bluuebunny/crossref_metadata_2025 huggingface dataset:
Communication: Free energy of ligand-receptor systems forming multimeric complexes
Authors: Di Michele Lorenzo , Bachmann Stephan J. , Parolini Lucia , Mognetti Bortolo M.
Published: April 2016

Ligand-receptor interactions are ubiquitous in biology and have become popular in materials in view of their applications to programmable self-assembly. Although complex functionalities often emerge from the simultaneous interaction of more than just two linker molecules, state of the art theoretical frameworks enable the calculation of the free energy only in systems featuring one-to-one ligand/receptor binding. In this Communication, we derive a general formula to calculate the free energy of systems featuring simultaneous direct interaction between an arbitrary number of linkers. To exemplify the potential and generality of our approach, we apply it to the systems recently introduced by Parolini et al. [ACS Nano 10, 2392 (2016)] and Halverson and Tkachenko [J. Chem. Phys. 144, 094903 (2016)], both featuring functionalized Brownian particles interacting via three-linker complexes.
All-optical control of microfiber resonator by graphene's photothermal effect
Authors: Wang Yadong , Gan Xuetao , Zhao Chenyang , Fang Liang , Mao Dong , Xu Yiping , Zhang Fanlu , Xi Teli , Ren Liyong , Zhao Jianlin
Published: April 2016

We demonstrate an efficient all-optical control of microfiber resonator assisted by graphene's photothermal effect. Wrapping graphene onto a microfiber resonator, the light-graphene interaction can be strongly enhanced via the resonantly circulating light, which enables a significant modulation of the resonance with a resonant wavelength shift rate of 71 pm/mW when pumped by a 1540 nm laser. The optically controlled resonator enables the implementation of low threshold optical bistability and switching with an extinction ratio exceeding 13 dB. The thin and compact structure promises a fast response speed of the control, with a rise (fall) time of 294.7 μs (212.2 μs) following the 10%–90% rule. The proposed device, with the advantages of compact structure, all-optical control, and low power acquirement, offers great potential in the miniaturization of active in-fiber photonic devices.
Perspective: Evolutionary design of granular media and block copolymer patterns
Authors: Jaeger Heinrich M. , de Pablo Juan J.
Published: April 2016

The creation of new materials “by design” is a process that starts from desired materials properties and proceeds to identify requirements for the constituent components. Such process is challenging because it inverts the typical modeling approach, which starts from given micro-level components to predict macro-level properties. We describe how to tackle this inverse problem using concepts from evolutionary computation. These concepts have widespread applicability and open up new opportunities for design as well as discovery. Here we apply them to design tasks involving two very different classes of soft materials, shape-optimized granular media and nanopatterned block copolymer thin films.
Schrödinger equation solved for the hydrogen molecule with unprecedented accuracy
Authors: Pachucki Krzysztof , Komasa Jacek
Published: April 2016

The hydrogen molecule can be used for determination of physical constants, including the proton charge radius, and for improved tests of the hypothetical long range force between hadrons, which require a sufficiently accurate knowledge of the molecular levels. In this work, we perform the first step toward a significant improvement in theoretical predictions of H2 and solve the nonrelativistic Schrödinger equation to the unprecedented accuracy of 10−12. We hope that it will inspire a parallel progress in the spectroscopy of the molecular hydrogen.
Overlapping double potential wells in a single optical microtube cavity with vernier-scale-like tuning effect
Authors: Madani A. , Bolaños Quiñones V. A. , Ma L. B. , Miao S. D. , Jorgensen M. R. , Schmidt O. G.
Published: April 2016

Spatially and temporally overlapping double potential wells are realized in a hybrid optical microtube cavity due to the coexistence of an aggregate of luminescent quantum dots embedded in the tube wall and the cone-shaped tube's geometry. The double potential wells produce two independent sets of optical modes with different sets of mode numbers, indicating phase velocity separation for the modes overlapping at the same frequency. The overlapping mode position can be tuned by modifying the tube cavity, where these mode sets shift with different magnitudes, allowing for a vernier-scale-like tuning effect.
Thermoelectric properties of In-rich InGaN and InN/InGaN superlattices
Authors: Ju James (Zi-Jian) , Sun Bo , Haunschild Georg , Loitsch Bernhard , Stoib Benedikt , Brandt Martin S. , Stutzmann Martin , Koh Yee Kan , Koblmüller Gregor
Published: April 2016

