The study of atmospheric ice-nucleating particles via microfluidically generated droplets

Ice-nucleating particles (INPs) play a significant role in the climate and hydrological cycle by triggering ice formation in supercooled clouds, thereby causing precipitation and affecting cloud lifetimes and their radiative properties. However, despite their importance, INP often comprise only 1 in 10³–10⁶ ambient particles, making it difficult to ascertain and predict their type, source, and concentration. The typical techniques for quantifying INP concentrations tend to be highly labour-intensive, suffer from poor time resolution, or are limited in sensitivity to low concentrations. Here, we present the application of microfluidic devices to the study of atmospheric INPs via the simple and rapid production of monodisperse droplets and their subsequent freezing on a cold stage. This device offers the potential for the testing of INP concentrations in aqueous samples with high sensitivity and high counting statistics. Various INPs were tested for validation of the platform, including mineral dust and biological species, with results compared to literature values. We also describe a methodology for sampling atmospheric aerosol in a manner that minimises sampling biases and which is compatible with the microfluidic device. We present results for INP concentrations in air sampled during two field campaigns: (1) from a rural location in the UK and (2) during the UK’s annual Bonfire Night festival. These initial results will provide a route for deployment of the microfluidic platform for the study and quantification of INPs in upcoming field campaigns around the globe, while providing a benchmark for future lab-on-a-chip-based INP studies

SSBC 2018: Sclera segmentation benchmarking competition

© 2018 IEEE. This paper summarises the results of the Sclera Segmentation Benchmarking Competition (SSBC 2018). It was organised in the context of the 11th IAPR International Conference on Biometrics (ICB 2018). The aim of this competition was to record the developments on sclera segmentation in the cross-sensor environment (sclera trait captured using multiple acquiring sensors). Additionally, the competition also aimed to gain the attention of researchers on this subject of research. For the purpose of benchmarking, we have developed two datasets of sclera images captured using different sensors. The first dataset was collected using a DSLR camera and the second one was collected using a mobile phone camera. The first dataset is the Multi-Angle Sclera Dataset (MASD version 1), which was used in the context of the previous versions of sclera segmentation competitions. The images in the second dataset were captured using.a mobile phone rear camera of 8-megapixel. As baseline manual segmentation mask of the sclera images from both the datasets were developed. Precision and recall-based statistical measures were employed to evaluate the effectiveness of the submitted segmentation technique and to rank them. Six algorithms were submitted towards the segmentation task. This paper analyses the results produced by these algorithms/system and defines a way forward for this subject of research. Both the datasets along with some of the accompanying ground truth/baseline mask will be freely available for research purposes upon request to authors by email

Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration

Background: It is still unknown if serum glial fibrillary acidic protein (GFAP) is a useful marker in frontotemporal lobar degeneration (FTLD). Objective: To assess the diagnostic and prognostic value of serum GFAP in a large cohort of patients with FTLD. Methods: In this retrospective study, performed on 406 participants, we measured serum GFAP concentration with an ultrasensitive Single molecule array (Simoa) method in patients with FTLD, Alzheimer's disease (AD), and in cognitively unimpaired elderly controls. We assessed the role of GFAP as marker of disease severity by analyzing the correlation with clinical variables, neurophysiological data, and cross-sectional brain imaging. Moreover, we evaluated the role of serum GFAP as a prognostic marker of disease survival. Results: We observed significantly higher levels of serum GFAP in patients with FTLD syndromes, except progressive supranuclear palsy, compared with healthy controls, but not compared with AD patients. In FTLD, serum GFAP levels correlated with measures of cognitive dysfunction and disease severity, and were associated with indirect measures of GABAergic deficit. Serum GFAP concentration was not a significant predictor of survival. Conclusion: Serum GFAP is increased in FTLD, correlates with cognition and GABAergic deficits, and thus shows promise as a biomarker of disease severity in FTLD

Plasma p-tau181 accurately predicts Alzheimer's disease pathology at least 8 years prior to post-mortem and improves the clinical characterisation of cognitive decline

The neuropathological confirmation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles (NFT) remains the gold standard for a definitive diagnosis of Alzheimer's disease (AD). Nowadays, the in vivo diagnosis of AD is greatly aided by both cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Although highly accurate, their broad implementation is restricted by high cost, limited accessibility and invasiveness. We recently developed a high-performance, ultrasensitive immunoassay for the quantification of tau phosphorylated at threonine-181 (p-tau181) in plasma, which identifies AD pathophysiology with high accuracy. However, it remains unclear whether plasma p-tau181, measured years before the death, can predict the eventual neuropathological confirmation of AD, and successfully discriminates AD from non-AD dementia pathologies. We studied a unique cohort of 115 individuals with longitudinal blood collections with clinical evaluation at 8, 4 and 2 years prior to neuropathological assessment at death. The results demonstrate that plasma p-tau181 associates better with AD neuropathology and Braak staging than a clinical diagnosis 8 years before post-mortem. Moreover, while all patients had a diagnosis of AD dementia during life, plasma p-tau181 proved to discriminate AD from non-AD pathologies with high accuracy (AUC = 97.4%, 95% CI = 94.1-100%) even 8 years before death. Additionally, the longitudinal trajectory of plasma p-tau181 was assessed in all patients. We found that the main increases in plasma p-tau181 occurred between 8 and 4 years prior to death in patients with AD neuropathology and later plateauing. In contrast, non-AD pathologies and controls exhibited minor, albeit significant, increases in p-tau181 up until death. Overall, our study demonstrates that plasma p-tau181 is highly predictive and specific of AD neuropathology years before post-mortem examination. These data add further support for the use of plasma p-tau181 to aid clinical management in primary care and recruitment for clinical trials.Open access funding provided by University of Gothenburg. This study represents independent research partly funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. Tissue samples were supplied by The London Neurodegenerative Diseases Brain Bank, which receives funding from the UK Medical Research Council and as part of the Brains for Dementia Research programme, jointly funded by Alzheimer’s Research UK and the Alzheimer’s Society. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. TKK holds a postdoctoral fellowship from the BrightFocus Foundation (#A2020812F), and was further supported by the Swedish Alzheimer Foundation (Alzheimerfonden; #AF-930627), the Swedish Brain Foundation (Hjärnfonden; #FO2020-0240), the Swedish Dementia Foundation (Demensförbundet), the Agneta Prytz-Folkes and Gösta Folkes Foundation, Gamla Tjänarinnor, the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, the Gun and Bertil Stohnes Foundation, and the Anna Lisa and Brother Björnsson’s Foundation. MSC received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie action grant agreement no. 752310, and currently receives funding from Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva Programme grant IJC2018-037478-I). AH is funded by Research Centre for Mental Health and Biomedical Research Unit for Dementia. KB holds the Torsten Söderberg Professorship in Medicine and is supported by grants from the Swedish Research Council, the Swedish Alzheimer Foundation, and the Swedish Brain Foundation. AH is funded by Research Centre for Mental Health and Biomedical Research Unit for Dementia. KB holds the Torsten Söderberg Professorship in Medicine and is supported by grants from the Swedish Research Council, the Swedish Alzheimer Foundation, and the Swedish Brain Foundation. KB holds the Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences, and is supported by the Swedish Research Council (#2017-00915), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), and a grant (#ALFGBG-715986) from the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement. NJA is supported by the Wallenberg Centre for Molecular and Translational Medicine, the Swedish Alzheimer Foundation (Alzheimerfonden), the Swedish Dementia Foundation (Demensförbundet), and Hjärnfonden, Sweden

Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study

Item does not contain fulltextDecreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program - Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given