bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrocaloric induced retarded ferroelectric switching
Authors: Buchacher Till , Rokosz Maciej , Dorey Robert , Allam Jeremy , Gregory Andrew
Published: January 2017

Ferroelectric (FE) switching in bulk materials, at modest electric fields, is a relatively fast process, occurring on time scales of microseconds and less. A secondary retarded switching phenomenon also occurs on time scales of seconds and has previously been attributed to defect induced elevated energy barriers between polarisation states. As ferroelectric switching is a thermally activated process, the barrier heights are also affected by temperature, which is not constant in ferroelectric materials due to the electrocaloric (EC) effect. Here, an additional EC induced retardation mechanism is proposed whereby EC induced temperature changes repeatedly temporarily prevent further FE switching during cooling cycles.
Defect-free Ni/GaN Schottky barrier behavior with high temperature stability
Authors: Reddy Pramod , Sarkar Biplab , Kaess Felix , Gerhold Michael , Kohn Erhard , Collazo Ramon , Sitar Zlatko
Published: January 2017

In this work, we report on defect-free homogeneous behavior of Ni Schottky contacts patterned on surface treated n-GaN by photolithography with unity ideality factor, high temperature stability, and low reverse leakage. The barrier height (0.7 eV) and ideality factor (1.02) are found to be independent of temperature, indicating a highly homogeneous contact. The contacts are found to be stable with no significant change in ideality factor or leakage current up to an annealing temperature of 600 °C. Temperature dependence of the reverse leakage current shows no evidence for the existence of surface defects that would provide leakage paths, and the behavior was modeled by ATLAS simulations with an ideal homogeneous barrier of 0.7 eV. Consequently, the forward and reverse bias characteristics are explained by a common set of parameters. The surface treatment after the development and prior to metallization included an acid-based surface treatment. X-ray photoelectron spectroscopy (XPS) studies indicate that the hydroxide-based development process during photolithography changes the nitride surface composition by introducing excess C that degrades the ideality factor and introduces barrier inhomogeneity and high leakage currents. XPS studies further demonstrate that the restoration of a stable, Ga-rich surface, similar to as-grown surface, occurs due to the acid-based surface treatment, which is responsible for the observed unity ideality factor, homogeneous barrier, low leakage current, and high temperature stability.
Superconductive PT-symmetry phase transition in metasurfaces
Authors: Wang Dongyang , Li Chun , Zhang Caihong , Kang Ming , Zhang Xueqian , Jin Biaobing , Tian Zhen , Li Yanfeng , Zhang Shuang , Han Jiaguang , Zhang Weili
Published: January 2017

We experimentally demonstrate a dynamic process of effective Parity-Time (PT)-symmetry breaking through eigen-polarization variation in a hybridized metasurface. The metasurface consists of two coupled resonators made from metal and type II superconductor niobium nitride, respectively. By varying the temperature from 2 to 13 K, the hybridized system is able to pass through the effective PT-symmetry phase transition point, providing a feasible way to investigate the dynamic PT-symmetry transition.
Abnormal hump in capacitance–voltage measurements induced by ultraviolet light in a-IGZO thin-film transistors
Authors: Tsao Yu-Ching , Chang Ting-Chang , Chen Hua-Mao , Chen Bo-Wei , Chiang Hsiao-Cheng , Chen Guan-Fu , Chien Yu-Chieh , Tai Ya-Hsiang , Hung Yu-Ju , Huang Shin-Ping , Yang Chung-Yi , Chou Wu-Ching
Published: January 2017

This work demonstrates the generation of abnormal capacitance for amorphous indium-gallium-zinc oxide (a-InGaZnO4) thin-film transistors after being subjected to negative bias stress under ultraviolet light illumination stress (NBIS). At various operation frequencies, there are two-step tendencies in their capacitance-voltage curves. When gate bias is smaller than threshold voltage, the measured capacitance is dominated by interface defects. Conversely, the measured capacitance is dominated by oxygen vacancies when gate bias is larger than threshold voltage. The impact of these interface defects and oxygen vacancies on capacitance-voltage curves is verified by TCAD simulation software.
With Trump in charge, uncharted waters lie ahead for science
Authors: Kramer David
Published: January 2017

Now that Congress and the White House are firmly in Republican control, President-elect Trump has a clear path to enact his science policy, when it emerges.
The Waitsia Field, onshore North Perth Basin, Western Australia
Authors: Tupper Neil , Matthews Eric , Cooper Gareth , Furniss Andy , Hicks Tim , Hunt Suzanne
Published: January 2017

The Waitsia Field represents a new commercial play for the onshore north Perth Basin with potential to deliver substantial reserves and production to the domestic gas market. The discovery was made in 2014 by deepening of the Senecio–3 appraisal well to evaluate secondary reservoir targets. The well successfully delineated the extent of the primary target in the Upper Permian Dongara and Wagina sandstones of the Senecio gas field but also encountered a combination of good-quality and tight gas pay in the underlying Lower Permian Kingia and High Cliff sandstones.
The drilling of the Waitsia–1 and Waitsia–2 wells in 2015, and testing of Senecio-3 and Waitsia-1, confirmed the discovery of a large gas field with excellent flow characteristics. Wireline log and pressure data define a gross gas column in excess of 350 m trapped within a low-side fault closure that extends across 50 km2. The occurrence of good-quality reservoir in the depth interval 3,000–3,800 m is diagenetically controlled with clay rims inhibiting quartz cementation and preserving excellent primary porosity.
Development planning for Waitsia has commenced with the likelihood of an early production start-up utilising existing wells and gas processing facilities before ramp-up to full-field development. The dry gas will require minimal processing, and access to market is facilitated by the Dampier–Bunbury and Parmelia gas pipelines that pass directly above the field.
The Waitsia Field is believed to be the largest conventional Australian onshore discovery for more than 30 years and provides impetus and incentive for continued exploration in mature and frontier basins. The presence of good-quality reservoir and effective fault seal was unexpected and emphasise the need to consider multiple geological scenarios and to test unorthodox ideas with the drill bit.
Reducing recurrence of bacterial skin infections in Aboriginal children in rural communities: new ways of thinking, new ways of working
Authors: Thomas Susan , Crooks Kristy , Taylor Kylie , Massey Peter D. , Williams Ruth , Pearce Glenn
Published: January 2017

Reports from health workers, school staff and community members in rural NSW suggested that bacterial skin infections are a significant health issue for Aboriginal children and their families, affecting quality of life and contributing to poor school attendance. Current NSW treatment guidelines do not incorporate important sociocultural factors or ways of living in Aboriginal communities. The aim of this qualitative study was to gain a deeper understanding of the experience of parents and carers of Aboriginal children affected by skin infections and of other community members, health workers and school staff, and what actions have been considered successful or unsuccessful in reducing the recurrence of infection. This study used a Participatory Action Research methodology. Interviews and focus groups were conducted with 38 health workers and managers, school staff, community members and parents and carers. Themes that emerged included: (i) skin infections have become normalised; (ii) skin infections are, in part, a consequence of transgenerational trauma; (iii) skin infections are interwoven with social determinants; (iv) families have survived but more could thrive; and (v) something can and should be done about the problem. The findings of this study will inform the development of more effective and acceptable options to reduce skin infections in Aboriginal children.
Global urban signatures of phenotypic change in animal and plant populations
Authors: Alberti Marina , Correa Cristian , Marzluff John M. , Hendry Andrew P. , Palkovacs Eric P. , Gotanda Kiyoko M. , Hunt Victoria M. , Apgar Travis M. , Zhou Yuyu
Published: January 2017

Significance

Ecoevolutionary feedbacks on contemporary timescales were hypothesized over half a century ago, but only recently has evidence begun to emerge. The role that human activity plays in such dynamics is still unclear. Through a metaanalysis of >1,600 phenotypic changes in species across regions and ecosystem types, we examine the evidence that the rate of phenotypic change has an urban signature. Our findings indicate greater phenotypic change in urbanizing systems compared with natural and nonurban anthropogenic systems. By explicitly linking urban development to trait changes that might affect ecosystem function, we provide insights into the potential ecoevolutionary implications for maintaining ecosystem function and the sustainability of human well-being.
Antibiotic stress selects against cooperation in the pathogenic bacterium
Pseudomonas aeruginosa
Authors: Vasse Marie , Noble Robert J. , Akhmetzhanov Andrei R. , Torres-Barceló Clara , Gurney James , Benateau Simon , Gougat-Barbera Claire , Kaltz Oliver , Hochberg Michael E.
Published: January 2017

Significance

The evolution of cooperation is a central issue in biology and the social sciences. Study of model systems of social microbes has focused on how “cooperators” and “cheats” interact but rarely accounts for the surrounding environment. We demonstrate how environmental stress in the form of antibiotics alters the evolution of public goods cooperation in a bacterium. Antibiotics accentuate the costs to cooperators, resulting in their rapid demise relative to cheats. In a more applied vein, antibiotic resistance was maximal in the presence of both producers and cheats, suggesting that knowledge about social strategies can be used to improve therapies. Our work emphasizes ecoevolutionary feedback in social evolution and demonstrates that social interactions may be considerably modified in natural, stressful environments.
Dinosaur incubation periods directly determined from growth-line counts in embryonic teeth show reptilian-grade development
Authors: Erickson Gregory M. , Zelenitsky Darla K. , Kay David Ian , Norell Mark A.
Published: January 2017

Significance

Little is known regarding nonavian dinosaur embryology. Embryological period relates to myriad aspects of development, life history, and evolution. In reptiles incubation is slow, whereas in birds it is remarkably rapid. Because birds are living dinosaurs, rapid incubation has been assumed for all dinosaurs. We discovered daily forming growth lines in teeth of embryonic nonavian dinosaurs revealing incubation times. These lines show slow reptilian-grade development spanning months. The rapid avian condition likely evolved within birds prior to the Cretaceous–Paleogene (K–Pg) mass extinction event. Prolonged incubation exposed nonavian dinosaur eggs and attending parents to destructive influences for long periods. Slow development may have affected their ability to compete with more rapidly generating populations of birds, reptiles, and mammals following the K–Pg cataclysm.
Ancient human disturbances may be skewing our understanding of Amazonian forests
Authors: McMichael Crystal N. H. , Matthews-Bird Frazer , Farfan-Rios William , Feeley Kenneth J.
Published: January 2017