The thermoelectric properties of n-type InGaN alloys with high In-content and InN/InGaN thin film superlattices (SL) grown by molecular beam epitaxy are investigated. Room-temperature measurements of the thermoelectric properties reveal that an increasing Ga-content in ternary InGaN alloys (0 < x(Ga) < 0.2) yields a more than 10-fold reduction in thermal conductivity (κ) without deteriorating electrical conductivity (σ), while the Seebeck coefficient (S) increases slightly due to a widening band gap compared to binary InN. Employing InN/InGaN SLs (x(Ga) = 0.1) with different periods, we demonstrate that confinement effects strongly enhance electron mobility with values as high as ∼820 cm2/V s at an electron density ne of ∼5×1019 cm−3, leading to an exceptionally high σ of ∼5400 (Ωcm)−1. Simultaneously, in very short-period SL structures S becomes decoupled from ne, κ is further reduced below the alloy limit (κ < 9 W/m-K), and the power factor increases to 2.5×10−4 W/m-K2 by more than a factor of 5 as compared to In-rich InGaN alloys. These findings demonstrate that quantum confinement in group-III nitride-based superlattices facilitates improvements of thermoelectric properties over bulk-like ternary nitride alloys.
Quantitative analysis of hydrogen in SiO2/SiN/SiO2 stacks using atom probe tomography
Authors: Kunimune Yorinobu , Shimada Yasuhiro , Sakurai Yusuke , Inoue Masao , Nishida Akio , Han Bin , Tu Yuan , Takamizawa Hisashi , Shimizu Yasuo , Inoue Koji , Yano Fumiko , Nagai Yasuyoshi , Katayama Toshiharu , Ide Takashi
Published: April 2016

We have demonstrated that it is possible to reproducibly quantify hydrogen concentration in the SiN layer of a SiO2/SiN/SiO2 (ONO) stack structure using ultraviolet laser-assisted atom probe tomography (APT). The concentration of hydrogen atoms detected using APT increased gradually during the analysis, which could be explained by the effect of hydrogen adsorption from residual gas in the vacuum chamber onto the specimen surface. The amount of adsorbed hydrogen in the SiN layer was estimated by analyzing another SiN layer with an extremely low hydrogen concentration (<0.2 at. %). Thus, by subtracting the concentration of adsorbed hydrogen, the actual hydrogen concentration in the SiN layer was quantified as approximately 1.0 at. %. This result was consistent with that obtained by elastic recoil detection analysis (ERDA), which confirmed the accuracy of the APT quantification. The present results indicate that APT enables the imaging of the three-dimensional distribution of hydrogen atoms in actual devices at a sub-nanometer scale.
Double-Headed Nucleotides: Building Blocks for New Nucleic Acid Architectures
Authors: Sharma Pawan K. , Kumar Pawan , Nielsen Poul
Published: April 2016

Double-headed nucleotides are nucleotides with two nucleobases. These have been investigated recently with the purpose of using the recognition potential of the additional nucleobases in various nucleic acid constructs. Presented here is a review of the double-headed nucleotide monomers investigated so far and their effects in nucleic acid duplexes and other secondary structures.
Interaction of HIF1α and β-catenin inhibits matrix metalloproteinase 13 expression and prevents cartilage damage in mice
Authors: Bouaziz Wafa , Sigaux Johanna , Modrowski Dominique , Devignes Claire-Sophie , Funck-Brentano Thomas , Richette Pascal , Ea Hang-Korng , Provot Sylvain , Cohen-Solal Martine , Haÿ Eric
Published: April 2016

Significance

Hypoxia-inducible factor 1α (HIF1α) is important for cell growth and survival. It modulates Wnt signaling, regulating cell differentiation and fate. Osteoarthritis (OA) is an increasingly frequent joint disorder characterized by progressive cartilage breakdown in which Wnt/β-catenin signaling triggers matrix metalloproteinase 13 (MMP13) expression and chondrocyte catabolism. Here we demonstrate HIF1α inhibits β-catenin signaling by blocking transcription factor 4 (TCF4)–β-catenin interaction and down-regulates MMP13 expression, thereby alleviating cartilage lesions, whereas the TCF4–β-catenin signaling induces an OA phenotype in mice. In OA joints, PKF118-310, a small molecule that blocked TCF4–β-catenin interaction, significantly reduced the progression of OA cartilage lesions. Thus, blockade of TCF4–β-catenin signaling by HIF1α represents a promising strategy to prevent articular cartilage loss in OA.
Astrocytes regulate cortical state switching in vivo
Authors: Poskanzer Kira E. , Yuste Rafael
Published: April 2016

Significance

Astrocytes—a type of glial cell—and neurons function together in neural circuits, but how astrocytes affect circuit function remains poorly understood. By measuring the fluorescent calcium activity of astrocytes while recording the electrophysiological oscillations in the mouse cortex, we find that astrocytes, through regulation of extracellular glutamate, are involved in triggering a slow neuronal rhythm in the brain that has been shown to be important in sleep and memory formation.
Eyespot-dependent determination of the phototactic sign in
Chlamydomonas reinhardtii
Authors: Ueki Noriko , Ide Takahiro , Mochiji Shota , Kobayashi Yuki , Tokutsu Ryutaro , Ohnishi Norikazu , Yamaguchi Katsushi , Shigenobu Shuji , Tanaka Kan , Minagawa Jun , Hisabori Toru , Hirono Masafumi , Wakabayashi Ken-ichi
Published: April 2016

