Predicting monthly to multi-annual foredune growth at a narrow beach

An open-source quantitative model for predicting coastal foredune growth at monthly to multi-annual (meso)temporal scales is developed. The model builds on the established fetch framework as a surrogate for the complex micro-scale aeolian processes on the beach, to which rain and groundwater-induced spatiotemporal surface moisture dynamics are added as factors limiting aeolian sand supply to foredunes. The model shows great skill in an application at Egmond aan Zee, The Netherlands, with a predicted growth of 16.5 m3/m/yr comparing favourably to the observed growth of 17.3 m3/m/yr. Rain, surface moisture dynamics as well as beach width reduction by storm-induced elevated sea levels are shown to be important factors that jointly reduce meso-scale sand supply below the potential (i.e., unlimited) maximum, in our case study by almost 5 m3/m/yr. These factors are most relevant for strong (here, above 15.5 m/s) onshore winds. Consistent with expectations from the literature, meso-scale foredune growth results primarily from moderately strong (9.5–12.5 m/s) shore-oblique winds, which are frequent and do not result in supply-limited conditions. At the study site these winds are most common in winter and hence foredune growth is predicted to vary seasonally, consistent with the observations. Because of the promising results we believe that our model has potential for quantifying how quickly a foredune can recover after an episodic erosion event because of storm waves

Predicting monthly to multi-annual foredune growth at a narrow beach

An open-source quantitative model for predicting coastal foredune growth at monthly to multi-annual (meso)temporal scales is developed. The model builds on the established fetch framework as a surrogate for the complex micro-scale aeolian processes on the beach, to which rain and groundwater-induced spatiotemporal surface moisture dynamics are added as factors limiting aeolian sand supply to foredunes. The model shows great skill in an application at Egmond aan Zee, The Netherlands, with a predicted growth of 16.5 m3/m/yr comparing favourably to the observed growth of 17.3 m3/m/yr. Rain, surface moisture dynamics as well as beach width reduction by storm-induced elevated sea levels are shown to be important factors that jointly reduce meso-scale sand supply below the potential (i.e., unlimited) maximum, in our case study by almost 5 m3/m/yr. These factors are most relevant for strong (here, above 15.5 m/s) onshore winds. Consistent with expectations from the literature, meso-scale foredune growth results primarily from moderately strong (9.5–12.5 m/s) shore-oblique winds, which are frequent and do not result in supply-limited conditions. At the study site these winds are most common in winter and hence foredune growth is predicted to vary seasonally, consistent with the observations. Because of the promising results we believe that our model has potential for quantifying how quickly a foredune can recover after an episodic erosion event because of storm waves

Prevention of mental illness within public health: An analysis of progress via systematic literature review and a pathway forward

Primary prevention is the cornerstone of public health. Prevention is especially important for chronic diseases of significant burden such as mental illnesses because many of them have limited treatment options, an onset in childhood or in adolescence, and are linked to adverse childhood experiences requiring a focus on early childhood and maternal-child health (MCH). Despite this need, there appears to be a paucity of research into prevention of mental illnesses within public health. To confirm this, we performed a systematic literature review to quantify the proportion of articles in public health that focus on prevention of mental illness versus intervention for these illnesses after their onset, and the proportion of published articles within MCH that focus on mental health. Between November 2019 and August 2021, we reviewed 211,794 published articles from 147 Scimago-ranked English public health journals with no limit on year of publication. As hypothesized, a very small portion (2.2%) of mental health articles included primary prevention and a small portion of MCH articles (7.8%) included mental health. These results are consistent with the existence of a research gap in mental illness prevention within the public health field. Given the early onset of mental illness, the importance of early childhood experiences in the later development of mental illness, and the importance of the social-emotional connection between mother and child for building resilience, public health professionals must incorporate evidence from the field of MCH to develop and assess more primary prevention programs for mental illness

Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of I-Ks, but preserved cAMP-dependent up-regulation

