bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of blue‐light cystoscopy on contemporary performance of urine cytology
Authors: Freifeld Yuval , Lotan Yair
Published: October 2018

Objective

To evaluate the performance of urine cytology based on contemporary data, including the effect of enhanced cystoscopic techniques.

Materials and Methods

Individual patient data were obtained from three prospective studies: the Photocure (PC) B305 and the PC B308 studies, evaluating the use of blue‐light cystoscopy with hexaminolevulinate (BLC‐H), and the Cxbladder monitoring study, evaluating the Cxbladder monitor test for the detection of recurrent urothelial carcinoma. The specificity and sensitivity of cytology in each study and for the overall cohort were calculated.

Results

A total of 1 487 urine samples from 1 375 patients were included in the analysis; overall 615 tumours were detected correlating to 41% of the cytological specimens. The pooled sensitivity and specificity for cytology were 40.8% and 92.8%, respectively. The pooled sensitivity was 11.4% for low‐grade/World Health Organization (WHO) grade 1 disease and 54.3% for high‐grade/WHO grade 3 disease. There were no differences in cytology sensitivity based on the type of cystoscopy used, with sensitivity of 41.3% and 40.4% in white‐light cystoscopy (WLC) and BLC‐H, respectively. Subgroup analysis including carcinoma in situ ( CIS) showed a trend towards lower cytology sensitivity in BLC‐H (54.5%) vs WLC (69.2%).

Conclusions

Based on analysis of contemporary data, the sensitivity of cytology for detecting high‐grade tumours and CIS remains low. On a per‐patient analysis, cytology sensitivity was not affected by the use of advanced cystoscopic techniques except in patients with CIS. The use of cytology as the main adjunct to cystoscopy in patients at high risk can lead to missed opportunities for early detection of recurrence and for determining which patients are not responding to intravesical therapies such as bacille Calmette‐Guérin.
WHAT AFFECTS EFFICIENCY IN LABOUR MARKET MATCHING AT DIFFERENT TERRITORIAL AGGREGATION LEVELS IN POLAND?
Authors: Antczak Elżbieta , Gałecka‐Burdziak Ewa , Pater Robert
Published: October 2018

We analyse efficiency of a labour market matching process at different levels of territorial aggregation and in different time horizons. We apply a stochastic matching frontier to random, job queuing and stock‐flow models. We use data for Poland, a country with highly regionally diversified unemployment. We find that search and matching mechanisms significantly differ with territorial aggregation. Higher efficiency in small regions results from lower frictions. Larger regions enjoy better structural matching if only labour market participants have time to search. Different policy measures should be designed to improve labour market matching efficiency at different regional levels.
Human rights violations as humanist performance: Dehumanizing criminalized refugee youth in Canada
Authors: Francis Jenny
Published: October 2018

This paper explores the dehumanization of criminalized refugee youth. The concept of “institutional humanism” is used to explicate how the ideology of humanism is deployed through the denial of rights to dehumanize, objectify, and animalize racialized and criminalized refugee youth in Canada, setting them in opposition to mainstream whites who are deemed normal, rational, and autonomous—in essence, human. Drawing on qualitative interviews with criminalized refugee youth and professional adults who work with them, the paper shows how institutional policy regulates inclusion in the human community by specifying who may be denied human rights. The interview data are set within the web of theoretical relationships among humanism, posthumanism, animalization, institutional policy, and categorizations based on race, gender, class, ability, age, and immigration status. The paper demonstrates how these theoretical nodes attain bolder relief when operationalized using a theory of performativity. In contrast to conventional analyses of dehumanization, rather than arguing for an extension of liberal humanism, the paper seeks a transformation away from humanism.
Genome‐wide association study identifies gastric cancer susceptibility loci at 12q24.11‐12 and 20q11.21
Authors: Tanikawa Chizu , Kamatani Yoichiro , Toyoshima Osamu , Sakamoto Hiromi , Ito Hidemi , Takahashi Atsushi , Momozawa Yukihide , Hirata Makoto , Fuse Nobuo , Takai‐Igarashi Takako , Shimizu Atsushi , Sasaki Makoto , Yamaji Taiki , Sawada Norie , Iwasaki Motoki , Tsugane Shoichiro , Naito Mariko , Hishida Asahi , Wakai Kenji , Furusyo Norihiro , Murakami Yoshinori , Nakamura Yusuke , Imoto Issei , Inazawa Johji , Oze Isao , Sato Naomi , Tanioka Fumihiko , Sugimura Haruhiko , Hirose Hiroshi , Yoshida Teruhiko , Matsuo Keitaro , Kubo Michiaki , Matsuda Koichi
Published: October 2018

Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large‐scale genome‐wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11‐12 (rs6490061, P = 3.20 × 10−8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10−10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10−13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10−11), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.
Impact of route of administration on genotoxic oestrogens concentrations using oral vs transdermal oestradiol in girls with Turner syndrome
Authors: Mauras Nelly , Torres‐Santiago Lournaris , Santen Richard , Mericq Veronica , Ross Judith , Colon‐Otero Gerardo , Damaso Ligeia , Hossain Jobayer , Wang Qingqing , Mesaros Clementina , Blair Ian A.
Published: October 2018

Objective

The established link between oestrogen and breast cancer occurs via both oestrogen receptor (ER)‐mediated and non ER‐mediated mechanisms. The term genotoxic estrogens describes mutagenic metabolites, including oestrogen catechols and quinones, which have been linked to breast carcinogenesis in post‐menopausal women. We aimed to assess whether the route of administration of 17β oestradiol (E2) affects the accumulation of genotoxic oestrogen metabolites in a model of ovarian failure in young girls with Turner syndrome.

