The serum opsonin L-ficolin is detected in lungs of human transplant recipients following fungal infections and modulates inflammation and killing of Aspergillus fumigatus.

BACKGROUND: Invasive aspergillosis (IA) is a life-threatening systemic fungal infection in immunocompromised individuals that is caused by Aspergillus fumigatus. The human serum opsonin, L-ficolin, has been observed to recognize A. fumigatus and could participate in fungal defense. METHODS: Using lung epithelial cells, primary human monocyte-derived macrophages (MDMs), and neutrophils from healthy donors, we assessed phagocytosis and killing of L-ficolin-opsonized live A. fumigatus conidia by flow cytometry and microscopy. Additionally, cytokines were measured by cytometric bead array, and L-ficolin was measured in bronchoalveolar lavage (BAL) fluid from lung transplant recipients by enzyme-linked immunosorbent assay. RESULTS: L-ficolin opsonization increased conidial uptake and enhanced killing of A. fumigatus by MDMs and neutrophils. Opsonization was also shown to manifest an increase in interleukin 8 release from A549 lung epithelial cells but decreased interleukin 1β, interleukin 6, interleukin 8, interleukin 10, and tumor necrosis factor α release from MDMs and neutrophils 24 hours after infection. The concentration of L-ficolin in BAL fluid from patients with fungal infection was significantly higher than that for control subjects (P = .00087), and receiving operating characteristic curve analysis highlighted the diagnostic potential of L-ficolin for lung infection (area under the curve, 0.842; P < .0001). CONCLUSIONS: L-ficolin modulates the immune response to A. fumigatus. Additionally, for the first time, L-ficolin has been demonstrated to be present in human lungs

Clustering of tau-immunoreactive pathology in chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder which may result from repetitive brain injury. A variety of tau-immunoreactive pathologies are present, including neurofibrillary tangles (NFT), neuropil threads (NT), dot-like grains (DLG), astrocytic tangles (AT), and occasional neuritic plaques (NP). In tauopathies, cellular inclusions in the cortex are clustered within specific laminae, the clusters being regularly distributed parallel to the pia mater. To determine whether a similar spatial pattern is present in CTE, clustering of the tau-immunoreactive pathology was studied in the cortex, hippocampus, and dentate gyrus in 11 cases of CTE and 7 cases of Alzheimer’s disease neuropathologic change (ADNC) without CTE. In CTE: (1) all aspects of tau-immunoreactive pathology were clustered and the clusters were frequently regularly distributed parallel to the tissue boundary, (2) clustering was similar in two CTE cases with minimal co-pathology compared with cases with associated ADNC or TDP-43 proteinopathy, (3) in a proportion of cortical gyri, estimated cluster size was similar to that of cell columns of the cortico-cortical pathways, and (4) clusters of the tau-immunoreactive pathology were infrequently spatially correlated with blood vessels. The NFT and NP in ADNC without CTE were less frequently randomly or uniformly distributed and more frequently in defined clusters than in CTE. Hence, the spatial pattern of the tau-immunoreactive pathology observed in CTE is typical of the tauopathies but with some distinct differences compared to ADNC alone. The spread of pathogenic tau along anatomical pathways could be a factor in the pathogenesis of the disease

Effect of helium ion irradiation on pure W, W-5Ta and W-5Re: a micro-tensile and nanoindentation investigation of mechanical properties

Micro-tensile testing has been used to study the response of pure tungsten and two tungsten alloys to helium ion irradiation. Commercially supplied plates of W, W-5Ta and W-5Re were irradiated using 6 MeV helium ions at room temperature. The ion energy was attenuated with an energy spreading device such that a uniform level of damage at 0.6 dpa (and 11,000 appm He) was deposited at the 3–9 µm depth. Focused ion beam milling was used to fabricate dog-bone shaped, micro-tensile samples 5 × 5 µm in cross-sectional area and 17 µm in length from the unirradiated and irradiated samples. All micro-tensile samples were tested at a quasi-static strain rate and the stress–strain curves were analysed to determine the mechanical properties. A close correlation was found between micro-tensile results and the bulk mechanical properties reported in the literature. Comparison between the unirradiated micro-tensile properties of W-5Re and W-5Ta with W showed that, as expected, W-5Re was softer than W whilst W-5Ta had only minor differences in micro-tensile properties compared with W. The micro-tensile results of the irradiated W, W-5Ta and W-5Re showed an increase in strength and an almost complete loss of ductility compared to the unirradiated samples. In comparing micro-tensile results to nanoindentation measurements, it was found that micro-tensile offers comparable level of precision in measurement of irradiation hardening amongst W, W-5Ta and W-5Re. The implications of the results with respect to the future performance of tungsten-based materials in the divertors in fusion reactors are discussed in detail. Graphical abstract: [Figure not available: see fulltext.

