581 research outputs found

    Hematologic Malignancies in Pregnancy

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    Localization of Quaternary slip rates in an active rift in 10(5) years: an example from central Greece constrained by U-234-Th-230 coral dates from uplifted paleoshorelines

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    Mapping, dating, and modeling of paleoshorelines uplifted in the footwall of the 1981 Gulf of Corinth earthquake fault, Greece (Ms 6.9–6.7), are used to assess its slip rate history relative to other normal faults in the area and study strain localization. The 234U-230Th coral ages from Cladocora caespitosa date uplifted shoreface sediments, and paleoshorelines from glacioeustatic sea level highstands at 76, (possibly) 100, 125, 175, 200, 216, 240, and 340 ka. Uplifted Quaternary and Holocene paleoshorelines decrease in elevation toward the western tip of the fault, exhibiting larger tilt angles with age, showing that uplift is due to progressive fault slip. Since 125 ka, uplift rates varied from 0.25 to 0.52 mm/yr over a distance of 5 km away from the fault tip. Tilting was also occurring prior to 125 ka, but uplift rates were lower because the 125 ka paleoshoreline is at 77% of the elevation of the 240 ka paleoshoreline despite being nearly half its age. Comparison of paleoshoreline elevations and sedimentology with the Quaternary sea level curve shows that slip rates increased by a factor of 3.2 ± 0.2 at 175 ± 75 ka, synchronous with cessation of activity on a neighboring normal fault at 382–112 ka. We suggest that the rapid localization of up to 10–15 mm/yr of extension into the narrow gulf (∼30 km wide) resulted from synchronous fault activity on neighboring faults followed by localization rather than sequential faulting, with consequences for the mechanism controlling localization of extension

    Determining the exposure of maternal medicines through breastfeeding:the UmbrelLACT study protocol - a contribution from the ConcePTION project

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    Introduction:Breastfeeding is beneficial for the health of the mother and child. However, at least 50% of postpartum women need pharmacotherapy, and this number is rising due to the increasing prevalence of chronic diseases and pregnancies at a later age. Making informed decisions on medicine use while breastfeeding is often challenging, considering the extensive information gap on medicine exposure and safety during lactation. This can result in the unnecessary cessation of breastfeeding, the avoidance of pharmacotherapy or the off-label use of medicines. The UmbrelLACT study aims to collect data on human milk transfer of maternal medicines, child exposure and general health outcomes. Additionally, the predictive performance of lactation and paediatric physiologically based pharmacokinetic (PBPK) models, a promising tool to predict medicine exposure in special populations, will be evaluated. Methods and analysis:Each year, we expect to recruit 5-15 breastfeeding mothers using pharmacotherapy via the University Hospitals Leuven, the BELpREG project (pregnancy registry in Belgium) or external health facilities. Each request and compound will be evaluated on relevance (ie, added value to available scientific evidence) and feasibility (including access to analytical assays). Participants will be requested to complete at least one questionnaire on maternal and child's general health and collect human milk samples over 24 hours. Optionally, two maternal and one child's blood samples can be collected. The maternal medicine concentration in human milk will be determined along with the estimation of the medicine intake (eg, daily infant dose and relative infant dose) and systemic exposure of the breastfed child. The predictive performance of PBPK models will be assessed by comparing the observed concentrations in human milk and plasma to the PBPK predictions. Ethics and dissemination:This study has been approved by the Ethics Committee Research UZ/KU Leuven (internal study number S67204). Results will be published in peer-reviewed journals and presented at (inter)national scientific meetings. Trial registration number NCT06042803.</p

    The Impact of Caesarean Delivery on Paracetamol and Ketorolac Pharmacokinetics: A Paired Analysis

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    Pharmacokinetics is a first, but essential step to improve population-tailored postoperative analgesia, also after Caesarean delivery. We therefore aimed to quantify the impact of caesarean delivery on the pharmacokinetics of intravenous (iv) paracetamol (2 g, single dose) and iv ketorolac tromethamine (30 mg, single dose) in 2 cohorts eachof 8 women at caesarean delivery and to compare these findings with postpartum to quantify intrapatient changes. We documented a higher median paracetamol clearance at delivery when compared to 10–15 weeks postpartum (11.7 to 6.4 L/h·m2, P < 0.01), even after correction for weight-related changes. Similar conclusions were drawn for ketorolac: median clearance was higher at delivery with a subsequent decrease (2.03 to 1.43 L/h·m2, P < 0.05) in postpartum (17–23 weeks). These differences likely reflect pregnancy- and caesarean-delivery-related changes in drug disposition. Moreover, postpartum paracetamol clearance was significantly lower when compared to estimates published in healthy young volunteers (6.4  versus  9.6 L/h·m2), while this was not the case for ketorolac (1.43  versus  1.48 L/h·m2). This suggests that postpartum is another specific status in young women that merits focused, compound-specific pharmacokinetic evaluation