Methods

Stored plasma samples obtained at 0 and 12 months were used from 40 adolescents with Turner syndrome who participated in a 12 months randomized controlled trial of the metabolic impact of E2 orally (2 mg/d) vs transdermally (100 µg/d); dose escalation allowed matching of unconjugated E2 levels in the parent study. We measured 12 oestrogen metabolites (total concentrations = conjugated and unconjugated) using a highly sensitive LCMSMS assay. Results from 48 normally menstruating adolescents were used for comparison.

Results

After treatment, least square mean (SE) total E2 concentrations were higher in the oral vs transdermal group (6784 pmol/L vs 1123 [1614], P < 0.0001), as was oestrone (E1) (91 060 pmol/L vs 19 278 [16 534], P < 0.0001). Also, higher after oral treatment were catechol‐oestrogens 4‐hydroxy‐E2 (149 vs 28 [±49] pmol/L), 2‐hydroxy‐E2 (300 vs 76 [±52]), 4‐hydroxy‐E1 (450 vs 105 [±113]), 2‐hydroxy‐E1 (3094 vs 740 [±684]) and 16α‐hydroxy‐E1 (3,007 vs 157 [±534]) (<0.001 between groups). Levels were much closer to controls in the transdermal group.

Conclusions

Common feminizing doses of oral oestradiol for 12 months result in substantial accumulation of unphysiologic, genotoxic oestrogens compared to transdermal oestradiol, expanding concerns about oral oestrogens’ first hepatic passage. Further studies assessing long‐term risks of these metabolites in women taking different forms of oestrogen are needed.
Phenotypic heterogeneity of astrocytes in motor neuron disease
Authors: Trias Emiliano , Barbeito Luis , Yamanaka Koji
Published: October 2018

Accumulating evidence has shown that astrocytes do not just support the function of neurons, but play key roles in maintaining the brain environment in health and disease. Contrary to the traditional understanding of astrocytes as static cells, reactive astrocytes possess more diverse functions and phenotypes than previously predicted. In the present focused review, we summarize the evidence showing that astrocytes are playing profound roles in the disease process of amyotrophic lateral sclerosis. Aberrantly activated astrocytes in amyotrophic lateral sclerosis rodents express microglial molecular markers and provoke toxicities to accelerate disease progression. In addition, TIR domain–containing adapter protein–inducing interferon‐β‐dependent innate immune pathway in astrocytes also has a novel function in terminating glial activation and neuroinflammation. Furthermore, heterogeneity in phenotypes and functions of astrocytes are also observed in various disease conditions, such as other neurodegenerative diseases, ischemia, aging and acute lesions in the central nervous system. Through accumulating knowledge of the phenotypic and functional diversity of astrocytes, these cells will become more attractive therapeutic targets for neurological diseases.
Immediate and early implant placement in single‐tooth gaps in the anterior maxilla: A prospective study on ridge dimensional, clinical, and aesthetic changes
Authors: Arora Himanshu , Ivanovski Saso
Published: October 2018

Objectives

This prospective study evaluated the impact of timing of placement (immediate and early) on the horizontal ridge dimensional changes, clinical, and aesthetic outcomes of implants placed in single‐tooth gaps in the anterior maxilla.

Materials and methods

Implants were placed in single‐tooth gaps in the anterior maxilla of 30 patients, either immediately after extraction (Group A, n = 15) or after a healing period of 4–8 weeks (Group B, n = 15). In both groups, implant placement was followed by a 3‐ to 4‐month period of non‐submerged healing, after which definitive crowns were placed. Study models were obtained before extraction (T0), at implant placement (T1), at the insertion of a definitive crown (T2), and 1‐year thereafter (T3). Horizontal ridge dimensional changes were measured by superimposing the optical scans of the study models from different time‐points. Radiographs and photographs were used to evaluate changes in marginal bone levels and soft tissue recession. Aesthetic evaluation was carried out using the Pink and White Esthetic Score (PES and WES) indices. Patient‐reported outcomes were measured using a subjective questionnaire.

Results

A 100% implant survival rate was observed in both groups after a 1‐year follow‐up. Analysis showed a labial horizontal tissue dimensional change of 0.61 mm and 0.72 mm from T0 to T3 in Groups A and B, respectively. Acceptable PES values were observed in both groups (Group A: 9.40; Group B: 9.27) after the 1‐year follow‐up period. No incidence of advanced mucosal recession was observed between definitive crown insertion and 1‐year follow‐up in both groups. No significant changes were observed for all other measured variables at different time‐points.

Conclusions

Immediate and early placed implants in single‐tooth gaps in the anterior maxilla showed similar ridge dimensional changes as well as acceptable clinical, aesthetic, and patient‐centred outcomes in the short‐term (1‐year follow‐up).
Comparison of autogenous and allograft bone rings in surgically created vertical bone defects around implants in a sheep model
Authors: Benlidayi Mehmet Emre , Tatli Ufuk , Salimov Fariz , Tükel Hüseyin Can , Yüksel Orcan
Published: October 2018

Objectives

The aim of this study was to compare autogenous and allograft bone rings in surgically created vertical bone defects.

