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Periodicals

Predicting survival from colorectal cancer histology slides using deep learning: A retrospective multicenter study

BACKGROUND: For virtually every patient with colorectal cancer (CRC), hematoxylin-eosin (HE)-stained tissue slides are available. These images contain quantitative information, which is not routinely used to objectively extract prognostic biomarkers. In the present study, we investigated whether deep convolutional neural networks (CNNs) can extract prognosticators directly from these widely available images. METHODS AND FINDINGS: We hand-delineated single-tissue regions in 86 CRC tissue slides, yielding more than 100,000 HE image patches, and used these to train a CNN by transfer learning, reaching a nine-class accuracy of >94% in an independent data set of 7,180 images from 25 CRC patients. With this tool, we performed automated tissue decomposition of representative multitissue HE images from 862 HE slides in 500 stage I-IV CRC patients in the The Cancer Genome Atlas (TCGA) cohort, a large international multicenter collection of CRC tissue. Based on the output neuron activations in the CNN, we calculated a "deep stroma score," which was an independent prognostic factor for overall survival (OS) in a multivariable Cox proportional hazard model (hazard ratio [HR] with 95% confidence interval [CI]: 1.99 [1.27-3.12], p = 0.0028), while in the same cohort, manual quantification of stromal areas and a gene expression signature of cancer-associated fibroblasts (CAFs) were only prognostic in specific tumor stages. We validated these findings in an independent cohort of 409 stage I-IV CRC patients from the "Darmkrebs: Chancen der Verhütung durch Screening" (DACHS) study who were recruited between 2003 and 2007 in multiple institutions in Germany. Again, the score was an independent prognostic factor for OS (HR 1.63 [1.14-2.33], p = 0.008), CRC-specific OS (HR 2.29 [1.5-3.48], p = 0.0004), and relapse-free survival (RFS; HR 1.92 [1.34-2.76], p = 0.0004). A prospective validation is required before this biomarker can be implemented in clinical workflows. CONCLUSIONS: In our retrospective study, we show that a CNN can assess the human tumor microenvironment and predict prognosis directly from histopathological images.

Architecture & Planning• 2019• Public Library of Science
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Periodicals

An Integrated Brain-Machine Interface Platform With Thousands of Channels

Brain-machine interfaces hold promise for the restoration of sensory and motor function and the treatment of neurological disorders, but clinical brain-machine interfaces have not yet been widely adopted, in part, because modest channel counts have limited their potential. In this white paper, we describe Neuralink’s first steps toward a scalable high-bandwidth brain-machine interface system. We have built arrays of small and flexible electrode “threads,” with as many as 3072 electrodes per array distributed across 96 threads. We have also built a neurosurgical robot capable of inserting six threads (192 electrodes) per minute. Each thread can be individually inserted into the brain with micron precision for avoidance of surface vasculature and targeting specific brain regions. The electrode array is packaged into a small implantable device that contains custom chips for low-power on-board amplification and digitization: The package for 3072 channels occupies less than 23×18.5×2 mm3. A single USB-C cable provides full-bandwidth data streaming from the device, recording from all channels simultaneously. This system has achieved a spiking yield of up to 70% in chronically implanted electrodes. Neuralink’s approach to brain-machine interface has unprecedented packaging density and scalability in a clinically relevant package.

Architecture & Planning• 2019• JMIR Publications
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Periodicals

