Persistent non-solar forcing of Holocene storm dynamics in coastal sedimentary archives

Considerable climatic variability on decadal to millennial timescales has been documented for the past 11,500 years of interglacial climate. This variability has been particularly pronounced at a frequency of about 1,500 years, with repeated cold intervals in the North Atlantic. However, there is growing evidence that these oscillations originate from a cluster of different spectral signatures, ranging from a 2,500-year cycle throughout the period to a 1,000-year cycle during the earliest millennia. Here we present a reappraisal of high-energy estuarine and coastal sedimentary records from the southern coast of the English Channel, and report evidence for five distinct periods during the Holocene when storminess was enhanced during the past 6,500 years.We find that high storm activity occurred periodically with a frequency of about 1,500 years, closely related to cold and windy periods diagnosed earlier. We show that millennial-scale storm extremes in northern Europe are phase-locked with the period of internal ocean variability in the North Atlantic of about 1,500 years. However, no consistent correlation emerges between spectral maxima in records of storminess and solar irradiation. We conclude that solar activity changes are unlikely to be a primary forcing mechanism of millennial-scale variability in storminess

Holocene salt-marsh sedimentary infilling and relative sea-level changes in West Brittany (France) using foraminifera-based transfer functions

International audienceIn order to reconstruct the former sea-levels and to better characterize the history of Holocene salt-marsh sedimentary infillings in West Brittany (western France), local foraminifera-based transfer functions were developed using Weighted-Average-Partial-Least-Squares (WA-PLS) regression, based on a modern dataset of 26 and 51 surface samples obtained from salt-marshes in both the bay of Tressseny and the bay of Brest. Fifty cores were retrieved from Tresseny, Porzguen, Troaon and Arun salt-marshes, which were litho- and biostratigraphicaly analyzed in order to reconstruct palaeoenvironmental changes. A total of 26 AMS 14C age determinations were performed within the sediment successions. The Holocene evolution of salt-marsh environments can be subdivided into four stages: (1) a development of brackish to freshwater marshes (from c. 6400 to 4500 cal. a BP); (2) salt-marsh formation behind gravel barriers in the bay of Brest (from 4500 to 2900 cal. a BP); (3) salt-marsh erosion and rapid changes of infilling dynamics due to the destruction of coastal barriers by storm events (c. 2900-2700 cal. a BP); (4) renewed salt-marsh deposition and small environmental changes (from 2700 cal. a BP to present). From the application of transfer functions to fossil assemblages, 14 new sea-level index points were obtained indicating a mean relative sea-level rise around 0.90±0.12 mm a-1 since 6300 cal. a BP

Growth and Nutritional Biomarkers of Preterm Infants Fed a New Powdered Human Milk Fortifier: A Randomized Trial.

The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium-chain triglycerides and docosahexaenoic acid. In this controlled, multicenter, double-blind study, a sample of preterm infants ≤32 weeks or ≤1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = -1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored. Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P < 0.001) and superiority margins (P = 0.01). Weight gain rate (unadjusted) was 18.3 (nHMF) and 16.8 g · kg · day (cHMF) between study days 1 and 21 (D1-D21). Length and head circumference (HC) gains between D1 and D21 were not different. Adjusted weight-for-age z score at D21 and HC-for-age z score at week 40 corrected age were greater in nHMF versus cHMF (P = 0.013, P = 0.003 respectively). nHMF had higher serum blood urea nitrogen, pre-albumin, alkaline phosphatase, and calcium (all within normal ranges; all P ≤ 0.019) at D21 versus cHMF. Both HMFs were well tolerated with similar incidence of gastrointestinal adverse events. nHMF providing more protein and fat compared to a control fortifier is safe, well-tolerated, and improves the weight gain of preterm infants

Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review.

Objectives: In this review, the current biopharmaceutical approaches for evaluation of oral formulation performance in paediatrics are discussed. Key findings: The paediatric gastrointestinal (GI) tract undergoes numerous morphological and physiological changes throughout its development and growth. Some physiological parameters are yet to be investigated, limiting the use of the existing in vitro biopharmaceutical tools to predict the in vivo performance of paediatric formulations. Meals and frequencies of their administration evolve during childhood and affect oral drug absorption. Furthermore, the establishment of a paediatric Biopharmaceutics Classification System (pBCS), based on the adult Biopharmaceutics Classification System (BCS), requires criteria adjustments. The usefulness of computational simulation and modeling for extrapolation of adult data to paediatrics has been confirmed as a tool for predicting drug formulation performance. Despite the great number of successful physiologically based pharmacokinetic models to simulate drug disposition, the simulation of drug absorption from the GI tract is a complicating issue in paediatric populations. Summary: The biopharmaceutics tools for investigation of oral drug absorption in paediatrics need further development, refinement and validation. A combination of in vitro and in silico methods could compensate for the uncertainties accompanying each method on its own