    Ten-year experience of a national multidisciplinary tumour board for cancer and pregnancy in the Netherlands

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    Background: Most physicians encounter pregnant women with cancer incidentally, leading to a lack of expertise or confidence to inform and treat these patients based on the most recent guidelines and expert opinions. In the Netherlands, a national multidisciplinary tumour board for cancer, infertility and pregnancy (CIP-MDT) was founded in December 2012, including 35 specialists from a variety of disciplines. This study evaluates the frequency of consultation of the CIP-MDT, the types of questions asked and the satisfaction of consulting physicians with its existence. Methodology: Of all requests to the CIP-MDT between December 2012 and June 2021, tumour type, stage, gestational age at diagnosis and recommendations were collected and analysed. For evaluating the methods of the CIP-MDT, a survey with questions regarding experiences with the CIP-MDT and its impact on treatment decisions was sent out to physicians that consulted the CIP-MDT. Results: Recommendations (n = 213) concerned preferred and safest options for imaging, treatment options during pregnancy, possible effects on the child and fertility preserving options. Most frequently discussed malignancies were breast cancer (n = 66), cervical cancer (n = 34), haematological malignancies (n = 32) and melanoma (n = 21). The questionnaire was completed by 54% of the physicians (n = 50). Satisfaction with the recommendations of the CIP-MDT was high, and 94% of the physicians informed their patients about consulting the CIP-MDT and felt supported by the received recommendations. Discussion: The national Dutch CIP-MDT contributes to a high level of satisfaction among physicians requesting advice. Further research should be executed to confirm that a CIP-MDT improves the outcomes for pregnant women and their children

    Quantitative dating of pleistocene deposits of the Kyrenia range, Northern Cyprus : implications for timing, rates of uplift and driving mechanisms

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    R.N.P. acknowledges the NERC CASE scholarship at the University of Edinburgh. Additional field and laboratory work was aided by the DARIUS Programme to A.H.F.R. and T.C.K. We are grateful for the additional financial support provided by the John Dixon Memorial Fund.The Kyrenia Range underwent tectonically driven uplift during the Pliocene to Pleistocene in response to the interaction of various tectonic processes. To understand the tectonic processes driving the uplift and how this is related to uplift of other areas of the Eastern Mediterranean, uranium-series disequilibrium and optically stimulated luminescence dating were applied to marine and non-marine terrace deposits exposed on the northern flank of the range. Palaeomagnetism and strontium isotope dating were used in conjunction to date the final stages of the marine environment adjacent to the Kyrenia Range prior to major surface uplift. Uplift rates range from >1.2 mm a−1, inferred during the Early Pleistocene, to <0.2 mm a−1during the Late Pleistocene. The new data show that the Kyrenia Range was uplifted contemporaneously with the Troodos Massif in southern Cyprus. The uplift of the Kyrenia Range appears to have been significantly faster than that affecting other comparable regions in the easternmost Mediterranean during the Pleistocene (e.g. Lebanon coast; southern Anatolian plateau). The driving mechanism for the uplift of both the Kyrenia Range and the Troodos Massif is inferred to be the collision of the Eratosthenes Seamount with the Cyprus trench to the south of Cyprus.Publisher PDFPeer reviewe

    Revealing the Compact Structure of Lactic Acid Bacterial Heteroexopolysaccharides by SAXS and DLS

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    Molecular structures of exopolysaccharides are required to understand their functions and the relationships between the structure and physical and rheological properties. Small-angle X-ray scattering and dynamic light scattering were used in conjunction with molecular modeling to characterize solution structures of three lactic acid bacterial heteroexopolysaccharides (HePS-1, HePS-2, and HePS-3). Values of radius of gyration <i>R</i><sub>G</sub>, cross-sectional radius of gyration <i>R</i><sub>XS</sub>, approximate length <i>L</i>, and hydrodynamic diameter were not directly proportional to the molar mass and indicated the HePSs adopted a compact coil-like rather than an extended conformation. Constrained molecular modeling of 15000 randomized HePS-1 conformers resulted in five best-fit structures with <i>R</i> factor of 3.9−4.6% revealing random coil-like structure. Φ and Ψ angle analysis of glycosidic linkages in HePS-1 structures suggests Gal<i>f</i> residues significantly influence the conformation. Ab initio scattering modeling of HePS-2 and HePS-3 gave excellent curve fittings with χ<sup>2</sup> of 0.43 and 0.34 for best-fit models, respectively, compatible with coil-like conformation. The findings disclose solution behavior of HePS relevant for their interactions with biomacromolecules, for example, milk proteins
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