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Background: Epstein-Barr virus (EBV) infection is believed to be a critical prerequisite for the development of multiple sclerosis (MS). This study aims to investigate whether anti-EBV titres are elevated before the onset of MS symptoms in people with radiologically isolated syndrome (pwRIS) and to evaluate their association with markers of adverse clinical outcomes. Methods: Epstein-Barr nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) titres were quantified in a cohort of 47 pwRIS and 24 healthy controls using Enzyme-Linked Immuno-Sorbent Assay. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were measured using single-molecule array. MRI lesion metrics and the development of MS symptoms over time were also evaluated. Results: EBNA1 titres were higher pwRIS compared to healthy controls (p=0.038), while VCA titres were not (p=0.237). A positive correlation was observed between EBNA1 titres and plasma GFAP in pwRIS (p=0.005). Neither EBNA1 nor VCA titres correlated with NfL. MRI lesion measures and the development of MS symptoms did not show any significant relationship with EBNA1 or VCA titres. Conclusions: Eelevated EBNA1 titres are detectable prior to MS symptom onset and correlate with GFAP, a biomarker associated with worse clinical outcomes. However, their role in disease progression and clinical outcomes requires further investigation.
Background: Radiologically isolated syndrome (RIS) is characterized by incidental MRI findings suggestive of multiple sclerosis in asymptomatic individuals. Emerging blood biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and chitinase 3-like 1 protein (CHI3L1) are promising tools for evaluating neuroinflammation and neurodegeneration. Methods: This cross-sectional analysis included 47 individuals with RIS who underwent MRI and plasma biomarker assessments. Plasma levels of CHI3L1, NfL, and GFAP were measured using highly sensitive assays. Correlations between biomarkers and MRI markers, including T1-black holes (BHs), central vein sign (CVS) positive lesions, paramagnetic rim lesions (PRLs), choroid plexus volume (CPV), and thalamic and hippocampal volumes, were analyzed using linear regression. Results: Plasma CHI3L1 levels correlated with increased CPV (β = 0.347, p = 0.017) and reduced thalamic (β = -0.309, p = 0.035) and hippocampal (β = -0.535, p < 0.001) volumes. Plasma GFAP levels were associated with BHs, CVS, and PRLs, whereas plasma NfL showed no correlations with MRI measures. Conclusions: Plasma CHI3L1 correlates with subcortical grey matter atrophy and CPV increase in RIS, distinct from correlations observed with GFAP or NfL. This suggests that plasma CHI3L1 may reflect neurodegeneration and inflammation in RIS and provide insights into disease activity not captured by other biomarkers.
We present the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY) Pilot Phase I Hi kinematic models. This first data release consists of Hi observations of three fields in the direction of the Hydra and Norma clusters, and the NGC 4636 galaxy group. In this paper, we describe how we generate and publicly release flat-disk tilted-ring kinematic models for 109/592 unique Hi detections in these fields. The modelling method adopted here—which we call the WALLABY Kinematic Analysis Proto-Pipeline (WKAPP) and for which the corresponding scripts are also publicly available—consists of combining results from the homogeneous application of the FAT and 3DBarolo algorithms to the subset of 209 detections with sufficient resolution and $S/N$ in order to generate optimised model parameters and uncertainties. The 109 models presented here tend to be gas rich detections resolved by at least 3–4 synthesised beams across their major axes, but there is no obvious environmental bias in the modelling. The data release described here is the first step towards the derivation of similar products for thousands of spatially resolved WALLABY detections via a dedicated kinematic pipeline. Such a large publicly available and homogeneously analysed dataset will be a powerful legacy product that that will enable a wide range of scientific studies.
Understand how the built environment can affect safety and efficiency outcomes during doffing of personal protective equipment (PPE) in the context of coronavirus disease 2019 (COVID-19) patient care.
Study design:
We conducted (1) field observations and surveys administered to healthcare workers (HCWs) performing PPE doffing, (2) focus groups with HCWs and infection prevention experts, and (3) a with healthcare design experts.
Settings:
This study was conducted in 4 inpatient units treating patients with COVID-19, in 3 hospitals of a single healthcare system.
