Understanding and modelling the economic impact of spinal cord injuries in the United Kingdom

Study design Economic modelling analysis. Objectives To determine lifetime direct and indirect costs from initial hospitalisation of all expected new traumatic and non-traumatic spinal cord injuries (SCI) over 12 months. Setting United Kingdom (UK). Methods Incidence-based approach to assessing costs from a societal perspective, including immediate and ongoing health, rehabilitation and long-term care directly attributable to SCI, as well as aids and adaptations, unpaid informal care and participation in employment. The model accounts for differences in injury severity, gender, age at onset and life expectancy. Results Lifetime costs for an expected 1270 new cases of SCI per annum conservatively estimated as £1.43 billion (2016 prices). This equates to a mean £1.12 million (median £0.72 million) per SCI case, ranging from £0.47 million (median £0.40 million) for an AIS grade D injury to £1.87 million (median £1.95 million) for tetraplegia AIS A–C grade injuries. Seventy-one percent of lifetime costs potentially are paid by the public purse with remaining costs due to reduced employment and carer time. Conclusions Despite the magnitude of costs, and being comparable with international estimates, this first analysis of SCI costs in the UK is likely to be conservative. Findings are particularly sensitive to the level and costs of long-term home and residential care. The analysis demonstrates how modelling can be used to highlight economic impacts of SCI rapidly to policymakers, illustrate how changes in future patterns of injury influence costs and help inform future economic evaluations of actions to prevent and/or reduce the impact of SCIs

Analysis of Differentially Expressed MicroRNAs in Serum and Lung Tissues from Individuals with Severe Asthma Treated with Oral Glucocorticoids

Biomarker; Individuals with severe asthma; Oral corticosteroidsBiomarcador; Persones amb asma greu; Corticosteroides oralsBiomarcador; Personas con asma grave; Corticosteroides oralesNowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR. Additionally, pathway enrichment analysis of deregulated miRNAs was conducted. We observed altered expression by the next-generation sequencing (NGS) of 11 miRNAs in serum, of which five (hsa-miR-148b-3p, hsa-miR-221-5p, hsa-miR-618, hsa-miR-941, and hsa-miR-769-5p) were validated by RT-qPCR, and three miRNAs in lung tissue (hsa-miR-144-3p, hsa-miR-144-5p, and hsa-miR-451a). The best multivariate logistic regression model to differentiate individuals with severe asthma, treated and untreated with OCS, was to combine the serum miRNAs hsa-miR-221-5p and hsa-miR-769-5p. Expression of hsa-miR-148b-3p and hsa-miR-221-5p correlated with FEV1/FVC (%) and these altered miRNAs act in key signaling pathways for asthma disease and the regulated expression of some genes (FOXO3, PTEN, and MAPK3) involved in these pathways. In conclusion, there are miRNA profiles differentially expressed in OCS-treated individuals with asthma and could be used as biomarkers of OCS treatment.This work was supported by ISCIII—Instituto de Salud Carlos III, FIS (Fondo de Investigación Sanitaria—Spanish Health Research Fund) grants PI18/00167, PI21/00896, and FI19/00067; Ciber de Enfermedades Respiratorias (CIBERES); RTC-2017-6501-1 (Ministerio de Ciencia, Innovación y Universidades), a Carlos III Institute of Health Initiative; and FEDER funds (Fondo Europeo de Desarrollo Regional)

Performance Testing of a Large-Format Reflection Grating Prototype for a Suborbital Rocket Payload

The soft X-ray grating spectrometer on board the Off-plane Grating Rocket Experiment (OGRE) hopes to achieve the highest resolution soft X-ray spectrum of an astrophysical object when it is launched via suborbital rocket. Paramount to the success of the spectrometer are the performance of the $>250$ reflection gratings populating its reflection grating assembly. To test current grating fabrication capabilities, a grating prototype for the payload was fabricated via electron-beam lithography at The Pennsylvania State University's Materials Research Institute and was subsequently tested for performance at Max Planck Institute for Extraterrestrial Physics' PANTER X-ray Test Facility. Bayesian modeling of the resulting data via Markov chain Monte Carlo (MCMC) sampling indicated that the grating achieved the OGRE single-grating resolution requirement of $R_{g}(\lambda/\Delta\lambda)>4500$ at the 94% confidence level. The resulting $R_g$ posterior probability distribution suggests that this confidence level is likely a conservative estimate though, since only a finite $R_g$ parameter space was sampled and the model could not constrain the upper bound of $R_g$ to less than infinity. Raytrace simulations of the system found that the observed data can be reproduced with a grating performing at $R_g=\infty$. It is therefore postulated that the behavior of the obtained $R_g$ posterior probability distribution can be explained by a finite measurement limit of the system and not a finite limit on $R_g$. Implications of these results and improvements to the test setup are discussed.Comment: 25 pages, 16 figures, preprint of an article accepted for publication in the Journal of Astronomical Instrumentation \copyright 2020 [copyright World Scientific Publishing Company] [https://www.worldscientific.com/worldscinet/jai

