bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the use of magnetic sector secondary ion mass spectrometry to investigate 14C distribution in Magnox reactor core graphite
Authors: Payne Liam , Heard Peter J. , Scott Thomas B.
Published: December 2015

Large quantities of irradiated graphite will arise from the decommissioning of the UK's Magnox power stations. Irradiated graphite contains 14C as well as other longer lived radionuclides (e.g. 36Cl). The potential use of magnetic sector secondary ion mass spectrometry (MS-SIMS) to examine the distribution of the 14C within trepanned graphite samples from a Magnox nuclear power station has been investigated. This work indicates that the methodology proposed has the potential to be used to analyse irradiated graphite samples with preliminary results highlighting a possible 14C enrichment in the carbonaceous deposit found on a channel wall sample. 14C concentrations in samples without this deposit were below the limits of detection of the instrument. The methodology used for these determinations ensured that possible mass interferences between 14C species and oxygen-bearing or nitrogen-bearing species were eliminated from the analysis. Future work will utilize the methodology proposed in this work on a larger number of samples.
Effect of solution composition on the recrystallization of kaolinite to feldspathoids in hyperalkaline conditions: limitations of pertechnetate incorporation by ion competition effects
Authors: Littlewood Janice , Shaw Samuel , Bots Pieter , Peacock Caroline L. , Trivedi Divyesh , Burke Ian T.
Published: December 2015

The incorporation of pertechnetate (TcO4–) into feldspathoids produced by alkaline alteration of aluminosilicate clays may offer a potential treatment route for 99Tc-containing groundwater and liquors. Kaolinite was aged in NaOH to determine the effect of base concentration, temperature, and solution composition on mineral transformation and pertechnetate uptake. In all reactions, increased temperature and NaOH concentration increased the rate of kaolinite transformation to feldspathoid phases. In reactions containing only NaOH, sodalite was the dominant alteration product; however, small amounts (6–15%) of cancrinite also formed. In experiments containing NaOH/Cl and NaOH/NO3 mixtures, sodalite and nitrate cancrinite were crystallized (at 70°C), with no reaction intermediates. The addition of SO42– crystallized sulfatic sodalite at 40 and 50°C, but at higher temperatures (60 and 70°C) sulfatic sodalite transforms to vishnevite (sulfatic cancrinite). In experiments where a pertechnetate tracer was added (at ∼1.5 μmol l–1), only 3–5% of the 99Tc was incorporated into the feldspathoid phases. This suggests that the larger pertechnetate anion was unable to compete as favourably for the internal vacancies with the smaller OH–, NO3–, SO42– or Cl– anions in solution, making this method likely to be unsuitable for groundwater treatment.
MEMS sensor-based monitoring system for engineered geological disposal facilities
Authors: Yang Wenbin , Lunn Rebecca , Tarantino Alessandro
Published: December 2015

The design of a novel MEMS (Micro-Electro-Mechanical System) sensor-based monitoring system is presented in this article for the in situ monitoring of the conditions (temperature, relative humidity) of an engineered bentonite barrier for the underground disposal of radioactive waste in a geological disposal facility (GDF). A first prototype of the monitoring system incorporating multiple state-of-the-art MEMS sensors has been developed on a PCB-based (Printed Circuit Board) structure, in order to measure the variation of temperature and relative humidity inside a cylindrical bentonite block during the hydration process. The monitoring system comprises separate sensor boards, the microcontroller-equipped interface board and the software user interface in the Labview environment. One of the main design priorities is to reduce the size of the embedded sensors in order to minimize their influence on the hydro-mechanical response of the bentonite block. The sensor boards are encapsulated in different manners to protect them from moisture, chemical corrosion and mechanical shocks. The sensor system has been tested and calibrated in the temperature range between –20°C and 120°C, and at different relative humidity levels implemented by saturated salt solutions in enclosed containers. Test results demonstrate that the sensors have shown good functionality and robustness in harsh test environments such as high temperature and high humidity. Both temperature and relative humidity sensors have shown satisfactory precision level and temporal stability, which are in good accordance with the design specification of these devices.
Consequence modelling of hypothetical post-closure criticality events for spent fuel disposal
Authors: Mason R. M. , Martin J. K. , Smith P. N. , Winsley R. J.
Published: December 2015

In support of the Radioactive Waste Management (RWM) safety case for a geological disposal facility (GDF) in the UK, there is a regulatory requirement to consider the likelihood and consequences of nuclear criticality. Waste packages are designed to ensure that criticality is not possible during the transport and operational phases of a GDF and for a significant period post-closure. However, over longer post-closure timescales, conditions in the GDF will evolve.

For waste packages containing spent fuel, it can be shown that, under certain conditions, package flooding could result in a type of criticality event referred to as 'quasi-steady-state' (QSS). Although unlikely, this defines a 'what-if' scenario for understanding the potential consequences of post-closure criticality. This paper provides an overview of a methodology to understand QSS criticality and its application to a spent fuel waste package.

