This review addresses the question of when spatial coincidence facilitates multisensory integration in humans. According to the spatial rule (which was first formulated on the basis of neurophysiological data in anesthetized animals), multisensory integration is enhanced when stimuli in different sensory modalities are presented from the same spatial location. While the spatial rule fits with the available data from studies of overt and covert spatial attentional orienting, and from the majority of those studies in which space has been somehow relevant to the participant's task, it is inconsistent with the evidence that has emerged from the majority of multisensory studies of stimulus identification and temporal perception. Such a mixed pattern of behavioral results suggests that the spatial rule does not represent a general constraint on multisensory integration in humans. Instead, it would appear to be a much more task-dependent phenomenon than is often realized. These results, however, are broadly consistent with a distinction between the processing of “where” and “what” (or “how”) information processing in the human brain.

The development of rivaroxaban (XARELTO®) is an important new medical advance in the field of oral anticoagulation. Thrombosis-mediated conditions constitute a major burden for patients, healthcare systems, and society. For more than 60 years, the prevention and treatment of these conditions have been dominated by oral vitamin K antagonists (such as warfarin) and the injectable heparins. Thrombosis can lead to several conditions, including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, and/or death. Prevention and treatment of thrombosis with an effective, convenient-to-use oral anticoagulant with a favorable safety profile is critical, especially in an aging society in which the risk of thrombosis, and the potential for bleeding complications, is increasing. Rivaroxaban acts to prevent and treat thrombosis by potently inhibiting coagulation Factor Xa in the blood. Factor Xa converts prothrombin to thrombin, which initiates the formation of blood clots by converting fibrinogen to clot-forming fibrin and leads to platelet activation. After a large and novel clinical development program in over 75,000 patients to date, rivaroxaban has received approval for multiple indications in the United States, European Union, and other countries worldwide to prevent and treat several thrombosis-mediated conditions. This review will highlight some of the unique aspects of the rivaroxaban development program.

Laterality in handgrip strength was assessed by analyzing dynamometric data of the right and left hand in three samples of Lithuanian boys and girls aged 7–20 years. In addition, the influence of general physical training on the laterality of handgrip strength was explored in a sample of conscripts. A negative secular trend in handgrip strength of schoolchildren has been detected since 1965, and with increasing age, right-handedness has become more pronounced. Children that were ambidextrous (by grip strength) showed negative deviations in physical status more often than their right- or left-handed peers. During one year of physical training, the conscripts had a larger increase in grip strength of the left than in the right hand, and a marked shift in handgrip laterality toward left-handed and ambidextrous individuals was observed. The different impact of schooling and physical training on handgrip strength laterality might partly explain variations in the prevalence of handedness in different societies with divergent cultures and lifestyles (e.g., more or less sedentary).

Advances in bioimaging have revolutionized our ability to study life phenomena at a microscopic scale. In particular, the stimulated emission process, a universal mechanism that competes with spontaneous emission, has emerged as a powerful driving force for advancing light microscopy. The present review summarizes and compares three related techniques that each measure a different physical quantity involved in the stimulated emission process in order to tackle various challenges in light microscopy. Stimulated emission depletion microscopy, which detects the residual fluorescence after quenching, can break the diffraction-limited resolution barrier in fluorescence microscopy. Stimulated emission microscopy is capable of imaging nonfluorescent but absorbing chromophores by detecting the intensity gain of the stimulated emission beam. Very recently, stimulated emission reduced fluorescence microscopy has been proposed, in which the reduced fluorescence due to focal stimulation is measured to extend the fundamental imaging-depth limit of two-photon microscopy. Thus, through ingenious spectroscopy design in distinct microscopy contexts, stimulated emission has opened up several new territories for bioimaging, allowing examination of biological structures that are ever smaller, darker, and deeper.

The study of evolution has entered a revolutionary new era, where quantitative and predictive methods are transforming the traditionally qualitative and retrospective approaches of the past. Genomic sequencing and modern computational techniques are permitting quantitative comparisons between variation in the natural world and predictions rooted in neo-Darwinian theory, revealing the shortcomings of current evolutionary theory, particularly with regard to large-scale phenomena like macroevolution. Current research spanning and uniting diverse fields and exploring the physical and chemical nature of organisms across temporal, spatial, and organizational scales is replacing the model of evolution as a passive filter selecting for random changes at the nucleotide level with a paradigm in which evolution is a dynamic process both constrained and driven by the informational architecture of organisms across scales, from DNA and chromatin regulation to interactions within and between species and the environment.

