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Quantitative sensory testing of pain in osteoporosis: a pilot randomized clinical trial with magnesium supplementation
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A nationwide 12‐month observatory of automated insulin delivery shows improved glucose control, sustained adoption, and reduced acute severe events
No full textInternational audienceAims: A nationwide observational study was conducted to assess the 12-month effectiveness of AID systems in the routine care of people with Type 1 diabetes (PwT1D).Methods: All PwT1D, adults, and children, who initiated AID between January 1, 2022, and December 31, 2022, were included across 79 centres. Clinical data, continuous glucose monitoring (CGM) parameters, acute severe events in the last year, and HbA1c levels were collected at AID initiation, and after 3, 6, and 12 months of AID treatment. Median values [interquartile range, IQR] and % PwT1D with acute severe events were reported. The primary outcome was the change in time in range (TIR; 3.9-10 mmol/L) after 1 year with AID.Results: A total of 2741 PwT1D were included: 44.4% male, age 38 years [29], BMI 24.5 kg/m2 [6.7], diabetes duration 19 years [20]. AID systems were MiniMed 780G in 49.7%, Tandem Control-IQ in 49.3%, others in 1%. After 12 months, TIR increased from 58.0 [21] to 70.1% [14] while HbA1c levels decreased from 7.6 [1.2] to 7.0% [0.8]. Percent PwT1D experiencing severe hypoglycaemia (SH) decreased from 4.1 to 0.9%, and ketoacidosis from 1.2 to 0.6%. All improvements were observed after 3 months, sustained through 12 months, and statistically significant (p < 0.05). Only 2.8% of PwT1D discontinued AID.Conclusions: Twelve months of AID use in routine care improved glucose control in PwT1D, among whom there was less experienced SH and a minor discontinuation
Impact of yeast cell wall incorporation on the mucoadhesion, stability, oral permeability and release profile of alginate/whey protein beads loaded with insulin
No full textInternational audienceThis study aimed to evaluate the impact of incorporating yeast cell wall (YCW) into alginate/whey protein (ALG/WP) particles as a strategy to improve oral insulin delivery. Insulin-loaded particles were produced by an extrusion–gelation process with or without YCW, and their physicochemical, mucoadhesive, and permeability properties were assessed in vitro, ex vivo, and in vivo. The inclusion of YCW increased the viscosity of the polymeric solution, resulting in more cohesive particles and a significant reduction in insulin loss during coating. Encapsulation efficiencies ranged from 65 to 99%. However, YCW did not significantly affect particle size or the release mechanism, which remained diffusion-controlled. Although YCW-containing beads exhibited enzyme inhibitory and mucoadhesive properties, insulin protection against enzymatic degradation was similar to that of control beads. YCW moderately enhanced insulin permeability in Caco-2 cell monolayers without cytotoxicity, consistent with a reversible reduction of transepithelial electrical resistance. This effect did not translate into a measurable increase in insulin absorption in ex vivo duodenum or in vivo duodenal administration, indicating that its contribution as an absorption enhancer is limited under physiologically complex conditions
Novel multi-level optimization-driven 2D/3D matching for reconstructing 3D fetal postures and motion from childbirth MRI during vaginal delivery
No full textInternational audienceBACKGROUND AND OBJECTIVE: The description of 3D fetal postures and movements during vaginal delivery is fundamental for a better understanding of the physiological delivery and the prediction of potential complications and related preventive actions. Recently, 2D dynamic MRI has been developed to characterize in vivo childbirth. However, only 2D information is available. The objective of the present study was to reconstruct the 3D fetal postures and movements from 2D dynamic MRI during vaginal delivery. METHODS: A multi-level optimization-driven 2D/3D matching procedure was developed and evaluated. Manual segmentation from 2D dynamic MRI was performed. A 3D generic fetal template model was used to match each segmented MRI slice. Fetal postures and associated motion trajectories were extracted and evaluated. RESULTS: Consistent results were obtained between the MRI images, segmented slices, and reconstructed 3D fetal postures. A maximum 36.20-degree head-neck extension angle was estimated. A range of torso-neck angles from 1.04 to -16.07 degrees was estimated during the vaginal delivery. CONCLUSIONS: We proposed a proof-of-concept study of a multi-level optimization-driven 2D/3D matching scheme to reconstruct 3D fetal postures and associated kinematic patterns from dynamic MRI data during vaginal delivery simulation. It is expected that this novel dataset will make a potential contribution to the future model development and evaluation of the childbirth process
Myostatin, activin-A and follistatin are produced by the tumor in head and neck cancer and likely contribute to sarcopenia: A case-control, cross-sectional exploratory study
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Seeing risk, seizing opportunity: How perceived political instability affects firm investment