The power of such a hypothetical criticality event is typically estimated to be a few kilowatts: comparable with international studies of similar systems and the decay heat for which waste packages are designed. This work has built confidence in the methodology and supports RWM's demonstration that post-closure criticality is not a significant concern.
Requirement of the assessment strategy for biosphere in mature safety cases for nuclear waste repositories – Finland case
Authors: Ikonen A. T. K.
Published: December 2015

In safety assessments for nuclear waste disposal, the biosphere is a completely open system, whereas the bedrock can be treated with comparably simple boundary conditions. The bedrock has a vital role in providing and maintaining favourable conditions for the waste, but the public interest tends to focus on the biosphere. More importantly, the bedrock groundwater does arrive from the biosphere. Also, the regulations usually set the safety criteria in terms of doses occurring in the biosphere. Thus, it is reasonable to address the biosphere as a part of the disposal system, performance of which should be described based on conceptual models that cover phenomena and processes controlling radionuclide release and transport. From these, the actual assessment models and data are expected to be derived based on high-level research and expertise obtained through empirical study. In this paper, the complexity expected of a biosphere assessment within a mature safety case is discussed through the example of the Finnish regulations and recent safety cases for nuclear waste disposal. Both elaborate and complex presentations and stylised approaches have their benefits, and a balance needs to be sought.
State-of-the-art and proof-of-concept installations for repository concepts based in crystalline rock
Authors: Kronberg Magnus , Gugala Jan , Haapala Keijo
Published: December 2015

Over the last five decades private and national energy programmes worldwide have been producing a variety of radioactive wastes. One of the safest ways of disposing of this waste is to bury it deep underground in purpose-built geological disposal facilities. Currently, there is no operating geological repository in Europe for high-level waste but the goal of the IGD-TP is that the first repository shall be fully operational before the year 2025. Several studies and experiments are ongoing at various potential repository sites in Europe with the goal to establish general approaches that can be adapted for any country in need of a geological repository.

The Swedish Nuclear Fuel and Waste Management Co (SKB) in Sweden and Posiva Oy in Finland are developing a method for geological disposal of high-level long-lived nuclear waste in crystalline rock, the KBS-3 method. KBS-3V (vertical) is both organizations reference design, but KBS-3H (horizontal) emplacement is also being researched as a potential alternative. Of high importance in the development is demonstrating the technical feasibilityin situof safe and reliable construction, manufacturing, disposal and sealing of such geological disposal facilities. Parts of these demonstrations are carried out under the framework of EurAtom/FP7 and one of these projects is the LUCOEX project where SKB is demonstrating horizontal emplacement, the Multi Purpose Test (MPT), and Posiva is demonstrating vertical buffer installation processes.

The MPT includes the key components of the horizontal design and comprises all essential steps; manufacturing of the full-scale components, their assembly, installation in the drift and monitoring of the early buffer evolution. The MPT installation was successfully performed in late 2013. By combining the components, an initial verification of the design implementation has been achieved. At the same time, integrating the components has meant the recognition of some design weaknesses and the design will be updated accordingly.

Posiva's KBS-3V buffer installation equipment that places buffer blocks with high precision in vertical deposition holes is currently being developed and will be tested during 2014 and 2015 in real underground conditions. The machine uses vacuum lifting tools for moving the buffer blocks and laser scanning technology to position both the machine and blocks. Functionality of the concept and equipment selected will be confirmed by the tests and the installation tests will provide important information about the suitability of the selected buffer dimensions and tolerances.
Multi-scale gas transport modelling for the EC FORGE project
Authors: Bond A. E. , Thatcher K. E. , Norris S.
Published: December 2015

The generation and migration of gas within and around proposed radioactive waste disposal facilities is potentially a safety critical process. A safety case for a facility that generates significant quantities of gas (e.g. through metal corrosion or radiolysis) will require demonstration that gas migration around and away from the waste is sufficiently understood and will not breach the safety case for the facility. Models can be used to understand the likely hydraulic evolution of such a disposal facility, but the models need to consider processes over a range of scales. A whole repository may extend over kilometres, with individual disposal cells at the scale of tens of metres and features which provide pathways for gas migration on a centimetre scale. All of these features may be significant from a safety perspective and capturing the impact of all of these features in a single model is a significant challenge.

