CORRESPONDENCE

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Use of azacitidine and its safety and efficacy in daily clinical practice in The Netherlands:the OCEAN study

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Long‐term evolution of the Old Rhine estuary : unraveling effects of changing boundary conditions and inherited landscape.

The long‐term morphodynamic evolution of estuaries depends on a combination of antecedent topography and boundary conditions, including fluvial input, sea‐level change and regional‐landscape interactions. Identifying effects of such boundary conditions on estuary evolution is important to anticipate future changes in specific boundary conditions and for hindcasting with numerical and physical models. A comprehensive synthesis of the evolution of the former Old Rhine estuary is presented here, together with its boundary conditions over its full lifespan from 6,500 to 1,000 cal. yr bp. This system formed during a period of sea‐level high stand, during which the estuary served as the main River Rhine outlet. The estuary went through three stages of evolution: a maturation phase in a wide infilling back‐barrier basin, a stable mature phase and an abandoning phase, both in a laterally confined setting. The Old Rhine River formed by a river avulsion around 6,500 cal. yr bp that connected to a tidal channel within a large back‐barrier basin. Decelerating sea‐level rise caused the back‐barrier basin to silt up around 5,700 cal. yr bp, resulting in shoreline progradation by beach‐barrier formation until ∼2,000 cal. yr bp. Beach‐barrier formation along the coast and natural levee formation along the river triggered peat formation in the coastal plain, laterally constraining the estuary and limiting overbank deposition, which caused most sediment to accumulate offshore. The abandoning phase started around 2,200 cal. yr bp when a series of upstream avulsions led to a substantial reduction in fluvial input. This induced a period of enhanced estuarine overbank clay deposition that continued into near‐complete silting up and estuary closure around 1200 ad. These findings exemplify how tidal systems, formed in wide coastal plains during sea‐level high stand, depend on antecedent conditions, and how they respond to connection and disconnection of a large river over long, millennial timescales

Evolution of Fe Species During the Synthesis of Over-Exchanged Fe/ZSM5 Obtained by Chemical Vapor Deposition of FeCl3

Abstract The evolution of iron in over-exchanged Fe/ZSM5 prepared via chemical vapor deposition of FeCl 3 was studied at each stage of the synthesis. Different characterization techniques (EXAFS, HR-XANES

Gene Expression and Functional Annotation of the Human Ciliary Body Epithelia

Purpose: The ciliary body (CB) of the human eye consists of the non-pigmented (NPE) and pigmented (PE) neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed molecular signatures for the NPE and PE and studied possible new clues for glaucoma. Methods: We isolated NPE and PE cells from seven healthy human donor eyes using laser dissection microscopy. Next, we performed RNA isolation, amplification, labeling and hybridization against 44×k Agilent microarrays. For microarray conformations, we used a literature study, RT-PCRs, and immunohistochemical stainings. We analyzed the gene expression data with R and with the knowledge database Ingenuity. Results: The gene expression profiles and functional annotations of the NPE and PE were highly similar. We found that the most important functionalities of the NPE and PE were related to developmental processes, neural nature of the tissue, endocrine and metabolic signaling, and immunological functions. In total 1576 genes differed statistically significantly between NPE and PE. From these genes, at least 3 were cell-specific for the NPE and 143 for the PE. Finally, we observed high expression in the (N)PE of 35 genes previously implicated in molecular mechanisms related to glaucoma. Conclusion: Our gene expression analysis suggested that the NPE and PE of the CB were quite similar. Nonetheless, cell-type specific differences were found. The molecular machineries of the human NPE and PE are involved in a range of neuro-endocrinological, developmental and immunological functions, and perhaps glaucoma

Web-based cognitive behavioural therapy (W-CBT) for diabetes patients with co-morbid depression: Design of a randomised controlled trial

Abstract Background Depression is common among people with diabetes, negatively affecting quality of life, treatment adherence and diabetes outcomes. In routine clinical care, diabetes patients have limited access to mental health services and depression therefore often remains untreated. Web-based therapy could potentially be an effective way to improve the reach of psychological care for diabetes patients, at relatively low costs. This study seeks to test the effectiveness of a web-based self-help depression programme for people with diabetes and co-morbid depression. Methods/Design The effectiveness of a web-based self-help course for adults with diabetes with co-morbid depression will be tested in a randomised trial, using a wait-list controlled design. The intervention consists of an 8-week, moderated self-help course that is tailored to the needs of persons living with diabetes and is offered on an individual basis. Participants receive feedback on their homework assignments by e-mail from their coach. We aim to include 286 patients (143/143), as power analyses showed that this number is needed to detect an effect size of 0.35, with measurements at baseline, directly after completing the web-based intervention and at 1, 3, 4 and 6 months follow-up. Patients in the control condition are placed on a waiting list, and follow the course 12 weeks after randomisation. Primary outcomes are depressive symptoms and diabetes-specific emotional distress. Secondary outcomes are satisfaction with the course, perceived health status, self-care behaviours, glycaemic control, and days in bed/absence from work. Questionnaires are administered via the Internet. Discussion The intervention being trialled is expected to help improve mood and reduce diabetes-specific emotional distress in diabetes patients with depression, with subsequent beneficial effects on diabetes self-care and glycaemic outcomes. When proven efficacious, the intervention could be disseminated to reach large groups of patients with diabetes and concurrent depressive symptoms

Een nieuwe en handzame lysimeter: eerste stap naar een nationaal netwerk voor de werkelijke verdamping?

