Psoriasis is one of the most chronic diseases in dermatology. Only a small percentage of patients ever experience relapse-free survival. The constant presence of plaques and comorbidities that affect the cardiovascular system, joints, and other organs greatly impair patients' quality of life. In addition, the life expectancy of psoriatic patients is shortened by several years. Hence, long-term and ideally systemic treatment with minimal adverse effects may be warranted.
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This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search,...
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Ever since the introduction of highly active antiretroviral therapy (ART) in 1995, HIV infection has been linked to "metabolic" complications (insulin resistance, dyslipidemia, osteoporosis, and others). Studies suggested increased rates of myocardial infarction, renal insufficiency, neurocognitive dysfunction, and fractures in HIV-postitive patients. Even long-term suppression of HIV seemed to be accompanied by an excess of deleterious inflammation that could promote these complications. The aims...
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Nanomedicines and follow-on versions (also called nanosimilars in the EU) have been on the market partially for decades although without recognition of their nano properties in the beginning; a substantial number is in clinical development. Nanomedicines are typically synthetic and belong to the non-biological complex drugs. They show a high variability in form, structure, and size. Additionally large molecule biologics show nano-characteristics meaning nano-dimension in size (1-100 nm) or specific...
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This study investigates the drug selection and dispensing behaviour of hospital pharmacists of intravenous iron products including iron sucrose and iron sucrose similar, with special emphasis on substitution and interchangeability in France and Spain. Iron-carbohydrate complex drugs represent different available intravenous iron drugs and are part of the non-biological complex drug (NBCD) class, an expanding drug class with up to 30 brands available in intravenous pharmacotherapy and over 50 in clinical...
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Phenytoin (PHT) is one of the most often used critical dose drugs, where insufficient or excessive dosing can have severe consequences such as seizures or toxicity. Thus, the monitoring and precise measuring of PHT concentrations in patients is crucial. This study develops and validates an LC-MS/MS method for the measurement of phenytoin concentrations in different body compartments (i.e., human brain dialysate, blood, and saliva) and compares it with a formerly developed GC-MS method that measures...
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Patients with mitochondrial disorders (MD) frequently present with gastrointestinal complaints, mainly gastrointestinal dysmotility, that interfere with their food intake. A deterioration of their nutritional state may worsen the course of the disease. Our study aimed to evaluate a simple screening tool to identify nutritional risk and perform an extended nutritional assessment to explore the potential presence of deficiencies in this population compared with controls.; A prospective cohort study...
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Apolipoprotein A-1 (Apo A-1) plays an important role in lipid transfer and obesity. Chemical unfolding of α-helical Apo A-1 is induced with guanidineHCl and monitored with differential scanning calorimetry (DSC) and CD spectroscopy. The unfolding enthalpy and the midpoint temperature of unfolding decrease linearly with increasing guanidineHCl concentration, caused by the weak binding of denaturant. At room temperature, binding of 50-60 molecules guanidineHCl leads to a complete Apo A-1 unfolding....
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Psoriasis is a chronic relapsing, remitting interleukin (IL)-23/IL-17-driven skin disease mediated by the interplay of T cells and polymorphonuclear granulocytes. Although preclinical studies have provided insights into the mechanisms of disease initiation, the underpinnings of natural disease remission remain largely unknown. Here, we addressed the contribution of regulatory Foxp3; +; T cells (Treg cells) in psoriasiform skin inflammation and remission using the Aldara-skin inflammation model in...
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Acne and hidradenitis suppurativa (HS) both centre on hair follicles. They often occur together as part of the acne tetrad, but are found in distinct localizations. Acne is primarily defined by the presence of comedones and inflammatory lesions. However, in HS the intertriginous localization and chronicity play equally important roles for the diagnosis to the inflammatory lesions. Genetics, bacteria, environmental factors and innate inflammation have all been found to play a role in acne and/or HS....
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Pathogenesis of cutaneous extraintestinal manifestations [EIM] in inflammatory bowel disease [IBD] remains elusive. Efficacy of anti-TNF agents suggests TNF-dependent mechanisms. The role of other biologics, such as anti-integrins or JAK-inhibitors, is not yet clear.; We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, and Hsp-27/70 on 240 intestinal [55 controls, 185 IBD] and 64 skin biopsies [11 controls, 18 erythema nodosum [EN], 13 pyoderma gangenosum...