This paper presents an approach to tackling this multi-scale problem, which allows the whole repository to be modelled in a computationally efficient manner. The approach involves identifying areas within the modelled domain that show very similar behaviour, and representing these areas with sub-models, so that small-scale features are retained, but computational overhead is decreased by using the results in more than one location in the model domain. The approach allowed a model of a whole repository to be run on a single processor core, whilst maintaining the small-scale features of the system. The model results were compared against more conventional upscaling techniques and show the advantage of a more detailed representation of small-scale features. The model results reflect the conceptual understanding of how gas would migrate in a repository.
Representation of estuarine, coastal and marine biosphere systems within post-closure performance assessments supporting geological disposal of higher activity radioactive wastes in the UK
Authors: Walke R. C. , Thorne M. C. , Smith J. T. , Kowe R.
Published: December 2015

Radioactive Waste Management Limited (RWM) is tasked with implementing geological disposal of the United Kingdom's (UK) higher activity radioactive wastes. This paper describes how RWM's biosphere modelling capability has been extended from a solely terrestrial model to allow potential contaminant releases to estuarine, coastal and marine systems around the UK to be represented. The new models aim to strike a balance between being as simple as can be justified, erring on the side of conservative estimates of potential doses, while also representing the features and processes required to reflect and distinguish UK coastal systems. Sediment dynamics (including meandering of estuaries and sediment accumulation) are explicitly represented in a simplified form that captures the accumulation and remobilization of radionuclides. Long-term transitions between biosphere systems (such as from a salt marsh to a terrestrial system) are outside the scope of the study. The models and supporting data draw on information about the UK that is representative of present-day conditions and represent potential exposures arising from both occupational and recreational habits.?

Generic calculations demonstrate that potential doses to humans arising from releases to estuarine, coastal and marine systems are typically more than two orders of magnitude lower than those for equivalent releases to terrestrial systems via well water and groundwater discharge to soil. The extended capability (i) ensures that RWM is able to undertake assessments for potential coastal site contexts, if and when required, and (ii) provides RWM with quantitative evidence to support the principal focus on terrestrial releases ( particularly for more generic assessments).
Identification of differential microRNA expression during tooth morphogenesis in the heterodont dentition of miniature pigs, SusScrofa
Authors: Li Ang , Li Ye , Song Tieli , Wang Fu , Liu Dayong , Fan Zhipeng , Cheng San , Zhang Chunmei , Wang Jinsong , He Junqi , Wang Songlin
Published: December 2015

Background

It has been found that microRNAs (miRNAs) play important roles in the regulation of tooth development, and most likely increase the complexity of the genetic network, thus lead to greater complexity of teeth. But there has been no research about the key microRNAs associated with tooth morphogenesis based on miRNAs expression profiles. Compared to mice, the pig model has plentiful types of teeth, which is similar with the human dental pattern. Therefore, we used miniature pigs as large-animal models to investigate differentially expressed miRNAs expression during tooth morphogenesis in the early developmental stages of tooth germ.

Results

A custom-designed miRNA microarray with 742 miRNA gene probes was used to analyze the expression profiles of four types of teeth at three stages of tooth development. Of the 591 detectable miRNA transcripts, 212 miRNAs were continuously expressed in all types of tooth germ, but the numbers of miRNA transcript among the four different types of teeth at each embryonic stage were statistically significant differences (p < 0.01). The hierarchical clustering and principal component analysis results suggest that the miRNA expression was globally altered by types and temporal changes. By clustering analysis, we predicted 11 unique miRNA sequences that belong to mir-103 and mir-107, mir-133a and mir-133b, and mir-127 isomiR families. The results of real-time reverse-transcriptase PCR and in situ hybridization experiments revealed that five representative miRNAs may play important roles during different developmental stages of the incisor, canine, biscuspid, and molar, respectively.

Conclusions

The present study indicated that these five miRNAs, including ssc-miR-103 and ssc-miR-107, ssc-miR-133a and ssc-miR-133b, and ssc-miR-127, may play key regulatory roles in different types of teeth during different stages and thus may play critical roles in tooth morphogenesis during early development in miniature pigs.
Incidence and outcome of adults with diabetic ketoacidosis admitted to ICUs in Australia and New Zealand
Authors: Venkatesh Balasubramanian , Pilcher David , Prins John , Bellomo Rinaldo , Morgan Thomas John , Bailey Michael
Published: December 2015

Background

Over the last two decades, there have been several improvements in the management of diabetes. Whether this has impacted on the epidemiology and outcome of diabetic ketoacidosis (DKA) requiring intensive care unit (ICU) admission is unknown.

Method

This was a retrospective study of 8533 patients with the diagnosis of DKA admitted to 171 ICUs in Australia and New Zealand between 2000–2013 with separate independent analysis of those on established insulin (Group I) or not on insulin (Group NI) at the time of hospitalisation.

Results

Of the 8553 patients, 2344 (27 %) were identified as NI. The incidence of ICU admission with DKA progressively increased fivefold from 0.97/100,000 (95 % CI 0.84–1.10) in 2000 to 5.3/100,000 (95 % CI 4.98–5.53) in 2013 (P < 0.0001), with the proportions between I and NI remaining stable. Rising incidences were observed mainly in rural and metropolitan hospitals (P < 0.01). In the first 24 hours in the ICU, mean worst pH increased over the study period from 7.20 ± 0.02 to 7.24 ± 0.01 (P < 0.0001), and mean lowest plasma bicarbonate from 12.1 ± 6.6 to 13.8 ± 6.6 mmol/L (P < 0.0001). In contrast, mean highest plasma glucose decreased from 26.3 ± 14 to 23.2 ± 13.1 mmol/L (P < 0.0001). Hospital mortality was significantly greater in NI as compared to I (2.4 % vs 1.1 %, P > 0.0001). Elevated plasma urea in the first 24 hours (≥25 mmol/L, adjusted odds ratio 20.6 (6.54–65.7), P < 0.0001) was the strongest individual predictor of mortality.

