Resource Variation Within and Between Patches: Where Exploitation Competition, Local Adaptation, and Kin Selection Meet.

AbstractIn patch- or habitat-structured populations, different processes can favor adaptive polymorphism at different scales. While spatial heterogeneity can generate spatially disruptive selection favoring variation between patches, local competition can lead to locally disruptive selection promoting variation within patches. So far, almost all theory has studied these two processes in isolation. Here, we use mathematical modeling to investigate how resource variation within and between habitats influences the evolution of variation in a consumer population where individuals compete in finite patches connected by dispersal. We find that locally and spatially disruptive selection typically act in concert, favoring polymorphism under a wider range of conditions than when in isolation. But when patches are small and dispersal between them is low, kin competition inhibits the emergence of polymorphism, especially when the latter is driven by local competition for resources. We further use our model to clarify what comparisons between trait and neutral genetic differentiation (QST/FST comparisons) can tell about the nature of selection. Overall, our results help us understand the interaction between two major drivers of polymorphism: locally and spatially disruptive selection, and how this interaction is modulated by the unavoidable effects of kin selection under limited dispersal.

GEC-ESTRO (ACROP)-ABS-CBG Consensus Brachytherapy Target Definition Guidelines for Recurrent Endometrial and Cervical Tumors in the Vagina.

PURPOSE: Representatives from the Gynecologic Groupe European de Curietherapie-European Society for Radiation Therapy and Oncology (GYN GEC-ESTRO), the American Brachytherapy Society (ABS), and the Canadian Brachytherapy Group (CBG) met to develop international consensus recommendations for target definitions for image-guided adaptive brachytherapy for vaginal recurrences of endometrial or cervical cancer. METHODS AND MATERIALS: Seventeen radiation oncologists and 2 medical physicists participated. Before an in-person meeting each participant anonymously contoured 3 recurrent endometrial/cervical cancer cases. Participants contoured the residual gross primary tumor volume (GTV-Tres), a high-risk clinical target volume (CTV-THR), and an intermediate-risk clinical target volume (CTV-TIR), on T2-weighted magnetic resonance images (MRIs). All contours were drawn using Falcon EduCase. Contours were reviewed at an in-person meeting during which a consensus document was created defining agreed-upon target definitions (Trial 1). After establishing these definitions, the group was sent one of the cases again (recurrent cervical cancer vaginal recurrence) and asked to contour the targets again (Trial 2). The Computerized Environment for Radiation Research (CERR) software (The Mathworks, Natwick, MA) was used to analyze the contours. Kappa statistics were generated to assess level of agreement between contours. A conformity index (CI), defined as the ratio between the intersection and union volume of a given pair of contours, was calculated. A simultaneous truth and performance level estimation (STAPLE) contour was created for the CTV-THR and CTV-TIR for the postmeeting case. RESULTS: Consensus definitions for GTV-Tres, CTV-THR, and CTV-TIR were established. Kappa statistics (Trial 1/Trial 2) for GTV-Tres, CTV-THR, and CTV-TIR were 0.536/0.583, 0.575/0.743 and 0.522/0.707. Kappa statistics for Trial 2 for the CTV-THR and CTV-TIR showed "substantial" agreement while the GTV-Tres remained at moderate agreement. CONCLUSIONS: This consensus provides recommendations to facilitate future collaborations for MRI-guided adaptive brachytherapy target definitions in endometrial/cervical vaginal recurrences.

A Trade-Off between Robustness to Environmental Fluctuations and Speed of Evolution.

