Difficult to control atopic dermatitis

Difficult to control atopic dermatitis (AD) presents a therapeutic challenge and often requires combinations of topical and systemic treatment. Anti-inflammatory treatment of severe AD most commonly includes topical glucocorticosteroids and topical calcineurin antagonists used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, the topical calcineurin inhibitors tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti-inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection contribute to disease exacerbation and thus justify additional antimicrobial / antiseptic treatment. Systemic antihistamines (H1) may relieve pruritus but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength. "Eczema school" educational programs have been proven to be helpful.

The Life and Times of Bills

Time is one of the scarcest resources in modern parliaments. In parliamentary systems of government the control of time in the chamber is a significant power resource enjoyed – to varying degrees – by parliamentary majorities and the governments they support. Minorities may not be able to muster enough votes to stop bills, but they may have – varying degrees of – delaying powers enabling them to extract concessions from majorities attempting to get on with their overall legislative programme. This paper provides a comparative analysis of the dynamics of the legislative process in 17 West European parliaments from the formal initiation of bills to their promulgation. The ‘biographies’ of a sample of bills are examined using techniques of event-history analysis (a) charting the dynamics of the legislative process both across the life-times of individual bills and different political systems and (b) examining whether, and to what extent, parliamentary rules and some general regime attributes influence the dynamics of this process, speeding up or delaying the passage of legislation. Using a veto-points framework and transaction cost politics as a theoretical framework, the quantitative analyses suggest a number of counter-intuitive findings (e.g., the efficiency of powerful committees) and cast doubt on some of the claims made by Tsebelis in his veto-player model.

Strategies for reducing fumigant loss to the atmosphere

A model is developed to describe transport and loss of methyl bromide (MeBr) in soil following application as a soil fumigant. The model is used to investigate the effect of soil and management factors on MeBr volatilization. Factors studied include depth of injection, soil water content, presence or absence of tarp, depth to downward barrier, and irrigation after injection. Of these factors, the most important was irrigation after injection followed by covering with the tarp, which increased the diffusive resistance of the soil and prevented early loss of MeBr. The model offers an explanation for the apparently contradictory observations of earlier field studies of MeBr volatilization from soils under different conditions. The model was also used to calculate the concentration-time index for various management alternatives, showing that the irrigation application did not make the surface soil more difficult to fumigate, except at very early times. Therefore, irrigation shows promise for reducing fumigant loss while at the same time permitting control of target organisms during fumigation.

Digital Technologies and Traditional Cultural Expressions : A Positive Look at a Difficult Relationship

Digital technologies have often been perceived as imperilling traditional cultural expressions (TCE). This angst has interlinked technical and socio-cultural dimensions. On the technical side, it is related to the affordances of digital media that allow, among other things, instantaneous access to information without real location constraints, data transport at the speed of light and effortless reproduction of the original without any loss of quality. In a socio-cultural context, digital technologies have been regarded as the epitome of globalisation forces - not only driving and deepening the process of globalisation itself but also spreading its effects. The present article examines the validity of these claims and sketches a number of ways in which digital technologies may act as benevolent factors. We illustrate in particular that some digital technologies can be instrumentalised to protect TCE forms, reflecting more appropriately the specificities of TCE as a complex process of creation of identity and culture. The article also seeks to reveal that digital technologies - and more specifically the Internet and the World Wide Web - have had a profound impact on the ways cultural content is created, disseminated, accessed and consumed. We argue that this environment may have generated various opportunities for better accommodating TCE, especially in their dynamic sense of human creativity.

Efficacy of lead-in silibinin and subsequent triple therapy in difficult-to-treat HIV/hepatitis C virus-coinfected patients

OBJECTIVES: The efficacy of current hepatitis C virus (HCV) triple therapy, including a protease inhibitor, is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and nonresponse to previous peginterferon-ribavirin. These patients have a low chance (only 30%) of achieving a sustained virological response (SVR) during triple therapy and cannot wait for next-generation anti-HCV drugs. In a pilot study, we investigated the efficacy of a lead-in therapy with silibinin before triple therapy in difficult-to-treat patients. METHODS: Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented failure of previous peginterferon-ribavirin treatment. Intervention was lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days. Subsequently, peginterferon-ribavirin combined with telaprevir was initiated for 12 weeks, followed by peginterferon-ribavirin dual therapy until week 48 after initiation of triple therapy. The outcome measurements were HCV RNA after silibinin lead-in, at weeks 2, 4 and 12 of triple therapy, and SVR at week 24 after the end of treatment. RESULTS: We examined six HIV/HCV-coinfected patients (four infected with genotype 1a). All had fibrosis grade METAVIR ≥F3 and were on fully suppressive antiretroviral therapy. Mean HCV RNA decline after silibinin therapy was 2.6 log10 IU/mL (range 2-3 log10 IU/mL). Five of the six patients were virologically suppressed at weeks 2 and 4, and all six at week 12 of triple therapy. One experienced a viral breakthrough thereafter. Four of five patients (80%) showed an SVR 24. One patient had an SVR 12 but has not yet reached week 24. CONCLUSIONS: A lead-in with silibinin before triple therapy is highly effective and increases the probability of HCV treatment success in difficult-to-treat HIV/HCV-coinfected patients with advanced liver fibrosis and previous failure of peginterferon-ribavirin.

Notch signaling in the brain: in good and bad times.

Notch signaling is an evolutionarily conserved pathway, which is fundamental for neuronal development and specification. In the last decade, increasing evidence has pointed out an important role of this pathway beyond embryonic development, indicating that Notch also displays a critical function in the mature brain of vertebrates and invertebrates. This pathway appears to be involved in neural progenitor regulation, neuronal connectivity, synaptic plasticity and learning/memory. In addition, Notch appears to be aberrantly regulated in neurodegenerative diseases, including Alzheimer's disease and ischemic injury. The molecular mechanisms by which Notch displays these functions in the mature brain are not fully understood, but are currently the subject of intense research. In this review, we will discuss old and novel Notch targets and molecular mediators that contribute to Notch function in the mature brain and will summarize recent findings that explore the two facets of Notch signaling in brain physiology and pathology.

Swiss tree rings reveal warm and wet summers during medieval times

We present a 1200 year drought reconstruction for the European Alpine region based on carbon isotope variations of tree rings from living larch trees and historic timber. The carbon isotope fractionation at the study site is sensitive to summer precipitation, temperature, and irradiance, resulting in a stable and high correlation with a drought index for interannual to decadal frequencies and possibly beyond (r(2)=0.58 for 1901-2004, July/August). When combining this information with maximum latewood density-derived summer temperature, a strongly reduced occurrence of summer droughts during the warm A.D. 900-1200 period is evident, coinciding with the Medieval Climate Anomaly (MCA), with a shift to colder and drier conditions for the subsequent centuries. The warm-wet MCA contrasts strongly with the climate of the drought-prone warm phase of the recent decades, indicating different forcing mechanism for these two warm periods and pointing to beneficial conditions for agriculture and human well-being during the MCA in this region.