Material and methods

Four male, 1‐year‐old sheep were used in this study. In each sheep, eight vertical bone defects 7 mm in diameter were created using trephine drill in the iliac wing. Autogenous and allograft bone rings 5 mm in height and 7 mm in diameter were used for vertical augmentation around implants. The study consisted of four groups according to the bone ring type and amount of vertical augmentation, autogenous 2 mm, allograft 2 mm, autogenous 4 mm, and allograft 4 mm. Two of the animals were sacrificed after 4 months, and the remaining two animals were sacrificed after 8 months. Undecalcified sections were prepared from harvested samples. Histological assessment and histomorphometric analysis were performed.

Results

Autogenous 2 mm group showed higher values than allograft 2 mm group, and autogenous 4 mm group showed higher values than allograft 4 mm group in terms of bone area and bone‐to‐implant contact (BIC) after 4 months. However, allograft 2 mm group showed higher bone area and BIC values than autogenous 2 mm group after 8 months. Also, autogenous 4 mm and allograft 4 mm groups showed comparable results after 8 months. Allograft 2 mm and allograft 4 mm groups showed higher bone area and BIC values at 8 months compared with 4 months.

Conclusions

Allograft bone ring looks promising in augmentation of surgically created vertical bone defects around implants after 8 months of healing.
A new unsupervised feature selection algorithm using similarity‐based feature clustering
Authors: Zhu Xiaoyan , Wang Yu , Li Yingbin , Tan Yonghui , Wang Guangtao , Song Qinbao
Published: October 2018

Unsupervised feature selection is an important problem, especially for high‐dimensional data. However, until now, it has been scarcely studied and the existing algorithms cannot provide satisfying performance. Thus, in this paper, we propose a new unsupervised feature selection algorithm using similarity‐based feature clustering, Feature Selection‐based Feature Clustering (FSFC). FSFC removes redundant features according to the results of feature clustering based on feature similarity. First, it clusters the features according to their similarity. A new feature clustering algorithm is proposed, which overcomes the shortcomings of K‐means. Second, it selects a representative feature from each cluster, which contains most interesting information of features in the cluster. The efficiency and effectiveness of FSFC are tested upon real‐world data sets and compared with two representative unsupervised feature selection algorithms, Feature Selection Using Similarity (FSUS) and Multi‐Cluster‐based Feature Selection (MCFS) in terms of runtime, feature compression ratio, and the clustering results of K‐means. The results show that FSFC can not only reduce the feature space in less time, but also significantly improve the clustering performance of K‐means.
Automated quantification of reference levels in liver and mediastinal blood pool for the Deauville therapy response classification using FDG‐PET/CT in Hodgkin and non‐Hodgkin lymphomas
Authors: Sadik May , Lind Erica , Polymeri Eirini , Enqvist Olof , Ulén Johannes , Trägårdh Elin
Published: October 2018

Background

18F‐FDG‐PET/CT has become a standard for assessing treatment response in patients with lymphoma. A subjective interpretation of the scan based on the Deauville 5‐point scale has been widely adopted. However, inter‐observer variability due to the subjectivity of the interpretation is a limitation. Our main goal is to develop an objective and automated method for evaluating response. The first step is to develop and validate an artificial intelligence (AI)‐based method, for the automated quantification of reference levels in the liver and mediastinal blood pool in patients with lymphoma.

Methods

The AI‐based method was trained to segment the liver and the mediastinal blood pool in CT images from 80 lymphoma patients, who had undergone 18F‐FDG‐PET/CT, and apply this to a validation group of six lymphoma patients. CT segmentations were transferred to the PET images to obtain automatic standardized uptake values (SUV). The AI‐based analysis was compared to corresponding manual segmentations performed by two radiologists.

Results

The mean difference for the comparison between the AI‐based liver SUV quantifications and those of the two radiologists in the validation group was 0·02 and 0·02, respectively, and 0·02 and 0·02 for mediastinal blood pool respectively.

Conclusions

An AI‐based method for the automated quantification of reference levels in the liver and mediastinal blood pool shows good agreement with results obtained by experienced radiologists who had manually segmented the CT images. This is a first, promising step towards objective treatment response evaluation in patients with lymphoma based on 18F‐FDG‐PET/CT.
Risk communication and risk perception: lessons from the 2011 floods in Brisbane, Australia
Authors: Kammerbauer Mark , Minnery John
Published: October 2018

Risk communication and risk perception are critical factors in disaster management. Governments at all levels play a part in communicating risk, whereas the perception of risk entails active roles by community participants, including potential and actual victims of disasters. This paper discusses these matters in relation to the floods in Brisbane, Australia, in 2011. The findings are based on interviews with representatives of households whose dwellings or business premises were fully or partially inundated by the waters. The research shows how important it is to recognise the problems of institutional fragmentation in terms of communication and the active engagement of recipients in understanding and interpreting flood risk information (especially for slow‐onset riverine flooding, such as that suffered by Brisbane). Locally targeted information on risk is of vital importance in avoiding the misinterpretation of warning information in relation to environmental cues and in promoting adequate responses. The paper concludes with some recommendations.
WEIGHING THE MILITARY OPTION: THE EFFECTS OF WARTIME CONDITIONS ON INVESTMENTS IN HUMAN CAPITAL
Authors: Duncan Brian , Mansour Hani , Rintala Bryson
Published: October 2018