In recent years, vitamin D has been received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries and the identification of extraskeletal effects of vitamin D, suggesting unexpected benefits of vitamin D in health and disease, beyond bone health. The possibility of extraskeletal effects of vitamin D was first noted with the discovery of the vitamin D receptor (VDR) in tissues and cells that are not involved in maintaining mineral homeostasis and bone health, including skin, placenta, pancreas, breast, prostate and colon cancer cells, and activated T cells. However, the biological significance of the expression of the VDR in different tissues is not fully understood, and the role of vitamin D in extraskeletal health has been a matter of debate. This report summarizes recent research on the roles for vitamin D in cancer, immunity and autoimmune diseases, cardiovascular and respiratory health, pregnancy, obesity, erythropoiesis, diabetes, muscle function, and aging.

Populations of many countries are becoming increasingly overweight and obese, driven largely by excessive calorie intake and reduced physical activity; greater body mass is accompanied by epidemic levels of comorbid metabolic diseases. At the same time, individuals are living longer. The combination of aging and the increased prevalence of metabolic disease is associated with increases in aging-related comorbid diseases such as Alzheimer's disease, cerebrovascular dementia, and sarcopenia. Here, correlative and causal links between diseases of overnutrition and diseases of aging and cognition are explored.

The molecular tools of genomics have great power to reveal patterns of genetic difference within or among species, but must be complemented by the mechanistic study of the genetic variants found if these variants’ evolutionary meaning is to be well understood. Central to this purpose is knowledge of the organisms’ genotype–phenotype–environment interactions, which embody biological adaptation and constraint and thus drive natural selection. The history of this approach is briefly reviewed. Strategies embracing the complementarity of genomics and specific-gene studies in evolution are considered. Implementation of these strategies, and examples showing their feasibility and power, are discussed. Initial generalizations emphasize: (1) reproducibility of adaptive mechanisms; (2) evolutionary co-importance of variation in protein sequences and expression; (3) refinement of rudimentary molecular functions as an origin of evolutionary innovations; (4) identification of specific-gene mechanisms as underpinnings of genomic or quantitative genetic variation; and (5) multiple forms of adaptive or constraining epistasis among genes. Progress along these lines will advance understanding of evolution and support its use in addressing urgent medical and environmental applications.

Recent technological advances allow analysis of genomic changes in cancer in unprecedented detail. The next challenge is to prioritize the multitude of genetic aberrations found and identify therapeutic opportunities. We recently completed a study that illustrates the use of unbiased genetic screens and murine cancer models to find therapeutic targets among complex genomic data. We genetically dissected the common deletion of chromosome 6q and identified the ephrin receptor A7 (EPHA7) as a tumor suppressor in lymphoma. Notably, EPHA7 encodes a soluble splice variant that acts as an extrinsic tumor suppressor. Accordingly, we developed an antibody-based strategy to specifically deliver EPHA7 back to tumors that have lost this gene. Recent sequencing studies have implicated EPHA7 in lung cancer and other tumors, suggesting a broader therapeutic potential for antibody-mediated delivery of this tumor suppressor for cancer therapy. Together, our comprehensive approach provides new insights into cancer biology and may directly lead to the development of new cancer therapies.

The temperature of the Sun increases over a short distance from a few thousand degrees in the photosphere to over a million degrees in the corona. To understand coronal heating is one of the major problems in astrophysics. There is general agreement that the energy source is convective motion in and below the photosphere. It remains to determine how this mechanical energy is transported outward into the corona and then deposited as heat. Two classes of models have been proposed, namely those that rely on magnetic reconnection and those that rely on waves, particularly Alfvén waves. There is increasing evidence that waves are ubiquitous in the corona. However, a difficulty for wave-driven models has been that most theories predict Alfvén waves to be undamped in the corona, and therefore they cannot dissipate their energy into heat. Our research has shown unambiguous observational evidence that the waves do damp at sufficiently low heights in the corona to be important for coronal heating.

