Alzheimer's Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not Correlate with CSF Volumes or CSF Production Rate.

Background: Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively.

Objective: To examine the outstanding question if CSF concentrations of AD associated biomarkers are influenced by variations in CSF volumes, CSF production rate, and intracranial pressure in healthy individuals.

Pulmonary Extracellular Vesicles as Mediators of Local and Systemic Inflammation.

Cells of the airways are constantly exposed to environmental hazards including cigarette smoke, irritants, pathogens, and mechanical insults. Maintaining barrier integrity is vital, and mounting responses to threats depends on intercellular communication. Extracellular vesicles (EVs), including exosomes and microvesicles, are major signal mediators between cells, shuttling cargo in health and disease.

A Bayesian heteroscedastic GLM with application to fMRI data with motion spikes.

We propose a voxel-wise general linear model with autoregressive noise and heteroscedastic noise innovations (GLMH) for analyzing functional magnetic resonance imaging (fMRI) data. The model is analyzed from a Bayesian perspective and has the benefit of automatically down-weighting time points close to motion spikes in a data-driven manner. We develop a highly efficient Markov Chain Monte Carlo (MCMC) algorithm that allows for Bayesian variable selection among the regressors to model both the mean (i.

SNP Variants in Major Histocompatibility Complex Are Associated with Sarcoidosis Susceptibility-A Joint Analysis in Four European Populations.

Sarcoidosis is a multiorgan inflammatory disorder with heritability estimates up to 66%. Previous studies have shown the major histocompatibility complex (MHC) region to be associated with sarcoidosis, suggesting a functional role for antigen-presenting molecules and immune mediators in the disease pathogenesis. To detect variants predisposing to sarcoidosis and to identify genetic differences between patient subgroups, we studied four genes in the MHC Class III region () and with tag-SNPs and their relation to alleles.

MuPeXI: prediction of neo-epitopes from tumor sequencing data.

Personalization of immunotherapies such as cancer vaccines and adoptive T cell therapy depends on identification of patient-specific neo-epitopes that can be specifically targeted. MuPeXI, the mutant peptide extractor and informer, is a program to identify tumor-specific peptides and assess their potential to be neo-epitopes. The program input is a file with somatic mutation calls, a list of HLA types, and optionally a gene expression profile.

Poor construction, not time, takes its toll on subsidised fences designed to deter large carnivores.

Large carnivore conservation may be considered as successful in Sweden, as wolf (Canis lupus), lynx (Lynx lynx), brown bear (Ursus arctos), golden eagles (Aquila chrysaetos), and wolverine (Gulo gulo) populations have recovered from extinction or near extinction to viable populations during the last three decades. Particularly the wolf and lynx populations have returned at the cost of an increasing number of carnivore attacks on domestic livestock. To support coexistence between carnivores and livestock production, the Swedish authorities subsidise interventions to prevent or reduce the number of carnivore attacks.

BIDS apps: Improving ease of use, accessibility, and reproducibility of neuroimaging data analysis methods.

The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package.

A defense of using resting-state fMRI as null data for estimating false positive rates.

A recent Editorial in Cognitive Neuroscience reconsiders the findings of our work on the accuracy of false positive rate control with cluster inference in functional magnetic resonance imaging (fMRI), in particular criticizing our use of resting-state fMRI as a source for null data in the evaluation of task fMRI methods. We defend this use of resting fMRI data, as while there is much structure in this data, we argue it is representative of task data noise and task analysis software should be able to accommodate this noise. We also discuss a potential problem with Slotnick's own method.

Order of magnitude improvement of nano-contact spin torque nano-oscillator performance.

Spin torque nano-oscillators (STNO) represent a unique class of nano-scale microwave signal generators and offer a combination of intriguing properties, such as nano sized footprint, ultrafast modulation rates, and highly tunable microwave frequencies from 100 MHz to close to 100 GHz. However, their low output power and relatively high threshold current still limit their applicability and must be improved. In this study, we investigate the influence of the bottom Cu electrode thickness (t) in nano-contact STNOs based on Co/Cu/NiFe GMR stacks and with nano-contact diameters ranging from 60 to 500 nm.

Intracranial and Intraocular Pressure During Various Degrees of Head-Down Tilt.

Background: More than half of astronauts develop ophthalmic changes during long-duration spaceflight consistent with an abnormal intraocular and intracranial pressure (IOP, ICP) difference. The aim of our study was to assess IOP and ICP during head-down tilt (HDT) and the additive or attenuating effects of 1% CO2 and lower body negative pressure (LBNP).

Methods: In Experiment I, IOP and ICP were measured in nine healthy subjects after 3.

Prey Selection of Scandinavian Wolves: Single Large or Several Small?

Research on large predator-prey interactions are often limited to the predators' primary prey, with the potential for prey switching in systems with multiple ungulate species rarely investigated. We evaluated wolf (Canis lupus) prey selection at two different spatial scales, i.e.

Fast Bayesian whole-brain fMRI analysis with spatial 3D priors.

Spatial whole-brain Bayesian modeling of task-related functional magnetic resonance imaging (fMRI) is a great computational challenge. Most of the currently proposed methods therefore do inference in subregions of the brain separately or do approximate inference without comparison to the true posterior distribution. A popular such method, which is now the standard method for Bayesian single subject analysis in the SPM software, is introduced in Penny et al.

A Stereotactic Probabilistic Atlas for the Major Cerebral Arteries.

Improved whole brain angiographic and velocity-sensitive MRI is pushing the boundaries of noninvasively obtained cerebral vascular flow information. The complexity of the information contained in such datasets calls for automated algorithms and pipelines, thus reducing the need of manual analyses by trained radiologists. The objective of this work was to lay the foundation for such automated pipelining by constructing and evaluating a probabilistic atlas describing the shape and location of the major cerebral arteries.

The lung microbiota in early rheumatoid arthritis and autoimmunity.

Background: Airway abnormalities and lung tissue citrullination are found in both rheumatoid arthritis (RA) patients and individuals at-risk for disease development. This suggests the possibility that the lung could be a site of autoimmunity generation in RA, perhaps in response to microbiota changes. We therefore sought to test whether the RA lung microbiome contains distinct taxonomic features associated with local and/or systemic autoimmunity.

Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function.

Smoking influences the immune system in different ways and, hypothetically, effects on pulmonary effector and regulatory T cells emerge as potentially detrimental. Therefore, we characterized the frequencies and characteristics of CD4+ and CD8+ T cell subsets in the blood and lungs of young tobacco smokers. Bronchoalveolar lavage (BAL) and peripheral blood were obtained from healthy moderate smokers (n = 18; 2-24 pack-years) and never-smokers (n = 15), all with normal lung function.

Distortion Product Otoacoustic Emissions and Intracranial Pressure During CSF Infusion Testing.

Background: A noninvasive method to monitor changes in intracranial pressure (ICP) is required for astronauts on long-duration spaceflight who are at risk of developing the Visual Impairment/Intracranial Pressure syndrome that has some, but not all of the features of idiopathic intracranial hypertension. We assessed the validity of distortion product otoacoustic emissions (DPOAEs) to detect changes in ICP.

Methods: Subjects were eight patients undergoing medically necessary diagnostic cerebrospinal fluid (CSF) infusion testing for hydrocephalus.

Pulmonary sarcoidosis is associated with exosomal vitamin D-binding protein and inflammatory molecules.

Background: Sarcoidosis is an inflammatory granulomatous disorder characterized by accumulation of T1-type CD4 T cells and immune effector cells within affected organs, most frequently the lungs. Exosomes are extracellular vesicles conveying intercellular communication with possible diagnostic and therapeutic applications.

Objectives: We aimed to provide an understanding of the proinflammatory role of bronchoalveolar lavage fluid (BALF) exosomes in patients with sarcoidosis and to find candidates for disease biomarkers.

Sarcoidosis incidence and prevalence: a nationwide register-based assessment in Sweden.

Our objective was to estimate the contemporary incidence and prevalence of sarcoidosis using Swedish population-based register data.Adults with any sarcoidosis-coded visit were identified from the National Patient Register (hospitalisations 1964-2013 and outpatient care 2001-2013). Demographic and medication dispensing data were retrieved from national registers.

Approach for Identifying Human Leukocyte Antigen (HLA)-DR Bound Peptides from Scarce Clinical Samples.

Immune-mediated diseases strongly associating with human leukocyte antigen (HLA) alleles are likely linked to specific antigens. These antigens are presented to T cells in the form of peptides bound to HLA molecules on antigen presenting cells, e.g.

Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus.

Objectives: Increased aqueduct cerebrospinal fluid (CSF) flow pulsatility and, recently, a reversed CSF flow in the aqueduct have been suggested as hallmarks of idiopathic normal pressure hydrocephalus (INPH). However, these findings have not been adequately confirmed. Our objective was to investigate the flow of blood and CSF in INPH, as compared to healthy elderly, in order to clarify which flow parameters are related to the INPH pathophysiology.

Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates.

The most widely used task functional magnetic resonance imaging (fMRI) analyses use parametric statistical methods that depend on a variety of assumptions. In this work, we use real resting-state data and a total of 3 million random task group analyses to compute empirical familywise error rates for the fMRI software packages SPM, FSL, and AFNI, as well as a nonparametric permutation method. For a nominal familywise error rate of 5%, the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference.

The pressure difference between eye and brain changes with posture.

Objective: The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in astronauts exposed to microgravity. The aim of this study was to determine the postural influence on the difference between simultaneously measured ICP and IOP.

Methods: Eleven healthy adult volunteers (age = 46 ± 10 years) were investigated with simultaneous ICP, assessed through lumbar puncture, and IOP measurements when supine, sitting, and in 9° head-down tilt (HDT).