Serving in the military is an important vehicle through which young Americans invest in their human capital. As such, changes in the desirability of military service may affect the attainment of enlistment requirements, such as a high school degree or equivalent. Using American Community Survey data, we find that exposure to home‐state combat fatalities during the Iraq and Afghanistan Wars decreased the probability of high school completion, and increased the probability of general equivalency diploma completion. Using military data, we confirm that exposure to home‐state fatalities selectively deterred some individuals from enlisting. The results suggest military service and educational investments are complements. (JEL I20, I26, J24)
Precopulatory mating and postzygotic isolation between two walnut‐infesting species of Rhagoletis from Mexican highlands
Authors: Tadeo Eduardo , Aluja Martín , Rull Juan
Published: October 2018

Pleistocene glacial and postglacial cycles producing contraction and expansion of temperate habitats have resulted in substantial diversification among several plant and animal taxa of Neararctic origin undergoing periods of isolation and secondary contact in high‐elevation areas of Mexico. One of such groups are walnut‐infesting fruit flies in the genus Rhagoletis (Diptera: Tephritidae), comprised of six recently derived species among which phylogenetic relationships have been difficult to unravel using conventional molecular methods. Here, we examined pre‐ and postzygotic isolation between two genetically similar and morphologically distinct species which are currently parapatric in central Mexico. Local adaptation driven by differences in host plant phenology between Rhagoletis zoqui Bush and Rhagoletis ramosae Hernández‐Ortíz resulted in allochronic isolation. Despite the existence of precopulatory mating isolation, there was a substantial number of hybrid matings in field cages where conspecific and heterospecific males and females were simultaneously released. The bulk of mating activity took place on host fruit. Rhagoletis zoqui females were more reluctant to mate with R. ramosae males than with males of their own species. Distinctive behavioral differences were observed between males during contests, fruit guarding, and approach to conspecifics on fruit. There was also some asymmetric postzygotic isolation, with the hybrid combination of R. zoqui males and R. ramosae females resulting in lower egg hatch than other mating combinations. Results were consistent with those of a phylogenetic study suggesting recent divergence of R. ramosae from Rhagoletis completa Cresson and R. zoqui in the Sierra Madre Oriental and the Mexican Trans Volcanic Belt.
The frequency architecture of brain and brain body oscillations: an analysis
Authors: Klimesch Wolfgang
Published: October 2018

Research on brain oscillations has brought up a picture of coupled oscillators. Some of the most important questions that will be analyzed are, how many frequencies are there, what are the coupling principles, what their functional meaning is, and whether body oscillations follow similar coupling principles. It is argued that physiologically, two basic coupling principles govern brain as well as body oscillations: (i) amplitude (envelope) modulation between any frequencies m and n, where the phase of the slower frequency m modulates the envelope of the faster frequency n, and (ii) phase coupling between m and n, where the frequency of n is a harmonic multiple of m. An analysis of the center frequency of traditional frequency bands and their coupling principles suggest a binary hierarchy of frequencies. This principle leads to the foundation of the binary hierarchy brain body oscillation theory. Its central hypotheses are that the frequencies of body oscillations can be predicted from brain oscillations and that brain and body oscillations are aligned to each other. The empirical evaluation of the predicted frequencies for body oscillations is discussed on the basis of findings for heart rate, heart rate variability, breathing frequencies, fluctuations in the BOLD signal, and other body oscillations. The conclusion is that brain and many body oscillations can be described by a single system, where the cross talk – reflecting communication – within and between brain and body oscillations is governed by m : n phase to envelope and phase to phase coupling.
Evaluation of videoendoscopic examinations of arytenoid function in the 2‐year‐old Thoroughbred: Can we all agree?
Authors: McLellan J. , Plevin S.
Published: October 2018

Background

Upper respiratory tract (URT) endoscopic examination is a routine part of prepurchase examinations. Discrepancies have been documented in the assessment of arytenoid function grades (AFG) between veterinarians.

Objectives

To document intra‐ and interobserver agreement for a population of multi‐experience level veterinarians for assessment of AFG of 2‐year‐old Thoroughbreds.

Study design

Observational cohort study.

Methods

One‐hundred and fourteen URT videoendoscopic examinations were evaluated by 10 veterinarians. Veterinarians were categorised based on experience, into five groups, each group with two veterinarians. Arytenoid function was graded using the Havemeyer ordinal scale and then reclassified by the authors dichotomously into ‘meets conditions of sale’ (MCS) or ‘does not meet conditions of sale’(DNMCS). Interobserver agreement of arytenoid function was assessed across all 10 veterinarians using Fleiss’ kappa and between veterinarians of similar experience levels in the five subgroups using Cohen's unweighted (k) and Cohen's linear weighted kappa (Ck). Intraobserver agreement was similarly calculated for each reviewer using 22 repeated video clips.

Results

Overall interobserver agreement using ordinal scales was fair (k = 0.27, 95% CI 0.22–0.31) to moderate (mean weighted Ck = 0.57, 95% CI 0.46–0.69) depending on statistical methodology used. Using the dichotomous classification, interobserver agreement was good (k = 0.7, 95% CI 0.63–0.77).

Overall intraobserver agreement using ordinal scales was fair (mean k = 0.26, 95% CI 0.14–0.38) to good (mean Ck = 0.61, 95% CI 0.50–0.71); and for the dichotomous reclassification it was good (k = 0.73, 95% CI 0.59–0.87). Experience level differences were identified.

