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142,208 result(s) for "David, P"
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NETWORKS, PLATFORMS, AND STRATEGY: EMERGING VIEWS AND NEXT STEPS
Research summary: A substantial and burgeoning body of research has described the influence of platform-mediated networks in a wide variety of settings, whereby users and complementors desire compatibility on a common platform. In this review, we outline extant views of these dynamics from the industrial organization (IO) economics, technology management, and strategic management perspectives. Using this review as a foundation, we propose a future research agenda in this domain that focuses the on the relative influence of network effects and platform quality in competitive outcomes, drivers of indirect network effects, the nature and attributes of complementors, and leveraging complementor dynamics for competitive advantage. Managerial summary: In many industries, such as social networks and video games, consumers place greater value on products with a large network of other users and a large variety of complementary products. Such \"network effects\" offer lucrative opportunities for firms that can leverage these dynamics to create dominant technology platforms. This article reviews current perspectives on network effects and the emergence of platforms, and offers several areas of future consideration for optimal strategies in these settings.
Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others
TP53, which encodes the tumour-suppressor protein p53, is the most frequently mutated gene across all cancer types. The presence of mutant p53 predisposes to cancer development, promotes the survival of cancer cells, and is associated with ineffective therapeutic responses and unfavourable prognoses. Despite these effects, no drug that abrogates the oncogenic functions of mutant p53 has yet been approved for the treatment of cancer. Current investigational therapeutic strategies are mostly aimed at restoring the wild-type activity of mutant p53, based on the assumption that all p53 mutants are functionally equal. Our increasing knowledge of mutant forms of p53, however, supports the antithetical hypothesis that not all p53 mutants have equivalent cellular effects; hence, a judicious approach to therapeutic targeting of mutant p53 is required. In this Review, we propose a categorization of the major classes of p53 mutants based on their functionality in tumour suppression and response to therapy. The emerging picture is that the mutations across TP53 form a 'rainbow of mutants', with varying degrees of functionality and different pathobiological consequences, necessitating the use of diverse therapeutic strategies to selectively target specific classes of mutation. The utility of this knowledge of TP53 mutations in developing selective therapeutic options, and in facilitating clinical decision-making is discussed.
Focused Ultrasound for Neuromodulation
For more than 70 years, the promise of noninvasive neuromodulation using focused ultrasound has been growing while diagnostic ultrasound established itself as a foundation of clinical imaging. Significant technical challenges have been overcome to allow transcranial focused ultrasound to deliver spatially restricted energy into the nervous system at a wide range of intensities. High-intensity focused ultrasound produces reliable permanent lesions within the brain, and low-intensity focused ultrasound has been reported to both excite and inhibit neural activity reversibly. Despite intense interest in this promising new platform for noninvasive, highly focused neuromodulation, the underlying mechanism remains elusive, though recent studies provide further insight. Despite the barriers, the potential of focused ultrasound to deliver a range of permanent and reversible neuromodulation with seamless translation from bench to the bedside warrants unparalleled attention and scientific investment. Focused ultrasound boasts a number of key features such as multimodal compatibility, submillimeter steerable focusing, multifocal, high temporal resolution, coregistration, and the ability to monitor delivered therapy and temperatures in real time. Despite the technical complexity, the future of noninvasive focused ultrasound for neuromodulation as a neuroscience and clinical platform remains bright.
A Global Analysis of Sentinel-2A, Sentinel-2B and Landsat-8 Data Revisit Intervals and Implications for Terrestrial Monitoring
Combination of different satellite data will provide increased opportunities for more frequent cloud-free surface observations due to variable cloud cover at the different satellite overpass times and dates. Satellite data from the polar-orbiting Landsat-8 (launched 2013), Sentinel-2A (launched 2015) and Sentinel-2B (launched 2017) sensors offer 10 m to 30 m multi-spectral global coverage. Together, they advance the virtual constellation paradigm for mid-resolution land imaging. In this study, a global analysis of Landsat-8, Sentinel-2A and Sentinel-2B metadata obtained from the committee on Earth Observation Satellite (CEOS) Visualization Environment (COVE) tool for 2016 is presented. A global equal area projection grid defined every 0.05° is used considering each sensor and combined together. Histograms, maps and global summary statistics of the temporal revisit intervals (minimum, mean, and maximum) and the number of observations are reported. The temporal observation frequency improvements afforded by sensor combination are shown to be significant. In particular, considering Landsat-8, Sentinel-2A, and Sentinel-2B together will provide a global median average revisit interval of 2.9 days, and, over a year, a global median minimum revisit interval of 14 min (±1 min) and maximum revisit interval of 7.0 days.
Complications of Cranioplasty in Relation to Material: Systematic Review, Network Meta-Analysis and Meta-Regression
Abstract BACKGROUND Cranioplasty is a ubiquitous neurosurgical procedure consisting of reconstruction of a pre-existing calvarial defect. Many materials are available, including polymethylmethacrylate in hand-moulded (hPMMA) and prefabricated (pPMMA) form, hydroxyapatite (HA), polyetheretherketone (PEEK) and titanium (Ti). OBJECTIVE To perform a network meta-analysis (NMA) to assess the relationship between materials and complications of cranioplasty. METHODS PubMed/MEDLINE, Google Scholar, EMBASE, Scopus, and The Cochrane Library were searched from January 1, 1990 to February 14, 2021. Studies detailing rates of any of infections, implant exposure, or revision surgery were included. A frequentist NMA was performed for each complication. Risk ratios (RRs) with 95% CIs were calculated for each material pair. RESULTS A total of 3620 abstracts were screened and 31 full papers were included. Surgical revision was reported in 18 studies and occurred in 316/2032 cases (14%; 95% CI 11-17). PEEK had the lowest risk of re-operation with a rate of 8/157 (5%; 95% CI 0-11) in 5 studies, superior to autografts (RR 0.20; 95% CI 0.07-0.57), hPMMA (RR 0.20; 95% CI 0.07-0.60), Ti (RR 0.39; 95% CI 0.17-0.92), and pPMMA (RR 0.14; 95% CI 0.04-0.51). Revision rate was 131/684 (19%; 95% CI 13-25; 10 studies) in autografts, 61/317 (18%; 95%CI 9-28; 7 studies) in hPMMA, 84/599 (13%; 95% CI 7-19; 11 studies) in Ti, 7/59 (9%; 95% CI 1-23; 3 studies) in pPMMA, and 25/216 (12%; 95% CI 4-24; 4 studies) in HA. Infection occurred in 463/4667 (8%; 95% CI 6-11) and implant exposure in 120/1651 (6%; 95% CI 4-9). CONCLUSION PEEK appears to have the lowest risk of cranioplasty revision, but further research is required to determine the optimal material. Graphical Abstract Graphical Abstract