Formation of supramolecular polymers by chrysene oligomers

Supramolecular assembly of π-conjugated systems is of large interested due to the possibility to use them in electronic devices.[1] Chrysene is a polyaromatic hydrocarbon which has been studied e.g for organic light-emitting diodes (OLEDs).[2] In continuation of our previous work involving the supramolecular polymerisation of pyrene oligomers [3] an oligomer consisting of three chrysenes linked by phophodiesters was synthesised (Chry3). UV-Vis measurements show that aggregates of Chry3 are formed in aqueous medium. This is illustrated by general hypochromicity, a change in vibronic band intensities and, in particular, the appearance of a red-shifted absorption band in the S0 → S2 transition. The data suggest the formation of J-aggregates. The formation of supramolecular polymers is further studied by temperature-dependent absorption- and fluorescence measurements, and by atomic force microscopy (AFM).

Towards the continuum limit in transport coefficient computations

The analytic continuation needed for the extraction of transport coefficients necessitates in principle a continuous function of the Euclidean time variable. We report on progress towards achieving the continuum limit for 2-point correlator measurements in thermal SU(3) gauge theory, with specific attention paid to scale setting. In particular, we improve upon the determination of the critical lattice coupling and the critical temperature of pure SU(3) gauge theory, estimating r0Tc ≃ 0.7470(7) after a continuum extrapolation. As an application the determination of the heavy quark momentum diffusion coefficient from a correlator of colour-electric fields attached to a Polyakov loop is discussed.

Dispersive analysis of the pion transition form factor

We analyze the pion transition form factor using dispersion theory. We calculate the singly-virtual form factor in the time-like region based on data for the e+e−→3π cross section, generalizing previous studies on ω,ϕ→3π decays and γπ→ππ scattering, and verify our result by comparing to e+e−→π0γ data. We perform the analytic continuation to the space-like region, predicting the poorly-constrained space-like transition form factor below 1GeV, and extract the slope of the form factor at vanishing momentum transfer aπ=(30.7±0.6)×10−3. We derive the dispersive formalism necessary for the extension of these results to the doubly-virtual case, as required for the pion-pole contribution to hadronic light-by-light scattering in the anomalous magnetic moment of the muon.

Elucidation of Nucleic Acid–Drug Interactions by Tandem Mass Spectrometry

In continuation of the long tradition of mass spectrometric research at the University of Bern, our group focuses on the characterization of nucleic acids as therapeutic agents and as drug targets. This article provides a short overview of our recent work on platinated single-stranded and higher-order nucleic acids. Nearly three decades ago the development of soft ionization techniques opened a whole new chapter in the mass spectrometric analysis of not only nucleic acids themselves, but also their interactions with potential drug candidates. In contrast to modern next generation sequencing approaches, though, the goal of the tandem mass spectrometric investigation of nucleic acids is by no means the complete sequencing of genetic DNA, but rather the characterization of short therapeutic and regulatory oligonucleotides and the elucidation of nucleic acid–drug interactions. The influence of cisplatin binding on the gas-phase dissociation of nucleic acids was studied by the means of electrospray ionization tandem mass spectrometry. Experiments on native and modified DNA and RNA oligomers confirmed guanine base pairs as the preferred platination site and laid the basis for the formulation of a gas-phase fragmentation mechanism of platinated oligonucleotides. The study was extended to double stranded DNA and DNA quadruplexes. While duplexes are believed to be the main target of cisplatin in vivo, the recently discovered DNA quadruplexes constitute another promising target for anti-tumor drugs owing to their regulatory functions in the cell cycle.

Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: results from a randomized controlled trial.

