995 research outputs found
Canine reference intervals for coagulation markers using the STA Satellite and the STA-R Evolution analyzers
The aim of the current study was to determine canine reference intervals for prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, and antithrombin (AT) according to international recommendations. The STA Satellite coefficients of variation of within-laboratory imprecision were 3.9%, 1.3%, 6.9%, and 5.1% for PT, APTT, fibrinogen, and AT, respectively. At 4uC, citrated specimens were stable up to 8 hr for whole blood and 36 hr for plasma, except for APTT, which increased slightly (<1 sec). Nonparametric reference intervals determined in citrated plasma from 139 healthy fasting purebred dogs were 6.9â8.8 sec, 13.1â17.2 sec, 1.24â4.30 g/l, and 104â188% for PT, APTT, fibrinogen, and AT, respectively. Based on PassingâBablok comparison between STA Satellite and STA-R Evolution using 60 frozen specimens from a canine plasma bank, the corresponding reference intervals were transferred to the STA-R Evolution: 7.1â9.2 sec, 12.9â17.3 sec, 1.20â4.43 g/l, and 94â159% for PT, APTT, fibrinogen, and AT, respectively
Abatacept to induce remission of peanut allergy during oral immunotherapy (ATARI): protocol for a phase 2a randomized controlled trial
ContextWhile oral immunotherapy (OIT) has been shown to promote the remission of mild peanut allergy in young children, there is still an unmet need for a disease-modifying intervention for older patients and those with severe diseases. In mice models, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immunoglobulin fusion protein, has been shown to promote immune tolerance to food when used as an adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept in promoting immune tolerance to food allergens during OIT in humans.MethodsIn this phase 2a proof-of-concept study (NCT04872218), 14 peanut-allergic participants aged from 14 to 55 years will be randomized at a 1:1 ratio to abatacept vs. placebo for the first 24 weeks of a peanut OIT treatment (target maintenance dose of 300 mg peanut protein). The primary outcome will be the suppression of the OIT-induced surge in peanut-specific IgE/total IgE at 24 weeks, relative to the baseline. Sustained unresponsiveness will be assessed as a secondary outcome starting at 36 weeks by observing incremental periods of peanut avoidance followed by oral food challenges.DiscussionThis is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in humans. As observed in preclinical studies, the ability of abatacept to modulate the peanut-specific immune response during OIT will serve as a proxy outcome for the development of clinical tolerance, given the small sample size. The study will also test a new patient-oriented approach to sustained tolerance testing in randomized controlled trials
Preparation of gem-difluorinated retrohydroxamic-fosmidomycin
International audienceFrom several decades, some organophosphorus compounds specifically designed to alterbiological systems were introduced on market as agrochemicals (ie glyphosate and glufosinate asherbicides). Nevertheless, it becomes necessary to find new compounds in order to counter plantresistances already observed with glyphosate. Fosmidomicyn and its N-acetyl analogues FR-900098 were perceived as starting points for elaboration of new herbicide candidates, targetingthe second enzyme of the non-mevalonate pathway in plants, the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DOXP reductoisomerase or DXR). It is expected that theenhancement of bioactivity compared to the parent compounds, might be reached by insertion oftwo fluorine atoms close to the phosphonate function. Indeed, the presence of both fluorineatoms could improve the lipophilicity, affect the pKa of the phosphonic acid function and theninduce better activities. Herein, the synthesis of gem-difluorinated analogues of retrohydroxamicfosmidomycin and FR-900098-ester is reported using a radical addition mediated by acobaloxime comple
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Smart Window Structures Based on Highly Conductive, Transparent Metal Nanomeshes and Thermochromic Perovskite Films
Smart windows are energy-efficient windows whose optical transparency can be switched between
highly transparent and opaque states in response to incident solar illumination. Transparent and
conductive metal nanomesh (NM) films are promising candidates for thermochromic smart
windows due to their excellent thermal conductivity, high optical transparency at near infrared
wavelengths, and outstanding stability. In this study, ZnO/Au/Al2O3 NM films with periodicities of
200 nm and 370 nm are reported. The ZnO/Au/Al2O3 NM film with a 370-nm periodicity exhibits a
transmittance over 90% at 550 nm and sheet resistance lower than 20 âŠ/sq. Based on a standard
figure of merit, this structure outperforms current state-of-the-art nanomesh films. We also
demonstrate the integration of ZnO/Au/Al2O3 NM films into a thermochromic perovskite (TC-PVK)
smart window. The transparency of the smart window structure is manipulated by transient
resistive heating to trigger the thermochromic transition to the opaque state, which can be then
maintained solely by 1-sun, AM 1.5 G illumination. This climate-adaptive, low power-activated, and
fast-switching smart window structure opens new pathways towards its practical application in the
real world.This work was partially supported by the National Science Foundation through the Center for
Dynamics and Control of Materials: an NSF MRSEC under Cooperative Agreement No. DMR-1720595
and by NSF Award No. CBET-2109842. This work was performed in part at the University of Texas
Microelectronics Research Center, a member of the National Nanotechnology Coordinated
Infrastructure (NNCI), which is supported by the National Science Foundation (grant ECCS-2025227).Center for Dynamics and Control of Material
Preventative services offered by veterinarians on sheep farms in England and Wales: opinions and drivers for proactive flock health planning
