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1.
Hum Reprod ; 39(4): 770-778, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38420661

ABSTRACT

STUDY QUESTION: How do oocyte donors and recipients perceive the genetic link related to the transfer of nuclear DNA between donors and offspring? SUMMARY ANSWER: Whether they are donors or recipients, individuals attach great importance to the transmission of their genetic heritage, since 94.5% would opt for the pronuclear transfer method to preserve this genetic link in the context of oocyte donation. WHAT IS KNOWN ALREADY: Since 1983, the use of oocyte donation has increased worldwide. Performed in France since the late 1980s and initially offered to women with premature ovarian insufficiency, its indications have progressively expanded and now it is proposed in many indications to prevent the transmission of genetically inherited diseases. This has resulted in an increase in the waiting time for access to oocyte donation due to the difficulty in recruiting oocyte donors in French ART centres. Several articles have discussed how to fairly distribute donor oocytes to couples, but few have interviewed women in the general population to record their feelings about oocyte donation, as either the donor or recipient and the importance given to the genetic link between the oocyte donors and the children born. Mitochondrial replacement therapy (MRT) is a technique originally developed for women at risk of transmitting a mitochondrial DNA mutation. Recently, MRT has been considered for embryo arrest and oocyte rejuvenation as it could help females to reproduce with their own genetic material through the transfer of their oocyte nucleus into a healthy donor oocyte cytoplasm. STUDY DESIGN, SIZE, DURATION: We conducted an opinion survey from January 2021 to December 2021, during which 1956 women completed the questionnaire. Thirteen participants were excluded from the analysis due to incomplete responses to all the questions. Consequently, 1943 women were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: We specifically developed a questionnaire for this study, which was created and distributed using the Drag'n Survey® software. The questionnaire consisted of 21 items presented alongside a video created with whiteboard animation software. The aim was to analyse whether certain factors, such as age, education level, marital status, number of children, use of ART for pregnancy, video viewing, and knowledge about oocyte donation, were associated with feelings towards oocyte donation, by using a univariate conditional logistic regression model. This statistical method was also used to assess whether women would be more inclined to consider oocyte donation with the pronuclear transfer technique rather than the whole oocyte donation. All parameters found to be statistically significant in the univariate analysis were subsequently tested in a multivariate model using logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Most women were concerned about the biological genetic contribution of the donated oocyte (94.8%). The most common reason for a women's reluctance to donate their oocytes was their unwillingness to pass on their genetic material (33.3%). Nearly 70% of women who were initially hesitant to donate their oocytes indicated that they would reconsider their decision if the oocyte donation was conducted using donated cytoplasm and the pronuclear transfer technique. Concomitantly, >75% of the respondents mentioned that it would be easier to receive a cytoplasm donation. The largest proportion of the population surveyed (94.5%) expressed their support for its legalization. LIMITATIONS, REASONS FOR CAUTION: In this study, a substantial portion of the responses came from individuals with medical or paramedical backgrounds, potentially introducing a recruitment bias among potential donors. The rate of missing responses to the question regarding the desire to become an oocyte donor was 13.6%, while the question about becoming an oocyte cytoplasm donor had a missing response rate of 23%. These missing responses may introduce a bias in the interpretation of the data. WIDER IMPLICATIONS OF THE FINDINGS: This study was the first to demonstrate that, for the French population studied, the combination of oocyte cytoplasm donation with pronuclear transfer could offer a promising approach to enhance the acceptance of oocyte donation for both the donor and the recipient. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Mitochondrial Replacement Therapy , Oocyte Donation , Pregnancy , Child , Humans , Female , Tissue Donors , DNA , France , Retrospective Studies
2.
J Inherit Metab Dis ; 47(2): 244-254, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38185897

