Etwas über die Rosenkultur auf der Insel Java

W. Reuschenbach

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Peri-implant bone loss of dental implants with platform-switching design after 5 years of loading: a cross-sectional study

OBJECTIVE The aim of this cross-sectional study was to estimate bone loss of implants with platform-switching design and analyze possible risk indicators after 5 years of loading in a multi-centered private practice network. METHOD AND MATERIALS Peri-implant bone loss was measured radiographically as the distance from the implant shoulder to the mesial and distal alveolar crest, respectively. Risk factor analysis for marginal bone loss included type of implant prosthetic treatment concept and dental status of the opposite arch. RESULTS A total of 316 implants in 98 study patients after 5 years of loading were examined. The overall mean value for radiographic bone loss was 1.02 mm (SD ± 1.25 mm, 95% CI 0.90- 1.14). Correlation analyses indicated a strong association of peri-implant bone loss > 2 mm for removable implant-retained prostheses with an odds ratio of 53.8. CONCLUSION The 5-year-results of the study show clinically acceptable values of mean bone loss after 5 years of loading. Implant-supported removable prostheses seem to be a strong co-factor for extensive bone level changes compared to fixed reconstructions. However, these results have to be considered for evaluation of the included special cohort under private dental office conditions.

Zur Ethnologie von West-Java : Mitteilungen aus Missionar S. Coolsmas "West Java"

von Dr. R. Teuscher

Rb-Sr and K-Ar data for Upper Vendian clayey rocks of the Russian Platform

Geochemical behavior of Rb-Sr and K-Ar systems in Upper Vendian clayey rocks of the Russian Platform is under consideredation. The use of additional data on grain size fractions of sedimentary rocks recovered from boreholes drilled in the Gavrilov Yam area made it possible to confirm the previous conclusion on two stages of epigenetic matter transformation (approximately 600 and 400 Ma ago). Distortions are related to transformation of sediments due to interaction in the water-rock system. Interaction degree was more intense in the upper part of the sedimentary section relative to its lower strata. These conclusions are substantiated by materials from boreholes that characterize different types of Vendian sections and different tectonic zones.

Accumulation rates of bulk sediment and total organic carbon for Ontong Java Plateau sediments

Organic geochemical investigations were performed on sediments of Leg 130 to reconstruct the depositional environment of the Ontong Java Plateau. The Miocene to Quaternary sediments collected during the drilling campaign are characterized by extremely low organic carbon contents. As indicated by C/N ratios and Rock-Eval data, most of the organic matter is probably of marine origin. Based on mass-accumulation rates of organic carbon, the paleoproductivity for the Miocene-Pliocene and the late Pliocene-Pleistocene time intervals as well as the modern surface-water production were estimated. The productivity values of the surface sediments (25-59 gC/m2/yr) reflect the various influences of the equatorial upwelling cell on the different sites. The accumulation rates of organic carbon are generally low; however, they show a distinct increase at 8 Ma and a decrease at 2 Ma.

Element contents, sulfur and oxygen isotopes, and molecular biomarkers of phosphatic crust samples from the Chimbote Platform of the shelf off Peru

Authigenic phosphatic laminites enclosed in phosphorite crusts from the shelf off Peru (10°01' S and 10°24' S) consist of carbonate fluorapatite layers, which contain abundant sulfide minerals including pyrite (FeS2) and sphalerite (ZnS). Low d34Spyrite values (average -28.8 per mill) agree with bacterial sulfate reduction and subsequent pyrite formation. Stable sulfur isotopic compositions of sulfate bound in carbonate fluorapatite are lower than that of sulfate from ambient sea water, suggesting bacterial reoxidation of sulfide by sulfide-oxidizing bacteria. The release of phosphorus and subsequent formation of the autochthonous phosphatic laminites are apparently caused by the activity of sulfate-reducing bacteria and associated sulfide-oxidizing bacteria. Following an extraction-phosphorite dissolution-extraction procedure, molecular fossils of sulfate-reducing bacteria (mono-O-alkyl glycerol ethers, di-O-alkyl glycerol ethers, as well as the short-chain branched fatty acids i/ai-C15:0, i/ai-C17:0 and 10MeC16:0) are found to be among the most abundant compounds. The fact that these molecular fossils of sulfate-reducing bacteria are distinctly more abundant after dissolution of the phosphatic laminite reveals that the lipids are tightly bound to the mineral lattice of carbonate fluorapatite. Moreover, compared with the autochthonous laminite, molecular fossils of sulfate-reducing bacteria are: (1) significantly less abundant and (2) not as tightly bound to the mineral lattice in the other, allochthonous facies of the Peruvian crusts consisting of phosphatic coated grains. These observations confirm the importance of sulfate-reducing bacteria in the formation of the phosphatic laminite. Model calculations highlight that organic matter degradation by sulfate-reducing bacteria has the potential to liberate sufficient phosphorus for phosphogenesis.

