Alopecia areata universalis elicited during treatment with adalimumab

Adalimumab is a fully humanized recombinant anti-tumour-necrosis-factor (TNF-alpha) monoclonal antibody which has been approved for rheumatoid arthritis, active ankylosing spondylitis, psoriatic arthritis and Crohn's disease. We report a case of alopecia areata (AA) universalis occurring 6 months after administration of adalimumab monotherapy in a patient with a long-standing history of psoriatic arthritis and psoriasis. The diagnosis was confirmed by a scalp biopsy which showed a peribulbar infiltrate of both CD4+ and CD8+ T cells, CD1a+ dendritic cells as well as CD68+ and CD163+ macrophages. In addition, immunofluorescence staining for TNF-alpha was found in the mononuclear cell infiltrate. This case suggests a complex role of TNF-alpha in the induction of AA.

Improved sampling for gradient-domain metropolis light transport

We present a generalized framework for gradient-domain Metropolis rendering, and introduce three techniques to reduce sampling artifacts and variance. The first one is a heuristic weighting strategy that combines several sampling techniques to avoid outliers. The second one is an improved mapping to generate offset paths required for computing gradients. Here we leverage the properties of manifold walks in path space to cancel out singularities. Finally, the third technique introduces generalized screen space gradient kernels. This approach aligns the gradient kernels with image structures such as texture edges and geometric discontinuities to obtain sparser gradients than with the conventional gradient kernel. We implement our framework on top of an existing Metropolis sampler, and we demonstrate significant improvements in visual and numerical quality of our results compared to previous work.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Der Koran und die Genealogie des Islam

Lange war man im Westen davon überzeugt gewesen, dass zwischen Religion, Gesellschaft und Staat in der Epoche der europäischen Aufklärung ein Einverständnis gefunden worden ist. Diese Sicherheit ist in den vergangenen Jahrzehnten ins Wanken geraten. Im Namen ‘des’ Islam werden Terroranschläge verübt und Kriege geführt. Von vielen Menschen wird ‘der’ Islam als eine Religion wahrgenommen, die nicht zwischen Religion und Zivilgesellschaft unterscheidet und den Friedenszustand gefährdet. Doch gibt es überhaupt ‘den’ Islam oder ‘den’ Koran? Der Islam wird oft in einer problematischen Vereinfachung auf den Koran und den Propheten Muḥammad reduziert. Daraus wird dann der Kurzschluss gezogen, der Islam lasse sich aus diesem Ursprung heraus definieren. Gegen dieses ahistorische Ursprungsdenken und die damit einhergehenden Stereotypen zu ‘dem’ Islam und ‘dem’ Koran bring Reinhard Schulze die Geschichte in Anschlag. Er verfolgt in seiner gelehrten und analytisch präzisen Studie die Geschichte der Entstehung der Schrift Koran über deren sprachliche Verfasstheit (das Arabische) und Intertexte; betrachtet die Offenbarung an Muḥammad aus historischer Perspektive und reflektiert – nicht zuletzt – über die Voraussetzungen und unhinterfragten Prämissen des wissenschaftlichen Diskurses über den Islam – so etwa im Orientalismus des 19. Jahrhunderts, in der Rede von der Religion als anthropologischer Konstante oder neurobiologischer ‘Programmierung’.

Antwort Sr. Maj. des Königs, an die Deputation der Bürger, vom zweiten Wahlbezirk, auf ihre Bitte, um Aufhebung des Belagerungs-Zustandes: Seine Majestät empfingen die Deputation ernst und sprachen Sich in kurzen Worten dahin aus ...

Welsch (Projektbearbeiter): Friedrich Wilhelm IV. lehnt die Bitte um Aufhebung des Belagerungszustandes mit der Begründung ab, er lasse sich durch nichts bestimmen, von dem, was er für gut und recht für sein Volk erachte, abzugehen und bezieht sich dabei auf den Inhalt des Liedes Nr. 205 des Porst'schen Evangelischen Kirchengesangbuches ("Gott selbsten hat dies Wort / der Wahrheit fest versiegelt ...")

European Dermatology Forum Guidelines on topical photodynamic therapy

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, squamous cell carcinoma in-situ, superficial and certain thin basal cell carcinomas. Recurrence rates are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as a lesional or as a field therapy and has the potential to delay/reduce the development of new lesions. PDT has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immunocompetent individuals. Many additional indications have been evaluated, including photo-rejuvenation and inflammatory and infective dermatoses. This S2 guideline considers all current and emerging indications for the use of topical photodynamic therapy in Dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence. An unabridged version of this guideline is available online at: http://www.euroderm.org/edf/index.php/edf-guidelines.

Molecular diagnostics of myeloproliferative neoplasms

Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. Whilst many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations are considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations, and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future play an increasing role in the molecular diagnosis of MPN. Accepted for publication 30 April 2015 doi:10.1111/ejh.12578

Gradient-domain Path Tracing

We introduce gradient-domain rendering for Monte Carlo image synthesis.While previous gradient-domain Metropolis Light Transport sought to distribute more samples in areas of high gradients, we show, in contrast, that estimating image gradients is also possible using standard (non-Metropolis) Monte Carlo algorithms, and furthermore, that even without changing the sample distribution, this often leads to significant error reduction. This broadens the applicability of gradient rendering considerably. To gain insight into the conditions under which gradient-domain sampling is beneficial, we present a frequency analysis that compares Monte Carlo sampling of gradients followed by Poisson reconstruction to traditional Monte Carlo sampling. Finally, we describe Gradient-Domain Path Tracing (G-PT), a relatively simple modification of the standard path tracing algorithm that can yield far superior results.

Recent Advances in Adaptive Sampling and Reconstruction for Monte Carlo Rendering

Monte Carlo integration is firmly established as the basis for most practical realistic image synthesis algorithms because of its flexibility and generality. However, the visual quality of rendered images often suffers from estimator variance, which appears as visually distracting noise. Adaptive sampling and reconstruction algorithms reduce variance by controlling the sampling density and aggregating samples in a reconstruction step, possibly over large image regions. In this paper we survey recent advances in this area. We distinguish between “a priori” methods that analyze the light transport equations and derive sampling rates and reconstruction filters from this analysis, and “a posteriori” methods that apply statistical techniques to sets of samples to drive the adaptive sampling and reconstruction process. They typically estimate the errors of several reconstruction filters, and select the best filter locally to minimize error. We discuss advantages and disadvantages of recent state-of-the-art techniques, and provide visual and quantitative comparisons. Some of these techniques are proving useful in real-world applications, and we aim to provide an overview for practitioners and researchers to assess these approaches. In addition, we discuss directions for potential further improvements.