Conclusions

The incidence of ICU admission of patients with DKA in Australia and New Zealand has increased fivefold over the last decade, with a significant proportion of patients not on insulin at presentation. Overall physiological status in the first 24 hours of ICU admission has progressively improved and mortality rates have remained stable. However, DKA patients not on established insulin therapy at presentation had significantly worse outcomes. This notion has epidemiologic, diagnostic and management implications.
Cognitive impact after short-term exposure to different proton pump inhibitors: assessment using CANTAB software
Authors: Akter Sanjida , Hassan Md. Rajib , Shahriar Mohammad , Akter Nahia , Abbas Md. Golam , Bhuiyan Mohiuddin Ahmed
Published: December 2015

Introduction

Studies have shown that proton pump inhibitors (PPIs) increase the brain burden of amyloid-beta (Aβ) and also create vitamin B12 deficiency. However, these two phenomena have deleterious effect on cognition and Alzheimer’s disease (AD). Since the use of PPIs has increased tremendously for the last few years, it is of great public health importance to investigate the cognitive impact of PPIs. Hence, the purpose of this study was to investigate the degree of neuropsychological association of each PPI with different cognitive functions.

Methods

Sixty volunteers of either gender were recruited and divided randomly into six groups: five test groups for five classes of PPIs and one control group. All the groups participated in the five computerized neuropsychological tests (nine subtests) of the Cambridge Neuropsychological Test Automated Battery twice: at the beginning of the study and 7 days thereafter.

Results

We found statistically and clinically significant impairment in visual memory, attention, executive function, and working and planning function. One-way analysis of variance findings showed that all PPIs had a similar negative impact on cognition. However, paired-samples t tests indicated that omeprazole showed significant (p < 0.05) results in seven subtests; lansoprazole and pantoprazole showed significant results in five subtests; and rabeprazole showed significant results in four subtests. Among five classes of PPIs, esomeprazole showed comparatively less impact on cognitive function with significant results in three subtests.

Conclusions

The present study reveals for the first time that different PPIs have varying degrees of influence on different cognitive domains and have associations with AD. These findings should be considered when balancing the risks and benefits of prescribing these medications. A study done for a longer period of time with a larger sample size might yield better results.
RETRACTED ARTICLE: Boundary behaviors of modified Green’s function with respect to the stationary Schrödinger operator and its applications
Authors: Li Zhiqiang
Published: December 2015

In this paper, we construct a modified Green’s function with respect to the stationary Schrödinger operator on cones. As applications, we not only obtain the boundary behaviors of generalized harmonic functions but also characterize the geometrical properties of the exceptional sets with respect to the Schrödinger operator.
Evaluating the referral preferences and consultation requests of primary care physicians with otolaryngology – head and neck surgery
Authors: Scott John R. , Wong Eric , Sowerby Leigh J
Published: December 2015

Background

No literature exists which examines referral preferences to, or the consultation process with, Otolaryngology. In a recent Canadian Medical Association nation-wide survey of General Practitioners and Family Physicians, Otolaryngology was listed as the second-most problematic specialty for referrals. The purpose of this study was to learn about and improve upon the referral process between primary care physicians (PCPs) and Otolaryngology at an academic centre in Southwestern Ontario.

Methods

PCPs who actively refer patients to Otolaryngology within the catchment area of Western University were asked to complete a short paper-based questionnaire. Data was analyzed using descriptive statistics.

Results

A total of 50 PCPs were surveyed. Subspecialty influenced 90.0 % of the referrals made. Specialist wait times altered 58.0 % of referrals. All PCPs preferred to communicate via fax. Half of those surveyed wanted clinical notes from every encounter. Seventy-four percent of respondents wanted inappropriate referrals forwarded to the proper specialist automatically. Twenty-two percent of those surveyed were satisfied with current wait times. A central referral system was favored by 74 % of PCPs.

Conclusion

Improvements could help streamline the referral and consultation practices with Otolaryngology in Southwestern Ontario. A central referral system and reduction in the frequency of consultative reports can be considered.
Tofogliflozin Improves Insulin Resistance in Skeletal Muscle and Accelerates Lipolysis in Adipose Tissue in Male Mice
Authors: Obata Atsushi , Kubota Naoto , Kubota Tetsuya , Iwamoto Masahiko , Sato Hiroyuki , Sakurai Yoshitaka , Takamoto Iseki , Katsuyama Hisayuki , Suzuki Yoshiyuki , Fukazawa Masanori , Ikeda Sachiya , Iwayama Kaito , Tokuyama Kumpei , Ueki Kohjiro , Kadowaki Takashi
Published: December 2015

