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Background: There is an unmet need for blood-based biomarkers that can reliably detect MS disease activity. Serum Biomarkers of interest includ Neurofilament-light-chain (NfL), Glial-fibrillary-strocyte-protein(GFAP) and Tau. Bone Marrow Transplantation (BMT) is reserved for aggressive forms of MS and has been shown to halt detectable CNS inflammatory activity for prolonged periods. Significant pre-treatment tissue damage at followed by inflammatory disease abeyance should be reflected longitudinal sera collected from these patients. Methods: Sera were collected from 23 MS patients pre-treatment, and following BMT at 3, 6, 9 and 12-months in addition from 33 non-inflammatory neurological controls. Biomarker quantification was performed with SiMoA. Results: Pre-AHSCT levels of serum NfL and GFAP but not Tau were elevated compared to controls (p=0.0001), and NfL correlated with lesion-based disease activity (6-month-relapse, MRI-T2 and Gadolinium-enhancement). 3-months post-treatment, while NfL levels remained elevated, Tau/GFAP paradoxically increased (p=0.0023/0.0017). These increases at 3m correlated with MRI ‘pseudoatrophy’ at 6-months. NfL/Tau levels dropped to that of controls by 6-months (p=0.0036/0.0159). GFAP levels dropped progressively after 6-months although even at 12-months remained higher than controls (p=0.004). Conclusions: NfL was the closest correlate of MS disease activity and treatment response. Chemotherapy-related toxicity may account for transient increases in NfL, Tau and MRI brain atrophy post-BMT.
In this paper, we will report about the implementation of the self-consistent Kröner–Eshelby model for the calculation of X-ray elastic constants for general, triclinic crystal symmetry. With applying appropriate symmetry relations, the point groups of higher crystal symmetries are covered as well. This simplifies the implementation effort to cover the calculations for any crystal symmetry. In the literature, several models can be found to estimate the polycrystalline elastic properties from single crystal elastic constants. In general, this is an intermediate step toward the calculation of the polycrystalline response to different techniques using X-rays, neutrons, or ultrasonic waves. In the case of X-ray residual stress analysis, the final goal is the calculation of X-ray Elastic constants. Contrary to the models of Reuss, Voigt, and Hill, the Kröner–Eshelby model has the benefit that, because of the implementation of the Eshelby inclusion model, it can be expanded to cover more complicated systems that exhibit multiple phases, inclusions or pores and that these can be optionally combined with a polycrystalline matrix that is anisotropic, i.e., contains texture. We will discuss a recent theoretical development where the approaches of calculating bounds of Reuss and Voigt, the tighter bounds of Hashin–Shtrikman and Dederichs–Zeller are brought together in one unifying model that converges to the self-consistent solution of Kröner–Eshelby. For the implementation of the Kröner–Eshelby model the well-known Voigt notation is adopted. The 4-rank tensor operations have been rewritten into 2-rank matrix operations. The practical difficulties of the Voigt notation, as usually concealed in the scientific literature, will be discussed. Last, we will show a practical X-ray example in which the various models are applied and compared.
Identifying Research Domain Criteria (RDoC) constructs in early childhood is essential for understanding etiological pathways of psychopathology. Our central goal was to identify early emotion knowledge and self-regulation difficulties across different RDoC domains and examine how they relate to typical versus atypical symptom trajectories between ages 3 and 10. Particularly, we assessed potential contributions of children's gender, executive control, delay of gratification, and regulation of frustration, emotion recognition, and emotion understanding at age 3 to co-occurring patterns of internalizing and externalizing across development. A total of 238 3-year-old boys and girls were assessed using behavioral tasks and parent reports and reassessed at ages 5 and 10 years. Results indicated that very few children developed “pure” internalizing or externalizing symptoms relative to various levels of co-occurring symptoms across development. Four classes of co-occurring internalizing and externalizing problems were identified: low, low-moderate, rising, and severe-decreasing trajectories. Three-year-old children with poor executive control but high emotion understanding were far more likely to show severe-decreasing than low/low-moderate class co-occurring internalizing and externalizing symptom patterns. Child gender and poor executive control differentiated children in rising versus low trajectories. Implications for early intervention targeting self-regulation of executive control are discussed.
