Variation in Size and Growth of the Great Scallop Pecten maximus along a Latitudinal Gradient

Understanding the relationship between growth and temperature will aid in the evaluation of thermal stress and threats to ectotherms in the context of anticipated climate changes. Most Pecten maximus scallops living at high latitudes in the northern hemisphere have a larger maximum body size than individuals further south, a common pattern among many ectotherms. We investigated differences in daily shell growth among scallop populations along the Northeast Atlantic coast from Spain to Norway. This study design allowed us to address precisely whether the asymptotic size observed along a latitudinal gradient, mainly defined by a temperature gradient, results from differences in annual or daily growth rates, or a difference in the length of the growing season. We found that low annual growth rates in northern populations are not due to low daily growth values, but to the smaller number of days available each year to achieve growth compared to the south. We documented a decrease in the annual number of growth days with age regardless of latitude. However, despite initially lower annual growth performances in terms of growing season length and growth rate, differences in asymptotic size as a function of latitude resulted from persistent annual growth performances in the north and sharp declines in the south. Our measurements of daily growth rates throughout life in a long-lived ectothermic species provide new insight into spatio-temporal variations in growth dynamics and growing season length that cannot be accounted for by classical growth models that only address asymptotic size and annual growth rate

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Accuracy of thyroid uptake calibration method: a multi-centric study with realistic phantoms.

International audienceAim/Introduction: measurement of the thyroid uptake is of interest in diagnostic and for treatment of benign thyroid disease. The sensitivity obtained from measurement in air or in a standard neck phantom does not take into account the real thyroid anatomy. The goal of this multi-centric study was to assess the accuracy of thyroid uptake measurement using a set of realistic thyroid phantoms of varying size. These measurements were carried-out according to the site-specific local procedure (Local) and according to a standardized protocol (Std). In this preliminary report sensitivities obtained with routine calibration objects were compared with those obtained with the set of phantoms, for both protocols. Material and methods: measurements were carried-out from October 2020 to June 2021 on 20 NaI gamma-cameras and 3 CZT cameras with parallel and pinhole collimators. Radionuclides were Tc-99m and I-123. Five thyroid phantoms between 3 and 30 mL were used. Images were centrally analyzed, a 3DSlicer module has been developed for automatic segmentation and calculation of the sensitivity. The mean sensitivity over five thyroid volumes was compared with the routine calibration factor (Srout) and with the sensitivity in air, obtained with a unique syringue (Sair). The three sensitivities were measured for both protocols. Results: 25 configurations have been analyzed (58% of final set). For pinhole Tc-99m measurements, the mean sensitivities Sair were 101 ±45 counts/MBq/s (Std, n=7) and 148 ±91 counts/MBq/s (Local, n=7). The difference being mainly due to different measurement distances in the protocols.For I-123 measurements with parallel collimators, the mean sensitivities Sair were 73 ±13 counts/MBq/s (Std, n=10) and 72 ±14 counts/MBq/s (Local, n=9). Sair was almost independent of radionuclides and protocol. For pinhole collimator the sensitivity decreased when the thyroid volume increased, whatever the radionuclide and protocol. For the 30 mL phantom, on mean, the sensitivity was 12% lower than . Considering the local protocol and both radionuclides the relative difference between Srout and was greater than 15% in 43% of the cases. The standard protocol did not reduce this difference. For parallel collimators the difference between Srout and was always less than 17%, almost independently of the protocol, radionuclide and parallel collimator model. Conclusion: with parallel collimators, the sensitivity was relatively independent of the thyroid volume and the routine calibration was suitable for thyroid uptake estimation. For pinhole collimators the calibration was strongly influenced by the volume and quantitative measurement were of limited accuracy

Spatial modelling of plant diversity from high-throughput environmental dna sequence data

National audienceThis paper considers a statistical modelling approach to investigate spatial cross-correlations between species in an ecosystem. A special feature is the origin of the data from high-troughput environmental DNA sequencing of soil samples. Here we use data collected at the Nourague CNRS Field Station in French Guiana. We describe bivariate spatial relationships in these data by a separable linear model of coregionalisation and estimate a cross-correlation parameter. Based on this estimate, we visualise plant taxa co-occurrence pattern in form of 'interaction graphs' which can be interpreted in terms of ecological interactions. Limitations of this approach are discussed along with possible alternatives.Cet article présente une approche statistique pour modéliser les corrélations spatiales entre espèces dans un écosystème. L'originalité réside dans la particularité des données, génerées par des séquençages à haut-débit de l'ADN environnemental d' echantillons de sol. Les données utilisées dans cet étude étaient recueillies à la station biologique CNRS des Nouragues, en Guyane Française. L' étude décrit les relations spatiales bivariées de ces données par un modèle linéaire de co-régionalisation séparable où l'on estime un paramètre de cross-corrélation. Sur la base de cette estimation, nous visualisons le modèle de co-occurrences sous forme de graphes d'interactions. Les limites de cette approche sont discutées ainsi que les alternatives possibles

