Weak Segregation Theory and Non-Conventional Morphologies in the Ternary ABC Triblock Copolymers

The Leibler weak segregation theory in molten diblock copolymers is generalized with due regard for the 2nd shell harmonics contributions defined in the paper and the phase diagrams are built for the linear and miktoarm ternary ABC triblock copolymers. The symmetric linear copolymers with the middle block non-selective with respect to the side ones are shown to undergo the continuous ODT not only into the lamellar phase but also into various non-conventional cubic phases (depending on the middle block composition it could be the simple cubic, face-centered cubic or non-centrosymmetric phase revealing the symmetry of space group No.214 first predicted to appear in molten block copolymers). For asymmetric linear ABC copolymers a region of compositions is found where the weakly segregated gyroid (double gyroid) phase exists between the planar hexagonal and lamellar or one of the non-conventional cubic phases up to the very critical point. In contrast, the miktoarm ABC block copolymers with one of its arm non-selective with respect to the two others are shown to reveal a pronounced tendency towards strong segregation, which is preceded by increase of stability of the conventional BCC phase and a peculiar weakly segregated BCC phase (BCC3), where the dominant harmonics belong to the 3rd co-ordination sphere of the reciprocal lattice. The validity region of the developed theory is discussed and outlined in the composition triangles both for linear and miktoarm copolymers.Comment: 61 pages, 12 figure

The long-term costs and effects of tubal flushing with oil-based versus water-based contrast during hysterosalpingography

Acknowledgements The authors would like to thank all the participating women, the hospitals and their staff, the research nurses and the staff of the Nationwide Consortium for Women's Health Research (NVOG Consortium; www.zorgevaluatienederland.nl ) for logistical support. Thanks also go to the H2Oil study group collaborators: Nan van Geloven, Jos W. R. Twisk, Peter M. van de Ven and Peter G. A. Hompes for their contributions to this study. The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The long-term follow-up study and economic analysis, both investigator-initiated studies, were funded by a research grant from Guerbet, France. The funders had no role in study design or collection, analysis or interpretation of the data. Declaration of interest: C.T.P. has received consultancy fees for external work from Guerbet, France. K.D. reports receiving travel and speakers fee from Guerbet. H.R.V. reports receiving consultancy fees from Ferring. M.G. works at the Department of Reproductive Medicine of the Amsterdam UMC (location AMC and location VUmc). Location VUmc has received several research and educational grants from Guerbet, Merck and Ferring. C.B.L. reports speakers fee from Ferring in the past, and his department receives research grants from Ferring, Merck and Guerbet. V.M. reports receiving travel and speakers fees as well as research grants from Guerbet. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437). B.W.J.M. has received research grants from Merck and Guerbet. The other authors report no financial or commercial conflicts of interest.Peer reviewedPublisher PD

ULTrasound-guided TRAnsfemoral puncture in COmplex Large bORe PCI: study protocol of the UltraCOLOR trial

Introduction Although recently published evidence favours transradial access (TRA) when using large-bore guiding catheters for percutaneous coronary intervention (PCI) of complex coronary lesions, the femoral artery will still be used in a considerate proportion of patients undergoing complex PCI, especially in PCI of chronic total occlusions (CTO). Ultrasound-guided puncture of the femoral artery may reduce clinically relevant access site complications, but robust evidence is lacking up to date. Methods and analysis A total of 542 patients undergoing complex PCI, defined as PCI of CTO, complex bifurcation, heavy calcified lesion or left main, in which the 7-F or 8-F transfemoral access is required, will be randomised to ultrasound-guided puncture or fluoroscopy-guided puncture. The primary outcome is the incidence of the composite end-point of clinically relevant access site related bleeding and/or vascular complications requiring intervention. Access site complications and major adverse cardiovascular events up to 1 month will also be compared between both groups. Ethics and dissemination Ethical approval for the study was granted by the local Ethics Committee ('Medisch Ethische Toetsing Commissie Isala Zwolle') for all Dutch sites, 'Comité Medische Ethiek Ziekenhuis Oost-Limburg' for Hospital Oost-Limburg, 'Comité d'éthique CHU-Charleroi - ISPPC' for Centre Hospilatier Universitaire de Charleroi and 'Ethik Kommission de Arztekammer Nordrhein' for Elisabeth-Krankenhaus). The trial outcomes will be published in peer-reviewed journals of the concerned literature. The ultrasound guided transfemoral access in complex large bore PCI trial has been administered in the ClinicalTrials.gov database, reference number: NCT03846752. Registration details ClinicalTrials.gov identifier: NCT03846752

