Explore the vast range of titles available.

\"This Book Will Be on the Test helps students make the most of their college investment by solving their academic, motivational, and career concerns with study skills, teaches students how to earn better grades in less time and shows parents what they can expect from their kids' college experiences\"-- Provided by publisher.

In the last 5 years, there has been a surge in evidence that hearing loss (HL) may be a risk factor for cognitive dysfunction, including dementia. At the same time, there has been an increase in the number of studies implicating vestibular loss in cognitive dysfunction. Due to the fact that vestibular disorders often present with HL and other auditory disorders such as tinnitus, it has been suggested that, in many cases, what appears to be vestibular-related cognitive dysfunction may be due to HL (e.g., Dobbels et al. Front Neurol 11:710, 2020). This review analyses the studies of vestibular-related cognitive dysfunction which have controlled HL. It is suggested that despite the fact that many studies in the area have not controlled HL, many other studies have (~ 19/44 studies or 43%). Therefore, although there is certainly a need for further studies controlling HL, there is evidence to suggest that vestibular loss is associated with cognitive dysfunction, especially related to spatial memory. This is consistent with the overwhelming evidence from animal studies that the vestibular system transmits specific types of information about self-motion to structures such as the hippocampus.

\"Many artists and scientists - including Buffon, Goethe, and Philipp Otto Runge - who observed the vivid coloured shadows that appear outdoors around dawn and dusk, or indoors when a candle burns under waning daylight, chose to describe their colours as 'beautiful'. Paul Smith explains what makes these ephemeral effects worthy of such appreciation - or how depictions of coloured shadows have genuine aesthetic and epistemological significance. This multi-disciplinary book synthesises methodologies drawn from art history (close pictorial analysis), psychology and neuroscience (theories of colour constancy), history of science (the changing paradigms used to explain coloured shadows), and philosophy (theories of perception and aesthetic value drawn from Wittgenstein and Merleau-Ponty). This title will be of interest to scholars in art history, art theory, and the history of science and technology\"-- Provided by publisher.

Species extinctions have defined the global biodiversity crisis, but extinction begins with loss in abundance of individuals that can result in compositional and functional changes of ecosystems. Using multiple and independent monitoring networks, we report population losses across much of the North American avifauna over 48 years, including once-common species and from most biomes. Integration of range-wide population trajectories and size estimates indicates a net loss approaching 3 billion birds, or 29% of 1970 abundance. A continent-wide weather radar network also reveals a similarly steep decline in biomass passage of migrating birds over a recent 10-year period. This loss of bird abundance signals an urgent need to address threats to avert future avifaunal collapse and associated loss of ecosystem integrity, function, and services.

Autoimmune skin diseases are characterized by significant local and systemic inflammation that is largely mediated by the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. Advanced understanding of this pathway has led to the development of targeted inhibitors of Janus kinases (JAKinibs). As a class, JAK inhibitors effectively treat a multitude of hematologic and inflammatory diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. Here we review the evolving data on the role of the JAK-STAT pathway in inflammatory dermatoses and the potential therapeutic benefit of JAK-STAT antagonism.

Key Points The RAS-regulated RAF–MEK–ERK signalling pathway transmits signals from growth factor receptors to the nucleus and other organelles to regulate cell proliferation, differentiation, survival and invasion. ERK pathway architecture places MEK1 and MEK2 in a unique position, where they process inputs from multiple upstream activating kinases so that ERK1 and ERK2 may be activated alone (following RAF activation) or together with other kinases such as JNK or p38. The majority of cancers exhibit hyper-activation of the ERK pathway owing to deregulation (mutation, gene fusions, amplification, and so on) of receptor tyrosine kinases, RAS, BRAF, CRAF, MEK1 or MEK2 or owing to the loss of negative pathway regulators, such as dual-specificity phosphatases (DUSPs) and NF1. In many cases, these mutations confer a range of pathway dependencies including classical 'oncogene addiction', providing a rationale for ERK pathway inhibitors as therapeutic agents. Melanomas carrying the mutation encoding BRAF-V600E are almost invariably addicted to BRAF activity, and first-generation BRAF inhibitors (BRAFis) have transformed the treatment of this disease. However, an inability to inhibit signalling by RAF dimers drives acquired resistance, and paradoxical RAF activation in tumours with wild-type BRAF limits the success or wider application of BRAFis. As RAF signalling proceeds via the activation of MEK1 and MEK2, and RAF-addicted tumour cells are also MEK-addicted, MEK1 and MEK2 are also attractive drug targets. Additionally, MEK1 and MEK2 contain a unique hydrophobic pocket adjacent to their ATP-binding site, which allows the binding of potent, non-ATP competitive, allosteric inhibitors. However, MEK1 and MEK2 are rarely mutated in cancer, so MEK inhibitors (MEKis) will not preferentially inhibit MEK1 and MEK2 in tumour cells compared with normal tissue; this may contribute to normal tissue toxicity. The first MEKi to receive US Food and Drug Administration approval, trametinib, is being used to treat BRAF -mutant melanoma in combination with first-generation BRAFis. A range of additional MEKis are in late-stage clinical development and exhibit various modes of action; for example, some MEKis can prevent the phosphorylation of MEK1 and MEK2 by RAF, and others can disrupt RAF–MEK1/MEK2 complexes. The extent to which these properties influence clinical activity is currently unclear. Factors that limit the efficacy of MEKis include loss of feedback inhibition and consequent reactivation of ERK1 and ERK2. Intrinsic resistance can be driven by the activation of parallel pathways, including the PI3K pathway, whereas acquired resistance to MEKis arises through the emergence of mutations in MEK1 or MEK2 or the amplification of BRAF V600E or mutant RAS. Adaptation and resistance to MEKis can be overcome by combinations with other targeted agents, including intrapathway dual inhibition. Clinical trials assessing MEKis in combination with other targeted agents or conventional chemotherapy are ongoing. MEK1 and MEK2 have key roles in tumorigenesis and, therefore, represent promising targets for cancer therapy. This Review discusses the mechanisms of action of different inhibitors of MEK1 and MEK2, the mechanisms of resistance to these inhibitors and their current clinical progress. The role of the ERK signalling pathway in cancer is thought to be most prominent in tumours in which mutations in the receptor tyrosine kinases RAS, BRAF, CRAF, MEK1 or MEK2 drive growth factor-independent ERK1 and ERK2 activation and thence inappropriate cell proliferation and survival. New drugs that inhibit RAF or MEK1 and MEK2 have recently been approved or are currently undergoing late-stage clinical evaluation. In this Review, we consider the ERK pathway, focusing particularly on the role of MEK1 and MEK2, the 'gatekeepers' of ERK1/2 activity. We discuss their validation as drug targets, the merits of targeting MEK1 and MEK2 versus BRAF and the mechanisms of action of different inhibitors of MEK1 and MEK2. We also consider how some of the systems-level properties (intrapathway regulatory loops and wider signalling network connections) of the ERK pathway present a challenge for the success of MEK1 and MEK2 inhibitors, discuss mechanisms of resistance to these inhibitors, and review their clinical progress.