bluuebunny/crossref_metadata_2025 huggingface dataset:
Comment on “Classification of Lie point symmetries for quadratic Liénard type equation ẍ+f(x)ẋ2+g(x)=” [J. Math. Phys. 54, 053506 (2013)] and its erratum [J. Math. Phys. 55, 059901 (2014)]
Authors: Paliathanasis A. , Leach P. G. L.
Published: January 2016

We demonstrate a simplification of some recent works on the classification of the Lie symmetries for a quadratic equation of Liénard type. We observe that the problem could have been resolved more simply.
Experimental evidence of zone-center optical phonon softening by accumulating holes in thin Ge
Authors: Kabuyanagi Shoichi , Nishimura Tomonori , Yajima Takeaki , Toriumi Akira
Published: January 2016

We discuss the impact of free carriers on the zone-center optical phonon frequency in germanium (Ge). By taking advantage of the Ge-on-insulator structure, we measured the Raman spectroscopy by applying back-gate bias. Phonon softening by accumulating holes in Ge film was clearly observed. This fact strongly suggests that the phonon softening in heavily-doped Ge is mainly attributed to the free carrier effect rather than the dopant atom counterpart. Furthermore, we propose that the free carrier effect on phonon softening is simply understandable from the viewpoint of covalent bonding modification by free carriers.
Clean localization super-resolution microscopy for 3D biological imaging
Authors: Mondal Partha P. , Curthoys Nikki M. , Hess Samuel T.
Published: January 2016

We propose clean localization microscopy (a variant of fPALM) using a molecule filtering technique. Localization imaging involves acquiring a large number of images containing single molecule signatures followed by one-to-one mapping to render a super-resolution image. In principle, this process can be repeated for other z-planes to construct a 3D image. But, single molecules observed from off-focal planes result in false representation of their presence in the focal plane, resulting in incorrect quantification and analysis. We overcome this with a single molecule filtering technique that imposes constraints on the diffraction limited spot size of single molecules in the image plane. Calibration with sub-diffraction size beads puts a natural cutoff on the actual diffraction-limited size of single molecules in the focal plane. This helps in distinguishing beads present in the focal plane from those in the off-focal planes thereby providing an estimate of the single molecules in the focal plane. We study the distribution of actin (labeled with a photoactivatable CAGE 552 dye) in NIH 3T3 mouse fibroblast cells.
Becoming a clinician researcher in allied health
Authors: Harvey Desley , Plummer David , Nielsen Ilsa , Adams Robyn , Pain Tilley
Published: January 2016

Objective
Combining research with clinical practice has benefits for health services and practitioners. There is limited information available on strategies used by health professionals to balance research with high clinical service demands. The aims of the present study were to examine how research is initiated and to identify the factors that influence the successful integration of research into a clinical work role.

Methods
Semistructured recursive-style interviews were conducted with 15 research-active allied health professionals at regional health services using a combination of criterion and purposive sampling. Interviews were recorded, transcribed and analysed using constant comparative techniques to identify dominant themes, which were integrated to create a conceptual model.

Results
Becoming a clinician researcher involved four phases: (1) a research debut; (2) building momentum; (3) developing a track record; and (4) becoming an established clinician researcher. A research debut was enabled by pre-entry exposure to research or through quality activities, predisposing personal characteristics and research opportunities at work. Quarantined time for research, a research-friendly workplace culture and supportive research relationships enabled a clinician to thrive as a researcher despite the challenges.

Conclusion
The clinician researcher career trajectory contributes to a better understanding of how a research career commences and develops in clinical settings. It may assist to develop strategies to support research capacity building.

What is known about the topic?
There are potential benefits for clinicians and health services that flow from incorporating research into clinical roles. Factors that motivate, enable and constrain allied health research in clinical settings have been identified, but little is known about how a research career is initiated and progresses over time.

What does this paper add?
The present study contributes an important career path understanding to the successful development of research capacity from a clinician perspective. The clinician researcher career trajectory delineates four phases and identifies enabling and constraining factors. The study highlights the combination of factors that can initiate a research debut and lead clinicians to thrive as researchers.

What are the implications for practitioners?
Conducting research can provide an opportunity for a professional challenge and increased job satisfaction. A research-friendly environment, supportive research relationships and quarantined time for research contribute to research output in clinical settings.
Self-Assembly of Square-Planar Halide Complexes of Trimethylphosphine-Stabilized Diphenyl-Arsenium, -Stibenium, and -Bismuthenium Hexafluorophosphates
Authors: Wielandt J. Wolfram , Petrie Simon , Kilah Nathan L. , Willis Anthony C. , Dewhurst Rian D. , Belaj Ferdinand , Orthaber Andreas , Stranger Robert , Wild S. Bruce
Published: January 2016

Square-planar halide complexes in which four trimethylphosphine-stabilized diphenyl-stibenium or -bismuthenium ions surround a central halide ion in discrete centrosymmetrical structures of C4h symmetry have been isolated and their structures determined by X-ray crystallography. The structures are stabilized by electrostatic interactions between the halide ion and four positively charged trimethylphosphine-stabilized diphenyl-stibenium or -bismuthenium ions, as well as four edge-to-face phenyl–phenyl embraces above and below the plane containing the nine main group elements. The parent halide-free trimethylphosphine-stabilized diphenyl-arsenium, -stibenium, and -bismuthenium hexaflurophosphate complexes have also been prepared and structurally characterized.
Modelling and quantifying the spatial distribution of post-wildfire ash loads
Authors: Chafer Chris J. , Santín Cristina , Doerr Stefan H.
Published: January 2016

Ash is generated in every wildfire, but its eco-hydro-geomorphic effects remain poorly understood and quantified, especially at large spatial scales. Here we present a new method that allows modelling the spatial distribution of ash loads in the post-fire landscape, based on a severe wildfire that burnt ~13 600 ha of a forested water supply catchment in October 2013 (2013 Hall Road Fire, 100 km south-west of Sydney, Australia). Employing an existing spectral ratio-based index, we developed a new spectral index using Landsat 8 satellite imagery: the normalised wildfire ash index (NWAI). Before- and after-fire images were normalised and a differenced wildfire ash image (dNWAI) computed. The relationship between dNWAI and ash loads (t ha−1) quantified in situ at nine sampling locations burnt under a range of fire severities was determined using a polynomial regression (R2 = 0.98). A spatially applied model was computed within a geographic information system (GIS) to illustrate the spatial distribution of ash across the area burnt and to estimate ash loads in the five subcatchments affected by the wildfire. Approximately 181 000 tonnes of ash was produced by the wildfire, with specific loads increasing with fire severity. This new tool to model wildfire ash distribution can inform decisions about post-fire land management in future wildfires in the region. It can also be adapted for its application in other fire-prone environments.
Ground penetrating radar as a non-invasive tool to better understand the population dynamics of a fossorial species: mapping the warrens of southern hairy-nosed wombats (Lasiorhinus latifrons)
Authors: Swinbourne Michael J. , Taggart David A. , Sparrow Elisa , Hatch Michael , Ostendorf Bertram
Published: January 2016

Context
Management of wildlife that may simultaneously be of conservation concern and pose problems for humans is difficult, particularly when knowledge of their population dynamics is elusive. Culling of southern hairy-nosed wombats (Lasiorhinus latifrons) is often carried out in agricultural areas, with no understanding of potential impacts on the species as a whole. Monitoring fossorial species via non-invasive means (that do not adversely impact animals by damaging their burrows) has always represented a challenge for wildlife researchers.

Aim
The aim of this research was to map the areal extent of different types of L. latifrons warrens to gain a better understanding of the relationship between the external warren signs and its subterranean structure. The findings will be used in the development of more accurate indices of population abundance to better inform management decisions.

Methods
Ground penetrating radar (GPR) was used to map warrens at four locations in the western regions of South Australia. Radar data were collected using a Mala X3M GPR system with 250 MHz and 500 MHZ antennas. 3D models of each site were then produced using the ReflexW GPR software processing package.

Key results
Subterranean warren structure varied from a mix of tunnel types in sandy-loam soil to a complex array of tunnels and caverns under sheet calcrete limestone.

Conclusions
This was the first non-invasive mapping of wombat warrens and the first mapping of a warren under a layer of calcrete limestone. In sandy-loam soil, the size and extent of the external spoil mound provided some indication of warren complexity. However, there were no external signs of the extent of the calcrete warren.

Implications
The lack of external cues regarding the extent of the calcrete limestone warren suggests that the current method of estimating population abundance based on a single index of wombats per active burrow is flawed. As a result, any management decisions in regard to culling may be based on inaccurate information. It is apparent that further research needs to be undertaken to develop a range of abundance indices that take into account local conditions such as soil type.
Determinants of translation ambiguity
Authors: Degani Tamar , Prior Anat , Eddington Chelsea M. , Arêas da Luz Fontes Ana B. , Tokowicz Natasha
Published: January 2016

Ambiguity in translation is highly prevalent, and has consequences for second-language learning and for bilingual lexical processing. To better understand this phenomenon, the current study compared the determinants of translation ambiguity across four sets of translation norms from English to Spanish, Dutch, German and Hebrew. The number of translations an English word received was correlated across these different languages, and was also correlated with the number of senses the word has in English, demonstrating that translation ambiguity is partially determined by within-language semantic ambiguity. For semantically-ambiguous English words, the probability of the different translations in Spanish and Hebrew was predicted by the meaning-dominance structure in English, beyond the influence of other lexical and semantic factors, for bilinguals translating from their L1, and translating from their L2. These findings are consistent with models postulating direct access to meaning from L2 words for moderately-proficient bilinguals.
International Law
Authors: Lowe Vaughan
Published: January 2016

Celebrated for their conceptual clarity, titles in the Clarendon Law Series offer concise, accessible overviews of major fields of law and legal thought. International Law is both an introduction to the subject and a critical consideration of its central themes and debates. The opening chapters of the volume explain how international law underpins the international political and economic system by establishing the basic principle of the independence of States, and their right to choose their own political, economic, and cultural systems. Subsequent chapters then focus on considerations that limit national freedom of choice (e.g. human rights, the interconnected global economy, the environment). Through the organizing concepts of territory, sovereignty, and jurisdiction the text shows how international law seeks to achieve an established set of principles according to which the power to make and enforce policies is distributed among States.
Bromley's Family Law
Authors: Lowe Nigel , Douglas Gillian
Published: January 2016