Notch signaling pathway: architecture, disease, and therapeutics

The NOTCH gene was identified approximately 110 years ago. Classical studies have revealed that NOTCH signaling is an evolutionarily conserved pathway. NOTCH receptors undergo three cleavages and translocate into the nucleus to regulate the transcription of target genes. NOTCH signaling deeply participates in the development and homeostasis of multiple tissues and organs, the aberration of which results in cancerous and noncancerous diseases. However, recent studies indicate that the outcomes of NOTCH signaling are changeable and highly dependent on context. In terms of cancers, NOTCH signaling can both promote and inhibit tumor development in various types of cancer. The overall performance of NOTCH-targeted therapies in clinical trials has failed to meet expectations. Additionally, NOTCH mutation has been proposed as a predictive biomarker for immune checkpoint blockade therapy in many cancers. Collectively, the NOTCH pathway needs to be integrally assessed with new perspectives to inspire discoveries and applications. In this review, we focus on both classical and the latest findings related to NOTCH signaling to illustrate the history, architecture, regulatory mechanisms, contributions to physiological development, related diseases, and therapeutic applications of the NOTCH pathway. The contributions of NOTCH signaling to the tumor immune microenvironment and cancer immunotherapy are also highlighted. We hope this review will help not only beginners but also experts to systematically and thoroughly understand the NOTCH signaling pathway.

Architecture & Planning• 2022• Springer Nature
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Periodicals

First M87 Event Horizon Telescope Results. II. Array and Instrumentation

Abstract The Event Horizon Telescope (EHT) is a very long baseline interferometry (VLBI) array that comprises millimeter- and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth. At a nominal operating wavelength of ∼1.3 mm, EHT angular resolution ( λ / D ) is ∼25 μ as, which is sufficient to resolve nearby supermassive black hole candidates on spatial and temporal scales that correspond to their event horizons. With this capability, the EHT scientific goals are to probe general relativistic effects in the strong-field regime and to study accretion and relativistic jet formation near the black hole boundary. In this Letter we describe the system design of the EHT, detail the technology and instrumentation that enable observations, and provide measures of its performance. Meeting the EHT science objectives has required several key developments that have facilitated the robust extension of the VLBI technique to EHT observing wavelengths and the production of instrumentation that can be deployed on a heterogeneous array of existing telescopes and facilities. To meet sensitivity requirements, high-bandwidth digital systems were developed that process data at rates of 64 gigabit s −1 , exceeding those of currently operating cm-wavelength VLBI arrays by more than an order of magnitude. Associated improvements include the development of phasing systems at array facilities, new receiver installation at several sites, and the deployment of hydrogen maser frequency standards to ensure coherent data capture across the array. These efforts led to the coordination and execution of the first Global EHT observations in 2017 April, and to event-horizon-scale imaging of the supermassive black hole candidate in M87.

Architecture & Planning• 2019• IOP Publishing
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Periodicals

A global perspective on domestic energy deprivation: Overcoming the energy poverty–fuel poverty binary

This paper offers an integrated conceptual framework for the research and amelioration of energy deprivation in the home. It starts from the premise that all forms of energy and fuel poverty – in developed and developing countries alike – are underpinned by a common condition: the inability to attain a socially and materially necessitated level of domestic energy services. We consider the functionings provided by energy demand in the residential domain in order to advance two claims: first, that domestic energy deprivation in its different guises and forms is fundamentally tied to the ineffective operation of the socio-technical pathways that allow for the fulfilment of household energy needs, and as such is best analyzed by understanding the constitution of different energy services (heating, lighting, etc.) in the home. Second, we emphasize the ability of vulnerability thinking to encapsulate the driving forces of domestic energy deprivation via a comprehensive analytical matrix. The paper identifies the main components and implications of energy service and vulnerability approaches as they relate to domestic energy deprivation across the world.

Architecture & Planning• 2015• Elsevier BV
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Periodicals

Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors. There have been recent concerns about increased prevalence, and this article seeks to elaborate on factors that may influence prevalence rates, including recent changes to the diagnostic criteria. The authors review evidence that ASD is a neurobiological disorder influenced by both genetic and environmental factors affecting the developing brain, and enumerate factors that correlate with ASD risk. Finally, the article describes how clinical evaluation begins with developmental screening, followed by referral for a definitive diagnosis, and provides guidance on screening for comorbid conditions.

