bluuebunny/crossref_metadata_2025 huggingface dataset:
Perilesional and contralateral white matter evolution and integrity in patients with periventricular nodular heterotopia and epilepsy: a longitudinal diffusion tensor imaging study
Authors: Liu W. , Yan B. , An D. , Niu R. , Tang Y. , Tong X. , Gong Q. , Zhou D.
Published: September 2017

Background and purpose

This study aimed to assess the evolution of perinodular and contralateral white matter abnormalities in patients with periventricular nodular heterotopia (PNH) and epilepsy.

Methods

Diffusion tensor imaging (DTI) (64 directions) and 3 T structural magnetic resonance imaging were performed in 29 PNH patients (mean age 27.3 years), and 16 patients underwent a second scan (average time between the two scans 1.1 years). Fractional anisotropy and mean diffusivity were measured within the perilesional and contralateral white matter.

Results

Longitudinal analysis showed that white matter located 10 mm from the focal nodule displayed characteristics intermediate to tissue 5 mm away, and normal‐appearing white matter (NAWM) also established evolution profiles of perinodular white matter in different cortical lobes. Compared to 29 age‐ and sex‐matched healthy controls, significant decreased fractional anisotropy and elevated mean diffusivity values were observed in regions 5 and 10 mm from nodules (P < 0.01), whilst DTI metrics of the remaining NAWM did not differ significantly from controls. Additionally, normal DTI metrics were shown in the contralateral region in patients with unilateral PNH.

Conclusions

Periventricular nodular heterotopia is associated with microstructural abnormalities within the perilesional white matter and the extent decreases with increasing distance from the nodule. In the homologous contralateral region, white matter diffusion metrics were unchanged in unilateral PNH. These findings have clinical implications with respect to the medical and surgical interventions of PNH‐related epilepsy.
A Python Script to Compute Isochrones for MODFLOW
Authors: Feo Alessandra , Zanini Andrea , Petrella Emma , Celico Fulvio
Published: September 2017

MODFLOW constitutes today the most popular modeling tool in the study of water flow in aquifers and in modeling aquifers. To simplify the interface to MODFLOW various GUI have been developed for the creation of model definition files and for the visualization and interpretation of results. Recently Bakker et al. (2016) developed the FloPy interface to MODFLOW that allows to import and use the produced simulation data using Python. This allows to construct model input files, run the models, read and plot simulations results through Python scripts. In this note, we present a Python program (that uses FloPy) interface that allows us to generate time‐related capture zones (isochrones) for confined 2D steady‐state groundwater flow in unbounded domains, with one or more wells. As an application, we show a validation of the approach and the results of four basic test cases: a homogenous aquifer with one well, a heterogeneous aquifer with one well, an aquifer with four wells located both longitudinal and perpendicular to the flow direction.
Gastric poorly cohesive carcinoma: a correlative study of mutational signatures and prognostic significance based on histopathological subtypes
Authors: Kwon Chae H , Kim Young K , Lee Sojeong , Kim Ahrong , Park Hye J , Choi Yuri , Won Yeo J , Park Do Y , Lauwers Gregory Y
Published: September 2017

Aims

Genome‐wide next‐generation sequencing has revealed several driver mutations and has allowed the establishment of a molecular taxonomy of gastric cancer. However, there are few detailed studies on the mutational spectrum of poorly cohesive gastric carcinoma. Thus, this study aim to investigate its mutation profile based on clinicopathological characteristics.

Methods and results

Herein, we analysed the mutational pattern of 77 genes in a cohort of 91 patients with poorly cohesive carcinoma by using targeted sequencing, and evaluated the clinicopathological significance of the various mutations based on histological pattern, either signet ring cell (SRC) or other types of poorly cohesive carcinoma (not otherwise specified) (PCC‐NOS). Panels of seven (PIK3CA, CDH1, PTEN, RHOA, HDCA9, KRAS, and ATM), three (PIK3CA, CTNNB1, and KRAS) and two (HDCA9 and IGF1R) genes were associated with a diffuse infiltrative growth pattern, lymphovascular invasion, and perineural invasion, respectively. Furthermore, PDGFRB mutations were associated with a favourable prognosis, whereas MET mutations were associated with a poor prognosis. The PCC‐NOS‐predominant type was associated with a greater depth of invasion, lymph node metastasis and poorer prognosis than the SRC‐predominant type. Mutations in TP53, BRAF, PI3CA, SMAD4 and RHOA were associated with PCC‐NOS. Interestingly, RHOA‐mutated gastric cancers showed a distinct morphology, as they were characterised by a superficial SRC or tubular component and a deep invasive PCC‐NOS component with desmoplasia.

