Current state of evidence on 'off-label' therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents, in Germany, Austria and Switzerland--a consensus report

Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include 'off-label' use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors' own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.

Approaching water stress in the Alps: Transdisciplinary co-production of systems, target and transformation knowledge

There is increasing recognition that transdisciplinary approaches are needed to create suitable knowledge for sustainable water management. However, there is no common understanding of what transdisciplinary research may be and there is very limited debate on potentials and challenges regarding its implementation. Against this background, this paper presents a conceptual framework for transdisciplinary co-production of knowledge in water management projects oriented towards more sustainable use of water. Moreover, first experiences with its implementation are discussed. In so doing, the focus lies on potentials and challenges related to the co-production of systems, target and transformation knowledge by researchers and local stakeholders.

Swiss Alps Jungfrau Aletsch UNESCO World Heritage Site - The state of this World Heritage region as a starting point for regional monitoring

The UNESCO listing as World Heritage Site confirms the outstanding qualities of the high-mountain region around the Great Aletsch Glacier. The region of the World Heritage Site now faces the responsibility to make these qualities visible and to preserve them for future generations. Consequently the qualities of the site must not be regarded in isolation but in the context of the entire region with its dynamics and developments. Regional monitoring is the observation and evaluation of temporal changes in target variables. It is thus an obligation towards UNESCO, who demands regular reports about the state of the listed World Heritage assets. It also allows statements about sustainable regional development and can be the basis for early recognition of threats to the outstanding qualities. Monitoring programmes face three major challenges: first, great care must be taken in defining the target qualities to be monitored or the monitoring would remain vague. Secondly, the selection of ideal indicators to describe these qualities is impeded by inadequate data quality and availability, compromises are inevitable. Thirdly, there is always an element of insecurity in the interpretation of the results as to what influences and determines the changes in the target qualities. The first survey of the monitoring programme confirmed the exceptional qualities of the region and also highlighted problematic issues.

Contamination of Alpine snow and ice at Colle Gnifetti, Swiss/Italian Alps, from nuclear weapons tests

Plutonium is present in the environment as a consequence of atmospheric nuclear tests, nuclear weapons production and industrial releases over the past 50 years. To study temporal trends, a high resolution Pu record was obtained by analyzing 52 discrete samples of an alpine firn/ice core from Colle Gnifetti (Monte Rosa, 4450 m a.s.l.), dating from 1945 to 1990. The 239Pu signal was recorded directly, without decontamination or preconcentration steps, using an Inductively Coupled Plasma - Sector Field Mass Spectrometer (ICP-SFMS) equipped with an high efficiency sample introduction system, thus requiring much less sample preparation than previously reported methods. The 239Pu profile reflects the three main periods of atmospheric nuclear weapons testing: the earliest peak lasted from 1954/55 to 1958 and was caused by the first testing period reaching a maximum in 1958. Despite a temporary halt of testing in 1959/60, the Pu concentration decreased only by half with respect to the 1958 peak due to long atmospheric residence times. In 1961/62 Pu concentrations rapidly increased reaching a maximum in 1963, which was about 40% more intense than the 1958 peak. After the signing of the "Limited Test Ban Treaty" between USA and USSR in 1964, Pu deposition decreased very sharply reaching a minimum in 1967. The third period (1967-1975) is characterized by irregular Pu concentrations with smaller peaks (about 20-30% of the 1964 peak) which might be related to the deposition of Saharan dust contaminated by the French nuclear tests of the 1960s. The data presented are in very good agreement with Pu profiles previously obtained from the Col du Dome ice core (by multi-collector ICP-MS) and Belukha ice core (by Accelerator Mass Spectrometry, AMS). Although a semi-quantitative method was employed here, the results are quantitatively comparable to previously published results.