Bromley's Family Law provides an accurate, detailed account of family law. The text presents a broad treatment of the key issues relating to adult and child law. This new edition has been edited and updated to take account of the latest case law and legislation, while also reflecting new debates and emerging issues in the area. Particular attention is also paid to the increasingly significant international dimension of family law, with a new chapter on this area. This edition has been updated to provide up-to-date coverage on cohabitation, the Marriage (Same Sex Couples) Act 2013 and Children and Families Act 2014. It also examines the proposals of the Family Justice Review. It considers in detail the Law Commission proposals for reform of the law on cohabitation, marital property agreements and needs, and non-matrimonial property on divorce.
An exploratory study using an openEHR 2-level modeling approach to represent common data elements
Authors: Lin Ching-Heng , Fann Yang-Cheng , Liou Der-Ming
Published: January 2016

Background and Objective In order to facilitate clinical research across multiple institutions, data harmonization is a critical requirement. Common data elements (CDEs) collect data uniformly, allowing data interoperability between research studies. However, structural limitations have hindered the application of CDEs. An advanced modeling structure is needed to rectify such limitations. The openEHR 2-level modeling approach has been widely implemented in the medical informatics domain. The aim of our study is to explore the feasibility of applying an openEHR approach to model the CDE concept.

Materials and Methods Using the National Institute of Neurological Disorders and Stroke General CDEs as material, we developed a semiautomatic mapping tool to assist domain experts mapping CDEs to existing openEHR archetypes in order to evaluate their coverage and to allow further analysis. In addition, we modeled a set of CDEs using the openEHR approach to evaluate the ability of archetypes to structurally represent any type of CDE content.

Results Among 184 CDEs, 28% (51) of the archetypes could be directly used to represent CDEs, while 53% (98) of the archetypes required further development (extension or specialization). A comprehensive comparison between CDEs and openEHR archetypes was conducted based on the lessons learnt from the practical modeling.

Discussion CDEs and archetypes have dissimilar modeling approaches, but the data structure of both models are essentially similar. This study proposes to develop a comprehensive structure to model CDE concepts instead of improving the structure of CED.

Conclusion The findings from this research show that the openEHR archetype has structural coverage for the CDEs, namely the openEHR archetype is able to represent the CDEs and meet the functional expectations of the CDEs. This work can be used as a reference when improving CDE structure using an advanced modeling approach.
Self-monitoring practices, attitudes, and needs of individuals with bipolar disorder: implications for the design of technologies to manage mental health
Authors: Murnane Elizabeth L , Cosley Dan , Chang Pamara , Guha Shion , Frank Ellen , Gay Geri , Matthews Mark
Published: January 2016

Objective To understand self-monitoring strategies used independently of clinical treatment by individuals with bipolar disorder (BD), in order to recommend technology design principles to support mental health management.

Materials and Methods Participants with BD (N = 552) were recruited through the Depression and Bipolar Support Alliance, the International Bipolar Foundation, and WeSearchTogether.org to complete a survey of closed- and open-ended questions. In this study, we focus on descriptive results and qualitative analyses.

Results Individuals reported primarily self-monitoring items related to their bipolar disorder (mood, sleep, finances, exercise, and social interactions), with an increasing trend towards the use of digital tracking methods observed. Most participants reported having positive experiences with technology-based tracking because it enables self-reflection and agency regarding health management and also enhances lines of communication with treatment teams. Reported challenges stem from poor usability or difficulty interpreting self-tracked data.

Discussion Two major implications for technology-based self-monitoring emerged from our results. First, technologies can be designed to be more condition-oriented, intuitive, and proactive. Second, more automated forms of digital symptom tracking and intervention are desired, and our results suggest the feasibility of detecting and predicting emotional states from patterns of technology usage. However, we also uncovered tension points, namely that technology designed to support mental health can also be a disruptor.

Conclusion This study provides increased understanding of self-monitoring practices, attitudes, and needs of individuals with bipolar disorder. This knowledge bears implications for clinical researchers and practitioners seeking insight into how individuals independently self-manage their condition as well as for researchers designing monitoring technologies to support mental health management.
Using the electronic health record for assessment of health insurance in community health centers
Authors: Hatch Brigit , Tillotson Carrie , Angier Heather , Marino Miguel , Hoopes Megan , Huguet Nathalie , DeVoe Jennifer
Published: January 2016

Objective To demonstrate use of the electronic health record (EHR) for health insurance surveillance and identify factors associated with lack of coverage.

Materials and Methods Using EHR data, we conducted a retrospective, longitudinal cohort study of adult patients ( n  = 279 654) within a national network of community health centers during a 2-year period (2012–2013).

Results Factors associated with higher odds of being uninsured (vs Medicaid-insured) included: male gender, age >25 years, Hispanic ethnicity, income above the federal poverty level, and rural residence ( P  < .01 for all). Among patients with no insurance at their initial visit ( n  = 114 000), 50% remained uninsured for every subsequent visit.

Discussion During the 2 years prior to 2014, many patients utilizing community health centers were unable to maintain stable health insurance coverage.