Clostridium difficile infection, also known as C. difficile-associated diarrhea (CDAD), is the most common cause of nosocomial diarrhea, typically initiated by the use of broad-spectrum antibiotics that disrupt gut flora, thereby allowing C. difficile to proliferate. It is an increasing cause of morbidity and mortality, especially in hospitals and long-term care facilities. A particularly challenging aspect to treating CDAD has been maintenance of clinical response: following initial treatment success, recurrence occurs in approximately 15–30% of patients after the first episode and up to 50–60% subsequently. Fidaxomicin, marketed as DIFICID® in the United States, is approved in multiple countries and is the first new drug to be approved for this indication in over 25 years. It is a novel, narrow spectrum antibiotic with potent bactericidal activity against C. difficile and low activity against the normal gut microbiota. In clinical trials, fidaxomicin has been shown to be noninferior in initial clinical response to CDAD compared to vancomycin, and superior in limiting recurrence and providing sustained clinical response. In this review, the development and characteristics of fidaxomicin are described.

Everolimus is a potent, oral inhibitor of the mammalian target of rapamycin (mTOR) that has been investigated in multiple clinical development programs since 1996. A unique collaboration between academic and pharmaceutical experts fostered research that progressed rapidly, with simultaneous indication findings across numerous tumor types. Initially developed for the prophylaxis of organ transplant rejection, everolimus has demonstrated efficacy and safety for the treatment of patients with various types of cancer (renal cell carcinoma, neuroendocrine tumors of pancreatic origin, and breast cancer) and for adult and pediatric patients with tuberous sclerosis complex. The FDA approval of everolimus for these diseases has addressed several unmet medical needs and is widely accepted by the medical community where treatment options may be limited. An extensive clinical development program is ongoing to establish the role of everolimus as monotherapy, or in combination with other agents, in the treatment of a broad spectrum of malignancies.

Tumor treating fields (TTFields) is a noninvasive, regional antimitotic treatment modality that has been approved for the treatment of recurrent glioblastoma by the U.S. FDA and has a CE mark in Europe. TTFields therapy delivers low-intensity (1–3 V/cm), intermediate-frequency (100–300 kHz), alternating electric fields to the tumor using transducer arrays placed on the skin around the region of the body containing the tumor. TTFields therapy affects metaphase, by disrupting mitotic spindle formation, and anaphase, by dielectrophoretic dislocation of intracellular constituents, resulting in apoptosis. TTFields therapy is frequency tuned to specific cancer cell types. The antimitotic effect of TTFields therapy has been demonstrated in multiple cell lines when the appropriate frequency was utilized. A phase III trial of TTFields monotherapy compared to active chemotherapy in recurrent glioblastoma patients established that TTFields therapy is associated with minimal toxicity, better quality of life, and comparable efficacy to chemotherapy. Ongoing and future trials will evaluate TTFields in newly diagnosed glioblastoma, solid tumor brain metastases, nonsmall cell lung cancer, and ovarian and pancreatic cancers.

Despite yearly advances in life-saving and preventive medicine, as well as strategic approaches by governmental and social agencies and groups, significant disparities remain in health, health quality, and access to health care within the United States. The determinants of these disparities include baseline health status, race and ethnicity, culture, gender identity and expression, socioeconomic status, region or geography, sexual orientation, and age. In order to renew the commitment of the medical community to address health disparities, particularly at the medical school level, we must remind ourselves of the roles of doctors and medical schools as the gatekeepers and the value setters for medicine. Within those roles are responsibilities toward the social mission of working to eliminate health disparities. This effort will require partnerships with communities as well as with academic centers to actively develop and to implement diversity and inclusion strategies. Besides improving the diversity of trainees in the pipeline, access to health care can be improved, and awareness can be raised regarding population-based health inequalities.

Diabesity has become a popular term to describe the specific form of diabetes that develops late in life and is associated with obesity. While there is a correlation between diabetes and obesity, the association is not universally predictive. Defining the metabolic characteristics of obesity that lead to diabetes, and how obese individuals who develop diabetes different from those who do not, are important goals. The use of large-scale omics analyses (e.g., metabolomic, proteomic, transcriptomic, and lipidomic) of diabetes and obesity may help to identify new targets to treat these conditions. This report discusses how various types of omics data can be integrated to shed light on the changes in metabolism that occur in obesity and diabetes.

Few invasion biologists consider the long-term evolutionary context of an invading organism and its invaded ecosystem. Here, I consider patterns of plant invasions across Eastern North America, Europe, and East/Far East Asia, and explore whether biases in exchanges of plants from each region reflect major selection pressures present within each region since the late Miocene, during which temperate Northern Hemisphere floras diverged taxonomically and ecologically. Although there are many exceptions, the European flora appears enriched in species well adapted to frequent, intense disturbances such as cultivation and grazing; the North American composite (Asteraceae) flora appears particularly well adapted to nutrient-rich meadows and forest openings; and the East Asian flora is enriched in shade-tolerant trees, shrubs, and vines of high forest-invasive potential. I argue that such directionality in invasions across different habitat types supports the notion that some species are preadapted to become invasive as a result of differences in historical selection pressures between regions.

There is extensive evidence for an early vertebrate origin of lateralized motor behavior and of related asymmetries in underlying brain systems. We investigate human lateralized motor functioning in a broad comparative context of evolutionary neural reorganization. We quantify evolutionary trends in the fronto-cerebellar system (involved in motor learning) across 46 million years of divergent primate evolution by comparing rates of evolution of prefrontal cortex, frontal motor cortex, and posterior cerebellar hemispheres along individual branches of the primate tree of life. We provide a detailed evolutionary model of the neuroanatomical changes leading to modern human lateralized motor functioning, demonstrating an increased role for the fronto-cerebellar system in the apes dating to their evolutionary divergence from the monkeys (∼30 million years ago (Mya)), and a subsequent shift toward an increased role for prefrontal cortex over frontal motor cortex in the fronto-cerebellar system in the Homo-Pan ancestral lineage (∼10 Mya) and in the human ancestral lineage (∼6 Mya). We discuss these results in the context of cortico-cerebellar functions and their likely role in the evolution of human tool use and speech.

Many historical and contemporary theorists have proposed that population-level behavioral and brain asymmetries are unique to humans and evolved as a consequence of human-specific adaptations such as language, tool manufacture and use, and bipedalism. Recent studies in nonhuman animals, notably primates, have begun to challenge this view. Here, I summarize comparative data on neuroanatomical asymmetries in the planum temporale (PT) and inferior frontal gyrus (IFG) of humans and chimpanzees, regions considered the morphological equivalents to Broca's and Wernicke's areas. I also review evidence of population-level handedness in captive and wild chimpanzees. When similar methods and landmarks are used to define the PT and IFG, humans and chimpanzees show similar patterns of asymmetry in both cortical regions, though humans show more pronounced directional biases. Similarly, there is good evidence that chimpanzees show population-level handedness, though, again, the expression of handedness is less robust compared to humans. These results stand in contrast to reported claims of significant differences in the distribution of handedness in humans and chimpanzees, and I discuss some possible explanations for the discrepancies in the neuroanatomical and behavioral data.

Modern neurostimulation approaches in humans provide controlled inputs into the operations of cortical regions, with highly specific behavioral consequences. This enables causal structure–function inferences, and in combination with neuroimaging, has provided novel insights into the basic mechanisms of action of neurostimulation on distributed networks. For example, more recent work has established the capacity of transcranial magnetic stimulation (TMS) to probe causal interregional influences, and their interaction with cognitive state changes. Combinations of neurostimulation and neuroimaging now face the challenge of integrating the known physiological effects of neurostimulation with theoretical and biological models of cognition, for example, when theoretical stalemates between opposing cognitive theories need to be resolved. This will be driven by novel developments, including biologically informed computational network analyses for predicting the impact of neurostimulation on brain networks, as well as novel neuroimaging and neurostimulation techniques. Such future developments may offer an expanded set of tools with which to investigate structure–function relationships, and to formulate and reconceptualize testable hypotheses about complex neural network interactions and their causal roles in cognition.

Right- and left-handedness run in families, show greater concordance in monozygotic than dizygotic twins, and are well described by single-locus Mendelian models. Here we summarize a large genome-wide association study (GWAS) that finds no significant associations with handedness and is consistent with a meta-analysis of GWASs. The GWAS had 99% power to detect a single locus using the conventional criterion of P < 5 × 10⁻⁸ for the single locus models of McManus and Annett. The strong conclusion is that handedness is not controlled by a single genetic locus. A consideration of the genetic architecture of height, primary ciliary dyskinesia, and intelligence suggests that handedness inheritance can be explained by a multilocus variant of the McManus DC model, classical effects on family and twins being barely distinguishable from the single locus model. Based on the ENGAGE meta-analysis of GWASs, we estimate at least 40 loci are involved in determining handedness.

