ABSTRACT
Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 1 , Adult , Blood Glucose , Blood Glucose Self-Monitoring , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Child , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Heart Disease Risk Factors , Humans , Prospective Studies , Risk FactorsABSTRACT
Time-Domain Nuclear Magnetic Resonance (TD-NMR) was used to quantify the lipid contents of 48 different organic waste substrates. Results obtained from TD-NMR were compared to those from Soxhlet extraction, currently the prevalent method for organic waste characterization, especially in the field of anaerobic digestion. Two calibration methods were tested. The first was a self-calibration process using pure oils (NMR1) which showed good repeatability compared to Soxhlet extraction with a better coefficient of variation (5%). Analyses of volatile fatty acids (VFA) and long-chain fatty acids (LCFA) by chromatography were carried out to understand why the NMR1 method produced underestimations for some samples. Statistical analysis showed that the presence of saturated fatty acids had a significant effect on differences between the Soxhlet and NMR1 methods. The second calibration method applied chemometrics to TD-NMR raw data (NMR2), taking Soxhlet extraction values as references. It provided a good prediction of lipid content and avoided the lengthy calibration procedure usually required for this type of study. Last, the NMR2 method was shown to be highly suited to the quantification of lipids in organic waste, demonstrating better repeatability than the classic Soxhlet method.
Subject(s)
Chemometrics , Lipids , Fatty Acids , Magnetic Resonance Spectroscopy , Plant OilsABSTRACT
Recycling phosphorus from waste activated sludge has attracted a lot of interest to tackle the problem of phosphorus stocks depletion and the increase in food demand. In this study, the use of fermentation processes was investigated to enhance phosphorus dissolution from waste activated sludge to improve its recycling. Two fermentation processes, bioacidification and dark fermentation, were used on two different sludges fermented with wheat starch syrup in continuous operating conditions. Hydrogen yield from the co-substrate fermentation with waste activated sludge reached 3.9 mmolH2.gCODcosubstrate-1 yield during dark fermentation process and was negligible during bioacidification. Dissolved phosphorus in the waste activated sludge increased by 68% during bioacidification and by 43% during dark fermentation. In both processes, phosphorus dissolution was accompanied by iron, calcium and magnesium dissolution. Results show that fermentation enhances phosphorus dissolution in waste activated sludge to improve its recovery along with hydrogen and organic acids.
Subject(s)
Phosphorus , Sewage , Fatty Acids, Volatile , Fermentation , Recycling , SolubilityABSTRACT
A new instrument dedicated to the kinetic study of low-temperature gas phase neutral-neutral reactions, including clustering processes, is presented. It combines a supersonic flow reactor with vacuum ultra-violet synchrotron photoionization time-of-flight mass spectrometry. A photoion-photoelectron coincidence detection scheme has been adopted to optimize the particle counting efficiency. The characteristics of the instrument are detailed along with its capabilities illustrated through a few results obtained at low temperatures (<100 K) including a photoionization spectrum of n-butane, the detection of formic acid dimer formation, and the observation of diacetylene molecules formed by the reaction between the C2H radical and C2H2.
ABSTRACT
Automated closed-loop (CL) insulin therapy has come of age. This major technological advance is expected to significantly improve the quality of care for adults, adolescents and children with type 1 diabetes. To improve access to this innovation for both patients and healthcare professionals (HCPs), and to promote adherence to its requirements in terms of safety, regulations, ethics and practice, the French Diabetes Society (SFD) brought together a French Working Group of experts to discuss the current practical consensus. The result is the present statement describing the indications for CL therapy with emphasis on the idea that treatment expectations must be clearly defined in advance. Specifications for expert care centres in charge of initiating the treatment were also proposed. Great importance was also attached to the crucial place of high-quality training for patients and healthcare professionals. Long-term follow-up should collect not only metabolic and clinical results, but also indicators related to psychosocial and human factors. Overall, this national consensus statement aims to promote the introduction of marketed CL devices into standard clinical practice.