Aims Mutations in KCNQ1, encoding for Kv7.1, the alpha-subunit of the I-Ks channel, cause long-QT syndrome type 1, potentially predisposing patients to ventricular tachyarrhythmias and sudden cardiac death, in particular, during elevated sympathetic tone. Here, we aim at characterizing the p.Lys557Glu (K557E) Kv7.1 mutation, identified in a Dutch kindred, at baseline and during (mimicked) increased adrenergic tone. Methods and results K557E carriers had moderate QTc prolongation that augmented significantly during exercise. I-Ks characteristics were determined after co-expressing Kv7.1-wild-type (WT) and/or K557E with minK and Yotiao in Chinese hamster ovary cells. K557E caused I-Ks loss of function with slowing of the activation kinetics, acceleration of deactivation kinetics, and a rightward shift of voltage-dependent activation. Together, these contributed to a dominant-negative reduction in I-Ks density. Confocal microscopy and western blot indicated that trafficking of K557E channels was not impaired. Stimulation of WT I-Ks by 3'-5'-cyclic adenosine monophosphate (cAMP) generated strong current up-regulation that was preserved for K557E in both hetero- and homozygosis. Accumulation of I-Ks at fast rates occurred both in WT and in K557E, but was blunted in the latter. In a computational model, K557E showed a loss of action potential shortening during beta-adrenergic stimulation, in accordance with the lack of QT shortening during exercise in patients. Conclusion K557E causes I-Ks loss of function with reduced fast rate-dependent current accumulation. cAMP-dependent stimulation of mutant I-Ks is preserved, but incapable of fully compensating for the baseline current reduction, explaining the long QT intervals at baseline and the abnormal QT accommodation during exercise in affected patients

Subepicardial phase 0 block and discontinuous transmural conduction underlie right precordial ST-segment elevation by a SCN5A loss-of-function mutation

Two mechanisms are generally proposed to explain right precordial ST-segment elevation in Brugada syndrome: 1) right ventricular (RV) subepicardial action potential shortening and/or loss of dome causing transmural dispersion of repolarization; and 2) RV conduction delay. Here we report novel mechanistic insights into ST-segment elevation associated with a Na+ current (INa) loss-of-function mutation from studies in a Dutch kindred with the COOH-terminal SCN5A variant p.Phe2004Leu. The proband, a man, experienced syncope at age 22 yr and had coved-type ST-segment elevations in ECG leads V1 and V2 and negative T waves in V2. Peak and persistent mutant INa were significantly decreased. INa closed-state inactivation was increased, slow inactivation accelerated, and recovery from inactivation delayed. Computer-simulated INa-dependent excitation was decremental from endo- to epicardium at cycle length 1,000 ms, not at cycle length 300 ms. Propagation was discontinuous across the midmyocardial to epicardial transition region, exhibiting a long local delay due to phase 0 block. Beyond this region, axial excitatory current was provided by phase 2 (dome) of the M-cell action potentials and depended on L-type Ca2+ current (“phase 2 conduction”). These results explain right precordial ST-segment elevation on the basis of RV transmural gradients of membrane potentials during early repolarization caused by discontinuous conduction. The late slow-upstroke action potentials at the subepicardium produce T-wave inversion in the computed ECG waveform, in line with the clinical ECG

Growth, health, and motor development of 5-year-old children born after preimplantation genetic diagnosis

Objective: To evaluate the growth, health, and motor development of children born after preimplantation genetic diagnosis (PGD). Design: Observational cohort study and comparison of 5-year-old children born after PGD to similar aged children born after IVF/intracytoplasmic sperm injection (ICSI) and children from families with a genetic disorder born after natural conception (NC). Setting: University hospital. Patient(s): One hundred three children were included in the PGD group. The two control groups consisted of 90 children born after IVF/ICSI and 58 children born after NC. Intervention(s): PGD. Main Outcome Measure(s): We measured height, weight, body circumferences, body mass index, and blood pressure and performed a dysmorphological and neurological examination. We also collected data about the children's medical history, health care consultations, and motor milestones. Result(s): The mean height, weight, and body mass index were comparable for all groups. Six (5.8%) PGD, four (4.4%) IVF/ICSI, and five (8.6%) NC children had a major congenital abnormality. The incidence of acute and chronic illnesses was similar in all groups. Motor milestones were achieved on time, but the IVF/ICSI group had a slightly younger mean sitting age. None of the children had severe neurological problems. Conclusion(s): Five-year-old children born after PGD show normal growth, health, and motor development when compared with children born after IVF/ICSI and NC children from families with a genetic disorder. Trial registration number: NCT02149485