PURPOSE This study assessed whether a cycle of "routine" therapeutic drug monitoring (TDM) for imatinib dosage individualization, targeting an imatinib trough plasma concentration (C min) of 1,000 ng/ml (tolerance: 750-1,500 ng/ml), could improve clinical outcomes in chronic myelogenous leukemia (CML) patients, compared with TDM use only in case of problems ("rescue" TDM). METHODS Imatinib concentration monitoring evaluation was a multicenter randomized controlled trial including adult patients in chronic or accelerated phase CML receiving imatinib since less than 5 years. Patients were allocated 1:1 to "routine TDM" or "rescue TDM." The primary endpoint was a combined outcome (failure- and toxicity-free survival with continuation on imatinib) over 1-year follow-up, analyzed in intention-to-treat (ISRCTN31181395). RESULTS Among 56 patients (55 evaluable), 14/27 (52 %) receiving "routine TDM" remained event-free versus 16/28 (57 %) "rescue TDM" controls (P = 0.69). In the "routine TDM" arm, dosage recommendations were correctly adopted in 14 patients (median C min: 895 ng/ml), who had fewer unfavorable events (28 %) than the 13 not receiving the advised dosage (77 %; P = 0.03; median C min: 648 ng/ml). CONCLUSIONS This first target concentration intervention trial could not formally demonstrate a benefit of "routine TDM" because of small patient number and surprisingly limited prescriber's adherence to dosage recommendations. Favorable outcomes were, however, found in patients actually elected for target dosing. This study thus shows first prospective indication for TDM being a useful tool to guide drug dosage and shift decisions. The study design and analysis provide an interesting paradigm for future randomized TDM trials on targeted anticancer agents.

Ancient History as a Means of Transforming Colonial India in the Late-Eighteenth and Early-Nineteenth Centuries

This article focuses on the studies and discourses of mostly British scholars of the early colonial period belonging to two schools of thought. It shows how the studies of both schools – European orientalism and utilitarianism – were intricately connected to the political development of the emerging British paramountcy over the South Asian sub-continent, as both were looking for means of establishing and/or strengthening colonial rule. Nevertheless, the debate was not just a continuation of discussions in Europe. Whereas the ideas of the European Enlightenment had some influence, the transformation of the Mughal Empire and especially the idea of a decline of Muslim rule offered ample opportunities for understanding the early history of India either as some sort of “Golden Age,” as the orientalists and their indigenous supporters did, or as something static and degenerate, as the utilitarians did, and from which the population of sub-continent had to be saved by colonial rule and colonial values. Fearing the spread of the ideas of the French Revolution, the first group of British scholars sought to persuade the native elites of South Asia to take the lessons of their past for the future development of their homeland. Just as the classicists back in Europe, these scholars were convinced that large-scale explanations of the past could also teach political and moral lessons for the present although it was important to deal with the distant past in an empirical manner. The utilitarians on the other hand believed that India had to be saved from its own depravity through the English language and Western values, which amounted to nothing less than the modern transformation of the true Classical Age.

Is postmenopausal hormone replacement therapy suitable after a cardio- or cerebrovascular event?

PURPOSE Vascular disease is the leading cause of death in women. One-third of acute events affect women below age 60, when the prevalence of menopausal symptoms is high. This raises the question if hormone replacement therapy (HRT) may be an appropriate treatment for individual women although vascular disease is generally considered a contraindication. METHODS Selective literature search was used for this study. RESULTS In healthy women, HRT increases risks for venous thromboembolism and ischemic stroke, but for cardiovascular disease apparently only beyond 10 years after menopause or 60 years of age. Limited data in women with cardio or cerebrovascular disease have not demonstrated an increased risk for a vascular recurrent event, but for the first year after initiation. In HRT users affected by a cardiovascular event continuation of HRT has not been found to be associated with adverse outcome. Low dose estradiol--preferentially as transdermal patches, if necessary combined with metabolically neutral progestins--appears to convey lower risk. CONCLUSIONS Safety data on HRT in survivors of cardiovascular events or ischemic stroke are limited, but exceptionally increased risk appears to be excluded. If off-label use of HRT is considered to be initiated or continued in women with cardio- or cerebrovascular disease, extensive counseling on the pros and cons of HRT is mandatory.

Generalised integrable λ- and η-deformations and their relation

We construct two-parameter families of integrable λ -deformations of two-dimensional field theories. These interpolate between a CFT (a WZW/gauged WZW model) and the non-Abelian T-dual of a principal chiral model on a group/symmetric coset space. In examples based on the SU(2) WZW model and the SU(2)/U(1) exact coset CFT, we show that these deformations are related to bi-Yang–Baxter generalisations of η-deformations via Poisson–Lie T-duality and analytic continuation. We illustrate the quantum behaviour of our models under RG flow. As a byproduct we demonstrate that the bi-Yang–Baxter σ-model for a general group is one-loop renormalisable.

Postnatal retention in HIV care: insight from the Swiss HIV Cohort Study over a 15-year observational period.

OBJECTIVES The aim of this study was to quantify loss to follow-up (LTFU) in HIV care after delivery and to identify risk factors for LTFU, and implications for HIV disease progression and subsequent pregnancies. METHODS We used data on pregnancies within the Swiss HIV Cohort Study from 1996 to 2011. A delayed clinical visit was defined as > 180 days and LTFU as no visit for > 365 days after delivery. Logistic regression analysis was used to identify risk factors for LTFU. RESULTS A total of 695 pregnancies in 580 women were included in the study, of which 115 (17%) were subsequent pregnancies. Median maternal age was 32 years (IQR 28-36 years) and 104 (15%) women reported any history of injecting drug use (IDU). Overall, 233 of 695 (34%) women had a delayed visit in the year after delivery and 84 (12%) women were lost to follow-up. Being lost to follow-up was significantly associated with a history of IDU [adjusted odds ratio (aOR) 2.79; 95% confidence interval (CI) 1.32-5.88; P = 0.007] and not achieving an undetectable HIV viral load (VL) at delivery (aOR 2.42; 95% CI 1.21-4.85; P = 0.017) after adjusting for maternal age, ethnicity and being on antiretroviral therapy (ART) at conception. Forty-three of 84 (55%) women returned to care after LTFU. Half of them (20 of 41) with available CD4 had a CD4 count < 350 cells/μL and 15% (six of 41) a CD4 count < 200 cells/μL at their return. CONCLUSIONS A history of IDU and detectable HIV VL at delivery were associated with LTFU. Effective strategies are warranted to retain women in care beyond pregnancy and to avoid CD4 cell count decline. ART continuation should be advised especially if a subsequent pregnancy is planned.

Plasma NGAL and glomerular filtration rate in cardiac transplant recipients treated with standard or reduced calcineurin inhibitor levels.

AIM Predictors of renal recovery following conversion from calcineurin inhibitor- to proliferation signal inhibitor-based therapy are lacking. We hypothesized that plasma NGAL (P-NGAL) could predict improvement in glomerular filtration rate (GFR) after conversion to everolimus. PATIENTS & METHODS P-NGAL was measured in 88 cardiac transplantation patients (median 5 years post-transplant) with renal dysfunction randomized to continuation of conventional calcineurin inhibitor-based immunosuppression or switching to an everolimus-based regimen. RESULTS P-NGAL correlated with measured GFR (mGFR) at baseline (R(2) = 0.21; p < 0.001). Randomization to everolimus improved mGFR after 1 year (median [25-75 % percentiles]: ΔmGFR 5.5 [-0.5-11.5] vs -1 [-7-4] ml/min/1.73 m(2); p = 0.006). Baseline P-NGAL predicted mGFR after 1 year (R(2) = 0.18; p < 0.001), but this association disappeared after controlling for baseline mGFR. CONCLUSION P-NGAL and GFR correlate with renal dysfunction in long-term heart transplantation recipients. P-NGAL did not predict improvement of renal function after conversion to everolimus-based immunosuppression.

Earthquake- induced Geomorphology: A Neotectonic Study at the Front of the Alps (Lake Thun & Aare Valley, Switzerland)

We present a multi-disciplinary two-step approach to assess the potential for seismic hazard of the Aare valley and perialpine Lake Thun (Switzerland). High-resolution seismic images and multibeam-bathymetric data, complemented by field observations represent the tools to identify potentially active seismogenic fault structures. Several second-order earthquake effects such as subaqueous mass movements, seismites and liquefaction structures have been observed in Lake Thun and ultimately document the seismic activity of the study area. A first investigation of possibly first-order active structures is presented in the scope of this study. Recently acquired bathymetric data in Lake Thun reveal significant morphologic depressions aligning with an observed lineament on land. Furthermore, high-resolution seismic images indicate potential fault structures in Lake Thun. However, their continuation with depth has to be verified with a multichannel seismic campaign, scheduled for March 2015.