Inductively coupled plasma mass spectrometry for stable isotope metabolic tracer studies of living systems

Sub-nanogram per gram levels of molybdenum (Mo) from human blood plasma are isolated by the use of anion exchange alumina microcolumns. Million-fold more concentrated spectral and matrix interferences such as sodium, chloride, sulfate, phosphate, etc. in the blood constituents are removed from the analyte. The recovery of Mo from the alumina column is 82 +/- 5% (n = 5). Isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS) is utilized for the quantitative ultra-trace concentration determination of Mo in bovine and human blood samples. The average Mo concentration in reference bovine serum determined by our method is 10.2 +/- 0.4 ng/g, while the certified value is 11.5 +/- 1.1 ng/g (95% confidence interval). The Mo concentration of one pool of human blood plasma from two healthy male donors is 0.5 +/- 0.1 ng/g;The inductively coupled plasma twin quadrupole mass spectrometer (ICP-TQMS) is used to measure the carbon isotope ratio from non-volatile organic compounds and bio-organic molecules to assess the ability as an alternative analytical method to gas chromatography combustion isotope ratio mass spectrometry (GC-combustion-IRMS). Trytophan, myoglobin, and beta-cyclodextrin are chosen for the study, initial observation of spectral interference of 13C+ with 12C1H+ comes from the incomplete dissociation of myoglobin and/or beta-cyclodextrin. The interference species is most sensitive to the aerosol gas flow rate. Carefully decreasing this parameter can eliminate 12C1H+ interference. 13C/12C ratios in myoglobin and beta-cyclodextrin can be determined precisely and quantitatively. The best relative standard deviation (RSD%) obtained in the 13C/12C study is 0.91%, which is close to the limiting precision predicted by counting statistics (1.16%);Many improvements have been made to the current ICP-TQMS device. A new skimmer interface together with the new ion optics arrangement improves the ion collection efficiency 19-fold. A second-generation ion beam splitter has been designed to reduce the background count rate and improve the ion transmission. A modified ion beam splitter transmits 5 times more ions while maintaining the performance characteristics of the ICP-TQMS system. The precision is further improved by measuring each data point for a longer dwell time (9s instead of 1.5s) and keeping the total ion collection time low ( ≤ 50s instead of 150s)

Image-Derived Input Function for Human Brain Using High Resolution PET Imaging with [11C](R)-rolipram and [11C]PBR28

The aim of this study was to test seven previously published image-input methods in state-of-the-art high resolution PET brain images. Images were obtained with a High Resolution Research Tomograph plus a resolution-recovery reconstruction algorithm using two different radioligands with different radiometabolite fractions. Three of the methods required arterial blood samples to scale the image-input, and four were blood-free methods. values was quantified using a scoring system. Using the image input methods that gave the most accurate results with Logan analysis, we also performed kinetic modelling with a two-tissue compartment model.)-rolipram, which has a lower metabolite fraction. Compartment modeling gave less reliable results, especially for the estimation of individual rate constants.C]PBR28), the more difficult it is to obtain a reliable image-derived input function; and 4) in association with image inputs, graphical analyses should be preferred over compartmental modelling

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. METHODS: The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised

Inductively coupled plasma mass spectrometry for stable isotope metabolic tracer studies of living systems

Sub-nanogram per gram levels of molybdenum (Mo) from human blood plasma are isolated by the use of anion exchange alumina microcolumns. Million-fold more concentrated spectral and matrix interferences such as sodium, chloride, sulfate, phosphate, etc. in the blood constituents are removed from the analyte. The recovery of Mo from the alumina column is 82 +/- 5% (n = 5). Isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS) is utilized for the quantitative ultra-trace concentration determination of Mo in bovine and human blood samples. The average Mo concentration in reference bovine serum determined by our method is 10.2 +/- 0.4 ng/g, while the certified value is 11.5 +/- 1.1 ng/g (95% confidence interval). The Mo concentration of one pool of human blood plasma from two healthy male donors is 0.5 +/- 0.1 ng/g;The inductively coupled plasma twin quadrupole mass spectrometer (ICP-TQMS) is used to measure the carbon isotope ratio from non-volatile organic compounds and bio-organic molecules to assess the ability as an alternative analytical method to gas chromatography combustion isotope ratio mass spectrometry (GC-combustion-IRMS). Trytophan, myoglobin, and beta-cyclodextrin are chosen for the study, initial observation of spectral interference of 13C+ with 12C1H+ comes from the incomplete dissociation of myoglobin and/or beta-cyclodextrin. The interference species is most sensitive to the aerosol gas flow rate. Carefully decreasing this parameter can eliminate 12C1H+ interference. 13C/12C ratios in myoglobin and beta-cyclodextrin can be determined precisely and quantitatively. The best relative standard deviation (RSD%) obtained in the 13C/12C study is 0.91%, which is close to the limiting precision predicted by counting statistics (1.16%);Many improvements have been made to the current ICP-TQMS device. A new skimmer interface together with the new ion optics arrangement improves the ion collection efficiency 19-fold. A second-generation ion beam splitter has been designed to reduce the background count rate and improve the ion transmission. A modified ion beam splitter transmits 5 times more ions while maintaining the performance characteristics of the ICP-TQMS system. The precision is further improved by measuring each data point for a longer dwell time (9s instead of 1.5s) and keeping the total ion collection time low ( ≤ 50s instead of 150s).</p