Développement d’un protocole d’étalonnage prenant en compte le volume thyroïdien pour l’amélioration du traitement des pathologies bénignes de la thyroïde

International audienceIntroduction. D’après les recommandations de l'EANM dédiées au traitement des maladies bénignes de la thyroïde, la dose absorbée doit être personnalisée en prenant en compte la variabilité de chaque individu. Par conséquent, le taux de captation en iode de la thyroïde doit être mesuré avec précision grâce à une sonde thyroïdienne ou une gamma-caméra. L’étalonnage de ces systèmes de mesure est aujourd’hui réalisé avec des fantômes éloignés de la réalité anatomique. Afin d’évaluer individuellement la fixation thyroïdienne, il est donc important de personnaliser l’étalonnage des systèmes. Dans ce contexte, un ensemble de fantômes thyroïdiens réalistes de volumes variables (3,24-30 cm3), appelé FANTHY, représentant des patients pédiatriques et adultes a été développé et imprimé en 3D (Figure 1), afin d’étudier l’impact de la procédure d’étalonnage utilisée en routine lors de la quantification de l’activité. De plus, une nouvelle méthode d’analyse a été développé afin d’améliorer la quantification de l’activité et pallier l’hétérogénéité des pratiques.Matériel et méthode. Pour les mesures, les fantômes thyroïdiens ont été remplis d’une solution radioactive d’123I ou d’131I. L'étude multicentrique a été réalisée avec 4 caméras gamma dans 3 services de médecine nucléaire français. Pour les mesures à l’123I, les caméras Siemens Symbia T2 et S équipées de collimateurs de basse énergie (LEHR) ont été utilisées. Les mesures à l’131I ont été réalisées avec la gamma-caméra Siemens Symbia T2 et la GE Discovery NMCT670 dotées de collimateurs de haute énergie (HE). Les fantômes ont été imagés à trois distances table-collimateur (10, 20 et 30 cm), afin d’étudier les limites du processus d’étalonnage utilisé en routine dans chaque service. Ces acquisitions ont également permis d’étudier l’influence de la distance et du volume thyroïdien sur la sensibilité. Afin de pallier la grande variabilité de fantômes et de protocoles utilisés pour l’étalonnage et la mesure de fixation thyroïdienne, une méthode de seuillage a été développée. Cette méthode d’analyse a la particularité d’être adaptée et adaptable à la routine clinique.Résultats. La procédure d’étalonnage utilisée en routine sous-estime l’activité retenue dans la thyroïde par rapport à un étalonnage avec des fantômes réalistes. Plus précisément pour l’123I, la différence de sensibilité était comprise entre +5% et -21%, selon la distance, le volume thyroïdien et la gamma-caméra utilisés. La méthode d’analyse retenue permet d’obtenir un seuil, et donc un coefficient d’étalonnage, dépendant de la distance de mesure mais pas du volume thyroïdien ni du type de fantôme utilisé. Ce traitement d’image permet de quantifier l’activité avec une incertitude réduite à 7% pour l’123I. Contrairement à certaines affirmations de la littérature, les mesures montrent un impact limité (<6%) du volume thyroïdien sur l’évaluation de la fixation thyroïdienne.Conclusion. Dans les pratiques cliniques actuelles, la fixation thyroïdienne est souvent sous-estimée. En utilisant le nouveau protocole d’étalonnage, basé sur les fantômes thyroïdiens réalistes, l'activité thérapeutique injectée au patient pourrait être réduite, dans certain cas, d’au moins 30% sans impacter l’efficacité du traitement. Un traitement des images, adapté à la routine clinique, pourrait également améliorer l'étalonnage des gamma-caméras. Les données 131I nécessitent une analyse plus approfondie. Une étude rétrospective, sur une trentaine de patient, est en cours pour estimer la différence entre les doses planifiées et les doses délivrées à la thyroïde lorsque le taux de captation en iode du patient est mesuré conformément au protocole développé