Sodium glucose cotransporter 2 inhibitors have attracted attention as they exert antidiabetic and antiobesity effects. In this study, we investigated the effects of tofogliflozin on glucose homeostasis and its metabolic consequences and clarified the underlying molecular mechanisms. C57BL/6 mice were fed normal chow containing tofogliflozin (0.005%) for 20 weeks or a high-fat diet containing tofogliflozin (0.005%) for 8 weeks ad libitum. In addition, the animals were pair-fed in relation to controls to exclude the influence of increased food intake. Tofogliflozin reduced the body weight gain, mainly because of fat mass reduction associated with a diminished adipocyte size. Glucose tolerance and insulin sensitivity were ameliorated. The serum levels of nonesterified fatty acid and ketone bodies were increased and the respiratory quotient was decreased in the tofogliflozin-treated mice, suggesting the acceleration of lipolysis in the white adipose tissue and hepatic β-oxidation. In fact, the phosphorylation of hormone-sensitive lipase and the adipose triglyceride lipase protein levels in the white adipose tissue as well as the gene expressions related to β-oxidation, such as Cpt1α in the liver, were significantly increased. The hepatic triglyceride contents and the expression levels of lipogenic genes were decreased. Pair-fed mice exhibited almost the same results as mice fed an high-fat diet ad libitum. Moreover, a hyperinsulinemic-euglycemic clamp revealed that tofogliflozin improved insulin resistance by increasing glucose uptake, especially in the skeletal muscle, in pair-fed mice. Taken together, these results suggest tofogliflozin ameliorates insulin resistance and obesity by increasing glucose uptake in skeletal muscle and lipolysis in adipose tissue.
Bayesian estimation of the shape parameter of generalized Rayleigh distribution under non-informative prior
Authors: Aliyu Yakubu , Yahaya Abubakar
Published: December 2015

A decade ago, two-parameter Burr Type X distribution was introduced by Surles and Padgett [14] which was described as Generalized Rayleigh Distribution (GRD). This skewed distribution can be used quiet effectively in modelling life time data. In this work, Bayesian estimation of the shape parameter of GRD was considered under the assumption of non-informative prior. The estimates were obtained under the squared error, Entropy and Precautionary loss functions. Extensive Monte Carlo simulations were carried out to compare the performances of the Bayes estimates with that of MLEs. It was observed that the estimate under the Entropy loss function is more stable than the estimates under squared error loss function, Precautionary loss function and MLEs.
Microbial biosensors for environmental monitoring
Authors: VOGRINC David , VODOVNIK Maša , MARINŠEK-LOGAR Romana
Published: December 2015

Microbial biosensors are analytical devices capable of sensing substances in the environment due to the specific biological reaction of the microorganism or its parts. Construction of a microbial biosensor requires knowledge of microbial response to the specific analyte. Linking this response with the quantitative data, using a transducer, is the crucial step in the construction of a biosensor. Regarding the transducer type, biosensors are divided into electrochemical, optical biosensors and microbial fuel cells. The use of the proper configuration depends on the selection of the biosensing element. With the use of transgenic E. coli strains, bioluminescence or fluorescence based biosensors were developed. Microbial fuel cells enable the use of the heterogeneous microbial populations, isolated from wastewater. Different microorganisms are used for different pollutants – pesticides, heavy metals, phenolic compounds, organic waste, etc. Biosensing enables measurement of their concentration and their toxic or genotoxic effects on the microbes. Increasing environmental awareness has contributed to the increase of interest for biomonitoring. Although technologies, such as bioinformatics and genetic engineering, allow us to design complex and efficient microbial biosensors for environmental pollutants, the transfer of the laboratory work to the field still remains a problem to solve.
Effect of different litter materials on foot pad dermatitis, hock burn and feather coverage in broiler chickens
Authors: TERČIČ Dušan , ŽOLGER Mirjana , PESTOTNIK Mojca
Published: December 2015

An experiment was conducted to evaluate the feather coverage on breast and thighs in meat type chickens, reared on three different types of litter materials, including wood shavings, shredded paper and chopped wheat straw. The experiment lasted for 72 days. A total of 447 one-day-old meat type chickens were randomly allotted to the three litter materials, giving 149 birds per litter. On days 24, 47 and 72 of the experimental period, feathering on the breast and thighs was scored according to a 1–4 scale. In addition, the severity of foot pad dermatitis (FPD) and hock burn (HB) was evaluated at the same days by attributing scores from 1−3. Litter characteristics (moisture content, water absorbing capacity, bulk density, pH) were determined at the end of the experiment. Severity of FPD varied significantly (P < 0.016) among the litter materials with chopped straw showing the highest severity scores and wood shavings showing the lowest. Litter material had no effect (P > 0.016) on the severity of HB and on thigh feathering. Birds reared on chopped wheat straw presented the lowest breast feather coverage. Straw litter had the highest moisture content and pH value. In conclusion, wood shavings proved to be best litter material for meat type chickens rearing among the three tested litter materials.
A Memory-Theory Perspective of Country-Image Formation
Authors: Lee Richard , Lockshin Larry , Greenacre Luke
Published: December 2015

