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| 3. |
- Geyer, C. E., et al.
(författare)
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Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer
- 2022
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 33:12, s. 1250-1268
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Tidskriftsartikel (refereegranskat)abstract
- Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.
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| 4. |
- Johnson, Taryn, et al.
(författare)
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Working Ethically with Ancient DNA from Composites in the United States
- 2024
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Ingår i: Advances in archaeological practice. - 2326-3768.
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Tidskriftsartikel (refereegranskat)abstract
- This article discusses ethical frameworks for planning and implementing composite research in the United States. Composites, defined here as archaeological materials with multiple genetic sources, include materials such as sediment, coprolites, birch pitch, and dental calculus. Although composites are increasingly used in genetic research, the ethical considerations of their use in ancient DNA studies have not been widely discussed. Here, we consider how composites' compositions, contexts, and potential to act as proxies can affect research plans and offer an overview of the primary ethical concerns of ancient DNA research. It is our view that ethical principles established for analyses of Ancestral remains and related materials can be used to inform research plans when working with composite evidence. This work also provides a guide to archaeologists unfamiliar with genetics analyses in planning research when using composite evidence from the United States with a focus on collaboration, having a clear research plan, and using lab methods that provide the desired data with minimal destruction. Following the principles discussed in this article and others allows for engaging in composite research while creating and maintaining positive relationships with stakeholders. El presente trabajo analiza las preocupaciones eticas para la planificacion e implementacion de investigaciones compuestas en los Estados Unidos. Los compuestos, definidos aqui como muestras arqueologicas con multiples fuentes geneticas, incluyen materiales como sedimentos, paleofecas, brea de abedul y calculo dental. Sin embargo, si bien los compuestos se han utilizado cada vez mas en la investigacion genetica arqueologica, las consideraciones eticas de su uso en estudios de aADN no se han discutido ampliamente. Aqui consideramos como las composiciones, los contextos y el potencial de los compuestos para actuar como sustitutos pueden afectar los planes de investigacion y ofrecer una vision general de las principales preocupaciones eticas de la investigacion del ADN antiguo. Es la opinion de los autores que los principios eticos establecidos para los analisis de restos humanos y materiales relacionados se pueden utilizar para informar los planes de investigacion cuando se trabaja con evidencia compuesta. Este trabajo ofrece tambien una guia para planificar la investigacion cuando se utiliza evidencia compuesta con un enfoque en la colaboracion, en planes de investigacion claros y uso de metodos de laboratorio que proporcionen los datos deseados con una destruccion minima de la muestra. Seguir los principios descritos en este documento permite participar en la investigacion compuesta sin dejar de lado la creacion y mantencion de relaciones positivas con las partes interesadas.
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- Liu, J. D., et al.
(författare)
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Optimal Strategy on Radiation Estimation for Calculating Universal Thermal Climate Index in Tourism Cities of China
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 19:13
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Tidskriftsartikel (refereegranskat)abstract
- The Universal Thermal Climate Index (UTCI) is believed to be a very powerful tool for providing information on human thermal perception in the domain of public health, but the solar radiation as an input variable is difficult to access. Thus, this study aimed to explore the optimal strategy on estimation of solar radiation to increase the accuracy in UTCI calculation, and to identify the spatial and temporal variation in UTCI over China. With daily meteorological data collected in 35 tourism cities in China from 1961 to 2020, two sunshine-based Angstrom and Ogelman models, and two temperature-based Bristow and Hargreaves models, together with neural network and support vector machine-learning methods, were tested against radiation measurements. The results indicated that temperature-based models performed the worst with the lowest NSE and highest RMSE. The machine-learning methods performed better in calibration, but the predictive ability decreased significantly in validation due to big data requirements. In contrast, the sunshine-based Angstrom model performed best with high NSE (Nash-Sutcliffe Efficiency) of 0.84 and low RMSE (Root Mean Square Error) of 35.4 J/m(2) s in validation, which resulted in a small RMSE of about 1.2 degrees C in UTCI calculation. Thus, Angstrom model was selected as the optimal strategy on radiation estimation for UTCI calculation over China. The spatial distribution of UTCI showed that days under no thermal stress were high in tourism cities in central China within a range from 135 to 225 days, while the largest values occurred in Kunming and Lijiang in southwest China. In addition, days under no thermal stress during a year have decreased in most tourism cities of China, which could be attributed to the asymmetric changes in significant decrease in frost days and slightly increase in hot days. However, days under no thermal stress in summer time have indeed decreased, accompanying with increasing days under strong stress, especially in the developed regions such as Yangze River Delta and Zhujiang River Delta. Based on the study, we conclude that UTCI can successfully depict the overall spatial distribution and temporal change of the thermal environments in the tourism cities over China, and can be recommend as an efficient index in the operational services for assessing and predicting thermal perception for public health. However, extreme cold and heat stress in the tourism cities of China were not revealed by UTCI due to mismatch of the daily UTCI with category at hourly scale, which makes it an urgent task to redefine category at daily scale in the next research work.
