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"Whitlock, Katie"
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Book Reviews: \The Medieval Theater of Cruelty: Rhetoric, Memory, Violence\
Reviews \"The Medieval Theater of Cruelty: Rhetoric, Memory, Violence,\" written by Jody Enders (Cornell University Press, 1999, 268p, $45). States that \"the author presents a provocative argument, utilizing the medieval theatre as proof and basis for her conceptual understanding of the theatre of cruelty in relation to the time period.\" Remarks that \"the variety of source material is extensive and well documented, but can be viewed as overwhelming in scope and narrow in focus.\"
Book Review
Reliable Detection of Loci Responsible for Local Adaptation: Inference of a Null Model through Trimming the Distribution of FST
Loci responsible for local adaptation are likely to have more genetic differentiation among populations than neutral loci. However, neutral loci can vary widely in their amount of genetic differentiation, even over the same geographic range. Unfortunately, the distribution of differentiation—as measured by an index such as FST—depends on the details of the demographic history of the populations in question, even without spatially heterogeneous selection. Many methods designed to detect FST outliers assume a specific model of demographic history, which can result in extremely high false positive rates for detecting loci under selection. We develop a new method that infers the distribution of FST for loci unlikely to be strongly affected by spatially diversifying selection, using data on a large set of loci with unknown selective properties. Compared to previous methods, this approach, called OutFLANK, has much lower false positive rates and comparable power, as shown by simulation.
Journal Article
Finding the Genomic Basis of Local Adaptation
Uncovering the genetic and evolutionary basis of local adaptation is a major focus of evolutionary biology. The recent development of cost-effective methods for obtaining high-quality genome-scale data makes it possible to identify some of the loci responsible for adaptive differences among populations. Two basic approaches for identifying putatively locally adaptive loci have been developed and are broadly used: one that identifies loci with unusually high genetic differentiation among populations (differentiation outlier methods) and one that searches for correlations between local population allele frequencies and local environments (genetic-environment association methods). Here, we review the promises and challenges of these genome scan methods, including correcting for the confounding influence of a species’ demographic history, biases caused by missing aspects of the genome, matching scales of environmental data with population structure, and other statistical considerations. In each case, we make suggestions for best practices for maximizing the accuracy and efficiency of genome scans to detect the underlying genetic basis of local adaptation. With attention to their current limitations, genome scan methods can be an important tool in finding the genetic basis of adaptive evolutionary change.
Journal Article
Convergent local adaptation to climate in distantly related conifers
When confronted with an adaptive challenge, such as extreme temperature, closely related species frequently evolve similar phenotypes using the same genes. Although such repeated evolution is thought to be less likely in highly polygenic traits and distantly related species, this has not been tested at the genome scale. We performed a population genomic study of convergent local adaptation among two distantly related species, lodgepole pine and interior spruce. We identified a suite of 47 genes, enriched for duplicated genes, with variants associated with spatial variation in temperature or cold hardiness in both species, providing evidence of convergent local adaptation despite 140 million years of separate evolution. These results show that adaptation to climate can be genetically constrained, with certain key genes playing nonredundant roles.
Journal Article
Reliable Detection of Loci Responsible for Local Adaptation: Inference of a Null Model through Trimming the Distribution of F^sub ST
Loci responsible for local adaptation are likely to have more genetic differentiation among populations than neutral loci. However, neutral loci can vary widely in their amount of genetic differentiation, even over the same geographic range. Unfortunately, the distribution of differentiation -- as measured by an index such as FST -- depends on the details of the demographic history of the populations in question, even without spatially heterogeneous selection. Many methods designed to detect FST outliers assume a specific model of demographic history, which can result in extremely high false positive rates for detecting loci under selection. We develop a new method that infers the distribution of FST for loci unlikely to be strongly affected by spatially diversifying selection, using data on a large set of loci with unknown selective properties. Compared to previous methods, this approach, called OutFLANK, has much lower false positive rates and comparable power, as shown by simulation.
Journal Article
Reliable Detection of Loci Responsible for Local Adaptation: Inference of a Null Model through Trimming the Distribution of F ST
Loci responsible for local adaptation are likely to have more genetic differentiation among populations than neutral loci. However, neutral loci can vary widely in their amount of genetic differentiation, even over the same geographic range. Unfortunately, the distribution of differentiation—as measured by an index such as F
ST—depends on the details of the demographic history of the populations in question, even without spatially heterogeneous selection. Many methods designed to detect F
ST outliers assume a specific model of demographic history, which can result in extremely high false positive rates for detecting loci under selection. We develop a new method that infers the distribution of F
ST for loci unlikely to be strongly affected by spatially diversifying selection, using data on a large set of loci with unknown selective properties. Compared to previous methods, this approach, called OutFLANK, has much lower false positive rates and comparable power, as shown by simulation.
Journal Article
Reliable Detection of Loci Responsible for Local Adaptation: Inference of a Null Model through Trimming the Distribution of F(ST)
Loci responsible for local adaptation are likely to have more genetic differentiation among populations than neutral loci. However, neutral loci can vary widely in their amount of genetic differentiation, even over the same geographic range. Unfortunately, the distribution of differentiation--as measured by an index such as F(ST)--depends on the details of the demographic history of the populations in question, even without spatially heterogeneous selection. Many methods designed to detect F(ST) outliers assume a specific model of demographic history, which can result in extremely high false positive rates for detecting loci under selection. We develop a new method that infers the distribution of F(ST) for loci unlikely to be strongly affected by spatially diversifying selection, using data on a large set of loci with unknown selective properties. Compared to previous methods, this approach, called OutFLANK, has much lower false positive rates and comparable power, as shown by simulation.
Journal Article
Evaluation of the safety and tolerability of spironolactone in patients with heart failure and chronic kidney disease
BackgroundSpironolactone reduces morbidity and mortality in patients with heart failure (HF) with reduced ejection fraction (EF) and decreases hospitalizations in HF with preserved EF. To minimize the risk of hyperkalemia, patients must have an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 and potassium < 5.0 mEq/L prior to initiation; however, spironolactone is prescribed outside these parameters. The objective of this study was to evaluate the safety and tolerability of spironolactone in patients with HF and chronic kidney disease (CKD).MethodsThis single-center, retrospective cohort study evaluated patients ≥ 18 years with HF and CKD stages 3–5 who received ≥ 48 h of spironolactone therapy and were hospitalized from February 2018 to August 2019. The primary outcome was incidence of hyperkalemia (potassium ≥ 5.5 mEq/L).ResultsOverall, 121 patients were evaluated: 52.1% (n = 63) had an EF > 40% and 47.9% (n = 58) had an EF ≤ 40% with 69.4% (n = 84) CKD stage 3, 24.8% (n = 30) stage 4, and 5.8% (n = 7) stage 5. Spironolactone was initiated prior to admission (PTA) for 54.5% (n = 66) of patients, while 45.5% (n = 55) of orders were initiated during hospitalization. Eight patients (6.6%) experienced inpatient hyperkalemia—all with PTA spironolactone. Patients who experienced inpatient hyperkalemia had a numerically lower eGFR that was not statistically significant (35.40 vs. 38.22 mL/min/1.73 m2; p = 0.730). Patients with CKD stage 3 (n = 4) had numerically higher rates of inpatient hyperkalemia than stages 4 (n = 1) or 5 (n = 3) (50%, 12.5%, and 37.5% respectively; p < 0.05).ConclusionSpironolactone may be safe to initiate in hospitalized patients with HF and CKD; however, appropriateness of therapy must be assessed upon admission to the hospital. Larger studies are needed for conclusive results.
Journal Article