Reconstruction of a 253-year long mast record of European beech reveals its association with large scale temperature variability and no long-term trend in mast frequencies

Synchronous production of large seed crops, or mast years (MYs), is a common feature of many Fagus species, which is closely linked to the dynamics of forest ecosystems, including regeneration of canopy trees and changes in animal population densities. To better understand its climatic controls and check for the presence of long-term temporal trends in MY frequencies, we reconstructed MY record of the European beech (Fagus sylvatica L.) for the southern Swedish province of Halland over 1753-2006. We used superimposed epoch analysis (SEA) to relate MY (a) to summer temperature fields over the European subcontinent and (b) to the patterns of 500 mb geopotential heights over the 35-75 degrees N. For the MY reconstruction, we used newly developed regional beech ring-width chronology (1753-2006), an available summer temperature reconstruction, and a discontinuous historical MY record. A Monte Carlo experiment allowed identification of the thresholds in both growth and summer temperature anomalies, indicative of historical MYs, which were verified by dividing data into temporally independent calibration and verification sub-periods.MYs were strongly associated with both the 500 mb height anomalies and average summer temperatures during two years preceding a MY: a mast year (t) followed a cold summer two years (t-2) prior to the mast year and a warm summer one year prior (t-1) to the mast year. During t-2 years, the geographical pattern of 500 mb height anomalies exhibited a strong height depression in the region centered in the Northern Sea and extending toward eastern North America and statistically significant (p<0.05) temperature anomalies covering predominantly southern Scandinavia (area below 60 N) and British Isles. A year immediately preceding a mast year (t-1) was characterized by a strong regional high pressure anomaly centered in southern Scandinavia with significant temperature anomalies extended mostly over southern Scandinavia and Germany.The long-term mean MY return interval was 6.3 years, with 50 and 90% probabilities of MY occurrence corresponding to 6 and 15 years, respectively. Periods with intervals significantly shorter than the long-term mean were observed around 1820-1860 and 1990-2006 (means 3.9 and 3.2 years, respectively). However, the difference in return intervals between two sub-periods themselves was not significant.Geographically large and temporally rapid changes in atmospheric circulation among years, responsible for summer temperature conditions in the Northern Europe, are likely primary environmental drivers of masting phenomenon. However, decadal and centurial variability in MY intervals is difficult to relate directly to temperature variability, suggesting the presence of conditions "canceling" would-be MYs. Long-term MY reconstruction demonstrates high variability of reproductive behavior in European beech and indicates that a period with shorter MY intervals at the end of 20th may be not unique in a multi-century perspective

Fire and the relative roles of weather, climate and landscape characteristics in the Great Lakes-St. Lawrence forest of Canada

Question: In deciduous-dominated forest landscapes, what are the relative roles of fire weather, climate, human and biophysical landscape characteristics for explaining variation in large fire occurrence and area burned? Location: The Great Lakes-St. Lawrence forest of Canada. Methods: We characterized the recent (1959-1999) regime of large (≥ 200 ha) fires in 26 deciduous-dominated landscapes and analysed these data in an information-theoretic framework to compare six hypotheses that related fire occurrence and area burned to fire weather severity, climate normals, population and road densities, and enduring landscape characteristics such as surficial deposits and large lakes. Results: 392 large fires burned 833 698 ha during the study period, annually burning on average 0.07% ± 0.42% of forested area in each landscape. Fire activity was strongly seasonal, with most fires and area burned occurring in May and June. A combination of antecedent-winter precipitation, fire season precipitation deficit/surplus and percent of landscape covered by well-drained surficial deposits best explained fire occurrence and area burned. Fire occurrence varied only as a function of fire weather and climate variables, whereas area burned was also explained by percent cover of aspen and pine stands, human population density and two enduring characteristics: percent cover of large water bodies and glaciofluvial deposits. Conclusion: Understanding the relative role of these variables may help design adaptation strategies for forecasted increases in fire weather severity by allowing (1) prioritization of landscapes according to enduring characteristics and (2) management of their composition so that substantially increased fire activity would be necessary to transform landscape structure and composition

Overstory influences on light attenuation patterns and understory plant community diversity and composition in southern boreal forests of Quebec

We have characterized overstory light transmission, understory light levels, and plant communities in mixedwood boreal forests of northwestern Quebec with the objective of understanding how overstory light transmission interacts with composition and time since disturbance to influence the diversity and composition of understory vegetation, and, in turn, the further attenuation of light to the forest floor by the understory. Overstory light transmission differed among three forest types (aspen, mixed deciduous-conifer, and old cedar-dominated), with old forests having higher proportions of high light levels than aspen and mixed forests, which were characterized by intermediate light levels. The composition of the understory plant communities in old forests showed the weakest correlation to overstory light transmission, although those forests had the largest range of light transmission. The strongest correlation between characteristics of overstory light transmission and understory communities was found in aspen forests. Species diversity indices were consistently higher in aspen forests but showed weak relationships with overstory light transmission. Light attenuation by the understory vegetation and total height of the understory vegetation were strongly and positively related to overstory light transmission but not forest type. Therefore, light transmission through the overstory influenced the structure and function of understory plants more than their diversity and composition. This is likely due to the strong effect of the upper understory layers, which tend to homogenize light levels at the forest floor regardless of forest type. The understory plant community acts as a filter, thereby reducing light levels at the forest floor to uniformly low levels

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

Oncogenic Signaling Pathways in The Cancer Genome Atlas

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFb signaling, p53 and beta-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing