bluuebunny/crossref_metadata_2025 huggingface dataset:
Management Roles and Sustainability Information. Exploring Corporate Practice
Authors: Schaltegger Stefan , Burritt Roger , Zvezdov Dimitar , Hörisch Jacob , Tingey‐Holyoak Joanne
Published: December 2015

Little empirical research has been conducted on perceptions of the types of sustainability information dealt with by different managers in internal company processes. In this study the roles of different managers are distinguished based on contingency theory and using the categorisation in the sustainability balanced scorecard concept. Expected sustainability information types are identified for these roles and hypotheses are derived and tested about perceptions of the types of sustainability information in different management roles. Interviews identified 116 roles involved with sustainability information in a set of leading German and UK sustainability reporting companies. Results from analysing sustainability information types contingent upon different management roles contribute to the understanding of sustainability accounting systems and practices and how companies can best support different management roles with appropriate sustainability information.
Choosing a Model of Maternity Care: Decision Support Needs of Australian Women
Authors: Stevens Gabrielle , Miller Yvette D. , Watson Bernadette , Thompson Rachel
Published: December 2015

Background

Access to information on the features and outcomes associated with the various models of maternity care available in Australia is vital for women's informed decision‐making. This study sought to identify women's preferences for information access and decision‐making involvement, as well as their priority information needs, for model of care decision‐making.

Methods

A convenience sample of adult women of childbearing age in Queensland, Australia were recruited to complete an online survey assessing their model of care decision support needs. Knowledge on models of care and socio‐demographic characteristics were also assessed.

Results

Altogether, 641 women provided usable survey data. Of these women, 26.7 percent had heard of all available models of care before starting the survey. Most women wanted access to information on models of care (90.4%) and an active role in decision‐making (99.0%). Nine priority information needs were identified: cost, access to choice of mode of birth and care provider, after hours provider contact, continuity of carer in labor/birth, mobility during labor, discussion of the pros/cons of medical procedures, rates of skin‐to‐skin contact after birth, and availability at a preferred birth location. This information encompassed the priority needs of women across age, birth history, and insurance status subgroups.

Conclusions

This study demonstrates Australian women's unmet needs for information that supports them to effectively compare available options for model of maternity care. Findings provide clear direction on what information should be prioritized and ideal channels for information access to support quality decision‐making in practice.
Decursin enhances TRAIL‐induced apoptosis through oxidative stress mediated‐ endoplasmic reticulum stress signalling in non‐small cell lung cancers
Authors: Kim Jaekwang , Yun Miyong , Kim Eun‐Ok , Jung Deok‐Beom , Won Gunho , Kim Bonglee , Jung Ji Hoon , Kim Sung‐Hoon
Published: December 2015

Background and Purpose

The TNF‐related apoptosis‐inducing ligand (TRAIL) is a promising anticancer agent due to its remarkable ability to selectively kill tumour cells. However, because most tumours exhibit resistance to TRAIL‐induced apoptosis, the development of combination therapies to overcome resistance to TRAIL is required for effective cancer therapy.

Experimental Approach

Cell viability and possible synergy between the plant pyranocoumarin decursin and TRAIL was measured by MTT assay and calcusyn software. Reactive oxygen species (ROS) and apoptosis were measured using dichlorodihydrofluorescein and annexin/propidium iodide in cell flow cytometry. Changes in protein levels were assessed with Western blotting.

Key Results

Combining decursin and TRAIL markedly decreased cell viability and increased apoptosis in TRAIL‐resistant non‐small‐cell lung cancer (NSCLC) cell lines. Decursin induced expression of the death receptor 5 (DR5). Inhibition of DR5 attenuated apoptotic cell death in decursin + TRAIL treated NSCLC cell lines. Interestingly, induction of DR5 and CCAAT/enhancer‐binding protein homologues protein by decursin was mediated through selective induction of the pancreatic endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) branch of the endoplasmic reticulum stress response pathway. Furthermore, enhancement of PERK/ATF4 signalling by decursin was mediated by ROS generation in NSCLC cell lines, but not in normal human lung cells. Decursin also markedly down‐regulated expression of survivin and Bcl‐xL in TRAIL‐resistant NSCLC cells.

Conclusions and Implications

ROS generation by decursin selectively activated the PERK/ATF4 axis of the endoplasmic reticulum stress signalling pathway, leading to enhanced TRAIL sensitivity in TRAIL‐resistant NSCLC cell lines, partly via up‐regulation of DR5.
Genotyping HLA‐B*5801 for Allopurinol‐Induced Severe Cutaneous Adverse Reactions: An Accurate and Prompt Method
Authors: Cheng Lin , Zhang Lihua , Gao Lichen , Zhang Wei , Chen Xiaoping , Zhou Hong‐Hao
Published: December 2015

Objectives

A new method of HLA‐B*5801 genotyping was compared with sequence‐based typing (SBT) to find an accurate and prompt method in genotyping HLA‐B*5801.

Methods

Two groups of patients from allopurinol‐induced cutaneous adverse reactions (SCARs) and allopurinol‐tolerant were both genotyped with PG5801 kit and SBT method. The genotyping results of HLA‐B*5801 were compared between the two groups.

Results

The PG5801 detection kit results were 100% (79/79) in agreement with the SBT genotyping results for identifying the HLA‐B*5801 (+) patients. No false‐positive or false‐negative errors were found. The sensitivity, specificity, rate of adherence, positive predictive value (PPV) and negative predictive value (NPV) were 100%.

Conclusion

The potential fast screening method is an ideal tool to rule out the high‐risk allopurinol‐induced SCARs patients.
Multiple phases in regulation of Nanog expression during pre‐implantation development
Authors: Komatsu Kouji , Fujimori Toshihiko
Published: December 2015

Nanog is a key transcriptional factor for the maintenance of pluripotency of ES cells, iPS cells or cells in early mammalian embryos. The expression of Nanog is mainly localized to the epiblast in the late blastocyst. The Nanog gene expression pattern varies between embryos and between blastomeres during blastocyst formation. In this report, we traced the changes of Nanog expression in each cell in developing preimplantation mouse embryos through time‐lapse observation of Nanog‐GFP transgenic mouse embryos. The expression pattern of Nanog was classified into four phases depending on the developmental stage. Nanog expression started at very low levels during cleavage stages. It increased stochastically during the morula stage, but its expression level had no clear correlation with future cell fates. After the 32‐cell stage, when embryos form the blastocyst cavity, Nanog expression was upregulated mainly in ICM cells while it was repressed in the future primitive endoderm lineage in an FGF signaling‐dependent manner in the later stages. These results indicate that there are multiple phases in the transcriptional regulation of Nanog during blastocyst formation.
Pou5f3.2‐induced proliferative state of embryonic cells during gastrulation of Xenopus laevis embryo
Authors: Nishitani Eriko , Li Chong , Lee Jaehoon , Hotta Hiroyo , Katayama Yuta , Yamaguchi Masahiro , Kinoshita Tsutomu
Published: December 2015

POU class V (POU‐V) transcription factors play the important role in maintenance of pluripotency and cell differentiation. Pou5f3.2 (Oct25), one of Xenopus POU‐V transcription factors, shows the zygotic expression prior to gastrulation. In order to know the molecular mechanism of pou5f3.2 expression at gastrula stage, we examined a responsiveness of pou5f3.2 to Nodal signaling. Animal cap assay demonstrated that Xnr2 activates the gene expression of pou5f3.2. In comparative analysis of the 5′‐flanking region of pou5f3.2 between Xenopus laevis and X. tropicalis, two conserved regions were detected within the flanking region. Reporter analyses showed that one of the conserved regions contained an enhancer region, which had several Smad2/3 and FoxH1 binding motifs. ChIP assay demonstrated that Smad2 binds to the enhancer region. These results suggest that Nodal signaling induces zygotic expression of pou5f3.2 at gastrula stage. To understand a role of pou5f3.2 in gastrula embryos, morpholino oligo DNA of pou5f3.2 was injected into the lateral side of one blastomere at the 2‐cell stage. The morphant embryos showed diminution of Xbra1 expression and gastrulation defect in the injection side, suggesting the essential role of pou5f3.2 at the gastrula stage. Xbra1 expression and gastrulation were also inhibited by injecting with the synthesized RNAs of pou5f3.2. Furthermore, in the pou5f3.2‐injected embryo, gene expression of p27Xic1 was drastically suppressed, and the number of dividing cells increased in the injection side. These results suggest that one role of pou5f3.2 is to keep the embryonic cells in undifferentiated and proliferative state during gastrulation.
Skill Balance and Entrepreneurship Evidence from Online Career Histories
Authors: Chen Li-Wei , Thompson Peter
Published: December 2015

Lazear's jack–of–all–trades theory suggests that individuals with balanced skills are more likely to become entrepreneurs, and that balanced skills can be accumulated by studying a varied curriculum, working in a variety of functions, and working for a variety of employers. We reexamine the theory using a matched case–control sample, constructed from a professional networking website that controls for unobserved heterogeneity in employer and job characteristics. We find evidence that variety predicts entry into entrepreneurship, largely through its positive association with the likelihood of having certain specific skills. However, our analysis also demonstrates that attempts to identify the effects of skill variety on entrepreneurship are likely to be highly sensitive to sample construction and regression specification.
Do the Self–Employed More Likely Emerge from Sequential or Parallel Work Experience in Business–Related Functions?
Authors: Hsieh Chihmao
Published: December 2015

Recent theory suggests generalists are more likely than specialists to become self–employed. However, little research examines whether different career paths of generalists are equally effective. I argue those experiencing business–related functions in parallel rather than sequentially more likely become self–employed—as a career proceeds over years—because “connections” detected across domains during parallel work experience are particularly valuable in discovery of future opportunities. Yet, positive effects of experiencing domains sequentially are more strongly amplified when individuals are analytically disposed. Analyzing careers of scientists and engineers, SESTAT data broadly support the hypotheses but mostly for male, incorporated, and/or nonacademic entrepreneurial self–employment.
The epidermal growth factor receptor decreases Stathmin 1 and triggers catagen entry in the mouse
Authors: Bichsel Kyle J. , Hammiller Brianna , Trempus Carol S. , Li Yanhua , Hansen Laura A.
Published: December 2015

