FDG-PET assessment of the locus coeruleus in Alzheimer’s disease

Sensitive and reliable in vivo imaging of the locus coeruleus (LC) is important to develop and evaluate its potential as a biomarker in neurodegenerative diseases such as Alzheimer’s disease (AD). It is not known whether AD-related alterations in LC integrity can be detected using 18F-labelled fluoro-2-deoxyglucose (FDG) positron emission tomography (PET). Mean FDG-PET images from AD patients (N ​= ​193) and controls (N ​= ​256) from the ADNI database were co-registered to a study-wise anatomical template. Regional LC median standardized uptake value ratio (SUVR) values were obtained using four previously published LC masks and normalized to values from pons and cerebellar vermis reference regions. To support the validity of our methods, other regions previously reported to be most and least affected metabolically in AD were also compared to controls. The LC did not show between-group differences in FDG-PET signal, whereas the mammillary bodies did, despite these regions having comparable volumes and SUVR ranges. Brain regions previously reported to be most and least affected metabolically in AD compared to controls showed medium-to-large and small effect sizes for SUVR differences respectively. The results do not support the current application of LC FDG-PET signal as an in vivo biomarker for AD. Methodological and demographic factors potentially contributing to these findings are discussed. Future research may investigate age-related differences in LC FDG-PET signal and higher resolution images to fully explore its biomarker potential

Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies.

PURPOSE: Mapping brain hypoxia is a major goal for stroke diagnosis, pathophysiology and treatment monitoring. 18F-fluoro-misonidazole (FMISO) positron emission tomography (PET) is the gold standard hypoxia imaging method. Normobaric hyperoxia (NBO) is a promising therapy in acute stroke. In this pilot study, we tested the straightforward hypothesis that NBO would markedly reduce FMISO uptake in ischemic brain in Wistar and spontaneously hypertensive rats (SHRs), two rat strains with distinct vulnerability to brain ischemia, mimicking clinical heterogeneity. METHODS: Thirteen adult male rats were randomized to distal middle cerebral artery occlusion under either 30% O2 or 100% O2. FMISO was administered intravenously and PET data acquired dynamically for 3hrs, after which magnetic resonance imaging (MRI) and tetrazolium chloride (TTC) staining were carried out to map the ischemic lesion. Both FMISO tissue uptake at 2-3hrs and FMISO kinetic rate constants, determined based on previously published kinetic modelling, were obtained for the hypoxic area. In a separate group (n = 9), tissue oxygen partial pressure (PtO2) was measured in the ischemic tissue during both control and NBO conditions. RESULTS: As expected, the FMISO PET, MRI and TTC lesion volumes were much larger in SHRs than Wistar rats in both the control and NBO conditions. NBO did not appear to substantially reduce FMISO lesion size, nor affect the FMISO kinetic rate constants in either strain. Likewise, MRI and TTC lesion volumes were unaffected. The parallel study showed the expected increases in ischemic cortex PtO2 under NBO, although these were small in some SHRs with very low baseline PtO2. CONCLUSIONS: Despite small samples, the apparent lack of marked effects of NBO on FMISO uptake suggests that in permanent ischemia the cellular mechanisms underlying FMISO trapping in hypoxic cells may be disjointed from PtO2. Better understanding of FMISO trapping processes will be important for future applications of FMISO imaging

Two-dimensional arrays self-assembled via interference of concentration modulation waves in drying solutions

Self-assembling of patterned nanostructures in solution-processed thin films with multiphase block-copolymers is possible. Generation of small and well-defined regular structures directly from single-phase polymer films is challenging. Here, 2-dimensional (2D) patterned array in single-phase polymers was self-assembled by a solution process. One-dimensional spinodal precipitation with a characteristic wavelength was created along a pinned contact line of the drying solution to form a one-dimensional periodic structure (1DPS) via geometry and concentration confinements. The latter was uncovered from the liquid by sequential depinning and repinning of the contact line. A new 1DPS with an inherited phase re-emerged and triggered depinning and repinning. The process was self-repeated and a 2D array formed with a tuneable lattice type and parameters, which was governed by the interference of two concentration-modulated waves.EPSRC Centre for Innovative Manufacturing in Ultra Precision (EP/I033491/1)

Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study protocol: a deep phenotyping cohort study of the role of brain inflammation in dementia, depression and other neurological illnesses