Main limitations

The low number of veterinarians in each experience subgroup.

Conclusions

Subjectivity exists in arytenoid function grading, despite the existence of a well‐defined scale. Agreement variation exists depending on the grading scales and statistical methods used for analysis. Future studies pre‐ and post veterinarian training are indicated to determine if agreement can be improved.
Ecosystem‐based management of Amazon fisheries and wetlands
Authors: Goulding Michael , Venticinque Eduardo , Ribeiro Mauro L. de B. , Barthem Ronaldo B. , Leite Rosseval G. , Forsberg Bruce , Petry Paulo , Lopes da Silva‐Júnior Urbano , Ferraz Polliana Santos , Cañas Carlos
Published: October 2018

Infrastructure development and overfishing in the Amazon make it imperative to define adequate scales for the ecosystem‐based management of commercial fisheries and the wetlands on which they depend. We mapped fisheries and fish ecology data from Brazil, Peru, Bolivia and Colombia to an explicit GIS framework of river basins and mainstems. Migratory species account for more than 80% of the known maximum catches of commercial fisheries across the Amazon. Of these migratory species, we nominated six long‐distance migratory fish taxa as flagship species to define the two main commercial fishery regions. The migrations of at least one goliath catfish species define a large‐scale longitudinal link joining the Andes, Amazon Lowlands and Amazon River estuary. Migratory Characiforms demonstrate interbasin wetland connectivity between nutrient‐rich and nutrient‐poor rivers over at least 2 million km2, or about one‐third of the Amazon Basin. We show that flooded forest area is the most important wetland variable explaining regional variations in migratory characiforme biomass as indicated by maximum annual fishery catches. The sustainable management of Amazon fisheries will require transnational cooperation and a paradigm shift from local community management alone to a more integrated approach that considers both rural and urban consumers and challenges, and the realistic life histories of migratory species.
Rate‐limiting step and substrate accessibility of cellobiohydrolase Cel6A from Trichoderma reesei
Authors: Christensen Stefan J. , Kari Jeppe , Badino Silke F. , Borch Kim , Westh Peter
Published: October 2018

The cellobiohydrolase (CBH) Cel6A is an important component of enzyme cocktails for industrial degradation of lignocellulosic biomass. However, the kinetics of this enzyme acting on its natural, insoluble substrate remains sparsely investigated. Here, we studied Cel6A from Trichoderma reesei with respect to adsorption, processivity, and kinetics both in the steady‐state and pre‐steady‐state regimes, on microcrystalline and amorphous cellulose. We found that slow dissociation (koff) was limiting the overall reaction rate, and we suggest that this leads to an accumulation of catalytically inactive complexes in front of obstacles and irregularities on the cellulose surface. The processivity number of Cel6A was low on both investigated substrates (5–10), and this suggested a rugged surface with short obstacle‐free path lengths. The turnover of the inner catalytic cycle (the reactions of catalysis in one processive step) was too fast to be fully resolved, but a minimum value of about 20 s−1 could be established. This is among the highest values reported hitherto for a cellulase, and it underscores the catalytic efficiency of Cel6A. Conversely, we found that Cel6A had a poor ability to recognize attack sites on the cellulose surface. On amorphous cellulose, for example, Cel6A was only able to initiate hydrolysis on about 4% of the sites to which it could adsorb. This probably reflects high requirements of Cel6A to the architecture of the site. We conclude that compared to the other CBH, Cel7A, secreted by T. reesei, Cel6A is catalytically more efficient but less capable of attacking a broad range of structurally distinct sites on the cellulose surface.

Enzymes

TrCel6A, nonreducing end‐acting cellobiohydrolase (EC3.2.1.91) from Trichoderma reesei; TrCel7A, reducing end‐acting cellobiohydrolase (EC3.2.1.176) from T. reesei.
A sluggish mid‐Proterozoic biosphere and its effect on Earth's redox balance
Authors: Ozaki Kazumi , Reinhard Christopher T. , Tajika Eiichi
Published: October 2018

The possibility of low but nontrivial atmospheric oxygen (O2) levels during the mid‐Proterozoic (between 1.8 and 0.8 billion years ago, Ga) has important ramifications for understanding Earth's O2 cycle, the evolution of complex life and evolving climate stability. However, the regulatory mechanisms and redox fluxes required to stabilize these O2 levels in the face of continued biological oxygen production remain uncertain. Here, we develop a biogeochemical model of the C‐N‐P‐O2‐S cycles and use it to constrain global redox balance in the mid‐Proterozoic ocean–atmosphere system. By employing a Monte Carlo approach bounded by observations from the geologic record, we infer that the rate of net biospheric O2 production was Tmol year−1 (1σ), or ~25% of today's value, owing largely to phosphorus scarcity in the ocean interior. Pyrite burial in marine sediments would have represented a comparable or more significant O2 source than organic carbon burial, implying a potentially important role for Earth's sulphur cycle in balancing the oxygen cycle and regulating atmospheric O2 levels. Our statistical approach provides a uniquely comprehensive view of Earth system biogeochemistry and global O2 cycling during mid‐Proterozoic time and implicates severe P biolimitation as the backdrop for Precambrian geochemical and biological evolution.
NGOs and the policy‐making process in Russia: The case of child welfare reform
Authors: Bindman Eleanor , Kulmala Meri , Bogdanova Elena
Published: October 2018