Conclusion As patients gain access to health insurance under the Affordable Care Act, the EHR provides a novel approach to help track coverage and support vulnerable patients in gaining and maintaining coverage.
Satellite accretion in action: a tidally disrupting dwarf spheroidal around the nearby spiral galaxy NGC 253
Authors: Romanowsky Aaron J. , Martínez-Delgado David , Martin Nicolas F. , Morales Gustavo , Jennings Zachary G. , GaBany R. Jay , Brodie Jean P. , Grebel Eva K. , Schedler Johannes , Sidonio Michael
Published: January 2016

We report the discovery of NGC 253-dw2, a dwarf spheroidal (dSph) galaxy candidate undergoing tidal disruption around a nearby spiral galaxy, NGC 253 in the Sculptor group: the first such event identified beyond the Local Group. The dwarf was found using small-aperture amateur telescopes, and followed up with Suprime-Cam on the 8 m Subaru Telescope in order to resolve its brightest stars. Using g- and Rc-band photometry, we detect a red giant branch consistent with an old, metal-poor stellar population at a distance of ∼3.5 Mpc. From the distribution of likely member stars, we infer a highly elongated shape with a semimajor axis half-light radius of (2 ± 0.4) kpc. Star counts also yield a luminosity estimate of ∼2 × 106 L⊙,V (MV ∼ −10.7). The morphological properties of NGC 253-dw2 mark it as distinct from normal dSphs and imply ongoing disruption at a projected distance of ∼50 kpc from the main galaxy. Our observations support the hierarchical paradigm wherein massive galaxies continuously accrete less massive ones, and provide a new case study for dSph infall and dissolution dynamics. We also note the continued efficacy of small telescopes for making big discoveries.
Mitochondrial DNA
Authors: Schäfer Simon T. , Franken Lars , Adamzik Michael , Schumak Beatrix , Scherag André , Engler Andrea , Schönborn Niels , Walden Jennifer , Koch Susanne , Baba Hideo A. , Steinmann Jörg , Westendorf Astrid M. , Fandrey Joachim , Bieber Thomas , Kurts Christian , Frede Stilla , Peters Jürgen , Limmer Andreas
Published: January 2016

AbstractAbstract

Mitochondrial DNA (mtDNA) serum concentrations of the mitochondrial genes D-Loop and adenosine triphosphatase 6 were determined (quantitative polymerase chain reaction) in 165 septic patients and 50 healthy volunteers. Furthermore, cytotoxic T-cell activity was analyzed in wild-type and TLR9 knockout mice, with/without previous mtDNA administration, followed by injection of an ovalbumin-expressing adenoviral vector. It was found that mtDNA concentration is increased in sepsis and, besides inflammatory effects, has powerful immunosuppressive effects and can evoke immunosuppression on its own.

Background

Critically ill patients are at high risk to suffer from sepsis, even in the absence of an initial infectious source, but the molecular mechanisms for their increased sepsis susceptibility, including a suppressed immune system, remain unclear. Although microbes and pathogen-associated molecular pattern are accepted inducers of sepsis and septic immunosuppression, the role of endogenous Toll-like receptor (TLR) ligands, such as mitochondrial DNA (mtDNA), in altering the immune response is unknown.

Methods

Mitochondrial DNA serum concentrations of the mitochondrial genes D-Loop and adenosine triphosphatase 6 were determined (quantitative polymerase chain reaction) in 165 septic patients and 50 healthy volunteers. Furthermore, cytotoxic T-cell activity was analyzed in wild-type and TLR9 knockout mice, with/without previous mtDNA administration, followed by injection of an ovalbumin-expressing adenoviral vector.

Results

Mitochondrial DNA serum concentrations were increased in septic patients (adenosine triphosphatase 6, 123-fold; D-Loop, 76-fold, P < 0.0001) compared with volunteers. Furthermore, a single mtDNA injection caused profound, TLR9-dependent immunosuppression of adaptive T-cell cytotoxicity in wild-type but not in TLR9 knockout mice and evoked various immunosuppressive mechanisms including the destruction of the splenic microstructure, deletion of cross-presenting dendritic cells, and up-regulation of programmed cell death ligand 1 and indoleamine 2,3-dioxygenase. Several of these findings in mice were mirrored in septic patients, and mtDNA concentrations were associated with an increased 30-day mortality.

Conclusions

The findings of this study imply that mtDNA, an endogenous danger associated molecular pattern, is a hitherto unknown inducer of septic immunoparalysis and one possible link between initial inflammation and subsequent immunosuppression in critically ill patients.
Resolvin D1 Inhibits Mechanical Hypersensitivity in Sciatica by Modulating the Expression of Nuclear Factor-κB, Phospho-extracellular Signal–regulated Kinase, and Pro- and Antiinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion
Authors: Liu Zhi-hua , Miao Gui-shen , Wang Jun-nan , Yang Cong-xian , Fu Zhi-jian , Sun Tao
Published: January 2016

AbstractAbstract

Nucleus pulposus induced a significant inflammatory response in dorsal root ganglia. Resolvin significantly suppressed this inflammatory response and reduced mechanical allodynia for up to 3 weeks. The data suggest that resolvins might serve as novel therapeutic agents for the treatment of neuropathic pain.

