The global distribution and burden of dengue.

Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes. For some patients, dengue is a life-threatening illness. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread. The contemporary worldwide distribution of the risk of dengue virus infection and its public health burden are poorly known. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Hospital care for children and young adults in the last year of life: a population-based study

BACKGROUND: To help design population-based pediatric palliative care services, we sought to describe the hospital care received in the last year of life by children and young adults who died. We also determined the proportion with complex chronic conditions (CCCs) and tested whether the use of hospital services increased as the date of death drew nearer. METHODS: For all deaths occurring under 25 years of age from 1990 to 1996 in Washington State, USA, we linked death certificate information to hospital utilization records and analyzed the timing and duration of hospitalizations and the nature of hospital procedures during the year prior to death. RESULTS: Of the 8 893 deaths, 25 % had CCCs. Among infants with CCCs, 84 % were hospitalized at the time of death and 50 % had been mechanically ventilated during their terminal admission. Among the 458 CCC neonates dying under a week of age, 92% of all days of life were spent in the hospital; among the 172 CCC neonates dying during the second to fourth weeks of life, 85 % of all days of life were spent hospitalized; among the 286 CCC infants dying during the second to twelfth month of life, 41 % of all days of life were spent hospitalized. Among children and young adults with CCCs, 55 % were hospitalized at the time of death, and 19 % had been mechanically ventilated during their terminal admission. For these older patients, the median number of days spent in the hospital during the year preceding death was 18, yet less than a third of this group was hospitalized at any point in time until the last week of their lives. The rate of hospital use increased as death drew near. For subjects who had received hospital care, 44 % had governmental insurance as the source of primary payment. CONCLUSIONS: Infants who died spent a substantial proportion of their lives in hospitals, whereas children and adolescents who died from CCCs predominantly lived outside of the hospital during the last year of life. To serve these patients, pediatric palliative and end-of-life care will have to be provided in an integrated, coordinated manner both in hospitals and home communities

Topical haemostatic agents for skin wounds: a systematic review

Background: Various agents and techniques have been introduced to limit intra-operative blood loss from skin lesions. No uniformity regarding the type of haemostasis exists and this is generally based on the surgeon's preference. To study the effectiveness of haemostatic agents, standardized wounds like donor site wounds after split skin grafting (SSG) appear particularly suitable. Thus, we performed a systematic review to assess the effectiveness of haemostatic agents in donor site wounds. Methods. We searched all randomized clinical trials (RCTs) on haemostasis after SSG in Medline, Embase and the Cochrane Library until January 2011. Two reviewers independently assessed trial relevance and quality and performed data analysis. Primary endpoint was effectiveness regarding haemostasis. Secondary endpoints were wound healing, adverse effects, and costs. Results: Nine relevant RCTs with a fair methodological quality were found, comparing epinephrine, thrombin, fibrin sealant, alginate dressings, saline, and mineral oil. Epinephrine achieved haemostasis significantly faster than thrombin (difference up to 2.5 minutes), saline or mineral oil (up to 6.5 minutes). Fibrin sealant also resulted in an up to 1 minute quicker haemostasis than thrombin and up to 3 minutes quicker than placebo, but was not directly challenged against epinephrine. Adverse effects appeared negligible. Due to lack of clinical homogeneity, meta-analysis was impossible. Conclusion: According to best available evidence, epinephrine and fibrin sealant appear superior to achieve haemostasis when substantial topical blood loss is anticipated, particularly in case of (larger) SSGs and burn debridement

Non-thermal emission processes in massive binaries

In this paper, I present a general discussion of several astrophysical processes likely to play a role in the production of non-thermal emission in massive stars, with emphasis on massive binaries. Even though the discussion will start in the radio domain where the non-thermal emission was first detected, the census of physical processes involved in the non-thermal emission from massive stars shows that many spectral domains are concerned, from the radio to the very high energies. First, the theoretical aspects of the non-thermal emission from early-type stars will be addressed. The main topics that will be discussed are respectively the physics of individual stellar winds and their interaction in binary systems, the acceleration of relativistic electrons, the magnetic field of massive stars, and finally the non-thermal emission processes relevant to the case of massive stars. Second, this general qualitative discussion will be followed by a more quantitative one, devoted to the most probable scenario where non-thermal radio emitters are massive binaries. I will show how several stellar, wind and orbital parameters can be combined in order to make some semi-quantitative predictions on the high-energy counterpart to the non-thermal emission detected in the radio domain. These theoretical considerations will be followed by a census of results obtained so far, and related to this topic... (see paper for full abstract)Comment: 47 pages, 5 postscript figures, accepted for publication in Astronomy and Astrophysics Review. Astronomy and Astrophysics Review, in pres

Initial response of young people with thyrotoxicosis to block and replace or dose titration thionamide

\ua9 2022 The authors Published by Bioscientifica Ltd.Objective: Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT). Design: A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy. Methods: Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with randomisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change. Results: There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There was no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had higher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31.7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0.57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentrations. Conclusions: DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT therapy

Nocturnal plant respiration is under strong non-temperature control

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: The leaf respiration data measured as part of this study and collected from the literature together with annual gridded JULES output generated in simulations of this study are available at https://doi.org/10.5281/zenodo.7037530. WFDEI meteorological forcing data is available at the DATAGURU website for climate-related data at Lund University (https://DATAGURU.lu.se, then go to “Explore available datasets”). This allows extraction of data from the global domain, a user-defined grid box or region for a specified time interval. Ftp downloads are possible via the unix/linux command line, site = ftp.iiasa.ac.at, username = rfdata and password = forceDATA, this takes the user to the WATCH Forcing DATA files, then switch to the WFDEI directory using: ‘cd WFDEI’. The /WFDEI directory includes files listing grid box elevations and locations Annual CO2 concentrations are available at https://gml.noaa.gov/ccgg/trends/gl_data.html Source data are provided with this paper.Code availability: Python code for data analysis is available under https://doi.org/10.5281/zenodo.7037530. This study uses JULES, two branches of JULES-vn5.2. https://code.metoffice.gov.uk/trac/jules/browser/main/branches/dev/linamercado/r14338_circadian at revision 22682 for TDQ10 simulations and https://code.metoffice.gov.uk/trac/jules/browser/main/branches/dev/douglasclark/vn5.2_diurnal_resp at revision 22681 for simulations with constant Q10 which are available on the Met Office Science Repository System (MOSRS; https://code.metoffice.gov.uk/trac/jules; registration required https://jules.jchmr.org/content/getting-started). Simulations were performed using Rose suites u-ce999 (new formulation) and u-ce859 for simulations with constant Q10, and u-bs101 (with new formulation) and u-ce767 for simulations with TDQ10 also available through MOSRS.Most biological rates depend on the rate of respiration. Temperature variation is typically considered the main driver of daily plant respiration rates, assuming a constant daily respiration rate at a set temperature. Here, we show empirical data from 31 species from temperate and tropical biomes to demonstrate that the rate of plant respiration at a constant temperature decreases monotonically with time through the night, on average by 25% after 8 h of darkness. Temperature controls less than half of the total nocturnal variation in respiration. A new universal formulation is developed to model and understand nocturnal plant respiration, combining the nocturnal decrease in the rate of plant respiration at constant temperature with the decrease in plant respiration according to the temperature sensitivity. Application of the new formulation shows a global reduction of 4.5 -6 % in plant respiration and an increase of 7-10% in net primary production for the present-day.Natural Environment Research Council (NERC)University of ExeterMet Office Hadley Centre Climate Programm

The Impact of the C-Terminal Domain on the Interaction of Human DNA Topoisomerase II α and β with DNA

<b>Background</b> Type II DNA topoisomerases are essential, ubiquitous enzymes that act to relieve topological problems arising in DNA from normal cellular activity. Their mechanism of action involves the ATP-dependent transport of one DNA duplex through a transient break in a second DNA duplex; metal ions are essential for strand passage. Humans have two isoforms, topoisomerase IIα and topoisomerase IIβ, that have distinct roles in the cell. The C-terminal domain has been linked to isoform specific differences in activity and DNA interaction. <b>Methodology/Principal Findings</b> We have investigated the role of the C-terminal domain in the binding of human topoisomerase IIα and topoisomerase IIβ to DNA in fluorescence anisotropy assays using full length and C-terminally truncated enzymes. We find that the C-terminal domain of topoisomerase IIβ but not topoisomerase IIα affects the binding of the enzyme to the DNA. The presence of metal ions has no effect on DNA binding. Additionally, we have examined strand passage of the full length and truncated enzymes in the presence of a number of supporting metal ions and find that there is no difference in relative decatenation between isoforms. We find that calcium and manganese, in addition to magnesium, can support strand passage by the human topoisomerase II enzymes. <b>Conclusions/Significance</b> The C-terminal domain of topoisomerase IIβ, but not that of topoisomerase IIα, alters the enzyme's KD for DNA binding. This is consistent with previous data and may be related to the differential modes of action of the two isoforms in vivo. We also show strand passage with different supporting metal ions for human topoisomerase IIα or topoisomerase IIβ, either full length or C-terminally truncated. They all show the same preferences, whereby Mg > Ca > Mn

Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension.

Genetic evidence implicates the loss of bone morphogenetic protein type II receptor (BMPR-II) signaling in the endothelium as an initiating factor in pulmonary arterial hypertension (PAH). However, selective targeting of this signaling pathway using BMP ligands has not yet been explored as a therapeutic strategy. Here, we identify BMP9 as the preferred ligand for preventing apoptosis and enhancing monolayer integrity in both pulmonary arterial endothelial cells and blood outgrowth endothelial cells from subjects with PAH who bear mutations in the gene encoding BMPR-II, BMPR2. Mice bearing a heterozygous knock-in allele of a human BMPR2 mutation, R899X, which we generated as an animal model of PAH caused by BMPR-II deficiency, spontaneously developed PAH. Administration of BMP9 reversed established PAH in these mice, as well as in two other experimental PAH models, in which PAH develops in response to either monocrotaline or VEGF receptor inhibition combined with chronic hypoxia. These results demonstrate the promise of direct enhancement of endothelial BMP signaling as a new therapeutic strategy for PAH

Analysis of synonymous codon usage in Hepatitis A virus

<p>Abstract</p> <p>Background</p> <p>Hepatitis A virus is the causative agent of type A viral hepatitis, which causes occasional acute hepatitis. Nevertheless, little information about synonymous codon usage pattern of HAV genome in the process of its evolution is available. In this study, the key genetic determinants of codon usage in HAV were examined.</p> <p>Results</p> <p>The overall extent of codon usage bias in HAV is high in <it>Picornaviridae</it>. And the patterns of synonymous codon usage are quite different in HAV genomes from different location. The base composition is closely correlated with codon usage bias. Furthermore, the most important determinant that results in such a high codon bias in HAV is mutation pressure rather than natural selection.</p> <p>Conclusions</p> <p>HAV presents a higher codon usage bias than other members of <it>Picornaviridae</it>. Compositional constraint is a significant element that influences the variation of synonymous codon usage in HAV genome. Besides, mutation pressure is supposed to be the major factor shaping the hyperendemic codon usage pattern of HAV.</p