We review evidence for and against lateralization of manual control, communication, visual processing, and auditory processing in nonhuman primates. Compared to humans and some other vertebrate species, manual specialization in nonhuman primates is relatively weak. A right-bias in chimpanzees may exist, but is so weak that many studies using simple tasks fail to reveal it. Slightly stronger biases may exist in baboons and chimpanzees for communicative signals in the manual and facial domains. Several studies have found robust visual side biases that depend on the object being viewed, in primates including chimpanzees. Evidence for lateralization of auditory processing remains inconclusive. We conclude that the robust, species-wide lateralization that exists in humans is unusual, and perhaps unique among primates, and discuss several possible evolutionary explanations for this strong asymmetry. In particular, we consider the hypothesis that preexisting hemispheric asymmetry for perception and language processing drove the evolution of human handedness.

Previous studies have shown a strong correspondence between long bone bilateral asymmetry and reported handedness. Here, we compare the pattern of asymmetry in mechanical properties of the humerus and second metacarpal of Pan troglodytes, recent British industrial and medieval populations, and a broad range of human hunter–gatherers, to test whether technological variation corresponds with lateralization in bone function. The results suggest that P. troglodytes are left-lateralized in the morphology of the humerus and right-lateralized in the second metacarpal, while all human populations are predominantly right-biased in the morphology of these bones. Among human populations, the second metacarpals of 63% of hunter–gatherers show right-hand bias, a frequency similar to that found among chimpanzees. In contrast, the medieval and recent British populations show over 80% right-lateralization in the second metacarpal. The proportion of individuals displaying right-directional asymmetry is less than the expected 90% among all human groups. The variation observed suggests that the human pattern of right-biased asymmetry developed in a mosaic manner throughout human history, perhaps in response to technological development.

This paper reviews the earliest documented manual and postural asymmetries, in the fetus and during the first months of life. I attempt to analyze which genetic and/or environmental factors are likely to trigger each one, as well as its consequences for the other ones. I conclude that right-handedness is prevalent in all cultures because an intrinsic tendency toward right-handedness has many occasions to be reinforced, from the uterine to the perinatal environment and from the familial to the cultural environment. Finally, the combination of potential genetic factors—direct (motoric) or indirect (postural)—with varied biological and cultural environmental influences over various periods during development may explain the high variability of handedness in typical populations (as long as hand preference is not equated with the hand used for writing).

Annett's right-shift theory proposes that human cerebral dominance (the functional and anatomical asymmetry or torque along the antero-posterior axis) and handedness are determined by a single “right-shift” gene. Familial transmission of handedness and specific deviations of cerebral dominance in sex chromosome aneuploidies implicate a locus within an X–Y homologous region of the sex chromosomes. The Xq21.3/Yp11.2 human-specific region of homology includes the protocadherin 11X/Y (PCDH11X/Y) gene pair, which encode cell adhesion molecules subject to accelerated evolution following the separation of the human and chimpanzee lineages six million years ago. PCDH11X and PCDH11Y, differentially regulated by retinoic acid, are highly expressed in the ventricular zone, subplate, and cortical plate of the developing cerebral cortex. Both proteins interact with β-catenin, a protein that plays a role in determining axis formation and regulating cortical size. In this way, the PCDH11X/Y gene pair determines cerebral asymmetry by initiating the right shift in Homo sapiens.

We examined hand preference in the intentional gestural communication of wild chimpanzees in the Budongo forest, Uganda. Individuals showed some tendency to be lateralized, although less than has been reported for begging and pointing gestures in captivity; on average, their absolute bias was around 0.25 (where 1.0 represents complete right- or left-hand use and 0.0 represents no bias). Lateralization was incomplete even in individuals with major manual disabilities. Where individuals had a stronger preference, this was more often toward the right hand; moreover, as age increased, the direction (but not the extent) of hand preference shifted toward the right. While the gestural repertoire as a whole was largely employed ambilateraly, object-manipulation gestures showed a strong right-hand bias.