Traditional country-of-origin strategy in international marketing uses a country-image halo to cue beliefs about the country's products. With expansive trade globalization, domestic consumers are likely to have experience with foreign products but know little of the products’ origin country. Thus, equally important as traditional theory is the question of whether product beliefs can imbue country image, but little is known of this reverse influence. If product beliefs can generalize into a favorable country image, a chain effect will then enable traditional country-of-origin effects to benefit the country's other products. In this study, the results of three surveys across two countries show that product beliefs can indeed influence country image. However, the influence weakens with increasing country familiarity and exists only when the product and country are congruent. Furthermore, the influence can operate outside of conscious awareness. The authors draw on the associative network theory of memory to explain their findings. This research improves the theoretical understanding of country- and product-image halo and provides the grounds for product and brand managers to work with government and tourist organizations for increasing mutual effectiveness.
TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic
Authors: Lamb Christopher A , Nühlen Stefanie , Judith Delphine , Frith David , Snijders Ambrosius P , Behrends Christian , Tooze Sharon A
Published: December 2015

Macroautophagy requires membrane trafficking and remodelling to form the autophagosome and deliver its contents to lysosomes for degradation. We have previously identified the TBC domain‐containing protein, TBC1D14, as a negative regulator of autophagy that controls delivery of membranes from RAB11‐positive recycling endosomes to forming autophagosomes. In this study, we identify the TRAPP complex, a multi‐subunit tethering complex and GEF for RAB1, as an interactor of TBC1D14. TBC1D14 binds to the TRAPP complex via an N‐terminal 103 amino acid region, and overexpression of this region inhibits both autophagy and secretory traffic. TRAPPC8, the mammalian orthologue of a yeast autophagy‐specific TRAPP subunit, forms part of a mammalian TRAPPIII‐like complex and both this complex and TBC1D14 are needed for RAB1 activation. TRAPPC8 modulates autophagy and secretory trafficking and is required for TBC1D14 to bind TRAPPIII. Importantly, TBC1D14 and TRAPPIII regulate ATG9 trafficking independently of ULK1. We propose a model whereby TBC1D14 and TRAPPIII regulate a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy.
TET‐catalyzed oxidation of intragenic 5‐methylcytosine regulates CTCF‐dependent alternative splicing
Authors: Marina Ryan J , Sturgill David , Bailly Marc A , Thenoz Morgan , Varma Garima , Prigge Maria F , Nanan Kyster K , Shukla Sanjeev , Haque Nazmul , Oberdoerffer Shalini
Published: December 2015

Intragenic 5‐methylcytosine and CTCF mediate opposing effects on pre‐mRNA splicing: CTCF promotes inclusion of weak upstream exons through RNA polymerase II pausing, whereas 5‐methylcytosine evicts CTCF, leading to exon exclusion. However, the mechanisms governing dynamic DNA methylation at CTCF‐binding sites were unclear. Here, we reveal the methylcytosine dioxygenases TET1 and TET2 as active regulators of CTCF‐mediated alternative splicing through conversion of 5‐methylcytosine to its oxidation derivatives. 5‐hydroxymethylcytosine and 5‐carboxylcytosine are enriched at an intragenic CTCF‐binding sites in the CD45 model gene and are associated with alternative exon inclusion. Reduced TET levels culminate in increased 5‐methylcytosine, resulting in CTCF eviction and exon exclusion. In vitro analyses establish the oxidation derivatives are not sufficient to stimulate splicing, but efficiently promote CTCF association. We further show genomewide that reciprocal exchange of 5‐hydroxymethylcytosine and 5‐methylcytosine at downstream CTCF‐binding sites is a general feature of alternative splicing in naïve and activated CD4+ T cells. These findings significantly expand our current concept of the pre‐mRNA “splicing code” to include dynamic intragenic DNA methylation catalyzed by the TET proteins.
Eradicating tumor drug resistance at its YAP‐biomechanical roots
Authors: Zanconato Francesca , Piccolo Stefano
Published: December 2015

Treatment with BRAF kinase inhibitors leads to rapid resistance and tumor regression in BRAF V600E mutant melanoma patients. However, the underlying mechanism of the developed tumor resistance is not fully clear. In this issue of The EMBO Journal, Kim and colleagues show that melanoma cells acquire resistance to BRAF inhibitors by changing cell shape, modifying their cytoskeleton and, in turn, activating the YAP/TAZ mechanotransduction pathway (Kim et al, ).
Algunos aspectos del artículo científico en la Revista Peruana de Biología
Authors: Romero Leonardo
Published: December 2015

En este trabajo se presentan algunas de las características de los artículos de la Revista Peruana de Biología. Se precisan algunos aspectos del proceso de revisiones, el tipo de artículo conocido como data paper, el problema en la falta de erudición en los trabajos presentados, la importancia de la reproducibilidad y la autoría.
Two-Generation Pediatric Care: A Modest Proposal
Authors: Zuckerman Barry
Published: December 2015