Conclusions

Taken together, our findings demonstrate that gastric poorly cohesive carcinomas show several mutational patterns associated with specific clinicopathological characteristics, and particularly show distinct morphological findings when associated with RHOA mutation.
2. CONFRONTING DEFEAT: CARL SCHMITT BETWEEN THE VICTORS AND THE VANQUISHED
Authors: TRAVERSO ENZO
Published: September 2017

Quoting a text on Tocqueville written by Carl Schmitt in 1946, Reinhart Koselleck hypothesized about the epistemological advantage of being vanquished in writing history. This essay analyzes Schmitt's intellectual and political positions in reaction to three successive defeats: the collapse of the German Empire in 1918; the end of the Weimar Republic in 1933; and the overthrow of the Third Reich in 1945. Schmitt was a German nationalist and, at least until Hitler's rise to power, an anti‐Nazi conservative, but he easily adapted to both the Weimar Republic in 1919 and National Socialism in 1933, two political turns that coincided with significant improvements in his academic career. He felt vanquished only in 1945, after his double imprisonment, the Nuremberg trial, and finally his retirement to Plettenberg. 1945 was a watershed that he symbolized through two metaphorical figures: the reactionary thinker of Spanish Absolutism Juan Donoso Cortés and Melville's literary character Benito Cereno. Thus, the case of Carl Schmitt does not confirm Koselleck's hypothesis, insofar as the most productive and creative part of his intellectual life does not fit into an awareness of being vanquished. Koselleck's statement deals with the gaze of the ruled, whereas Schmitt belonged to a different tradition of political thinkers interested in building domination and smashing revolution (Hobbes, Maistre, Donoso Cortés). He was a thinker of action, not of mourning. Defeat did not inspire, but rather paralyzed his thought.
3. CARL SCHMITT'S CONTRIBUTION TO A THEORY OF POLITICAL MYTH
Authors: LARA MARÍA PÍA
Published: September 2017

My goal in this essay is to show that myths have played a larger role than we might think in politics and in political theory and that myths are essential to politics. For this purpose I will use Schmitt's theory of myth, since he elaborated his theory with strong interpretations of two different myths: Hobbes's Leviathan and Shakespeare's Hamlet. I will compare Schmitt's interpretations of Hamlet with my own, as doing so will provide a critical view of Schmitt's conclusions, and it will enable me to develop my own conception of myth and its relations to political theory and history.
NOTES ON CAMPS, OR, COUNTERFACTUAL FÜHRERS AND THE STRUCTURE OF THE JOKE
Authors: Wurgaft Benjamin Aldes
Published: September 2017

In this review essay I explore the dynamics of “normalization” in historical and fictional depictions of the National Socialist past, examining both the “organic” normalization of catastrophic events through the passage of time, and efforts to normalize the Nazi past through aesthetics. Focusing on Gavriel Rosenfeld's Hi, Hitler: How the Nazi Past is Being Normalized in Contemporary Culture, I argue against many dimensions of Rosenfeld's account of normalization, particularly his claim that aesthetic normalization can undermine our moral judgments regarding the Holocaust. Drawing on Sigmund Freud on jokes, and Susan Sontag on Camp aesthetics, I argue that every effort to normalize the Holocaust, especially ones that work through humor and jokes (a major topic of Rosenfeld's book), actually maintain the Holocaust's status as a series of historical events resistant to “normalization.” If “normalization” is a process through which extraordinary, or morally charged, historical events lose their moral charge, then aesthetic efforts to normalize the Holocaust actually reinscribe the special moral status that Rosenfeld believes they erase.
METHODOLOGICAL INDIVIDUALISM VS. COLLECTIVIST HOLISM IN HISTORICAL EXPLANATION
Authors: Eldridge Richard
Published: September 2017

This review essay surveys and assesses Rage and Denials: Collectivist Philosophy, Politics, and Art Historiography, 1890–1947 by Branko Mitrović, focusing on a) Mitrović's case that German art‐historical practices during this period were factually ill‐founded, inconsistent, and motivated by narcissism and ethnic prejudice, and b) the broader issue of whether collectivist historical explanations of artistic and cultural developments can ever be apt.
Women, Drugs and the Death Penalty: Framing Sandiford
Authors: FLEETWOOD JENNIFER , SEAL LIZZIE
Published: September 2017

This article examines the impact and significance of women subject to capital punishment for drug offences. Women are subject to the death penalty for drug offences; wherever data are available they describe low‐level offenders, primarily drug mules. Sandiford's death sentence prompts widespread discussion about her, her culpability and the appropriateness of her punishment drawing on drug war discourse, and death penalty tropes. Framing analysis reveals the powerful and persistent nature of gendered binaries. The use of capital punishment against female mules troubles the gendered binaries that underpin US‐led drug war discourse, and highlights the death penalty as a gendered punishment.
Meteorological and environmental variables affect flight behaviour and decision‐making of an obligate soaring bird, the California Condor Gymnogyps californianus
Authors: Poessel Sharon A. , Brandt Joseph , Miller Tricia A. , Katzner Todd E.
Published: September 2017

The movements of animals are limited by evolutionary constraints and ecological processes and are strongly influenced by the medium through which they travel. For flying animals, variation in atmospheric conditions is critically influential in movement. Obligate soaring birds depend on external sources of updraft more than do other flying species, as without that updraft they are unable to sustain flight for extended periods. These species are therefore good models for understanding how the environment can influence decisions about movement. We used meteorological and topographic variables to understand the environmental influences on the decision to engage in flight by obligate soaring and critically endangered California Condors Gymnogyps californianus. Condors were more likely to fly, soared at higher altitudes and flew over smoother terrain when weather conditions promoted either thermal or orographic updrafts, for example when turbulence and solar radiation were higher and when winds from the east and north were stronger. However, increased atmospheric stability, which is inconsistent with thermal development but may be associated with orographic updrafts, was correlated with a somewhat higher probability of being in flight at lower altitudes and over rougher terrain. The close and previously undescribed linkages between Condor flight and conditions that support development of thermal and orographic updrafts provide important insight into the behaviour of obligate soaring birds and into the environmental parameters that may define the currently expanding distribution of Condors within and outside the state of California.
Thirty‐day mortality after systemic anticancer treatment as a real‐world, quality‐of‐care indicator: the Northland experience
Authors: Ang Edmond , Newton Los Vincent
Published: September 2017

