Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these ...men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy.
At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes).
Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis.
After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).
Forest soils store large amounts of carbon (C) and nitrogen (N), yet how predicted shifts in forest composition will impact long‐term C and N persistence remains poorly understood. A recent ...hypothesis predicts that soils under trees associated with arbuscular mycorrhizas (AM) store less C than soils dominated by trees associated with ectomycorrhizas (ECM), due to slower decomposition in ECM‐dominated forests. However, an incipient hypothesis predicts that systems with rapid decomposition—e.g. most AM‐dominated forests—enhance soil organic matter (SOM) stabilization by accelerating the production of microbial residues. To address these contrasting predictions, we quantified soil C and N to 1 m depth across gradients of ECM‐dominance in three temperate forests. By focusing on sites where AM‐ and ECM‐plants co‐occur, our analysis controls for climatic factors that covary with mycorrhizal dominance across broad scales. We found that while ECM stands contain more SOM in topsoil, AM stands contain more SOM when subsoil to 1 m depth is included. Biomarkers and soil fractionations reveal that these patterns are driven by an accumulation of microbial residues in AM‐dominated soils. Collectively, our results support emerging theory on SOM formation, demonstrate the importance of subsurface soils in mediating plant effects on soil C and N, and indicate that shifts in the mycorrhizal composition of temperate forests may alter the stabilization of SOM.
We quantified soil carbon (C) and nitrogen (N) to 1‐m depth across gradients of ectomycorrhizal (ECM)‐ vs. arbuscular mycorrhizal (AM)‐associated tree dominance within three temperate broadleaf forests. Contrary to previous hypotheses, we found that AM‐dominated soils store more C and N overall, and more C and N in the putatively most stable pools—deep and mineral‐associated soil organic matter. Our data support the emerging hypothesis that systems with fast decomposition should store more stable soil organic matter.
How did human societies evolve from small groups, integrated by face-to-face cooperation, to huge anonymous societies of today, typically organized as states? Why is there so much variation in the ...ability of different human populations to construct viable states? Existing theories are usually formulated as verbal models and, as a result, do not yield sharply defined, quantitative predictions that could be unambiguously tested with data. Here we develop a cultural evolutionary model that predicts where and when the largest-scale complex societies arose in human history. The central premise of the model, which we test, is that costly institutions that enabled large human groups to function without splitting up evolved as a result of intense competition between societies—primarily warfare. Warfare intensity, in turn, depended on the spread of historically attested military technologies (e.g., chariots and cavalry) and on geographic factors (e.g., rugged landscape). The model was simulated within a realistic landscape of the Afroeurasian landmass and its predictions were tested against a large dataset documenting the spatiotemporal distribution of historical large-scale societies in Afroeurasia between 1,500 BCE and 1,500 CE. The model-predicted pattern of spread of large-scale societies was very similar to the observed one. Overall, the model explained 65% of variance in the data. An alternative model, omitting the effect of diffusing military technologies, explained only 16% of variance. Our results support theories that emphasize the role of institutions in state-building and suggest a possible explanation why a long history of statehood is positively correlated with political stability, institutional quality, and income per capita.
Soil phosphorus (P) availability in lowland tropical rainforests influences the distribution and growth of tropical tree species. Determining the P-acquisition strategies of tropical tree species ...could therefore yield insight into patterns of tree β-diversity across edaphic gradients. In particular, the synthesis of root phosphatases is likely to be of significance given that organic P represents a large pool of potentially available P in tropical forest soils. It has also been suggested that a high root phosphatase activity in putative nitrogen (N) -fixing legumes might explain their high abundance in lowland neotropical forests under low P supply. Here, we measured phosphomonoesterase (PME) activity on the first three root orders of co-occurring tropical tree species differing in their N-fixation capacity, growing on soils of contrasting P availability in Panama. Our results show that root PME activity was higher on average in P-poor than in P-rich soils, but that local variation in PME activity among co-occurring species within a site was larger than that explained by differences in soil P across sites. Legumes expressed higher PME activity than nonlegumes, but nodulated legumes (i.e., actively fixing nitrogen) did not differ from legumes without nodules, indicating that PME activity is unrelated to N fixation. Finally, PME activity declined with increasing root order, but the magnitude of the decline varied markedly among species, highlighting the importance of classifying fine roots into functional groups prior to measuring root traits. Our results support the hypothesis that low-P promotes a high root PME activity, although the high local variation in this trait among co-occurring species points toward a high functional diversity in P-acquisition strategies within an individual community.
Tropical forest vegetation is shaped by climate and by soil, but understanding how the distributions of individual tree species respond to specific resources has been hindered by high diversity and ...consequent rarity. To study species over an entire community, we surveyed trees and measured soil chemistry across climatic and geological gradients in central Panama and then used a unique hierarchical model of species occurrence as a function of rainfall and soil chemistry to circumvent analytical difficulties posed by rare species. The results are a quantitative assessment of the responses of 550 tree species to eight environmental factors, providing a measure of the importance of each factor across the entire tree community. Dry-season intensity and soil phosphorus were the strongest predictors, each affecting the distribution of more than half of the species. Although we anticipated clear-cut responses to dry-season intensity, the finding that many species have pronounced associations with either high or low phosphorus reveals a previously unquantified role for this nutrient in limiting tropical tree distributions. The results provide the data necessary for understanding distributional limits of tree species and predicting future changes in forest composition.