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- Liu, J. D., et al.
(författare)
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Spatial and Temporal Variations in the Potential Yields of Highland Barley in Relation to Climate Change in Three Rivers Region of the Tibetan Plateau from 1961 to 2020
- 2022
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 14:13
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Tidskriftsartikel (refereegranskat)abstract
- Spatial and temporal variations in the potential yields of highland barley is important for making policies on adaptation of agriculture to climate change in the Three Rivers Region (TRR), one of the main highland barley growing areas on the Tibetan Plateau. This research tries to explore a suitable strategy for simulating potential yields of highland barley by the WOFOST (WOrld FOod STudies) crop growth model, and further to identify variations in climate conditions and potential yields in TRR from 1961 to 2020 for making policies on adaptation of agricultural production to the climate change impacts on the Tibetan Plateau. Validation results indicated that WOFOST could accurately simulate the potential yields of highland barley with the global radiation estimated by the calibrated Angstrom model. The global radiation during the growth periods decreased at a rate of 0.047 MJ/m(2)a, while the temperature during the growth periods increased at rates ranging from 0.019 to 0.087 degrees C/a, which was greater than the average warming rate of the globe. The simulated potential yields ranged from 10,300 to 14,185 kg/ha in TRR, with an average decreasing rate of 28 kg/ha/a. The decrease in the potential yields was mainly attributed to the shortened critical period caused by warming effects, so cultivation of new varieties of highland barley with longer growth periods is suggested as an achievable strategy for the adaptation of highland barley to climate change in TRR.
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| 7. |
- Razis, E., et al.
(författare)
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Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force
- 2022
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally. Patients and methods: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site. Results: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific. Conclusions: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.
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| 8. |
- Shi, F., et al.
(författare)
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Ensemble standardization constraints on the influence of the tree growth trends in dendroclimatology
- 2020
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894.
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Tidskriftsartikel (refereegranskat)abstract
- Tree growth trends can affect the interpretation of the response of tree-ring proxies (especially tree-ring width) to climate in the low-frequency band, which in turn may limit quantitative understanding of centennial-scale climate variability. As such, it is difficult to determine if long-term trends in tree-ring measurements are caused by age-dependent growth effects or climate. Here, a trend similarity ranking method is proposed to define the range of tree growth effects on tree-ring width chronologies. This method quantifies the inner and outer boundaries of the tree growth effect following two extreme standardization methods: curve fitting standardization and regional curve standardization. The trend similarity ranking method classifies and detrends tree-ring measurements according to the ranking similarity between the regional growth curve and their long-term trends through curve fitting. This standardization process mainly affects the secular trend in tree-ring chronologies, and has no effect on their inter-annual to multi-decadal variations. Applications of this technique to the Yamal and Tornetrask tree-ring width datasets and the maximum latewood density dataset from northern Scandinavia reveals that multi-centennial and millennial-scale temperature variations in the three regions provide substantial positive contributions to the linear warming trends in the instrumental period, and that the summer warming rate during the 20th century is not unprecedented over the past two millennia in any of the three regions.
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| 9. |
- Treydte, Kerstin, et al.
(författare)
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Recent human-induced atmospheric drying across Europe unprecedented in the last 400 years
- 2024
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Ingår i: NATURE GEOSCIENCE. - 1752-0894 .- 1752-0908. ; 17, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- The vapor pressure deficit reflects the difference between how much moisture the atmosphere could and actually does hold, a factor that fundamentally affects evapotranspiration, ecosystem functioning, and vegetation carbon uptake. Its spatial variability and long-term trends under natural versus human-influenced climate are poorly known despite being essential for predicting future effects on natural ecosystems and human societies such as crop yield, wildfires, and health. Here we combine regionally distinct reconstructions of pre-industrial summer vapor pressure deficit variability from Europe's largest oxygen-isotope network of tree-ring cellulose with observational records and Earth system model simulations with and without human forcing included. We demonstrate that an intensification of atmospheric drying during the recent decades across different European target regions is unprecedented in a pre-industrial context and that it is attributed to human influence with more than 98% probability. The magnitude of this trend is largest in Western and Central Europe, the Alps and Pyrenees region, and the smallest in southern Fennoscandia. In view of the extreme drought and compound events of the recent years, further atmospheric drying poses an enhanced risk to vegetation, specifically in the densely populated areas of the European temperate lowlands. The atmosphere has dried across most regions of Europe in recent decades, a trend that can be attributed primarily to human impacts, according to tree ring records spanning 400 years and Earth system model simulations.
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| 10. |
- Tutt, A. N. J., et al.
(författare)
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Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer
- 2021
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 384:25, s. 2394-2405
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. METHODS We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. RESULTS A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life.
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