Background

Systemic anticancer treatment (SACT) at the end of life is considered poor practice due to its futility and associated toxicities. Consequently, 30‐day mortality after SACT is increasingly recognised as a potential real‐world quality‐of‐care indicator in medical oncology.

Aims

Whangarei Base Hospital (WBH) provides outpatient SACT treatment to all patients living in the Northland region of New Zealand. The goal of this study was to report our 30‐day mortality after SACT and to contribute to the experience of its use in Australasia.

Methods

In this retrospective study, the WBH electronic database was searched to identify all patients who had received SACT in WBH from 1 January 2012 to 31 December 2016. Patients who died within 30 days of their last treatment were shortlisted. Records were reviewed identifying key demographic, disease, treatment and mortality data. Composite 30‐day mortality index and that of each tumour stream were calculated. Key findings were described using descriptive statistics.

Results

Over 5 years, 1103 patients received SACT in WBH, with 57 patients dying within 30 days of treatment, resulting in a composite 30‐day mortality rate of 5.17%. One patient died receiving curative intent SACT. More deaths occurred in SACT‐naïve patients and during the first two cycles of therapy. Of the deaths, 28% was attributed to SACT, while 59.7% was attributed to cancer progression.

Conclusion

Thirty‐day mortality rates were comparable to studies from larger institutions. We demonstrated the feasibility of this index for auditing practice in smaller oncology units over a longer timeframe.
Update on Aire and thymic negative selection
Authors: Passos Geraldo A. , Speck‐Hernandez Cesar A. , Assis Amanda F. , Mendes‐da‐Cruz Daniella A.
Published: September 2017

Twenty years ago, the autoimmune regulator (Aire) gene was associated with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy, and was cloned and sequenced. Its importance goes beyond its abstract link with human autoimmune disease. Aire identification opened new perspectives to better understand the molecular basis of central tolerance and self–non‐self distinction, the main properties of the immune system. Since 1997, a growing number of immunologists and molecular geneticists have made important discoveries about the function of Aire, which is essentially a pleiotropic gene. Aire is one of the functional markers in medullary thymic epithelial cells (mTECs), controlling their differentiation and expression of peripheral tissue antigens (PTAs), mTEC–thymocyte adhesion and the expression of microRNAs, among other functions. With Aire, the immunological tolerance became even more apparent from the molecular genetics point of view. Currently, mTECs represent the most unusual cells because they express almost the entire functional genome but still maintain their identity. Due to the enormous diversity of PTAs, this uncommon gene expression pattern was termed promiscuous gene expression, the interpretation of which is essentially immunological – i.e. it is related to self‐representation in the thymus. Therefore, this knowledge is strongly linked to the negative selection of autoreactive thymocytes. In this update, we focus on the most relevant results of Aire as a transcriptional and post‐transcriptional controller of PTAs in mTECs, its mechanism of action, and its influence on the negative selection of autoreactive thymocytes as the bases of the induction of central tolerance and prevention of autoimmune diseases.
Impact of Political Identity and Past Crisis Experience on Water Attitudes
Authors: Callison Coy , Holland Derrick
Published: September 2017

With stories of regional diminishing water resources and tainted municipal water supplies consistently populating the news, a nationwide survey was conducted to gauge overall concern and attitudes toward water scarcity and water pollution, as well as scientists and scientific information regarding water crises. Of particular interest was the question of how political ideology and past experience with scarcity and/or pollution impact pro‐water attitudes and intention to exhibit positive water behaviors. Multivariate analyses of data suggest that Liberals are more concerned about water scarcity and pollution and more likely to conserve and combat pollution than their Conservative counterparts. People who have experienced a past water crisis are also more concerned and act more favorably toward water than those without crises experience. The interaction between political ideology and water crises experience is such that Conservatives with experience display more water concern than do Conservatives without experience. Liberals, regardless of experience, exhibit water concern and favorable action. Results offer direction to policy makers, water resource managers, and strategic communicators regarding how constituent audiences can be segmented.
Land Use Modification and Changing Redox Conditions Releases Selenium and Sulfur from Historic Marsh Sediments
Authors: Hibbs Barry J. , Lee Monica , Ridgway Rachel
Published: September 2017

