Supermassive Black Hole Tests of General Relativity with eLISA

Motivated by the parameterized post-Einsteinian (ppE) scheme devised by Yunes and Pretorius, which introduces corrections to the post-Newtonian coefficients of the frequency domain gravitational waveform in order to emulate alternative theories of gravity, we compute analytical time domain waveforms that, after a numerical Fourier transform, aim to represent (phase corrected only) ppE waveforms. In this formalism, alternative theories manifest themselves via corrections to the phase and frequency, as predicted by General Relativity (GR), at different post-Newtonian (PN) orders. In order to present a generic test of alternative theories of gravity, we assume that the coupling constant of each alternative theory is manifestly positive, allowing corrections to the GR waveforms to be either positive or negative. By exploring the capabilities of massive black hole binary GR waveforms in the detection and parameter estimation of corrected time domain ppE signals, using the current eLISA configuration (as presented for the ESA Cosmic Vision L3 mission), we demonstrate that for corrections arising at higher than 1PN order in phase and frequency, GR waveforms are sufficient for both detecting and estimating the parameters of alternative theory signals. However, for theories introducing corrections at the 0 and 0.5 PN order, GR waveforms are not capable of covering the entire parameter space, requiring the use of non-GR waveforms for detection and parameter estimation.Comment: 13 pages, 5 figure

A Time Domain Waveform for Testing General Relativity

Gravitational-wave parameter estimation is only as good as the theory the waveform generation models are based upon. It is therefore crucial to test General Relativity (GR) once data becomes available. Many previous works, such as studies connected with the ppE framework by Yunes and Pretorius, rely on the stationary phase approximation (SPA) to model deviations from GR in the frequency domain. As Fast Fourier Transform algorithms have become considerably faster and in order to circumvent possible problems with the SPA, we test GR with corrected time domain waveforms instead of SPA waveforms. Since a considerable amount of work has been done already in the field using SPA waveforms, we establish a connection between leading-order-corrected waveforms in time and frequency domain, concentrating on phase-only corrected terms. In a Markov Chain Monte Carlo study, whose results are preliminary and will only be available later, we will assess the ability of the eLISA detector to measure deviations from GR for signals coming from supermassive black hole inspirals using these corrected waveforms.Comment: 5 pages. Proceedings of LISA Symposium X, submitted to Journal of Physics: Conference Serie

Robust utility maximisation under proportional transaction costs for c\`adl\`ag price processes

We consider robust utility maximisation in continuous-time financial markets with proportional transaction costs under model uncertainty. For this, we work in the framework of Chau and R\'asonyi (2019), where robustness is achieved by maximising the worst-case expected utility over a possibly uncountable class of models that are all given on the same underlying filtered probability space with incomplete filtration. In this setting, we give sufficient conditions for the existence of an optimal trading strategy extending the result for utility functions on the positive half-line of Chau and R\'asonyi (2019) from continuous to general strictly positive c\`adl\`ag price processes. This allows us to provide a positive answer to an open question pointed out in Chau and R\'asonyi (2019) and shows that the embedding into a countable product space is not essential

Efficacy and safety of moxidectin, synriam, synriam-praziquantel versus praziquantel against schistosoma haematobium and S. mansoni infections: a randomized, exploratory phase 2 trial