Background

Accumulating evidence indicates that spinal inflammatory and immune responses play an important role in the process of radicular pain caused by intervertebral disk herniation. Resolvin D1 (RvD1) has been shown to have potent antiinflammatory and antinociceptive effects. The current study was undertaken to investigate the analgesic effect of RvD1 and its underlying mechanism in rat models of noncompressive lumbar disk herniation.

Methods

Rat models of noncompressive lumber disk herniation were established, and mechanical thresholds were evaluated using the von Frey test during an observation period of 21 days (n = 8/group). Intrathecal injection of vehicle or RvD1 (10 or 100 ng) was performed for three successive postoperative days. On day 7, the ipsilateral spinal dorsal horns and L5 dorsal root ganglions (DRGs) were removed to assess the expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-10, and transforming growth factor-β1 (TGF-β1) and the activation of nuclear factor-κB (NF-κB)/p65 and phospho-extracellular signal–regulated kinase (p-ERK) signaling (n = 30/group).

Results

The application of nucleus pulposus to L5 DRG induced prolonged mechanical allodynia, inhibited the production of IL-10 and TGF-β1, and up-regulated the expression of TNF-α, IL-1β, NF-κB/p65, and p-ERK in the spinal dorsal horns and DRGs. Intrathecal injection of RvD1 showed a potent analgesic effect, inhibited the up-regulation of TNF-α and IL-1β, increased the release of IL-10 and TGF-β1, and attenuated the expression of NF-κB/p65 and p-ERK in a dose-dependent manner.

Conclusions

The current study showed that RvD1 might alleviate neuropathic pain via regulating inflammatory mediators and NF-κB/p65 and p-ERK pathways. Its antiinflammatory and proresolution properties may offer novel therapeutic approaches for the management of neuropathic pain.
Perioperative Opioids and Public Health
Authors: Kharasch Evan D. , Brunt L. Michael
Published: January 2016

Prescription opioid diversion, abuse, addiction, and overdose are epidemic. Although unclear whether postoperative opioid prescribing is contributory, or how anesthesiologists and surgeons can contribute to a solution, nonetheless awareness and a research agenda are needed.
Propofol-induced Inhibition of Catecholamine Release Is Reversed by Maintaining Calcium Influx
Authors: Han Liping , Fuqua Stephen , Li Quanlin , Zhu Liyu , Hao Xiaoyan , Li Aiping , Gupta Sangeeta , Sandhu Ravinder , Lonart György , Sugita Shuzo
Published: January 2016

AbstractAbstract

Clinically relevant concentrations of propofol (10 to 30 μM) indeed inhibited the depolarization (by K+)-dependent norepinephrine release in cultured PC12 cells (which are derived from rat adrenal chromaffin cells) and synaptosomes. Unexpectedly, the same propofol concentrations that inhibited depolarization-dependent norepinephrine release increased ionomycin (a Ca2+ ionophore)-triggered catecholamine release in a Ca2+-dependent manner. The Ca2+-dependent propofol-induced increase in ionomycin-triggered catecholamine release was abolished in the presence of the Ca2+ chelator, EGTA.

Background

Propofol (2,6-diisopropylphenol) is one of the most frequently used anesthetic agents. One of the main side effects of propofol is to reduce blood pressure, which is thought to occur by inhibiting the release of catecholamines from sympathetic neurons. Here, the authors hypothesized that propofol-induced hypotension is not simply the result of suppression of the release mechanisms for catecholamines.

Methods

The authors simultaneously compared the effects of propofol on the release of norepinephrine triggered by high K+-induced depolarization, as well as ionomycin, by using neuroendocrine PC12 cells and synaptosomes. Ionomycin, a Ca2+ ionophore, directly induces Ca2+ influx, thus bypassing the effect of ion channel modulation by propofol.

Results

Propofol decreased depolarization (high K+)-triggered norepinephrine release, whereas it increased ionomycin-triggered release from both PC12 cells and synaptosomes. The propofol (30 μM)-induced increase in norepinephrine release triggered by ionomycin was dependent on both the presence and the concentration of extracellular Ca2+ (0.3 to 10 mM; n = 6). The enhancement of norepinephrine release by propofol was observed in all tested concentrations of ionomycin (0.1 to 5 μM; n = 6).

Conclusions

Propofol at clinically relevant concentrations promotes the catecholamine release as long as Ca2+ influx is supported. This unexpected finding will allow for a better understanding in preventing propofol-induced hypotension.
Classically Activated Macrophages Protect against Lipopolysaccharide-induced Acute Lung Injury by Expressing Amphiregulin in Mice
Authors: Xu Younian , Meng Chen , Liu Guilin , Yang Dong , Fu Lisha , Zhang Min , Zhang Zhao , Xia Huimin , Yao Shanglong , Zhang Shihai
Published: January 2016

AbstractAbstract

Amphiregulin was expressed in alveolar macrophages after acute lung injury. Exogenous amphiregulin protected, whereas amphiregulin antibodies exacerbated lung injury. The results are consistent with the notion up-regulation of amphiregulin in activated alveolar macrophages can exert a protective effect on the lung tissue in a model of acute lung injury.

Supplemental Digital Content is available in the text.