ABSTRACT

Off-label repurposing of empagliflozin allows pathomechanism-based treatment of neutropenia/neutrophil-dysfunction in glycogen storage disease type Ib (GSDIb). From a value-based healthcare (VBHC) perspective, we here retrospectively studied patient-reported, clinical and pharmacoeconomic outcomes in 11 GSDIb individuals before and under empagliflozin at two centers (the Netherlands [NL], Austria [AT]), including a budget impact analysis, sensitivity-analysis, and systematic benefit-risk assessment. Under empagliflozin, all GSDIb individuals reported improved quality-of-life-scores. Neutrophil dysfunction related symptoms allowed either granulocyte colony-stimulating factor cessation or tapering. Calculated cost savings per patient per year ranged between € 6482-14 190 (NL) and € 1281-41 231 (AT). The budget impact analysis estimated annual total cost savings ranging between € 75 062-225 716 (NL) and € 37 697-231 790 (AT), based on conservative assumptions. The systematic benefit-risk assessment was favorable. From a VBHC perspective, empagliflozin treatment in GSDIb improved personal and clinical outcomes while saving costs, thereby creating value at multiple pillars. We emphasize the importance to reimburse empagliflozin for GSDIb individuals, further supported by the favorable systematic benefit-risk assessment. These observations in similar directions in two countries/health care systems strongly suggest that our findings can be extrapolated to other geographical areas and health care systems.


Subject(s)
Benzhydryl Compounds , Glucosides , Glycogen Storage Disease Type I , Value-Based Health Care , Humans , Retrospective Studies , Risk Assessment
3.
Pharmaceuticals (Basel) ; 16(11)2023 Nov 08.
Article in English | MEDLINE | ID: mdl-38004440

ABSTRACT

Long-term usage of linezolid can result in adverse events such as peripheral neuropathy, anemia and thrombocytopenia. Therapeutic drug monitoring data from 75 drug-resistant tuberculosis patients treated with linezolid were analyzed using a time-to-event (TTE) approach for peripheral neuropathy and anemia and indirect response modelling for thrombocytopenia. Different time-varying linezolid pharmacokinetic exposure indices (AUC0-24h,ss, Cav, Cmax and Cmin) and patient characteristics were investigated as risk factors. A treatment duration shorter than 3 months was considered dropout and was modelled using a TTE approach. An exposure-response relationship between linezolid Cmin and both peripheral neuropathy and anemia was found. The exposure index which best described the development of thrombocytopenia was AUC0-24h. The final TTE dropout model indicated an association between linezolid Cmin and dropout. New safety targets for each adverse event were proposed which can be used for individualized linezolid dosing. According to the model predictions at 6 months of treatment, a Cmin of 0.11 mg/L and 1.4 mg/L should not be exceeded to keep the cumulative probability to develop anemia and peripheral neuropathy below 20%. The AUC0-24h should be below 111 h·mg/L or 270 h·mg/L to prevent thrombocytopenia and severe thrombocytopenia, respectively. A clinical utility assessment showed that the currently recommended dose of 600 mg once daily is safer compared to a 300 mg BID dosing strategy considering all four safety endpoints.

4.
Am J Primatol ; 85(2): e23463, 2023 02.
Article in English | MEDLINE | ID: mdl-36594448

ABSTRACT

The self-initiated split of a social group, known as fission, is a challenge faced by many group-living animals. The study of group fission and the social restructuring process in real time provides insights into the mechanism of this biologically important process. Previous studies on fission in Japanese macaques (Macaca fuscata) assigned individuals to newly reorganized groups mainly using behavioral observations and group attendance records based on periods before or after fission itself. Here, we present a novel framework for group classification during the process of fission that uses quantifiable behavioral variables and statistical analyses. The framework was tested on a group fission process at Affenberg Landskron (Austria), a park that housed around 160 semi-free-ranging Japanese macaques. The behavioral data were collected for 26 days during fission. We analyzed three behavioral developments recurrent in fissions in Japanese macaques, that is, independence of behavior, participation in group movements, and separation of nomadic ranges. These analyses were combined to assign individuals to different groups. Our study resulted in one main group (N = 33), one subgroup (N = 36) and 56 individuals whose group membership was still undefined. The demographic characteristics of these newly formed groups were comparable with those of fissioned groups in wild populations. Furthermore, we found that these newly forming groups showed early social dynamics of fission five months before group level movements, that is: grouping based on spatial proximity and spatial withdrawal of the subgroup to the periphery. These results underline the validity of our novel framework to study social dynamics in Japanese macaques during the process of fission. It represents an important addition to existing methods, and we recommend testing its scope in other primate societies.


Subject(s)
Macaca fuscata , Macaca , Animals , Social Dominance , Austria
5.
Mol Cell Pediatr ; 9(1): 20, 2022 Dec 21.
Article in English | MEDLINE | ID: mdl-36542240

ABSTRACT

Insulin is used to treat neonatal hyperglycaemia when blood glucose concentrations are consistently high, and to treat neonatal diabetes. Within this brief report, a review of the existing literature is conducted to determine if intravenous administration of insulin should be proceeded by priming of the intravenous system, adding of albumin, or non-priming to get a stable insulin dose. Within this literature search, we focused on experimental insulin adsorption data (in vitro studies).

7.
Antimicrob Agents Chemother ; 66(7): e0000322, 2022 07 19.
Article in English | MEDLINE | ID: mdl-35727060

ABSTRACT

Pyrazinamide is one of the first-line antituberculosis drugs. The efficacy of pyrazinamide is associated with the ratio of 24-h area under the concentration-time curve (AUC24) to MIC. The objective of this study was to develop and validate a limited sampling strategy (LSS) based on a population pharmacokinetic (popPK) model to predict AUC24. A popPK model was developed using an iterative two-stage Bayesian procedure and was externally validated. Using data from 20 treatment-naive adult tuberculosis (TB) patients, a one compartment model with transit absorption and first-order elimination best described pyrazinamide pharmacokinetics and fed state was the only significant covariate for absorption rate constant (ka). External validation, using data from 26 TB patients, showed that the popPK model predicted AUC24 with a slight underestimation of 2.1%. LSS were calculated using Monte Carlo simulation (n = 10,000). External validation showed LSS with time points 0 h, 2 h, and 6 h performed best with RMSE of 9.90% and bias of 0.06%. Food slowed absorption of pyrazinamide, but did not affect bioavailability, which may be advantageous in case of nausea or vomiting in which food can be used to diminish these effects. In this study, we successfully developed and validated a popPK model and LSS, using 0 h, 2 h, and 6 h postdose samples, that could be used to perform therapeutic drug monitoring (TDM) of pyrazinamide in TB patients.


Subject(s)
Pyrazinamide , Tuberculosis , Adult , Antitubercular Agents/pharmacokinetics , Antitubercular Agents/therapeutic use , Bayes Theorem , Drug Monitoring/methods , Humans , Pyrazinamide/pharmacokinetics , Pyrazinamide/therapeutic use , Tuberculosis/drug therapy
8.
Biomedicines ; 10(4)2022 Apr 13.
Article in English | MEDLINE | ID: mdl-35453646

ABSTRACT

Background: Presurgical treatment with an α-adrenergic receptor blocker is recommended to antagonize the catecholamine-induced α-adrenergic receptor mediated vasoconstriction in patients with pheochromocytoma or sympathetic paraganglioma (PPGL). There is, however, a considerable interindividual variation in the dose-response relationship regarding the magnitude of blood pressure reduction or the occurrence of side effects. We hypothesized that genetically determined differences in α-adrenergic receptor activity contribute to this variability in dose-response relationship. Methods: Thirty-one single-nucleotide polymorphisms (SNPs) of the α1A, α1B, α1D adrenoreceptor (ADRA1A, ADRA1B, ADRA1D) and α2A, α2B adrenoreceptor (ADRA2A, ADRA2B) genes were genotyped in a group of 116 participants of the PRESCRIPT study. Haplotypes were constructed after determining linkage disequilibrium blocks. Results: The ADRA1B SNP rs10515807 and the ADRA2A SNPs rs553668/rs521674 were associated with higher dosages of α-adrenergic receptor blocker (p < 0.05) and with a higher occurrence of side effects (rs10515807) (p = 0.005). Similar associations were found for haplotype block 6, which is predominantly defined by rs10515807. Conclusions: This study suggests that genetic variability of α-adrenergic receptor genes might be associated with the clinically observed variation in beneficial and adverse therapeutic drug responses to α-adrenergic receptor blockers. Further studies in larger cohorts are needed to confirm our observations.

9.
Pharmaceutics ; 14(4)2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35456587

ABSTRACT

Linezolid is an efficacious medication for the treatment of drug-resistant tuberculosis but has been associated with serious safety issues that can result in treatment interruption. The objectives of this study were thus to build a population pharmacokinetic model and to use the developed model to establish a model-informed precision dosing (MIPD) algorithm enabling safe and efficacious dosing in patients with multidrug- and extensively drug-resistant tuberculosis. Routine hospital therapeutic drug monitoring data, collected from 70 tuberculosis patients receiving linezolid, was used for model development. Efficacy and safety targets for MIPD were the ratio of unbound area under the concentration versus time curve between 0 and 24 h over minimal inhibitory concentration (fAUC0-24h/MIC) above 119 and unbound plasma trough concentration (fCmin) below 1.38 mg/L, respectively. Model building was performed in NONMEM 7.4.3. The final population pharmacokinetic model consisted of a one-compartment model with transit absorption and concentration- and time-dependent auto-inhibition of elimination. A flat dose of 600 mg once daily was appropriate in 67.2% of the simulated patients from an efficacy and safety perspective. Using the here developed MIPD algorithm, the proportion of patients reaching the efficacy and safety target increased to 81.5% and 88.2% using information from two and three pharmacokinetic sampling occasions, respectively. This work proposes an MIPD approach for linezolid and suggests using three sampling occasions to derive an individualized dose that results in adequate efficacy and fewer safety concerns compared to flat dosing.

10.
Antimicrob Agents Chemother ; 66(2): e0182921, 2022 02 15.
Article in English | MEDLINE | ID: mdl-34807758

ABSTRACT

Moxifloxacin is an attractive drug for the treatment of isoniazid-resistant rifampicin-susceptible tuberculosis (TB) or drug-susceptible TB complicated by isoniazid intolerance. However, co-administration with rifampicin decreases moxifloxacin exposure. It remains unclear whether this drug-drug interaction has clinical implications. This retrospective study in a Dutch TB center investigated how rifampicin affected moxifloxacin exposure in patients with isoniazid-resistant or -intolerant TB. Moxifloxacin exposures were measured between 2015 and 2020 in 31 patients with isoniazid-resistant or -intolerant TB receiving rifampicin, and 20 TB patients receiving moxifloxacin without rifampicin. Moxifloxacin exposure, i.e., area under the concentration-time curve (AUC0-24h), and attainment of AUC0-24h/MIC > 100 were investigated for 400 mg moxifloxacin and 600 mg rifampicin, and increased doses of moxifloxacin (600 mg) or rifampicin (900 mg). Moxifloxacin AUC0-24h and peak concentration with a 400 mg dose were decreased when rifampicin was co-administered compared to moxifloxacin alone (ratio of geometric means 0.61 (90% CI (0.53, 0.70) and 0.81 (90% CI (0.70, 0.94), respectively). Among patients receiving rifampicin, 65% attained an AUC0-24h/MIC > 100 for moxifloxacin compared to 78% of patients receiving moxifloxacin alone; this difference was not significant. Seven out of eight patients receiving an increased dose of 600 mg moxifloxacin reached the target AUC0-24h/MIC > 100. This study showed a clinically significant 39% decrease in moxifloxacin exposure when rifampicin was co-administered. Moxifloxacin dose adjustment may compensate for this drug-drug interaction. Further exploring the impact of higher doses of these drugs in patients with isoniazid resistance or intolerance is paramount.