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Although anti-tumor necrosis factor (TNF) agents are highly effective in the treatment of psoriasis, 2-5% of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. The pathogenesis of this side effect and its distinction from classical psoriasis remain unknown. Here we show that skin lesions from patients with paradoxical psoriasis are characterized by a selective overexpression of type I interferons, dermal accumulation of plasmacytoid dendritic cells (pDC), and reduced...
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Repetitive skin manipulation is the key symptom in skin picking disorder (SPD) or acne excoriée des jeunes filles Brocq. The diagnostic and statistical manual of mental disorders (DSM-5) has recognized SPD as an independent disease, namely an obsessive-compulsive disorder. Thus, psychiatric treatment is indicated. Therefore, in a large cohort of SPD, we asked whether dermatologists' treatment strategy includes routine referrals to psychiatry. In addition, we describe epidemiological data, treatments...
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Tumor necrosis factor α (TNFα) blocking drugs are in use for a wide range of autoimmune disorders. In up to 5% of patients, this class of drugs produces puzzling cutaneous side effects that are the subject of this investigation, namely psoriasiform and eczema-like skin inflammation. These side effects can occur after any time of treatment and regardless of the underlying disorders. The exact pathophysiology is as yet unknown.; A total of 33 patients (19 female, average age 52 years) who had a cutaneous...
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Here we report the case of a patient with psoriasis who developed ulcerative colitis most likely caused by adalimumab. After cessation of adalimumab, colitis improved significantly. However, as psoriasis worsened, the patient was switched to ustekinumab, which resulted in complete cessation of colitis. During the 2-year follow-up under ustekinumab therapy, no further gastrointestinal complaints occurred. Paradoxical psoriasis manifestations in inflammatory bowel disease (IBD) under tumour necrosis...
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We show that in-plane magnetic-field-assisted spectroscopy allows extraction of the in-plane orientation and full 3D size parameters of the quantum mechanical orbitals of a single electron GaAs lateral quantum dot with subnanometer precision. The method is based on measuring the orbital energies in a magnetic field with various strengths and orientations in the plane of the 2D electron gas. From such data, we deduce the microscopic confinement potential landscape and quantify the degree by which...
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Measurements of quantum systems inevitably involve disturbance in various forms. Within the limits imposed by quantum mechanics, there exists an ideal projective measurement that does not introduce a back action on the measured observable, known as a quantum non-demolition (QND) measurement; 1,2; . Here we demonstrate an all-electrical QND measurement of a single electron spin in a gate-defined quantum dot. We entangle the single spin with a two-electron, singlet-triplet ancilla qubit via the exchange...
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Antiferromagnetic skyrmion crystals are magnetic phases predicted to exist in antiferromagnets with Dzyaloshinskii-Moriya interactions. Their spatially periodic noncollinear magnetic texture gives rise to topological bulk magnon bands characterized by nonzero Chern numbers. We find topologically protected chiral magnonic edge states over a wide range of magnetic fields and Dzyaloshinskii-Moriya interaction values. Moreover, and of particular importance for experimental realizations, edge states appear...
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We theoretically study the thermal Hall effect by magnons in skyrmion crystal phases of ferrimagnets in the vicinity of the angular momentum compensation point (CP). To this end, we start by deriving the equation of motion for magnons in the background of an arbitrary equilibrium spin texture, which gives rise to the fictitious electromagnetic field for magnons. As the net spin density varies, the resultant equation of motion interpolates between the relativistic Klein-Gordon equation at the CP and...
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The Klebsiella pneumoniae species complex includes important opportunistic pathogens which have become public health priorities linked to major hospital outbreaks and the recent emergence of multidrug-resistant hypervirulent strains. Bacterial virulence and the spread of multidrug resistance have previously been linked to toxin-antitoxin (TA) systems. TA systems encode a toxin that disrupts essential cellular processes, and a cognate antitoxin which counteracts this activity. Whilst associated with...
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Acute generalized exanthematous pustulosis (AGEP) is a dramatic generalized pustular rash of severe onset, which is considered a serious cutaneous adverse reaction to drugs. However, even though the clinical features are impressive and are often accompanied by systemic inflammation, it can be controlled quickly and safely by topical steroids subsequent to interruption of the offending drug. Here, we describe the management of a case and the evolution of the pustular rash. An elderly woman consulted...
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Subcorneal pustular dermatosis (SCPD, Sneddon-Wilkinson disease) is a rare chronic-relapsing skin disorder that typically manifests as flaccid sterile pustules without systemic symptoms. Although the accumulation of neutrophils is acknowledged to be a hallmark of SCPD, its exact pathomechanism is still not known. Several chemotactic factors have been implicated in neutrophil recruitment and invasion, including the proinflammatory cytokine TNF-α. These findings correspond well with clinical reports...
