What is the Total Deuterium Abundance in the Local Galactic Disk?

Analyses of spectra obtained with the Far Ultraviolet Spectroscopic Explorer (FUSE) satellite, together with spectra from the Copernicus and IMAPS instruments, reveal an unexplained very wide range in the observed deuterium/hydrogen (D/H) ratios for interstellar gas in the Galactic disk beyond the Local Bubble. We argue that spatial variations in the depletion of deuterium onto dust grains can explain these local variations in the observed gas-phase D/H ratios. We present a variable deuterium depletion model that naturally explains the constant measured values of D/H inside the Local Bubble, the wide range of gas-phase D/H ratios observed in the intermediate regime (log N(H I} = 19.2-20.7), and the low gas-phase D/H ratios observed at larger hydrogen column densities. We consider empirical tests of the deuterium depletion hypothesis: (i) correlations of gas-phase D/H ratios with depletions of the refractory metals iron and silicon, and (ii) correlation with the molecular hydrogen rotational temperature. Both of these tests are consistent with deuterium depletion from the gas phase in cold, not recently shocked, regions of the ISM, and high gas-phase D/H ratios in gas that has been shocked or otherwise heated recently. We argue that the most representative value for the total (gas plus dust) D/H ratio within 1 kpc of the Sun is >=23.1 +/- 2.4 (1 sigma) parts per million (ppm). This ratio constrains Galactic chemical evolution models to have a very small deuterium astration factor, the ratio of primordial to total (D/H) ratio in the local region of the Galactic disk, which we estimate to be f_d <= 1.19 +/-0.16 (1 sigma) or <= 1.12 +/- 0.14 (1 sigma) depending on the adopted light element nuclear reaction rates.Comment: 19 pages, 9 figure

Recruitment failure and futility were the most common reasons for discontinuation of clinical drug trials. Results of a nationwide inception cohort study in the Netherlands

Objectives The objective of the study was to identify the reasons for discontinuation of clinical drug trials and to evaluate whether efficacy-related discontinuations were adequately planned in the trial protocol. Study Design and Setting All clinical drug trials in the Netherlands, reviewed by institutional review boards in 2007, were followed until December 2015. Data were obtained through the database of the Dutch competent authority (Central Committee on Research Involving Human Subjects [CCMO]) and a questionnaire to the principal investigators. Reasons for trial discontinuation were the primary outcome of the study. Three reasons for discontinuation were analyzed separately: all cause, recruitment failure, and efficacy related (when an interim analysis had demonstrated futility or superiority). Among the efficacy-related discontinuations, we examined whether the data monitoring committee, the stopping rule, and the moment of the interim analysis in the trial progress were specified in the trial protocol. Results Of the 574 trials, 102 (17.8%) were discontinued. The most common reasons were recruitment failure (33 of 574; 5.7%) and solely efficacy related (30 of 574; 5.2%). Of the efficacy-related discontinuations, 10 of 30 (33.3%) of the trial protocols reported all three aspects in the trial protocol, and 20 of 30 (66.7%) reported at least one aspect in the trial protocol. Conclusion One out of five clinical drug trials is discontinued before the planned trial end, with recruitment failure and futility as the most common reasons. The target sample size of trials should be feasible, and interim analyses should be adequately described in trial protocols

Outcome registry of early intensive neurorehabilitation in patients with disorders of consciousness: study protocol of a prospective cohort study

Background: Prolonged disorders of consciousness (PDOC) may occur after severe brain injury. Two diagnostic entities are distinguished within PDOC: unresponsive wakefulness syndrome (UWS, previously known as vegetative state) and minimally conscious state (MCS). Patients with PDOC may benefit from early intensive neurorehabilitation (EIN). In the Netherlands, the EIN programme is provided by one designated expert rehabilitation centre and forms the starting point of a dedicated chain of specialised rehabilitation and care for this group. This study project, called DOCTOR: Disorders of Consciousness; Treatment and Outcomes Registry, sets up a registry and systematically investigates multiple short- and long-term outcomes of patients with PDOC who receive EIN. Methods: Single-centre prospective cohort study with a 2-year follow-up period. Patients with PDOC due to acute brain injury who receive EIN, aged 16 years and older are included. Measurements will take place at start EIN, in week 5, 10, and at discharge from the EIN programme (duration = max 14 weeks) and at week 28, 40, 52, and 104 after admission to the EIN programme, following patients through the health-care chain. Outcome measures are the changes over time in level of consciousness, using the Coma Recovery Scale-Revised; the frequency and type of medical complications; the mortality rate; level of disability, including the level of motor, cognitive, behavioural and emotional functioning; participation; and quality of life. Secondary outcomes include self-efficacy of caregivers, caregivers’ strain and cost-effectiveness of the programme. Discussion: The DOCTOR study will provide insight in the recovery patterns and predictors of recovery for multiple outcomes in PDOC patients after following EIN. The results of the study will enable us to benchmark and improve EIN and the organisation of the health-care chain, both for patients with PDOC and for their families. Trial registration: Netherlands Trial Register, NL 8138. Retrospectively registered 6 November 2019