Architecture & Planning• 2020• AME Publishing Company
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Periodicals

Sustainable Energy Transition for Renewable and Low Carbon Grid Electricity Generation and Supply

The greatest sustainability challenge facing humanity today is the greenhouse gas emissions and the global climate change with fossil fuels led by coal, natural gas and oil contributing 61.3% of global electricity generation in the year 2020. The cumulative effect of the Stockholm, Rio, and Johannesburg conferences identified sustainable energy development (SED) as a very important factor in the sustainable global development. This study reviews energy transition strategies and proposes a roadmap for sustainable energy transition for sustainable electricity generation and supply in line with commitments of the Paris Agreement aimed at reducing greenhouse gas emissions and limiting the rise in global average temperature to 1.5°C above the preindustrial level. The sustainable transition strategies typically consist of three major technological changes namely, energy savings on the demand side, generation efficiency at production level and fossil fuel substitution by various renewable energy sources and low carbon nuclear. For the transition remain technically and economically feasible and beneficial, policy initiatives are necessary to steer the global electricity transition towards a sustainable energy and electricity system. Large-scale renewable energy adoption should include measures to improve efficiency of existing nonrenewable sources which still have an important cost reduction and stabilization role. A resilient grid with advanced energy storage for storage and absorption of variable renewables should also be part of the transition strategies. From this study, it was noted that whereas sustainable development has social, economic, and environmental pillars, energy sustainability is best analysed by five-dimensional approach consisting of environmental, economic, social, technical, and institutional/political sustainability to determine resource sustainability. The energy transition requires new technology for maximum use of the abundant but intermittent renewable sources a sustainable mix with limited nonrenewable sources optimized to minimize cost and environmental impact but maintained quality, stability, and flexibility of an electricity supply system. Technologies needed for the transition are those that use conventional mitigation, negative emissions technologies which capture and sequester carbon emissions and finally technologies which alter the global atmospheric radiative energy budget to stabilize and reduce global average temperature. A sustainable electricity system needs facilitating technology, policy, strategies and infrastructure like smart grids, and models with an appropriate mix of both renewable and low carbon energy sources.

Architecture & Planning• 2022• Frontiers Media
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Periodicals

Multi-Agent Systems for Power Engineering Applications—Part I: Concepts, Approaches, and Technical Challenges

This is the first part of a two-part paper that has arisen from the work of the IEEE Power Engineering Society's Multi-Agent Systems (MAS) Working Group. Part I of this paper examines the potential value of MAS technology to the power industry. In terms of contribution, it describes fundamental concepts and approaches within the field of multi-agent systems that are appropriate to power engineering applications. As well as presenting a comprehensive review of the meaningful power engineering applications for which MAS are being investigated, it also defines the technical issues which must be addressed in order to accelerate and facilitate the uptake of the technology within the power and energy sector. Part II of this paper explores the decisions inherent in engineering multi-agent systems for applications in the power and energy sector and offers guidance and recommendations on how MAS can be designed and implemented.

Architecture & Planning• 2007• Institute of Electrical and Electronics Engineers
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Periodicals