Vrijwel overal op aarde verdampt meer dan de helft van het neerslagwater, ook in Nederland. Toch wordt deze grote verliespost in ons land slechts sporadisch gemeten. Door inspanningen van kennisinstituten, bedrijven en overheid is daarom een lysimeter ontwikkeld. Metingen in 2014 en 2015 op twee locaties vertonen opvallende verschillen, maar ook grote overeenkomsten, met eddy-correlatiemetingen. Schattingen van de verdamping via satellietdata zijn hoger dan de metingen. Tijd daarom, om metingen in het veld te combineren met modellen en waarnemingen vanuit de ruimt

GRB 010921: Discovery of the First HETE Afterglow

We report the discovery of the optical and radio afterglow of GRB 010921, the first gamma-ray burst afterglow to be found from a localization by the High Energy Transient Explorer (HETE) satellite. We present optical spectroscopy of the host galaxy which we find to be a dusty and apparently normal star-forming galaxy at z = 0.451. The unusually steep optical spectral slope of the afterglow can be explained by heavy extinction, A_V > 0.5 mag, along the line of sight to the GRB. Dust with similar A_V for the the host galaxy as a whole appears to be required by the measurement of a Balmer decrement in the spectrum of the host galaxy. Thanks to the low redshift, continued observations of the afterglow will enable the strongest constraints, to date, on the existence of a possible underlying supernova.Comment: 16 pages, 3 figures. Submitted to the Astrophsical Journal Letter

Somatic insulin signaling regulates a germline starvation response in Drosophila egg chambers

AbstractEgg chambers from starved Drosophila females contain large aggregates of processing (P) bodies and cortically enriched microtubules. As this response to starvation is rapidly reversed upon re-feeding females or culturing egg chambers with exogenous bovine insulin, we examined the role of endogenous insulin signaling in mediating the starvation response. We found that systemic Drosophila insulin-like peptides (dILPs) activate the insulin pathway in follicle cells, which then regulate both microtubule and P body organization in the underlying germline cells. This organization is modulated by the motor proteins Dynein and Kinesin. Dynein activity is required for microtubule and P body organization during starvation, while Kinesin activity is required during nutrient-rich conditions. Blocking the ability of egg chambers to form P body aggregates in response to starvation correlated with reduced progeny survival. These data suggest a potential mechanism to maximize fecundity even during periods of poor nutrient availability, by mounting a protective response in immature egg chambers

On the origin of proteins in human drusen : the meet, greet and stick hypothesis

This research was part-supported by de Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB), de Stichting Blinden-Penning, de Gelderse Blinden Stichting, de Landelijke Stichting voor Blinden en Slechtzienden (LSBS), Stichting Oogfonds Nederland, Stichting MD Fonds and Stichting Retina Nederland Fonds (represented by Uitzicht, grants 2011-6 and 2014-7 to A.A.B.), de Rotterdamse Stichting Blindenbelangen (RSB), de Haagse Stichting Blindenhulp, Stichting Lijf en Leven, Stichting voor Ooglijders (to A.A.B.); ZonMW grant nr 446001002 (to A.A.B. and C.K.); the Bill Brown Charitable Trust, Moorfields Eye Hospital Special Trustees, Mercer Fund from Fight for Sight, the Eye-Risk project funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634479 (I.L. and E.E.), Fight for Sight project grant (I.L. and A.S.), the Bright Focus Foundation grant nr M2015370 (to SMH).Retinal drusen formation is not only a clinical hallmark for the development of age-related macular degeneration (AMD) but also for other disorders, such as Alzheimer's disease and renal diseases. The initiation and growth of drusen is poorly understood. Attention has focused on lipids and minerals, but relatively little is known about the origin of drusen-associated proteins and how they are retained in the space between the basal lamina of the retinal pigment epithelium and the inner collagenous layer space (sub-RPE-BL space). While some authors suggested that drusen proteins are mainly derived from cellular debris from processed photoreceptor outer segments and the RPE, others suggest a choroidal cell or blood origin. Here, we reviewed and supplement the existing literature on the molecular composition of the retina/choroid complex, to gain a more complete understanding of the sources of proteins in drusen. These “drusenomics” studies showed that a considerable proportion of currently identified drusen proteins is uniquely originating from the blood. A smaller, but still large fraction of drusen proteins comes from both blood and/or RPE. Only a small proportion of drusen proteins is uniquely derived from the photoreceptors or choroid. We next evaluated how drusen components may “meet, greet and stick” to each other and/or to structures like hydroxyapatite spherules to form macroscopic deposits in the sub-RPE-BL space. Finally, we discuss implications of our findings with respect to the previously proposed homology between drusenogenesis in AMD and plaque formation in atherosclerosis.PostprintPeer reviewe