Subject(s)
Diabetes Mellitus, Type 1 , Insulin Infusion Systems , Insulin , Adolescent , Adult , Child , Diabetes Mellitus, Type 1/drug therapy , France , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosageSubject(s)
Cardiologists/organization & administration , Diabetes Mellitus, Type 2/therapy , Diabetic Angiopathies/therapy , Endocrinologists/organization & administration , Patient Care Team/organization & administration , Clinical Trials as Topic/methods , Clinical Trials as Topic/organization & administration , Cooperative Behavior , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/economics , Diabetes Mellitus, Type 2/mortality , Diabetic Angiopathies/economics , Diabetic Angiopathies/mortality , Diabetic Angiopathies/prevention & control , Health Care Costs , Humans , Hypoglycemic Agents/therapeutic use , Interdisciplinary Communication , Preventive Medicine , Research Design , Risk FactorsABSTRACT
BACKGROUND: The impact of 7-day real-time continuous glucose monitoring (RT-CGM) on type 1 diabetes (T1D) management remains unknown in youths with suboptimal control by multiple daily injections (MDI). The DIACCOR Study aimed to describe treatment decisions and glucose outcomes after a short-term RT-CGM sequence in real-life conditions. METHODS: This French multicenter longitudinal observational study included T1D youths with HbA1c>7.5% or a history of severe hypoglycemia (SH) or recurrent documented hypoglycemia. A sensor was inserted at the study-inclusion visit, and one of three predefined treatment changes was proposed by the investigator within 7-15 days: INT=MDI intensification, CSII=switch to continuous insulin infusion, or ER=educational reinforcement with no change in insulin regimen and a 4-month follow-up visit (M4) was scheduled. RESULTS: A total of 229 children (12.2±3.5 years old) were recruited by 74 pediatricians; 12.8% had a history of SH, 22.2% had recurrent hypoglycemia. Baseline HbA1c was 8.7±1.5% (>7.5% in 82.8%). Overall, 139 (79.4%), 19 (10.9%), and 17 patients (9.7%) were, respectively, included in the INT, CSII, and ER subgroups. At M4, the global incidence of SH and recurrent hypoglycemia dropped (3.4% vs. 12.8% and 6.0% vs. 22.2%, respectively) as well as the incidence of ketoacidosis (2.1% vs. 8.1%) or ketosis (6.9% vs. 11.4%). The HbA1c decrease was significant overall and in the INT subgroup (adjusted difference -0.29%, P=0.009). The satisfaction rate was≥93.0% among children. CONCLUSION: In a real-life setting, a 1-week RT-CGM can promote treatment optimization in youths with uncontrolled T1D resulting mostly in less acute events. CGM acceptance may improve with new-generation sensors.
Subject(s)
Blood Glucose Self-Monitoring/methods , Blood Glucose/metabolism , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Adolescent , Blood Glucose Self-Monitoring/instrumentation , Child , Child, Preschool , Computer Systems , Drug Administration Schedule , Female , Humans , Hypoglycemic Agents/therapeutic use , Injections , Insulin/therapeutic use , Longitudinal Studies , Male , Treatment OutcomeABSTRACT
PURPOSE: Posaconazole is a triazole antifungal widely used for prophylaxis of invasive fungal disease (IFI). Posaconazole tablets allow reaching higher plasma levels than the oral suspension, but safety data with this formulation in real life are scarce. This study aimed at evaluating the safety profile, the pharmacokinetic variability, and the concentration-toxicity relationship of posaconazole tablets in patients with haematological malignancies. METHODS: Sixty neutropenic patients treated with posaconazole tablets for prophylaxis of IFI were prospectively included in the study. Adverse drug reactions (ADR) were recorded and analyzed by the Regional Pharmacovigilance Centre to assess posaconazole implication. Blood samples were drawn once a week and plasma trough concentrations (C min) were assayed by LC-MS/MS. The rates of ADR by quartile of C min were compared. RESULTS: Eighteen patients (30%) experienced at least one ADR attributed to posaconazole. Liver function test (LFT) abnormalities were encountered in 20% of patients and resulted in four (6.7%) treatment discontinuations. Posaconazole median (range) C min was 1.36 (< 0.1-3.44) µg/mL (inter-patient CV = 43.9%). During follow-up, 28.6% of patients had at least one concentration < 0.7 µg/mL, and 35.7% had at least one concentration > 2 µg/mL. Rates of ADR by quartile of C min were not different. CONCLUSIONS: Posaconazole was well tolerated; however, LFT abnormalities were frequent. ADR occurrence was not linked to posaconazole exposure. Because posaconazole concentrations were highly variable, TDM can be helpful to avoid underexposure to the drug and increase its efficacy in preventing IFI. Conversely, a large proportion of patients was overexposed and might have benefited of a dose reduction.
Subject(s)
Triazoles/administration & dosage , Triazoles/adverse effects , Administration, Oral , Adult , Aged , Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Antifungal Agents/pharmacokinetics , Drug Monitoring/methods , Female , Hematologic Neoplasms/blood , Hematologic Neoplasms/metabolism , Humans , Male , Middle Aged , Prospective Studies , Tablets , Triazoles/blood , Triazoles/pharmacokinetics , Young AdultABSTRACT
Atomic sulfur and silicon are important constituents of the interstellar matter and are both used as tracers of the physical conditions in interstellar shocks and outflows. We present an investigation of the spin-orbit (de-)excitation of S(3P) and Si(3P) atoms induced by collisions with helium with the aim to improve the determination of atomic sulfur and silicon abundances in the interstellar medium from S and Si emission spectra. Quantum-mechanical calculations have been performed in order to determine rate coefficients for the fine-structure transitions in the 5-1000 K temperature range. The scattering calculations are based on new highly correlated ab initio potentials. The theoretical results show that the (de-)excitation of Si is much faster than that of S. The rate coefficients deduced from this study are in good agreement with previous experimental and theoretical findings despite some deviations at low temperatures. From the computation of critical densities defined as the ratios between Einstein coefficients and the sum of the relevant collisional de-excitation rate coefficients, we show that local thermodynamic equilibrium conditions are not fulfilled for analyzing S and Si emission spectra observed in the interstellar medium. Hence, the present rate coefficients will be extremely useful for the accurate determination of interstellar atomic sulfur and silicon abundances.
ABSTRACT
The use by diabetes patients of real-time continuous interstitial glucose monitoring (CGM) or the FreeStyle Libre® (FSL) flash glucose monitoring (FGM) system is becoming widespread and has changed diabetic practice. The working group bringing together a number of French experts has proposed the present practical consensus. Training of professionals and patient education are crucial for the success of CGM. Also, institutional recommendations must pay particular attention to the indications for and reimbursement of CGM devices in populations at risk of hypoglycaemia. The rules of good practice for CGM are the precursors of those that need to be enacted, given the oncoming emergence of artificial pancreas devices. It is necessary to have software combining user-friendliness, multiplatform usage and average glucose profile (AGP) presentation, while integrating glucose and insulin data as well as events. Expression of CGM data must strive for standardization that facilitates patient phenotyping and their follow-up, while integrating indicators of variability. The introduction of CGM involves a transformation of treatment support, rendering it longer and more complex as it also includes specific educational and technical dimensions. This complexity must be taken into account in discussions of organization of diabetes care.
Subject(s)
Blood Glucose Self-Monitoring , Patient Education as Topic , Practice Guidelines as Topic , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/therapy , France , Humans , Retrospective StudiesABSTRACT
We present an experimental and theoretical investigation of the deactivation rate of S(1D) atoms by collisions with argon. Kinetic measurements were performed at temperatures from 5.8 K to 298 K in cold uniform supersonic flows using a CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme or Reaction Kinetics in a Uniform Supersonic Flow) apparatus. In order to simulate them, ab initio electronic structure calculations using internally contracted MRCI methodology were performed to describe the interaction. Starting from them, close-coupling calculations were carried out to determine collisional quenching probabilities for the transition S(1D) â S(3P) in the energy range 1-3000 K (1 K ≈ 0.7 cm-1), sufficient to calculate thermal rate coefficients up to 300 K. Stückelberg-like oscillations in the quenching probabilities as a function of the energy are found and interpreted using a semiclassical model. Differences between the temperature dependence of the experimental and theoretical rate coefficients are detected at low temperatures. They are discussed in the light of a study of the high sensitivity of the theoretical results to the potential curves, due to the interference mechanisms which underlie the process.
ABSTRACT
The insect juvenile hormone receptor is a basic helix-loop-helix (bHLH), Per-Arnt-Sim (PAS) domain protein, a novel type of hormone receptor. In higher flies like Drosophila, the ancestral receptor germ cell-expressed (gce) gene has duplicated to yield the paralog Methoprene-tolerant (Met). These paralogous receptors share redundant function during development but play unique roles in adults. Some aspects of JH function apparently require one receptor or the other. To provide a foundation for studying JH receptor function, we have recapitulated endogenous JH receptor expression with single cell resolution. Using Bacteria Artificial Chromosome (BAC) recombineering and a transgenic knock-in, we have generated a spatiotemporal expressional atlas of Met and gce throughout development. We demonstrate JH receptor expression in known JH target tissues, in which temporal expression corresponds with periods of hormone sensitivity. Larval expression largely supports the notion of functional redundancy. Furthermore, we provide the neuroanatomical distribution of JH receptors in both the larval and adult central nervous system, which will serve as a platform for future studies regarding JH action on insect behavior.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/genetics , Drosophila Proteins/genetics , Drosophila/genetics , Gene Expression Regulation, Developmental , Juvenile Hormones/metabolism , Transcription Factors/genetics , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Drosophila/growth & development , Drosophila/metabolism , Drosophila Proteins/metabolism , Larva/metabolism , Transcription Factors/metabolismABSTRACT
Essentials Bleeding incidence as hemorrhagic risk factors are unknown in palliative care inpatients. We conducted a multicenter observational study (22 Palliative Care Units, 1199 patients). At three months, the cumulative incidence of clinically relevant bleeding was 9.8%. Cancer, recent bleeding, thromboprophylaxis and antiplatelet therapy were independent risk factors. SUMMARY: Background The value of primary thromboprophylaxis in patients admitted to palliative care units is debatable. Moreover, the risk of bleeding in these patients is unknown. Objectives Our primary aim was to assess the bleeding risk of patients in a real-world practice setting of hospital palliative care. Our secondary aim was to determine the incidence of symptomatic deep vein thrombosis and to identify risk factors for bleeding. Patients/Methods In this prospective, observational study in 22 French palliative care units, 1199 patients (median age, 71 years; male, 45.5%), admitted for the first time to a palliative care unit for advanced cancer or pulmonary, cardiac or neurologic disease were included. The primary outcome was adjudicated clinically relevant bleeding (i.e. a composite of major and clinically relevant non-major bleeding) at 3 months. The secondary outcome was symptomatic deep vein thrombosis. Results The most common reason for palliative care was cancer (90.7%). By 3 months, 1087 patients (91.3%) had died and 116 patients had presented at least one episode of clinically relevant bleeding (fatal in 23 patients). Taking into account the competing risk of death, the cumulative incidence of clinically relevant bleeding was 9.8% (95% confidence interval [CI], 8.3-11.6). Deep vein thrombosis occurred in six patients (cumulative incidence, 0.5%; 95% CI, 0.2-1.1). Cancer, recent bleeding, antithrombotic prophylaxis and antiplatelet therapy were independently associated with clinically relevant bleeding at 3 months. Conclusions Decisions regarding the use of thromboprophylaxis in palliative care patients should take into account the high risk of bleeding in these patients.
Subject(s)
Hemorrhage , Neoplasms/complications , Neoplasms/therapy , Palliative Care , Venous Thrombosis/complications , Venous Thrombosis/prevention & control , Aged , Anticoagulants/therapeutic use , Female , France , Heparin, Low-Molecular-Weight/therapeutic use , Hospitalization , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasms/pathology , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/therapeutic use , Prospective Studies , Risk Factors , Severity of Illness Index , Terminally Ill , Treatment OutcomeABSTRACT
Product detection studies of C(3P) atom reactions with butene (C4H8) isomers (but-1-ene, cis-but-2-ene, trans-but-2-ene) are carried out in a flow tube reactor at 353 K and 4 Torr under multiple collision conditions. Ground state carbon atoms are generated by 248 nm laser photolysis of tetrabromomethane, CBr4, in a buffer of helium. Thermalized reaction products are detected using synchrotron tunable VUV photoionization and time-of-flight mass spectrometry. The temporal profiles of the detected ions are used to discriminate products from side or secondary reactions. For the C(3P) + trans-but-2-ene and C(3P) + cis-but-2-ene reactions, various isomers of C4H5 and C5H7 are identified as reaction products formed via CH3 and H elimination. Assuming equal ionization cross sections for all C4H5 and C5H7 isomers, C4H5:C5H7 branching ratios of 0.63:1 and 0.60:1 are derived for the C(3P) + trans-but-2-ene and the C(3P) + cis-but-2-ene reactions, respectively. For the C(3P) + but-1-ene reaction, two reaction channels are observed: the H-elimination channel, leading to the formation of the ethylpropargyl isomer, and the C3H3 + C2H5 channel. Assuming equal ionization cross sections for ethylpropargyl and C3H3 radicals, a branching ratio of 1:0.95 for the C3H3 + C2H5 and H + ethylpropargyl channels is derived. The experimental results are compared to previous H atom branching ratios and used to propose the most likely mechanisms for the reaction of ground state carbon atoms with butene isomers.