Recent independent UK government reports and studies have highlighted the importance, but lack, of flock health services provided by veterinarians. Qualitative interviews were analysed by thematic analysis to construct belief statements to understand veterinarians' opinions on preventative advice and drivers for current services to sheep farmers. A postal questionnaire was sent to 515 sheep practices registered with the Royal College of Veterinary Surgeon (RCVS) in England and Wales in 2012 to gather quantitative data on these belief statements and to gather demographic information and current services provided by the veterinarian. Exploratory factor analysis with heuristic approaches was conducted on the respondents' belief statements to identify common factors of veterinarian beliefs. Three main factors were identified: motivation for proactiveness, perceived capability to offer preventative services and perceived opportunity to deliver these services. A beta regression model was built to identify the factors significantly associated with the time veterinarians spent in an advisory role. The relative proportion of time increased by 10% (1.01-1.19), 16% (1.03-1.30) and 29% (CI: 1.09-1.53) for each unit increase in score for factor 1 motivation, factor 2 capability and factor 3 opportunity respectively, indicating that these latent factors explained time veterinarians spent in an advisory role with sheep clients. There was a significant correlation between these factors suggesting influence of the associated beliefs between factors. This study provides insight into the nature and drivers of veterinarians' current behaviour and beliefs. These results could be further tested in behaviour intervention studies and help in designing efficient strategies aiming at promoting proactive health services offered by veterinarians on sheep farms in England and Wales
WJMSC-Derived Small Extracellular Vesicle Enhance T Cell Suppression Through PD-L1
© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles Both mesenchymal stem cells (MSCs) and their corresponding small extracellular vesicles (sEVs, commonly referred to as exosomes) share similar immunomodulatory properties that are potentially beneficial for the treatment of acute graft versus host disease (aGvHD). We report that clinical grade Wharton\u27s Jelly-derived MSCs (WJMSCs) secrete sEVs enriched in programmed death-ligand 1 (PD-L1), an essential ligand for an inhibitory immune checkpoint. A rapid increase in circulating sEV-associated PD-L1 was observed in patients with aGvHD and was directly associated with the infusion time of clinical grade WJMSCs. In addition, in vitro inhibitory antibody mediated blocking of sEV-associated PD-L1 restored T cell activation (TCA), suggesting a functional inhibitory role of sEVs-PD-L1. PD-L1-deficient sEVs isolated from WJMSCs following CRISPR-Cas9 gene editing fail to inhibit TCA. Furthermore, we found that PD-L1 is essential for WJMSC-derived sEVs to modulate T cell receptors (TCRs). Our study reveals an important mechanism by which therapeutic WJMSCs modulate TCR-mediated TCA through sEVs or sEV-carried immune checkpoints. In addition, our clinical data suggest that sEV-associated PD-L1 may be not only useful in predicting the outcomes from WJMSC clinical administration, but also in developing cell-independent therapy for aGvHD patients
Barriers and facilitators of purchasing from short food supply chains in europe: insights from a stakeholder perspective
Thirty-two expert stakeholder (e.g., consumer advice center, state parliament at regional level, European Network for Rural Development, university and research center, chamber of tourism, rural development association, and social cooperative enterprise) interviews were conducted to examine consumer attitudes, values and preferences in relation to short food supply chains. These stakeholders have expertise in policy, consumer behaviour, the tourism sector and regulation. The interviewees represented the views of consumers, producers, and other actors who work with or within short food supply in seven European countries (Belgium, Germany, Greece, Hungary, the Netherlands, Spain, and Switzerland).
Consumers were generally perceived to be aware of the environmental impact of food production. In terms of preferences, consumers would like to shop for local food the way they shop at the supermarket: having variety of products, accessibility, and availability. The relative lack of convenience and high prices associated with short food supply chains products were seen as the major barriers to their purchase. Consumers were thought to buy the products because of health and environmental benefits, a desire to support their local community, and a preference for tradition. However, relatively few consumers purchase products regularly from SFSC. The main segments are people who believe in short food supply chains values, middle class families with young children and elderly people. More can be done to educate and engage consumers regarding these chains, and market research is needed to inform which strategy is likely to be most effective in specific contexts such as the regional level
Using an evidence-based online module to improve parentsâ ability to manage their child with Developmental Coordination Disorder
Background : Developmental coordination disorder (DCD) is a prevalent neurodevelopmental disorder. Best practices include raising parentsâ awareness and building capacity but few interventions incorporating these best practices are documented.
Objective : To examine whether an evidence-based online module can increase the perceived knowledge and skills of parents of children with DCD, and lead to behavioral changes when managing their childâs health condition.
Methods : A mixed-methods, before-after design guided by the theory of planned behavior was employed. Data about the knowledge, skills and behaviors of parents of children with DCD were collected using questionnaires prior to completing the module, immediately after, and three months later. Paired T-tests, sensitivity analyses and thematic analyses were performed on data as appropriate.
Results: One hundred-sixteen, 81 and 58 participants respectively completed the three questionnaires. For knowledge and skills, post- and follow-up scores were significantly higher than baseline scores (p<0.01). Fifty-two (64%) participants reported an intention to change behavior post-intervention and 29 (50%) participants had tried recommended strategies at follow-up. Three themes emerged to describe parentsâ behavioral change: sharing information, trialing strategies and changing attitudes. Factors influencing parentsâ ability to implement these behavioral changes included clear recommendations, time, and ârightâ attitude. Perceived outcomes associated with the parental behavioral changes involved improvement in well-being for the children at school, at home, and for the family as a whole.
Conclusions : The online module increased parentsâ self-reported knowledge and skills in DCD management. Future research should explore its impacts on childrenâs long-term outcomes
Altimetry for the future: Building on 25 years of progress
In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ââGreenâ Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instrumentsâ development and satellite missionsâ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion
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