Differential development of umbilical and systemic arteries. II. Contractile proteins

In fetal sheep, umbilical responsiveness to ANG II exceeds systemic vascular responsiveness. Fetal systemic vascular smooth muscle (VSM) exhibits an immature phenotype with decreased contractile protein contents, low 200-kDa myosin heavy chain (MHC) SM2, and significant nonmuscle MHC-B expression, whereas umbilical VSM phenotype is incompletely described. We tested the hypothesis that differences in vascular responsiveness could reflect dissimilarities in VSM phenotype. Actin, MHC, MHC isoforms, and active stresses were compared in strips of femoral arteries and aorta from near-term fetal (n = 12) and adult (n = 12) sheep to those in external and intra-abdominal umbilical arteries. Actin contents in fetal femoral artery and aorta were less (

Beethoven

Die Beiträge dieses Bandes blicken aus ganz unterschiedlichen Perspektiven auf die ersten beiden Lebensjahrzehnte des großen Komponisten und Musikers. Von seiner Taufe im Dezember 1770 in Bonn bis zu seinem Weggang nach Wien im November 1792, der kein endgültiger hatte sein sollen, werden zahlreiche Facetten seines Lebens und seiner Sozialisation in der kurfürstlichen Haupt- und Residenzstadt beschrieben.Dabei geht es vor allem um seine wichtigsten Prägungen: seine Herkunftsfamilie, seinen Freundeskreis, seine Weggefährten, Förderer und Lehrer – Familie von Breuning, der Zehrgarten-Kreis, Eichhoff, Neefe, Ries, Simrock, Wegeler –, das opulente Musikleben am Hof und in der Stadt und schließlich die aufklärerischen Kreise, wie der Hof, die kurfürstliche Akademie oder die einflussreiche Lesegesellschaft.Thematisiert wird Beethovens erster Wienaufenthalts 1786/87, die Reise der Bonner Hofmusik nach Mergentheim 1791 und die Bedeutung des Kur- und Badeortes Godesberg für den jungen Musiker. Ein Blick auf die Reaktion auf Beethovens Tod in Bonn bildet den Abschluss eines Bandes, der sowohl bisherige Forschungsergebnisse zusammenfasst und dabei Manches neu bewertet als auch mit überraschenden Ergebnissen und Neuinterpretationen aufwartet

Beethoven

Die Beiträge dieses Bandes blicken aus ganz unterschiedlichen Perspektiven auf die ersten beiden Lebensjahrzehnte des großen Komponisten und Musikers. Von seiner Taufe im Dezember 1770 in Bonn bis zu seinem Weggang nach Wien im November 1792, der kein endgültiger hatte sein sollen, werden zahlreiche Facetten seines Lebens und seiner Sozialisation in der kurfürstlichen Haupt- und Residenzstadt beschrieben.Dabei geht es vor allem um seine wichtigsten Prägungen: seine Herkunftsfamilie, seinen Freundeskreis, seine Weggefährten, Förderer und Lehrer – Familie von Breuning, der Zehrgarten-Kreis, Eichhoff, Neefe, Ries, Simrock, Wegeler –, das opulente Musikleben am Hof und in der Stadt und schließlich die aufklärerischen Kreise, wie der Hof, die kurfürstliche Akademie oder die einflussreiche Lesegesellschaft.Thematisiert wird Beethovens erster Wienaufenthalts 1786/87, die Reise der Bonner Hofmusik nach Mergentheim 1791 und die Bedeutung des Kur- und Badeortes Godesberg für den jungen Musiker. Ein Blick auf die Reaktion auf Beethovens Tod in Bonn bildet den Abschluss eines Bandes, der sowohl bisherige Forschungsergebnisse zusammenfasst und dabei Manches neu bewertet als auch mit überraschenden Ergebnissen und Neuinterpretationen aufwartet