Is human handedness unique? That is, do our nearest living relations, chimpanzee and bonobo (Pan spp.) show species-wide handedness, as is seen in living Homo sapiens? The answer may depend on definition: Handedness (congruence across subjects and across tasks) should be distinguished from hand preference (within subject and task), manual specialization (within subject, across tasks), and task specialization (across subjects, within task). Comparison is required at both population and species level. Several methodological issues (e.g., ecological validity) are crucial, as are major confounding variables (e.g., bimanuality). The behavioral manual laterality of chimpanzees is well-studied in a variety of contexts. Especially important is tool use, which seems to enhance extent of lateralization, but this varies both within and across populations. There is much evidence for task specialization in chimpanzees, but no conclusive evidence of handedness in the strictest sense. Thus, human handedness seems to be unique among living hominoids.

Competition has always been a cornerstone of evolutionary biology, and aggression is the predominant form of direct competition in animals, but the evolutionary effects of aggression between species are curiously understudied. Only in the past few years, existing theoretical frameworks have been extended to include interspecific aggression, and significant empirical advances have been made. After arguing that agonistic character displacement (ACD) theory provides the most suitable theoretical framework, we review new empirical evidence for ACD and the results of mathematical models of the process. We consider how ACD can be distinguished empirically from ecological and reproductive character displacement and the additional challenges posed by developmental plasticity. We also provide the first taxonomically broad review of theoretical and empirical work on the effects of interspecific aggression on species coexistence and range limits. We conclude by highlighting promising directions for future research on the evolutionary effects of interspecific aggression.

Compared to related taxa, birds have exceptionally enlarged and diversified skeletal muscles, features that are closely associated with skeletal diversification and are commonly explained by a diversity of avian ecological niches and locomotion types. The thermogenic muscle hypothesis (TMH) for the origin of birds proposes that such muscle hyperplasia and the associated skeletal innovations are instead the consequence of the avian clade originating from an ancestral population that underwent several successive episodes of loss of genes associated with thermogenesis, myogenesis, and skeletogenesis. Direct bird ancestors met this challenge with a combination of behavioral strategies (e.g., brooding of nestlings) and acquisition of a variety of adaptations for enhanced nonshivering thermogenesis in skeletal muscle. The latter include specific biochemical alterations promoting muscle heat generation and dramatic expansion of thigh and breast muscle mass. The TMH proposes that such muscle hyperplasia facilitated bipedality, freeing upper limbs for new functions (e.g., flight, swimming), and, by altering the mechanical environment of embryonic development, generated skeletal novelties, sometimes abruptly, that became distinctive features of the avian body plan.

The nine-spined stickleback (Pungitius pungitius) is emerging as a model for evolutionary biology, genetic, and behavioral research in the wake of its better-known relative, the three-spined stickleback (Gasterosteus aculeatus). This interest has been fed by its fascinating biological features, such as the repeated evolution of similar phenotypes in isolated pond populations. A large body of recent research has uncovered the finding that pond nine-spined sticklebacks have evolved numerous morphological, life history, neuroanatomical, and behavioral adaptations—possibly in response to reduced threat of fish predation—which differentiate them from their marine conspecifics. These features, together with insights from recent population genetic studies, suggest that this species provides an interesting model for studies aiming to understand—and differentiate between—genetic convergence and parallelism as underlying mechanism(s) of evolution of similar phenotypes in multiple independent sites. This review provides a synopsis of and reflections on the insights borne out of recent studies of nine-spined sticklebacks—the little sister of ecology's “new supermodel.”

High-volume horizontal hydraulic fracturing (HVHHF) for mining natural gas from the Marcellus and Utica shales is widespread in Pennsylvania and potentially throughout approximately 280,000 km² of the Appalachian Basin. Physical and chemical impacts of HVHHF include pollution by toxic synthetic chemicals, salt, and radionuclides, landscape fragmentation by wellpads, pipelines, and roads, alteration of stream and wetland hydrology, and increased truck traffic. Despite concerns about human health, there has been little study of the impacts on habitats and biota. Taxa and guilds potentially sensitive to HVHHF impacts include freshwater organisms (e.g., brook trout, freshwater mussels), fragmentation-sensitive biota (e.g., forest-interior breeding birds, forest orchids), and species with restricted geographic ranges (e.g., Wehrle's salamander, tongue-tied minnow). Impacts are potentially serious due to the rapid development of HVHHF over a large region.