Background

Alveolar macrophages (AMs) activated into M1 phenotype are involved in the development of lipopolysaccharide-induced acute lung injury (ALI). However, whether AMs express amphiregulin and what roles amphiregulin plays in lipopolysaccharide-induced ALI remain poorly understood.

Methods

Acute lung injury was induced by intratracheal instillation of lipopolysaccharide in male C57BL/6 mice. Lung injury scores, level of protein, and level of neutrophils in bronchial alveolar lavage fluid of lipopolysaccharide-induced ALI mice were compared with those in mice challenged with recombinant exogenous amphiregulin and antiamphiregulin antibody. Amphiregulin expression in macrophages and neutrophils in bronchial alveolar lavage fluid of lipopolysaccharide-induced ALI mice was determined by using immunofluorescence technique and further detected in M0, M1, and M2 phenotypes of both peritoneal macrophages and AMs. The effect of amphiregulin on apoptosis of MLE12 cells and activation of epithelial growth factor receptor-AKT pathway were, respectively, examined by using flow cytometry and western blotting.

Results

Alveolar macrophages were found to highly express amphiregulin in ALI mice. Amphiregulin neutralization aggravated, whereas recombinant exogenous amphiregulin attenuated lipopolysaccharide-induced ALI in mice (n = 6). In cultured AMs and peritoneal macrophages, amphiregulin was mainly generated by M1, rather than M0 or M2 phenotype (n = 5). Apoptosis ratio of lipopolysaccharide-challenged MLE12 cells was significantly reduced by recombinant exogenous amphiregulin from 16.60 ± 1.82 to 9.47 ± 1.67% (n = 5) but significantly increased from 17.45 ± 1.13 to 21.67 ± 1.10% (n = 5) after stimulation with supernatant of M1-polarized AM media conditioned with amphiregulin-neutrolizing antibody. Western blotting revealed that amphiregulin activated epithelial growth factor receptor and AKT in the lung tissues and MLE12 cells (n = 5).

Conclusions

Different from the common notion that classically activated AMs have just a detrimental effect on the lung tissues, the results of this study showed that classically activated AMs also exerted a protective effect on the lung tissues by producing high-level amphiregulin in lipopolysaccharide-induced ALI.
Anesthesia-induced Suppression of Human Dorsal Anterior Insula Responsivity at Loss of Volitional Behavioral Response
Authors: Warnaby Catherine Elizabeth , Seretny Marta , Ní Mhuircheartaigh Roísín , Rogers Richard , Jbabdi Saad , Sleigh Jamie , Tracey Irene
Published: January 2016

AbstractAbstract

Simultaneous electroencephalography and functional magnetic resonance imaging in 15 healthy volunteers undergoing ultraslow induction of propofol anesthesia identified suppression of stimulus-evoked activity in the right dorsal anterior insula cortex coincident with reduced functional connectivity with frontoparietal regions at loss of responsiveness. The dorsal anterior insula cortex is a potential cortical gate underlying loss of responsiveness that might mediate subsequent loss of functional connectivity and information integration at deeper levels of anesthesia.

Background

It has been postulated that a small cortical region could be responsible for the loss of behavioral responsiveness (LOBR) during general anesthesia. The authors hypothesize that any brain region demonstrating reduced activation to multisensory external stimuli around LOBR represents a key cortical gate underlying this transition. Furthermore, the authors hypothesize that this localized suppression is associated with breakdown in frontoparietal communication.

Methods

During both simultaneous electroencephalography and functional magnetic resonance imaging (FMRI) and electroencephalography data acquisition, 15 healthy volunteers experienced an ultraslow induction with propofol anesthesia while a paradigm of multisensory stimulation (i.e., auditory tones, words, and noxious pain stimuli) was presented. The authors performed separate analyses to identify changes in (1) stimulus-evoked activity, (2) functional connectivity, and (3) frontoparietal synchrony associated with LOBR.

Results

By using an FMRI conjunction analysis, the authors demonstrated that stimulus-evoked activity was suppressed in the right dorsal anterior insula cortex (dAIC) to all sensory modalities around LOBR. Furthermore, the authors found that the dAIC had reduced functional connectivity with the frontoparietal regions, specifically the dorsolateral prefrontal cortex and inferior parietal lobule, after LOBR. Finally, reductions in the electroencephalography power synchrony between electrodes located in these frontoparietal regions were observed in the same subjects after LOBR.

Conclusions

The authors conclude that the dAIC is a potential cortical gate responsible for LOBR. Suppression of dAIC activity around LOBR was associated with disruption in the frontoparietal networks that was measurable using both electroencephalography synchrony and FMRI connectivity analyses.
Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery
Authors: Deschamps Alain , Hall Richard , Grocott Hilary , Mazer C. David , Choi Peter T. , Turgeon Alexis F. , de Medicis Etienne , Bussières Jean S. , Hudson Christopher , Syed Summer , Seal Doug , Herd Stuart , Lambert Jean , Denault André
Published: January 2016

AbstractAbstract

Eight Canadian centers randomized 201 patients. Cerebral desaturation (10% relative reduction from baseline) was common and nearly always reversible. Consequently, saturation was far better preserved in patients randomized to intervention than routine care.

Background

Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes. Before a large multicenter randomized controlled trial (RCT) on the impact of preventing desaturations on perioperative outcomes, the authors undertook a randomized prospective, parallel-arm, multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations.