Local opinion leaders: effects on professional practice and health care outcomes

BACKGROUND: Clinical practice is not always evidence-based and, therefore, may not optimise patient outcomes. Opinion leaders disseminating and implementing 'best evidence' is one method that holds promise as a strategy to bridge evidence-practice gaps. OBJECTIVES: To assess the effectiveness of the use of local opinion leaders in improving professional practice and patient outcomes. SEARCH STRATEGY: We searched Cochrane EPOC Group Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, HMIC, Science Citation Index, Social Science Citation Index, ISI Conference Proceedings and World Cat Dissertations up to 5 May 2009. In addition, we searched reference lists of included articles. SELECTION CRITERIA: Studies eligible for inclusion were randomised controlled trials investigating the effectiveness of using opinion leaders to disseminate evidence-based practice and reporting objective measures of professional performance and/or health outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each study and assessed its risk of bias. For each trial, we calculated the median risk difference (RD) for compliance with desired practice, adjusting for baseline where data were available. We reported the median adjusted RD for each of the main comparisons. MAIN RESULTS: We included 18 studies involving more than 296 hospitals and 318 PCPs. Fifteen studies (18 comparisons) contributed to the calculations of the median adjusted RD for the main comparisons. The effects of interventions varied across the 63 outcomes from 15% decrease in compliance to 72% increase in compliance with desired practice. The median adjusted RD for the main comparisons were: i) Opinion leaders compared to no intervention, +0.09; ii) Opinion leaders alone compared to a single intervention, +0.14; iii) Opinion leaders with one or more additional intervention(s) compared to the one or more additional intervention(s), +0.10; iv) Opinion leaders as part of multiple interventions compared to no intervention, +0.10. Overall, across all 18 studies the median adjusted RD was +0.12 representing a 12% absolute increase in compliance in the intervention group. AUTHORS' CONCLUSIONS: Opinion leaders alone or in combination with other interventions may successfully promote evidence-based practice, but effectiveness varies both within and between studies. These results are based on heterogeneous studies differing in terms of type of intervention, setting, and outcomes measured. In most of the studies the role of the opinion leader was not clearly described, and it is therefore not possible to say what the best way is to optimise the effectiveness of opinion leaders.

Architecture & Planning• 2011• Elsevier BV
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Periodicals

Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors

Appropriate localization and migration of T cells is a prerequisite for antitumor immune surveillance. Studies using fixed tumor samples from human patients have shown that T cells accumulate more efficiently in the stroma than in tumor islets, but the mechanisms by which this occurs are unknown. By combining immunostaining and real-time imaging in viable slices of human lung tumors, we revealed that the density and the orientation of the stromal extracellular matrix likely play key roles in controlling the migration of T cells. Active T cell motility, dependent on chemokines but not on β1 or β2 integrins, was observed in loose fibronectin and collagen regions, whereas T cells migrated poorly in dense matrix areas. Aligned fibers in perivascular regions and around tumor epithelial cell regions dictated the migratory trajectory of T cells and restricted them from entering tumor islets. Consistently, matrix reduction with collagenase increased the ability of T cells to contact cancer cells. Thus, the stromal extracellular matrix influences antitumor immunity by controlling the positioning and migration of T cells. Understanding the mechanisms by which this collagen network is generated has the potential to aid in the development of new therapeutics.

Architecture & Planning• 2012• American Society for Clinical Investigation
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Aging and Environmental Exposures Alter Tissue-Specific DNA Methylation Dependent upon CpG Island Context

Epigenetic control of gene transcription is critical for normal human development and cellular differentiation. While alterations of epigenetic marks such as DNA methylation have been linked to cancers and many other human diseases, interindividual epigenetic variations in normal tissues due to aging, environmental factors, or innate susceptibility are poorly characterized. The plasticity, tissue-specific nature, and variability of gene expression are related to epigenomic states that vary across individuals. Thus, population-based investigations are needed to further our understanding of the fundamental dynamics of normal individual epigenomes. We analyzed 217 non-pathologic human tissues from 10 anatomic sites at 1,413 autosomal CpG loci associated with 773 genes to investigate tissue-specific differences in DNA methylation and to discern how aging and exposures contribute to normal variation in methylation. Methylation profile classes derived from unsupervised modeling were significantly associated with age (P<0.0001) and were significant predictors of tissue origin (P<0.0001). In solid tissues (n = 119) we found striking, highly significant CpG island-dependent correlations between age and methylation; loci in CpG islands gained methylation with age, loci not in CpG islands lost methylation with age (P<0.001), and this pattern was consistent across tissues and in an analysis of blood-derived DNA. Our data clearly demonstrate age- and exposure-related differences in tissue-specific methylation and significant age-associated methylation patterns which are CpG island context-dependent. This work provides novel insight into the role of aging and the environment in susceptibility to diseases such as cancer and critically informs the field of epigenomics by providing evidence of epigenetic dysregulation by age-related methylation alterations. Collectively we reveal key issues to consider both in the construction of reference and disease-related epigenomes and in the interpretation of potentially pathologically important alterations.