Participants:
The study included 24 nurses, 2 physicians, 1 respiratory therapist, and 2 infection preventionists.
Results:
The doffing task sequence and the layout of doffing spaces varied considerably across sites, with field observations showing most doffing tasks occurring around the patient room door and PPE support stations. Behaviors perceived as most risky included touching contaminated items and inadequate hand hygiene. Doffing space layout and types of PPE storage and work surfaces were often associated with inadequate cleaning and improper storage of PPE. Focus groups and the design charrette provided insights on how design affording standardization, accessibility, and flexibility can support PPE doffing safety and efficiency in this context.
Conclusions:
There is a need to define, organize and standardize PPE doffing spaces in healthcare settings and to understand the environmental implications of COVID-19–specific issues related to supply shortage and staff workload. Low-effort and low-cost design adaptations of the layout and design of PPE doffing spaces may improve HCW safety and efficiency in existing healthcare facilities.
Necrotising otitis externa is a severe ear infection for which there are no established diagnostic or treatment guidelines.
Method
This study described clinical characteristics, management and outcomes for patients managed as necrotising otitis externa cases at a UK tertiary referral centre.
Results
A total of 58 (63 per cent) patients were classified as definite necrotising otitis externa cases, 31 (34 per cent) as probable cases and 3 (3 per cent) as possible cases. Median duration of intravenous and oral antimicrobial therapy was 6.0 weeks (0.49–44.9 weeks). Six per cent of patients relapsed a median of 16.4 weeks (interquartile range, 23–121) after stopping antimicrobials. Twenty-eight per cent of cases had complex disease. These patients were older (p = 0.042), had a longer duration of symptoms prior to imaging (p < 0.0001) and higher C-reactive protein at diagnosis (p = 0.005). Despite longer courses of intravenous antimicrobials (23 vs 14 days; p = 0.032), complex cases were more likely to relapse (p = 0.016).
Conclusion
A standardised case-definition of necrotising otitis externa is needed to optimise diagnosis, management and research.
Background: Standardized magnetic resonance imaging (MRI) guidelines published in 2015 by the Europoean MAGNIMS group and in 2016 by the CMSC are important for the diagnosis and monitoring of patients with multiple sclerosis (MS) and for the appropriate use of MRI in routine clinical practice. Methods: Two panels of experts convened to update existing guidelines for a standardized MRI protocol. The MAGNIMS panel convened in Graz, Austria in April 2019. The CMSC NAIMS panel met separately and independently in Newark, USA in October 2019. Subsequently, the MAGNIMS, NAIMS, and CMSC working groups combined their efforts to reach an international consensus Results: The revised guidelines on MRI in MS merges recommendations from MAGNIMS, CMSC, and NAIMS to improve the use of MRI for diagnosis, prognosis and monitoring of individuals with MS. 3D acquisitions are emphasized for optimal comparison over time. Core brain sequences include a 3D-T2wFLAIR for lesion identification and monitoring treatment effectiveness. Gadolinium-based contrast is recommended for diagnostic studies and judicious use for routine monitoring of MS patients. DWI sequences are recommended for PML safety monitoring. Conclusions: The international consensus guidelines strive for global acceptance of a useful and usable standard of care for patients with MS.
We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive (${>}7 \times 10^{10} {\mathrm{M}}_\odot$) central galaxies at $0.25 < z <0.35$ in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics ($0.6-0.8$ arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at $0.25 < z <0.35$, as well as hundreds of emission-line sources at $z < 6$. This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at $z\approx 0.3$. MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.
With the increase in regulations regarding the use of antibiotic growth promoters and the rise in consumer demand for poultry products from ‘Raised Without Antibiotics’ or ‘No Antibiotics Ever’ flocks, the quest for alternative products or approaches has intensified in recent years. A great deal of research has focused on the development of antibiotic alternatives to maintain or improve poultry health and performance. This review describes the potential for the various alternatives available to increase animal productivity and help poultry perform to their genetic potential under existing commercial conditions. The classes of alternatives described include probiotics, prebiotics, synbiotics, organic acids, enzymes, phytogenics, antimicrobial peptides, hyperimmune egg antibodies, bacteriophages, clay, and metals. A brief description of the mechanism of action, efficacy, and advantages and disadvantages of their uses are also presented. Though the beneficial effects of many of the alternatives developed have been well demonstrated, the general consensus is that these products lack consistency and the results vary greatly from farm to farm. Furthermore, their mode of action needs to be better defined. Optimal combinations of various alternatives coupled with good management and husbandry practices will be the key to maximize performance and maintain animal productivity, while we move forward with the ultimate goal of reducing antibiotic use in the animal industry.