Weed interference during crop establishment is a serious concern for Florida strawberry [Fragaria×ananassa (Weston) Duchesne ex Rozier (pro sp.) [chiloensis×virginiana]] producers. In situ remote detection for precision herbicide application reduces both the risk of crop injury and herbicide inputs. Carolina geranium (Geranium carolinianum L.) is a widespread broadleaf weed within Florida strawberry production with sensitivity to clopyralid, the only available POST broadleaf herbicide. Geranium carolinianum leaf structure is distinct from that of the strawberry plant, which makes it an ideal candidate for pattern recognition in digital images via convolutional neural networks (CNNs). The study objective was to assess the precision of three CNNs in detecting G. carolinianum. Images of G. carolinianum growing in competition with strawberry were gathered at four sites in Hillsborough County, FL. Three CNNs were compared, including object detection–based DetectNet, image classification–based VGGNet, and GoogLeNet. Two DetectNet networks were trained to detect either leaves or canopies of G. carolinianum. Image classification using GoogLeNet and VGGNet was largely unsuccessful during validation with whole images (Fscore<0.02). CNN training using cropped images increased G. carolinianum detection during validation for VGGNet (Fscore=0.77) and GoogLeNet (Fscore=0.62). The G. carolinianum leaf–trained DetectNet achieved the highest Fscore (0.94) for plant detection during validation. Leaf-based detection led to more consistent detection of G. carolinianum within the strawberry canopy and reduced recall-related errors encountered in canopy-based training. The smaller target of leaf-based DetectNet did increase false positives, but such errors can be overcome with additional training images for network desensitization training. DetectNet was the most viable CNN tested for image-based remote sensing of G. carolinianum in competition with strawberry. Future research will identify the optimal approach for in situ detection and integrate the detection technology with a precision sprayer.
Parameters such as pretreatment method, enzyme type and concentration, determine the conversion efficiency of biomass’ cellulose and hemicellulose to glucose and mainly xylose in biomass-based fuel production. Chemical quantification of these processes offers no information on the effect of enzymatic hydrolysis (EH) on particle morphology. We report on the development of a microscopy method for imaging pretreated biomass particles at different EH stages. The method was based on acquiring large field of view images, typically 20×10 mm2 containing thousands of particles. Morphology of particles with lengths between 2 μm and 5 mm could be visualized and analyzed. The particle length distribution of corn stover samples, pretreated with increasing amounts of sulfuric acid at different EH stages, was measured. Particle size was shown to be dependent on pretreatment severity and EH time. The methodology developed could offer an alternative method for characterization of EH of biomass for second generation biofuels and visualization of recalcitrant structures.
This article describes a CDI outbreak in a long-term care (LTC) facility that used molecular typing techniques and whole-genome sequencing to identify widespread dissemination of the clonal strain in the environment which was successfully removed after terminal cleaning.
This study was conducted in a long-term care facility in Texas.
A recently hospitalized LTC patient was diagnosed with CDI followed shortly thereafter by 7 subsequent CDI cases. A stool specimen was obtained from each patient for culturing and typing. An environmental point-prevalence study of the facility was conducted before and after terminal cleaning of the facility to assess environmental contamination. Cultured isolates were typed using ribotyping, multilocus variant analysis, and whole-genome sequencing.
Stool samples were available for 5 of 8 patients; of these specimens, 4 grew toxigenic C. difficile ribotype 027. Of 50 environmental swab samples collected throughout the facility prior to the facility-wide terminal cleaning, 19 (38%) grew toxigenic C. difficile (most commonly ribotype 027, 79%). The terminal cleaning was effective at reducing C. difficile spores in the environment and at eradicating the ribotype 027 strain (P<.001). Using multilocus variance analysis and whole-genome sequencing, clinical and environmental strains were highly related and, in some cases, were identical.
Using molecular typing techniques, we demonstrated reduced environmental contamination with toxigenic C. difficile and the eradication of a ribotype 027 clone. These techniques may help direct infection control efforts and decrease the burden of CDI in the healthcare system.