Quaternary oxygen isotope record of planktonic foraminifera from ODP Site 805 on the Ontong Java Plateau

The oxygen isotope records of G. sacculifer and Pulleniatina in the uppermost three cores at Ocean Drilling Program Hole 805C span the last 1.6 m.y., an estimate based on Fourier stratigraphy. The last 700,000 yr are dominated by both eccentricity and obliquity-related orbital fluctuations. The range of variation of delta18O values is about 1.5?, of which ca. 75% may be assigned to global ice-volume effect. The remainder of the range is shared by the effects of surface temperature variation, thermocline depth change (in the case of Pulleniatina, especially), and differential dissolution. Before 1 Ma, obliquity-related fluctuations dominate. The transition between obliquity- and eccentricity-dominated time occurs between ca. 1 and 0.7 Ma. It is marked by irregularities in phase relationships, the source of which is not clear. The age of the Brunhes/Matuyama boundary is determined as 794,000 yr by obliquity counting. However, an age of 830,000 yr also is compatible with the counts of both eccentricity and obliquity cycles. In the first case, Stage 19 (which contains the boundary) is coincident with the crest of the 19th obliquity cycle, setting the first crest downcore equal to zero, and counting backward (o19). In the second, Stage 19 coincides with o20. No evidence was found for fluctuations related to precession (23 and 19 k.y.) rising above the noise level, using plain Fourier expansion on the age model of the entire series. Detailed stratigraphic comparison with the Quaternary record of Hole 806B allows the recognition of major dissolution events (which increase the difference in delta18O values of G. sacculifer at the two sites). These occur at Stages 11-13, 16-17, and near 1.5 Ma (below o33).

Stable carbon isotope in bottom water and Cibicidoides wuellerstorfi on the Ontong Java Plateau and Emperor Seamount

We have measured the carbon isotopic composition of dissolved inorganic carbon in bottom waters of the Ontong Java Plateau (western equatorial Pacific) and on the northern Emperor Seamounts (northwest Pacific). Each of these locations is several hundred miles from the nearest Geochemical Ocean Sections Study (GEOSECS) stations, and the observed delta13C values at each site differ substantially from regionally averaged GEOSECS delta13C profiles. We discuss the possible causes of these differences, including horizontal variability, near-bottom effects, and problems with the Pacific GEOSECS delta13C data. We also measured the isotopic composition (C and O) of core top C. wuellerstorfi from a depth transect of cores at each location. The delta18O data are used to verify that our samples are Holocene. Comparison of foraminiferal and bottom water delta13C values shows that this species faithfully records bottom water delta13C at both sites and demonstrates that there is no depth-related artifact in the dissolved inorganic carbon-C. wuellerstorfi delta13C relationship at these sites.

The Fohsella chronocline in middle Miocene sediments from the Ontong Java Plateau, Pacific Ocean

Micropaleontologists have traditionally recognized the mid-Miocene Fohsella lineage as a flagship for phyletic gradualism within the planktic foraminifera. However, study of a deep-sea record from the western equatorial Pacific (ODP Site 806) reveals that coiling ratios within this clade suddenly (<5 kyr) shift after a prolonged, ancestral state of near randomness (~50%) to a transient phase (13.42-13.43 Ma) of dextral dominance (~75%) immediately following the first common occurrence of keeled fohsellids. This brief period of dextral dominance was abruptly (<5 kyr) succeeded by an irreversible change to sinistral dominance (~96%). Fohsellid abundances decline markedly through the interval in which the sinistral preference is established. The shift to sinistrality (13.42 Ma) predated the deepening of fohsellid depth ecology by ~240-488 kyr, indicating that these two events were unrelated. This view is supported by a lack of delta 18O evidence for depth-habitat differences between the two chiral forms, which refutes the notion that sinistral fohsellids were "pre-adapted" for ensuing hydrographic change because they occupied a deeper depth habitat than their dextral counterparts. Planktic foraminiferal assemblages become strongly oligotrophic in character through the interval in which the fohsellid delta 18O increase is recorded, indicating that the migration to deeper depths was fostered by an expansion of the mixed layer in the western equatorial Pacific. Salient aspects of this brief, but conspicuous faunal change are a marked increase in the abundance of symbiont-bearing globigerinoidids, a concomitant collapse of local Jenkinsella mayeri/siakensis populations, and reduced fohsellid abundances. The rapid and permanent nature of the Fohsella sinistral shift provides a distinct, unequivocal datum that may prove useful for correlating mid-Miocene sections throughout the Caribbean Sea and tropical regions in the western sectors of the Pacific and Atlantic. The coiling ratio changes that occurred during the evolution of the Fohsella chronocline probably reflect changing population dynamics between cryptic genotypes with different coiling preferences.