Architecture & Planning• 2009• Public Library of Science
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Periodicals

Ultra Wideband Indoor Positioning Technologies: Analysis and Recent Advances

In recent years, indoor positioning has emerged as a critical function in many end-user applications; including military, civilian, disaster relief and peacekeeping missions. In comparison with outdoor environments, sensing location information in indoor environments requires a higher precision and is a more challenging task in part because various objects reflect and disperse signals. Ultra WideBand (UWB) is an emerging technology in the field of indoor positioning that has shown better performance compared to others. In order to set the stage for this work, we provide a survey of the state-of-the-art technologies in indoor positioning, followed by a detailed comparative analysis of UWB positioning technologies. We also provide an analysis of strengths, weaknesses, opportunities, and threats (SWOT) to analyze the present state of UWB positioning technologies. While SWOT is not a quantitative approach, it helps in assessing the real status and in revealing the potential of UWB positioning to effectively address the indoor positioning problem. Unlike previous studies, this paper presents new taxonomies, reviews some major recent advances, and argues for further exploration by the research community of this challenging problem space.

Architecture & Planning• 2016• Multidisciplinary Digital Publishing Institute
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Google Earth Engine Cloud Computing Platform for Remote Sensing Big Data Applications: A Comprehensive Review

Remote sensing (RS) systems have been collecting massive volumes of datasets for decades, managing and analyzing of which are not practical using common software packages and desktop computing resources. In this regard, Google has developed a cloud computing platform, called Google Earth Engine (GEE), to effectively address the challenges of big data analysis. In particular, this platform facilitates processing big geo data over large areas and monitoring the environment for long periods of time. Although this platform was launched in 2010 and has proved its high potential for different applications, it has not been fully investigated and utilized for RS applications until recent years. Therefore, this study aims to comprehensively explore different aspects of the GEE platform, including its datasets, functions, advantages/limitations, and various applications. For this purpose, 450 journal articles published in 150 journals between January 2010 and May 2020 were studied. It was observed that Landsat and Sentinel datasets were extensively utilized by GEE users. Moreover, supervised machine learning algorithms, such as Random Forest, were more widely applied to image classification tasks. GEE has also been employed in a broad range of applications, such as Land Cover/land Use classification, hydrology, urban planning, natural disaster, climate analyses, and image processing. It was generally observed that the number of GEE publications have significantly increased during the past few years, and it is expected that GEE will be utilized by more users from different fields to resolve their big data processing challenges.

Architecture & Planning• 2020• Institute of Electrical and Electronics Engineers
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A Comprehensive Review of the COVID-19 Pandemic and the Role of IoT, Drones, AI, Blockchain, and 5G in Managing its Impact

The unprecedented outbreak of the 2019 novel coronavirus, termed as COVID-19 by the World Health Organization (WHO), has placed numerous governments around the world in a precarious position. The impact of the COVID-19 outbreak, earlier witnessed by the citizens of China alone, has now become a matter of grave concern for virtually every country in the world. The scarcity of resources to endure the COVID-19 outbreak combined with the fear of overburdened healthcare systems has forced a majority of these countries into a state of partial or complete lockdown. The number of laboratory-confirmed coronavirus cases has been increasing at an alarming rate throughout the world, with reportedly more than 3 million confirmed cases as of 30 April 2020. Adding to these woes, numerous false reports, misinformation, and unsolicited fears in regards to coronavirus, are being circulated regularly since the outbreak of the COVID-19. In response to such acts, we draw on various reliable sources to present a detailed review of all the major aspects associated with the COVID-19 pandemic. In addition to the direct health implications associated with the outbreak of COVID-19, this study highlights its impact on the global economy. In drawing things to a close, we explore the use of technologies such as the Internet of Things (IoT), Unmanned Aerial Vehicles (UAVs), blockchain, Artificial Intelligence (AI), and 5G, among others, to help mitigate the impact of COVID-19 outbreak.