Schistosomiasis affects millions of people, yet treatment options are limited. The antimalarial Synriam (piperaquine 150 mg/arterolane 750 mg) and the anthelminthic moxidectin revealed promising antischistosomal properties in preclinical or clinical studies.; We conducted two single-blind, randomized exploratory Phase 2 trials in Schistosoma mansoni and S. haematobium-infected adolescents in northern and central Côte d'Ivoire. Our primary endpoints were cure rates (CRs) and egg reduction rates (ERRs) based on geometric mean and safety. Each subject was asked to provide two stool samples (S. mansoni trial) for Kato-Katz analysis or three urine samples (S. haematobium trial) for urine filtration and one finger prick for malaria screening at baseline and follow-up. Participants were randomly assigned to either moxidectin, Synriam, Synriam plus praziquantel or praziquantel.; 128 adolescents (age: 12-17 years) were included in each study. Against S. haematobium moxidectin and Synriam revealed low efficacy. On the other hand, Synriam plus praziquantel and praziquantel yielded CRs of 60.0% and 38.5% and ERRs of 96.0% and 93.5%, respectively. CRs observed in the treatment of S. mansoni were 13.0%, 6.7%, 27.0%, and 27.6% for moxidectin, Synriam, Synriam plus praziquantel and praziquantel, respectively. ERRs ranged from 64.9% (Synriam) to 87.5% (praziquantel).; Synriam and moxidectin show low efficacy against S. haematobium, hence an ancillary benefit is not expected when these drugs are used for treating onchocerciasis and malaria in co-endemic settings. Further studies are needed to corroborate our findings that moxidectin and Synriam show moderate ERRs against S. mansoni

Pharmacokinetic study of praziquantel enantiomers and its main metabolite R-trans-4-OH-PZQ in plasma, blood and dried blood spots in Opisthorchis viverrini-infected patients

Praziquantel (PZQ) is the treatment of choice for infections with the liver fluke Opisthorchis viverrini, a major health problem in Southeast Asia. However, pharmacokinetic (PK) studies investigating the disposition of PZQ enantiomers (R- and S-PZQ) and its main metabolite, R-trans-4-OH-PZQ, in diseased patients are lacking. The implementation of a dried blood spot (DBS) sampling technique would ease the performance of PK studies in remote areas without clinical facilities. The aim of the present study is to provide data on the disposition of PZQ enantiomers and R-trans-4-OH-PZQ in opisthorchiasis patients and to validate the use of DBS compared to plasma and blood sampling.; PZQ was administered to nine O. viverrini-infected patients at 3 oral doses of 25 mg/kg in 4 h intervals. Plasma, blood and DBS were simultaneously collected at selected time points from 0 to 24 h post-treatment. PK parameters were determined using non-compartmental analysis. Drug concentrations and areas under the curve (AUC0-24h) measured in the 3 matrices were compared using Bland-Altman analysis. We observed plasma AUC0-24hs of 1.1, 9.0 and 188.7 μg/ml*h and half-lives of 1.1, 3.3 and 6.4 h for R-PZQ, S-PZQ and R-trans-4-OH, respectively. Maximal plasma concentrations (Cmax) of 0.2, 0.9 and 13.9 μg/ml for R-PZQ, S-PQZ and R-trans-4-OH peaked at 7 h for PZQ enantiomers and at 8.7 h for the metabolite. Individual drug concentration measurements and patient AUC0-24hs displayed ratios of blood or DBS versus plasma between 79-94% for R- and S-PZQ, and between 108-122% for R-trans-4-OH.; Pharmacodynamic (PD) in vitro studies on PZQ enantiomers and R-trans-4-OH-PZQ are necessary to be able to correlate PK parameters with efficacy. DBS appears to be a valid alternative to conventional venous sampling for PK studies in PZQ-treated patients

Can the ice-water test predict the outcome of intradetrusor injections of botulinum toxin in patients with neurogenic bladder dysfunction?

The aim of this project was to evaluate the ice-water test as a predictor of the response to intradetrusor botulinum toxin injection in patients with neurogenic detrusor overactivity. We retrospectively evaluated the urodynamic parameters in 22 patients with neurogenic bladder dysfunction and positive ice-water test. Maximum cystometric capacity (MCC), reflex volume (RV), maximum detrusor pressure during voiding (MVP) and bladder compliance (BC) were compared before and after intradetrusor injection of 300units botulinum toxin and calculated as a quotient. The ice-water test was performed before the injection, and the maximum pressure rise and the time to maximum pressure were measured. Furthermore, the ratio between maximum pressure and time to reach maximum pressure was calculated as the velocity of pressure rise. Correlations between the ice-water test criteria and the quotients of the cystometric data before and after injection were determined by the Spearmen's Rho coefficient. The increase in MCC and RV after botulinum toxin A injection showed a small positive, but insignificant correlation of 0.25 and 0.2 to the velocity of pressure rise of the ice-water test. A small negative, but insignificant correlation was found in change of BC and MVP with −0.17 and −0.2, respectively. Based on our population the ice-water test cannot predict the efficacy of intradetrusor botulinum toxin injections in patients with neurogenic detrusor overactivit

