejecta is efficient

Depression, Anxiety and Glucose Metabolism in the General Dutch Population: The New Hoorn Study

BACKGROUND: There is a well recognized association between depression and diabetes. However, there is little empirical data about the prevalence of depressive symptoms and anxiety among different groups of glucose metabolism in population based samples. The aim of this study was to determine whether the prevalence of increased levels of depression and anxiety is different between patients with type 2 diabetes and subjects with impaired glucose metabolism (IGM) and normal glucose metabolism (NGM). METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional data from a population-based cohort study of 2667 residents, 1261 men and 1406 women aged 40-65 years from the Hoorn region, the Netherlands. Depressive symptoms and anxiety were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D, score >or=16) and the Hospital Anxiety and Depression Scale--Anxiety Subscale (HADS-A, score >or=8), respectively. Glucose metabolism status was determined by oral glucose tolerance test. In the total study population the prevalence of depressive symptoms and anxiety for the NGM, IGM and type 2 diabetes were 12.5, 12.2 and 21.0% (P = 0.004) and 15.0, 15.3 and 19.9% (p = 0.216), respectively. In men, the prevalence of depressive symptoms was 7.7, 9.5 and 19.6% (p<0.001), and in women 16.4, 15.8 and 22.6 (p = 0.318), for participants with NGM, IGM and type 2 diabetes, respectively. Anxiety was not associated with glucose metabolism when stratified for sex. Intergroup differences (NGM vs. IGM and IGM vs. type 2 diabetes) revealed that higher prevalences of depressive symptoms are mainly manifested in participants with type 2 diabetes, and not in participants with IGM. CONCLUSIONS: Depressive symptoms, but not anxiety are associated with glucose metabolism. This association is mainly determined by a higher prevalence of depressive symptoms in participants with type 2 diabetes and not in participants with IGM

Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

Genomic profiling of CHEK2*1100delC-mutated breast carcinomas

Background: CHEK2*1100delC is a moderate-risk breast cancer susceptibility allele with a high prevalence in the Netherlands. We performed copy number and gene expression profiling to investigate whether CHEK2*1100delC breast cancers harbor characteristic genomic aberrations, as seen for BRCA1 mutated breast cancers. Methods: We performed high-resolution SNP array and gene expression profiling of 120 familial breast carcinomas selected from a larger cohort of 155 familial breast tumors, including BRCA1, BRCA2, and CHEK2 mutant tumors. Gene expression analyses based on a mRNA immune signature was used to identify samples with relative low amounts of tumor infiltrating lymphocytes (TILs), which were previously found to disturb tumor copy number and LOH (loss of heterozygosity) profiling. We specifically compared the genomic and gene expression profiles of CHEK2*1100delC breast cancers (n = 14) with BRCAX (familial non-BRCA1/BRCA2/CHEK2*1100delC mutated) breast cancers (n = 34) of the luminal intrinsic subtypes for which both SNP-array and gene expression data is available. Results: High amounts of TILs were found in a relatively small number of luminal breast cancers as compared to breast cancers of the basal-like subtype. As expected, the

Emissions of NO and NH3 from a Typical Vegetable-Land Soil after the Application of Chemical N Fertilizers in the Pearl River Delta

Conceived and designed the experiments: DL. Performed the experiments: DL. Analyzed the data: DL. Contributed reagents/materials/analysis tools: DL. Wrote the paper: DL.Cropland soil is an important source of atmospheric nitric oxide (NO) and ammonia (NH3). Chinese croplands are characterized by intensive management, but limited information is available with regard to NO emissions from croplands in China and NH3 emissions in south China. In this study, a mesocosm experiment was conducted to measure NO and NH3 emissions from a typical vegetable-land soil in the Pearl River Delta following the applications of 150 kg N ha−1 as urea, ammonium nitrate (AN) and ammonium bicarbonate (ABC), respectively. Over the sampling period after fertilization (72 days for NO and 39 days for NH3), mean NO fluxes (± standard error of three replicates) in the control and urea, AN and ABC fertilized mesocosms were 10.9±0.9, 73.1±2.9, 63.9±1.8 and 66.0±4.0 ng N m−2 s−1, respectively; mean NH3 fluxes were 8.9±0.2, 493.6±4.4, 144.8±0.1 and 684.7±8.4 ng N m−2 s−1, respectively. The fertilizer-induced NO emission factors for urea, AN and ABC were 2.6±0.1%, 2.2±0.1% and 2.3±0.2%, respectively. The fertilizer-induced NH3 emission factors for the three fertilizers were 10.9±0.2%, 3.1±0.1% and 15.2±0.4%, respectively. From the perspective of air quality protection, it would be better to increase the proportion of AN application due to its lower emission factors for both NO and NH3.Yeshttp://www.plosone.org/static/editorial#pee