AbstractUnderstanding how a species' life history affects its capacity to cope with environmental changes is important in the context of rapid climate changes. Reinterpreting previous results from a well-developed theoretical framework, we show that a trade-off exists between a species' ability to genetically adapt to long-term gradual environmental changes and its ability to demographically resist short-term environmental perturbations, causing variation in its vital rates. Surprisingly, this important insight has not been made formally explicit before. Choosing archetypal life histories along the fast-slow pace-of-life continuum and modeling their eco-evolutionary dynamics, we further show that long-lived species have larger demographic robustness to interannual fluctuations but limited trait evolutionary responses in gradually changing environments. In contrast, short-lived species had larger evolvability but reduced demographic robustness. This trade-off bears heavily on extinction probabilities of populations tracking fast trait changes in stochastic environments. Faster trait evolution in short-lived species came at the expense of their higher sensitivity to short-term fluctuations, causing higher extinction rates than for long-lived species. Long-lived species persisted better on short timescales but built maladaptation and an extinction debt over time. This work shows how modeling species' eco-evolutionary dynamics can help to assess species vulnerability to environmental changes.

Oxy-Combustion of Solid Recovered Fuel in a Semi-Industrial CFB Reactor: On the Implications of Gas Atmosphere and Combustion Temperature.

Oxy-fuel combustion of refuse waste is gaining considerable attention as a viable CO2 negative technology that can enable the continued use of stationary combustion plants during the transition to renewable energy sources. Compared to fossil fuels, waste-derived fuels tend to be highly heterogeneous and to contain a greater amount of alkaline metals and chlorine. Therefore, experimental studies are mandatory to thoroughly elucidate refuse materials' combustion and pollutant formation behavior. This paper presents an experimental investigation on the air and oxy-fuel combustion of solid recovered fuel at a 200 kWth circulating fluidized bed facility. In the course of two experimental campaigns, the effects of combustion atmosphere and temperature on pollutant formation (i.e., NO x , SO2, and HCl) and reactor hydrodynamics were systematically studied. In contrast to air-firing conditions, the experimental results showed that oxy-fuel combustion enhanced the volume concentration of NO x by about 50% while simultaneously decreasing the fuel-specific NO x emissions (by about 33%). The volume concentrations of SO2 and HCl were significantly influenced by the absorption capacity of calcium-containing ash particles, yielding corresponding values close to 10 and 200 ppmv at 871-880 °C under oxy-fuel combustion conditions. In addition, the analysis of hydrodynamic data revealed that smooth temperature profiles are indispensable to mitigate bed sintering and agglomeration risks during oxy-fuel operation. The results included in this study provide a valuable contribution to the database of experimental information on the oxy-fuel combustion of alternative fuels, which can be applied in future process model validations and scale-up studies.

Dosimetric impact of target definition in brachytherapy for cervical cancer - Computed tomography and trans rectal ultrasound versus magnetic resonance imaging.

Background and Purpose: Magnetic Resonance Imaging (MRI) based target definition in cervix brachytherapy is limited by its availability, logistics and financial implications, therefore, use of computed tomography (CT) and Trans Rectal UltraSonography (TRUS) has been explored. The current study evaluated the dosimetric impact of CT + TRUS based target volumes as compared to gold standard MRI. Methods and Materials: Images of patients (n = 21) who underwent TRUS followed by MRI and CT, were delineated with High-Risk Clinical Target Volume in CT (CTVHR-CT) and in MRI (CTVHR-MR). CTVHR-CT was drawn on CT images with TRUS assistance. For each patient, two treatment plans were made, on MRI and CT, followed by fusion and transfer of CTVHR-MR to the CT images, referred as CTVHR-MRonCT. The agreement between CTVHR-MRonCT and CTVHR-CT was evaluated for dosimetric parameters (D90, D98 and D50; Dose received by 90%, 98% and 50% of the volumes) using Bland-Altman plots, linear regression, and Pearson correlation. Results: No statistically significant systematic difference was found between MRI and CT. Mean difference (±1.96 SD) of D90, D98 and D50 between CTVHR-MRonCT and CTVHR-CT was 2.0, 1.2 and 5.6 Gy respectively. The number of patients who have met the dose constraints of D90 > 85 Gy were 90% and 80% in MR and in CT respectively, others were in the borderline, with a minimum dose of 80 Gy. The mean ± SD dose-difference between MR and CT plans for bladder was significant (5 ± 13 Gy; p = 0.12) for D0.1cm3, while others were statistically insignificant. Conclusion: CT + TRUS based delineation of CTVHR appear promising, provide useful information to optimally utilize for brachytherapy planning, however, MRI remains the gold standard.