Green Production of Anionic Surfactant Obtained from Pea Protein

A pea protein isolate was hydrolyzed by a double enzyme treatment method in order to obtain short peptide sequences used as raw materials to produce lipopeptides-based surfactants. Pea protein hydrolysates were prepared using the combination of Alcalase and Flavourzyme. The influence of the process variables was studied to optimize the proteolytic degradation to high degrees of hydrolysis. The average peptide chain lengths were obtained at 3–5 amino acid units after a hydrolysis of 30 min with the mixture of enzymes. Then, N-acylation in water, in presence of acid chloride (C12 and C16), carried out with a conversion rate of amine functions of 90%, allowed to obtain anionic surfactant mixtures (lipopeptides and sodium fatty acids). These two steps were performed in water, in continuous and did not generate any waste. This process was therefore in line with green chemistry principles. The surface activities (CMC, foaming and emulsifying properties) of these mixtures were also studied. These formulations obtained from natural renewable resources and the reactions done under environmental respect, could replace petrochemical based surfactants for some applications

SN 2015bh: NGC 2770’s 4th supernova or a luminous blue variable on its way to a Wolf-Rayet star?

Very massive stars in the final phases of their lives often show unpredictable outbursts that can mimic supernovae, so-called, “SN impostors”, but the distinction is not always straightforward. Here we present observations of a luminous blue variable (LBV) in NGC 2770 in outburst over more than 20 yr that experienced a possible terminal explosion as type IIn SN in 2015, named SN 2015bh. This possible SN (or “main event”) had a precursor peaking ~40 days before maximum. The total energy release of the main event is ~1.8 × 1049 erg, consistent with a <0.5 M⊙ shell plunging into a dense CSM. The emission lines show a single narrow P Cygni profile during the LBV phase and a double P Cygni profile post maximum suggesting an association of the second component with the possible SN. Since 1994 the star has been redder than an LBV in an S-Dor-like outburst. SN 2015bh lies within a spiral arm of NGC 2770 next to several small star-forming regions with a metallicity of ~0.5 solar and a stellar population age of 7–10 Myr. SN 2015bh shares many similarities with SN 2009ip and may form a new class of objects that exhibit outbursts a few decades prior to a “hyper eruption” or final core-collapse. If the star survives this event it is undoubtedly altered, and we suggest that these “zombie stars” may evolve from an LBV to a Wolf-Rayet star over the timescale of only a few years. The final fate of these stars can only be determined with observations a decade or more after the SN-like event

Childhood/adolescent smoking and adult smoking and cessation: The International Childhood Cardiovascular Cohort (i3C) Consortium

Background: Despite declining US adolescent smoking prevalence from 40% among 12th graders in 1995 to around 10% in 2018, adolescent smoking is still a significant problem. Using the International Childhood Cardiovascular Cohort (i3C) Consortium, which includes 7 international cohorts recruited in childhood and followed into adulthood, the present study was designed to confirm the important relation between adolescent smoking and daily adult smoking and present new data on adult smoking into the forties and comparison of smoking in the United States, Finland, and Australia. Methods and Results: Childhood smoking experience during ages 6 to 19 in the 1970s and 1980s was classifiable in 6687 i3C participants who also provided smoking status in their twenties and forties through 2011-2018. Prevalence of daily smoking in their twenties was directly related to degree of smoking during adolescence and inversely related to the age at which that smoking experience occurred (P trend, P trend, Conclusions: These long-term follow-up data show that smoking intensity increased throughout adolescence. Prevalence of adult smoking and cessation by the forties were both correlated with levels of childhood smoking intensity. These data lend support to preventive strategies designed to reduce, delay, or eliminate any youth access to cigarettes

Re-examining Paul Broca’s initial presentation of M. Leborgne: understanding the impetus for brain and language research

The 150th anniversary affords an opportunity to revisit the circumstances surrounding Paul Broca’s case report celebrated today as the moment of discovery of aphasia. The proceedings from January to June 1861 of the Paris Society of Anthropology are examined to reconstruct the events surrounding the report of M. Leborgne on April 18th. From a close reading of the presentations and discussions which took place during this period it is apparent that Broca’s case report was a minor diversion to a debate about cranial measurements and their relation to intelligence in individuals and racial groups. Moreover, it appears that little attention was granted to Broca’s first case at the time. While his ideas about localization and specialization developed and change over the next decade, it represented a minor field of interest for him. Nevertheless Broca’s work on aphasia inspired research throughout Europe and North America and went on to have a lasting impact on both aphasiology and neuropsychology

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed