DiffErenCes in AntihypertenSive Drug Blood Levels in Patients with HypertensiON (DECISION):Protocol for a Prospective Observational Study Comparing Pharmacokinetics and Pharmacodynamics Between Young and Elderly Patients

Adequate controlled blood pressure decreases the risk of cardiovascular events. However, the elderly are more vulnerable and thereby more prone to side effects of antihypertensive drugs. A lack of pharmacokinetic and pharmacodynamic (PK/PD) studies in older patients makes specific and tailored advices towards antihypertensive drug therapy difficult. The aim of our study, DiffErenCes In antihypertenSive drug levels In patients with hypertensiON (DECISION), is to fill in this PK/PD knowledge gap and move towards precision dosing. DECISION is a prospective observational PK/PD study set up to determine the difference in exposure to the antihypertensive drugs, losartan and perindopril, measured by drug levels in blood. The area under the curve (AUC; PK) and furthermore the association between the AUC and the effect on blood pressure (PD) will be compared between elderly and younger patients

An Exact Bosonization Rule for c=1 Noncritical String Theory

We construct a string field theory for c=1 noncritical strings using the loop variables as the string field. We show how one can express the nonrelativistic free fermions which describes the theory, in terms of these string fields.Comment: 17 pages, to appear in JHE

Geographical variation in serological responses to recombinant Pneumocystis jirovecii major surface glycoprotein antigens

AbstractThe use of recombinant fragments of the major surface glycoprotein (Msg) of Pneumocystis jirovecii has proven useful for studying serological immune responses of blood donors and human immunodeficiency virus (HIV)-positive (HIV+) patients. Here, we have used ELISA to measure antibody titres to Msg fragments (MsgA, MsgB, MsgC1, MsgC3, MsgC8 and MsgC9 in sera isolated in the USA (n=200 and Spain (n=326), to determine whether geographical location affects serological responses to these antigens. Blood donors from Seville exhibited a significantly greater antibody titre to MsgC8, and significantly lower responses to MsgC3 and MsgC9, than did Cincinnati (USA) donors. Spanish blood donors (n=162 also exhibited elevated responses to MsgC1, MsgC8 and MsgC9 as compared with Spanish HIV+ (n=patients. HIV+ patients who had Pneumocystis pneumonia (PcP+) exhibited a higher response to MsgC8 than did HIV+ PcP- patients. These data show that geographical location plays a role in responsiveness to Msg fragments. Additionally, these fragments have utility in differentiating HIV+ PcP and HIV+ PcP+ among patient populations

A single-step sizing and radiofrequency ablation catheter for circumferential ablation of Barrett's esophagus: Results of a pilot study

Background: The 360 Express balloon catheter (360 Express) has the ability to self-adjust to the esophageal lumen, ensuring optimal tissue contact. Objective: The objective of this article is to evaluate the efficacy and safety of the 360 Express for radiofrequency ablation (RFA) treatment of Barrett's esophagus (BE). Methods: BE patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD) or early cancer (EC) were included. Visible lesions were removed by endoscopic resection (ER) prior to RFA. RFA was performed with the 360 Express using the standard ablation regimen (12J/cm2–clean–12J/cm2). Primary outcome: BE regression percentage at three months. Secondary outcomes: procedure time, adverse events, complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM). Results: Thirty patients (median BE C4M6) were included. Eight patients underwent ER prior to RFA. Median BE regression: 90%. Median procedure time: 31 minutes. Adverse events (13%): laceration (n = 1); atrial fibrillation (n = 1); vomiting and dysphagia (n = 1); dysregulated diabetes (n = 1). After subsequent treatment CE-D and CE-IM was achieved in 97% and 87%, respectively. In 10% a stenosis developed during additional treatment requiring a median of one dilation. Conclusion: This study shows that circumferential RFA using the 360 Express may shorten procedure time, while maintaining efficacy compared to standard circumferential RFA

Notes on the algebraic curves in (p,q) minimal string theory

Loop amplitudes in (p,q) minimal string theory are studied in terms of the continuum string field theory based on the free fermion realization of the KP hierarchy. We derive the Schwinger-Dyson equations for FZZT disk amplitudes directly from the W_{1+\infty} constraints in the string field formulation and give explicitly the algebraic curves of disk amplitudes for general backgrounds. We further give annulus amplitudes of FZZT-FZZT, FZZT-ZZ and ZZ-ZZ branes, generalizing our previous D-instanton calculus from the minimal unitary series (p,p+1) to general (p,q) series. We also give a detailed explanation on the equivalence between the Douglas equation and the string field theory based on the KP hierarchy under the W_{1+\infty} constraints.Comment: 61 pages, 1 figure, section 2.5 and Appendix B added, references added, final version to appear in JHE

Exceptionally Slow Rise in Differential Reflectivity Spectra of Excitons in GaN: Effect of Excitation-induced Dephasing

Femtosecond pump-probe (PP) differential reflectivity spectroscopy (DRS) and four-wave mixing (FWM) experiments were performed simultaneously to study the initial temporal dynamics of the exciton line-shapes in GaN epilayers. Beats between the A-B excitons were found \textit{only for positive time delay} in both PP and FWM experiments. The rise time at negative time delay for the differential reflection spectra was much slower than the FWM signal or PP differential transmission spectroscopy (DTS) at the exciton resonance. A numerical solution of a six band semiconductor Bloch equation model including nonlinearities at the Hartree-Fock level shows that this slow rise in the DRS results from excitation induced dephasing (EID), that is, the strong density dependence of the dephasing time which changes with the laser excitation energy.Comment: 8 figure

The influence of gene expression time delays on Gierer-Meinhardt pattern formation systems

There are numerous examples of morphogen gradients controlling long range signalling in developmental and cellular systems. The prospect of two such interacting morphogens instigating long range self-organisation in biological systems via a Turing bifurcation has been explored, postulated, or implicated in the context of numerous developmental processes. However, modelling investigations of cellular systems typically neglect the influence of gene expression on such dynamics, even though transcription and translation are observed to be important in morphogenetic systems. In particular, the influence of gene expression on a large class of Turing bifurcation models, namely those with pure kinetics such as the Gierer–Meinhardt system, is unexplored. Our investigations demonstrate that the behaviour of the Gierer–Meinhardt model profoundly changes on the inclusion of gene expression dynamics and is sensitive to the sub-cellular details of gene expression. Features such as concentration blow up, morphogen oscillations and radical sensitivities to the duration of gene expression are observed and, at best, severely restrict the possible parameter spaces for feasible biological behaviour. These results also indicate that the behaviour of Turing pattern formation systems on the inclusion of gene expression time delays may provide a means of distinguishing between possible forms of interaction kinetics. Finally, this study also emphasises that sub-cellular and gene expression dynamics should not be simply neglected in models of long range biological pattern formation via morphogens

Two-dimensional superstrings and the supersymmetric matrix model

We present evidence that the supersymmetric matrix model of Marinari and Parisi represents the world-line theory of N unstable D-particles in type II superstring theory in two dimensions. This identification suggests that the matrix model gives a holographic description of superstrings in a two-dimensional black hole geometry.Comment: 22 pages, 2 figures; v2: corrected eqn 4.6; v3: corrected appendices and discussion of vacua, added ref

Towards precision dosing of aripiprazole in children and adolescents with autism spectrum disorder:Linking blood levels to weight gain and effectiveness

Aims: Aripiprazole is one of the most commonly prescribed antipsychotic drugs to children and adolescents worldwide, but it is associated with serious side-effects, including weight gain. This study assessed the population pharmacokinetics of aripiprazole and its active metabolite and investigated the relationship between pharmacokinetic parameters and body mass index (BMI) in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side-effects and drug effectiveness. Methods: Twenty-four children and adolescents (15 males, 9 females) aged 6–18 years were included in a 24-week prospective observational trial. Drug plasma concentrations, side-effects and drug effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were determined. Nonlinear mixed-effects modelling (NONMEM®) was used for a population pharmacokinetic analysis with 92 aripiprazole and 91 dehydro-aripiprazole concentrations. Subsequently, model-based trough concentrations, maximum concentrations and 24-h area under the curves (AUCs) were analysed to predict outcomes using generalized and linear mixed-effects models. Results: For both aripiprazole and dehydro-aripiprazole, one-compartment models best described the measured concentrations, with albumin and BMI as significant covariates. Of all the pharmacokinetic parameters, higher sum (aripiprazole plus dehydro-aripiprazole) trough concentrations best predicted higher BMI z-scores (P &lt;.001) and higher Hb1Ac levels (P =.03) during follow-up. No significant association was found between sum concentrations and effectiveness. Conclusions: Our results indicate a threshold with regard to safety, which suggests that therapeutic drug monitoring of aripiprazole could potentially increase safety in children and adolescents with ASD and behavioural problems.</p