San Diego Creek Watershed forms the southern end of the Coastal Plain that covers much of Los Angeles County and Orange County, California. Prior to 1900, the central part of the watershed was marshland, and the edges of the watershed were used for grazing sheep and cattle. After 1900, cattle and sheep grazing were displaced by irrigated agriculture. Drainage ditches and channels were constructed to drain the marshes to “reclaim” the land for agriculture. Today, the drainage ditches and channels still exist in the watershed, which has undergone massive urban growth. Shallow groundwater discharges into these channels and ditches, which then flows as surface water, into Upper Newport Bay a thriving ecological habitat. Surface flows in these channels usually exceed the United States Environmental Protection Agency (EPA) aquatic water quality criterion for selenium (Se) of 3.1 μg/L (lotic) for protection of aquatic life. Selenium in surface flows is caused by groundwater inflows. The highest concentrations of Se in shallow groundwater in the watershed coincide with the marshland area that was displaced by agriculture. Concentrations of Se in shallow groundwater beneath the former marsh area often exceed 25 μg/L and are as high as 478 μg/L. In areas where marshes were absent, concentrations of Se in groundwater are usually less than 25 μg/L. In the marsh, Se accumulated due to chemically reducing conditions in the organic‐rich marshland soils that caused it to precipitate as elemental Se(0) and metal selenides, Se(−II). We hypothesize that the elevated concentrations of Se in groundwater where the marshes once existed are a direct result of the destruction of the marsh. Today, oxidizing groundwater flows through the soils where the marshes once existed, remobilizing Se as selenate, a water soluble and oxidized form of Se(+VI) that is highly mobile in aquifer systems.
Low temperature ferroelectric behavior in morphotropic Pb (Zr1−xTix)O3
Authors: Chapman Jacob B. J. , Gindele Oliver T. , Vecchini Carlo , Thompson Paul , Stewart Mark , Cain Markys G. , Duffy Dorothy M. , Kimmel Anna V.
Published: September 2017

We provide an insight into the switching of near‐morphotropic composition of PZT, using molecular dynamics simulations and electrical measurements. The simulations and experiments exhibit qualitatively similar hysteretic behavior of the polarization for different temperatures showing widening of the P‐E loops and the decrease in the coercive field toward high temperatures. Remarkably, we have shown that polarization switching at low temperatures occurs via polarization rotation, that is a fundamentally different mechanism from high‐temperature switching, which is nucleation driven.
Emergence of defect fluorite structure in nano‐sized thoria through doping with some divalent transition‐metal ions
Authors: Kumar Manish , Tripathi Vikash Kumar , Nagarajan Rajamani
Published: September 2017

With the objective of incorporating some divalent transition‐metal ions in thoria and to comprehend its effect on the crystal structure, electronic as well as catalytic properties, Ni2+, Cu2+ and Cd2+ substituted thoria samples were synthesized by the epoxide gel method. Of the two concentrations investigated, 10 mol% of Ni2+, Cu2+, and Cd2+ could be substituted retaining the fluorite structure and phase separation into individual oxides was noticed for 15 mol%. The average crystallite size of thoria and 10 mol% substituted samples was 14 nm. Le‐Bail structural refinements of Powder X‐ray diffraction (PXRD) patterns indicated marginal increase in unit cell constant for the Cd2+ substituted sample and a decrease for Ni2+ and Cu2+ substituted samples. In addition to broadening of the band at around 460 cm−1 (F2g vibration of the fluorite), less intense band near 560‐590 cm−1 emerged for all the transition‐metal ion‐containing samples in the Raman spectra implying the formation of oxygen defects. The absorption edge in the UV‐visible spectra moved toward higher wavelength for Cd2+, Ni2+ and Cu2+ containing samples as compared to pure thoria. In addition, d‐d transition was observable for Ni2+ and Cu2+ containing samples. By virtue of these changes in the electronic structure of transition‐metal ion‐containing samples, they were examined as catalysts for the degradation of aqueous Rhodamine‐6G (Rh‐6G) dye solutions under visible radiation.
Interaction of a ceria‐based anode functional layer with a stabilized zirconia electrolyte: Considerations from a materials perspective
Authors: Lenser Christian , Jeong Hyeondeok , Sohn Yoo Jung , Russner Niklas , Guillon Olivier , Menzler Norbert H.
Published: September 2017

We report on the materials interaction of gadolinium‐doped ceria (GDC) and yttria‐stabilized zirconia (YSZ) in the context of high‐temperature sintering during manufacturing of anode supported solid oxide fuel cells (AS–SOFC). While ceria‐based anodes are expected to show superior electrochemical performance and enhanced sulfur and coking tolerance in comparison to zirconia‐based anodes, we demonstrate that the incorporation of a Ni–GDC anode into an ASC with YSZ electrolyte decreases the performance of the ASC by approximately 50% compared to the standard Ni–YSZ cell. The performance loss is attributed to interdiffusion of ceria and zirconia during cell fabrication, which is investigated using powder mixtures and demonstrated to be more severe in the presence of NiO. We examine the physical properties of a GDC–YSZ mixed phase under reducing conditions in detail regarding ionic and electronic conductivity as well as reducibility, and discuss the expected impact of cation intermixing between anode and electrolyte.
Addressing the Life Cycle of Sewers in Contrasting Cities through an Eco‐Efficiency Approach
Authors: Petit‐Boix Anna , Arnal Carla , Marín Desirée , Josa Alejandro , Gabarrell Xavier , Rieradevall Joan
Published: September 2017

Evaluating the sustainability of the urban water cycle is not straightforward, although a variety of methods have been proposed. Given the lack of integrated data about sewers, we applied the eco‐efficiency approach to two case studies located in Spain with contrasting climate, population, and urban and sewer configurations. Our goal was to determine critical variables and life cycle stages and provide results for decision making. We used life cycle assessment and life cycle costing to evaluate their environmental and economic impacts. Results showed that both cities have a similar profile, albeit their contrasting features, that is, operation and maintenance, was the main environmental issue (50% to 70% of the impacts) and pipe installation registered the greatest economic capital expenditure (70% to 75%) due to labor. The location of the wastewater treatment plant (WWTP) is an essential factor in our analysis mainly due to the topography effects (e.g., the annual pump energy was 13 times greater in Calafell). Using the eco‐efficiency portfolio, we observed that sewers might be less eco‐efficient than WWTPs and that we need to envision their design in the context of an integrated WWTP‐sewer management to improve sewer performance. In terms of methodological approach, the bidimensional nature of eco‐efficiency enables the benchmarking of product systems and might be more easily interpreted by the general public. However, there are still some constraints that should be addressed to improve communication, such as the selection of indicators discussed in the article.
A Retrospective Cohort Study of the Cumulative Survival Rate of Obturator Prostheses for Marsupialization
Authors: Murakami Mamoru , Nishi Yasuhiro , Nishio Misaki , Minemoto Yoko , Shimizu Takaharu , Nishimura Masahiro
Published: September 2017

Purpose

After marsupialization of benign tumors and jawbone cysts, insertion of an obturator prosthesis maintains the surgical opening and improves hygiene. To date, there have been no reports clarifying the relationship between the obturator design and treatment outcomes. The purpose of this study was to examine the survival rate of three types of obturator, and to investigate the factors that expedite the removal of the obturator.

Materials and Methods

The subject group comprised 100 patients who had an obturator inserted after marsupialization at Kagoshima University Hospital between May 31, 2012 and March 31, 2015; 73 patients with lesions in the mandible were eligible. Three types of mandibular obturator were designed and inserted, considering the teeth missing, the anteroposterior position of the lesion, and the buccolingual direction of marsupialization. The endpoint of this study was defined as the removal of the obturator. The analyzed predictor values for the endpoint were age, gender, remaining teeth, nature of primary disease, anteroposterior location of primary disease, buccolingual direction of marsupialization, type of obturator, and dates of insertion and removal.

Results

No significant differences were found in the cumulative survival rate among the three types of obturator. Early obturator removal was more frequent in patients with cysts, anterior lesions, and/or marsupialization from the occlusal direction

Conclusions

Because obturator design had minimal effect on the ability of the appliance to maintain the surgical opening, it is preferable to use the least invasive design. Our findings also suggest that the follow‐up examination should account for the type of primary disease, the anteroposterior location of the lesion, and the buccolingual direction of marsupialization.
Volumetric Evaluation of Void/Gap Formation and Microleakage Cementing Fiber Posts on Extracted Teeth with Three Different Cements
Authors: Yikilgan İhsan , Uzun Ozgur , Gürel Mügem , Bala Oya , Ömürlü Hüma , Kayaoglu Guven
Published: September 2017

Purpose

To evaluate microleakage in roots restored with fiber posts cemented using three different luting cements, to measure the volume of voids/gaps within the obturated/postcemented root canals, and to examine whether microleakage and the volume of voids/gaps were correlated.

Materials and Methods

Thirty‐six extracted human mandibular incisors were decoronated, and the root canals were obturated using gutta‐percha and sealer in the experimental groups (n = 30). Six roots were used as controls. A standard post space was prepared, and an identically sized fiber post was cemented in each experimental specimen using one of three luting cements (Panavia F2.0, Bifix SE, GC FujiCEM; n = 10 each). The specimens were scanned using micro–computed tomography, and the volume of voids/gaps was determined. The specimens were then subjected to a fluid filtration assay to evaluate microleakage.

Results

The volume of voids/gaps was significantly lower in the GC FujiCEM group, and significantly less microleakage occurred in the Bifix SE group compared with other groups (both p < 0.001). A significant correlation between the volume of voids/gaps and leakage was found only in the Panavia F2.0 group (p = 0.003; r = 0.830). No such correlation was found in the analysis of all groups combined.

Conclusions

The group with the greatest volume of voids/gaps (Bifix SE) showed the least microleakage, and the group with the smallest volume of voids/gaps (GC FujiCEM) showed the most microleakage. Panavia F2.0 ranked between and exhibited significant correlation.
Preferences Related to the Use of Mobile Apps as Dental Patient Educational Aids: A Pilot Study
Authors: Bohn Courtney E. , McQuistan Michelle R. , McKernan Susan C. , Askelson Natoshia M.
Published: September 2017

Purpose

Numerous patient education apps have been developed to explain dental treatment. The purpose of this study was to assess perceptions and preferences regarding the use of apps in dental settings.

Materials and Methods

Four patient education apps describing fixed partial dentures were demonstrated to participants (N = 25). Questions about each app were asked using a semi‐structured interview format to assess participants’ opinions about each app's content, images, features, and use. Sessions were analyzed via note‐based methods for thematic coding.

Results

Participants believed that apps should be used in conjunction with a dentist's explanation about a procedure. They desired an app that could be tailored for scope of content. Participants favored esthetic images of teeth that did not show structural anatomy, such as tooth roots, and preferred interactive features.

Conclusions

Patient education apps may be a valuable tool to enhance patient‐provider communication in dental settings. Participants exhibited varying preferences for different features among the apps and expressed the desire for an app that could be personalized to each patient. Additional research is needed to assess whether the use of apps improves oral health literacy and informed consent among patients.
Unintentional fatal child drowning in the bath: A 12‐year Australian review (2002–2014)
Authors: Peden Amy E , Franklin Richard C , Pearn John H
Published: September 2017

Aim

To establish the prevalence of unintentional fatal drowning in baths involving children <18 years in Australia and to identify causal factors to underpin prevention.

Methods

We report a total population study of all childhood (0–17 years) unintentional drowning fatalities in baths (bathtubs, spa baths and showers) in Australia between 1 July 2002 and 30 June 2014. Demographic, forensic and aetiological data (including co‐bathing, use of bath aids, supervision and enactment of cardiopulmonary resuscitation) were documented for each victim.

Results

Seventy‐eight children were identified; two thirds (66.7%) were under 2 years old, of which 43.6% were aged less than 1 year (1.0/100 000/annum) and 23.1% 1–2 years (0.27/100 000/annum). Nine older children (10–17 years) also drowned. Common causes included: infants and children unable to hold their head out of water while unsupervised and associated pre‐existing medical conditions, including epilepsy. All children who drowned were left without adult supervision. No child drowned in a bath with water deeper than 40 cm (M = 19.4 cm). Custodian‐reported ‘time left unsupervised’ ranged from 30 s to 60 min. Children with pre‐existing medical conditions were, on average, older (9.9 years; confidence interval: 7.9–11.9) and left unsupervised for longer (M = 15.4 min; confidence interval: 3.8–27.1) than those without.

Conclusions

On average, 6.5 children drown every year in baths in Australia. Children aged younger than 1 year are most affected, with both genders equally represented. Infants and toddlers left unsupervised, false confidence in the preventive role of bath aids, unrealistic expectations in the supervisory capabilities of co‐bathing children and epilepsy remain threats to children in the bath.
β-2-himachalen-6-ol protects against skin cancer development in vitro and in vivo
Authors: Daaboul Hamid E , Daher Costantine F , Taleb Robin I , Boulos Joelle , Bodman-Smith Kikki , Boukamp Petra , Shebaby Wassim N , Dagher Carol , El-Sibai Mirvat , Mroueh Mohamad A
Published: September 2017

Background

Previous studies in our laboratory showed that Daucus carota oil extract (DCOE) possesses remarkable in-vitro anticancer activity and antitumour promoting effect against DMBA/TPA skin carcinogenesis in mice. Chemical analysis of DCOE led to the isolation of the β-2-himachalen-6-ol (HC), major sesquiterpene with a potent anticancer activity against various colon, breast, brain and skin cancer cells. This study investigated the anticancer activity of HC against invasive epidermal squamous cell carcinoma cells and evaluated its effect in a DMBA/TPA skin carcinogenesis Balb/c murine model.

Methods

HaCaT-ras II-4 epidermal squamous cells were treated with HC (1, 5, 10, 25 and 50 μg/ml), and cell viability was evaluated with WST 1 assay kit. Cell cycle analysis was carried out by flow cytometry, and pro/anti-apoptotic proteins were measured using Western blot. The effect of topical and intraperitoneal (IP) treatment with HC in mice was assessed using the DMBA/TPA skin carcinogenesis model. Cisplatin (2.5 mg/kg; IP) was used as a positive control. Papilloma incidence, yield and volume were monitored, and isolated papillomas were assessed for their pro/anti-apoptotic proteins and morphology.

Results

β-2-himachalen-6-ol showed a dose-dependent decrease in cell survival with an IC50 and IC90 of 8 and 30 μg/ml, respectively. Flow cytometry analysis revealed that treatment with 10 μg/ml HC significantly increased the number of cells undergoing late apoptosis (28%), while 25 μg/ml caused a larger cell shift towards late apoptosis (46.6%) and necrosis (39%). A significant decrease in protein levels of p53 and Bcl-2 and a significant increase in p21 and Bax were observed. Also, there was a significant decrease in p-Erk and p-Akt protein levels. The treatment of mice (IP and topical) with HC caused a significant decrease in papilloma yield, incidence and volume. Similar effects were observed with cisplatin treatment, but HC-treated groups exhibited twofold to threefold increase in survival rates. Similar patterns in the pro- and anti-apoptotic proteins were observed in mice treated with HC, except for a significant increase in p53 protein.

Conclusions

In conclusion, HC treatment induced cell cycle arrest (low dose) and promoted apoptosis partly via inhibition of the MAPK/ERK and PI3K/AKT pathways with no significant toxicity to laboratory mice.
Development of extended-release solid dispersion granules of tacrolimus: evaluation of release mechanism and human oral bioavailability
Authors: Tsunashima Daisuke , Yamashita Kazunari , Ogawara Ken-ichi , Sako Kazuhiro , Hakomori Tadashi , Higaki Kazutaka
Published: September 2017

Objectives

We aimed to prepare a once-daily modified-release oral formulation of tacrolimus by utilizing an extended-release granules (ERG).