$\textit{Introduction}$ Inflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such neuroinflammation relates to other aspects of neuropathology (e.g., tau and amyloid pathology) as well as to structural and functional changes in the brain and symptoms (as assessed via MRI and clinical and neuropsychological assessment). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows $\textit{in vivo}$ imaging of inflammation, amyloid and tau deposition, together with neuropsychological profiling, magnetic resonance imaging (MRI) and peripheral biomarker analysis. \textit{Methods & analysis} Using PET imaging of the ligand [11C]PK11195 we will test for increased neuroinflammation $\textit{in vivo}$ in patients with Alzheimer’s disease, Lewy body dementia, frontotemporal dementia, progressive supranuclear palsy, late onset depression and mild cognitive impairment, when compared to healthy controls. We will assess whether areas of inflammatory change are associated with amyloid and tau deposition (assessed using $^{11}$C-labelled Pittsburgh Compound B ([$^{11}$C]PiB) and $^{18}$F-labelled AV-1451 respectively), as well as structural and functional connectivity changes found on MRI. Inflammatory biomarker analysis and immune-phenotyping of peripheral blood monocytes will determine the correlation between central (i.e., neural) and peripheral inflammation. Finally, we will examine whether neuroinflammatory changes seen on PET imaging are associated with global and domain specific cognitive impairments, or predict cognitive decline over 12 months. \textit{Ethics & dissemination} The study protocol was approved by the local ethics committee, East of England - Cambridge Central Research Ethics Committee (reference: 13/EE/0104). The study is also ARSAC approved as part of this process. Data will be disseminated by presentation at national and international conferences and by publication, predominantly in journals of neuroscience as well as clinical neurology and psychiatry. $\textit{Strengths}$ Multimodal deep phenotyping Comparisons between diseases as well as with controls Longitudinal neuropsychology data Comparison of central and peripheral inflammation $\textit{Weaknesses}$ Lack of longitudinal neuroimaging Not a prospective study, unable to assess causationThe study is funded by the UK National Institute of Health Research Cambridge Biomedical Research Unit in Dementia (Project 4 - RNAG/293). JBR is supported by the Wellcome Trust (103838). JPC is supported by the UK National Institute of Health Research Biomedical Research Centre at Cambridge. PVR is supported by the PSP Association

Fabrication of one-dimensional Ag/multiwalled carbon nanotube nano-composite

Composite made of multiwalled carbon nanotubes coated with silver was fabricated by an electroless deposition process. The thickness of silver layer is about 40 to 60 nm, characterized as nano-crystalline with (111) crystal orientation along the nanotube's axial direction. The characterization of silver/carbon nanotube [Ag/CNT] nanowire has shown the large current carrying capability, and the electric conductivity is similar to the pure silver nanowires that Ag/CNT would be promising as building blocks for integrated circuits

An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

The Down syndrome brain in the presence and absence of fibrillar β-amyloidosis

People with Down syndrome (DS) have a neurodevelopmentally distinct brain and invariably developed amyloid neuropathology by age 50. This cross-sectional study aimed to provide a detailed account of DS brain morphology and the changes occuring with amyloid neuropathology. Forty-six adults with DS underwent structural and amyloid imaging-the latter using Pittsburgh compound B (PIB) to stratify the cohort into PIB-positive (n = 19) and PIB-negative (n = 27). Age-matched controls (n = 30) underwent structural imaging. Group differences in deep gray matter volumetry and cortical thickness were studied. PIB-negative people with DS have neurodevelopmentally atypical brain, characterized by disproportionately thicker frontal and occipitoparietal cortex and thinner motor cortex and temporal pole with larger putamina and smaller hippocampi than controls. In the presence of amyloid neuropathology, the DS brains demonstrated a strikingly similar pattern of posterior dominant cortical thinning and subcortical atrophy in the hippocampus, thalamus, and striatum, to that observed in non-DS Alzheimer's disease. Care must be taken to avoid underestimating amyloid-associated morphologic changes in DS due to disproportionate size of some subcortical structures and thickness of the cortex.This work was supported by the Medical Research Council (grant number: 98480 ). Additional support was received from the NIHR Cambridge Biomedical Research Centre, the NIHR Collaborations in Leadership for Applied Health Research and Care (CLAHRC) for the East of England, the NIHR Cambridge Dementia Biomedical Research Unit, the Down Syndrome Association and the Health Foundation

SCUBA-2 Ultra Deep Imaging EAO Survey (STUDIES). IV. Spatial Clustering and Halo Masses of Submillimeter Galaxies

We analyze an extremely deep 450 μm image (1σ = 0.56 mJy beam−1) of a sime300 arcmin2 area in the CANDELS/COSMOS field as part of the Sub-millimeter Common User Bolometric Array-2 Ultra Deep Imaging EAO Survey. We select a robust (signal-to-noise ratio ≥4) and flux-limited (≥4 mJy) sample of 164 submillimeter galaxies (SMGs) at 450 μm that have K-band counterparts in the COSMOS2015 catalog identified from radio or mid-infrared imaging. Utilizing this SMG sample and the 4705 K-band-selected non-SMGs that reside within the noise level ≤1 mJy beam−1 region of the 450 μm image as a training set, we develop a machine-learning classifier using K-band magnitude and color–color pairs based on the 13-band photometry available in this field. We apply the trained machine-learning classifier to the wider COSMOS field (1.6 deg2) using the same COSMOS2015 catalog and identify a sample of 6182 SMG candidates with similar colors. The number density, radio and/or mid-infrared detection rates, redshift and stellar-mass distributions, and the stacked 450 μm fluxes of these SMG candidates, from the S2COSMOS observations of the wide field, agree with the measurements made in the much smaller CANDELS field, supporting the effectiveness of the classifier. Using this SMG candidate sample, we measure the two-point autocorrelation functions from z = 3 down to z = 0.5. We find that the SMG candidates reside in halos with masses of sime(2.0 ± 0.5) × 1013 h −1 M ☉ across this redshift range. We do not find evidence of downsizing that has been suggested by other recent observational studies