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حياة الحيوان
يعرف الكتاب متى ظهرت الثدييات على الأرض وما أنواع تضع بيوضا ولماذا نقول أن الشرغوف يتحول وما رخويات تعيش في قوقعة وسيعرف كيف يحفر الخلد نفقه وبماذا يبطن القندس قعر عشه وكم سنا يمكن للقرش أن يستهلك في حياته وماذا تطرح البومة الصماء بعد أن تأكل وما فراشة تتنكر في زي ورقة وماذا تشبه بقع النمر ولماذا تتألف الديدان اللامعة وهذا قليل مما سيتعرف إليه الصغار عن عالم الحيوان من خلال هذا الكتاب الذي يوقظ بمعلوماته حس المعرفة في الصغير.
BOOK
Impact of variants of concern on SARS-CoV-2 viral dynamics in non-human primates
The impact of variants of concern (VoC) on SARS-CoV-2 viral dynamics remains poorly understood and essentially relies on observational studies subject to various sorts of biases. In contrast, experimental models of infection constitute a powerful model to perform controlled comparisons of the viral dynamics observed with VoC and better quantify how VoC escape from the immune response. Here we used molecular and infectious viral load of 78 cynomolgus macaques to characterize in detail the effects of VoC on viral dynamics. We first developed a mathematical model that recapitulate the observed dynamics, and we found that the best model describing the data assumed a rapid antigen-dependent stimulation of the immune response leading to a rapid reduction of viral infectivity. When compared with the historical variant, all VoC except beta were associated with an escape from this immune response, and this effect was particularly sensitive for delta and omicron variant (p<10 −6 for both). Interestingly, delta variant was associated with a 1.8-fold increased viral production rate (p = 0.046), while conversely omicron variant was associated with a 14-fold reduction in viral production rate (p<10 −6 ). During a natural infection, our models predict that delta variant is associated with a higher peak viral RNA than omicron variant (7.6 log 10 copies/mL 95% CI 6.8–8 for delta; 5.6 log 10 copies/mL 95% CI 4.8–6.3 for omicron) while having similar peak infectious titers (3.7 log 10 PFU/mL 95% CI 2.4–4.6 for delta; 2.8 log 10 PFU/mL 95% CI 1.9–3.8 for omicron). These results provide a detailed picture of the effects of VoC on total and infectious viral load and may help understand some differences observed in the patterns of viral transmission of these viruses.
Journal Article
Breast milk protein content at week 3 after birth and neurodevelopmental outcome in preterm infants fed fortified breast milk
Background
Feeding supplemented mother milk during hospital stay improves neurodevelopment in preterm infants. Yet the composition of mother milk varies widely between subjects. The relationship between this variation and outcome is unknown.
Objective
To determine whether the protein content in native breast milk (BM) correlates with 2-year infant outcome.
Design
In a monocentric prospective observational study, LACTACOL, preterm infants born between 28 and 34 weeks of gestation, whose mothers decided to exclusively breastfeed, were enrolled during the first week of life. Samples of expressed breast milk obtained at several times of the day were pooled over a 24-h period, and such pool was used for macronutrient analysis, using mid-infrared analyzer. Age and Stages questionnaire (ASQ) was used to assess 2-year neurodevelopmental outcome. We analyzed the relationship between protein content in BM, and (i) infant neurodevelopment at 2-year (primary outcome), and (ii) growth until 2-year (secondary outcome).
Results
138 infants were enrolled. The main analysis concerned 130 infants (including 40 twin infants) and 110 mothers with BM samples collected at week 3 after birth. Native BM samples were ranked in three tertiles of protein content (g/100 ml): 0.91 ± 0.09 (lower), 1.14 ± 0.05 (middle) and 1.40 ± 0.15 (upper); 48, 47 and 35 infants were ranked, respectively, in these three tertiles. Infants in the upper tertile were more often singleton (
P
= 0.012) and were born with lower birth weight and head circumference Z-scores (
P
= 0.005 and 0.002, respectively). Differences in weight and head circumference were no longer observed at 2-year. ASQ score at age 2 did not differ between the three tertiles (
P
= 0.780). Sensitivity analyses with imputations, including all 138 infants, confirmed the main analysis as well as analyses based on fortified BM as exposure.
Conclusions
Protein content of BM (native or fortified) is not associated with preterm infant neurodevelopment at 2-year. Higher protein content was associated with a lower birth weight.