The epidermal growth factor receptor (EGFR) is necessary for normal involution of hair follicles after the growth phase of anagen, although the mechanisms through which it acts are not well understood. In this report, we used transcriptional profiling of microdissected hair follicles from mice with skin‐targeted deletion of Egfr to investigate how EGFR activation triggers catagen. Immunofluorescence for phospho‐EGFR in mouse skin revealed increased activation of EGFR in follicular keratinocytes at catagen onset. Consistent with other models of EGFR deficiency, mice with skin‐targeted deletion of Egfr (Krt14‐Cre+/Egfrfl/fl) exhibited a delayed and asynchronous catagen entry. Transcriptional profiling at the time of normal catagen onset at post‐natal day (P) 17 revealed increased expression of the mitotic regulator Rcc2 in hair follicles lacking EGFR. Rcc2 protein was strongly immunopositive in the nuclei of control follicular keratinocytes at P16 then rapidly decreased until it was undetectable between P18 and 21. In contrast, Rcc2 expression continued in Egfr mutant follicles throughout this period. Proliferation, measured by bromodeoxyuridine incorporation, was also significantly increased in Egfr mutant follicular keratinocytes compared to controls at P18‐21. Similarly, Rcc2‐regulated mitotic regulator Stathmin 1 was strikingly reduced in control but not Egfr mutant follicles between P17 and P19. Deletion of Stmn1, in turn, accelerated catagen entry associated with premature cessation of proliferation in the hair follicles. These data reveal EGFR suppression of mitotic regulators including Rcc2 and Stathmin 1 as a mechanism for catagen induction in mouse skin.
Dynamics of internalization and recycling of the prometastatic membrane type 4 matrix metalloproteinase (MT4‐MMP) in breast cancer cells
Authors: Truong Alice , Yip Cassandre , Paye Alexandra , Blacher Silvia , Munaut Carine , Deroanne Christophe , Noel Agnès , Sounni Nor Eddine
Published: December 2015

Membrane type 4 matrix metalloproteinase (MT4‐MMP) [matrix metalloproteinase (MMP) 17] is a GPI‐anchored membrane‐type MMP expressed on the cell surface of human breast cancer cells. In triple‐negative breast cancer cells, MT4‐MMP promotes primary tumour growth and lung metastases. Although the trafficking and internalization of the transmembrane membrane type 1 MMP have been extensively investigated, little is known about the regulatory mechanisms of the GPI‐anchored MT4‐MMP. Here, we investigated the fate and cellular trafficking of MT4‐MMP by analysing its homophilic complex interactions, internalization and recycling dynamics as compared with an inert form, MT4‐MMP‐E249A. Oligomeric and dimeric complexes were analysed by cotransfection of cells with FLAG‐tagged or Myc‐tagged MT4‐MMP in reducing and nonreducing immunoblotting and coimmunoprecipitation experiments. The trafficking of MT4‐MMP was studied with an antibody feeding assay and confocal microscopy analysis or cell surface protein biotinylation and western blot analysis. We demonstrate that MT4‐MMP forms homophilic complexes at the cell surface, and internalizes in early endosomes, and that some of the enzyme is either autodegraded or recycled to the cell surface. Our data indicate that MT4‐MMP is internalized by the clathrin‐independent carriers/GPI‐enriched early endosomal compartments pathway, a mechanism that differs from that responsible for the internalization of other membrane‐type MMP members. Although MT4‐MMP localizes with caveolin‐1, MT4‐MMP internalization was not affected by inhibitors of caveolin‐1 or clathrin endocytosis pathways, but was reduced by CDC42 or RhoA silencing with small interfering RNA. We provide a new mechanistic insight into the regulatory mechanisms of MT4‐MMP, which may have implications for the design of novel therapeutic strategies for metastatic breast cancer.
Disturbance history influences stressor impacts: effects of a fungicide and nutrients on microbial diversity and litter decomposition
Authors: Gardeström Johanna , Ermold Matti , Goedkoop Willem , McKie Brendan G.
Published: December 2015

Streams draining agricultural catchments are severely degraded by multiple stressors, including nutrient enrichment and pesticides. The understanding of how such stressors interact to alter ecosystem structure and function, and how responses of biota reflect their longer‐term disturbance history, remains limited.

We conducted a multifactorial stream microcosm experiment to investigate how elevated nutrients and a fungicide (azoxystrobin) interact to affect multiple variables associated with leaf decomposition: the biomass, sporulation rate and diversity of aquatic hyphomycete decomposers, litter decomposition rates and detritivore growth.

We further manipulated decomposer species composition by using three distinct fungal assemblages drawn from streams with contrasting histories of agricultural disturbance: a forest stream, a mixed land‐use stream subject to nutrient enrichment but little pesticide use, and an agricultural stream subjected to both intensive nutrient and pesticide use. We also varied the presence of the detritivorous isopod Asellus aquaticus.

The fungicide azoxystrobin reduced both biomass and diversity of aquatic hyphomycetes and growth of A. aquaticus, and had negative knock‐on effects on leaf decomposition and fungal sporulation. These impacts further varied with nutrient concentration.

Impacts of the fungicide differed markedly among the three fungal assemblages. The agricultural assemblages were dominated by tolerant species and showed some capacity for maintaining processes under pesticide exposure, whereas diversity and functioning were strongly suppressed in the forest stream assemblage, which was dominated by stress‐intolerant species.