Significance

The phototactic behavior of the unicellular green alga
Chlamydomonas reinhardtii
is thought to rely on photoreception by the eyespot apparatus. Here, we isolated an eyespot-less mutant that clearly exhibits phototaxis. Intriguingly, the phototactic sign (the direction of cell migration) in this mutant is opposite to that of the wild type after treatment with reagents that enhance the sign, a property that we also detected in previously reported eyespot-less mutants. The reversed phototactic-sign phenotype was attributed to the fact that the photoreceptors were exposed to condensed light from their rear side. This report demonstrates the importance of the eyespot, in which carotenoid layers shield the photoreceptors from light condensed by the cell body, which functions as a convex lens.
Weak Banach-Saks property and Komlós’ theorem for preduals of JBW*-triples
Authors: Peralta Antonio , Pfitzner Hermann
Published: April 2016

We show that the predual of a JBW

∗

^*

-triple has the weak Banach-Saks property, that is, reflexive subspaces of a JBW

∗

^*

-triple predual are super-reflexive. We also prove that JBW

∗

^*

-triple preduals satisfy the Komlós property (which can be considered an abstract version of the weak law of large numbers). The results rely on two previous papers from which we infer the fact that, like in the classical case of

L
1

L^1

, a subspace of a JBW

∗

^*

-triple predual contains

ℓ
1

\ell _1

as soon as it contains uniform copies of

ℓ
1
n

\ell _1^n

.
Dynamic myosin activation promotes collective morphology and migration by locally balancing oppositional forces from surrounding tissue
Authors: Aranjuez George , Burtscher Ashley , Sawant Ketki , Majumder Pralay , McDonald Jocelyn A.
Published: April 2016

Migrating cells need to overcome physical constraints from the local microenvironment to navigate their way through tissues. Cells that move collectively have the additional challenge of negotiating complex environments in vivo while maintaining cohesion of the group as a whole. The mechanisms by which collectives maintain a migratory morphology while resisting physical constraints from the surrounding tissue are poorly understood. Drosophila border cells represent a genetic model of collective migration within a cell-dense tissue. Border cells move as a cohesive group of 6−10 cells, traversing a network of large germ line–derived nurse cells within the ovary. Here we show that the border cell cluster is compact and round throughout their entire migration, a shape that is maintained despite the mechanical pressure imposed by the surrounding nurse cells. Nonmuscle myosin II (Myo-II) activity at the cluster periphery becomes elevated in response to increased constriction by nurse cells. Furthermore, the distinctive border cell collective morphology requires highly dynamic and localized enrichment of Myo-II. Thus, activated Myo-II promotes cortical tension at the outer edge of the migrating border cell cluster to resist compressive forces from nurse cells. We propose that dynamic actomyosin tension at the periphery of collectives facilitates their movement through restrictive tissues.
Rail-dbGaP: analyzing dbGaP-protected data in the cloud with Amazon Elastic MapReduce
Authors: Nellore Abhinav , Wilks Christopher , Hansen Kasper D. , Leek Jeffrey T. , Langmead Ben
Published: April 2016

Motivation: Public archives contain thousands of trillions of bases of valuable sequencing data. More than 40% of the Sequence Read Archive is human data protected by provisions such as dbGaP. To analyse dbGaP-protected data, researchers must typically work with IT administrators and signing officials to ensure all levels of security are implemented at their institution. This is a major obstacle, impeding reproducibility and reducing the utility of archived data.

Results: We present a protocol and software tool for analyzing protected data in a commercial cloud. The protocol, Rail-dbGaP, is applicable to any tool running on Amazon Web Services Elastic MapReduce. The tool, Rail-RNA v0.2, is a spliced aligner for RNA-seq data, which we demonstrate by running on 9662 samples from the dbGaP-protected GTEx consortium dataset. The Rail-dbGaP protocol makes explicit for the first time the steps an investigator must take to develop Elastic MapReduce pipelines that analyse dbGaP-protected data in a manner compliant with NIH guidelines. Rail-RNA automates implementation of the protocol, making it easy for typical biomedical investigators to study protected RNA-seq data, regardless of their local IT resources or expertise.

Availability and Implementation: Rail-RNA is available from http://rail.bio. Technical details on the Rail-dbGaP protocol as well as an implementation walkthrough are available at https://github.com/nellore/rail-dbgap. Detailed instructions on running Rail-RNA on dbGaP-protected data using Amazon Web Services are available at http://docs.rail.bio/dbgap/.

Contacts: anellore@gmail.com or langmea@cs.jhu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Will they participate? Predicting patients’ response to clinical trial invitations in a pediatric emergency department
Authors: Ni Yizhao , Beck Andrew F , Taylor Regina , Dyas Jenna , Solti Imre , Grupp-Phelan Jacqueline , Dexheimer Judith W
Published: April 2016

Objective (1) To develop an automated algorithm to predict a patient’s response (ie, if the patient agrees or declines) before he/she is approached for a clinical trial invitation; (2) to assess the algorithm performance and the predictors on real-world patient recruitment data for a diverse set of clinical trials in a pediatric emergency department; and (3) to identify directions for future studies in predicting patients’ participation response.

Materials and Methods We collected 3345 patients’ response to trial invitations on 18 clinical trials at one center that were actively enrolling patients between January 1, 2010 and December 31, 2012. In parallel, we retrospectively extracted demographic, socioeconomic, and clinical predictors from multiple sources to represent the patients’ profiles. Leveraging machine learning methodology, the automated algorithms predicted participation response for individual patients and identified influential features associated with their decision-making. The performance was validated on the collection of actual patient response, where precision, recall, F-measure, and area under the ROC curve were assessed.