Significance

The Amazon harbors thousands of species and plays a vital role in the Earth’s climate and carbon cycles. Much of what we know about the Amazon is based on censuses of only a small number of forest inventory plots, an even smaller number of which are censused repeatedly and used to study forest dynamics and carbon fluxes. The effects of ancient human impacts have never been properly assessed or accounted for in studies of Amazonian plots. New spatial analyses show that plots significantly oversample areas with high abundances of archaeological evidence of past human activities. This suggests that our interpretations of the Amazon’s structure, composition, and function are based disproportionately on forests still reflecting the legacies of past human disturbances.
Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure
Authors: Le Nouën Cyril , McCarty Thomas , Brown Michael , Smith Melissa Laird , Lleras Roberto , Dolan Michael A. , Mehedi Masfique , Yang Lijuan , Luongo Cindy , Liang Bo , Munir Shirin , DiNapoli Joshua M. , Mueller Steffen , Wimmer Eckard , Collins Peter L. , Buchholz Ursula J.
Published: January 2017

Significance

Recoding viral genomes by numerous synonymous substitutions provided live attenuated vaccine candidates predicted to have a low risk of reversion. However, their stability under selective pressure was largely unknown. We evaluated the phenotypic reversion of representative genome-scale deoptimized human respiratory syncytial virus (RSV) vaccine candidates in the context of strong selective pressure. We found that a virus bearing a deoptimized L-polymerase ORF evolved to escape temperature sensitivity restriction by mutations in L and multiple other proteins. Additional analysis revealed that single mutations in the M2-1 ORF were able to substantially escape the restriction imposed by the deoptimized polymerase. Based on this information, we generated a stable deoptimized RSV vaccine candidate with improved attenuation and immunogenicity suitable for additional development.
Convergence liberalism and the problem of disagreement concerning public justification
Authors: Billingham Paul
Published: January 2017

The ‘convergence conception’ of political liberalism has become increasingly popular in recent years. Steven Wall has shown that convergence liberals face a serious dilemma in responding to disagreement about whether laws are publicly justified. What I call the ‘conjunctive approach’ to such disagreement threatens anarchism, while the ‘non-conjunctive’ approach appears to render convergence liberalism internally inconsistent. This paper defends the non-conjunctive approach, which holds that the correct view of public justification should be followed even if some citizens do not consider enacted laws to be publicly justified. My argument sheds light on the fundamental structure of convergence liberalism.
Development of immersion vaccine for bacterial cold-water disease in ayu Plecoglossus altivelis
Authors: Nakayama Hitoshi , Mori Mariko , Takita Teisuke , Yasukawa Kiyoshi , Tanaka Keisuke , Hattori Shunji , Aikawa Hideaki , Hasegawa Osamu , Okamura Takashi , Takegami Kentarou , Motokawa Shogo , Kuwahara Masakazu , Amano Kenichi
Published: January 2017

Flavobacterium psychrophilum (F. psychrophilum) is the causative agent of bacterial cold-water disease (BCWD) that occurs in ayu Plecoglossus altivelis. Formalin-killed cell of F. psychrophilum has long been studied as an immersion vaccine for BCWD. In this study, we explored the possibility of F. psychrophilum collagenase (fpcol) for use as the immersion vaccine. BCWD convalescent ayu sera contained specific IgM antibodies against somatic F. psychrophilum and fpcol, meaning that fpcol is a promising antigen for the vaccine development. The recombinant fpcol was successfully expressed in Escherichia coli and Brevibacillus chosinensis (B. chosinensis). The culture supernatant of the B. chosinensis was used as an immersion vaccine solution. The vaccinated ayu were then challenged by soaking into F. psychrophilum culture. In two experimental groups, the relative percentages of survivals were 63 and 38%, respectively, suggesting that fpcol is promising as the immersion vaccine for ayu-BCWD.
Immunocytochemical detection of rhamnogalacturonan II on forming cell plates in cultured tobacco cells
Authors: Zhou Ye , Awano Tatsuya , Kobayashi Masaru , Matoh Toru , Takabe Keiji
Published: January 2017

Rhamnogalacturonan II (RG-II) is a region of pectin macromolecules that is present in plant primary cell walls. The RG-II region serves as the site of borate cross-linking within pectin, via which pectin macromolecules link together to form a gel. In this study, we examined whether RG-II is present in the cell plate, the precursor of primary cell walls that forms during cytokinesis. A structure inside dividing cells was labeled with a rabbit polyclonal anti-RG-II antibody and detected by immunofluorescence microscopy. An antibody against callose, a marker polysaccharide for the cell plate, also labeled the structure. In immunoelectron microscopy analyses using the anti-RG-II antibody, gold particles were distributed in electron-lucent vesicular structures that appeared to correspond to the forming cell plates in late anaphase cells. Together, these results suggest that RG-II is present in cell plates from the early phase of their assembly.
Community-Based Mental Health Treatment Preceding Jail Detention Among Adults with Serious Mental Illness
Authors: Swartz James A. , Tabahi Suhad
Published: January 2017