Assessment of age-related changes in pediatric gastrointestinal solubility

PurposeCompound solubility serves as a surrogate indicator of oral biopharmaceutical performance. Between infancy and adulthood, marked compositional changes in gastrointestinal (GI) fluids occur. This study serves to assess how developmental changes in GI fluid composition affects compound solubility.MethodsSolubility assessments were conducted in vitro using biorelevant media reflective of age-specific pediatric cohorts (i.e., neonates and infants). Previously published adult media (i.e., FaSSGF, FeSSGF, FaSSIF.v2, and FeSSIF.v2) were employed as references for pediatric media development. Investigations assessing age-specific changes in GI fluid parameters (i.e., pepsin, bile acids, pH, osmolality, etc.) were collected from the literature and served to define the composition of neonatal and infant media. Solubility assessments at 37°C were conducted for seven BCS Class II compounds within the developed pediatric and reference adult media.ResultsFor six of the seven compounds investigated, solubility fell outside an 80–125% range from adult values in at least one of the developed pediatric media. This result indicates a potential for age-related alterations in oral drug performance, especially for compounds whose absorption is delimited by solubility (i.e., BCS Class II).ConclusionDevelopmental changes in GI fluid composition can result in relevant discrepancies in luminal compound solubility between children and adults.<br/

Effects on Fatty Acid Metabolism of a New Powdered Human Milk Fortifier Containing Medium-Chain Triacylglycerols and Docosahexaenoic Acid in Preterm Infants

Preterm infants require fortification of human milk (HM) with essential fatty acids (FA) to ensure adequate post-natal development. As part of a larger randomized controlled study, we investigated FA metabolism in a subset of 47 clinically stable preterm infants (birth weight &le;1500 g or gestational age &le;32 weeks). Infants were randomized to receive HM supplemented with either a new HM fortifier (nHMF; n = 26) containing 12.5 g medium-chain FA (MCFA), 958 mg linoleic acid (LA), 417 mg &alpha;-linolenic acid (ALA), and 157 mg docosahexaenoic acid (DHA) per 100 g of powder (in compliance with the latest guidelines) or a fat-free HMF (cHMF; n = 21). Plasma phospholipid (PL) and triacylglycerol (TAG), and red blood cell phosphatidylcholine (RBC-PC) and phosphatidylethanolamine (RBC-PE) FA profiles were assessed before and after 21 days of feeding. In the nHMF group, significantly increased levels of n-9 monounsaturated fatty acids were observed, formed most likely by elongation and desaturation of dietary saturated fatty acids present in HM. ALA fortification increased ALA assimilation into plasma TAG. Similarly, DHA fortification enriched the DHA content in RBC-PE, which, in this compartment, was not associated with lower arachidonic acid levels as observed in plasma TAG and phospholipids. RBC-PE, a reliable indicator of FA metabolism and accretion, was the most sensitive compartment in this study

Dynamique de construction d'un prisme sédimentaire littoral en régime mégatidal (la Baie du Mont-Saint-Michel)

The Bay of Mt-St-Michel is a megatidal environment, the Holocene sedimentary infill of which began some 8000 years ago. The present-day Bay consists in various sub-environments: an embayment in the West, an estuary in the East, and a sandy barrier subject to wave action in the NE. Thanks to VHR seismic data and cores, different architectures are highlighted: progradational to aggradational in the embayment, aggradational to chanelized in the estuary and along the NE shoreline. The infill model established with all the data is characterised as follows: a transgressive systems tract of low volume; a well-developed highstand systems tract; a tidal ravinement surface of large extent, reaching locally the substrate; a wave ravinement surface locally present along the estuary margins; an accommodation for sequence preservation of tidal origin in the estuary, and of eustatic origin along the margins. At the basin scale, discrepancies in time-and-space of the preservation potential of sedimentary sequences observed into the infill are very important. As soon as the transgression rate slow down from 6500 yB.P., the key-control of local factors (hydrodynamics, sediment supply, substrate morphology) is evidenced. Sequences preserved along the estuary margins record environmental changes interpreted as the result of climate crisis of 1500-year period. Although the origin of these climate cycles is uncertain (Bond cycles, long term tidal cycles, combination of both?), their control on coastal system evolution should be considered as major.La Baie du Mt-St-Michel est un milieu mégatidal dont le remplissage holocène a débuté il y a 8000 ans BP. La Baie présente aujourd'hui des environnements contrastés : une baie sensus stricto à l'Ouest, un système estuarien à l'Est, et un littoral sableux exposé aux houles au NE. A partir de données de sismique THR et de carottage, des architectures de remplissage différentes sont mises en évidence : progradante puis aggradante dans la baie, aggradante puis chenalisante dans le domaine estuarien et le long du littoral NE. L'ensemble des résultats permet d'établir un modèle de remplissage caractérisé par : un cortège transgressif de faible volume ; un cortège de haut niveau marin très développé ; une surface de ravinement tidale de grande extension, pouvant localement atteindre le substratum ; une surface de ravinement par la houle présente en marge de l'axe estuarien ; une préservation de séquences sédimentaires liée à une accommodation d'origine tidale dans l'axe estuarien, et d'origine eustatique sur les marges. A l'échelle du bassin, les disparités spatio-temporelles du potentiel de préservation des séquences sont très importantes. Dès que la vitesse de la transgression holocène diminue à partir de 6500 B.P., l'importance des facteurs locaux (hydrodynamisme, apports, morphologie du substratum) est mise en évidence. Les séquences préservées en marge de l'estuaire enregistrent des changements environnementaux interprétés comme le résultat de crises climatiques d'une périodicité de 1500 ans. Si l'origine de ces crises est incertaine (cycles de Bond, cycles tidaux long terme, combinaison des deux), leur rôle dans l'évolution des littoraux doit être considéré comme majeur