Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer

Purpose: Zoledronic acid (ZA) or denosumab treatment reduces skeletal-related events; however, the safety of prolonged therapy has not been adequately studied. Here, we describe safety results of extended denosumab therapy in patients with bone metastases from the open-label extension phase of two phase 3 trials. Methods: Patients with metastatic breast or prostate cancer received subcutaneous denosumab 120 mg Q4W or intravenous ZA 4 mg Q4W in a double-blinded fashion. Denosumab demonstrated superior efficacy in the blinded treatment phase; thus, patients were offered open-label denosumab for up to an additional 2 years. Results: Cumulative median (Q1, Q3) denosumab exposure was 19.1 (9.2, 32.2) months in the breast cancer trial (n = 1019) and 12.0 (5.6, 21.3) months in the prostate cancer trial (n = 942); 295 patients received denosumab for >3 years. No new safety signals were identified during the open-label phase, or among patients who switched from ZA to denosumab. During the blinded treatment phase, exposure-adjusted subject incidences of osteonecrosis of the jaw (ONJ) were 49 (1.9 %) and 31 (1.2 %) in the denosumab and ZA groups, respectively. In total, 32 (6.9 %) and 25 (5.5 %) new cases of ONJ (not adjusted for exposure) were reported for patients continuing and switching to denosumab, respectively. The incidences of hypocalcemia were 4.3 and 3.1 %, in patients continuing and switching to denosumab, respectively. Conclusion: These results describe the safety profile of denosumab after long-term exposure, or after switching to denosumab from ZA. No new safety signals were identified. Hypocalcemia rates were similar in the blinded treatment and open-label phases. ONJ rates increased with increasing exposure to antiresorptives, consistent with previous reports

Bacterial endophyte communities in Pinus flexilis are structured by host age, tissue type, and environmental factors

Background and aims: Forest tree microbiomes are important to forest dynamics, diversity, and ecosystem processes. Mature limber pines (Pinus flexilis) host a core microbiome of acetic acid bacteria in their foliage, but the bacterial endophyte community structure, variation, and assembly across tree ontogeny is unknown. The aims of this study were to test if the core microbiome observed in adult P. flexilis is established at the seedling stage, if seedlings host different endophyte communities in root and shoot tissues, and how environmental factors structure seedling endophyte communities. Methods: The 16S rRNA gene was sequenced to characterize the bacterial endophyte communities in roots and shoots of P. flexilis seedlings grown in plots at three elevations at Niwot Ridge, Colorado, subjected to experimental treatments (watering and heating). The data was compared to previously sequenced endophyte communities from adult tree foliage sampled in the same year and location. Results: Seedling shoots hosted a different core microbiome than adult tree foliage and were dominated by a few OTUs in the family Oxalobacteraceae, identical or closely related to strains with antifungal activity. Shoot and root communities significantly differed from each other but shared major OTUs. Watering but not warming restructured the seedling endophyte communities. Conclusions: The results suggest differences in assembly and ecological function across conifer life stages. Seedlings may recruit endophytes to protect against fungi under increased soil moisture

Towards a caring society? An analysis of social development policy in Malaysia

Die Studie praesentiert die Ergebnisse eines Forschungsprojekts zur Wohlfahrtspolitik in zwei Schritten: (1) Die Entwicklung eines begrifflich-theoretischen Bezugsrahmens, der sich auf Modelle der Sozialpolitik und Sozialen Entwicklung stuetzt. Diese Modelle stammen aus Analysen der sozialen Marktwirtschaft, des Neoliberalismus und Kommunitarismus; (2) Die Nachzeichnung und Bewertung der Entwicklung der oekonomischen und sozialpolitischen Entwicklung Malaysias seit 1969. Dieser Prozess wird hinsichtlich der folgenden Komponenten analysiert: Wertorientierung und Ziele, Programme und ihre Substrukturen, erwarteter Output (Effekte), aktuelle Leistungen und Gesamterfolg (outcome), Evaluation der Effizienz der Massnahmen, Effektivitaet des Programms, Nachhaltigkeit der Implementation und Schlussfolgerungen fuer die Reformpolitik. Die Darstellung der Ergebnisse wird fuer die verschiedenen sozialpolitischen Akteure gesondert aufbereitet. (pre)German title: Auf dem Wege zu einer Wohlfahrtsgesellschaft? Eine Analyse der sozialen Entwicklungspolitik in MalaysiaAvailable from UuStB Koeln(38)-990106233 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Evidence for foliar endophytic nitrogen fixation in a widely distributed subalpine conifer.

Coniferous forest nitrogen (N) budgets indicate unknown sources of N. A consistent association between limber pine (Pinus flexilis) and potential N2 -fixing acetic acid bacteria (AAB) indicates that native foliar endophytes may supply subalpine forests with N. To assess whether the P. flexilis-AAB association is consistent across years, we re-sampled P. flexilis twigs at Niwot Ridge, CO and characterized needle endophyte communities via 16S rRNA Illumina sequencing. To investigate whether endophytes have access to foliar N2 , we incubated twigs with (13) N2 -enriched air and imaged radioisotope distribution in needles, the first experiment of its kind using (13) N. We used the acetylene reduction assay to test for nitrogenase activity within P. flexilis twigs four times from June to September. We found evidence for N2 fixation in P. flexilis foliage. N2 diffused readily into needles and nitrogenase activity was positive across sampling dates. We estimate that this association could provide 6.8-13.6 μg N m(-2)  d(-1) to P. flexilis stands. AAB dominated the P. flexilis needle endophyte community. We propose that foliar endophytes represent a low-cost, evolutionarily stable N2 -fixing strategy for long-lived conifers. This novel source of biological N2 fixation has fundamental implications for understanding forest N budgets

Erratum to: Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer

SCOPUS: er.jinfo:eu-repo/semantics/publishe

Erratum to: Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer [Supportive Care in Cancer, (2015), DOI:10.1007/s00520-015-2904-5]

SCOPUS: er.jinfo:eu-repo/semantics/publishe

Photometry of dust grains of comet 67P and connection with nucleus regions

International audienceMultiple pairs of high-resolution images of the dust coma of comet 67P/Churyumov-Gerasimenko have been collected by OSIRIS onboard Rosetta allowing extraction and analysis of dust grain tracks. We developed a quasi automatic method to recognize and to extract dust tracks in the Osiris images providing size, FWHM and photometric data. The dust tracks characterized by a low signal-to-noise ratio were checked manually. We performed the photometric analysis of 70 dust grain tracks observed on two different Narrow Angle Camera images in the two filters F24 and F28, centered at lambda = 480.7 nm and at lambda = 743.7 nm, respectively, deriving the color and the reddening of each one. We then extracted several images of the nucleus observed with the same filters and with the same phase angle to be compared with the dust grain reddening. Most of the dust grain reddening is very similar to the nucleus values, confirming they come from the surface or subsurface layer. The histogram of the dust grain reddening has a secondary peak at negative values and shows some grains with values higher than the nucleus, suggesting a different composition from the surface grains. One hypothesis comes from the negative values point at the presence of hydrated minerals in the comet