Results Compared to the random response predictor that simulated the current practice, the machine learning algorithms achieved significantly better performance (Precision/Recall/F-measure/area under the ROC curve: 70.82%/92.02%/80.04%/72.78% on 10-fold cross validation and 71.52%/92.68%/80.74%/75.74% on the test set). By analyzing the significant features output by the algorithms, the study confirmed several literature findings and identified challenges that could be mitigated to optimize recruitment.

Conclusion By exploiting predictive variables from multiple sources, we demonstrated that machine learning algorithms have great potential in improving the effectiveness of the recruitment process by automatically predicting patients’ participation response to trial invitations.
Core informatics competencies for clinical and translational scientists: what do our customers and collaborators need to know?
Authors: Valenta Annette L , Meagher Emma A , Tachinardi Umberto , Starren Justin
Published: April 2016

Since the inception of the Clinical and Translational Science Award (CTSA) program in 2006, leaders in education across CTSA sites have been developing and updating core competencies for Clinical and Translational Science (CTS) trainees. By 2009, 14 competency domains, including biomedical informatics, had been identified and published. Since that time, the evolution of the CTSA program, changes in the practice of CTS, the rapid adoption of electronic health records (EHRs), the growth of biomedical informatics, the explosion of big data, and the realization that some of the competencies had proven to be difficult to apply in practice have made it clear that the competencies should be updated. This paper describes the process undertaken and puts forth a new set of competencies that has been recently endorsed by the Clinical Research Informatics Workgroup of AMIA. In addition to providing context and background for the current version of the competencies, we hope this will serve as a model for revision of competencies over time.
Genetics and Epidemiology of Multiple Sclerosis
Authors: Deluca Gabriele C. , Yates Richard L. , Sadovnick A. Dessa
Published: April 2016

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Despite decades of research, its etiology remains unknown. It has been established that environmental and genetic factors contribute to multiple sclerosis disease risk. Although the identification of risk factors for multiple sclerosis has not yet radically advanced understanding of the pathophysiology, it has shed light on the complex epidemiology of this disease. This chapter highlights key epidemiologic features of multiple sclerosis, with a focus on environmental and genetic factors known to influence disease risk. The interplay between environmental and genetic factors in multiple sclerosis pathogenesis is discussed.
Taking a Microscopic Look at Multiple Sclerosis
Authors: Guo Yong , Lucchinetti Claudia F.
Published: April 2016

The pathology of multiple sclerosis is complex, extends beyond the white matter plaque, and is influenced by stage of demyelinating activity, clinical course, disease duration, and treatment. Technological advances in immunology, molecular biology, and “omic” biology have provided novel insights into the mechanisms for development of white matter plaques, axonal damage, cortical demyelination, and disease progression. Detailed, systematic, and statistically rigorous pathological studies on clinically well-characterized MS cohorts have helped define the heterogeneous pathological substrates of MS and unravel the complex molecular pathogenic mechanisms, with the ultimate goal of identifying targets for therapeutic interventions. It is increasingly clear that the use of human tissues is imperative to improve current diagnostic, prognostic, and therapeutic modalities. Preclinical animal models have been invaluable for discovery of key immune processes, basic disease mechanisms, and candidate immune targeting strategies, but the conclusions have yet be reconciled with the essential features of the human disease.
The Importance and Utility of Cerebrospinal Fluid Evaluation in the Diagnosis of Central Demyelinating Diseases
Authors: Freedman Mark S. , Abdoli Mohammad
Published: April 2016

This chapter aims to highlight the diagnostic and prognostic value of cerebrospinal fluid (CSF) findings in multiple sclerosis with a special consideration of distinguishing it from neuromyelitis optica (NMO) and NMO spectrum disorder. Interpretation of CSF findings in daily clinical practice in patients with MS is thoroughly explained. New advances in CSF analysis and recently identified biomarkers may be helpful for diagnosis, help elucidate disease subtype and activity, or aid in prognosis and monitoring of the response to treatment. Characteristics of CSF changes in different subtypes of multiple sclerosis, clinically isolated syndrome (CIS), and radiologically isolated syndrome (RIS) are discussed. CSF findings in NMO spectrum disease as a diagnostic and differentiating marker are explained separately.
Outcome Measures in Multiple Sclerosis
Authors: Herndon Robert M.
Published: April 2016

This chapter discusses the challenges involved in measuring disease activity and progression in multiple sclerosis and how different aspects of the disease are measured in clinical trials. Metrics have been developed to assess multiple aspects of the disease., These include, in addition to more global instruments, measures of specific functions such as, cognition, mobility, quality of life, fatigue, and so on. These scales are discussed along with their strengths and weaknesses.
Cerebellar and Brainstem Dysfunction in Multiple Sclerosis
Authors: Mayadev Angeli S. , Kraft George H.
Published: April 2016