No full textInternational audienceDoes firm managers’ perception of political instability influence firms’ investment decisions? Using a large firm-level survey data of over 147,000 firms operating in 153 countries, we find evidence that a higher perception of political instability is positively related to firms’ investments. This effect is observed both on the extensive margin (likelihood to invest) and intensive margin (amount invested) and for investment in both land and equipment. Perception of political instability also influence how firms finance their investments: firms hold more cash on hand and borrow more from banks when they perceive political instability to be high. We also document that this effect is only observable for small and medium enterprises and those operating in less democratic regimes. The actual level of political instability in a country, however, has no effect on firm investment. Our results are robust to a battery of sensitivity tests
Impact of ph1 and ph2 mutation on homoeologous recombination in wheat
No full textInternational audienceDiversification of the hexaploid (bread) wheat genetic pool using wild genetic Q11 resources relies on effective meiotic recombination (crossover) between wheatchromosomes and their counterparts from related species (homoeologues).However, crossover between homoeologues is normally suppressed by two major genes, ZIP4-5B (Ph1) and MSH7-3D (Ph2). We investigated the effect of introducing zip4-5B and/or msh7-3D mutations into interspecific hybrids derived from crosses between wheat and Aegilops variabilis. Single and double mutants were exploited in Chinese Spring (CS) and Cadenza (Cad) genetic backgrounds, as well as in a CS/Cad recombinant background. Meiotic cells at metaphase I were scored for univalents, bivalents, and multivalents, from which chiasma numbers were deduced. We demonstrated a non-cumulative effect ofsimultaneous zip4-5B and msh7-3D mutations on homoeologous recombination, as homoeologous crossovers reached a maximum when ZIP4-5B alone was mutated. We also showed that hybrids carrying both the zip4-5B and msh7-3D mutations in the same genetic background exhibited a higher recombination rate compared to a double mutant in the CS/Cad recombinant background. The progression of meiosis was also monitored in the various interspecific hybrids mutants, revealing clear disruptions. Thus, our studyprovides key insights for optimizing the introgression of beneficial alleles from wild relatives into elite wheat germplasm; first by demonstrating the efficiency of ZIP4-5B and MSH7-3D mutations independently and in combination and second by elucidating the influence of the genetic background in which these mutations are present in an interspecific hybrid context
Exploiter les motifs graduels pour améliorer l’explicabilité des modèles
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Understanding cultural persistence and change: A replication of Giuliano and Nunn (2021)
No full textInternational audienceGiuliano and Nunn (2021) provide econometric evidence that ancestral climatic variability reduces the current importance of tradition. We conduct a “deep reproduction”, comparing the precise descriptions of the individual‐level regressions in their article with the corresponding code. This analysis uncovers several major inconsistencies, also related to the code not included in their replication package. A published corrigendum addresses some inconsistencies we had also communicated to the Editor of REStud, but several remain, relating to a substantial portion of the observations. A realignment of the code with the text reveals a more nuanced relationship between ancestral climatic variability and tradition
Target trial emulation to replicate randomised clinical trials using registry data in multiple sclerosis
No full textInternational audienceBackground: Target trial emulation (TTE) offers a formal framework for causal inference using observational data, but its validity must be evaluated in each research domain by replicating randomised clinical trials (RCTs). We aimed to replicate eight RCTs evaluating the efficacy of disease-modifying therapies (DMTs) in multiple sclerosis (MS) using French registry data.Methods: This multicentre, retrospective, observational study was conducted using data extracted in December 2023 from the Observatoire Français de la Sclérose en Plaques (OFSEP) database. For each emulated trial, patients were included when they initiated one of the DMT evaluated in the corresponding RCT and met its inclusion criteria. Clinical outcomes were the annualised relapse rate and 3-month confirmed Expanded Disability Status Scale progression. Radiological outcomes were new/enlarged T2-lesions and new gadolinium-enhanced T1-lesions on a brain MRI. A targeted maximum likelihood estimator was used to estimate the treatment effect adjusted for confounding factors between groups and corrected for censoring and missing outcome assessment.Results: 14 111 patients were included in eight emulated trials: ASSESS (fingolimod vs glatiramer acetate), BEYOND (interferon beta vs glatiramer acetate), CONFIRM (dimethyl fumarate (DMF) vs glatiramer acetate), OPERA (ocrelizumab vs interferon beta), REGARD (interferon beta vs glatiramer acetate), RIFUND-MS (rituximab vs DMF), TENERE (teriflunomide vs interferon beta) and TRANSFORMS (fingolimod vs interferon beta). Treatment effects estimated in emulated trials were concordant with RCT findings in seven of eight trials for relapse rate, and in all six trials assessing disability progression. Radiological outcomes were more challenging to replicate; concordance was achieved in three of five trials for new T2-lesions, and one of four trials for new gadolinium-enhanced T1-lesions.Conclusion: The combined use of a TTE methodology and high-quality registry data is a valid tool to evaluate treatment effectiveness in MS