Pesticides, in interaction with other agricultural stressors, can impact microbial diversity and key ecosystem processes underlying the delivery of ecosystem services from streams. The extent of such impacts vary according to the longer‐term disturbance history of the biota, and might be most acute when agricultural activity expands into previously uncultivated catchments, as is currently occurring in many regions of the world.
Temporal dynamics influenced by global change: bee community phenology in urban, agricultural, and natural landscapes
Authors: Leong Misha , Ponisio Lauren C. , Kremen Claire , Thorp Robbin W. , Roderick George K.
Published: December 2015

Urbanization and agricultural intensification of landscapes are important drivers of global change, which in turn have direct impacts on local ecological communities leading to shifts in species distributions and interactions. Here, we illustrate how human‐altered landscapes, with novel ornamental and crop plant communities, result not only in changes to local community diversity of floral‐dependent species, but also in shifts in seasonal abundance of bee pollinators. Three years of data on the spatio‐temporal distributions of 91 bee species show that seasonal patterns of abundance and species richness in human‐altered landscapes varied significantly less compared to natural habitats in which floral resources are relatively scarce in the dry summer months. These findings demonstrate that anthropogenic environmental changes in urban and agricultural systems, here mediated through changes in plant resources and water inputs, can alter the temporal dynamics of pollinators that depend on them. Changes in phenology of interactions can be an important, though frequently overlooked, mechanism of global change.
Xylem morphology determines the drought response of two Arundo donax ecotypes from contrasting habitats
Authors: Haworth Matthew , Centritto Mauro , Giovannelli Alessio , Marino Giovanni , Proietti Noemi , Capitani Donatella , De Carlo Anna , Loreto Francesco
Published: December 2015

Arundo donax exhibits rapid growth and requires little nutrient input, making it an ideal perennial biomass crop species. However, this growth is accompanied by high rates of water use, potentially restricting the use of A. donax in rain‐fed marginal lands. Here, we investigated the physiological and morphological responses to drought in two ecotypes of A. donax from contrasting habitats: one from an arid environment in Morocco, and the second from a warm humid sub‐Mediterranean climate in central Italy. Prolonged drought resulted in identical reductions in leaf‐level photosynthesis (PN) and stomatal conductance (Gs) in the two ecotypes. However, water deficit induced an increase in xylem vessel diameter in the Moroccan plants, improving the movement of water along the stem, but also likely reducing the resistance to embolism. In contrast, the Italian ecotype reduced xylem vessel area, thus increasing resistance to water transport and xylem embolism. The increased xylem vessel size and associated vulnerability to embolism in the Moroccan plants may have contributed to an increase in the loss of leaf numbers, but also to higher relative water content (RWC) in the remaining leaves in comparison to the Italian ecotype, where a greater number of leaves persisted. Despite the Moroccan plants possessing stems with a lower basal area than their Italian counterparts, both ecotypes exhibited identical leaf to supporting stem area ratios under both control and water deficit conditions. This may account for the similarities observed in leaf area measures of PN and Gs in this and previous studies of different A. donax ecotypes. Selection of A. donax ecotypes on the basis of xylem responses to drought may facilitate the development of varieties suited to arid environments prone to severe drought and wetter habitats where prolonged droughts occur less frequently.
Impact of multimodal treatment on prognosis for patients with metastatic upper urinary tract urothelial cancer: Subanalysis of the multi‐institutional nationwide case series study of the Japanese Urological Association
Authors: Inokuchi Junichi , Naito Seiji , Fujimoto Hiroyuki , Hara Tomohiko , Sakura Mizuaki , Nishiyama Hiroyuki , Miyazaki Jun , Kikuchi Eiji , Hinotsu Shiro , Koie Takuya , Ohyama Chikara ,   the Cancer Registration Committee of the Japanese Urological Association
Published: December 2015

Objectives

To describe the nature of metastatic upper urinary tract urothelial cancer and determine the prognostic predictors or treatment modality associated with all‐cause mortality.

Methods

Within the nationwide case series study of the Japanese Urological Association, consisting of 1509 patients with urinary tract urothelial cancer diagnosed in 2005, we identified 102 patients with metastatic urinary tract urothelial cancer. Univariate and multivariate survival analyses identified prognostic outcome variables.

Results

Predominant sites of distant metastasis at diagnosis were the lungs (54.9%), distant lymph nodes (37.3%), bone (32.4%) and liver (19.6%). Of 102 patients, 70 patients (68.6%) died during the median follow‐up period of 6 months, and the 2‐year overall survival rate was estimated at 22%. The median survival time to all‐cause mortality was 8.5 months (95% confidence interval 6.4–10.7 months). On multivariate analysis, independent predictive factors for all‐cause mortality were age (hazard ratio 2.36, P = 0.015) and liver metastasis (hazard ratio 2.35, P = 0.037). Patients who received multimodal treatment including chemotherapy and surgery showed significantly better prognosis (median survival time 25.8 months) compared with patients treated with chemotherapy alone (median survival time 7.3 months) or best supportive care (median survival time 4.3 months).

