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151.
The end-Permian mass extinction event (∼252 Mya) is associated with one of the largest global carbon cycle perturbations in the Phanerozoic and is thought to be triggered by the Siberian Traps volcanism. Sizable carbon isotope excursions (CIEs) have been found at numerous sites around the world, suggesting massive quantities of 13C-depleted CO2 input into the ocean and atmosphere system. The exact magnitude and cause of the CIEs, the pace of CO2 emission, and the total quantity of CO2, however, remain poorly known. Here, we quantify the CO2 emission in an Earth system model based on new compound-specific carbon isotope records from the Finnmark Platform and an astronomically tuned age model. By quantitatively comparing the modeled surface ocean pH and boron isotope pH proxy, a massive (∼36,000 Gt C) and rapid emission (∼5 Gt C yr−1) of largely volcanic CO2 source (∼−15%) is necessary to drive the observed pattern of CIE, the abrupt decline in surface ocean pH, and the extreme global temperature increase. This suggests that the massive amount of greenhouse gases may have pushed the Earth system toward a critical tipping point, beyond which extreme changes in ocean pH and temperature led to irreversible mass extinction. The comparatively amplified CIE observed in higher plant leaf waxes suggests that the surface waters of the Finnmark Platform were likely out of equilibrium with the initial massive centennial-scale release of carbon from the massive Siberian Traps volcanism, supporting the rapidity of carbon injection. Our modeling work reveals that carbon emission pulses are accompanied by organic carbon burial, facilitated by widespread ocean anoxia.

The end-Permian mass extinction (EPME) that occurred at 251.941 ± 0.037 Mya is considered the most severe biodiversity loss in Earth history (1, 2). The EPME coincides with the eruption of the Siberian Traps, a voluminous large igneous province (LIP) that occupies 6 million square kilometers (km2) in Siberia, Russia (35). The volcanic activity of this LIP is linked to SO2 and CO2 degassing generated by sill intrusion (610). The large amount of CO2 injected into the atmosphere is thought to have led to severe global warming (1114), catastrophic ocean anoxia (15, 16), and extreme ocean and terrestrial acidification (1721) being lethal for life on land and in the sea (22). To date, no agreement has been reached regarding the source of the 13C-depleted carbon that triggered the global carbon cycle perturbation, the decrease in ocean pH, and the global warming across the EPME. Additionally, atmospheric CO2 levels following the initial pulse of Siberian Traps volcanism and across the EPME remain poorly known (23, 24), limiting our understanding of the climate feedbacks that occur upon greenhouse gas release during this time.To address this critical gap in our knowledge, we constrain the source, pace and total amount of CO2 emissions using an Earth system model of intermediate complexity (i.e., carbon centric-Grid Enabled Integrated Earth system model [cGENIE]; SI Appendix) forced by new astronomically tuned δ13C records from well-preserved lipid biomarkers preserved in sediments from the Finnmark Platform, Norway. The Finnmark Platform is located offshore northern Norway on the Eastern Barents Sea shelf, hosting an expanded shallow marine section (paleo-water depth roughly 50 to 100 m) where two drill cores were collected (7128/12-U-01 and 7129/10-U-01) spanning the Permian–Triassic transition (Fig. 1). A previously generated bulk organic carbon isotope record (δ13Corg) from the same core shows a two-step decline with a total carbon isotope excursion (CIE) magnitude of ∼4‰ (25). Although the sedimentary organic carbon was considered primarily of terrestrial origin, small contributions from marine organic carbon production could not be excluded. Here, we use compound-specific carbon isotope analysis of both long-chain and short-chain n-alkanes preserved in marine sediments in the Finnmark Platform to generate