This study examined the lifetime and past-year community mental health treatment use of 282 male and 149 female jail detainees with SMI. Although most participants reported high lifetime rates of mental health treatment they believed effective, only a minority accessed treatment in the year and month before arrest. Women were less likely to receive treatment than men and more often left treatment against medical advice. Both substance use and post-traumatic stress disorder were significantly undertreated and care was provided predominantly by psychiatrists. The implications for expanding treatment availability and access to critical services such as housing and employment are discussed.
Supplementary bilateral comparison of the national AC/DC voltage transfer references between VNIIM (Russia) and Ukrmetrteststandard (Ukraine) (COOMET.EM-S1)
Authors: Telitchenko G P
Published: January 2017

This intercomparison was fulfilled in conformity with the agreed project of COOMET under ref. No 273-a/RU/03 at ELECTRICITY area. It is bilateral comparison between Ukrmetrteststandard (Ukraine) and VNIIM (Russia) (pilot laboratory). This project was arranged with an aim to establish degree of equivalence between Ukraine and Russia measurement standards and to confirm uncertainties declared by the participants. The results of the comparison will be used for confirmation calibration and measurement capabilities provided by Ukrmetrteststandard (Ukraine). VNIIM (Russia) (pilot laboratory) participated in CCEM-K6.a and has already presented their CMC in this area. The measurements had started in November 2004 and completed in February 2005

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Final report of CCQM-K130 nitrogen mass fraction measurements in glycine
Authors: Medvedevskikh Maria , Krasheninina Maria , do Rego Eliane C P , Wollinger Wagner , Monteiro Tânia M , de Carvalho Lucas J , Garcia Steve Ali Acco , Haraldsson Conny , Rodriguez M Alejandra , Rodriguez Gabriela , Salvo Karino , Gavrilkin Vladimir , Kulyk Sergij , Samuel Laly
Published: January 2017

CCQM key comparison K-130 in the field of nitrogen mass fracton has been performed by the Inorganic Analysis Working Group (IAWG) of the Consultative Committee for Amount of Substance (CCQM).

The aim of this key comparison CCQM-K130 is to support National Measurement Institutes (NMIs) and Designated Institutes (DIs) to demonstrate the validity of the procedures the employed for determination of nitrogen mass fraction in glycine. Mass fraction of nitrogen is very important pointer because the results of these measurements are often used for determination of protein mass fraction that is an important indicator of the quality of the vast majority of food products and raw materials, in particular dry milk powder. Proteins-enzymes catalyze chemical reactions, protein along with fats and carbohydrates is one of the indicators characterizing the energy value of food, so its definition is mandatory for all food products.

The study material for this key comparison has been selected to be representative as one of the aminoacid - the simplest part of the protein. Glycine is an amino acid, single acid that does not have any isomers (melting point -290 °C; specific heat of evaporation - 528,6 J/kg; specific melting heat - 981,1 J/kg; pKa - 2, 34, molar mass - 75,07 g/mol, density - 1,607 g/cm3).

Ural Scientific Research Institute for Metrology (UNIIM) acted as the coordinating laboratory of this comparison.

Nine NMIs participated in this key comparison and one NMI participated in Pilot study that was condacted in parallel.

Report A contains the results of key comparison and pilot study. The results of Pilot study were excluded from the Report B

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Genome-wide characterization of lncRNAs in acute myeloid leukemia
Authors: Lei Lijun , Xia Siyu , Liu Dan , Li Xiaoqing , Feng Jing , Zhu Yaqi , Hu Jun , Xia Linjian , Guo Lieping , Chen Fei , Cheng Hui , Chen Ke , Hu Hanyang , Chen Xiaohua , Li Feng , Zhong Shan , Mittal Nupur , Yang Guohua , Qian Zhijian , Han Leng , He Chunjiang
Published: January 2017

Long noncoding RNAs (lncRNAs) are a large family of noncoding RNAs that play a critical role in various normal bioprocesses as well as tumorigenesis. However, the expression patterns and biological functions of lncRNAs in acute leukemia have not been well studied. Here, we performed transcriptome-wide lncRNA expression profiling of acute myeloid leukemia (AML) patient samples, along with non-leukemia control hematopoietic samples. We found that lncRNAs were differentially expressed in AML samples relative to control samples. Notably, we identified that lncRNAs upregulated in AML (relative to the control samples) are associated with a lower degree of DNA methylation and a higher ratio of being bound by transcription factors such as SP1, STAT4, ATF-2 and ELK-1 compared with those downregulated in AML. Moreover, an enrichment of H3K4me3 and a depletion of H3K27me3 were observed in upregulated lncRNAs in AML. Expression patterns of three types of lncRNAs (antisense, enhancer and intergenic lncRNAs) have previously been characterized. Of the identified lncRNAs, we found that high expression level lncRNA LOC285758 is associated with the poor prognosis in AML patients. Furthermore, we found that LOC285758 regulates proliferation of AML cell lines by enhancing the expression of HDAC2, a key factor in carcinogenesis. Collectively, our study depicts a landscape of important lncRNAs in AML and provides novel potential therapeutic targets and prognostic markers for AML treatment.
Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children
Authors: Lewinsohn David M. , Leonard Michael K. , LoBue Philip A. , Cohn David L. , Daley Charles L. , Desmond Ed , Keane Joseph , Lewinsohn Deborah A. , Loeffler Ann M. , Mazurek Gerald H. , O’Brien Richard J. , Pai Madhukar , Richeldi Luca , Salfinger Max , Shinnick Thomas M. , Sterling Timothy R. , Warshauer David M. , Woods Gail L.
Published: January 2017

Background.

Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain.

Methods.

A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Results.

Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional.

Conclusions.

These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.
T-Helper 17 Cell Cytokine Responses in Lyme Disease Correlate With Borrelia burgdorferi Antibodies During Early Infection and With Autoantibodies Late in the Illness in Patients With Antibiotic-Refractory Lyme Arthritis
Authors: Strle Klemen , Sulka Katherine B. , Pianta Annalisa , Crowley Jameson T. , Arvikar Sheila L. , Anselmo Anthony , Sadreyev Ruslan , Steere Allen C.
Published: January 2017

Background.

Control of Lyme disease is attributed predominantly to innate and adaptive T-helper 1 cell (TH1) immune responses, whereas the role of T-helper 17 cell (TH17) responses is less clear. Here we characterized these inflammatory responses in patients with erythema migrans (EM) or Lyme arthritis (LA) to elucidate their role early and late in the infection.

Methods.

Levels of 21 cytokines and chemokines, representative of innate, TH1, and TH17 immune responses, were assessed by Luminex in acute and convalescent sera from 91 EM patients, in serum and synovial fluid from 141 LA patients, and in serum from 57 healthy subjects. Antibodies to Borrelia burgdorferi or autoantigens were measured by enzyme-linked immunosorbent assay.

Results.

Compared with healthy subjects, EM patients had significantly higher levels of innate, TH1, and TH17-associated mediators (P ≤ .05) in serum. In these patients, the levels of inflammatory mediators, particularly TH17-associated cytokines, correlated directly with B. burgdorferi immunoglobulin G antibodies (P ≤ .02), suggesting a beneficial role for these responses in control of early infection. Late in the disease, in patients with LA, innate and TH1-associated mediators were often >10-fold higher in synovial fluid than serum. In contrast, the levels of TH17-associated mediators were more variable, but correlated strongly with autoantibodies to endothelial cell growth factor, matrix metalloproteinase 10, and apolipoprotein B-100 in joints of patients with antibiotic-refractory LA, implying a shift in TH17 responses toward an autoimmune phenotype.

Conclusions.

Patients with Lyme disease often develop pronounced TH17 immune responses that may help control early infection. However, late in the disease, excessive TH17 responses may be disadvantageous by contributing to autoimmune responses associated with antibiotic-refractory LA.
Intensity-modulated radiotherapy using two static ports of tomotherapy for breast cancer after conservative surgery: dosimetric comparison with other treatment methods and 3-year clinical results
Authors: Nagai Aiko , Shibamoto Yuta , Yoshida Masanori , Inoda Koji , Kikuchi Yuzo
Published: January 2017

This study investigated the differences in dose–volume parameters for the breast and normal tissues during TomoDirectTM (TD) intensity-modulated radiation therapy (IMRT), TD-3D conformal radiotherapy (3DCRT) and 3DCRT plans, all using two beams, and analyzed treatment outcomes of two-beam TD-IMRT for breast cancer after breast-conserving surgery. Between August 2011 and January 2015, 152 patients were treated using two-beam TD-IMRT with 50 Gy/25 fractions. Among them, 20 patients with left-sided breast cancer were randomly chosen, and two-beam TD-IMRT, TD-3DCRT and 3DCRT plans were created for each patient. The homogeneity and conformity indices and various dose–volume parameters for the planning target volume and OARs were evaluated. Clinical outcomes were evaluated at 3 years. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. TD-IMRT and TD-3DCRT showed better whole-breast coverage than 3DCRT (P < 0.001). Most of the mean values of dosimetric endpoints for OARs were better in TD-IMRT than in TD-3DCRT and 3DCRT. Overall survival rates were 97.7% and local control rates were 99.1% at 3 years. Regional control and distant metastasis control rates at 3 years were 98.6% and 96.8%, respectively. Twenty-four of the 152 patients had Grade 2 or higher acute radiation dermatitis. Four patients (4/146 = 2.7%) had Grade 2 radiation pneumonitis. There were no late adverse events of Grade 2 or higher. Two-beam TD-IMRT appeared to yield better dose distribution for whole-breast external-beam radiation therapy than TD-3DCRT and two-beam 3DCRT. The treatment appeared to provide low skin toxicity and acceptable tumor control.
Differences in sustained alterations in protein expression between livers of mice exposed to high-dose-rate and low-dose-rate radiation
Authors: Nakajima Tetsuo , Wang Bing , Ono Tetsuya , Uehara Yoshihiko , Nakamura Shingo , Ichinohe Kazuaki , Braga-Tanaka Ignacia , Tanaka Satoshi , Tanaka Kimio , Nenoi Mitsuru
Published: January 2017