Should any new light rail line provide real estate gains, or not? The case of the T3 line in Paris

This paper presents a research to assess real estate gains brought by a new light railinfrastructure: the T3 tramway line in Paris opened in December 2006. Based oncomprehensive geo-located data, it mainly focuses on econometric hedonic modelling where accessibility gains are included besides other intrinsic and extrinsic variables. In spite of different specifications, no model yielded any significant effect of the new line. Finally, the rationale for such an outcome is discussed, and by comparison with other studies, the factors for a new line to provide significant gains are listed

A survey on the calibration and validation of integrated land use and transportation models

International audienceA fundamental goal of Land Use – Transport Interaction (LUTI) models is to capture the strong interplay between land use and transportation in metropolitan areas. Inherently, sector-specific models, transport and urban alike, cannot take this interaction into account and thus miss one side of the story. LUTI models aim to fill this gap, and ultimately to provide better decision helping tools for urban and regional long term planning. LUTI models first appeared in the 1960s. The complexity of LUTI models, combined with computational limitations at the time, caused a pause in their development. However, interest in LUTI models has risen again in the 1990s and their number and complexity have been growing steadily ever since. This goes hand in hand with increasing expectations from end users as well as with new theoretical developments and a drastic increase in computational capacities, the latter enabling for instance the development of micro-simulation models.While spatial economics models may be mathematically more complex to handle, due to the requirement of reaching an equilibrium for a complex set of parameters and equations, activity-based models usually have more parameters and larger data requirements for their instantiation. Besides these differences, all LUTI models share several needs, among which – like for most models in general – a need for calibration (parameter estimation) methods in order to instantiate them and for validation approaches in order to justify their operational capacity. Both of these, parameter estimation and model validation, are complex issues; in this document we focus on numerical/computational aspects. The survey reported here is motivated by our conviction that the high complexity of current LUTI models requires the best possible numerical tools for calibration and validation. Developing and applying these tools is the primary objective set by the CITiES project funded by the French ANR (Agence Nationale de la Recherche). A starting point of this endeavor is a survey of existing state of the art reported in the LUTI literature. This document describes the scope of this ongoing study and some intermediate conclusions

AUC ratio (mean ± SD) calculated for each method and for both whole-blood and plasma curves for each tracer.

<p>The AUC ratio is on average more accurate for blood-based methods than for blood-free methods. For [¹¹C]PBR28, but not for [¹¹C](<i>R</i>)-rolipram, the parent AUC ratios of the blood-based methods are less accurate than the whole-blood AUC ratios.</p

Image/blood ratio of the individual rate constants obtained with an unconstrained two-tissue compartment model.

<p>Image/blood ratio of the individual rate constants obtained with an unconstrained two-tissue compartment model.</p

Transaxial slices from a [¹¹C](<i>R</i>)-rolipram brain scan of a healthy volunteer and from a simulated study using a digital phantom.

<p>Upper row: [¹¹C](<i>R</i>)-rolipram images across the thalamus summed over the whole duration of the scan from a phantom (<b>A</b>) and a healthy volunteer (<b>B</b>). The phantom images are realistic and quite similar to those from the real subjects. The external rim of activity surrounding the brain, in both the subject and the phantom, is scalp activity. Middle row: images summed over the first two minutes at the carotid level. The carotids are well visible near the temporal lobes for both the phantom (<b>C</b>) and the healthy volunteer (<b>D</b>). The regions of high activity visible in the lower part of the cerebellum of the subject (<b>D</b>) are the cerebellar venous sinuses (not simulated in the phantom studies). Bottom row: late images (three summed frames taken at about 1 hour after injection) from a phantom (<b>E</b>) and a subject (<b>F</b>). At late times the carotids are not well visible anymore and the spill-over effect from surrounding tissues becomes more important.</p