Subject(s)
Rifampin , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/therapeutic use , Humans , Isoniazid/therapeutic use , Moxifloxacin/therapeutic use , Retrospective Studies , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy
11.
Animals (Basel) ; 11(6)2021 May 21.
Article in English | MEDLINE | ID: mdl-34064235

ABSTRACT

Cooperation occurs amongst individuals embedded in a social environment. Consequently, cooperative interactions involve a variety of persistent social influences such as the dynamics of partner choice and reward division. To test for the effects of such dynamics, we conducted cooperation experiments in a captive population of Japanese macaques (Macaca fuscata, N = 164) using a modified version of the loose-string paradigm in an open-experiment design. We show that in addition to becoming more proficient cooperators over the course of the experiments, some of the macaques showed sensitivity to the presence of potential partners and adjusted their behavior accordingly. Furthermore, following an unequal reward division, individuals receiving a lesser reward were more likely to display aggressive and stress-related behaviors. Our experiments demonstrate that Japanese macaques have some understanding of the contingencies involved in cooperation as well as a sensitivity to the subsequent reward division suggestive of an aversion to inequity.

12.
Rheumatol Int ; 41(5): 879-885, 2021 05.
Article in English | MEDLINE | ID: mdl-33433729

ABSTRACT

Physicians are sometimes hesitant to use disease-modifying antirheumatic drugs (DMARDs) in elderly patients with rheumatoid arthritis (RA), as they are deemed too fragile, although there are no sufficient scientific evidence. We aimed to compare DMARD treatment retention in early RA patients from the ESPOIR cohort, according to age upon inclusion. Overall, treatment retention was evaluated as the percentage of patients whose DMARDs were not stopped, with stratification by age group: < 50, 50-64, and > 65 years. Survival curves were measured using the Kaplan-Meier method. Of the entire ESPOIR cohort (n = 813), 7% were > 65 years old. Methotrexate (MTX) was used by 521 patients, and was the sole DMARD for 198 patients. MTX treatment retention appeared better in patients > 65 years old compared to < 50 years old [HR 0.45 (0.25; 0.81); p = 0.008, n = 195/198] with adjustment on sex, smoking, positive anti-cyclic citrullinated peptide antibodies, positive rheumatoid factor, body mass index, changes in DAS28 and corticosteroid treatment. The proportion of patients using etanercept (n = 111), and this drug's retention rate, did not differ according to patient age. The proportion of patients treated with adalimumab (n = 104) was significantly higher in patients < 50 years old (p = 0.003), and treatment retention was marginally better among younger patients [HR 1.68 (0.88; 3.22), p = 0.12]. Within the ESPOIR cohort, DMARD retention did not appear to differ according to age-except for better retention of MTX treatment in patients 50-64 years old, and of adalimumab in patients < 50 years old.


Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Adult , Age Distribution , Aged , Antirheumatic Agents/adverse effects , Biological Products/administration & dosage , Biological Products/adverse effects , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Longitudinal Studies , Male , Middle Aged , Practice Patterns, Physicians'/statistics & numerical data
13.
Article in English | MEDLINE | ID: mdl-33385770

ABSTRACT

For the quantification of the sedative and anesthetic drug midazolam and its main (active) metabolites 1-hydroxymidazolam, 4-hydroxymidazolam and 1-hydroxymidazolam glucuronide in human serum, human EDTA plasma, human heparin plasma and human urine a single accurate method by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed. Protein precipitation as sample preparation, without the need of a time-consuming deglucuronidation step for the quantification of 1-hydroxymidazolam glucuronide, resulted in a simple and rapid assay suitable for clinical practice with a total runtime of only 1.1  min. The four components and the isotope-labeled internal standards were separated on a C18 column and detection was performed with a triple-stage quadrupole mass spectrometer operating in positive ionization mode. The method was validated based on the "Guidance for Industry Bioanalytical Method Validation" (Food and Drug Administration, FDA) and the "Guideline on bioanalytical method validation" of the European Medicines Agency (EMA). Linearity was proven over the ranges of 5-1500 µg/L for midazolam, 1-hydroxymidazolam and 4-hydroxymidazolam and 25-5000 µg/L for 1-hydroxymidazolam glucuronide, using a sample volume of 100 µL. Matrix comparison indicated that the assay is also applicable to other human matrices like EDTA and heparin plasma and urine. Stability experiments showed good results for the stability of midazolam, 1-hydroxymidazolam and 1-hydroxymidazolam glucuronide in serum, EDTA and heparin plasma and urine stored for 7 days under different conditions. At room temperature, 4-hydroxymidazo-lam is stable for 7 days in EDTA plasma, but stable for only 3 days in serum and heparin plasma and less than 24 h in urine. All four compounds were found to be stable in serum, EDTA plasma, heparin plasma and urine for 7 days after sample preparation and for 3 freeze-thaw cycles. The assay has been applied in therapeutic drug monitoring of midazolam for (pediatric) intensive care patients.