The regional and global significance of nitrogen removal in lakes and reservoirs

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Biogeochemistry 93 (2009): 143-157, doi:10.1007/s10533-008-9272-x.Human activities have greatly increased the transport of biologically available N through watersheds to potentially sensitive coastal ecosystems. Lentic water bodies (lakes and reservoirs) have the potential to act as important sinks for this reactive N as it is transported across the landscape because they offer ideal conditions for N burial in sediments or permanent loss via denitrification. However, the patterns and controls on lentic N removal have not been explored in great detail at large regional to global scales. In this paper we describe, evaluate, and apply a new, spatially explicit, annual-scale, global model of lentic N removal called NiRReLa (Nitrogen Retention in Reservoirs and Lakes). The NiRReLa model incorporates small lakes and reservoirs than have been included in previous global analyses, and also allows for separate treatment and analysis of reservoirs and natural lakes. Model runs for the mid-1990s indicate that lentic systems are indeed important sinks for N and are conservatively estimated to remove 19.7 Tg N yr-1 from watersheds globally. Small lakes (< 50 km2) were critical in the analysis, retaining almost half (9.3 Tg N yr-1) of the global total. In model runs, capacity of lakes and reservoirs to remove watershed N varied substantially (0-100%) both as a function of climate and the density of lentic systems. Although reservoirs occupy just 6% of the global lentic surface area, we estimate they retain approximately 33% of the total N removed by lentic systems, due to a combination of higher drainage ratios (catchment surface area : lake or reservoir surface area), higher apparent settling velocities for N, and greater N loading rates in reservoirs than in lakes. Finally, a sensitivity analysis of NiRReLa suggests that, on-average, N removal within lentic systems will respond more strongly to changes in land use and N loading than to changes in climate at the global scale.The NSF26 Research Coordination Network on denitrification for support for collaboration (award number DEB0443439 to S.P. Seitzinger and E.A. Davidson). This project was also supported by grants to J.A. Harrison from California Sea Grant (award number RSF8) and from the U.S. Geological Survey 104b program and R. Maranger (FQRNT Strategic Professor)

Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study

Background Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. Methods In this modelling study, we included people with mild cognitive impairment (MCI) from single-centre and multicentre cohorts in Europe and North America: the European Medical Information Framework for Alzheimer's Disease (EMIF-AD; n=883), Alzheimer's Disease Neuroimaging Initiative (ADNI; n=829), Amsterdam Dementia Cohort (ADC; n=666), and the Swedish BioFINDER study (n=233). Inclusion criteria were a baseline diagnosis of MCI, at least 6 months of follow-up, and availability of a baseline Mini-Mental State Examination (MMSE) and MRI or CSF biomarker assessment. The primary endpoint was clinical progression to any type of dementia. We evaluated performance of previously developed risk prediction models—a demographics model, a hippocampal volume model, and a CSF biomarkers model—by evaluating them across cohorts, incorporating different biomarker measurement methods, and determining prognostic performance with Harrell's C statistic. We then updated the models by re-estimating parameters with and without centre-specific effects and evaluated model calibration by comparing observed and expected survival. Finally, we constructed a model combining markers for amyloid deposition, tauopathy, and neurodegeneration (ATN), in accordance with the National Institute on Aging and Alzheimer's Association research framework. Findings We included all 2611 individuals with MCI in the four cohorts, 1007 (39%) of whom progressed to dementia. The validated demographics model (Harrell's C 0·62, 95% CI 0·59–0·65), validated hippocampal volume model (0·67, 0·62–0·72), and updated CSF biomarkers model (0·72, 0·68–0·74) had adequate prognostic performance across cohorts and were well calibrated. The newly constructed ATN model had the highest performance (0·74, 0·71–0·76). Interpretation We generated risk models that are robust across cohorts, which adds to their potential clinical applicability. The models could aid clinicians in the interpretation of CSF biomarker and hippocampal volume results in individuals with MCI, and help research and clinical settings to prepare for a future of precision medicine in Alzheimer's disease. Future research should focus on the clinical utility of the models, particularly if their use affects participants' understanding, emotional wellbeing, and behaviour

Stream denitrification across biomes and its response to anthropogenic nitrate loading

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 452 (2008): 202-205, doi:10.1038/nature06686.Worldwide, anthropogenic addition of bioavailable nitrogen (N) to the biosphere is increasing and terrestrial ecosystems are becoming increasingly N saturated, causing more bioavailable N to enter groundwater and surface waters. Large-scale N budgets show that an average of about 20-25% of the N added to the biosphere is exported from rivers to the ocean or inland basins, indicating substantial sinks for N must exist in the landscape. Streams and rivers may be important sinks for bioavailable N owing to their hydrologic connections with terrestrial systems, high rates of biological activity, and streambed sediment environments that favor microbial denitrification. Here, using data from 15N tracer experiments replicated across 72 streams and 8 regions representing several biomes, we show that total biotic uptake and denitrification of nitrate increase with stream nitrate concentration, but that the efficiency of biotic uptake and denitrification declines as concentration increases, reducing the proportion of instream nitrate that is removed from transport. Total uptake of nitrate was related to ecosystem photosynthesis and denitrification was related to ecosystem respiration. Additionally, we use a stream network model to demonstrate that excess nitrate in streams elicits a disproportionate increase in the fraction of nitrate that is exported to receiving waters and reduces the relative role of small versus large streams as nitrate sinks.Funding for this research was provided by the National Science Foundation

Win-stay, lose-switch and public information strategies for patch fidelity of songbirds with rare extra-pair paternity

Determining where organisms breed and understanding why they breed in particular locations are fundamental biological questions with conservation implications. Breeding-site fidelity is common in migratory, territorial songbirds and is typically thought to occur following reproductive success with a social mate and success of nearby conspecifics. It is currently unknown if frequency of extra-pair paternity in a population influences use of information about reproductive success of nearby conspecifics for site fidelity decisions. We investigated patch fidelity of white-eyed vireos (Vireo griseus) based on reproductive success and quantified frequency of extra-pair paternity. We found support only for females making patch fidelity decisions following reproductive success with a social mate. Patch fidelity of males was not associated with reproductive success of nearby conspecifics, suggesting males may not use this information when extra-pair paternity is infrequent or the association is non-existent in this species