Brainstem and cerebellar plaques often result in some of the most disabling symptoms experienced by persons with multiple sclerosis, and may be among the most challenging to treat. The impairments resulting from these lesions may also be a significant source of secondary complications such as falls, aspiration, and poor nutrition. This chapter outlines the anatomical origin of dysfunction, clinical findings, and treatment options available to patients and providers. Medical, surgical, and rehabilitative methods for the treatment of tremors, ataxia, vertigo, dysphagia, dysarthria, dysphonia, trigeminal neuralgia, and facial nerve palsy are reviewed.
Assessment and Treatment of Sexual Dysfunction in Multiple Sclerosis
Authors: Foley Frederick W.
Published: April 2016

This chapter discusses the signs and symptoms of sexual dysfunction that are common in persons with multiple sclerosis. The epidemiology of sexual dysfunction in this patient population is presented, along with techniques and instruments for screening for sexual dysfunction. Definitions of primary, secondary, and tertiary sexual dysfunction are reviewed, and a detailed discussion of treatment strategies is presented, including pharmacologic agents, devices, and behavioral interventions.
Multiple Sclerosis and Pain
Authors: Namerow Norman S.
Published: April 2016

Pain is one of the most prevalent symptoms in persons with MS, and may also complicate other symptoms due to MS such as fatigue, impaired mobility and sleep disturbances. Thus, diagnosis and treatment of pain has become an increasingly important aspect in MS management. The epidemiology of pain in patients with multiple sclerosis is reviewed in this chapter, and a pain classification is presented. Pain syndromes are also reviewed, and appropriate treatments are described. Neuropathic pain in particular is discussed, including current views on the pathophysiology of pain production. An algorithm for medication use is presented that illustrates the utility of pharmacology with multiple agents in treating this condition.
Fatigue in Multiple Sclerosis
Authors: Bhise Vikram , Charvet Leigh , Krupp Lauren B.
Published: April 2016

Fatigue is the most frequent symptom in individuals with multiple sclerosis. Fatigue can be measured with self-report instruments, performance-based measures, or a combination of both. The pathophysiology of fatigue is complicated because it is both intrinsic to the disease and secondary to other disease-related factors. Fatigue has been linked to neuroimaging markers, findings on polysomnography, and experimental test measures of vigilance and attention. Treatment relies primarily on nonpharmacologic interventions including exercise programs, energy conservation, mindfulness, and cognitive behavioral therapy. Most clinical trials with medications have had mixed results. Current research work is focused on improved measurement approaches and innovative treatment strategies.
Multiple Sclerosis Nursing
Authors: Nygren Kirstin , Hartley Gail
Published: April 2016

At each point across the disease spectrum, the MS nurse plays a pivotal role in the symptom management and comprehensive care of patients with multiple sclerosis. Multiple sclerosis most often affects young adults in the prime of life, derailing and interrupting goals and plans for the future. Whereas a neurologist might look at the disease burden of the brain, the MS nurse looks at the burden on a patient’s life. This nursing approach enables the MS nurse to help patients adjust and adapt to changes and symptoms as disease progression occurs and to empower them to live with the highest quality of life possible. As patients adjust to major life changes or advancing levels of disability, MS nurses can offer support and instill a sense of hope. This support is also important in promoting empowerment and wellness for persons with MS.
Immunomodulatory Agents for Relapsing-Remitting Multiple Sclerosis
Authors: Robb Jessica F. , Samkoff Lawrence M.
Published: April 2016

The treatment of multiple sclerosis has become much more complicated with the development of new oral and other disease-modifying therapies (DMT) that have been added to the formulary of older injectables and natalizumab. To date, twelve medications have been approved in the United States for use in cases of relapsing multiple sclerosis. Neurologists managing patients with multiple sclerosis must integrate numerous variables when selecting the appropriate agent for each individual. This chapter presents an overview of the DMTs currently approved by the U.S. Food and Drug Administration for multiple sclerosis and suggests a therapeutic algorithm to aid in choosing among these medications.
Relapses, Immunosuppressive and Novel Therapies
Authors: Giesser Barbara S.
Published: April 2016

This chapter presents information about treatment of acute attacks of multiple sclerosis and identification of precipitating factors. Additionally, it includes a detailed discussion of immunosuppressive agents that are used (largely off label) as disease-modifying therapies and data that support their use. Many clinical trials are currently focused on testing agents for use in progressive disease as well as agents that may be neuroprotective or neurorestorative. Results of recent trials of several of these various new and experimental agents are also reviewed.
Basic Science in Multiple Sclerosis Research
Authors: Gilmore Wendy , Weiner Leslie P.
Published: April 2016

Through the lens of basic science, this chapter provides an overview of research in multiple sclerosis, with a focus on progress and promise in the study of neuropathological and immunological characteristics of the disease and the influence of genetics, environmental factors, and gender. The stage for discussion is set with consideration for the challenges presented by the complexity and heterogeneity inherent in multiple features of the disease. Key research questions are identified and discussed, along with the importance of contributions from advancements in technology and from animal models. The chapter seeks to illuminate the overall goals of basic research, which are to develop new insights into the causes, triggers, and mechanisms of disease activity in multiple sclerosis and to translate them into strategies to prevent, treat, and ultimately cure this enigmatic disease.
Design of the ICU
Authors: Halpern Neil A.
Published: April 2016