Two Enabling Strategies for the Stereoselective Conversion of Internal Alkynes into Trisubstituted Alkenes

An expedient method for the C-methylation of alkenylstannanes with formation of trisubstituted alkenes is described, which relies on the use of MeI in combination with copper thiophene-2-carboxylate (CuTC) as promotor and tetra-n-butylammonium diphenylphosphinate as an effective tin scavenger; in some cases, it proved beneficial to further supplement the mixture with catalytic amounts of Pd(PPh3)4. Under these conditions, the reaction is robust, high yielding, and compatible with many functional groups that might not subsist under more traditional conditions used to C-alkylate organotin derivatives. A qualitative analysis of the reaction profile suggested that the in situ formation of a reactive organocopper intermediate and its interception by MeI is only barely faster than O-methylation of the phosphinate additive by the same alkylating agent. To guarantee high yields and prevent net protodestannation from occurring, the reaction protocol had to be optimized such that these competing processes are properly decoupled. The new method is particularly well suited for the stereoselective preparation of the (E)-2-methylbut-2-en-1-ol motif that is present in numerous natural products. Alternatively, this particular target structure can be accessed starting from α-hydroxy alkenylsiloxane precursors, which get C-methylated upon exposure to CuI/LiOtBu and MeI by what is thought to be a Brook rearrangement/ alkylation sequence. The required substrates are best prepared by ruthenium-catalyzed trans-hydrosilylation or trans-hydrostannation of propargyl alcohols

Modulation of transendothelial permeability and expression of ATP-binding cassette transporters in cultured brain capillary endothelial cells by astrocytic factors and cell-culture conditions

Confluent cell monolayers of brain capillary endothelial cells (BCEC) are used widely as an in vitro cell culture model of the blood-brain barrier. The present study describes the influence of cell-culture conditions on tight junctions, filamentous-actin cytoskeleton, and expression of ATP-binding cassette (ABC) transporters in primary cell cultures of porcine BCEC. Astrocyte as well as C6 glioma-conditioned cell culture medium was used in combination with retinoic acid, dexamethasone, cyclic adenosine monophosphate (cAMP) analogs, or 1,25-dihydroxyvitamin D3. It was shown that C6-conditioned medium led to a reorganization of filamentous actin and to an improved staining of zonula occludens-associated protein-1 (ZO-1). Further optimization of these culture conditions was achieved with cAMP analogs and dexamethasone. Retinoic acid, as well as 1,25-dihydroxyvitamin D3, did not improve cellular tight junctions as judged by filamentous actin, ZO-1 rearrangement, and transcellular electrical resistance (TER) measurements. However, these morphological changes did not influence the paracellular permeability of the extracellular marker sucrose. Expression of ABC transporters such as P-glycoprotein, multidrug resistance-associated protein-1( MRP1), and MRP2 were compared by measuring messenger RNA (mRNA) levels in whole-brain tissue, isolated brain capillaries, and cultured cells. In freshly isolated BCEC, mRNA levels of MRP2 and P-glycoprotein dropped by two- to sevenfold, respectively, whereas MRP1 mRNA levels were slightly increased. During cell culture, mRNA levels of MRP1 and MRP2 decreased by up to fivefold, while P-glycoprotein levels remained constant. These results were unaltered by different cell-culture conditions. In conclusion, the present study suggests that paracellular permeability, as well as mRNA expression of the studied ABC transporters in primary cultures, of porcine BCEC are insensitive toward changes in cell-culture condition