Motivated by recent observations of intense electric fields and elevated energetic particle fluxes within flow bursts beyond geosynchronous altitude (Runov et al., 2009, 2011), we apply modeling of ...particle guiding centers in prescribed but realistic electric fields to improve our understanding of energetic particle acceleration and transport toward the inner magnetosphere through model‐data comparisons. Representing the vortical nature of an earthward traveling flow burst, a localized, westward‐directed transient electric field flanked on either side by eastward fields related to tailward flow is superimposed on a nominal steady state electric field. We simulate particle spectra observed at multiple THEMIS spacecraft located throughout the magnetotail and fit the modeled spectra to observations, thus constraining properties of the electric field model. We find that a simple potential electric field model is capable of explaining the presence and spectral properties of both geosynchronous altitude and “trans‐geosynchronous” injections at higher L‐shells (L > 6.6 RE) in a manner self‐consistent with the injections' inward penetration. In particular, despite the neglect of the magnetic field changes imparted by dipolarization and the inductive electric field associated with them, such a model can adequately describe the physics of both dispersed injections and depletions (“dips”) in energy flux in terms of convective fields associated with earthward flow channels and their return flow. The transient (impulsive), localized, and vortical nature of the earthward‐propagating electric field pulse is what makes this model particularly effective.
Key Points
We adapted a numerical model of particle GC motion in prescribed electric fields
We simulate (trans‐)geosynchronous injection features: eflux enhancements & dips
We explain e‐ acceleration & transport by impulsive, localized electric E‐fields
Tropical forests are renowned for their high diversity, yet in many sites a single tree species accounts for the majority of the individuals in a stand. An explanation for these monodominant forests ...remains elusive, but may be linked to mycorrhizal symbioses. We tested three hypotheses by which ectomycorrhizas might facilitate the dominance of the tree, Oreomunnea mexicana, in montane tropical forest in Panama. We tested whether access to ectomycorrhizal networks improved growth and survival of seedlings, evaluated whether ectomycorrhizal fungi promote seedling growth via positive plant–soil feedback, and measured whether Oreomunnea reduced inorganic nitrogen availability. We found no evidence that Oreomunnea benefits from ectomycorrhizal networks or plant–soil feedback. However, we found three‐fold higher soil nitrate and ammonium concentrations outside than inside Oreomunnea‐dominated forest and a correlation between soil nitrate and Oreomunnea abundance in plots. Ectomycorrhizal effects on nitrogen cycling might therefore provide an explanation for the monodominance of ectomycorrhizal tree species worldwide.
Body size is a classic quantitative trait with evolutionarily significant variation within many species. Locating the alleles responsible for this variation would help understand the maintenance of ...variation in body size in particular, as well as quantitative traits in general. However, successful genome-wide association of genotype and phenotype may require very large sample sizes if alleles have low population frequencies or modest effects. As a complementary approach, we propose that population-based resequencing of experimentally evolved populations allows for considerable power to map functional variation. Here, we use this technique to investigate the genetic basis of natural variation in body size in Drosophila melanogaster. Significant differentiation of hundreds of loci in replicate selection populations supports the hypothesis that the genetic basis of body size variation is very polygenic in D. melanogaster. Significantly differentiated variants are limited to single genes at some loci, allowing precise hypotheses to be formed regarding causal polymorphisms, while other significant regions are large and contain many genes. By using significantly associated polymorphisms as a priori candidates in follow-up studies, these data are expected to provide considerable power to determine the genetic basis of natural variation in body size.
Hyperexcitability of the anterior cingulate cortex (ACC) is thought to drive aversion associated with chronic neuropathic pain. Here, we studied the contribution of input from the mediodorsal ...thalamus (MD) to ACC, using sciatic nerve injury and chemotherapy-induced mouse models of neuropathic pain. Activating MD inputs elicited pain-related aversion in both models. Unexpectedly, excitatory responses of layer V ACC neurons to MD inputs were significantly weaker in pain models compared to controls. This caused the ratio between excitation and feedforward inhibition elicited by MD input to shift toward inhibition, specifically for subcortically projecting (SC) layer V neurons. Furthermore, direct inhibition of SC neurons reproduced the pain-related aversion elicited by activating MD inputs. Finally, both the ability to elicit pain-related aversion and the decrease in excitation were specific to MD inputs; activating basolateral amygdala inputs produced opposite effects. Thus, chronic pain-related aversion may reflect activity changes in specific pathways, rather than generalized ACC hyperactivity.
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•Activating MD thalamus-ACC inputs exacerbates pain-related aversion•In pain, MD inputs to subcortically projecting ACC neurons shift toward inhibition•Inhibiting subcortically projecting ACC neurons exacerbates pain-related aversion•Unlike MD-ACC input, BLA-ACC input is strengthened in pain and mitigates aversion
Meda et al. show that in chronic pain states, mediodorsal thalamic (MD) inputs to the anterior cingulate cortex (ACC) undergo pathway-specific changes. As a result, MD-ACC inputs suppress the activity of many subcortically projecting ACC neurons, thereby driving negative pain-related affect.
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