Methods

Eight Canadian sites randomized 201 patients between April 2012 and October 2013. The primary outcome was the success rate of reversing cerebral desaturations below 10% relative to baseline in the intervention group. Anesthesiologists were blinded to the cerebral saturation values in the control group. Intensive care unit personnel were blinded to cerebral saturation values for both groups. Secondary outcomes included the area under the curve of cerebral desaturation load, enrolment rates, and a 30-day follow-up for adverse events.

Results

Cerebral desaturations occurred in 71 (70%) of the 102 intervention group patients and 56 (57%) of the 99 control group patients (P = 0.04). Reversal was successful in 69 (97%) of the intervention group patients. The mean cerebral desaturation load (SD) in the operating room was smaller for intervention group patients compared with control group patients (104 [217] %.min vs. 398 [869] %.min, mean difference, −294; 95% CI, −562 to −26; P = 0.03). This was also true in the intensive care unit (P = 0.02). There were no differences in adverse events between the groups.

Conclusions

Study sites were successful in reversal of desaturation, patient recruitment, randomization, and follow-up in cardiac surgery, supporting the feasibility of conducting a large multicenter RCT.
Laryngeal Mask Ventilation During Lumbar Spine Neurosurgery in Knee-Chest Position is Feasible
Authors: Hurtado Paola , Fàbregas Neus , Forero Carolina , Tercero Javier , Carrero Enrique , de Riva Nicolas , Gracia Isabel , Lopez Anna M. , Valero Ricard
Published: January 2016

Background:

This study describes our experience with laryngeal mask (LM) inserted after anesthetic induction in patients already in knee-chest position for lumbar neurosurgery.

Methods:

Airway management (need for LM repositioning, orotracheal intubation because of failed LM insertion), anticipated difficult airway, and airway complications were registered. Statistics were compared between groups with the t test or the χ2 test, as appropriate.

Results:

A total of 358 cases were reviewed from 2008 to 2013. Tracheal intubation was performed in 108 patients and LM was chosen for 250 patients (69.8%). Intubated patients had a higher mean age and rate of anticipated difficult airway; duration of surgery was longer (P<0.001, all comparisons). LM insertion and anesthetic induction proved effective in 97.2% of the LM-ventilated patients; 7 patients (2.8%) were intubated because of persistent leakage. Incidences with airway management were resolved without compromising patient safety.

Conclusion:

LM airway management during lumbar neurosurgery in knee-chest position is feasible for selected patients when the anesthetist is experienced.
Popliteal cysts in children: another look
Authors: Harcke Howard T. , Niedzielski Anastasia , Thacker Mihir M.
Published: January 2016

This retrospective review of 46 popliteal cysts seen in 44 patients at a pediatric orthopedic referral center clarifies the presenting symptomatology, associated conditions, and likely duration of a popliteal cyst, and the need for intervention. The patients were followed up for more than 1 year. Thirty-six of the 46 cysts with duration data showed no resolution of the popliteal cyst during the period of observation (average, 32.1 months). The 10 cysts that showed clinical resolution were present for an average of 16.9 months. The benign course of action for virtually all patients obviated the need for intervention and supports the adequacy of only clinical examination, with no need for recurrent sonography.
Withdrawal of Life-Sustaining Therapy in Patients With Intracranial Hemorrhage: Self-Fulfilling Prophecy or Accurate Prediction of Outcome?*
Authors: Weimer Jonathan M. , Nowacki Amy S. , Frontera Jennifer A.
Published: January 2016

Objectives:

Withdrawal of life-sustaining therapy may lead to premature limitations of life-saving treatments among patients with intracranial hemorrhage, representing a self-fulfilling prophecy. We aimed to determine whether our algorithm for the withdrawal of life-sustaining therapy decision would accurately identify patients with a high probability of poor outcome, despite aggressive treatment.

Design:

Retrospective analysis of prospectively collected data.

Setting:

Tertiary-care Neuro-ICU.

Patients:

Intraparenchymal, subdural, and subarachnoid hemorrhage patients.

Interventions:

Baseline demographics, clinical status, and hospital course were assessed to determine the predictors of in-hospital mortality and 12-month death/severe disability among patients receiving maximal therapy. Multivariable logistic regression models developed on maximal therapy patients were applied to patients who underwent withdrawal of life-sustaining therapy to predict their probable outcome had they continued maximal treatment. A validation cohort of propensity score–matched patients was identified from the maximal therapy cohort, and their predicted and actual outcomes compared.

Measurements and Main Results:

Of 383 patients enrolled, there were 128 subarachnoid hemorrhage (33.4%), 134 subdural hematoma (35.0%), and 121 intraparenchymal hemorrhage (31.6%). Twenty-six patients (6.8%) underwent withdrawal of life-sustaining therapy and died, 41 (10.7%) continued maximal therapy and died in hospital, and 316 (82.5%) continued maximal therapy and survived to discharge. The median predicted probability of in-hospital death among withdrawal of life-sustaining therapy patients was 35% had they continued maximal therapy, whereas the median predicted probability of 12-month death/severe disability was 98%. In the propensity-matched validation cohort, 16 of 20 patients had greater than or equal to 80% predicted probability of death/severe disability at 12 months, matching the observed outcomes and supporting the strength and validity of our prediction models.