This article explores the issue of the major reform of the child welfare sector that has been carried out in Russia in recent years. Focusing on deinstitutionalization and a child's right to a family, this reform moves Russia in the direction of international trends in this area and represents a break with previous state‐ and institution‐dominated approach to “problem families.” The article explores how and why this process has come about in a traditionally top‐down hybrid regime and applies the Multiple Streams Framework first developed by Kingdon to argue that Russian child welfare nongovernmental organizations have acted in concert with government officials to act as policy entrepreneurs in framing the policy problem and presenting solutions to it in a way that has influenced national priorities in this area. At the same time, the article acknowledges that major challenges remain in terms of implementing the reform at the regional level of government in Russia.
Regulation of LRG1 expression by RNA‐binding protein Puf5 in the budding yeast cell wall integrity pathway
Authors: Viet Nguyen Thi Minh , Duy Duong Long , Saito Kazuhiro , Irie Kaoru , Suda Yasuyuki , Mizuno Tomoaki , Irie Kenji
Published: October 2018

The PUF RNA‐binding protein Puf5 is involved in regulation of the cell wall integrity (CWI) pathway in yeast. Puf5 negatively regulates expression of LRG1 mRNA, encoding for a GTPase‐activating protein for Rho1 small GTPase. Here, we further analyzed the effect of Puf5 on LRG1 expression, together with Ccr4 and Pop2 deadenylases, Dhh1 decapping activator, and other PUF proteins. We found that the growth defect of puf5∆ mutant was enhanced by ccr4∆ mutation, which was partially suppressed by LRG1 deletion. Consistently, Lrg1 protein level was much more up‐regulated in ccr4Δ puf5Δ double mutant than in each single mutant. Interestingly, LRG1 poly(A) tail length was longer in ccr4∆ mutant but not in puf5∆ mutant. Thus, Puf5 regulates LRG1 expression independently from Ccr4, although Puf5 recruits the Ccr4‐Not deadenylase complex for mRNA destabilization. Unexpectedly, puf6Δ mutation suppressed the growth defect caused by ccr4Δ puf5∆ mutation. Loss of Rpl43a and Rpl43b ribosomal proteins, the previously identified Puf6 interactors, also suppressed the growth defect of ccr4Δ puf5Δ mutant. Our results suggest that Puf5 functions in the CWI pathway by regulating LRG1 expression in a deadenylase‐independent manner, and that Puf6 is involved in the Ccr4‐ and Puf5‐mediated regulation of cell growth through association with Rpl43.
Proteomic profile of root canal contents in teeth with post‐treatment endodontic disease
Authors: Francisco P. A. , Delboni M. G. , Lima A. R. , Xiao Y. , Siqueira W. L. , Gomes B. P. F. A.
Published: October 2018

Aim

To characterize the proteome of 20 root canals in teeth with post‐treatment endodontic disease using mass spectrometry and to correlate the identified proteins with clinical features.

Methodology

Twenty patients with radiographic evidence of apical periodontitis and need for root canal re‐treatment were selected. Samples from the root canal contents were collected and processed using two‐dimensional capillary nano‐flow liquid chromatography and electrospray ionization tandem mass spectrometry. The acquired spectra were separately searched against specific protein database. The results obtained were analysed using descriptive statistics. Additionally, Pearson's chi‐square test or one‐sided Fisher's exact test, as appropriate, was chosen to examine the null hypothesis that there is no relationship between each clinical feature and the presence of specific microbial or human proteins. Significance levels were set at 5% (P < 0.05).

Results

A total of 1153 human and 720 microbial UniProt accession numbers corresponding to proteins were recovered. The greater prevalence of proteins was related to biological functions, such as cellular and metabolic processes. A considerable number of microbial proteins with clinical relevance functions, such as pathogenesis/virulence, proteolysis, cell adhesion and drug resistance, were detected. Common endodontic pathogens related to post‐treatment endodontic disease such as Enterococcus spp., Propionibacterium spp. and Streptococcus spp. were associated with 23, 40 and 94 distinct proteins, respectively. As for human proteins, many factors related to the immune system process were detected. No significant correlations were found between microbial and human proteins and the clinical features investigated (P > 0.05).

Conclusions

A considerable number of microbial and human proteins were identified using proteomic analyses, being mainly related to processes indicating cell viability. No significant correlation was found between proteins and clinical features. These findings suggest a network of important microbial pathogenic functions that may be responsible for the host immune system response.
Association between missed canals and apical periodontitis
Authors: Costa F. F. N. P. , Pacheco‐Yanes J. , Siqueira J. F. , Oliveira A. C. S. , Gazzaneo I. , Amorim C. A. , Santos P. H. B. , Alves F. R. F.
Published: October 2018

Aim

To evaluate the frequency of post‐treatment apical periodontitis associated with root filled teeth with at least one untreated root canal.

Methodology

Eight hundred and seven cone beam computed tomography images containing at least one root filled tooth were selected from a collection of 1543 images from Brazilian individuals. Scans were taken using ICAT Classic devices (Imaging Sciences, Hatfield, PA, USA) in a private oral radiology clinic from January to April 2015. All root filled teeth were analysed for the presence of missed canals and apical periodontitis. The chi‐square and odds ratio tests were used to verify if there were an association and risk relationship between the occurrence of untreated canals and apical periodontitis.