ABSTRACT
We present a combined experimental and theoretical low temperature kinetic study of water cluster formation. Water cluster growth takes place in low temperature (23-69 K) supersonic flows. The observed kinetics of formation of water clusters are reproduced with a kinetic model based on theoretical predictions for the first steps of clusterization. The temperature- and pressure-dependent association and dissociation rate coefficients are predicted with an ab initio transition state theory based master equation approach over a wide range of temperatures (20-100 K) and pressures (10^{-6}-10 bar).
ABSTRACT
In 2018, it is expected that there will be a major revision of the International System of Units (SI) which will result in all of the seven base units being defined by fixing the values of certain atomic or fundamental constants. As part of this revision, the kelvin, unit of thermodynamic temperature, will be redefined by assigning a value to the Boltzmann constant k. This explicit-constant definition will define the kelvin in terms of the SI derived unit of energy, the joule. It is sufficiently wide to encompass any form of thermometry. The planned redefinition has motivated the creation of an extended mise en pratique ('practical realization') of the definition of the kelvin (MeP-K), which describes how the new definition can be put into practice. The MeP-K incorporates both of the defined International Temperature Scales (ITS-90 and PLTS-2000) in current use and approved primary-thermometry methods for determining thermodynamic temperature values. The MeP-K is a guide that provides or makes reference to the information needed to perform measurements of temperature in accord with the SI at the highest level. In this article, the background and the content of the extended second version of the MeP-K are presented.
ABSTRACT
BARD, the BioAssay Research Database (https://bard.nih.gov/) is a public database and suite of tools developed to provide access to bioassay data produced by the NIH Molecular Libraries Program (MLP). Data from 631 MLP projects were migrated to a new structured vocabulary designed to capture bioassay data in a formalized manner, with particular emphasis placed on the description of assay protocols. New data can be submitted to BARD with a user-friendly set of tools that assist in the creation of appropriately formatted datasets and assay definitions. Data published through the BARD application program interface (API) can be accessed by researchers using web-based query tools or a desktop client. Third-party developers wishing to create new tools can use the API to produce stand-alone tools or new plug-ins that can be integrated into BARD. The entire BARD suite of tools therefore supports three classes of researcher: those who wish to publish data, those who wish to mine data for testable hypotheses, and those in the developer community who wish to build tools that leverage this carefully curated chemical biology resource.
Subject(s)
Biological Assay , Databases, Factual , High-Throughput Screening Assays , Data Mining , Internet , Molecular Probes , SoftwareABSTRACT
The BIPM graphite calorimeter standard for absorbed dose to water has been used in conjunction with an ionization chamber of known volume and with Monte Carlo simulations of these arrangements to determine the value for Wair in (60)Co radiation and in accelerator photon beams up to 25 MV. The results show no evidence for a variation in Wair at the 0.2% level over this energy range. Taking the constancy of Wair as established, the best estimate is Wair = 34.03 eV with a standard uncertainty of 0.21%. Consistent with this analysis, and assuming the use of the grain density in evaluating the stopping power of graphite, is the value Ic = 81.1 eV for the mean excitation energy for graphite, with standard uncertainty 1.8 eV.
Subject(s)
Graphite , Photons/therapeutic use , Radiometry/instrumentation , Radiometry/standards , Calorimetry , Cobalt Radioisotopes/therapeutic use , Monte Carlo Method , Particle Accelerators , Reference Standards , Uncertainty , WaterABSTRACT
The structure and composition of the fouling deposits caused by pig slurry heated in a tubular heat exchanger were characterized to understand their formation and thus be able to minimize fouling and define effective routine cleaning methods. Two temperatures (55 °C and 80 °C) were investigated. Two types of fouling were identified: organic/mineral and biofilm. The first only formed at temperatures above 50 °C, often during the heating phase, and was the main problem encountered in treatments at 80 °C. Organic/mineral deposits formed a thin compact sub-layer and a thick porous top layer composed of 67-76% minerals, 9-15% proteins, 8-20% carbohydrates and 0-5% fats. Biofilms formed at temperatures between 25 °C and 70 °C in both the cooling and heating sections of the exchanger. This type of fouling predominated at temperatures below 55 °C. The biofilm covered a thin mineral base layer. Strongly acidic or alkaline washing cycle are recommended to clean Type I deposits, while in-line gas-rumbling is recommended for Type II fouling.