We present recent observation results of Sgr A* at millimeter obtained with VLBI arrays in Korea and Japan.
7 mm monitoring of Sgr A* is part of our AGN large project. The results at 7 epochs during 2013-2014, including high resolution maps, flux density and two-dimensional size measurements are presented. The source shows no significant variation in flux and structure related to the G2 encounter in 2014. According to recent MHD simulations by kawashima et al., flux and magnetic field energy can be expected to increase several years after the encounter; We will keep our monitoring in order to test this prediction.
Astrometric observations of Sgr A* were performed in 2015 at 7 and 3.5 millimeter simultaneously. Source-frequency phase referencing was applied and a combined ”core-shift” of Sgr A* and a nearby calibrator was measured. Future observations and analysis are necessary to determine the core-shift in each source.
Background: A definitive diagnosis of multiple sclerosis (MS), as distinct from a clinically isolated syndrome, requires one of two conditions: a second clinical attack or particular magnetic resonance imaging (MRI) findings as defined by the McDonald criteria. MRI is also important after a diagnosis is made as a means of monitoring subclinical disease activity. While a standardized protocol for diagnostic and follow-up MRI has been developed by the Consortium of Multiple Sclerosis Centres, acceptance and implementation in Canada have been suboptimal. Methods: To improve diagnosis, monitoring, and management of a clinically isolated syndrome and MS, a Canadian expert panel created consensus recommendations about the appropriate application of the 2010 McDonald criteria in routine practice, strategies to improve adherence to the standardized Consortium of Multiple Sclerosis Centres MRI protocol, and methods for ensuring effective communication among health care practitioners, in particular referring physicians, neurologists, and radiologists. Results: This article presents eight consensus statements developed by the expert panel, along with the rationale underlying the recommendations and commentaries on how to prioritize resource use within the Canadian healthcare system. Conclusions: The expert panel calls on neurologists and radiologists in Canada to incorporate the McDonald criteria, the Consortium of Multiple Sclerosis Centres MRI protocol, and other guidance given in this consensus presentation into their practices. By improving communication and general awareness of best practices for MRI use in MS diagnosis and monitoring, we can improve patient care across Canada by providing timely diagnosis, informed management decisions, and better continuity of care.
Enterotoxigenic Escherichia coli (ETEC) is now recognized as a common cause of foodborne outbreaks. This study aimed to describe the first ETEC O169 outbreak identified in Korea. In this outbreak, we identified 1642 cases from seven schools. Retrospective cohort studies were performed in two schools; and case-control studies were conducted in five schools. In two schools, radish kimchi was associated with illness; and in five other schools, radish or cabbage kimchi was found to have a higher risk among food items. Adjusted relative risk of kimchi was 5·87–7·21 in schools that underwent cohort studies; and adjusted odds ratio was 4·52–12·37 in schools that underwent case-control studies. ETEC O169 was isolated from 230 affected students, and was indistinguishable from the isolates detected from the kimchi product distributed by company X, a food company that produced and distributed kimchi to all seven schools. In this outbreak, we found that the risk of a kimchi-borne outbreak of ETEC O169 infection is present in Korea. We recommend continued monitoring regarding food safety in Korea, and strengthening surveillance regarding ETEC O169 infection through implementation of active laboratory surveillance to confirm its infection.
Although livestock production accounts for a sizeable share of global greenhouse gas emissions, numerous technical options have been identified to mitigate these emissions. In this review, a subset of these options, which have proven to be effective, are discussed. These include measures to reduce CH4 emissions from enteric fermentation by ruminants, the largest single emission source from the global livestock sector, and for reducing CH4 and N2O emissions from manure. A unique feature of this review is the high level of attention given to interactions between mitigation options and productivity. Among the feed supplement options for lowering enteric emissions, dietary lipids, nitrates and ionophores are identified as the most effective. Forage quality, feed processing and precision feeding have the best prospects among the various available feed and feed management measures. With regard to manure, dietary measures that reduce the amount of N excreted (e.g. better matching of dietary protein to animal needs), shift N excretion from urine to faeces (e.g. tannin inclusion at low levels) and reduce the amount of fermentable organic matter excreted are recommended. Among the many ‘end-of-pipe’ measures available for manure management, approaches that capture and/or process CH4 emissions during storage (e.g. anaerobic digestion, biofiltration, composting), as well as subsurface injection of manure, are among the most encouraging options flagged in this section of the review. The importance of a multiple gas perspective is critical when assessing mitigation potentials, because most of the options reviewed show strong interactions among sources of greenhouse gas (GHG) emissions. The paper reviews current knowledge on potential pollution swapping, whereby the reduction of one GHG or emission source leads to unintended increases in another.
This paper describes an adaptive control system for an articulated robot with n joints carrying a variable load. The robot is a complex nonlinear time-varying MIMO plant with dynamic interaction between its inputs and outputs. However, the design of the control system is relatively straightforward and does not require any prior knowledge about the plant. This is because the control system is based on using neural networks which can capture the dynamic characteristics of the plant automatically. Three neural networks are employed in total, the first to learn the dynamics of the robot, the second to model its inverse dynamics and the third, a copy of the second neural network, to control the robot.
Increased semantic priming is an influential theory of thought disorder in schizophrenia. However, studies to date have had conflicting findings.
Aims
To investigate semantic memory in patients with schizophrenia with and without thought disorder.
Method
Data were pooled from 36 studies comparing patients with schizophrenia and normal controls in semantic priming tasks. Data from 18 studies comparing patients with thought disorder with normal controls, and 13 studies comparing patients with and without thought disorder were also pooled.
Results
There was no support for altered semantic priming in schizophrenia as a whole. Increased semantic priming in patients with thought disorder was supported, but this was significant only in comparison with normal controls and not in comparison with patients without thought disorder. Stimulus onset asynchrony (SOA) and general slowing of reaction time moderated the effect size for priming in patients with thought disorder.
Conclusions
Meta-analysis provides qualified support for increased semantic priming as a psychological abnormality underlying thought disorder. However, the possibility that the effect is an artefact of general slowing of reaction time in schizophrenia has not been excluded.
Benthic macroinvertebrates collected at seven different streams displaying different pollution levels were used to investigatespecies abundance patterns in polluted streams. Community response to disturbances in streams was analysed using speciesabundance distribution (SAD) for benthic macroinvertebrates across different levels of pollution. The slopes of rank abundancewere characteristically steeper with decreasing species richness at the polluted sample sites, while the slopes were less steep withhigher species richness at the clean or slightly disturbed sample sites. The SADs were broadly fitted to the log normaldistribution in benthic macroinvertebrate communities across different levels of pollution. A geometric series was partly acceptedfor the communities at the severely polluted sites where new species could not be readily introduced. A power law was applied tothe SADs, and the parameters reflected the states pertaining to the sample sites. The SADs were also efficient in revealingecological state of communities where physico-chemical indicators could not be easily differentiated for stressful conditions instreams.
We present an overview of recent astrometric results with VERA. Since 2004, we have been conducting astrometry of tens of Galactic maser sources with VERA, and recently obtained trigonometric parallaxes for several sources, with distances ranging from 180 pc to 5.3 kpc. In this paper, we briefly summarize the results for Galactic star-forming regions, including S269, Orion-KL, NGC 1333, ρ-oph, NGC 281 and others.