Results

A total of 2294 teeth with evidence of root fillings were identified. Two hundred and eighty‐one teeth had at least one untreated missed canal (12%). The frequency of apical periodontitis in teeth with at least one untreated canal was significantly greater in comparison to teeth with all canals treated (274/281, 98% versus 1736/2013, 86%) (P < 0.01). The odds for apical periodontitis to be present was 6.25 times greater for teeth with an untreated canal. The mesiobuccal roots of maxillary first molars had the greatest frequency of untreated canals (114/154, 74%), with the second mesiobuccal canal being the most frequently missed (n = 106/114, 93%).

Conclusion

Root filled teeth with at least one missed canal had a high prevalence of post‐treatment apical periodontitis.
Bi2O3–TiO2–Nd2O3 lead‐free material for microwave device applications
Authors: Slavov Stanislav S. , Soreto Teixeira Silvia , Graça Manuel P. F. , Costa Luis C. , Popova Venetka , Dimitriev Yanko B.
Published: October 2018

Lead‐free Bi2O3–TiO2–Nd2O3 system and its potential application for microwave devices applications were studied. The samples were synthesized using the melt quenching method. According to the X‐Ray Diffraction analysis, the samples are polycrystalline with three different crystal phases. Measurements of the dielectric complex permittivity function were made at 2.7 GHz, using a resonant cavity and the small perturbation theory. The values of the dielectric permittivity of the prepared materials were compared with the commercial ones, and we conclude that these new lead‐free materials have a good potential to replace lead‐containing devices for microwave frequency applications.
Outcomes of 219 chronic myeloid leukaemia patients with additional chromosomal abnormalities and/or tyrosine kinase domain mutations
Authors: Xue Mingming , Cheng Juan , Zhao Jiangyun , Zhang Shuling , Jian Jinli , Qiao Yanhong , Liu Bei
Published: October 2018

Introduction

To confirm the role of additional chromosomal abnormalities (ACAs) and kinase domain (KD) mutations in the progression and outcomes of Chronic myeloid leukaemia (CML) patients and the connection between them, we analysed the ACAs and KD mutations of 219 CML patients admitted to our hospital.

Methods

Cytogenetic analysis of metaphases was performed to detect ACAs, and the BCR‐ABL1 KD was sequenced to detect KD mutations.

Results

Twenty‐four patients (11.0%) had ACAs in addition to the BCR‐ABL1 or t(9;22)(q34;q11) translocation. The most common abnormality was trisomy 8. Twelve different KD mutations were observed in 13 out of 53 imatinib‐resistant patients (24.5%). p.(Y235H) (n = 3; 23.07%), p.(F359V) and p.(T315I) (n = 2; 15.38%) presented most frequently. KD mutations subtypes (p.(E255K), p.(T315I), p.(F359V), p.(M244V) and p.(L298V)) coexisted with ACAs. The incidence of CML progression was 12/22 (54.5%) in the group of patients with ACAs and/or KD mutations and 2/143 (1.4%) in the group of patients without ACAs or KD mutations (CI 95%, P < 0.001) and was higher in the KD mutations group than in the ACAs group (P = 0.046). The group of patients with ACAs and/or KD mutations had more men than the group of patients without ACAs or KD mutations (P = 0.013).

Conclusion

We conclude that ACAs and/or KD mutations are related to CML progression and are adverse outcome factors. Their presence exhibits gender differences and is more common in males. p.(E255K), p.(T315I), p.(F359V), p.(M244V) and p.(L298V) emerge more frequently when ACAs and KD mutations coexist.
Barriers to medication adherence in patients prescribed medicines for the prevention of cardiovascular disease: a conceptual framework
Authors: Easthall Claire , Taylor Natalie , Bhattacharya Debi
Published: October 2018

Objectives

To identify barriers to medication adherence in patients prescribed medicines for the prevention of cardiovascular disease and map these to the Theoretical Domains Framework (TDF), to produce a conceptual framework for developing a questionnaire-based medication adherence tool.

Methods

A scoping review of barriers to medication adherence in long-term conditions was conducted to generate an initial pool of barriers. After preliminary mapping to the TDF, these barriers were presented to two focus groups of patients prescribed medicines for the prevention of cardiovascular disease (n = 14) to stimulate discussion. The group discussions enabled the patients’ interpretations of the adherence barriers to be determined, provided validity from the patient perspective and identified additional barriers unrepresented in the scoping review.

Key findings

The preliminary pool of adherence barriers was identified from 47 studies across a range of long-term conditions. The majority of TDF domains were represented by these literature-identified barriers except ‘social/professional role and identity’ and ‘behavioural regulation’. Barrier mapping was largely endorsed by focus group participants, who also contributed additional barriers, including those relating to not having a ‘system’ in place for managing their medicines and the negative emotions evoked by medicine taking.

