Multiproxy reconstructions of monthly and seasonal surface temperature fields for Europe back to 1500 show that the late 20th- and early 21st-century European climate is very likely (>95% confidence level) warmer than that of any time during the past 500 years. This agrees with findings for the entire Northern Hemisphere. European winter average temperatures during the period 1500 to 1900 were reduced by approximately 0.5 degrees C (0.25 degrees C for annual mean temperatures) compared to the 20th century. Summer temperatures did not experience systematic century-scale cooling relative to present conditions. The coldest European winter was 1708/1709; 2003 was by far the hottest summer.

In stage II-III colon cancer, the KRAS mutation status does not have major prognostic value. BRAF is prognostic for OS in MS-L/S tumors.

Spatially and temporally high-resolution estimates of past natural climate variability are important to assess recent significant climate trends. The mid-latitude atmospheric circulation is the dominant factor for regional changes in temperature, rainfall, and other climatic variables. Here we present reconstructions of gridded monthly sea level pressure (SLP) fields back to 1659 and seasonal reconstructions from 1500-1658 for the eastern North Atlantic-European region (30°W to 40°E; 30°N to 70°N). These were developed using principal component regression analysis based on the combination of early instrumental station series (pressure, temperature and precipitation) and documentary proxy data from Eurasian sites. The relationships were derived over the 1901-1960 calibration period and verified over 1961-1990. Under the assumption of stationarity in the statistical relationships, a transfer function derived over the 1901-1990 period was used to reconstruct the 500-year largescale SLP fields. Systematic quality testing indicated reliable winter reconstructions throughout the entire period. Lower skill was obtained for the other seasons, although meaningful monthly reconstructions were available from around 1700 onwards, when station pressure series became available. The quality and the reconstructed SLP fields for two exceptionally cold years (1573, 1740) are discussed and climatologically interpreted. An EOF analysis of the 1500-1999 winter SLP revealed, firstly, a zonal flow pattern with pronounced decadal to centenial time scale variations, secondly, a monopole pattern over northwest Europe and thirdly, a pattern modulating the meridional flow component over Europe. These 500year SLP reconstructions should be useful for modelling studies, particulary for analyses of low-frequency atmospheric variability and for circulation dynamics.

We evaluate variability, trends, uncertainties, and change of extremes of reconstructed and observed European spring and autumn temperature back to 1500. Spring and autumn temperature experienced systematic century‐scale cooling compared to present conditions. The coldest springs appeared during the Maunder Minimum (ΔT = −1 K wrt 1901–2000). The amplitude of spring temperature variations at decadal and multidecadal scales doubles that of autumn and is most expressed in northeastern Europe. The decade 1995–2004 was very likely the warmest of the last half millennium. Anomalously warm springs and autumns have generally become more extreme in recent decades. However, the recent changes are statistically not significant with respect to the pre‐industrial period.

GemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.

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Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. On the basis of our toxicity experience, we recommend use of capecitabine in combination with oxaliplatin 130 mg/m(2) at an initial dose of 1,250 mg/m(2) bid in nonpretreated patients and at a dose of 1,000 mg/m(2) bid in pretreated patients.

BackgroundTotal joint replacements represent a considerable part of day-to-day orthopaedic routine and a substantial proportion of patients undergoing unilateral total hip arthroplasty require a contralateral treatment after the first operation. This report compares complications and functional outcome of simultaneous versus early and delayed two-stage bilateral THA over a five-year follow-up period.MethodsThe study is a post hoc analysis of prospectively collected data in the framework of the European IDES hip registry. The database query resulted in 1819 patients with 5801 follow-ups treated with bilateral THA between 1965 and 2002. According to the timing of the two operations the sample was divided into three groups: I) 247 patients with simultaneous bilateral THA, II) 737 patients with two-stage bilateral THA within six months, III) 835 patients with two-stage bilateral THA between six months and five years.ResultsWhereas postoperative hip pain and flexion did not differ between the groups, the best walking capacity was observed in group I and the worst in group III. The rate of intraoperative complications in the first group was comparable to that of the second. The frequency of postoperative local and systemic complication in group I was the lowest of the three groups. The highest rate of complications was observed in group III.ConclusionsFrom the point of view of possible intra- and postoperative complications, one-stage bilateral THA is equally safe or safer than two-stage interventions. Additionally, from an outcome perspective the one-stage procedure can be considered to be advantageous.