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Comparative and functional fungal genomics
By
R. A. Dean, Center for Integrated Fungal Research Department of Plant Pathology 1200 Partners Building II Box 7251 North Carolina State University Raleigh NC 27695 USA,
T. Mitchell, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA,
R. Kulkarni, RTI 3040 Cornwallis Road Research Triangle Park NC 27709 USA,
N. Donofrio, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA,
A. Powell, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA,
Y. Y. Oh, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA,
S. Diener, North Carolina State University Department of Plant Pathology Campus Box 7253 Raleigh NC 27695–7253 USA,
H. Pan, RTI 3040 Cornwallis Road Research Triangle Park NC 27709 USA,
D. Brown, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA,
J. Deng, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA,
I. Carbone, North Carolina State University Department of Plant Pathology Campus Box 7244 Raleigh NC 27695–7244 USA,
D. J. Ebbole, Department of Plant Pathology and Microbiology Peterson Building Rm 120 MS# 2132 Texas A&M University College Station TX 77843–2132 USA,
M. Thon, Department of Computer Science 320C Peterson Building MS# 2132 Texas A&M University College Station TX 77843–2132 USA,
M. L. Farman, Department of Plant Pathology University of Kentucky 1405 Veterans Drive Lexington KY 40546–0312 USA,
M. J. Orbach, Department of Plant Pathology University of Arizona Forbes Room 105 PO Box 210036 Tucson AZ 85721–0036 USA,
C. Soderlund, Director of Bioinformatics Department of Plant Science 303 Forbes Building Tucson AZ 85721 USA,
J-R. Xu, Department of Botany and Plant Pathology 915 West State Street Purdue University West Lafayette IN 47906 USA,
Y-H. Lee, Seoul National University School of Agricultural Biotechnology Suwon 441–744 Korea,
N. J. Talbot, Department of Biological Sciences University of Exeter Hatherly Laboratories Prince of Wales Road Exeter EX4 4PS UK,
S. Coughlan, Agilent Technologies Inc. Little Falls Site 2850 Centerville Road Wilmington DE 19808 USA,
J. E. Galagan, The Broad Institute Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge MA 02139–4307 USA,
B. W. Birren, The Broad Institute Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge MA 02139–4307 USA
Rice blast disease, caused by the filamentous fungus Magnaporthe grisea, is a serious and recurrent problem in all rice-growing regions of the world (Talbot, 2003; Valent & Chumley, 1991). It is estimated that each year enough rice is destroyed by rice blast disease to feed 60 million people. Control of this disease is difficult; new host-specific forms develop quickly to overcome host resistance and chemical control is typically not cost effective (Ou, 1987). Infections occur when fungal spores land and attach themselves to leaves using a special adhesive released from the tip of each spore (Hamer et al., 1988). The germinating spore develops an appressorium, a specialized infection cell, which generates enormous turgor pressure – up to 8 MPa – that ruptures the leaf cuticle allowing invasion of the underlying leaf tissue (de Jong et al., 1997; Dean, 1997). Subsequent colonization of the leaf produces disease lesions from which the fungus sporulates and spreads to new plants. When rice blast infects young rice seedlings, whole plants often die, while spread of the disease to the stems, nodes or panicle of older plants results in nearly total loss of the rice grain. Recent reports have further shown that the fungus has the capacity to infect plant roots (Sesma & Osbourn, 2004). Different host-limited forms of Magnaporthe also infect a broad range of grass species including wheat, barley and millet.
We show how estimates of parameters characterizing inflation-based theories of structure formation localized over the past year when large scale structure (LSS) information from galaxy and cluster surveys was combined with the rapidly developing cosmic microwave background (CMB) data, especially from the recent Boomerang and Maxima balloon experiments. All current CMB data plus a relatively weak prior probability on the Hubble constant, age and LSS points to little mean curvature (Ωtot = 1.08±0.06) and nearly scale invariant initial fluctuations (ns = 1.03±0.08), both predictions of (non-baroque) inflation theory. We emphasize the role that degeneracy among parameters in the Lpk = 212 ± 7 position of the (first acoustic) peak plays in defining the Ωtot range upon marginalization over other variables. Though the CDM density is in the expected range (Ωcdmh2 = 0.17 ± 0.02), the baryon density Ωbh2 = 0.030 ± 0.005 is somewhat above the independent 0.019 ± 0.002 nucleosynthesis estimates. CMB+LSS gives independent evidence for dark energy (ΩΛ = 0.66 ± 0.06) at the same level as from supernova (SN1) observations, with a phenomenological quintessence equation of state limited by SN1+CMB+LSS to wQ < −0.7 cf. the wQ=−1 cosmological constant case.