separate yet directly comparable records of δ13C for the terrestrial and the marine realm, respectively, across the EPME. Long-chain n-alkanes with a strong odd-over-even predominance (n-C27 and n-C29) are produced by higher plant leaf waxes, and their isotopic composition (δ13Cwax) relates to their main carbon source (i.e., atmospheric CO2) (26). On the other hand, short-chain alkanes (n-C17 and n-C19) are derived from marine algae, and their δ13C values (δ13Calgae) represent carbon in the marine realm (27, 28). To date, only a few EPME compound-specific carbon isotope studies have been reported, all of which are limited by unfavorable sedimentary facies or high thermal maturity of the organic matter (29, 30). In the present study, the exceptionally low thermal maturity of the organic matter is evident from the yellow color of pollen and spores, indicating a color index 2 out of 7 on the thermal alteration scale of Batten (31), which is equivalent to a vitrinite reflectance R0 of 0.3%. Moreover, the high sedimentation rate (discussed in Carbon Cycle Quantification Using Astrochronology and Earth System Model) of the siliciclastic sediments at the study site allows for studying both marine and terrestrial CIE across the EPME in unprecedented detail. Taken together, the Finnmark sedimentary records enable the reconstruction of individual yet directly comparable carbon isotope records for the terrestrial and the marine realm that can be astronomically tuned and used to quantitatively assess the source, pace, and total amount of 13C-depleted carbon released during the Siberian Traps eruption that led to the EPME. Using our new compound-specific carbon isotope records, rather than marine carbonates, has several advantages: 1) new astrochronology enables a 104-year temporal resolution for our paired marine and terrestrial carbon isotope records; 2) we do not need to assume a constant sedimentation rate between tie point or using diachronous biozones to compare age like those used in global compilations (24) (see Fig. 4A); 3) the δ13Calgae data are not artificially smoothed as in ref. 32 to avoid underestimation of the CIE magnitude; and 4) our records are not affected by dissolution or truncation, a phenomenon common to shallow marine carbonates due to the presumed ocean acidification occurred during the EPME (18, 33). In addition, the directly comparable records of δ13C for the atmosphere and the ocean offer further insights into the size of the true CIE and rate and duration of carbon emissions.Open in a separate windowFig. 1.(A) Paleogeographical map of the Late Permian, with former and current coastlines. Indicated are 1) the location of Finnmark cores 7128/12-U-01 and 7129/10-U-01, 2) the East Greenland site at Kap Stosch discussed in ref. 52, 3) the GSSP site for the base of the Triassic at Meishan, China, and 4) the Kuh-e-Ali Bashi site of Iran (66, 107). The map was modified after ref. 61. (B) Paleogeography and paleobathymetry of the Late Permian used in cGENIE.Open in a separate windowFig. 4.Synthesized proxy records of carbon isotopes from marine carbonates and fossil C3 land plants remains, sea surface temperature, and pH. (A) Comparison between δ13Calgae and global marine carbonate carbon isotopes from sites at Abadeh, Kuh-e-Ali Bashi, Shahreza, and Zal in Iran, Meishan, Wenbudangsang, and Yanggou in South China, at Bálvány North in Hungary, and at Nhi Tao in Vietnam (24). (B) Comparison between δ13Cleaf wax and the δ13C of sedimentary leaf cuticles and wood of C3 land plants from South China (24). (C) Reconstructed sea surface temperature data using conodont fossils (circles) (24) and brachiopods (triangles) (14). The conodont-based temperature data are from sites in the Paleo-Tethys, including Chanakhchi, Kuh-e Ali Bashi, Meishan, Shangsi, and Zal. (D) Relative changes in sea surface pH based on boron isotope proxy from ref. 17 and ref. 20. Pink and red circles are data from scenario 1 and scenario 2 in ref. 17, and green and blue diamonds are data from scenario 1 and scenario 2 in ref. 20.  相似文献   
152.