Methods

Extended-release granules were prepared using ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC) and lactose via a solvent evaporation method with ethanol. Physicochemical and biopharmaceutical studies were performed to determine the formulation with optimum release profile of tacrolimus from ERG.

Key findings

Tacrolimus existed in an amorphous state in ERG. Tacrolimus release from ERG was attenuated by EC and facilitated by lactose, suggesting that drug release kinetics could adequately be regulated by these components. Those release profiles were consistent with Higuchi's equation, suggesting a diffusion-type release mechanism. Smooth surface of ERG changed to the structure with pores after the release test, likely derived from the dissolution of HPMC and lactose. But ERG structure formed by EC was still maintained after the release test, leading to the longer maintenance of diffusion-type release. Two ERG formulations selected by blood concentration simulation successfully provided long-term retention of tacrolimus in blood in a human absorption study.

Conclusions

We successfully developed the formulation exhibiting a significant reduction in Cmax, the longer mean residence time and AUC close to that of an immediate-release tacrolimus formulation, being preferred from the viewpoint of safe and effective immunosuppressant pharmacotherapy.
Weak bones in diabetes mellitus – an update on pharmaceutical treatment options
Authors: Lin Daphne P L , Dass Crispin R
Published: September 2017

Objectives

Diabetes mellitus is often associated with a number of complications such as nephropathy, neuropathy, retinopathy and foot ulcers. However, weak bone is a diabetic complication that is often overlooked. Although the exact mechanism for weak bones within diabetes mellitus is unclear, studies have shown that the mechanism does differ in both type I (T1DM) and type II diabetes (T2DM). This review, however, investigates the application of mesenchymal stem cells, recombinant human bone morphogenetic protein-2, teriparatide, insulin administration and the effectiveness of a peroxisome proliferator-activated receptor-ϒ modulator, netoglitazone in the context of diabetic weak bones.

Key findings

In T1DM, weak bones may be the result of defective osteoblast activity, the absence of insulin's anabolic effects on bone, the deregulation of the bone–pancreas negative feedback loop and advanced glycation end product (AGE) aggregation within the bone matrix as a result of hyperglycaemia. Interestingly, T2DM patients placed on insulin administration, thiazolidinediones, SGLT2 inhibitors and sulfonylureas have an associated increased fracture risk. T2DM patients are also observed to have high sclerostin levels that impair osteoblast gene transcription, AGE aggregation within bone, which compromises bone strength and a decrease in esRAGE concentration resulting in a negative association with vertebral fractures.

Effective treatment options for weak bones in the context of diabetes are currently lacking. There is certainly scope for discovery and development of novel agents that could alleviate this complication in diabetes patients.
Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies
Authors: Cao Lei , Kwara Awewura , Greenblatt David J
Published: September 2017

Objectives

Excessive exposure to acetaminophen (APAP, paracetamol) can cause liver injury through formation of a reactive metabolite that depletes hepatic glutathione and causes hepatocellular oxidative stress and damage. Generation of this metabolite is mediated by Cytochrome-P450 (CYP) isoforms, mainly CYP2E1. A number of naturally occurring flavonoids can mitigate APAP-induced hepatotoxicity in experimental animal models. Our objective was to determine the mechanism of these protective effects and to evaluate possible human applicability.

Methods

Two flavonoids, luteolin and quercetin, were evaluated as potential inhibitors of eight human CYP isoforms, of six UDP-glucuronosyltransferase (UGT) isoforms and of APAP glucuronidation and sulfation. The experimental model was based on in-vitro metabolism by human liver microsomes, using isoform-specific substrates.

Key findings

Luteolin and quercetin inhibited human CYP isoforms to varying degrees, with greatest potency towards CYP1A2 and CYP2C8. However, 50% inhibitory concentrations (IC50 values) were generally in the micromolar range. UGT isoforms were minimally inhibited. Both luteolin and quercetin inhibited APAP sulfation but not glucuronidation.

Conclusions

Inhibition of human CYP activity by luteolin and quercetin occurred with IC50 values exceeding customary in-vivo human exposure with tolerable supplemental doses of these compounds. The findings indicate that luteolin and quercetin are not likely to be of clinical value for preventing or treating APAP-induced hepatotoxicity.
Alkaline extractive crude polysaccharide from Russula senecis possesses antioxidant potential and stimulates innate immunity response
Authors: Khatua Somanjana , Acharya Krishnendu
Published: September 2017

Objectives

Over past decades, investigation on bioactive polysaccharides extracted from mushroom by heated water reflux has been an emerging field of biomedicine especially in the area of immune stimulation. While studies with macromolecules isolated from remainder residue of aqueous extraction are scarce. In this context, crude polysaccharide from a traditionally edible macrofungus, Russula senecis, was prepared (RuseCap) by alkaline solvent using leftover residue of that conventional process and its structural along with therapeutic properties were evaluated.

Key findings

Investigation by FT-IR, HPTLC, GC-MS and spectrophotometry showed that the fraction was mainly consisted of carbohydrate with backbone of xylose, rhamnose, mannose and glucose (mostly β-glucan). Besides, RuseCap exhibited strong antioxidant activity evident by radical scavenging (superoxide, hydroxyl, DPPH, ABTS), chelating ability and reduction power where EC50 values ranged from 257 to 4068 μg/ml concentration. In addition, it also exhibited immune-boosting potentiality as the treatment effectively induced proliferation, phagocytosis, nitric oxide production, intracellular reactive oxygen species generation, morphological changes and increased transcription level of iNOS, COX-2, TNF-α, IL-6 genes in macrophage cells.