Ammonia and nitrous oxide emission factors for excreta deposited by livestock and land-applied manure

Manure application to land and deposition of urine and dung by grazing animals are major sources of ammonia (NH3 ) and nitrous oxide (N2 O) emissions. Using data on NH3 and N2 O emissions following land-applied manures and excreta deposited during grazing, emission factors (EFs) disaggregated by climate zone were developed, and the effects of mitigation strategies were evaluated. The NH3 data represent emissions from cattle and swine manures in temperate wet climates, and the N2 O data include cattle, sheep, and swine manure emissions in temperate wet/dry and tropical wet/dry climates. The NH3 EFs for broadcast cattle solid manure and slurry were 0.03 and 0.24 kg NH3 -N kg-1 total N (TN), respectively, whereas the NH3 EF of broadcast swine slurry was 0.29. Emissions from both cattle and swine slurry were reduced between 46 and 62% with low-emissions application methods. Land application of cattle and swine manure in wet climates had EFs of 0.005 and 0.011 kg N2 O-N kg-1 TN, respectively, whereas in dry climates the EF for cattle manure was 0.0031. The N2 O EFs for cattle urine and dung in wet climates were 0.0095 and 0.002 kg N2 O-N kg-1 TN, respectively, which were three times greater than for dry climates. The N2 O EFs for sheep urine and dung in wet climates were 0.0043 and 0.0005, respectively. The use of nitrification inhibitors reduced emissions in swine manure, cattle urine/dung, and sheep urine by 45-63%. These enhanced EFs can improve national inventories; however, more data from poorly represented regions (e.g., Asia, Africa, South America) are needed

DATAMAN: A global database of nitrous oxide and ammonia emission factors for excreta deposited by livestock and land-applied manure

Nitrous oxide (N2 O), ammonia (NH3 ), and methane (CH4 ) emissions from the manure management chain of livestock production systems are important contributors to greenhouse gases (GHGs) and NH3 emitted by human activities. Several studies have evaluated manure-related emissions and associated key variables at regional, national, or continental scales. However, there have been few studies focusing on the drivers of these emissions using a global dataset. An international project was created (DATAMAN) to develop a global database on GHG and NH3 emissions from the manure management chain (housing, storage, and field) to identify key variables influencing emissions and ultimately to refine emission factors (EFs) for future national GHG inventories and NH3 emission reporting. This paper describes the "field" database that focuses on N2 O and NH3 EFs from land-applied manure and excreta deposited by grazing livestock. We collated relevant information (EFs, manure characteristics, soil properties, and climatic conditions) from published peer-reviewed research, conference papers, and existing databases. The database, containing 5,632 observations compiled from 184 studies, was relatively evenly split between N2 O and NH3 (56 and 44% of the EF values, respectively). The N2 O data were derived from studies conducted in 21 countries on five continents, with New Zealand, the United Kingdom, Kenya, and Brazil representing 86% of the data. The NH3 data originated from studies conducted in 17 countries on four continents, with the United Kingdom, Denmark, Canada, and The Netherlands representing 79% of the data. Wet temperate climates represented 90% of the total database. The DATAMAN field database is available at http://www.dataman.co.nz

CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the haematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other haematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that is dependent on CLEC-2 and Syk. These studies demonstrate that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behaviour in vitro

Le Forum, Vol. 43 #4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1102/thumbnail.jp

COVID-19 vaccination in patients with immune thrombocytopenia

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by low platelet count and increased bleeding risk. COVID-19 vaccination has been described as risk factor for de novo ITP, but the effects of COVID-19 vaccination in patients with ITP are unknown. Our aims were to investigate the effects of COVID-19 vaccination in ITP patients on platelet count, bleeding complications and ITP exacerbation (any of: ≥50% decline in platelet count; or nadir platelet count 20% decrease from baseline; or use of rescue therapy). Platelet counts of ITP patients and healthy controls were collected immediately before, 1 and 4 weeks after first and second vaccination. Linear mixed-effects modelling was applied to analyze platelet counts over time. We included 218 ITP patients (50.9% female, mean age 55 years and median platelet count of 106x109/L) and 200 healthy controls (60.0% female, mean age 58 years and median platelet count of 256x109/L). Platelet counts decreased by 6.3% after vaccination. We observed no difference in decrease between the groups. Thirty ITP patients (13.8%, 95%CI 9.5%-19.1%) had an exacerbation and 5 (2.2%, 95%CI 0.7%-5.3%) suffered from a bleeding event. Risk factors for ITP exacerbation were platelet count <50x109/L (OR 5.3, 95%CI 2.1-13.7), ITP treatment at time of vaccination (OR 3.4, 95%CI 1.5-8.0) and age (OR 0.96 per year, 95%CI 0.94-0.99). Our study highlights safety of COVID-19 vaccination in ITP patients and importance of close monitoring platelet counts in a subgroup of ITP patients. ITP patients with exacerbation responded well on therapy