Retention of mouth-to-mouth, mouth-to-mask and mouth-to-face shield ventilation

Background: Retention of mouth-to-mouth, mouth-to-mask and mouth-to-face shield ventilation techniques is poorly understood.Methods: A prospective randomised clinical trial was undertaken in January 2004 in 70 candidates randomly assigned to training in mouth-to-mouth, mouth-to-mask or mouth-to-face shield ventilation. Each candidate was trained for 10 min, after which tidal volume, respiratory rate, minute volume, peak airway pressure and the presence or absence of stomach inflation were measured. 58 subjects were reassessed 1 year later and study parameters were recorded again. Data were analysed with ANOVA, \textgreekq2 and McNemar tests.Results: Tidal volume, minute volume, peak airway pressure, ventilation rate and stomach inflation rate increased significantly at reassessment with all ventilation techniques compared with the initial assessment. However, at reassessment, mean (SD) tidal volume (960 (446) vs 1008 (366) vs 1402 (302) ml; p<0.05), minute volume (12 (5) vs 13 (7) vs 18 (3) l/min; p<0.05), peak airway pressure (14 (8) vs 17 (13) vs 25 (8) cm H2O; p<0.05) and stomach inflation rate (63% vs 58% vs 100%; p<0.05) were significantly lower with mouth-to-mask and mouth-to-face shield ventilation than with mouth-to-mouth ventilation. The ventilation rate at reassessment did not differ significantly between the ventilation techniques.Conclusions: One year after a single episode of ventilation training, lay persons tended to hyperventilate; however, the degree of hyperventilation and resulting stomach inflation were lower when a mouth-to-mask or a face shield device was employed. Regular training is therefore required to retain ventilation skills; retention of skills may be better with ventilation devices

Hypoxia induced downregulation of hepcidin is mediated by platelet derived growth factor BB

OBJECTIVE: Hypoxia affects body iron homeostasis; however, the underlying mechanisms are incompletely understood. DESIGN: Using a standardised hypoxia chamber, 23 healthy volunteers were subjected to hypoxic conditions, equivalent to an altitude of 5600 m, for 6 h. Subsequent experiments were performed in C57BL/6 mice, CREB-H knockout mice, primary hepatocytes and HepG2 cells. RESULTS: Exposure of subjects to hypoxia resulted in a significant decrease of serum levels of the master regulator of iron homeostasis hepcidin and elevated concentrations of platelet derived growth factor (PDGF)-BB. Using correlation analysis, we identified PDGF-BB to be associated with hypoxia mediated hepcidin repression in humans. We then exposed mice to hypoxia using a standardised chamber and observed downregulation of hepatic hepcidin mRNA expression that was paralleled by elevated serum PDGF-BB protein concentrations and higher serum iron levels as compared with mice housed under normoxic conditions. PDGF-BB treatment in vitro and in vivo resulted in suppression of both steady state and BMP6 inducible hepcidin expression. Mechanistically, PDGF-BB inhibits hepcidin transcription by downregulating the protein expression of the transcription factors CREB and CREB-H, and pharmacological blockade or genetic ablation of these pathways abrogated the effects of PDGF-BB toward hepcidin expression. CONCLUSIONS: Hypoxia decreases hepatic hepcidin expression by a novel regulatory pathway exerted via PDGF-BB, leading to increased availability of circulating iron that can be used for erythropoiesis

Studies on the mechanism of vitamin K-dependent carboxylation reaction: corboxylation without the concurrent formation of vitamin K 2,3-epoxide

Bio-organic Synthesi

The role of innate immunity and bioactive lipid mediators in COVID-19 and influenza

In this review, we discuss spatiotemporal kinetics and inflammatory signatures of innate immune cells specifically found in response to SARS-CoV-2 compared to influenza virus infection. Importantly, we cover the current understanding on the mechanisms by which SARS-CoV-2 may fail to engage a coordinated type I response and instead may lead to exaggerated inflammation and death. This knowledge is central for the understanding of available data on specialized pro-resolving lipid mediators in severe SARS-CoV-2 infection pointing toward inhibited E-series resolvin synthesis in severe cases. By investigating a publicly available RNA-seq database of bronchoalveolar lavage cells from patients affected by COVID-19, we moreover offer insights into the regulation of key enzymes involved in lipid mediator synthesis, critically complementing the current knowledge about the mediator lipidome in severely affected patients. This review finally discusses different potential approaches to sustain the synthesis of 3-PUFA-derived pro-resolving lipid mediators, including resolvins and lipoxins, which may critically aid in the prevention of acute lung injury and death from COVID-19.Proteomic

Computational Study of Aero-acoustic Sources in Perforate Silencers

Reynolds Averaged Navier Stokes and Large Eddy Simulations of two perforate plates at a overall pressure ratio of 1.45 have been performed to allow analysis of the sensitivity of acoustic noise sources to porosity. Two geometries are presented: A 23% porosity and a 40% porosity 1mm plate with 2mm diameter holes. Results presented in this paper show the initial jetlet and fully merged jet flow-field to be sensitive to the porosity and the presence of partial holes around the circumference of the plate. The increase in porosity reduces the available entrainment flow, and increases the local jetlet interaction and resultant turbulence levels. This interaction fundamentally changes the flow structure from coherent vortex rings (found at low porosity) to a helical structure. The 2nd and 4th order spatio- temporal correlation Rij and Rij,kl are presented as suggested validation data for acoustic source modeling together with far-field noise spectra obtained via a Ffowcs-Williams & Hawkings surface integral method

Stable population structure in Europe since the Iron Age, despite high mobility

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000-3000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia and France). We found that most regions show remarkable inter-individual heterogeneity. At least 7% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring geography. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empire's mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history

The genetic study of three population microisolates in South Tyrol (MICROS): study design and epidemiological perspectives

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries.</p> <p>Methods</p> <p>The MICROS study is a population-based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-1 (2002/03) genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL) were undertaken.</p> <p>Results</p> <p>Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each). A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score ≥ 3 when the QTL specific heritability is ≥ 20%.</p> <p>Conclusion</p> <p>The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a powerful resource for the study of diseases in many fields of medicine. Recent successes and simulation studies give us confidence that our pedigrees can be valuable both in finding new candidates loci and to confirm existing candidate genes.</p

International Asteroid Warning Network Timing Campaign : 2019 XS

Peer reviewe

Stable population structure in Europe since the Iron Age, despite high mobility

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000–3000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia and France). We found that most regions show remarkable inter-individual heterogeneity. At least 7% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring geography. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empire’s mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history

Economic Valuation for Information Security Investment: A Systematic Literature Review

Research on technological aspects of information security risk is a well-established area and familiar territory for most information security professionals. The same cannot be said about the economic value of information security investments in organisations. While there is an emerging research base investigating suitable approaches measuring the value of investments in information security, it remains difficult for practitioners to identify key approaches in current research. To address this issue, we conducted a systematic literature review on approaches used to evaluate investments in information security. Following a defined review protocol, we searched several databases for relevant primary studies and extracted key details from the identified studies to answer our research questions. The contributions of this work include: a comparison framework and a catalogue of existing approaches and trends that would help researchers and practitioners navigate existing work; categorisation and mapping of approaches according to their key elements and components; and a summary of key challenges and benefits of existing work, which should help focus future research efforts