Patients with mast cell activation symptoms and elevated baseline serum tryptase level have unique bone marrow morphology

Background: Patients with mast cell (MC) activation symptoms and elevated baseline serum tryptase level (MCAS-T) may not necessarily have a clonal MC disorder. Many are diagnosed with hereditary a-tryptasemia (HaT), a genetic trait characterized by autosomal dominant inheritance of multiple copies of TPSAB1 encoding a-tryptase and increased risk for severe anaphylaxis. Objective: The aim of our study was to identify and characterize bone marrow MC histopathologic features specific for MCAS-T. Methods: A total of 43 patients with MCAS-T underwent evaluation, including bone marrow biopsy, for a MC disorder. The results of the work-up for clonal MC disorders such as systemic mastocytosis and monoclonal MC activation syndrome were negative. Bone marrow MC histopathology was reviewed to identify characteristic features of MCAS-T. A subgroup of patients was available for tryptase genotyping. Results: Patients with MCAS-T showed unique morphologic and histologic features when compared with controls. MCs were larger (P < .01), hypogranular (P < .01), frequently detected in paratrabecular (P < .05) and perivascular (P < .01) locations, and associated with bone marrow eosinophilia (P < .01). A total of 10 patients who were available for tryptase genotyping were all confirmed to have HaT. This subgroup was representative of the larger MCAS-T cohort. Conclusion: We report unique bone marrow MC phenotypic and histopathologic changes in patients with MCAS-T. These morphologic changes are associated with an elevated tryptase level that has been confirmed to be caused by HaT in all patients available for testing. (J Allergy Clin Immunol 2021;147:1497-501.

Hospital trajectories and early predictors of clinical outcomes differ between SARS-CoV-2 and influenza pneumonia

BACKGROUND: A comparison of pneumonias due to SARS-CoV-2 and influenza, in terms of clinical course and predictors of outcomes, might inform prognosis and resource management. We aimed to compare clinical course and outcome predictors in SARS-CoV-2 and influenza pneumonia using multi-state modelling and supervised machine learning on clinical data among hospitalised patients. METHODS: This multicenter retrospective cohort study of patients hospitalised with SARS-CoV-2 (March-December 2020) or influenza (Jan 2015-March 2020) pneumonia had the composite of hospital mortality and hospice discharge as the primary outcome. Multi-state models compared differences in oxygenation/ventilatory utilisation between pneumonias longitudinally throughout hospitalisation. Differences in predictors of outcome were modelled using supervised machine learning classifiers. FINDINGS: Among 2,529 hospitalisations with SARS-CoV-2 and 2,256 with influenza pneumonia, the primary outcome occurred in 21% and 9%, respectively. Multi-state models differentiated oxygen requirement progression between viruses, with SARS-CoV-2 manifesting rapidly-escalating early hypoxemia. Highly contributory classifier variables for the primary outcome differed substantially between viruses. INTERPRETATION: SARS-CoV-2 and influenza pneumonia differ in presentation, hospital course, and outcome predictors. These pathogen-specific differential responses in viral pneumonias suggest distinct management approaches should be investigated. FUNDING: This project was supported by NIH/NCATS UL1 TR002345, NIH/NCATS KL2 TR002346 (PGL), the Doris Duke Charitable Foundation grant 2015215 (PGL), NIH/NHLBI R35 HL140026 (CSC), and a Big Ideas Award from the BJC HealthCare and Washington University School of Medicine Healthcare Innovation Lab and NIH/NIGMS R35 GM142992 (PS)

SMARTER Teamwork: System for Management, Assessment, Research, Training, Education, and Remediation for Teamwork

SMARTER Teamwork: System for Management, Assessment, Research, Training, Education, and Remediation for TeamworkThe rapid adoption of Team-Maker and the Comprehensive Assessment of Team MemberEffectiveness (CATME) tools for team formation and peer evaluation make it possible to extendtheir success to have a significant impact on the development of team skills in higher education.The web-based systems have been used by more than 110,000 students of more than 2400faculty at more than 500 institutions internationally—the figure below shows the growth of theuser base. 2400 The system has had 113,373 unique student users. 2200 Fitted curves are third order. 2000 1800 Faculty and staff 1600 1400 1200 Number of 1000 users 800 Institutions 600 400 Aug Oct. 2005 2012 200 0 0 1 2 3 4 5 6 7 Years since software was releasedThis paper and its accompanying poster will describe strategies for broadening the scope of thosetools into a complete system for the management of teamwork in undergraduate education. TheSystem for the Management, Assessment, Research, Training, Education, and Remediation ofTeamwork (SMARTER Teamwork) has three specific goals: 1) to equip students to work inteams by providing them with training and feedback, 2) to equip faculty to manage student teamsby providing them with information and tools to facilitate best practices, and 3) to equipresearchers to understand teams by broadening the system’s capabilities to collect additionaltypes of data so that a wider range of research questions can be studied through a secureresearcher interface. The three goals of the project support each other in hierarchical fashion:research informs faculty practice, faculty determine the students’ experience, which, if wellmanaged based on research findings, equips students to work in teams. Our strategies forachieving these goals are based on a well-accepted training model that has five elements:information, demonstration, practice, feedback, and remediation.The paper that will be submitted and the poster presented at the conference will focus on newfeatures of the system, the development of training materials, and the deployment of a partnerwebsite that shares information about the SMARTER tools for teamwork and provides basicinformation about teamwork and team management