Architecture & Planning• 2020• Institute of Electrical and Electronics Engineers
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Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the Stratum Corneum

The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.

Architecture & Planning• 2015• Multidisciplinary Digital Publishing Institute
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WORLD: A Vocoder-Based High-Quality Speech Synthesis System for Real-Time Applications

A vocoder-based speech synthesis system, named WORLD, was developed in an effort to improve the sound quality of real-time applications using speech. Speech analysis, manipulation, and synthesis on the basis of vocoders are used in various kinds of speech research. Although several high-quality speech synthesis systems have been developed, real-time processing has been difficult with them because of their high computational costs. This new speech synthesis system has not only sound quality but also quick processing. It consists of three analysis algorithms and one synthesis algorithm proposed in our previous research. The effectiveness of the system was evaluated by comparing its output with against natural speech including consonants. Its processing speed was also compared with those of conventional systems. The results showed that WORLD was superior to the other systems in terms of both sound quality and processing speed. In particular, it was over ten times faster than the conventional systems, and the real time factor (RTF) indicated that it was fast enough for real-time processing.

Architecture & Planning• 2016• Institute of Electronics, Information and Communication Engineers
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survival with an asymmetrical brain: advantages and disadvantages of cerebral lateralization

Recent evidence in natural and semi-natural settings has revealed a variety of left-right perceptual asymmetries among vertebrates. These include preferential use of the left or right visual hemifield during activities such as searching for food, agonistic responses, or escape from predators in animals as different as fish, amphibians, reptiles, birds, and mammals. There are obvious disadvantages in showing such directional asymmetries because relevant stimuli may be located to the animal's left or right at random; there is no a priori association between the meaning of a stimulus (e.g., its being a predator or a food item) and its being located to the animal's left or right. Moreover, other organisms (e.g., predators) could exploit the predictability of behavior that arises from population-level lateral biases. It might be argued that lateralization of function enhances cognitive capacity and efficiency of the brain, thus counteracting the ecological disadvantages of lateral biases in behavior. However, such an increase in brain efficiency could be obtained by each individual being lateralized without any need to align the direction of the asymmetry in the majority of the individuals of the population. Here we argue that the alignment of the direction of behavioral asymmetries at the population level arises as an "evolutionarily stable strategy" under "social" pressures occurring when individually asymmetrical organisms must coordinate their behavior with the behavior of other asymmetrical organisms of the same or different species.

Architecture & Planning• 2005• Cambridge University Press
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A developmental, mentalization-based approach to the understanding and treatment of borderline personality disorder

The precise nature and etiopathogenesis of borderline personality disorder (BPD) continues to elude researchers and clinicians. Yet, increasing evidence from various strands of research converges to suggest that affect dysregulation, impulsivity, and unstable relationships constitute the core features of BPD. Over the last two decades, the mentalization-based approach to BPD has attempted to provide a theoretically consistent way of conceptualizing the interrelationship between these core features of BPD, with the aim of providing clinicians with a conceptually sound and empirically supported approach to BPD and its treatment. This paper presents an extended version of this approach to BPD based on recently accumulated data. In particular, we suggest that the core features of BPD reflect impairments in different facets of mentalization, each related to impairments in relatively distinct neural circuits underlying these facets. Hence, we provide a comprehensive account of BPD by showing how its core features are related to each other in theoretically meaningful ways. More specifically, we argue that BPD is primarily associated with a low threshold for the activation of the attachment system and deactivation of controlled mentalization, linked to impairments in the ability to differentiate mental states of self and other, which lead to hypersensitivity and increased susceptibility to contagion by other people's mental states, and poor integration of cognitive and affective aspects of mentalization. The combination of these impairments may explain BPD patients' propensity for vicious interpersonal cycles, and their high levels of affect dysregulation and impulsivity. Finally, the implications of this expanded mentalization-based approach to BPD for mentalization-based treatment and treatment of BPD more generally are discussed.

Architecture & Planning• 2009• Cambridge University Press
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