Conclusions

Age at diagnosis and the presence of liver metastasis seem to have an impact on survival of metastatic urinary tract urothelial cancer patients. Multimodal treatment including systemic chemotherapy and surgery might result in better prognosis in some of these patients.
Enhancing Statistics Education by Including Qualitative Research
Authors: Ograjenšek Irena , Gal Iddo
Published: December 2015

In this paper, we propose to re‐examine the role of qualitative thinking in the early stages of learning statistics and, where relevant, integrate selected elements of qualitative research methods into statistics curricula. We believe that this can help to improve statistics education, deepen desired student understanding of the role of statistics in providing answers to real‐world problems and address recurring concerns about student motivation. The paper clarifies the logic underlying our proposal, examines existing connections between qualitative and quantitative research during instruction that often go unacknowledged and can be built upon, explores practical implementation issues and discusses advantages as well as limitations of the proposed approach.
A quartet method based on variable neighborhood search for biomedical literature extraction and clustering
Authors: Consoli Sergio , Stilianakis Nikolaos I.
Published: December 2015

Medline/PubMed is the largest reference database collecting, organizing, and analyzing biomedical literature. We propose an automated methodology that is capable of searching relevant references for systematic reviews and meta‐analysis from the Medline/PubMed database, and then to visualize the retrieved bibliography through an intuitive method based on a graph layout. In particular, document relationships are represented via the quartet method of hierarchical clustering. As this novel approach is based on an NP‐hard combinatorial problem, a reduced variable neighborhood search is used for producing the graph of document clusters as output from the input distance matrix whereby the number of clusters is not known in advance. The distance matrix is derived from the link‐ranking XML data returned by PubMed with the search results. It is demonstrated how the method allows to retrieve biomedical related bibliography, to find the structure of the literature collection examined, and to detect linked works within thematic areas of interest. With this methodology, scientists are assisted in the analysis of complex citations networks from the biomedical literature.
Late Holocene expansion of ponderosa pine (Pinus ponderosa) in the Central Rocky Mountains, USA
Authors: Norris Jodi R. , Betancourt Julio L. , Jackson Stephen T.
Published: December 2015

Aim

Ponderosa pine (Pinus ponderosa) experienced one of the most extensive and rapid post‐glacial plant migrations in western North America. We used plant macrofossils from woodrat (Neotoma) middens to reconstruct its spread in the Central Rocky Mountains, identify other vegetation changes coinciding with P. ponderosa expansion at the same sites, and relate P. ponderosa migrational history to both its modern phylogeography and to a parallel expansion by Utah juniper (Juniperus osteosperma).

Location

Central Rocky Mountains, Wyoming and Montana, and Black Hills, Wyoming and South Dakota, USA.

Methods

Plant macrofossils were analysed in 90 middens collected at 14 widely separated sites in the northern part of the range of P. ponderosa var. scopulorum. Middens with and without P. ponderosa were 14C dated to pinpoint time of appearance at each site. Sensitivity experiments using a bioclimatic model were used to evaluate potential climatic drivers of late Holocene expansion.

Results

Pinus ponderosa colonized the Black Hills region by at least 3850 yr bp (all ages given in calendar years before present). It expanded into the eastern Bighorn Mountains of northern Wyoming by 2630 yr bp, quickly spreading north in the western Bighorns from 1400 to 1000 yr bp. Concurrent with the latter expansion, P. ponderosa spread c. 350 km to the Little Belt and Big Belt Mountains in western Montana, establishing its northern limit and the modern introgression zone between var. scopulorum and var. ponderosa. Expansion in the Central Rockies of P. ponderosa involved two known haplotypes.

Main conclusions

Pinus ponderosa expanded its range across large parts of northern Wyoming and central Montana during the late Holocene, probably in response to both northward and westward increases in summer temperature and rainfall. The underlying climatic driver may be the same as for the contemporaneous expansion of J. osteosperma, but will remain undetermined without focused development and integration of independent palaeoclimate records in the region.
Reductions in Mean 24‐Hour Ambulatory Blood Pressure After 6‐Week Treatment With Canagliflozin in Patients With Type 2 Diabetes Mellitus and Hypertension
Authors: Townsend Raymond R. , Machin Israel , Ren Jimmy , Trujillo Angelina , Kawaguchi Masato , Vijapurkar Ujjwala , Damaraju Chandrasekharrao V. , Pfeifer Michael
Published: December 2015

This randomized, double‐blind, placebo‐controlled study evaluated the early effects of canagliflozin on blood pressure (BP) in patients with type 2 diabetes mellitus (T2DM) and hypertension. Patients were randomized to canagliflozin 300 mg, canagliflozin 100 mg, or placebo for 6 weeks and underwent 24‐hour ambulatory BP monitoring before randomization, on day 1 of treatment, and after 6 weeks. The primary endpoint was change in mean 24‐hour systolic BP (SBP) from baseline to week 6. Overall, 169 patients were included (mean age, 58.6 years; glycated hemoglobin, 8.1%; seated BP 138.5/82.7 mm Hg). At week 6, canagliflozin 300 mg provided greater reductions in mean 24‐hour SBP than placebo (least squares mean −6.2 vs −1.2 mm Hg, respectively; P=.006). Numerical reductions in SBP were observed with canagliflozin 100 mg. Canagliflozin was generally well tolerated, with side effects similar to those reported in previous studies. These results suggest that canagliflozin rapidly reduces BP in patients with T2DM and hypertension.
Functional decoupling between flowers and leaves in the Ameroglossum pernambucense complex can facilitate local adaptation across a pollinator and climatic heterogeneous landscape
Authors: Wanderley A. M. , Galetto L. , Machado I. C. S.
Published: December 2015