A multiprotein occupancy map of the mRNP on the 3′ end of histone mRNAs

The animal replication-dependent (RD) histone mRNAs are coordinately regulated with chromosome replication. The RD-histone mRNAs are the only known cellular mRNAs that are not polyadenylated. Instead, the mature transcripts end in a conserved stem–loop (SL) structure. This SL structure interacts with the stem–loop binding protein (SLBP), which is involved in all aspects of RD-histone mRNA metabolism. We used several genomic methods, including high-throughput sequencing of cross-linked immunoprecipitate (HITS-CLIP) to analyze the RNA-binding landscape of SLBP. SLBP was not bound to any RNAs other than histone mRNAs. We performed bioinformatic analyses of the HITS-CLIP data that included (i) clustering genes by sequencing read coverage using CVCA, (ii) mapping the bound RNA fragment termini, and (iii) mapping cross-linking induced mutation sites (CIMS) using CLIP-PyL software. These analyses allowed us to identify specific sites of molecular contact between SLBP and its RD-histone mRNA ligands. We performed in vitro crosslinking assays to refine the CIMS mapping and found that uracils one and three in the loop of the histone mRNA SL preferentially crosslink to SLBP, whereas uracil two in the loop preferentially crosslinks to a separate component, likely the 3′hExo. We also performed a secondary analysis of an iCLIP data set to map UPF1 occupancy across the RD-histone mRNAs and found that UPF1 is bound adjacent to the SLBP-binding site. Multiple proteins likely bind the 3′ end of RD-histone mRNAs together with SLBP

"Cognitive Penetrability" - Ch 3 of Seemings and Epistemic Justification

In this chapter I introduce the thesis that perceptual appearances are cognitively penetrable and analyse cases made against phenomenal conservatism hinging on this thesis. In particular, I focus on objections coming from the externalist reliabilist camp and the internalist inferentialist camp. I conclude that cognitive penetrability doesn’t yield lethal or substantive difficulties for phenomenal conservatism

Short-Term Forecasting and Detection of Explosions During the 2016–2017 Eruption of Bogoslof Volcano, Alaska

We describe a multidisciplinary approach to forecast, rapidly detect, and characterize explosive events during the 2016–2017 eruption of Bogoslof volcano, a back-arc shallow submarine volcano in Alaska’s Aleutian arc. The eruptive sequence began in December 2016 and included about 70 discrete explosive events. Because the volcano has no local monitoring stations, we used distant stations on the nearest volcanoes, Okmok (54 km) and Makushin (72 km), combined with regional infrasound sensors and lightning detection from the Worldwide Lightning Location Network (WWLLN). Pre-eruptive seismicity was detected for 12 events during the first half of the eruption; for all other events co-eruptive signals allowed for detection only. Monitoring of activity used a combination of scheduled checks combined with automated alarms. Alarms triggered on real-time data included real-time seismic amplitude measurement (RSAM); infrasound from several arrays, the closest being on Okmok; and lightning strokes detected from WWLLN within a 20-km radius of the volcano. During periods of unrest, a multidisciplinary response team of four people fulfilled specific roles to evaluate geophysical and remote-sensing data, run event-specific ash-cloud dispersion models, ensure interagency coordination, and develop and distribute of formalized warning products. Using this approach, for events that produced ash clouds ≥7.5 km above sea level, Alaska Volcano Observatory (AVO) called emergency response partners 15 min, and issued written notices 30 min, after event onset (mean times). Factors that affect timeliness of written warnings include event size and number of data streams available; bigger events and more data both decrease uncertainty and allow for faster warnings. In remote areas where airborne ash is the primary hazard, the approach used at Bogoslof is an effective strategy for hazard mitigation

Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19:phase 3 randomised controlled trial (CORONAVIT)

OBJECTIVE: To determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) on risk of all cause acute respiratory tract infection and covid 19. DESIGN: Phase 3 open label randomised controlled trial. SETTING: United Kingdom. PARTICIPANTS: 6200 people aged ≥16 years who were not taking vitamin D supplements at baseline. INTERVENTIONS: Offer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, compared with no offer of testing or supplementation (n=3100). Follow-up was for six months. MAIN OUTCOME MEASURES: The primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat. RESULTS: Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH)D concentrations <75 nmol/L and received vitamin D supplements (n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 (5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and 76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group (1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to 1.63). CONCLUSIONS: Among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04579640

Crop Updates 2000 Cereals - part 3

This session covers eighteen papers from different authors: BARLEY AND OAT AGRONOMY 1. Unicorn barley must meet malting specifications to be a viable option, Roslyn Jettnerand Blakely Paynter, Agriculture Western Australia 2. Optimum oat seed rates, Glenn McDonald, Agriculture Western Australia 3. Production and Quality of export Oaten Hay (1998 and 1989), Pierre Fievez, Pierre Fievez and Associates FROST 4. Climatology of Frost in Southern Western Australia, Ian Foster, Agriculture Western Australia 5. Flowering calculator, David Tennant, Agriculture Western Australia 6. Some options for managing the risk of frost damage, Wal Anderson, Agriculture Western Australia PASTURE 7. TIMERITE® Control of redlegged earth mite in south western Australia with a spring spray to pastures, James Ridsdill-Smith and Celia Pavri, CSIRO Entomology, University of Western Australia 8. The pattern of seed softening in subterranean clover in relation to presicted false break risk, Ross Chapman and Senthold Asseng, CSIRO Plant Industry, Centre for Mediterranean Agricultural Research 9. Charano serradella – a viable option for 1:1 cropping, Steve Carr and Brad Nutt IAMA Agri-Services Western Australia and Centre for Legumes in Mediterranean Agriculture, University of Western Australia 10. Alfalfa mosaic virus in alternative annual pasture and forage legumes, Lindrea Latham and Roger Jones, Crop Improvement Institute, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture, University of Western Australia 11. Pasture mixture performs better than single-species-based pasture – 1999, Anyou Liu, Clinton Revell and David Ferris, Centre for Cropping Systems, Agriculture Western Australia 12. Better pasture management improves performance of following crops – 1999, Anyou Liu, Clinton Revell and David Ferris, Centre for Cropping Systems, Agriculture Western Australia 13. Lucerne Benefits Crop Production, Roy Latta1, Lisa-Jane Blacklow2, Chris Matthews1 1Agriculture Western Australia 2University of Western Australia 14. Does size count? Determining optimum release number of red apion for biocontrol of doublegee, Tim Woodburn and Paul Yeoh, CSIRO Entomology/CRC Weed Management Systems, Perth 15. Herbicide tolerance of some new cultivars of annual pasture legumes, Clinton Revell and Ian Rose, Centre for Cropping Systems, Agriculture Western Australia 16. Lucerne – crop rotations in the Esperance region, Anita Lyons, Roy Latta and Chris Matthews,Agriculture Western Australia PRECISION AGRICULTURE 17. Assessing the results of on-farm experiments using yield monitors, Simon Cook and Matthew Adams, CSIRO Land and Water 18. Achiever: A GIS based achievable yield and fertiliser recommendation system for precision agriculture, Robert J. Corner, Matthew L. Adams, Precision Agriculture Research Group CSIRO Land and Wate

Prospective study design and data analysis in UK Biobank

Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.</p

Reflection and the art of coaching: fostering high-performance in olympic ski cross

In preparation for the 2010 Vancouver Winter Olympic Games, the lead author engaged in systematic reflection in an attempt to implement coaching behaviours and create practice environments that promoted athlete development (psycho-social and physical performance). The research was carried out in relation to his work as head Ski Cross coach working with (primarily) three athletes in their quest for Olympic qualification and subsequent performance success in the Olympic Games. This project sought to examine coach-athlete interactions. Of particular interest were coach and athlete responses regarding the implementation of autonomy supportive coaching behaviours in a high context. Autonomy supportive coaching behaviours have previously been strongly associated with positive athlete psycho-social and performance outcomes, however, a paucity of research has examined its implementation in high-performance contexts. Through the use of participant ethnography, it was possible to gain considerable insights regarding athletes' perceptions of choice, implications of perceived athletic hierarchies, as well as cultural and experience-related influences on training and performance expectations