Conclusions:

The withdrawal of life-sustaining therapy decision may contribute to premature in-hospital death in some patients who may otherwise have been expected to survive to discharge. However, based on probability models, nearly all of the patients who underwent withdrawal of life-sustaining therapy would have died or remained severely disabled at 12 months had maximal therapy been continued. Withdrawal of life-sustaining therapy may not represent a self-fulfilling prophecy.
Outcomes of Protocol-Driven Care of Critically Ill Severely Anemic Patients for Whom Blood Transfusion Is Not an Option*
Authors: Shander Aryeh , Javidroozi Mazyar , Gianatiempo Carmine , Gandhi Nisha , Lui John , Califano Frank , Kaufman Margit , Naqvi Sajjad , Syed Faraz , Aregbeyen Oshuare
Published: January 2016

Objective:

To compare the outcomes of severely anemic critically ill patients for whom transfusion is not an option (“bloodless” patients) with transfused patients.

Design:

Cohort study with propensity score matching.

Setting:

ICU of a referral center.

Patients:

One hundred seventy-eight bloodless and 441 transfused consecutive severely anemic, critically ill patients, admitted between May 1996 and April 2011, and having at least one hemoglobin level less than or equal to 8 g/dL within 24 hours of ICU admission. Patients with diagnosis of brain injury, acute myocardial infarction, or status postcardiac surgery were excluded.

Interventions:

Allogeneic RBC transfusion during ICU stay.

Measurements and Main Results:

Primary outcome was in-hospital mortality. Other outcomes were ICU mortality, readmission to ICU, new electrocardiographic or cardiac enzyme changes suggestive of cardiac ischemia or injury, and new positive blood culture result. Transfused patients were older, had higher hemoglobin level at admission, and had higher Acute Physiology and Chronic Health Evaluation II score. Hospital mortality rates were 24.7% in bloodless and 24.5% in transfused patients (odds ratio, 1.01; 95% CI, 0.68–1.52;p= 0.95). Adjusted odds ratio of hospital mortality was 1.52 (95% CI, 0.95–2.43;p= 0.08). No significant difference in ICU readmission or positive blood culture results was observed. Analysis of propensity score–matched cohorts provided similar results.

Conclusions:

Overall risk of mortality in severely anemic critically ill bloodless patients appeared to be comparable with transfused patients, albeit the latter group had older age and higher Acute Physiology and Chronic Health Evaluation II score. Use of a protocol to manage anemia in these patients in a center with established patient blood management and bloodless medicine and surgery programs is feasible and likely to contribute to improved outcome, whereas more studies are needed to better delineate the impact of such programs.
A Pilot Randomized Trial Comparing Weaning From Mechanical Ventilation on Pressure Support Versus Proportional Assist Ventilation*
Authors: Bosma Karen J. , Read Brooke A. , Bahrgard Nikoo Mohammad J. , Jones Philip M. , Priestap Fran A. , Lewis James F.
Published: January 2016

Objectives:

Despite protocols incorporating spontaneous breathing trials, 31% of ICU patients experience difficult or prolonged weaning from mechanical ventilation. Nonfatiguing modes such as pressure support ventilation are recommended. Proportional assist ventilation provides assistance in proportion to patient effort, which may optimize weaning. However, it is not known how proportional assist ventilation performs relative to pressure support ventilation over a prolonged period in the complex ICU setting. The purpose of this study was to compare the physiologic and clinical performance (failure rate), safety, and feasibility of protocols using daily spontaneous breathing trial plus pressure support ventilation versus proportional assist ventilation until ventilation discontinuation.

Design:

Single-center, unblinded pilot randomized controlled trial.

Setting:

Medical-surgical ICU of a tertiary-care hospital.

Patients:

Adult patients intubated greater than 36 hours were randomized if they met eligibility criteria for partial ventilatory support, tolerated pressure support ventilation greater than or equal to 30 minutes, and either failed or did not meet criteria for a spontaneous breathing trial.

Interventions:

Patients were randomized to the pressure support ventilation or proportional assist ventilation protocol (PAV+, Puritan Bennett 840; Covidien, Boulder, CO). Both protocols used progressive decreases in level of assistance as tolerated, coupled with daily assessment for spontaneous breathing trials.

Measurements and Main Results:

Of 54 patients randomized, outcome data are available for 50 patients; 27 were randomized to receive proportional assist ventilation and 23 to receive pressure support ventilation. There were no adverse events linked to the study interventions, and protocol violations were infrequent. Recruitment was slower than projected (1.3 patients per month). The median (interquartile range) time from randomization to successful extubation was 3.9 days (2.8–8.4 d) on proportional assist ventilation versus 4.9 days (2.9–26.3 d) on pressure support ventilation (p = 0.39). Time to live ICU discharge was 7.3 days (5.2–11.4 d) on proportional assist ventilation versus 12.4 days (7.5–30.8 d) on pressure support ventilation (p = 0.03).

Conclusion:

This pilot study demonstrates the utility, safety, and feasibility of the weaning protocols and provides important information to guide the design of a future randomized controlled trial comparing weaning from mechanical ventilation on pressure support ventilation versus proportional assist ventilation.