This chapter on intensive care unit (ICU) design looks at the ICU from three perspectives—concept to occupancy, the patient room, and supportive services, and advanced informatics. The design process is complex and time-consuming, and relies upon a design team composed of the main users, architects, and hospital administrative representatives; they must develop a vision for the new unit, which includes its purpose, bed number, staffing, workflow and healing environment. The team must then balance innovation with practicality, disparate technologies with standardization and timely purchase, and desires for the best of everything with physical, space, and fiscal limitations. The ICU patient room is the core of the ICU patient, family member, and staff experiences and should be similarly designed and equipped. Supportive spaces fully integrated with the patient rooms and hospital logistic areas and systems help optimize throughput. Informatics systems that electronically integrate the patient room with all aspects of care should be deployed to intelligently utilize and smartly present and display data, manage alarms, monitor the ICU environment, develop virtual device communities, provide real time locating systems, and address local or remote telemedicine requirements.
In-hospital transfer of the critically ill
Authors: Eyre Lorna , Whiteley Simon
Published: April 2016

While focus has traditionally been on the planning, logistics, and outcome of inter-hospital transfers of the critically-ill patient, attention is turning to in-hospital transfers. Numerically, more in-hospital transfers occur and there is growing evidence that these are associated with a high incidence of adverse events, and increased morbidity and mortality. Appropriate planning, communication, and preparation are essential. Patients should be resuscitated and stabilized (optimized) prior to transfer, to prevent deterioration or instability during transfer. Endotracheal tubes and vascular access devices should be secure. The minimum recommended standards of monitoring should be applied. All drugs and equipment likely to be required during the transfer should be checked and available. Critically-ill patients should be accompanied by personnel with the appropriate knowledge skills and experience to carry out the transfer safely and to deal with any complications or incidents that arise.
Pre- and inter-hospital transport of the critically ill and injured
Authors: Klein Kelly R. , Pepe Paul E.
Published: April 2016

Pre- and inter-hospital transport medicine has become a highly specialized branch of critical care and emergency medicine practices, and is an integral part of modern health care. It can have a significant impact on mortality and morbidity when used appropriately. However, it also poses very unique challenges involving extension of hospital resources into often unfamiliar and sometimes austere and hostile arenas in the out-of-hospital setting. The very nature of critical care also means that the patient is profoundly ill or injured, and needs intensive monitoring and treatment with limited secondary support and personnel in the limited space of an ambulance, helicopter, or fixed wing aircraft. Accordingly, to optimize safety and patient care under these circumstances, specific guidelines and strict regulations regarding critical care transport have been implemented. Protocols and policies need to be in place to ensure optimal care, and safety for both patients and transport crews with contingencies for unanticipated weather and altitude challenges, and should also address key issues.
Effective teamwork in the ICU
Authors: Brindley Peter G.
Published: April 2016

The Institute for Health Improvement argues that medical errors contribute to tens-of-thousands of deaths annually in the USA alone. Others have posited the need to make a ‘science of team performance’ and a ‘science of managing complexity’. Experts also believe that if our goal should be to maximize patient safety; thus we must tackle our ‘missing curriculum’ to minimize the disconnection between what should be and what is usual. Growing evidence shows that teamwork and communication is key to bridging these ‘care gaps’. This chapter outlines how critical care team skills (and ‘verbal dexterity’) can match procedural dexterity and factual know-how, using practical strategies from other high-stakes industries. Whether we think in team terms is a comment on medical culture. Regardless, given teamwork’s importance, it is time to argue that there really is no ‘I in ICU’!
Simulation training for critical care
Authors: Shippey Ben , Nimmo Graham
Published: April 2016

Simulation in various guises can be an extremely useful educational methodology. Its use should be planned carefully to maximize educational efficiency and minimize disruption to patient care. It requires the facilitator to enable the participants to behave as they would in the real clinical environment. Fidelity is one aspect of the simulated clinical environment that helps participants engage with the clinical material. The participants should be debriefed after the simulated experience. Video-assisted debriefing facilitates reflection on elements of behaviour that affect patient safety. Many styles of debriefing exist, but there are common elements. Debriefing should be carefully facilitated by faculty with the necessary skills. Simulation is increasingly being used as an assessment tool, but the validity of summative assessments using simulation is unclear.
Patient safety in the ICU
Authors: Winters Bradford D. , Pronovost Peter J.
Published: April 2016

While patient safety and quality have become a major focus of health care providers, policy makers, and customers over the last decade and a half, progress has been limited and wide quality gaps, where patient do not receive the care they should, remain. While technical improvements have gone a long way in these efforts, adaptive improvements in the culture of safety need to be more vigorously addressed. Likewise, quality metrics and a scientific approach to patient safety is necessary to ensure that interventions actually work. The Comprehensive Unit Safety Program (CUSP) strategy and its embedded Learning from Defects (LFD) process are central to creating a sustainable improvement in the culture of patient safety and quality, and in real outcomes and process improvements. CUSP is a bottom-up approach that relies on the wisdom and efforts of front-line providers who best know the safety issues in their immediate environment. The LFD process seeks to translate evidence into practice (TRiP model) building interventions and tools to improve safety and close the quality gap. The development of these interventions and tools are guided by the principles of safe design and the application of the four E’s (engagement, education, execution, and evaluation) can be successfully implemented into the health care environment with substantial improvements in safety and quality.
Policies, bundles, and protocols in critical care
Authors: Mazer Jeffrey , Levy Mitchell M.
Published: April 2016