Genomic vulnerability to rapid climate warming in a tree species with a long generation time.

The ongoing increase in global temperature affects biodiversity, especially in mountain regions where climate change is exacerbated. As sessile, long-lived organisms, trees are especially challenged in terms of adapting to rapid climate change. Here, we show that low rates of allele frequency shifts in Swiss stone pine (Pinus cembra) occurring near the treeline result in high genomic vulnerability to future climate warming, presumably due to the species' long generation time. Using exome sequencing data from adult and juvenile cohorts in the Swiss Alps, we found an average rate of allele frequency shift of 1.23 × 10-2 /generation (i.e. 40 years) at presumably neutral loci, with similar rates for putatively adaptive loci associated with temperature (0.96 × 10-2 /generation) and precipitation (0.91 × 10-2 /generation). These recent shifts were corroborated by forward-in-time simulations at neutral and adaptive loci. Additionally, in juvenile trees at the colonisation front we detected alleles putatively beneficial under a future warmer and drier climate. Notably, the observed past rate of allele frequency shift in temperature-associated loci was decidedly lower than the estimated average rate of 6.29 × 10-2 /generation needed to match a moderate future climate scenario (RCP4.5). Our findings suggest that species with long generation times may have difficulty keeping up with the rapid climate change occurring in high mountain areas and thus are prone to local extinction in their current main elevation range.

Species' Range Dynamics Affect the Evolution of Spatial Variation in Plasticity under Environmental Change.

While clines in environmental tolerance and phenotypic plasticity along a single species' range have been reported repeatedly and are of special interest in the context of adaptation to environmental changes, we know little about their evolution. Recent empirical findings in ectotherms suggest that processes underlying dynamic species' ranges can give rise to spatial differences in environmental tolerance and phenotypic plasticity within species. We used individual-based simulations to investigate how plasticity and tolerance evolve in the course of three scenarios of species' range shifts and range expansions on environmental gradients. We found that regions of a species' range that experienced a longer history or larger extent of environmental change generally exhibited increased plasticity or tolerance. Such regions may be at the trailing edge when a species is tracking its ecological niche in space (e.g., in a climate change scenario) or at the front edge when a species expands into a new habitat (e.g., in an expansion/invasion scenario). Elevated tolerance and plasticity in the distribution center was detected when asymmetric environmental change (e.g., polar amplification) led to a range expansion. However, tolerance and plasticity clines were transient and slowly flattened out after range dynamics because of genetic assimilation.

The EMBRACE II study: The outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies.

The publication of the GEC-ESTRO recommendations one decade ago was a significant step forward for reaching international consensus on adaptive target definition and dose reporting in image guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. Since then, IGABT has been spreading, particularly in Europe, North America and Asia, and the guidelines have proved their broad acceptance and applicability in clinical practice. However, a unified approach to volume contouring and reporting does not imply a unified administration of treatment, and currently both external beam radiotherapy (EBRT) and IGABT are delivered using a large variety of techniques and prescription/fractionation schedules. With IGABT, local control is excellent in limited and well-responding tumours. The major challenges are currently loco-regional control in advanced tumours, treatment-related morbidity, and distant metastatic disease. Emerging evidence from the RetroEMBRACE and EMBRACE I studies has demonstrated that clinical outcome is related to dose prescription and technique. The next logical step is to demonstrate excellent clinical outcome with the most advanced EBRT and brachytherapy techniques based on an evidence-based prospective dose and volume prescription protocol. The EMBRACE II study is an interventional and observational multicentre study which aims to benchmark a high level of local, nodal and systemic control while limiting morbidity, using state of the art treatment including an advanced target volume selection and contouring protocol for EBRT and brachytherapy, a multi-parametric brachytherapy dose prescription protocol (clinical validation of dose constraints), and use of advanced EBRT (IMRT and IGRT) and brachytherapy (IC/IS) techniques (clinical validation). The study also incorporates translational research including imaging and tissue biomarkers.

A dynamic eco-evolutionary model predicts slow response of alpine plants to climate warming.

Withstanding extinction while facing rapid climate change depends on a species' ability to track its ecological niche or to evolve a new one. Current methods that predict climate-driven species' range shifts use ecological modelling without eco-evolutionary dynamics. Here we present an eco-evolutionary forecasting framework that combines niche modelling with individual-based demographic and genetic simulations. Applying our approach to four endemic perennial plant species of the Austrian Alps, we show that accounting for eco-evolutionary dynamics when predicting species' responses to climate change is crucial. Perennial species persist in unsuitable habitats longer than predicted by niche modelling, causing delayed range losses; however, their evolutionary responses are constrained because long-lived adults produce increasingly maladapted offspring. Decreasing population size due to maladaptation occurs faster than the contraction of the species range, especially for the most abundant species. Monitoring of species' local abundance rather than their range may likely better inform on species' extinction risks under climate change.

Repetitive flanking sequences challenge microsatellite marker development: a case study in the lepidopteran Melanargia galathea.

Microsatellite DNA families (MDF) are stretches of DNA that share similar or identical sequences beside nuclear simple-sequence repeat (nSSR) motifs, potentially causing problems during nSSR marker development. Primers positioned within MDFs can bind several times within the genome and might result in multiple banding patterns. It is therefore common practice to exclude MDF loci in the course of marker development. Here, we propose an approach to deal with multiple primer-binding sites by purposefully positioning primers within the detected repetitive element. We developed a new protocol to determine the family type and the primer position in relation to MDFs using the software packages repark and repeatmasker together with an in-house R script. We re-evaluated newly developed nSSR markers for the lepidopteran Marbled White (Melanargia galathea) and explored the implications of our results with regard to published data sets of the butterfly Euphydryas aurinia, the grasshopper Stethophyma grossum, the conifer Pinus cembra and the crucifer Arabis alpina. For M. galathea, we show that it is not only possible to develop reliable nSSR markers for MDF loci, but even to benefit from their presence in some cases: We used one unlabelled primer, successfully binding within an MDF, for two different loci in a multiplex PCR, combining this family primer with uniquely binding and fluorescently labelled primers outside of MDFs, respectively. As MDFs are abundant in many taxa, we propose to consider these during nSSR marker development in taxa concerned. Our new approach might help in reducing the number of tested primers during nSSR marker development.

Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome.

OBJECTIVE: To delineate a novel autosomal recessive multiple congenital anomaly-mental retardation (MCA-MR) syndrome in 2 female siblings of a consanguineous pedigree and to identify the disease-causing mutation. STUDY DESIGN: Both siblings were clinically characterized and homozygosity mapping and sequencing of candidate genes were applied. The contribution of nonsense-mediated messenger RNA (mRNA) decay to the expression of mutant mRNA in fibroblasts of a healthy carrier and a control was studied by pyrosequencing. RESULTS: We identified the first homozygous SALL1 mutation, c.3160C > T (p.R1054*), in 2 female siblings presenting with multiple congenital anomalies, central nervous system defects, cortical blindness, and absence of psychomotor development (ie, a novel recognizable, autosomal recessive MCA-MR). The mutant SALL1 transcript partially undergoes nonsense-mediated mRNA decay and is present at 43% of the normal transcript level in the fibroblasts of a healthy carrier. CONCLUSION: Previously heterozygous SALL1 mutations and deletions have been associated with dominantly inherited anal-renal-radial-ear developmental anomalies. We identified an allelic recessive SALL1-related MCA-MR. Our findings imply that quantity and quality of SALL1 transcript are important for SALL1 function and determine phenotype, and mode of inheritance, of allelic SALL1-related disorders. This novel MCA-MR emphasizes SALL1 function as critical for normal central nervous system development and warrants a detailed neurologic investigation in all individuals with SALL1 mutations.