Conclusion

The TDF enabled full exploration of adherence barriers including those relating to emotions which have received limited attention in the literature. This work has provided a conceptual framework for developing a questionnaire to identify an individual’s adherence barriers which may then be coupled with appropriate behaviour change techniques to deliver a theory-based intervention tailored for individual need.
The Case of Anar Meshimbayeva
Authors: Tarran Brian
Published: October 2018

Kazakhstan's former chief statistician was released from prison earlier this year, but her trial and conviction barely registered in the wider world. Brian Tarran hears her story
Air Quality in the USA
Authors: Mannshardt Elizabeth , Naess Liz
Published: October 2018

Elizabeth Mannshardt and Liz Naess explain how the US Environmental Protection Agency uses statistics to assess risks and trends in air pollution, to inform both environmental policy and the public
Gerrymandering, Redistricting and Statistics: A Q&A with Vince Barabba
Authors: Tarran Brian
Published: October 2018

Vince Barabba is a former head of the US Census Bureau, the founder of the Market Insight Corporation and a former president of the American Statistical Association. He was also one of the first 14 people picked to serve on a California commission that put redistricting decisions in the hands of state citizens. He sat down with Significance over email to discuss this experience, what other states can learn from California's experiment, and what role statisticians should play in helping combat the practice of gerrymandering. Edited by Brian Tarran
Ethics in Statistical Practice and Communication: Five Recommendations
Authors: Gelman Andrew
Published: October 2018

Ethics in statistics is about more than good practice. It extends to the communication of uncertainty and variation. Andrew Gelman presents five recommendations for dealing with fundamental dilemmas
Ni‐YSZ(001) solid‐solid interfacial energy and orientation relationships
Authors: Nahor Hadar , Kaplan Wayne D.
Published: October 2018

Equilibrated Ni particles were produced via solid‐state dewetting of continuous Ni films deposited on the (001) surface of yttrium stabilized zirconia (YSZ). The solid‐solid interface energy of the equilibrated Ni(111)‐YSZ(001) interface was determined using Winterbottom analysis. Two low‐index orientation relationships (ORs) were found using the selected area electron diffraction patterns in transmission electron microscopy: (OR1) and (OR2). However, many particles were found to deviate from these low‐index ORs while maintaining the out‐of‐plane orientation, . The interface energy was measured to be 2.5 ± 0.1 J/m2 regardless of the in‐plane orientation. The orientation distribution was determined using electron backscattered diffraction for Ni particles on both (111) and (001) YSZ substrates and was found to correlate well with the interface energies measured in a previous study for the Ni‐YSZ(111) interface and in the present study for the Ni‐YSZ(001) interface.
Molten salt synthesis of BaTiO3 nanorods: Dielectric, optical properties, and structural characterizations
Authors: Xue Piaojie , Wu Heng , Xia Weiren , Pei Zhipeng , Lu Yao , Zhu Xinhua
Published: October 2018

Single‐crystalline perovskite BaTiO3 (BTO) nanorods were synthesized by (BaTi2O5‐template) molten salt synthesis (MSS) methods. The effects of process parameters (eg, calcination temperature, reaction time, molten salt content, as well as different phase structures of TiO2 and barium oxides) on the formation of BTO nanorods and their structural characteristics were systematically investigated. The BTO nanorods synthesized at 800°C for 5 hours by MSS method with the molar salt ratios of BaCO3:TiO2 (anatase):NaCl:KCl equal to 1:1:60:60, exhibited smooth and clean surfaces through their lengths. Their diameters were in the range of 130‐200 nm with average length of 5 μm. Large‐scale amount of BTO nanorods was synthesized by BaTi2O5‐template MSS method at 650°C with molar salt ratios of BaC2O4:BaTi2O5 (template):NaCl:KCl equal to 1:1:60:60. The BTO nanorods successfully retained the one‐dimensional morphology of the BaTi2O5 templates and their lengths were in the range of 5‐10 μm with an average diameter of ~300 nm. The single‐crystalline nature of individual BTO nanorod was revealed by its selected area electron diffraction patterns and high‐resolution TEM images. The BTO nanorods exhibited good optical properties with optical bandgaps in the range of 2.5‐2.6 eV. Such optical bandgaps make the present BTO nanorods promising candidates for ferroelectric photovoltaic devices. Dielectric properties of the BTO nanorods synthesized by MSS method were comparatively investigated with the BTO nanorods synthesized by the BaTi2O5‐template MSS method. It is found that the later BTO nanorods exhibit better dielectric properties and their synthesized temperature is also much lower than the former ones.
Novel device for in situ process characterization of oxide/oxide ceramic matrix composites fabricated by flexible injection
Authors: Scola Alessandro , Podgorski Michaël , Eberling‐Fux Nicolas , Turenne Sylvain , Ruiz Edu
Published: October 2018

In this work, a new manufacturing process of CMC by liquid molding was studied. An instrumented device has been developed to characterize the through‐thickness impregnation of ceramic fibers by a slurry charged with submicron ceramic particles. This instrument was used to characterize the permeability of the fibrous reinforcement and the formation of the ceramic cake by filtration of a ceramic particle suspension. Slurries containing different concentrations (10, 25, 33, and 40 vol%) of mono‐dispersed alumina particles were filtered under different pressure conditions (345, 415, 485 kPa) to optimize the cake formation and filling of fibrous reinforcements while controlling the porosity level. Ceramic cakes exhibited an average permeability of 1.0 × 10−17 m2 while the manufactured all‐oxide composites resulted in a permeability of 0.6 × 10−17 m2. Furthermore, a mathematical model based on Darcy's law was developed in this study to predict the rate of filtering and cake formation during injection using the permeability and filtration data measured with the experimental device. This mathematical model allows to determine the filtration time to produce a dense ceramic composite with an accuracy of ±15%, which corresponds to an error of less than 0.1 mm on the thickness of formed CMC.