Conclusions

Overall, the study provided blueprint for extended utilization of R. senecis basidiocarps beyond hot water process and defined use of RuseCap as potent therapeutic agent against free radicals as well as deprived immunity.
Phytochemistry and pharmacological potential of Cassia absus – a review
Authors: Ahmad Saeed , Hassan Ayesha , Abbasi Waheed Mumtaz , Rehman Tayyeba
Published: September 2017

Objectives

Cassia absus is a plant of the family fabaceae with Ayurvedic ethnomedical records. It is used in traditional medicine for the treatment of bronchitis, asthma, cough, conjunctivitis, leucoderma, renal and hepatic diseases, constipation, tumors, venereal ulcer, headache, hemorrhoids and wound healing. Preliminary in vitro and in vivo studies have provided valuable scientific evidence for its use. This review aims to summarize reported pharmacognosy, traditional uses, phytochemistry and pharmacological potential of C. absus while identifying potential areas of further research of plant.

Key findings

The review comprises literature pertaining to the evidence base therapeutic potential, pharmacognosy and phytochemistry of C. absus spanning from 1935 to 2016 using published articles in peer-reviewed journals, ethno botanical text books, and worldwide accepted scientific databases via electronic search (Elsevier, Google Scholar, PubMed, Scopus, Springer, Web of Science, Wiley online library). Kew Botanical Garden databases and the Plant List were used to authenticate the scientific names. Different pharmacological experiments in many in-vitro and in-vivo models have proved the potential of C. absus with antihypertensive, antifertility, antifungal, anti-inflammatory, anti-hyperglycemic, anti-glycation, antibacterial activity, α– amylase inhibitory activity, antioxidant and reducing activitity etc. chaksine, iso-chaksine, saturated and unsaturated fatty acids, chrysophanol, aloe-emodin and a wide range of chemical compounds have also been reported. Toxicity studies reveal the nontoxic nature of C. absus at a dose of 2000 mg/kg, however, plant possess reproductive toxicity and can be used as birth control or abortifacient.

Reported activities suggest that there is sufficient pharmacological potential for developing C. absus as a drug for hypertension, infections, diabetes and its complications. However, heterogeneity in study protocol and conflicting results mask the ability to replicate these studies. So, future studies should be replicated in line with best practices. More toxicological studies would aid the progress to clinical trial studies. Various ethno medical uses of C. absus have not been evaluated yet.
Psychosocial Correlates of Ever Having a Pap Test and Abnormal Pap Results in a Sample of Rural Appalachian Women
Authors: Mark Kristen P. , Crosby Richard A. , Vanderpool Robin C.
Published: September 2017

Background

Despite known prevention and screening efforts, there are higher invasive cervical cancer rates in Appalachia than in other areas of the United States and higher mortality rates in the Appalachian region of Kentucky compared to Appalachian regions of other states.

Purpose

The primary purpose of this study was to investigate the association of psychosocial factors relevant to cervical cancer and the outcome of ever having a Pap test in a rural sample of women. The secondary purpose was to determine whether any of the same psychosocial factors were also associated with ever having an abnormal Pap test result among women with a self‐reported history of having one or more Pap tests in their lifetime.

Methods

Data were collected in fall of 2013 from 393 women in 8 economically distressed counties of rural Appalachian Kentucky. Women completed an interviewer‐administered survey assessing sociodemographic and health information as well as beliefs about cervical cancer.

Findings

Multivariate logistic regression results indicated that low income and greater perceived local fatalism were significant predictors of never having a Pap test. Lack of personal control over prevention, and peer and family influences were significant predictors of ever having an abnormal Pap test result.

Conclusions

Educational efforts targeted in rural Appalachia would be supported by encouraging the benefits of early and consistent screening, altering the established norms of community fatalism and lack of personal control over prevention, and creating targeted messages through public campaigns that convince rural Appalachian women that cervical cancer is highly preventable and screenable.
A patent defence approach to sharing aquaculture genetic resources across jurisdictional areas
Authors: Humphries Fran
Published: September 2017

Access and benefit sharing (ABS) of genetic resources is a concept that is increasingly important for product development in aquaculture. ABS regulates the way aquatic genetic resources can be accessed from the world's waters and how the benefits that result from their use are shared between the providers and users of genetic resources and their derivatives. This article gives an overview of the multiple approaches to sharing aquaculture genetic resources under ABS regimes across the three jurisdictional areas in which they are found—waters within national jurisdiction, beyond national jurisdictions and in the Antarctic Treaty Area. It highlights the complexity and inconsistencies relating to obligations for technology transfer across the various regimes and the implications this has for sharing genetic resources for use in aquaculture. It offers a practical solution to navigating this complexity by using an evolving patent defence approach consistent with the World Trade Organisation's Agreement on Trade‐Related Aspects of Intellectual Property Rights (TRIPS). It concludes that this approach can guide the resolution of legal challenges that ABS regimes across the jurisdictional areas have in common, which concern derivatives and commercial use of genetic resources.