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"Williams, D."
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Neural activity induced by sensory stimulation can drive large-scale cerebrospinal fluid flow during wakefulness in humans
Cerebrospinal fluid (CSF) flow maintains healthy brain homeostasis, facilitating solute transport and the exchange of brain waste products. CSF flow is thus important for brain health, but the mechanisms that control its large-scale movement through the ventricles are not well understood. While it is well established that CSF flow is modulated by respiratory and cardiovascular dynamics, recent work has also demonstrated that neural activity is coupled to large waves of CSF flow in the ventricles during sleep. To test whether the temporal coupling between neural activity and CSF flow is in part due to a causal relationship, we investigated whether CSF flow could be induced by driving neural activity with intense visual stimulation. We manipulated neural activity with a flickering checkerboard visual stimulus and found that we could drive macroscopic CSF flow in the human brain. The timing and amplitude of CSF flow was matched to the visually evoked hemodynamic responses, suggesting neural activity can modulate CSF flow via neurovascular coupling. These results demonstrate that neural activity can contribute to driving CSF flow in the human brain and that the temporal dynamics of neurovascular coupling can explain this effect.
Journal Article
Controversies around epithelial–mesenchymal plasticity in cancer metastasis
Experimental evidence accumulated over decades has implicated epithelial–mesenchymal plasticity (EMP), which collectively encompasses epithelial–mesenchymal transition and the reverse process of mesenchymal–epithelial transition, in tumour metastasis, cancer stem cell generation and maintenance, and therapeutic resistance. However, the dynamic nature of EMP processes, the apparent need to reverse mesenchymal changes for the development of macrometastases and the likelihood that only minor cancer cell subpopulations exhibit EMP at any one time have made such evidence difficult to accrue in the clinical setting. In this Perspectives article, we outline the existing preclinical and clinical evidence for EMP and reflect on recent controversies, including the failure of initial lineage-tracing experiments to confirm a major role for EMP in dissemination, and discuss accumulating data suggesting that epithelial features and/or a hybrid epithelial–mesenchymal phenotype are important in metastasis. We also highlight strategies to address the complexities of therapeutically targeting the EMP process that give consideration to its spatially and temporally divergent roles in metastasis, with the view that this will yield a potent and broad class of therapeutic agents.
Journal Article
The atlas of forgotten places : a novel
\"After a long career as an aid worker, Sabine Hardt has retreated to her native Germany for a quieter life. But when her American niece Lily disappears while volunteering in Uganda, Sabine must return to places and memories she once thought buried in order to find her. In Uganda, Rose Akulu--haunted by a troubled past with the Lord's Resistance Army--becomes distressed when her lover Ocen vanishes without a trace. Side by side, Sabine and Rose must unravel the tangled threads that tie Lily and Ocen's lives together--ultimately discovering that the truth of their loved ones' disappearance is inescapably entwined to the secrets the two women carry.\"-- Provided by publisher.
Book
Physiological adaptations for breeding in birds
Physiological Adaptations for Breeding in Birdsis the most current and comprehensive account of research on avian reproduction. It develops two unique themes: the consideration of female avian reproductive physiology and ecology, and an emphasis on individual variation in life-history traits. Tony Williams investigates the physiological, metabolic, energetic, and hormonal mechanisms that underpin individual variation in the key female-specific reproductive traits and the trade-offs between these traits that determine variation in fitness.
The core of the book deals with the avian reproductive cycle, from seasonal gonadal development, through egg laying and incubation, to chick rearing. Reproduction is considered in the context of the annual cycle and through an individual's entire life history. The book focuses on timing of breeding, clutch size, egg size and egg quality, and parental care. It also provides a primer on female reproductive physiology and considers trade-offs and carryover effects between reproduction and other life-history stages. In each chapter, Williams describes individual variation in the trait of interest and the evolutionary context for trait variation. He argues that there is only a rudimentary, and in some cases nonexistent, understanding of the physiological mechanisms that underpin individual variation in the major reproductive life-history traits, and that research efforts should refocus on these key unresolved problems by incorporating detailed physiological studies into existing long-term population studies, generating a new synthesis of physiology, ecology, and evolutionary biology.
eBook
The Reliability and Validity of the Loadsol® under Various Walking and Running Conditions
The assessment of loading during walking and running has historically been limited to data collection in laboratory settings or with devices that require a computer connection. This study aims to determine if the loadsol®—a single sensor wireless insole—is a valid and reliable method of assessing force. Thirty (17 male and 13 female) recreationally active individuals were recruited for a two visit study where they walked (1.3 m/s) and ran (3.0 and 3.5 m/s) at a 0%, 10% incline, and 10% decline, with the visits approximately one week apart. Ground reaction force data was collected on an instrumented treadmill (1440 Hz) and with the loadsol® (100 Hz). Ten individuals completed the day 1 protocol with a newer 200 Hz loadsol®. Intraclass correlation coefficients (ICC3,k) were used to assess validity and reliability and Bland–Altman plots were generated to better understand loadsol® validity. Across conditions, the peak force ICCs ranged from 0.78 to 0.97, which increased to 0.84–0.99 with the 200 Hz insoles. Similarly, the loading rate ICCs improved from 0.61 to 0.97 to 0.80–0.96 and impulse improved from 0.61 to 0.97 to 0.90–0.97. The 200 Hz insoles may be needed for loading rate and impulse in running. For both walking and running, the loadsol® has excellent between-day reliability (>0.76).
Journal Article
Fighting for peace in Somalia : a history and analysis of the African Union Mission (AMISOM), 2007-2017.
Fighting for Peace in Somalia provides the first comprehensive analysis of the African Union Mission in Somalia (AMISOM), an operation deployed in 2007 to stabilize the country and defend its fledgling government from one of the world's deadliest militant organizations, Harakat al-Shabaab.00The book's two parts provide a history of the mission from its genesis in an earlier, failed regional initiative in 2005 up to mid-2017, as well as an analysis of the mission's six most important challenges, namely, logistics, security sector reform, civilian protection, strategic communications, stabilization, and developing a successful exit strategy. These issues are all central to the broader debates about how to design effective peace operations in Africa and beyond.
Book
Asymmetric Responses to Earnings News: A Case for Ambiguity
This study empirically examines the role of shocks to macro-uncertainty in shaping the responses of stock market participants to firm-specific earnings news. Specifically, I find that investors place greater weight on bad news following an increase in macro-uncertainty. By contrast, I find that investors place equal weight on both good and bad news following a decrease in macro-uncertainty. Furthermore, my findings show that these effects are more pronounced (1) for firms whose prior returns are more correlated with macro-uncertainty, (2) for firms that experience abnormally low trading volume during the earnings announcement, (3) for firms with relatively lower levels of institutional ownership, and (4) for firms with relatively higher information uncertainty. In sum, these findings provide novel empirical evidence that investors behave in a manner consistent with ambiguity aversion, with the effects strongest among unsophisticated investors.
Journal Article