Integrating cognition in the laboratory with cognition in the real world: the time cognition takes, task fidelity, and finding tasks when they are mixed together.

It is now possible for real-life activities, unfolding over their natural range of temporal and spatial scales, to become the primary targets of cognitive studies. Movement toward this type of research will require an integrated methodological approach currently uncommon in the field. When executed hand in hand with thorough and ecologically valid empirical description, properly developed laboratory tasks can serve as model systems to capture the essentials of a targeted real-life activity. When integrated together, data from these two kinds of studies can facilitate causal analysis and modeling of the mental and neural processes that govern that activity, enabling a fuller account than either method can provide on its own. The resulting account, situated in the activity's natural environmental, social, and motivational context, can then enable effective and efficient development of interventions to support and improve the activity as it actually unfolds in real time. We believe that such an integrated multi-level research program should be common rather than rare and is necessary to achieve scientifically and societally important goals. The time is right to finally abandon the boundaries that separate the laboratory from the outside world.

Hand Transplants, Daily Functioning, and the Human Capacity for Limb Regeneration.

Unlike some of our invertebrate and vertebrate cousins with the capacity to regenerate limbs after traumatic loss, humans do not have the ability to regrow arms or legs lost to injury or disease. For the millions of people worldwide who have lost a limb after birth, the primary route to regaining function and minimizing future complications is via rehabilitation, prosthetic devices, assistive aids, health system robustness, and social safety net structures. The majority of limbs lost are lower limbs (legs), with diabetes and vascular disorders being significant causal contributors. Upper limbs (arms) are lost primarily because of trauma; digits and hands are the most common levels of loss. Even if much of the arm remains intact, upper limb amputation significantly impacts function, largely due to the loss of the hand. Human hands are marvels of evolution and permit a dexterity that enables a wide variety of function not readily replaced by devices. It is not surprising, therefore, for some individuals, dissatisfaction with available prosthetic options coupled with remarkable advances in hand surgery techniques is resulting in patients undertaking the rigors of a hand transplantation. While not "regeneration" in the sense of the enviable ability with which Axolotls can replace a lost limb, hand transplants do require significant regeneration of tissues and nerves. Regaining sophisticated hand functions also depends on "reconnecting" the donated hand with the areas of the human brain responsible for the sensory and motor processing required for complex actions. Human hand transplants are not without controversy and raise interesting challenges regarding the human regenerative capacity and the status of transplants for enabling function. More investigation is needed to address medical and ethical questions prior to expansion of hand transplants to a wider patient population.

Sex differences in health and disease: A review of biological sex differences relevant to cancer with a spotlight on glioma.

The influence of biological sex differences on human health and disease, while being increasingly recognized, has long been underappreciated and underexplored. While humans of all sexes are more alike than different, there is evidence for sex differences in the most basic aspects of human biology and these differences have consequences for the etiology and pathophysiology of many diseases. In a disease like cancer, these consequences manifest in the sex biases in incidence and outcome of many cancer types. The ability to deliver precise, targeted therapies to complex cancer cases is limited by our current understanding of the underlying sex differences. Gaining a better understanding of the implications and interplay of sex differences in diseases like cancer will thus be informative for clinical practice and biological research. Here we review the evidence for a broad array of biological sex differences in humans and discuss how these differences may relate to observed sex differences in various diseases, including many cancers and specifically glioblastoma. We focus on areas of human biology that play vital roles in healthy and disease states, including metabolism, development, hormones, and the immune system, and emphasize that the intersection of sex differences in these areas should not go overlooked. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.

Play, attention, and learning: how do play and timing shape the development of attention and influence classroom learning?

The behavioral and neurobiological connections between play and the development of critical cognitive functions, such as attention, remain largely unknown. We do not yet know how these connections relate to the formation of specific abilities, such as spatial ability, and to learning in formal environments, such as in the classroom. Insights into these issues would be beneficial not only for understanding play, attention, and learning individually, but also for the development of more efficacious systems for learning and for the treatment of neurodevelopmental disorders. Different operational definitions of play can incorporate or exclude varying types of behavior, emphasize varying developmental time points, and motivate different research questions. Relevant questions to be explored in this area include, How do particular kinds of play relate to the development of particular kinds of abilities later in life? How does play vary across societies and species in the context of evolution? Does play facilitate a shift from reactive to predictive timing, and is its connection to timing unique or particularly significant? This report will outline important research steps that need to be taken in order to address these and other questions about play, human activity, and cognitive functions.

Neurological principles and rehabilitation of action disorders: computation, anatomy, and physiology (CAP) model.

This chapter outlines the basic computational, anatomical, and physiological (CAP) principles underlying upper-limb actions, such as reaching for a cup and grasping it or picking up a key, inserting it into a lock, and turning it.

Neurological principles and rehabilitation of action disorders: common clinical deficits.

In this chapter, the authors use the computation, anatomy, and physiology (CAP) principles to consider the impact of common clinical problems on action. They focus on 3 major syndromes: paresis, apraxia, and ataxia. They also review mechanisms that could account for spontaneous recovery, using what is known about the best-studied clinical dysfunction--paresis--and also ataxia. Together, this and the previous chapter lay the groundwork for the third chapter in this series, which reviews the relevant rehabilitative interventions.

Neurological principles and rehabilitation of action disorders: rehabilitation interventions.

This third chapter discusses the evidence for the rehabilitation of the most common movement disorders of the upper extremity. The authors also present a framework, building on the computation, anatomy, and physiology (CAP) model, for incorporating some of the principles discussed in the 2 previous chapters by Frey et al and Sathian et al in the practice of rehabilitation and for discussing potentially helpful interventions based on emergent neuroscience principles.