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To evaluate the adverse events profile of oral prednisolone among adult asthma patients in the UK.; Using data from the UK-based Clinical Practice Research Datalink, we conducted a series of cohort studies to quantify incidence rates and incidence rate ratios, and a series of nested case-control analyses to estimate crude and adjusted odds ratios, of 11 different potential corticosteroid-related adverse events (bone-related conditions, hypertension, peptic ulcer, severe infections, herpes zoster,...
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In many areas of psychology, it has been argued that people are equipped with a repertoire of strategies to solve the problems they face. Past work has also shown that in situations in which people receive feedback about the correctness of their inferences, substantial learning effects occur, such that simple heuristics that perform well in an environment also do well in describing people's inferences (e.g., Rieskamp, 2006; Rieskamp & Otto, 2006). This work has been challenged by Jekel and Glocker...
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Smoke from forest fires in the western part of North America reached the High Altitude Research Station Jungfraujoch, Switzerland, at the beginning of September 2017. Number concentration of ice nucleating particles (INPs) active at -15 degrees C or warmer decreased by about half during its passage. This is different to observations of enhanced INP concentrations in fresh plumes from forest fires. We hypothesise that INPs initially present in a smoke plume are lost or deactivated during long-range...
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Märkte haben fundamentale Bedeutung im Wirtschaftsleben. Neben den Märkten der Realwirtschaft, wie den Märkten für Güter und für Arbeit, werden auch viele der in der Finanzwirtschaft betrachteten Objekte wie Wertpapiere, Kredite, Beteiligungen und Rechte an Investitionen über Märkte oder auf marktähnliche Weise als Verträge abgeschlossen und weitergegeben. Zu den konkreten Organisationen, die das Marktgeschehen für Wertpapiere abwickeln, gehören die Börsen. Doch auch Intermediäre, besonders Banken,...
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Diversification represents the idea of choosing variety over uniformity. Within the theory of choice, desirability of diversification is axiomatized as preference for a convex combination of choices that are equivalently ranked. This corresponds to the notion of risk aversion when one assumes the von Neumann–Morgenstern expected utility model, but the equivalence fails to hold in other models. This paper analyzes axiomatizations of the concept of diversification and their relationship to the related...
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Maximum drawdown, the largest cumulative loss from peak to trough, is one of the most widely used indicators of risk in the fund management industry, but one of the least developed in the context of measures of risk. We formalize drawdown risk as Conditional Expected Drawdown (CED), which is the tail mean of maximum drawdown distributions. We show that CED is a degree one positive homogenous risk measure, so that it can be linearly attributed to factors; and convex, so that it can be used in quantitative...
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Hohe Löhne von CEOs sorgen immer wieder für hitzige Diskussionen. Und das nicht erst, seit die 1:12-Initiative im Jahr 2013 das Verhältnis zwischen Höchst- und Tiefstlöhnen in einem Unternehmen regulieren wollte. Ein Anstieg der Managementvergütungen in den letzten Jahrzehnten ist empirisch nicht von der Hand zu weisen. Für Unmut gesorgt haben insbesondere die Löhne bei Banken wie Lehman Brothers und Bear Stearns, deren Insolvenz den Höhepunkt der Finanzkrise markiert hat. Fast schon zynisch mutet...
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This article comments on the role of empirical subjective well-being research in public policy within a constitutional, procedural perspective of government and state. It rejects the idea that, based on the promises of the measurement, we should adopt a new policy perspective that is oriented towards a decision rule maximizing some aggregate measure of subjective well-being. This social engineering perspective, implicit in much reasoning about well-being policy, neglects i) important motivation problems...
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Do emotions affect the decision between change and the status quo? We exploit exogenous variation in emotions caused by rain and analyze data on more than 870,000 municipal vote outcomes in Switzerland to address this question. The empirical tests are based on administrative ballot outcomes and individual postvote survey data. We find that rain decreases the share of votes for political change. Our robustness checks suggest that this finding is not driven by changes in the composition of the electorate...
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We evaluate one of the most prevalent prohibitory policies: banning the sales of tobacco to teens. We exploit the staggered introduction of sales bans across Switzerland and the European Union from 1990 to 2016. The estimates indicate a less than 1 percentage point reduction in teen smoking because of the bans. The reduction is substantially lower than the 5 percentage point reduction expected by health officials. We examine additional outcomes relevant to assessing any prohibitory policy. We find...
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