Decoupling between floral and leaf traits is expected in plants with specialized pollination systems to assure a precise flower–pollinator fit, irrespective of leaf variation associated with environmental heterogeneity (functional modularity). Nonetheless, developmental interactions among floral traits also decouple flowers from leaves regardless of selection pressures (developmental modularity). We tested functional modularity in the hummingbird‐pollinated flowers of the Ameroglossum pernambucense complex while controlling for developmental modularity. Using two functional traits responsible for flower–pollinator fit [floral tube length (TL) and anther–nectary distance (AN)], one floral trait not linked to pollination [sepal length (SL), control for developmental modularity] and one leaf trait [leaf length (LL)], we found evidence of flower functional modularity. Covariation between TL and AN was ca. two‐fold higher than the covariation of either of these traits with sepal and leaf lengths, and variations in TL and AN, important for a precise flower–pollinator fit, were smaller than SL and LL variations. Furthermore, we show that previously reported among‐population variation of flowers associated with local pollinator phenotypes was independent from SL and LL variations. These results suggest that TL and AN are functionally linked to fit pollinators and sufficiently decoupled from developmentally related floral traits (SL) and vegetative traits (LL). These results support previous evidences of population differentiation due to local adaptation in the A. pernambucense complex and shed light on the role of flower–leaf decoupling for local adaptation in species distributed across biotic and abiotic heterogeneous landscapes.
Buying Decision Coordination and Monopoly Pricing of Network Goods
Authors: Sääskilahti Pekka
Published: December 2015

We analyze how uncertainty about consumers' preferences affects the pricing of a network device and the interaction usage it enables. A premium device price may give high hardware profits, but adoption will be low reducing the profits from interaction services. The firm internalizing this adjusts its hardware price downward, and prices as if it was getting the maximal interaction usage profits from the full network. Profits decrease in uncertainty, whereas consumer surplus increases in uncertainty, but only if the level of uncertainty is high. Bundling the device and services is profitable if uncertainty relates mostly to consumers' private information.
Small and large fiber neuropathy in those with type 1 and type 2 diabetes: a 5‐year follow‐up study
Authors: Løseth Sissel , Stålberg Erik V. , Lindal Sigurd , Olsen Edel , Jorde Rolf , Mellgren Svein I.
Published: December 2015

The purpose of this study was to evaluate progression of diabetic polyneuropathy and differences in the spectrum and evolution of large‐ and small‐fiber involvement in patients with diabetes type 1 and 2 over 5 years. Fifty‐nine patients (35 type 1 and 24 type 2) were included. Nerve conduction studies (NCS), quantitative sensory testing, skin biopsy for quantification of intraepidermal nerve fiber density (IENFD), symptom scoring and clinical evaluations were performed. Z‐scores were calculated to adjust for the physiologic effects of age and height/gender. Neuropathic symptoms were not significantly more frequent in type 2 than in type 1 diabetic patients at follow‐up (54% vs. 37%). The overall mean NCS Z‐score remained within the normal range, but there was a small significant decline after 5 years in both groups: type 1 (p = 0.004) and type 2 (p = 0.02). Mean IENFD Z‐scores changed from normal to abnormal in both groups, but only significantly in those with type 2 diabetes (reduction from 7.9 ± 4.8 to 4.3 ± 2.8 fibers/mm, p = 0.006). Cold perception threshold became more abnormal only in those with type 2 diabetes (p = 0.049). There was a minimal progression of large fiber neuropathy in both groups. Reduction of small fibers predominated and progressed more rapidly in those with type 2 diabetes.
Chromium picolinate reduces insulin resistance in polycystic ovary syndrome: Randomized controlled trial
Authors: Ashoush Sherif , Abou‐Gamrah Amgad , Bayoumy Hassan , Othman Noura
Published: December 2015

Aim

To investigate the effect of chromium picolinate (CrP) on insulin resistance (IR) in polycystic ovary syndrome (PCOS).

Methods

This double blinded randomized controlled trial was conducted in the Gynecology outpatient clinics at Ain Shams University Women's Hospital. Using closed and randomly mixed envelopes, 100 women were selected out of 400 PCOS patients. Eighty‐five patients finished the study and were analyzed, 44 in group I and 41 in group II. They were randomly allocated to 6 months of either 1000 μg CrP (50 patients), or placebo capsules (50 patients). Patients were seen monthly to encourage similar diet control and physical exercise plans. The primary outcome was fasting glucose insulin ratio (FGIR), secondary outcomes included ovulation, regularity of the cycle, body mass index (BMI), fasting blood sugar (FBS), fasting serum insulin (FSI), and serum testosterone level.

Results

There were no significant differences between women of both groups regarding pretreatment levels of FBS, FSI, FGIR, and serum testosterone. Use of CrP for 6 months was associated with significant reduction of BMI (P < 0.001) and FSI (P = 0.007), and significant rise in FGIR (P = 0.045). CrP significantly increased the chances of ovulation (P = 0.011) and regular menstruation (P = 0.002) by almost twofold after the fifth month of treatment.

