Water Management Solution of Reservoir Storage Function Under Condition of Measurement Uncertainties in Hydrological Input Data

AbstractThe paper describes a possible procedure of the rate uncertainty implementation to the continuous water stage measurement and uncertainties of state - discharge rating curve point positions, which the stage -discharge rating curves were fitted into the uncertainties of the real discharge series members. Then the members of discharge series under uncertainty impact were tested on the calculated values of the reservoir storage volume. The next step was the implementation of the uncertainties of the real discharge series members on the generation of the artificial discharge series of mean monthly discharge using the AR and ARMA generators and the determination of their impact on the calculated values of the reservoir storage volume

Determination of organohalogenated contaminants in liver of harbour porpoises (Phocoena phocoena) stranded on the Belgian North Sea coast

Peer reviewe

Cumulative live birth rates in low-prognosis women

No external funds were obtained for the present study. The OPTIMIST study was funded by The Netherlands Organization for Health Research and Development (ZonMW number 171102020).Peer reviewedPublisher PD

Individualized versus standard FSH dosing in women starting IVF/ICSI:An RCT. Part 2: The predicted hyper responder

STUDY QUESTION: Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety? SUMMARY ANSWER: Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrome (OHSS) as compared to a standard dose (150 IU/day), a higher first cycle cancellation rate and similar severe OHSS rate were observed. WHAT IS KNOWN ALREADY: Excessive ovarian response to controlled ovarian stimulation (COS) for IVF/ICSI may result in increased rates of cycle cancellation, the occurrence of OHSS and suboptimal live birth rates. In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can be used to predict response to COS. No consensus has been reached on whether ORT-based FSH dosing improves effectiveness and safety in women with a predicted hyper response. STUDY DESIGN SIZE, DURATION: Between May 2011 and May 2014, we performed an open-label, multicentre RCT in women with regular menstrual cycles and an AFC > 15. Women with polycystic ovary syndrome (Rotterdam criteria) were excluded. The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. Secondary outcomes included the occurrence of OHSS and cost-effectiveness. Since this RCT was embedded in a cohort study assessing over 1500 women, we expected to randomize 300 predicted hyper responders. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with an AFC > 15 were randomized to an FSH dose of 100 IU or 150 IU/day. In both groups, dose adjustment was allowed in subsequent cycles (maximum 25 IU in the reduced and 50 IU in the standard group) based on pre-specified criteria. Both effectiveness and cost-effectiveness were evaluated from an intention-to-treat perspective. MAIN RESULTS AND THE ROLE OF CHANCE: We randomized 255 women to a daily FSH dose of 100 IU and 266 women to a daily FSH dose of 150 IU. The cumulative live birth rate was 66.3% (169/255) in the reduced versus 69.5% (185/266) in the standard group (relative risk (RR) 0.95 [95%CI, 0.85-1.07], P = 0.423). The occurrence of any grade of OHSS was lower after a lower FSH dose (5.2% versus 11.8%, RR 0.44 [95%CI, 0.28-0.71], P = 0.001), but the occurrence of severe OHSS did not differ (1.3% versus 1.1%, RR 1.25 [95%CI, 0.38-4.07], P = 0.728). As dose reduction was not less expensive (€4.622 versus €4.714, delta costs/woman €92 [95%CI, -479-325]), there was no dominant strategy in the economic analysis. LIMITATIONS, REASONS FOR CAUTION: Despite our training programme, the AFC might have suffered from inter-observer variation. Although strict cancellation criteria were provided, selective cancelling in the reduced dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as first cycle live birth rates did not differ from the cumulative results, the open design probably did not mask a potential benefit for the reduced dosing group. As this RCT was embedded in a larger cohort study, the power in this study was unavoidably lower than it should be. Participants had a relatively low BMI from an international perspective, which may limit generalization of the findings. WIDER IMPLICATIONS OF THE FINDINGS: In women with a predicted hyper response scheduled for IVF/ICSI, a reduced FSH dose does not affect live birth rates. A lower FSH dose did reduce the incidence of mild and moderate OHSS, but had no impact on severe OHSS. Future research into ORT-based dosing in women with a predicted hyper response should compare various safety management strategies and should be powered on a clinically relevant safety outcome while assessing non-inferiority towards live birth rates. STUDY FUNDING/COMPETING INTEREST(S): This trial was funded by The Netherlands Organization for Health Research and Development (ZonMW, Project Number 171102020). SCO, TCvT and HLT received an unrestricted research grant from Merck Serono (the Netherlands). CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV and Merck Serono for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657. TRIAL REGISTRATION DATE: 20 December 2010. DATE OF FIRST PATIENT’S ENROLMENT: 12 May 2011

Recombinant production of periodic polypeptides. Introducing structural order in polymeric materials

Contains fulltext : 29851.pdf (publisher's version ) (Open Access)This PhD thesis describes the recombinant production of periodic beta-sheet, silk-like polypeptides in Escherichia coli. Polypeptides with the repetitive sequence [(AG)3EG]n (n = 10 - 50; A = alanine, G = glycine and E = glutamic acid) were prepared with a yield of approximately 20 mg per liter of cell culture (n = 20). The polypeptides [(AG)3EG]n (n = 10 and 20) with N- and C-terminal cysteine residues were used for the preparation of hybrid triblock copolymers containing poly(ethylene glycol) (PEG; Mn = 750, 2000 and 5000 g/mol) end blocks. In the solid state, the polypeptide block is known to adopt a regular antiparallel beta-sheet conformation with glutamic acid residues at the turn positions. This conformation was retained upon conjugation with the various PEGs as was indicated by infra-red spectroscopy. Whereas the polypeptide alone formed large aggregates, transmission electron microscopy (TEM) analysis showed well-defined fibrillar structures with a width of approximately 12 nm for [(AG)3EG]20-PEG750 triblock copolymer. Based on TEM and atomic force microscopy microscopy (AFM) data fibril formation is proposed to occur in the beta-sheet stacking direction. The presence of reactive groups at the fibril surface could be useful, for example, as a scaffold in the generation of conducting nanowires. Furthermore, the design of an alpha-helical polypeptide is presented, which could act as a scaffold for the preparation of well-defined glycopolymers. A designed polypeptide with the repetitive sequence [(MAKA)2MAA]n (M = methionine) harbours methionine and lysine residues at opposing sides of the helical axis. Whereas lysine residues can be directly used for chemical functionalization, replacement of methionine with the non-proteinogenic analogue 2-amino-5-hexynoic acid, should provide a handle for an efficient conjugation via [3+2]-cycloaddition. Although circular dichroism analysis of small peptides showed that the designed sequence was prone to adopt an alpha-helical conformation, the recombinant production of longer polypeptides in Escherichia coli was unsuccessful.Radboud University Nijmegen,, 21 november 2006Promotores : Hest, J.C.M. van, Stunnenberg, H.G.154 p

Psychological interference in in vitro fertilization treatment.

Contains fulltext : 58010.pdf (publisher's version ) (Closed access)Because several studies indicate that psychological factors play a role in dropping out of IVF treatment, the question arises as to whether psychological interference is indicated

Peptide-containing block copolymers: Synthesis and potential applications of bio-mimetic materials

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Well-defined polymer architectures for controlled assembly: Beta-sheet containing hybrid block copolymers

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Polymer protein hybrids

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