Spatial patterns of the tau pathology in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is characterized neuropathologically by neuronal loss, gliosis, and the presence of tau-immunoreactive neuronal and glial cell inclusions affecting subcortical and some cortical regions. The objectives of this study were to determine (1) the spatial patterns of the tau-immunoreactive pathology, viz., neurofibrillary tangles (NFT), oligodendroglial inclusions (GI), tufted astrocytes (TA), and Alzheimer's disease-type neuritic plaques (NP) in PSP and (2) to investigate the spatial correlations between the histological features. Post-mortem material of cortical and subcortical regions of eight PSP cases was studied. Spatial pattern analysis was applied to the NFT, GI, TA, NP, abnormally enlarged neurons (EN), surviving neurons, and glial cells. NFT, GI, and TA were distributed either at random or in regularly distributed clusters. The EN and NP were mainly randomly distributed. Clustering of NFT and EN was more frequent in the cortex and subcortical regions, respectively. Variations in NFT density were not spatially correlated with the densities of either GI or TA, but were positively correlated with the densities of EN and surviving neurons in some regions. (1) NFT were the most widespread tau-immunoreactive pathology in PSP being distributed randomly in subcortical regions and in regular clusters in cortical regions, (2) GI and TA were more localized and exhibited a regular pattern of clustering in subcortical regions, and (3) neuronal and glial cell pathologies were not spatially correlated. © 2012 Springer-Verlag

Sustainable production of glucaric acid from corn stover via glucose oxidation: An assessment of homogeneous and heterogeneous catalytic oxidation production routes

Glucaric acid is being used increasingly as a food additive, corrosion inhibitor, in deicing, and in detergents, and is also a potential starting material for the production of adipic acid, the key monomer for nylon-66. This work describes a techno-economic analysis of a potential bio-based process for the production of pure glucaric acid from corn stover (biomass). Two alternative routes for oxidation of glucose to glucaric acid are considered: via heterogeneous catalytic oxidation with air, and by homogeneous glucose oxidation using nitric acid. Techno-economic and lifecycle assessments (TEA, LCA) are made for both oxidation routes and cover the entire process from biomass to pure crystalline glucaric acid that can be used as a starting material for the production of valuable chemicals. This is the first TEA of pure glucaric acid production incorporating ion exchange and azeotropic evaporation below 50 °C to avoid lactone formation. The developed process models were simulated in Aspen Plus V9. The techno-economic assessment shows that both production routes are economically viable leading to minimum selling prices of glucaric acid of ∼$2.53/kg and ∼$2.91/kg for the heterogeneous catalytic route and the homogeneous glucose oxidation route respectively. It is shown that the heterogeneous catalytic oxidation route is capable of achieving a 22% lower environmental impact than the homogeneous glucose oxidation route. Opportunities for further improvement in sustainable glucaric acid production at industrial scale are identified and discussed

Evaluating Forecasting Methods

Ideally, forecasting methods should be evaluated in the situations for which they will be used. Underlying the evaluation procedure is the need to test methods against reasonable alternatives. Evaluation consists of four steps: testing assumptions, testing data and methods, replicating outputs, and assessing outputs. Most principles for testing forecasting methods are based on commonly accepted methodological procedures, such as to prespecify criteria or to obtain a large sample of forecast errors. However, forecasters often violate such principles, even in academic studies. Some principles might be surprising, such as do not use R-square, do not use Mean Square Error, and do not use the within-sample fit of the model to select the most accurate time-series model. A checklist of 32 principles is provided to help in systematically evaluating forecasting methods

Investigation of attentional bias in obsessive compulsive disorder with and without depression in visual search