Conclusion

Chromium picolinate is useful in PCOS to reduce IR and stimulate ovulation.
Stakeholder Relationship Bonds
Authors: Bosse Douglas A. , Coughlan Richard
Published: December 2015

Scholars and managers continue to seek a better explanation for the behaviours displayed by various stakeholders. An enhanced understanding of the drivers of these behaviours ought to improve an organization's ability to appropriately manage relationships with stakeholders, thereby improving firm performance. This paper provides a detailed look at the concept of a relationship, from the perspective of the stakeholder, by focusing on the perceived psychological bonds that drive a stakeholder to decide whether to continue a relationship with the firm and, if the relationship does continue, how much pro‐relationship behaviour to exert. Our analysis works out how the strength of the perceived psychological bond is measured and establishes the conditions under which bonds will be broken. We also develop conditions that either promote or quash stakeholders’ pro‐relationship behaviour.
Ultrasound of the salivary glands is a strong predictor of labial gland biopsy histopathology in patients with sicca symptoms
Authors: Astorri Elisa , Sutcliffe Nurhan , Richards Polly S. , Suchak Krishna , Pitzalis Costantino , Bombardieri Michele , Tappuni Anwar R.
Published: December 2015

Background

The international classification criteria for Sjögren's syndrome necessitate the presence of either extractable nuclear antibody or a characteristic focal inflammatory infiltrate in a minor salivary gland. Thus, patients who are extractable nuclear antibody‐negative will need to have a labial salivary gland biopsy, which is an invasive procedure associated with morbidity. The aim of this study was to evaluate the viability of ultrasound imaging of the major salivary glands as a predictor of the histology to explore whether ultrasound can help in stratifying Sjögren's patients and reduce the need for biopsy.

Methods

The records of 85 patients suspected of having Sjögren's syndrome and who have had biopsy and ultrasound were analysed retrospectively. The histology and the ultrasound were reported by experts independently. The reporting was impartial as the examiners were blinded to the results of the other investigations and to the diagnosis.

Results

Out of the 85 patients, 34 had positive ultrasound, 29 of whom also had positive histology. Fifty‐one patients had negative ultrasound, of whom 49 were also negative for histological features of Sjögren's syndrome. The results show that the ultrasound had a positive predictive value of 85% and a striking negative predicative value of 96% of the histology results. The overall concordance between the ultrasound and the histology was 91% (Kappa = 0.826).

Conclusions

Our study shows that potentially the ultrasound has a role in stratifying patients who are extractable nuclear antibody‐negative and can help to prioritize the biopsy for those who have sonographic evidence of SS.
Evaluation of prolidase activity and oxidative stress in patients with oral lichen planus and oral lichenoid contact reactions
Authors: Batu Şule , Ofluoğlu Duygu , Ergun Sertan , Warnakulasuriya Saman , Uslu Ezel , Güven Yegane , Tanyeri Hakkı
Published: December 2015

Objective

The aim of this study was to evaluate prolidase activity and oxidative stress in patients with oral lichen planus (OLP) and oral lichenoid contact reactions (OLCR) using serum and salivary samples and to compare these biomarkers with each other as well as with a group of healthy subjects in order to be able to opine their role in the estimation of OLP and OLCR.

Patients and Methods

Eighteen recently diagnosed patients with OLP, 32 patients with OLCR and 18 healthy controls with matched periodontal status were recruited to the study. Prolidase activity, lipid peroxidation product malondialdehyde (MDA), sialic acid (SA), and advanced oxidation protein products (AOPPs) levels in both serum and saliva were determined. Additionally, salivary flow rate and its buffering capacity were estimated. Statistical analyses were performed using the chi‐square test, t‐test, Mann–Whitney U‐test, and Spearman's rho correlation coefficient.

Results

No statistically significant differences were observed between the study groups and the control group regarding to the basic characteristics and the periodontal status (P > 0.05). There were no statistically significant differences between OLP and OLCR groups regarding to the distribution of lesions' type, severity, and location (P > 0.05). No significant differences were found between the two study groups with regard to Prolidase activity, MDA, SA, and AOPPs (P ˃ 0.05), whereas statistically significant differences were found between the two study groups and the control group with regard to all evaluated parameters except of serum prolidase (P ˂ 0.01). Moderate correlation was found between salivary MDA and the OLP/OLCR lesion severity, whereas a weak correlation was observed between serum SA and the OLP/OLCR lesion severity (P ˂ 0.05).

Conclusions

The findings of this study suggest an increased prolidase activity and oxidative stress and imbalance in the antioxidant defense system in biological fluids of patients with OLP and OLCR when compared with the healthy subjects. Both OLP and OLCR patients revealed almost similar prolidase activity and oxidative stress levels although these two conditions have different etiopathogenesis.
Genomic aberrations of MDM2, MDM4, FGFR1 and FGFR3 are associated with poor outcome in patients with salivary gland cancer
Authors: Ach Tobias , Schwarz‐Furlan Stephan , Ach Stephanie , Agaimy Abbas , Gerken Michael , Rohrmeier Christian , Zenk Johannes , Iro Heinrich , Brockhoff Gero , Ettl Tobias
Published: December 2015

Fibroblast growth factor receptor 1 and 3 (FGFR1, FGFR3) impact on tissue homoeostasis, embryonic development and carcinogenesis. Murine double minute protein 4 (MDM4) and mouse double minute 2 homologue (MDM2) are regulators of p53‐protein and may be the origin of an apoptosis overpowering cascade.

A collective of 266 carcinomas of salivary glands were investigated for MDM2, MDM4, FGFR1 and FGFR3 aberrations by fluorescence in situ hybridization (FISH). The results were matched with clinicopathological parameters and with expression of PTEN and p53.