To reduce inequities in child health, we need to reduce the gap between what we know and what we do. We must challenge our practices and traditions, develop new solutions and have the strength and courage to change how we practice. Based on my experience that the best way to help children is to help their parents, and the best way to reach parents is through their children, I propose a new frame of a 2-generation approach that focuses not only on the child but also on the parents and their relationship to guide our innovation and target improvements. Pediatricians’ knowledge and empathy for families is a special base to use new strategies to test ideas on a small number of families with minimal time and cost. Examples from our work includes the following: (1) identify and refer parents with mental health conditions and lack of effective contraception, (2) develop more effective approaches to explain illness and disease to parents, and (3) educate parents about the impact of social relations from infancy on; love can amplify and stress can impair brain and child development. I encourage clinicians to think about what should be changed and more importantly to be excited and brave enough to take the first steps to design and test an idea.
Rescue Medicine for Epilepsy in Education Settings
Authors: Hartman Adam L. , Devore Cynthia Di Laura ,   and the SECTION ON NEUROLOGY,   COUNCIL ON SCHOOL HEALTH, Kang Peter B. , Gilbert Donald , Gropman Andrea , Hartman Adam L. , Joshi Sucheta , Partap Sonia , Okamoto Jeffrey , Allison Mandy , Ancona Richard , Attisha Elliott , De Pinto Cheryl , Holmes Breena , Kjolhede Christopher , Lerner Marc , Minier Mark , Weiss-Harrison Adrienne , Young Thomas
Published: December 2015

Children and adolescents with epilepsy may experience prolonged seizures in school-associated settings (eg, during transportation, in the classroom, or during sports activities). Prolonged seizures may evolve into status epilepticus. Administering a seizure rescue medication can abort the seizure and may obviate the need for emergency medical services and subsequent care in an emergency department. In turn, this may save patients from the morbidity of more invasive interventions and the cost of escalated care. There are significant variations in prescribing practices for seizure rescue medications, partly because of inconsistencies between jurisdictions in legislation and professional practice guidelines among potential first responders (including school staff). There also are potential liability issues for prescribers, school districts, and unlicensed assistive personnel who might administer the seizure rescue medications. This clinical report highlights issues that providers may consider when prescribing seizure rescue medications and creating school medical orders and/or action plans for students with epilepsy. Collaboration among prescribing providers, families, and schools may be useful in developing plans for the use of seizure rescue medications.
Gemcitabine-Based Chemoradiation in the Treatment of Locally Advanced Head and Neck Cancer: Systematic Review of Literature and Meta-Analysis
Authors: Vanderveken Olivier M. , Szturz Petr , Specenier Pol , Merlano Marco C. , Benasso Marco , Van Gestel Dirk , Wouters Kristien , Van Laer Carl , Van den Weyngaert Danielle , Peeters Marc , Vermorken Jan
Published: December 2015

Background.

Platinum-based concurrent chemoradiation (CCRT) improves locoregional control and overall survival of locoregionally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) when compared to radiotherapy alone, but this approach is hampered by significant toxicity. Therefore, alternative ways to enhance the radiation effects are worth investigating. Gemcitabine (2′,2′-difluorodeoxycytidine), in addition to its activity against a variety of solid tumors, including SCCHN, is one of the most potent radiosensitizers, and it has an overall favorable safety profile. In this paper, the clinical experience with gemcitabine-based chemoradiation in the treatment of patients with LA-SCCHN is reviewed.

Methods.

We conducted a review of the literature on the clinical experience with radiotherapy combined with either single-agent gemcitabine or gemcitabine/cisplatin-based polychemotherapy for the treatment of patients with LA-SCCHN. We also searched abstracts in databases of major international oncology meetings from the last 20 years. A meta-analysis was performed to calculate pooled proportions with 95% confidence intervals (CIs) for complete response rate and grade 3–4 acute mucositis rate.

Results.

A total of 13 papers were eligible for the literature review. For schedules using a gemcitabine dose intensity (DI) below 50 mg/m2 per week, the complete response rate was 86% (95% CI, 74%–93%) with grade 3–4 acute mucositis rate of 38% (95% CI, 27%–50%) and acceptable late toxicity. In one of the studies employing such low DIs, survival data were provided showing a 3-year overall survival of 50%. Compared with DI ≥50 mg/m2 per week, there was no difference in the complete response rate (71%; 95% CI, 55%–83%; p = .087) but a significantly higher (p < .001) grade 3–4 acute mucositis rate of 74% (95% CI, 62%–83%), often leading to treatment interruptions (survival data provided in 8 studies; 3-year overall survival, 27%–63%). Late toxicity comprising mainly dysphagia was generally underreported, whereas information about xerostomia and skin fibrosis was scarce.

Conclusion.