Subject(s)
Chromatography, High Pressure Liquid/methods , Midazolam , Tandem Mass Spectrometry/methods , Aged , Drug Stability , Female , Humans , Infant, Newborn , Limit of Detection , Linear Models , Midazolam/analogs & derivatives , Midazolam/blood , Midazolam/pharmacokinetics , Midazolam/urine , Reproducibility of Results
14.
BMJ Open ; 11(12): e049777, 2021 12 30.
Article in English | MEDLINE | ID: mdl-35344503

ABSTRACT

OBJECTIVES: Malnutrition is associated with a twofold higher risk of dying in patients with tuberculosis (TB) and considered an important potentially reversible risk factor for failure of TB treatment. The construct of malnutrition has three domains: intake or uptake of nutrition; body composition and physical and cognitive function. The objectives of this systematic review are to identify malnutrition assessment methods, and to quantify how malnutrition assessment methods capture the international consensus definition for malnutrition, in patients with TB. DESIGN: Different assessment methods were identified. We determined the extent of capturing of the three domains of malnutrition, that is, intake or uptake of nutrition, body composition and physical and cognitive function. RESULTS: Seventeen malnutrition assessment methods were identified in 69 included studies. In 53/69 (77%) of studies, body mass index was used as the only malnutrition assessment method. Three out of 69 studies (4%) used a method that captured all three domains of malnutrition. CONCLUSIONS: Our study focused on published articles. Implementation of new criteria takes time, which may take longer than the period covered by this review. Most patients with TB are assessed for only one aspect of the conceptual definition of malnutrition. The use of international consensus criteria is recommended to establish uniform diagnostics and treatment of malnutrition. PROSPERO REGISTRATION NUMBER: CRD42019122832.


Subject(s)
Malnutrition , Tuberculosis , Adult , Body Mass Index , Humans , Malnutrition/diagnosis , Malnutrition/etiology , Nutrition Assessment , Nutritional Status , Tuberculosis/complications , Tuberculosis/diagnosis
15.
Br J Dermatol ; 185(2): 405-411, 2021 08.
Article in English | MEDLINE | ID: mdl-33314029

ABSTRACT

BACKGROUND: Clinical and histological diagnosis of Sézary syndrome (SS) and mycosis fungoides (MF) is challenging in clinical routine. OBJECTIVES: We investigated five blood markers previously described for SS (T-plastin, Twist, KIR3DL2, NKp46 and Tox) in a prospective validation cohort of patients. METHODS: We included 447 patients in this study and 107 patients were followed up for prognosis. The markers were analysed by reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) on peripheral blood leucocytes and CD4+ T cells in a cohort of consecutive patients with early MF, erythrodermic MF and SS and compared with patients presenting with benign inflammatory dermatoses (BID) and erythrodermic BID. The markers were assessed in parallel to gold standard values such as CD4/CD8 ratio, loss of CD7 and CD26 membrane expression and CD4 absolute values. Sensitivity and specificity were analysed by receiver operator characteristic curves. The prognostic value of selected markers was analysed on a subset of patients. This study was conducted in one centre. RESULTS: We defined cut-off values for each marker. T-plastin, Twist and KIR3DL2 had the best validity. SS may be overrepresented. The combination of T-plastin and Twist was able to differentiate between erythrodermic MF or BID and SS. The additional analysis of KIR3DL2 may be useful to predict the prognosis. CONCLUSIONS: We propose T-plastin, Twist and KIR3DL2 measured by RT-qPCR as new diagnostic markers for Sézary syndrome.