MDM2 gene amplification (n = 9) and chromosomal aberrations (trisomy, n = 47; high polysomy, n = 7) are linked to high‐grade malignancy (P < 0.001), lymph node metastasis (P = 0.001), advanced tumour size (P = 0.013) and stage (P < 0.001), gender (P = 0.002) and age (P = 0.001). MDM4 gene amplification (n = 19) and chromosomal aberrations (trisomy, n = 34; high polysomy, n = 31) are correlated to high‐grade malignancy (P < 0.001), lymph node metastasis (P = 0.008), advanced tumour size (P = 0.039), stage (P = 0.004) and loss of PTEN (P < 0.001). Only, high‐grade malignancy (P < 0.001), lymph node metastasis (P = 0.036) and advanced tumour stage (P = 0.025) are associated with FGFR3 amplification (n = 1) or chromosomal aberrations (low polysomy, n = 61; high polysomy, n = 55) but not with MDM4 alterations.

FGFR1 amplifications (n = 5) and chromosomal aberrations (trisomy, n = 38; high polysomy, n = 30) are associated with high‐grade malignancy (P < 0.001), advanced tumour size (P = 0.026) and stage (P = 0.004), gender (P = 0.016) and age (P = 0.023).

Aberrations of MDM2, MDM4, FGFR1 and FGFR3 correlate with aggressive tumour growth and nodal metastasis. MDM2 (P < 0.001), MDM4 (P = 0.005) and FGFR3 (P = 0.006) alterations are associated with worse overall survival of patients with salivary gland cancer.
INTEGRATION OF BIODEGRADATION AND MIGRATION OF HYDROCARBONS IN A 2D PETROLEUM SYSTEMS MODEL: APPLICATION TO THE POTIGUAR BASIN, NE BRAZIL
Authors: Ducros M. , Carpentier B. , Wolf S. , Cacas M‐C.
Published: December 2015

Biodegradation is probably the most important in‐reservoir alteration process and is responsible for the majority of the known heavy oil accumulations. In the present study, biodegradation processes were integrated within a forward basin and petroleum systems model applied to the Potiguar Basin, NE Brazil. This basin was chosen because it has been studied in detail and data from previous investigations are publically available. In order to account for processes occurring during the biodegradation of hydrocarbons, the evolution of fluid properties was simulated through time. In the model, a new approach was developed in order to determine the intensity of microbial activity and the evolution of the oil‐water contact, the zone within which biodegradation is confined. The numerical results obtained by applying the forward simulator to a 2D model of the Potiguar Basin fit the observed data concerning the composition and quality of the oil in a series of oilfields. These accumulations are located along the NE‐SW oriented “Carnaubais trend” and show progressive biodegradation along the migration path from the offshore kitchen area. Our results show that the biodegradation trend observed along the cross‐section can in general be explained by the fact that reservoirs are successively filled as a result of spilling from previous reservoirs, with continuous hydrocarbon degradation occurring within the reservoirs. This charge history resulted in differences in the composition of oils transported from upstream to downstream reservoirs, and in the evolution over time of the ratio between biodegradation and reservoir filling rates. Thus, in addition to residence time in the biodegradation temperature window, the rate of reservoir infill, the rate of oil degradation and the migration pathways are key factors controlling biodegradation. This study also demonstrates how the approach developed within our petroleum system simulator, which integrates both migration and biodegradation, may improve the assessment of oil quantity, quality and migration timing.
GEOCHEMICAL CHARACTERIZATION OF THE PERMIAN–TRIASSIC TRANSITION AT OUTCROP, CENTRAL SAUDI ARABIA
Authors: Eltom H. A. , Abdullatif O. M. , Babalola L. O. , Bashari M. A. , Yassin M. , Osman M. S. , Abdulraziq A. M.
Published: December 2015

This study presents the results of chemostratigraphic analyses and spectral gamma‐ray logging integrated with sedimentological data across the Permian‐Triassic boundary at a measured outcrop section in central Saudi Arabia. The studied section encompasses the uppermost part of the Midhnab Member and the Lower and Upper Khartam Members of the Khuff Formation. Lithofacies were interpreted to have been deposited in subtidal, tidal to supratidal, lacustrine and meandering fluvial / flood plain, marginal marine and lagoonal depositional environments. Integration of bulk geochemical and carbon isotope (δ13C) data allowed the identification of a stratigraphic interval with a negative shift in δ13C ratio values, which was interpreted to correspond to the end‐Permian mass extinction event. The end of this “first negative shift in δ13C values” is taken to mark the Permian‐Triassic boundary. Above this boundary and just below an interval containing scattered thrombolites, a second negative shift in δ13C ratios was observed, and corresponds to an interval with long‐term uranium depletion as indicated by the bulk sediment geochemical and spectral gamma‐ray uranium data.

The Permian‐Triassic boundary (PTrB) was placed at the transition between marginal‐marine and subtidal deposits. This stratigraphic position corresponds to the end of the “first negative δ13C shift” and the point of greatest uranium depletion. Although previous studies on outcrops of the Khuff Formation in Saudi Arabia identified a major sequence boundary between the Lower and Upper Khartam Members and interpreted it as the P TrB, no evidence is presented in this study for exposure and dissolution at this surface. Accordingly, the Permian‐Triassic transition is placed in the transgressive portion of the Upper Khartam Member, while the sequence boundary below is interpreted to correspond to the end‐Permian extinction.

Correlation of Khuff time‐equivalent units in the Arabian Plate is challenging, and this study will contribute to an improved understanding of this important stratigraphic unit, which contains prolific non‐associated gas reservoirs. The identification of the Permian‐Triassic boundary in central Saudi Arabia will help in the construction of a sequence‐stratigraphic scheme for the Khuff, and with the correlation of lithofacies within this heterogeneous reservoir unit.