Copyright: © 2013 Morein-Zamir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedWhether Obsessive Compulsive Disorder (OCD) is associated with an increased attentional bias to emotive stimuli remains controversial. Additionally, it is unclear whether comorbid depression modulates abnormal emotional processing in OCD. This study examined attentional bias to OC-relevant scenes using a visual search task. Controls, non-depressed and depressed OCD patients searched for their personally selected positive images amongst their negative distractors, and vice versa. Whilst the OCD groups were slower than healthy individuals in rating the images, there were no group differences in the magnitude of negative bias to concern-related scenes. A second experiment employing a common set of images replicated the results on an additional sample of OCD patients. Although there was a larger bias to negative OC-related images without pre-exposure overall, no group differences in attentional bias were observed. However, OCD patients subsequently rated the images more slowly and more negatively, again suggesting post-attentional processing abnormalities. The results argue against a robust attentional bias in OCD patients, regardless of their depression status and speak to generalized difficulties disengaging from negative valence stimuli. Rather, post-attentional processing abnormalities may account for differences in emotional processing in OCD.Peer reviewedFinal Published versio

Volunteering in the care of people with severe mental illness: a systematic review

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Confronting and mitigating the risk of COVID-19 associated pulmonary aspergillosis.

Cases of COVID-19 associated pulmonary aspergillosis (CAPA) are being increasingly reported and physicians treating patients with COVID-19-related lung disease need to actively consider these fungal co-infections. The SARS-CoV-2 (COVID-19) virus causes a wide spectrum of disease in healthy individuals as well as those with common comorbidities [1]. Severe COVID-19 is characterised acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis, treatment of which may require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [2]. Clinicians are alert to the possibility of bacterial co-infection as a complication of lower respiratory tract viral infection; for example a recent review found that 72% of patients with COVID-19 received antimicrobial therapy [3]. However, the risk of fungal co-infection, in particular COVID-19 associated pulmonary aspergillosis (CAPA), remains underappreciated. Fungal disease consistent with invasive aspergillosis (IA) has been observed with other severe Coronaviruses such as Severe Acute Respiratory Syndrome (SARS-CoV-2003) [4, 5] and Middle East Respiratory Syndrome (MERS-CoV) [6]. From the outset of the COVID-19 pandemic, there were warning signs of secondary invasive fungal infection; Aspergillus flavus was isolated from the respiratory tract from one of 99 patients in the first COVID-19 cohort from Wuhan to be reported in any detail [2] and Aspergillus spp. were isolated from 2/52 (3.8%) of a subsequent cohort of critically unwell patients from this region [7]. More recently, retrospective case series from Belgium [8], France [9], The Netherlands [10] and Germany [11] have reported evidence of CAPA in an alarming 20–35% of mechanically ventilated patients

Durability associated efficacy of long-lasting insecticidal nets after five years of household use

<p>Abstract</p> <p>Background</p> <p>Long-lasting insecticidal nets (LLINs) have been strongly advocated for use to prevent malaria in sub-Saharan Africa and have significantly reduced human-vector contact. PermaNet^®2.0 is among the five LLINs brands which have been given full approval by the WHO Pesticide Evaluation Scheme (WHOPES). The LLINs are expected to protect the malaria endemic communities, but a number of factors within the community can affect their durability and efficacy. This study evaluated the durability, efficacy and retention of PermaNet^®2.0 after five years of use in a Tanzanian community.</p> <p>Method</p> <p>Two to three day- old non blood-fed female mosquitoes from an insectary susceptible colony (<it>An. gambiae </it>s.s, this colony was established at TPRI from Kisumu, Kenya in 1992) and wild mosquito populations (<it>An. arabiensis </it>and <it>Culex quinquefasciatus</it>) were used in cone bioassay tests to assess the efficacy of mosquito nets.</p> <p>Findings</p> <p>The knockdown effect was recorded after three minutes of exposure, and mortality was recorded after 24 hours post-exposure. Mortality of <it>An. gambiae </it>s.s from insectary colony was 100% while <it>An. arabiensis </it>and <it>Cx.quinquefasciatus </it>wild populations had reduced mortality. Insecticide content of the new (the bed net of the same brand but never used before) and used PermaNet^®2.0 was determined using High Performance Liquid Chromatography (HPLC).</p> <p>Conclusion</p> <p>The results of this study suggest that, in order to achieve maximum protection against malaria, public health education focusing on bed net use and maintenance should be incorporated into the mass distribution of nets in communities.</p