The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
A fundamental understanding of the filament thinning of viscoelastic fluids is important in practical applications such as spraying and printing of complex materials. Here, we present direct numerical simulations of the two-phase axisymmetric momentum equations using the volume-of-fluid technique for interface tracking and the log-conformation transformation to solve the viscoelastic constitutive equation. The numerical results for the filament thinning are in excellent agreement with the theoretical description developed with a slender body approximation. We show that the off-diagonal stress component of the polymeric stress tensor is important and should not be neglected when investigating the later stages of filament thinning. This demonstrates that such numerical methods can be used to study details not captured by the one-dimensional slender body approximation, and pave the way for numerical studies of viscoelastic fluid flows.
OBJECTIVES/SPECIFIC AIMS: Increased retinal protein O-GlcNAcylation occurs in response to hyperglycemia and contributes to diabetic retinopathy. Renin-angiotensin system (RAS) blockers reduce the incidence of diabetic retinopathy. Beneficial effects of RAS blockers are often attributed to production of angiotensin-(1-7) (Ang1-7). The objective here is to determine the impact of Ang1-7 on retinal protein O-GlcNAcylation. METHODS/STUDY POPULATION: C57/BL6 mice were fed a high-fat diet for 8 weeks and then treated for 3 weeks with either a vehicle control, the RAS blocker captopril, or captopril and the Ang1-7 receptor antagonist A779. R28 cells were used to assess levels of O-GlcNAcylated proteins in response to Ang1-7, and the role of cAMP was investigated with addition of forskolin, 6-Bnz-cAMP-AM, and 8-pCPT-2-O-Me-cAMP-AM to cell culture medium. RESULTS/ANTICIPATED RESULTS: Captopril attenuated retinal protein O-GlcNAcylation in mice fed a high-fat diet. This effect was reversed by A779. Ang1-7 attenuated protein O-GlcNAcylation and increased cAMP levels. Forskolin and the EPAC selective cAMP analog 8-pCPT-2-O-Me-cAMP-AM, but not the PKA selective cAMP analog 6-Bnz-cAMP-AM, attenuated O-GlcNAcylation. Inhibiting EPAC blocked the effect of forskolin, whereas inhibiting PKA did not. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates a novel role for Ang1-7 in the retina and identifies a potential EPAC-dependent mechanism that regulates protein O-GlcNAcylation. Thus, future therapeutics targeted at an Ang1-7/EPAC axis in retina may be used to address DR.
A series of in vitro and in vivo experiments were conducted to characterise the dialogue between embryo and maternal units relative to the mechanisms controlling embryo survival in dairy cattle. Endometrial explants from pregnant cows had an attenuated PGF2α secretory response following treatment with melittin (stimulator of PLA2) and phorbol 12, 13 dibutyrate (PDBu). Thus previous exposure to the conceptus appears to regulate the endometrial synthetic pathway at a point coincident with or distal to PLA2 as well as inhibit PKC or PKC mediated events. Endometrial explants collected from cows receiving intrauterine infusions of rblFN-τ had a reduced secretory response following stimulation with PDBu indicating attenuation in PKC activity. Based upon tyrosine-phosphorylation of STAT-proteins and their translocation to the nucleus after treatment with rbIFN-τ, the JAK-STAT pathway is functional in immortalised bovine endometrial cells (BEND cells). Bend cells, exposed to rblFN-τ, reduced PDBu induction of PGF2α secretion and also decreased protein expression of Cox-2 and PLA. RblFN-τ clearly reduced PKC mediated events leading to an antiluteolytic response in endometrial cells. Feeding diets containing 2.6, 5.2 and 7.8% Menhaden fish meal to lactating dairy cows reduced uterine secretion of PGF2α following sequential injections of oestradiol and oxytocin. Thus antiluteolytic effects in early pregnancy may be amplified by feeding by-pass fats. Pregnancy rate to a timed insemination at first service post-partum is increased in association with injection of bST(500 mg; sc) given at insemination. Furthermore injection of bST at time of insemination in superovulated donor cows increased the number of blastocysts and reduced number of unfertilised embryos. Prospects of integrating novel strategies to improve embryo development and survival into reproductive management systems appear to be attainable in high producing dairy cows.
There is little debate that the health workforce is a key component of the health care system. Since the training of doctors and nurses takes several years, and the building of new schools even longer, projections are needed to allow for the development of health workforce policies. Our work develops a projection model for the demand of doctors and nurses by Organisation for Economic Co-operation and Development (OECD) countries in the year 2030. The model is based on a country’s demand for health services, which includes the following factors: per capita income, out-of-pocket health expenditures and the ageing of its population. The supply of doctors and nurses is projected using country-specific autoregressive integrated moving average models. Our work shows how dramatic imbalances in the number of doctors and nurses will be in OECD countries should current trends continue. For each country in the OECD with sufficient data, we report its demand, supply and shortage or surplus of doctors and nurses for 2030. We project a shortage of nearly 400,000 doctors across 32 OECD countries and shortage of nearly 2.5 million nurses across 23 OECD countries in 2030. We discuss the results and suggest policies that address the shortages.
Death assemblages that occupy the upper tens of centimeters of sediment in shallow-marine settings are often subject to extensive mixing, thereby limiting their usefulness in assessing environmentally mediated compositional changes through time in the local biota. Here, we provide evidence that dense, Thalassia-rich seagrass beds preserve a stratigraphic record of biotic variation because their dense root–rhizome mats inhibit mixing. We sampled benthic mollusk assemblages at seven localities in Thalassia-rich beds around St. Croix, USVI, collecting three separate sediment intervals of ~13 cm each to a total depth of ~40 cm below the sediment–water interface, and found evidence that sedimentary intervals preserved compositional stratigraphy. Further, some localities displayed systematic, directional changes down-core. An examination of interval-to-interval changes in composition revealed that compositional variation was unique from locality to locality rather than reflecting coordinated, island-wide transitions. In general, however, relative abundances of epifaunal gastropods and small lucinid bivalves tended to decrease with depth below the sediment–water interface. Quantitative comparisons of life-to-death assemblages from each successive sedimentary interval demonstrated that the shallowest death assemblages were typically more similar to the life assemblages than were deeper assemblages, suggesting that deeper intervals provide records of earlier community states.
Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any ‘gold standard’. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability.
When citizens hold multiple values relevant to their policy opinions, they might experience value conflict, value reconciliation or make a value trade-off. Yet, it is unclear which individuals are able to manage their multiple values in these ways. We posit a sophistication-interaction theory of value pluralism where the most politically sophisticated individuals are able to reconcile the existence of multiple values, thus increasing the stability of their policy opinions. We test this hypothesis using a series of heteroskedastic graded item response theory models of public opinion toward policies related to climate change. We find that people structure their policy preferences toward climate change policies in values toward the environment and the economy, but only the most sophisticated citizens are able to reconcile the potential conflict between these values.
We present results of a detailed investigation of surface motion across the tongue of a polythermal glacier, midre Lovenbreen, Svalbard, during the 1999 summer. Surface velocities in the warm-based upper tongue increased during periods of enhanced surface melting and rainfall events, and force-balance analysis indicates that these velocity variations were locally forced, probably by fluctuations in subglacial water pressure. Surface speed-ups were also observed on the cold-based lower tongue (which acted as a sticky spot, through which there was minimal subglacial drainage for most of the summer), but these were largely non-locally forced by longitudinal coupling to the faster-moving ice up-glacier. On one occasion, however, a large, rapid input of surface water to the glacier reduced the basal drag beneath the cold-based lower tongue, presumably due to hydraulic jacking. This resulted in locally forced enhanced surface velocities across the entire tongue, accompanied by a breaching of the lower tongue and an outburst of subglacially stored water.
Occasional cases of classical bovine spongiform encephalopathy (BSE) still continue to occur within the European Union (EU) for animals born after reinforced feed bans (BARBs), which should in theory have eliminated all risk of infection. The study aimed to determine (i) whether a common rate of decline of BSE infection was evident across EU member states, i.e. to determine whether control measures have been equally effective in all member states, (ii) whether there was any evidence of spontaneous occurrence of BSE in the data and (iii) the expected date for the last BSE case in UK. It was found that there was no significant difference in the rate of decline of BSE prevalence between member states, with a common rate of decline of 33·9% per annum (95% CI 30·9–37%) in successive annual birth cohorts. Trend analysis indicated an ultimate decline to 0 prevalence, suggesting that spontaneous occurrence does not explain the majority of cases. Projecting forward the trends from the back-calculation model indicated that there was approximately a 50% probability of further cases in the UK, and should the current rate of decline continue, there remains the possibility of further occasional cases up until 2026.