Platelet Inhibition, Endothelial Function, and Clinical Outcome in Patients Presenting With ST-Segment-Elevation Myocardial Infarction Randomized to Ticagrelor Versus Prasugrel Maintenance Therapy: Long-Term Follow-Up of the REDUCE-MVI Trial

Background Off-target properties of ticagrelor might reduce microvascular injury and improve clinical outcome in patients with ST-segment-elevation myocardial infarction. The REDUCE-MVI (Evaluation of Microvascular Injury in Revascularized Patients with ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel) trial reported no benefit of ticagrelor regarding microvascular function at 1 month. We now present the follow-up data up to 1.5 years. Methods and Results We randomized 110 patients with ST-segment-elevation myocardial infarction to either ticagrelor 90 mg twice daily or prasugrel 10 mg once a day. Platelet inhibition and peripheral endothelial function measurements includi

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

Ethnic Inequalities in Psychological Distress : A Population Data Linkage Study on the Pacific Island of Guåhån/Guam

Psychological distress and mental illness has been found to be elevated in migrant groups living in sovereign countries, as well as for indigenous people living under colonial or administrative rule. The north Pacific island of Guam is unusual in its ethnic composition as it has no majority ethnic group, has a large indigenous population and remains a territory of the U.S. This study aimed to identify ethnic differences in self-reported psychological distress between the main ethnic groups on Guam. The study uses a cross sectional design with data linkage methodology, drawing on the Guam Census and the Behavioral Risk Factor Surveillance System health survey for Guam. The results showed that the native Chamorro population had worse self-reported psychological distress (defined as a ‘mental health condition or emotional problem’) than White/Caucasians (OR 2.09, 95% CI 1.52–2.87), particularly for severe distress (OR 3.61, 95% CI 1.33–2.77). This relationship persisted even after adjusting for a wide range of socio-demographic and economic factors (OR 2.58, 95% CI 1.15–5.76). Other Pacific Islanders also had higher psychological distress compared to White/Caucasians, but this association was largely explained by the adjusted factors. The findings are discussed in terms of social and economic disadvantage for Pacific Island peoples on Guam, as well as the impact of colonial administration, disaffection, and lack of autonomy for the Chamorro of Guam. Recommendations are made to improve psychiatric treatment for these groups by considering wider socio-political factors in assessment and treatment, as well as broader implications for the national dialogue on self-determination.Peer reviewe

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

Contains fulltext : 109739.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. METHODS/DESIGN: Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. DISCUSSION: The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. TRIAL REGISTRATION: NTR2657

Individualized versus standard FSH dosing in women starting IVF/ICSI:An RCT. Part 1: The predicted poor responder

STUDY QUESTION: Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? SUMMARY ANSWER: In women with a predicted poor ovarian response (AFC <11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). WHAT IS KNOWN ALREADY: In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. STUDY DESIGN, SIZE, DURATION: Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC <11 (Dutch Trial Register NTR2657). The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. We needed 300 women to assess whether an increased dose strategy would increase the cumulative live birth rate from 25 to 40% (two-sided alpha-error 0.05, power 80%). PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with an AFC ≤ 7 were randomized to an FSH dose of 450 IU/day or 150 IU/day, and women with an AFC 8–10 were randomized to 225 IU or 150 IU/day. In the standard group, dose adjustment was allowed in subsequent cycles based on pre-specified criteria. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8–10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78–1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562–1591)], standard FSH dosing was the dominant strategy in our economic analysis. LIMITATIONS, REASONS FOR CAUTION: Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. WIDER IMPLICATIONS OF THE FINDINGS: Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC <11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women

Prejunctional and postjunctional inhibitory actions of eprosartan and candesartan in the isolated rabbit mesenteric artery