Molecular mechanisms of radiation dose-rate effects are not well understood. Among many possibilities, long-lasting sustained alterations in protein levels would provide critical information. To evaluate sustained effects after acute and chronic radiation exposure, we analyzed alterations in protein expression in the livers of mice. Acute exposure consisted of a lethal dose of 8 Gy and a sublethal dose of 4 Gy, with analysis conducted 6 days and 3 months after irradiation, respectively. Chronic irradiation consisted of a total dose of 8 Gy delivered over 400 days (20 mGy/day). Analyses following chronic irradiation were done immediately and at 3 months after the end of the exposure. Based on antibody arrays of protein expression following both acute lethal and sublethal dose exposures, common alterations in the expression of two proteins were detected. In the sublethal dose exposure, the expression of additional proteins was altered 3 months after irradiation. Immunohistochemical analysis showed that the increase in one of the two commonly altered proteins, MyD88, was observed around blood vessels in the liver. The alterations in protein expression after chronic radiation exposure were different from those caused by acute radiation exposures. Alterations in the expression of proteins related to inflammation and apoptosis, such as caspase 12, were observed even at 3 months after the end of the chronic radiation exposure. The alterations in protein expression depended on the dose, the dose rate, and the passage of time after irradiation. These changes could be involved in long-term effects of radiation in the liver.
Diversity Within the Psychotic Continuum
Authors: Luhrmann T. M.
Published: January 2017

There has been great interest in the hallucination-like events experienced by the general nonclinical population. Many psychiatric scientists have come to identify these as part of a “psychotic continuum” and have begun to ask what we might learn from these experiences that will enable us to better understand and treat psychosis. While sympathetic to this goal, this paper argues that many of these events in the nonclinical population may be associated with the attention to inner imagery characteristic of much religious practice like unscripted prayer. Many of these hallucination-like events are phenomenologically distinct, culturally salient, and are predicted both by a measure of absorption, which probes for an interest in inner imagery, and by inner sense cultivation practice. These observations suggest that rare, brief, and positive sensory events may not be associated with psychotic vulnerability. They also suggest there may be an absorption-dissociation pathway, with or without trauma, for more frequent hallucinations.
Effect of Saline Organic Acid Solutions Applied During Wheat Tempering on Flour Functionality
Authors: Sabillón Luis , Bianchini Andréia , Stratton Jayne , Rose Devin J.
Published: January 2017

Previously, we showed that tempering with saline organic acid solutions can reduce the aerobic plate count of wheat by as much as 4.3 log CFU/g. The purpose of this study was to evaluate the impact of these tempering solutions on the functional properties of resulting whole grain (WGF) and straight‐grade (SGF) flours. Wheat was tempered to 15.5% moisture by tempering with sterile distilled water (control) or solutions containing NaCl (26% [w/v]) together with organic acid (acetic or lactic 2.5 and 5.0% [v/v]). After milling, fractions were collected and recombined as needed to obtain WGF or SGF. The acid content in WGF was higher than in SGF, indicating limited penetration of the organic acids into the endosperm of the grain. In WGF, the saline organic acid treatments caused a decrease in paste viscosity and bread crumb cell sizes in breads. In SGF, the saline organic acid treatments caused significant changes in paste viscosity and some Mixograph parameters; however, principal components analysis indicated that the treatments did not substantially affect SGF functionality. Thus, WGF was altered by the saline organic acid solutions, whereas SGF functionality was minimally affected by tempering treatments, perhaps because of acids only partially penetrating into the endosperm.
A “Resident-as-Teacher” Curriculum Using a Flipped Classroom Approach: Can a Model Designed for Efficiency Also Be Effective?
Authors: Chokshi Binny D. , Schumacher Heidi K. , Reese Kristen , Bhansali Priti , Kern Jeremy R. , Simmens Samuel J. , Blatt Benjamin , Greenberg Larrie W.
Published: January 2017

Problem

The Accreditation Council for Graduate Medical Education requires training that enhances resident teaching skills. Despite this requirement, many residency training programs struggle to implement effective resident-as-teacher (RAT) curricula, particularly within the context of the 80-hour resident workweek.

Approach

In 2013, the authors developed and evaluated an intensive one-day RAT curriculum using a flipped classroom approach. Twenty-nine second-year residents participated in daylong RAT sessions. The curriculum included four 1-hour workshops focusing on adult learning principles, giving feedback, teaching a skill, and orienting a learner. Each workshop, preceded by independent reading, featured peer co-teaching, application, and feedback. The authors evaluated the curriculum using pre- and postworkshop objective structured teaching examinations (OSTEs) and attitudinal and self-efficacy teaching questionnaires.

Outcomes

Residents demonstrated statistically significant improvements in performance between pre- and postworkshop OSTEs on each of three core skills: giving feedback (P = .005), orienting a learner (P < .001), and teaching a skill (P < .001). Residents expressed positive attitudes surrounding teaching on the retrospective pre–post attitudinal instrument (P < .001) and rated themselves as more effective teachers (P < .001) after the training.

Next Steps

The authors have demonstrated that the flipped classroom approach is an efficient and effective method for training residents to improve teaching skills, especially in an era of work hour restrictions. They have committed to the continuation of this curriculum and are planning to include assessment of its long-term effects on resident behavior change and educational outcomes.
Implementing an Entrustable Professional Activities Framework in Undergraduate Medical Education: Early Lessons From the AAMC Core Entrustable Professional Activities for Entering Residency Pilot
Authors: Lomis Kimberly , Amiel Jonathan M. , Ryan Michael S. , Esposito Karin , Green Michael , Stagnaro-Green Alex , Bull Janet , Mejicano George C.
Published: January 2017

In 2014, the Association of American Medical Colleges (AAMC) published a list of 13 Core Entrustable Professional Activities for Entering Residency (Core EPAs) that medical school graduates might be expected to perform, without direct supervision, on the first day of residency. Soon after, the AAMC commissioned a five-year pilot with 10 medical schools across the United States, seeking to implement the Core EPA framework to improve the transition from undergraduate to graduate medical education.

In this article, the pilot team presents the organizational structure and early results of collaborative efforts to provide guidance to other institutions planning to implement the Core EPA framework. They describe the aims, timeline, and organization of the pilot as well as findings to date regarding the concepts of entrustment, assessment, curriculum development, and faculty development. On the basis of their experiences over the first two years of the pilot, the authors offer a set of guiding principles for institutions intending to implement the Core EPA framework. They also discuss the impact of the pilot, its limitations, and next steps, as well as how the pilot team is engaging the broader medical education community. They encourage ongoing communication across institutions to capitalize on the expertise of educators to tackle challenges related to the implementation of this novel approach and to generate common national standards for entrustment. The Core EPA pilot aims to better prepare medical school graduates for their professional duties at the beginning of residency with the ultimate goal of improving patient care.
Finding a Path to Entrustment in Undergraduate Medical Education: A Progress Report From the AAMC Core Entrustable Professional Activities for Entering Residency Entrustment Concept Group
Authors: Brown David R. , Warren Jamie B. , Hyderi Abbas , Drusin Ronald E. , Moeller Jeremy , Rosenfeld Melvin , Orlander Philip R. , Yingling Sandra , Call Stephanie , Terhune Kyla , Bull Janet , Englander Robert , Wagner Dianne P.
Published: January 2017

Problem

To better prepare graduating medical students to transition to the professional responsibilities of residency, 10 medical schools are participating in an Association of American Medical Colleges pilot to evaluate the feasibility of explicitly teaching and assessing 13 Core Entrustable Professional Activities for Entering Residency. The authors focused on operationalizing the concept of entrustment as part of this process.

Approach

Starting in 2014, the Entrustment Concept Group, with representatives from each of the pilot schools, guided the development of the structures and processes necessary for formal entrustment decisions associated with students’ increased responsibilities at the start of residency.

Outcomes

Guiding principles developed by the group recommend that formal, summative entrustment decisions in undergraduate medical education be made by a trained group, be based on longitudinal performance assessments from multiple assessors, and incorporate day-to-day entrustment judgments by workplace supervisors. Key to entrustment decisions is evidence that students know their limits (discernment), can be relied on to follow through (conscientiousness), and are forthcoming despite potential personal costs (truthfulness), in addition to having the requisite knowledge and skills. The group constructed a developmental framework for discernment, conscientiousness, and truthfulness to pilot a model for transparent entrustment decision making.

Next Steps

The pilot schools are studying a number of questions regarding the pathways to and decisions about entrustment. This work seeks to inform meaningful culture change in undergraduate medical education through a shared understanding of the assessment of trust and a shared trust in that assessment.
Chronic Lateral Epicondylalgia Does Not Exhibit Mechanical Pain Modulation in Response to Noxious Conditioning Heat Stimulus
Authors: Lim Edwin Choon Wyn , Sterling Michele , Vicenzino Bill
Published: January 2017

Objectives:

The impaired attenuation of pain by the application of a noxious conditioning stimulus at a segmentally distinct site, known as conditioned pain modulation (CPM), has been implicated in clinical pain states. Chronic lateral epicondylalgia (LE), which is characterized by lower pressure pain thresholds (PPTs) at sites remote to the affected elbow and spinal cord hyperexcitability, is a clinical pain state that might plausibly involve less efficacious CPM. This study aimed to determine whether LE exhibits a less efficacious CPM compared with that in pain-free controls.

Results:

Results: Twenty participants with LE, aged 50.7 years (SD=7.05) and who had their condition for 10.2 months (range: 2 to 80 mo), were matched by age and sex to 22 pain-free participants. All participants indicated their PPT over the lateral epicondyle(s) before and during a conditioning noxious heat stimulus that was applied over the calf. A CPM score was calculated as the difference between the PPT before and during the heat pain-conditioning stimulus expressed as a percentage of PPT before the heat pain-conditioning stimulus. The condition (LE vs. control) by side (affected vs. unaffected) analysis of variance revealed a significant condition effect (P=0.001), but not side effect (P=0.192) or side-by-condition interaction effect (P=0.951). Follow-up tests for the effect of condition revealed a mean deficit in CPM of −24.5% (95% confidence interval, −38.0 to −11.0) in LE compared with that in pain-free participants.

Discussion:

The results that suggest an impaired ability to modulate pain might be associated with the previously observed spinal cord hyperexcitability and the mechanical hyperalgesia that characterizes LE.
Proinflammatory Cytokines Mediate GPCR Dysfunction
Authors: Mohan Maradumane L. , Vasudevan Neelakantan T. , Naga Prasad Sathyamangla V.
Published: January 2017

Proinflammatory reaction by the body occurs acutely in response to injury that is considered primarily beneficial. However, sustained proinflammatory cytokines observed with chronic pathologies such as metabolic syndrome, cancer, and arthritis are detrimental and in many cases is a major cardiovascular risk factor. Proinflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor α (TNFα) have long been implicated in cardiovascular risk and considered to be a major underlying cause for heart failure (HF). The failure of the anti-TNFα therapy for HF indicates our elusive understanding on the dichotomous role of proinflammatory cytokines on acutely beneficial effects versus long-term deleterious effects. Despite these well-described observations, less is known about the mechanistic underpinnings of proinflammatory cytokines especially TNFα in pathogenesis of HF. Increasing evidence suggests the existence of an active cross-talk between the TNFα receptor signaling and G-protein–coupled receptors such as β-adrenergic receptor (βAR). Given that βARs are the key regulators of cardiac function, the review will discuss the current state of understanding on the role of proinflammatory cytokine TNFα in regulating βAR function.
Cardiac GPCR–Mediated EGFR Transactivation: Impact and Therapeutic Implications
Authors: Grisanti Laurel A. , Guo Shuchi , Tilley Douglas G.
Published: January 2017

G protein–coupled receptors (GPCRs) remain primary therapeutic targets for numerous cardiovascular disorders, including heart failure (HF), because of their influence on cardiac remodeling in response to elevated neurohormone signaling. GPCR blockers have proven to be beneficial in the treatment of HF by reducing chronic G protein activation and cardiac remodeling, thereby extending the lifespan of patients with HF. Unfortunately, this effect does not persist indefinitely, thus next-generation therapeutics aim to selectively block harmful GPCR-mediated pathways while simultaneously promoting beneficial signaling. Transactivation of epidermal growth factor receptor (EGFR) has been shown to be mediated by an expanding repertoire of GPCRs in the heart, and promotes cardiomyocyte survival, thus may offer a new avenue of HF therapeutics. However, GPCR-dependent EGFR transactivation has also been shown to regulate cardiac hypertrophy and fibrosis by different GPCRs and through distinct molecular mechanisms. Here, we discuss the mechanisms and impact of GPCR-mediated EGFR transactivation in the heart, focusing on angiotensin II, urotensin II, and β-adrenergic receptor systems, and highlight areas of research that will help us to determine whether this pathway can be engaged as future therapeutic strategy.
Dalbavancin Pharmacokinetics and Safety in Children 3 Months to 11 Years of Age
Authors: Gonzalez Daniel , Bradley John S. , Blumer Jeffrey , Yogev Ram , Watt Kevin M. , James Laura P. , Palazzi Debra L. , Bhatt-Mehta Varsha , Sullivan Janice E. , Zhang Li , Murphy Jennifer , Ussery Xilla T. , Puttagunta Sailaja , Dunne Michael W. , Cohen-Wolkowiez Michael
Published: January 2017

Background:

Dalbavancin is a novel lipoglycopeptide antibiotic that has potent in vitro activity against Gram-positive microorganisms.

Methods:

We performed a phase 1, open-label, multicenter study to investigate the pharmacokinetics (PK) and safety of a single dose of intravenous dalbavancin in hospitalized pediatric subjects 3 months to 11 years of age. We combined these data with previously collected adolescent PK data and performed a population PK analysis.

Results:

Model development was performed using 311 dalbavancin plasma concentrations from 43 subjects. The median age was 5.9 years (range: 0.3–16.9). A 3-compartment, linear PK model was developed. Based on simulations, the following age-dependent dosing regimen was found to achieve similar dalbavancin exposure to that in adults administered a 2-dose regimen: children 6 to <18 years of age, 12 mg/kg (1000 mg maximum) on day 1 and 6 mg/kg (500 mg maximum) on day 8 and children 3 months to <6 years of age, 15 mg/kg (1000 mg maximum) on day 1 and 7.5 mg/kg (500 mg maximum) on day 8. Similarly, the following age-dependent regimen was found to match adult exposure after a single-dose (1500 mg): 6 to <18 years of age, 18 mg/kg (1500 mg maximum) on day 1 and 3 months to <6 years of age, 22.5 mg/kg (1500 mg maximum) on day 1. Nineteen subjects experienced 36 treatment-emergent adverse events. Five of 36 adverse events were assessed as possibly or probably related to treatment.

Conclusions:

Dalbavancin pediatric dosing that matched adult exposure was identified. Overall, dalbavancin was well tolerated in our study population.
Valproic Acid: Special Considerations and Targeted Monitoring
Authors: Collins-Yoder Angela , Lowell Jordan
Published: January 2017

Valproic acid (VPA) is a medication used to treat multiple neuroscience conditions. It is an inexpensive and useful medication, with a low incidence of adverse drug events. Nonetheless, optimal clinical outcomes require that a series of screening and laboratory steps be followed before the initiation of VPA therapy. An additional aspect of pharmacovigilance is to recognize clinical patterns signaling genetic traits that preclude VPA, background of the black box warnings, targeted assessments, and laboratory monitoring indicated while on VPA. The intention of this article is to provide a focused summary of published information clinically relevant to prescribing and monitoring these patients.