Recently, the medicine community has been driven to think about patient safety in new ways, and with this new found interest in patient safety, large health care systems and individual institutions have been forced to develop mechanisms to track and measure performance. There is ample evidence that physicians and systems can do better. The tools of this new craft include checklists, protocols, guidelines, and bundles. These tools help to decrease variability in care and enhance the translation of evidence-based medicine to bedside care. Ongoing measurement of both performance and clinical outcomes is central to this movement. This allows for rapid detection of both successes and possible unintended consequences associated with the rapid translation of evidence into practice. As hospitals and intensive care units (ICU) worldwide have embraced the field of quality improvement (QI), many lessons have been learned about the process. QI includes four essential phases—development, implementation, evaluation, and maintenance. Essential to the QI process and each of these QI phases is that the project must be tailored to each individual ICU and/or Institution. A one-size-fits-all project is less efficient, less effective, and at times unnecessary compare with a locally-driven process.
ICU admission and discharge criteria
Authors: Bion Julian , Dennis Anna
Published: April 2016

The decision to admit patients to intensive care or discharge them, is a daily task for intensivists, a life-changing event for patients and families, and a major strategic issue for health care systems worldwide. Decisions must often be made rapidly, in conditions of uncertainty, involving substituted judgements about relative risks and benefits, framed by sociocultural factors that are not well characterized. The outcomes are strongly influenced by available resources, staffing, and skills throughout the patient pathway. The decision to admit should be based on the severity of illness, chronic health and physiological reserve, and therapeutic susceptibility, informed by the patient’s wishes. Discharge decisions are equally complex and involve balancing the needs of individual patients against those of society. Scoring systems and guidelines can aid decision making. The process involves collaboration between intensivist, referring team, patient, and family. The provision of futile care is usually driven by family expectations and lack of agreement among the treating team. Discussions involve value judgements. Effective admission and discharge processes will minimize avoidable morbidity, mortality, and readmissions, and maximize family and patient satisfaction, and cost-efficacy. However, reaching the most effective level of practice involves balances and compromises. Experienced clinical judgement remains a key element in defining suitability of individual patients for ICU admission and discharge.
Resource management and budgeting in critical care
Authors: Takala Jukka
Published: April 2016

Resource management is a core task for intensive care unit (ICU) leadership. Budgeting covers optimizing resource use, planning for future needs, and continuous monitoring of actual resource use. Short-term budgeting is operational planning, whereas mid- and long-term budgeting should focus on strategy. Resource management is an integral and continuous part of the ICU management process. Hence, the regional and local availability of health care services rarely depends on rational or objective factors alone. For budgeting purposes, the needs for intensive care for the population of the main referral area of the hospital, the actual structure of the local health care system and probable changes during the strategic planning period should be considered. The resources needed for emergency admissions is relatively constant as long as the referral population the indications for intensive care and the treatments offered do not change. The ICU is part of a multidisciplinary, horizontal care process. The amount and level of care provided in all the participating units must be considered.
Evidence-based practice in critical care
Authors: Terblanche Marius , Scales Damon C.
Published: April 2016

Evidence-based practice (EBP) is the integration of the best available evidence with clinical expertise to make decisions about the care of individual patients. This chapter explains how EBP can benefit patients by introducing new treatments, reducing the harm associated with necessary treatments, and questioning the continued use of ineffective or harmful therapies. To practice EBP, clinicians should become acquainted with techniques, and stay up-to-date with current and new publications, and research findings. When high quality evidence is unavailable to answer specific clinical questions, practitioners of EBP still rely on clinical judgment and expertise to decide upon the best treatment strategies for their patients. However, they should be wary of the potential harms of unproven therapies. The controversy that has accompanied the adoption of EBP is discussed, including debate about potential limitations and unintended consequences. Suggestions on how to implement EBP into your own practice are provided.
Medico-legal liability in critical care
Authors: Rie Michael A.
Published: April 2016

The Oxford Textbook of Critical Care is an English language international text that recognizes the English Common Law as the foundation of contemporary judicial precedents governing obligations and responsibilities within the patient–doctor relationship. Although medical ethics and their recognition are generally known, Common Law interpretation of resource consumption and entitlement limits to critical care services has varied widely. Case examples of enduring professional negligence are offered. While legal systems may have differing origins, the imbalance between resource allocation and lawful definition of entitlement limitations requires further clarity within the law. Preserving professional integrity requires active public education and professional group dialogue with governments and the courts. Such patient advocacy will both preserve the rule of law and patient trust in all critical care professionals.
Anti-anginal agents in critical illness
Authors: Suri Ajay , McEwan Jean R.
Published: April 2016