Effects of angiotensin H type I (AT(1)) receptor antagonists eprosartan and candesartan and AT(2) receptor antagonist PD123319 on Ana II-induced facilitation of noradrenergic neurotransmission were investigated in isolated rabbit mesenteric artery under isometric conditions. Sympathoinhibitory potency of AT(1) blockers was compared with their potency concerning inhibition of direct vasoconstrictor effect of Ana II. To investigate blockade of presynaptic AT(1) and AT(2) receptors, effects of Ang II on electrical field stimulation (EFS)-induced contractions in presence or absence of eprosartan, candesartan. or PD123319 were studied. To investigate blockade of postsynaptic AT, receptors, effects of either eprosartan or candesartan on concentration-response curves of Ana II were studied. In addition, effect of Ana 11 on postsynaptic alpha-adrenoceptor-mediated responses was studied using noradrenaline. EFS (1, 2, and 4 Hz) caused an increase of contractile force. At stimulation frequencies of 1, 2, and 4 Hz, a subpressor concentration of Ana II (0.5 nM) increased stimulation-induced vasoconstrictor responses by 2.8 +/- 0.5, 2.4 +/- 0.4. and 1.6 +/- 0.1 of control values, respectively (p <0.05 compared with control for all frequencies). The enhancement could be antagonized by eprosartan (1 nM-0.1 muM) and candesartan (1 nM-0.1 muM). The AT(2) antagonist PD123319 (10 nM) did not influence Ang II-induced facilitation of stimulation-induced contractions. Contractile responses to exogenous noradrenaline were unaltered in presence of Ana 11 0.5 nM. Ana 11 (1 nM-0.3 muM) caused a concentration-dependent increase in contractile force, which could be antagonized by eprosartan (pD(2)' 8.8 +/- 0.19) and candesartan (pD(2)' 11.3 +/- 0.23). Thus, the facilitating effect of Ana II on noradrenergic neurotransmission is mediated by presynaptically located AT, receptors and not by AT(2) receptors. For eprosartan, sympathoinhibition was achieved at concentrations that also block AT, receptors on vascular smooth muscle. In contrast, for candesartan, presynaptic inhibitory concentrations were considerably higher than those required for postsynaptic inhibitio

Decreased facilitation by angiotensin II of noradrenergic neurotransmission in isolated mesenteric artery of rabbits with chronic heart failure

Both in human and in experimental heart failure (HF), the renin-angiotensin system and the sympathetic nervous system are activated. In a previous study a facilitatory action of angiotensin II (Ang II) was shown in the rabbit mesenteric artery, which was mediated via prejunctionally located Ang II type I (AT(1)) receptors. Very little is known about the effects of Ang II on sympathetic neurotransmission at the peripheral level in congestive heart failure (CFH). Accordingly, in the isolated mesenteric arteries obtained from rabbits with experimentally induced CHF, as well as in age-matched control rabbits, the effect of Ang II on contractions provoked by electrical field stimulation was investigated in the presence and absence of the AT(1) receptor antagonist eprosartan. Additionally, to investigate a possible postjunctional facilitation, the effects of Ang II on alpha-adrenoceptor-mediated responses were studied using noradrenaline (NA). Lastly, the vasoconstrictor effects of Ang II were compared between HF rabbits and controls, by constructing concentration-response curves to Ang II. In control rabbits, Ang II 0.5 nM caused an enhancement of stimulation-induced responses by a factor 3.2 +/- 0.5, 2.4 +/- 0.3, and 1.5 +/- 0.08, at 1, 2, and 4 Hz, respectively (P <0.05 at all frequencies compared with vehicle). In rabbits with HF, the enhancement by Ang II (0.5 ng amounted to a factor 2.1 +/- 0.2, 1.7 +/- 0.1, and 1.2 +/- 0.04, at 1, 2, and 4 Hz, respectively (P <0.05 compared with vehicle at all frequencies). Accordingly, the enhancing effect of Ang II was more pronounced in the control group compared with rabbits with HF (P <0.05 at each frequency). Eprosartan (1 nM-0.1 μg) could inhibit the facilitatory effects of Ang II in arteries from HF as well as from control rabbits. Contractile responses to exogenous NA (3 nM-0.1 mM) were the same in HF rabbits and controls, and they were unaltered in the presence of Ang II 0.5 nM. Ang II (0.1 nM-1 μM) caused a concentration-dependent increase in contractile force, which was the same in HF rabbits and controls. From these findings it can be concluded that in rabbits with CHF as well as in control animals, Ang II facilitates the stimulation-induced vasoconstrictor responses via prejunctionally located AT(1) receptors. The facilitating effect was decreased in vessels obtained from rabbits with CHF, whereas responses to exogenous Ang II were unchanged. These findings may be explained by downregulation or uncoupling of the prejunctional AT(1) recepto