Subject(s)
Mycosis Fungoides , Sezary Syndrome , Skin Neoplasms , Biomarkers , Humans , Mycosis Fungoides/diagnosis , Prognosis , Sezary Syndrome/diagnosis , Skin Neoplasms/diagnosis
16.
J Microsc ; 282(1): 45-59, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33216353

ABSTRACT

A new high-temperature detector dedicated to the collection of backscattered electrons is used in combination with heating stages up to 1050°C, in high-vacuum and low-vacuum modes in order to evaluate its possibilities through signal-to-noise ration measurements and different applications. Four examples of material transformations occurring at high temperature are herein reported: grain growth during annealing of a rolled platinum foil, recrystallisation of a multiphased alloy, oxidation of a Ni-based alloy and complex phase transformations occurring during the annealing of an Al-Si coated boron steel. The detector could be potentially adapted to any type of SEM and it offers good opportunities to perform high-temperature experiments in various atmospheres.

17.
Rheumatology (Oxford) ; 60(2): 549-556, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33159797

ABSTRACT

OBJECTIVES: Despite classic analgesic or effective treatments in rheumatic diseases, such as synthetic DMARDs in RA, patients remain in pain and often turn to non-prescribed pharmacological alternatives, such as cannabis self-therapeutic use. However, this medical use of cannabis has not been thoroughly studied. METHODS: We performed a systematic literature review up to June 2020. The incidence of cannabis consumption was calculated by metaproportion. Differences between cannabis users and non-users were expressed as standardized mean differences using the inverse-variance method. We also assessed the effects of cannabis on pain. RESULTS: A total of 2900 patients reported cannabis consumption in a sample of 10 873 patients [incidence 40.4% (95% confidence interval (CI): 0.28, 0.54)], and 15.3% (95% CI: 0.07, 0.27) specified that they were currently taking cannabis. Cannabis use was higher in the four fibromyalgia studies [68.2% (95% CI: 0.41, 0.90), n = 611] compared with seven articles concerning RA or lupus [26.0% (95% CI: 0.14, 0.41), n = 8168]. Cannabis consumption was associated with a decrease in pain intensity [VAS pain at baseline 8.2 (2.9) vs 5.6 (3.5) mm over time; pooled effect size -1.75 (95% CI: -2.75, -0.76)]. Cannabis users were younger [58.4 (11.4) vs 63.6 (12.1) years; P <0.001], more often smokers [OR 2.91 (95% CI: 1.84, 4.60)] or unemployed [OR 2.40 (95% CI: 1.31, 4.40)], and had higher pain intensity [5.0 (2.4) vs 4.1(2.6) mm; P <0.001] than non-users. CONCLUSION: Nearly 20% of patients suffering from rheumatologic diseases actively consume cannabis, with an improvement in pain. The issue of cannabis use in the management of these patients should be addressed during medical consultation, essentially with cannabis-based standardized pharmaceutical products.


Subject(s)
Medical Marijuana/therapeutic use , Pain Management/methods , Pain/drug therapy , Rheumatic Diseases/complications , Humans , Pain/etiology , Rheumatic Diseases/therapy , Treatment Outcome
20.
Nat Nanotechnol ; 15(5): 348-355, 2020 05.
Article in English | MEDLINE | ID: mdl-32367078

ABSTRACT

The advancement of additional methods for freshwater generation is imperative to effectively address the global water shortage crisis. In this regard, extraction of the ubiquitous atmospheric moisture is a powerful strategy allowing for decentralized access to potable water. The energy requirements as well as the temporal and spatial restrictions of this approach can be substantially reduced if an appropriate sorbent is integrated in the atmospheric water generator. Recently, metal-organic frameworks (MOFs) have been successfully employed as sorbents to harvest water from air, making atmospheric water generation viable even in desert environments. Herein, the latest progress in the development of MOFs capable of extracting water from air and the design of atmospheric water harvesters deploying such MOFs are reviewed. Furthermore, future directions for this emerging field, encompassing both material and device improvements, are outlined.


Subject(s)
Atmosphere/chemistry , Humidity , Metal-Organic Frameworks/chemistry , Water Supply , Water/chemistry , Adsorption , Models, Molecular
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