Surface molecules exclusively expressed by cells of the bone marrow (BM) are candidate targets for delivering therapeutic agents to this tissue. To identify ligands specific for the BM, we performed a series of pannings in vivo with random peptide phage displayed libraries (RPPDL). We could show that phages bind to bone marrow endothelium (BME) independently of the peptide insert, suggesting that the BM, similarly to spleen and liver, is part of the reticulo-endothelial system (RES). Furthermore, this strong "natural" affinity to the BME was abrogated by polyanions, indicating that phage trapping by this endothelium is mediated by scavenger receptors (SR). To circumvent interference by SR, polyinosinic acid was administered before phage panning in vivo. This led to the identification of a consensus motif that confers binding specificity for a subpopulation of hemopoietic marrow cells. Thus, SR inhibition, by avoiding phage trapping by the endothelium, seems to allow phage particles to extravasate and reach parenchymal cells. Accordingly, this panning strategy in vivo may be useful for the identification of targeting motifs specific for cells located in the extravascular space of various tissues.  相似文献   
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BACKGROUND AND PURPOSE: In the prospectively, randomized Dutch Bone Metastasis Study on the effect of a single fraction of 8 Gy versus 24 Gy in six fractions on painful bone metastases, 28% of the patients survived for more than 1 year. Purpose of the present study was to analyze the palliative effect of radiotherapy in long-term surviving patients, and to identify prognostic factors for survival. MATERIAL AND METHODS: Response rates were compared in all patients surviving>52 weeks. The Cox proportional hazards model stratified by primary tumour was used for multivariate (MV) analyses of prognostic factors for survival. RESULTS: In 320 patients surviving>52 weeks, responses were 87% after 8 Gy and 85% after 24 Gy (P=0.54). Duration of response and progression rates were similar. For all primary tumours, prognostic factors for survival were a good Karnofsky Performance Score, no visceral metastases, and non-opioid analgesics intake (all factors, MV P<0.001). CONCLUSIONS: Single fraction radiotherapy should be the standard dose schedule for all patients with painful bone metastases, including patients with an expected favourable survival. General prognosticators as the Karnofsky Performance Score and metastatic tumour load are useful in predicting survival.  相似文献   
156.
OBJECTIVES: To describe and discuss the challenges in evaluation of a participatory action research with street-involved youth. METHODS: A combination of quantitative and qualitative methods were utilized for both process and outcome evaluations. Process evaluation methods included in-depth individual interviews, focus groups, participant observation, and session debriefing forms. Summative evaluation research included focus testing of the harm reduction video and a survey of video users. FINDINGS: Members of the youth team reported favourably on the experience, citing friendship, skills development, fun, and pride of accomplishment among the key benefits of participation. Political tensions arose because of the focus on reducing harm from drug use rather than encouraging abstension. The heavy demands of participatory research and development, resource constraints and the priority given to product development in these kinds of projects necessarily precludes extensive youth participation in the design, implementation and analysis of additional evaluation research. Even when resources are directed towards evaluation, there is a tendency to focus on data collection, which may limit time and resources for data analysis. Finally, there is an inclination to focus on the product development rather than dissemination and impact of the product. INTERPRETATION: Despite the challenges inherent in participatory action research and its evaluation, this project was regarded as an empowering experience by the street youth who participated in it. It is worthwhile to direct resources to evaluation which optimally gives proportional attention to data collection as well as data analysis, and focusses not only on product development but also on its dissemination and impact.  相似文献   
157.
We evaluated the Oral Physician Program, a dental residency sponsored by Harvard Medical School, Harvard School of Dental Medicine, and the Cambridge Health Alliance that offers an innovative model for training dentists to provide limited primary care. The didactic and clinical experiences increased residents'' medical knowledge and interviewing skills, and faculty assessments supported their role as oral physicians. Oral physicians could increase patients''—especially patients from underserved groups—access to integrated oral and primary care services.Static and fragmented curricula are failing to prepare graduates of health professional schools for current population health challenges, including the growing burden of chronic diseases.1 Primary care must be a pillar of clinical training,1,2 and dentists, as oral physicians, should be trained to provide limited preventive primary care and disease prevention.3 During their predoctorate clinical training years, dentists learn about the oral manifestations of more than 100 genetic and systemic disorders,4 including developmental and eating disorders, cardiovascular disease, diabetes, osteoporosis, and cancers, as well as substance and child abuse.5 Thus, dentists should be well positioned to identify numerous systemic conditions in addition to oral diseases, often at an early stage, through oral manifestations.Advanced oral physician training following dental school can provide skill strengthening and the practice necessary to adapt to the changing health needs of today’s most vulnerable populations by increasing early disease detection and referral. Dentists practice as oral physicians, for example, when providing or overseeing complete dental care and aspects of primary care,6 such as taking vital signs, screening for diabetes and other major health problems, and administering vaccines.7 By providing a range of preventive health care services, dentists can help increase access to care and improve the health of the community as part of the primary care prevention and referral system.8 The training model of the oral physician decompartmentalizes oral and general health and meets the primary care training objective of “interprofessional and transprofessional education that breaks down professional silos.”1(p1924)  相似文献   
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