Angina is chest pain resulting from the lack of blood supply to heart muscle most commonly due to obstructive atherosclerotic. Intensive care unit patients are subject to various stresses that will increase the demand on the heart and are in a pro-thrombotic state. Patients in an intensive treatment unit may be sedated and so cardiac ischaemia may be detected by electrocardiogram, haemodynamic monitoring, and echocardiographic imaging of function. These signs may indicate critical coronary perfusion heralding a myocardial infarction and are alleviated by anti-anginal drugs. Beta-blockers and calcium channel blockers are the usual first-line treatments for angina, but may not be ideal in the critically-ill patient. Nitrates reduce blood pressure without typically affecting heart rate. Nicorandil is a similar mechanism of action and tends to be given orally, while ivabridine, an If channel blocker, is a newer anti-anginal, which acts by reducing heart rate, while not affecting blood pressure. Ranolazine is the one of the newest anti-anginal agents and is believed to alter the transcellular late sodium current thereby decreasing sodium entry into ischaemic myocardial cells.
Anti-arrhythmics in critical illness
Authors: LeMaitre John , Kornder Jan
Published: April 2016

Anti-arrhythmic drugs (AADs) are an important component of the pharmacological arsenal used in the management of the critically-ill patient. The benefits of AADs, as well as their potential disadvantageous side effects, largely depend on their effects upon the cardiac action potential. AADs can be broadly grouped according to their cellular actions, upon which their clinical effects depend. However, there is substantial cross-over amongst the groups in terms of these actions and efficacy for particular arrhythmias, and also for side effects. Amiodarone exhibits a broad spectrum of antiarrhythmic activity and is often the most useful AAD for the critically-ill patient where short-term use reduces concerns relating to toxic side effects associated with chronic administration. However, each of the other available AADs have their uses for particular scenarios in the critically-ill patient, although attention needs to be paid to comorbidities to attenuate the risk of adverse response. AADs are pro-arryhthmic in 5-10% of patients with potential lethal consequences, and the use of AADs in the critically-ill patient should be considered very carefully as correction of the underlying substrate may be sufficient in some circumstances to resolve the index arryhthmia.
Gastrointestinal motility drugs in critical illness
Authors: Fruhwald Sonja , Holzer Peter
Published: April 2016

Gastrointestinal motility disturbances in critically-ill patients often require treatment with prokinetic drugs. The aetiology of motility disturbances is complex, and involves electrolyte imbalances, hypervolaemia, reduced intestinal secretion, adverse effects of drugs (catecholamines, opioids, or sedatives) and disease- or treatment-related changes of microflora. However, the choice of prokinetics is narrow, and the multiplicity of pathophysiological mechanisms often limits their efficacy. Gastroparesis can be managed with gastrokinetics such as domperidone, metoclopramide and erythromycin. Their choice depends not only on efficacy, but also on adverse effect profile. The arrhythmogenic potential of domperidone limits maximum daily dose and treatment duration. Metoclopramide and erythromycin induce tachyphylaxis, which restricts treatment duration. The combination of metoclopramide and erythromycin serves as rescue therapy in severe gastroparesis. Neostigmine and laxatives are used to manage colonic paralysis, and these treatment options may eventually be extended by drug candidates, such as prucalopride, lubiprostone, and linaclotide, whose utility in the ICU awaits to be evaluated. Neostigmine’s prokinetic efficacy in colonic paralysis is limited, but well documented in patients with acute colonic pseudo-obstruction (Ogilvie syndrome). Care is advocated in dosing because higher doses of neostigmine inhibit motility. Alternative options include osmotic and stimulant laxatives, especially for prophylactic use. The opioid receptor antagonist alvimopan is used for the short-term management of post-operative ileus, while methylnaltrexone is indicated in palliative care and chronic pain management. Since its efficacy in critically-ill patients remains to be proven, the use of methylnaltrexone in the ICU is off-label and requires proper documentation.
Stress ulcer prophylaxis and treatment drugs in critical illness
Authors: Alhazzani Waleed , Cook Deborah J.
Published: April 2016

Many changes have occurred over the last three decades in the field of stress ulcer gastrointestinal bleeding and its prevention. The topic is controversial, fuelled by disparate data, studies at risk of bias, and the impression that the problem is not as serious as it once was. Indeed, compared with over four decades ago when mucosal ulceration of the stomach causing serious bleeding was first described, a relatively small proportion of critically-ill patients now develop clinically important bleeding. Acid suppression is commonly prescribed for stress ulcer prophylaxis (SUP), targeting subgroups of patients at high risk in the intensive care unit (ICU), rather than universal prevention. The randomized clinical trials to date suggest a significant reduction in CIB with use of histamine-2-receptor antagonists (H2RAs) compared with no SUP, with no impact on pneumonia, ICU mortality, or length of stay. However, these trials are of moderate quality. More recent RCTs suggest proton pump inhibitors compared with H2RAs may significantly reduce the risk of CIB without influencing the risk of pneumonia, ICU mortality, or length of stay. These trials are also of moderate quality. Today, the decision whether to use SUP, and which agent to use, is complex. Clinical considerations include local epidemiological data (for centres documenting these outcomes), and patient-specific risks of gastrointestinal bleeding and infection, indexed to case mix.