This review highlights the radiosensitizing potential of gemcitabine and suggests that even very low dosages (less than 50 mg/m2 per week) provide a sufficient therapeutic ratio and therefore should be further investigated. Refinements in radiation schemes, including intensity-modulated radiation therapy, in combination with low-dose gemcitabine and targeted agents, such as cetuximab, are currently being investigated.
Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials
Authors: Coca Steven G. , Zabetian Azadeh , Ferket Bart S. , Zhou Jing , Testani Jeffrey M. , Garg Amit X. , Parikh Chirag R.
Published: December 2015

Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short–term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between–group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo–controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials.
Do Long-haul Truckers Undervalue Future Fuel Savings?
Authors: Adenbaum Jacob , Copeland Adam , Stevens John J.
Published: December 2015

The U.S. federal government enacted fuel efficiency standards for medium and heavy trucks for the first time in September 2011. Rationales for using this policy tool typically depend upon frictions existing in the marketplace or consumers being myopic, such that vehicle purchasers undervalue the future fuel savings from increased fuel efficiency. We measure by how much long-haul truck owners undervalue future fuel savings by employing recent advances to the classic hedonic approach to estimate the distribution of willingness-to-pay for fuel efficiency. We find significant heterogeneity in truck owners’ willingness to pay for fuel efficiency, with the elasticity of fuel efficiency to price ranging from 0.51 at the 10th percentile to 1.33 at the 90th percentile, and an average of 0.91. Combining these results with estimates of future fuel savings from increases in fuel efficiency, we find that long-haul truck owners’ willingness-to-pay for a 1 percent increase in fuel eff iciency is, on average, just 29.5 percent of the expected future fuel savings. These results suggest that introducing fuel efficiency standards for heavy trucks might be an effective policy tool to raise medium and heavy trucks’ fuel economy.
Czech Journalists’ Refreshed Sense of Ethics in the Midst of Media Ownership Turmoil
Authors: Hájek Roman , Štefaniková Sandra , Láb Filip , Tejkalová Alice N.
Published: December 2015

In recent years, the Czech Republic has seen the largest changes in media ownership since the early 1990s. Most striking was the purchase of one of the largest publishing houses Mafra by the tycoon Andrej Babiš in June 2013, followed by the takeover of the Czech branch of Ringier by other Czech businessmen later that year. The first case in particular instigated immense discussion about the economic and ethical crisis facing Czech journalism since Babiš is also a powerful political figure (currently the Minister of Finance). In response, a significant number of leading, well-known journalists left media owned by big business and launched projects of quality or “slow” journalism which had until that point been merely discussed theoretically. This paper—based on the results of the Czech part of the Worlds of Journalism Study project—addresses the shift in the ways journalists perceive their roles and ethical responsibilities before and after the 2013 ownership changes. We also present the manner in which these changes are reflected in emerging media projects. It seems that those journalists not affected by the ownership change tend to view journalism ethics and the ability of journalism to exert power more seriously than before.
One Country, Two Polarised Audiences: Estonia and the Deficiency of the Audiovisual Media Services Directive
Authors: Jõesaar Andres
Published: December 2015

This article argues that until recent times, the Estonian media policy has mainly been interpreted as an economic issue and it did not account for the strategic need to build a comprehensive media field to serve all groups in society. This has happened despite the fact the Estonian media policy is in line with the European Union (EU) media policy, which should ensure freedom of information, diversity of opinion and media pluralism. Findings of the Estonian case study show that despite these noble aims, Estonia has two radically different information fields: one for Estonian speaking audiences and one for Russian speakers. Events in Ukraine have added to the democratic media policy paradigm a question of national security. Now it is a challenge for the policy makers to unite polarised media fields and how to minimise the impact of Russian propaganda. On the EU level, one supportive measure could be a revision of the Audiovisual Media Service Directive.
Revisiting National Journalism Cultures in Post-Communist Countries: The Influence of Academic Scholarship
Authors: Harro-Loit Halliki
Published: December 2015

The aim of this exploratory study is to develop the concept of the actor approach and journalism culture by adding a factor that has been more or less overlooked: academic scholarship. The paper also proposes to use the concept “discursive institutionalism” in order to clarify what knowledge and opinions about media are formed in the interaction of media institutions and academia with other institutions in society (e.g. educational, political and judicial). The concept “discursive institutionalism” includes the role of academia in providing new knowledge by conducting and disseminating research on the national and international levels, and this deserves greater attention. Although it is a common understanding that the role of academia is to prepare young professionals, it is less discussed how national media research and journalism education, in synergy, can create and maintain a collective understanding regarding the role and performance of national journalism in turbulent times. The paper is a meta-analysis of published research, and the empirical part of the study includes a close reading of academic articles, reports and conference presentations that are available in English about media in Central and Eastern European (CEE) countries. Examples of research from selected CEE countries provide a descriptive view of problems and tendencies concerning media performance in these countries. The proposed analytical approach aims to connect these problems and provide ideas for further research.