Journal Article
Breast Milk Lipidome Is Associated with Early Growth Trajectory in Preterm Infants
Human milk is recommended for feeding preterm infants. The current pilot study aims to determine whether breast-milk lipidome had any impact on the early growth-pattern of preterm infants fed their own mother’s milk. A prospective-monocentric-observational birth-cohort was established, enrolling 138 preterm infants, who received their own mother’s breast-milk throughout hospital stay. All infants were ranked according to the change in weight Z-score between birth and hospital discharge. Then, we selected infants who experienced “slower” (n = 15, −1.54 ± 0.42 Z-score) or “faster” (n = 11, −0.48 ± 0.19 Z-score) growth; as expected, although groups did not differ regarding gestational age, birth weight Z-score was lower in the “faster-growth” group (0.56 ± 0.72 vs. −1.59 ± 0.96). Liquid chromatography–mass spectrometry lipidomic signatures combined with multivariate analyses made it possible to identify breast-milk lipid species that allowed clear-cut discrimination between groups. Validation of the selected biomarkers was performed using multidimensional statistical, false-discovery-rate and ROC (Receiver Operating Characteristic) tools. Breast-milk associated with faster growth contained more medium-chain saturated fatty acid and sphingomyelin, dihomo-γ-linolenic acid (DGLA)-containing phosphethanolamine, and less oleic acid-containing triglyceride and DGLA-oxylipin. The ability of such biomarkers to predict early-growth was validated in presence of confounding clinical factors but remains to be ascertained in larger cohort studies.
Journal Article
Atezolizumab and paclitaxel as first line therapy in advanced triple-negative breast cancer patients included in the French early access program
Following the results of the IMpassion130 trial, an early access program (EAP) was opened in France, allowing patients with PD-L1-positive advanced triple negative breast cancer (aTNBC) to receive a combination of paclitaxel and atezolizumab as first line therapy. This EAP was later discontinued when the IMpassion131 trial read out with negative results. We performed a retrospective multicentric analysis in patients who were prospectively enrolled in the French EAP. Efficacy and toxicity data were obtained on 64 patients treated from August 2019 to August 2020 in 10 French cancer centers. Median progression-free survival (PFS) and overall survival (OS) were 4.1 months (95% CI [3.0–5.8]) and 17.9 months (95% CI [12.4–NR]), respectively. The 6-months PFS rate was 28% (95% CI [16–40%]) (N = 18/64), while N = 33/64 patients (52%, 95% CI [38–63%]) experienced a tumor response. Exploratory subgroup analyses retrieved that corticosteroid use at inclusion in the EAP, before treatment initiation, was the only independent unfavorable prognostic factor for PFS (HR 2.7, 95% CI [1.3–5.6]). No new safety signal was observed. This real-life study, unique by its setting (EAP granted by anticipation and later withdrawn), suggests atezolizumab and paclitaxel has a limited efficacy in PD-L1-positive aTNBC, especially in patients receiving corticosteroids as comedication before treatment start.
Journal Article
Can we trust untargeted metabolomics? Results of the metabo-ring initiative, a large-scale, multi-instrument inter-laboratory study
The metabo-ring initiative brought together five nuclear magnetic resonance instruments (NMR) and 11 different mass spectrometers with the objective of assessing the reliability of untargeted metabolomics approaches in obtaining comparable metabolomics profiles. This was estimated by measuring the proportion of common spectral information extracted from the different LCMS and NMR platforms. Biological samples obtained from 2 different conditions were analysed by the partners using their own in-house protocols. Test #1 examined urine samples from adult volunteers either spiked or not spiked with 32 metabolite standards. Test #2 involved a low biological contrast situation comparing the plasma of rats fed a diet either supplemented or not with vitamin D. The spectral information from each instrument was assembled into separate statistical blocks. Correlations between blocks (e.g., instruments) were examined (RV coefficients) along with the structure of the common spectral information (common components and specific weights analysis). In addition, in Test #1, an outlier individual was blindly introduced, and its identification by the various platforms was evaluated. Despite large differences in the number of spectral features produced after post-processing and the heterogeneity of the analytical conditions and the data treatment, the spectral information both within (NMR and LCMS) and across methods (NMR vs. LCMS) was highly convergent (from 64 to 91 % on average). No effect of the LCMS instrumentation (TOF, QTOF, LTQ-Orbitrap) was noted. The outlier individual was best detected and characterised by LCMS instruments. In conclusion, untargeted metabolomics analyses report consistent information within and across instruments of various technologies, even without prior standardisation.
Journal Article
Effect of the time of day for vaccination on the immune response to Ebola Virus Disease vaccines: A modeling study from PREVAC randomized trial
Emerging evidence suggests that the time in the day of vaccination may influence post-vaccination immunogenicity. The main objective of this study was to assess the association between the time of vaccination and the anti-EBOV GP1,2 IgG antibody response at 12 mo following vaccination against Ebola virus disease (EVD).
This study utilized data from a randomized, double-blind, placebo-controlled international phase 2b clinical trial (PREVAC) evaluating the immunogenicity of three vaccination strategies against Ebola virus disease (rVSVΔG-ZEBOV-GP one and two doses, and Ad26.ZEBOV/MVA-BN-Filo) in 1,859 healthy Western Africans. In the overall population, we measured a statistically significant association between the time of day of first vaccination and anti-Ebola virus immunoglobulin G levels at 12 mo (p = 0.02). The magnitude of this association was small, participants vaccinated at 1600 h were estimated to have 1-7% lower antibody levels at 12 mo compared to those vaccinated at 1000 h.
An effect of the time of first vaccination on the antibody responses was found but remains modest and unlikely to impact the EVD vaccine effectiveness.
ClinicalTrials.gov registration: NCT02876328.
Journal Article