Conservation translocation of species varies from restoring historic populations to managing the relocation of imperiled species to new locations. We review the literature in three areas—translocation, managed relocation, and conservation decision making—to inform conservation translocation under changing climates. First, climate change increases the potential for conflict over both the efficacy and the acceptability of conservation translocation. The emerging literature on managed relocation highlights this discourse. Second, conservation translocation works in concert with other strategies. The emerging literature in structured decision making provides a framework for prioritizing conservation actions—considering many possible alternatives that are evaluated based on expected benefit, risk, and social–political feasibility. Finally, the translocation literature has historically been primarily concerned with risks associated with the target species. In contrast, the managed relocation literature raises concerns about the ecological risk to the recipient ecosystem. Engaging in a structured decision process that explicitly focuses on stakeholder engagement, problem definition and specification of goals from the outset will allow creative solutions to be developed and evaluated based on their expected effectiveness.

Passed in 1972, the Marine Mammal Protection Act has two fundamental objectives: to maintain U.S. marine mammal stocks at their optimum sustainable populations and to uphold their ecological role in the ocean. The current status of many marine mammal populations is considerably better than in 1972. Take reduction plans have been largely successful in reducing direct fisheries bycatch, although they have not been prepared for all at-risk stocks, and fisheries continue to place marine mammals as risk. Information on population trends is unknown for most (71%) stocks; more stocks with known trends are improving than declining: 19% increasing, 5% stable, and 5% decreasing. Challenges remain, however, and the act has generally been ineffective in treating indirect impacts, such as noise, disease, and prey depletion. Existing conservation measures have not protected large whales from fisheries interactions or ship strikes in the northwestern Atlantic. Despite these limitations, marine mammals within the U.S. Exclusive Economic Zone appear to be faring better than those outside, with fewer species in at-risk categories and more of least concern.

The species–area relationship (SAR) predicts that smaller areas contain fewer species. This is the basis of the SAR method that has been used to forecast large numbers of species committed to extinction every year due to deforestation. The method has a number of issues that must be handled with care to avoid error. These include the functional form of the SAR, the choice of equation parameters, the sampling procedure used, extinction debt, and forest regeneration. Concerns about the accuracy of the SAR technique often cite errors not much larger than the natural scatter of the SAR itself. Such errors do not undermine the credibility of forecasts predicting large numbers of extinctions, although they may be a serious obstacle in other SAR applications. Very large errors can arise from misinterpretation of extinction debt, inappropriate functional form, and ignoring forest regeneration. Major challenges remain to understand better the relationship between sampling protocol and the functional form of SARs and the dynamics of relaxation, especially in continental areas, and to widen the testing of extinction forecasts.

American ginseng (Panax quinquefolius L.) is an uncommon to rare understory plant of the eastern deciduous forest. Harvesting to supply the Asian traditional medicine market made ginseng North America's most harvested wild plant for two centuries, eventually prompting a listing on CITES Appendix II. The prominence of this representative understory plant has led to its use as a phytometer to better understand how environmental changes are affecting many lesser-known species that constitute the diverse temperate flora of eastern North America. We review recent scientific findings concerning this remarkable phytometer species, identifying factors through its history of direct and indirect interactions with humans that have led to the current condition of the species. Harvest, deer browse, and climate change effects have been studied in detail, and all represent unique interacting threats to ginseng's long-term persistence. Finally, we synthesize our current understanding by portraying ginseng's existence in thousands of small populations, precariously poised to either escape or be drawn further toward extinction by the actions of our own species.

Alterations in natural fire patterns have negatively affected fire-prone ecosystems in many ways. The historical range of variability (HRV) concept evolved as a management target for natural vegetation composition and fire regimes in fire-prone ecosystems. HRV-based management inherently assumes that ecosystem resilience is reflected in observed ranges of past vegetation and fire dynamics, typically without knowledge of where thresholds exist beyond these dynamics. Given uncertainty in future conditions, some have argued that HRV may not adequately reflect ecosystem resilience to future fire activity. We suggest a refinement that includes concepts from the thresholds of potential concern (TPC) framework, which emphasizes tipping points at the extremes of ecosystem dynamics and other socially unacceptable outcomes. We propose bounded ranges of variation (BRV), an approach focused on building resilience by using historical information, but also by identifying socio-ecological thresholds to avoid and associated management action triggers. Here, we examine nonnative species and carbon sequestration as examples of how the BRV framework could be used in the context of conservation and fire management.