bluuebunny/crossref_metadata_2025 huggingface dataset:
Manually controlled targeted prostate biopsy with real‐time fusion imaging of multiparametric magnetic resonance imaging and transrectal ultrasound: An early experience
Authors: Shoji Sunao , Hiraiwa Shinichiro , Endo Jun , Hashida Kazunobu , Tomonaga Tetsuro , Nakano Mayura , Sugiyama Tomoko , Tajiri Takuma , Terachi Toshiro , Uchida Toyoaki
Published: October 2014

Objectives

To report our early experience with manually controlled targeted biopsy with real‐time multiparametric magnetic resonance imaging and transrectal ultrasound fusion images for the diagnosis of prostate cancer.

Methods

A total of 20 consecutive patients suspicious of prostate cancer at the multiparametric magnetic resonance imaging scan were recruited prospectively. Targeted biopsies were carried out for each cancer‐suspicious lesion, and 12 systematic biopsies using the BioJet system. Pathological findings of targeted and systematic biopsies were analyzed.

Results

The median age of the patients was 70 years (range 52–83 years). The median preoperative prostate‐specific antigen value was 7.4 ng/mL (range 3.54–19.9 ng/mL). Median preoperative prostate volume was 38 mL (range 24–68 mL). The number of cancer‐detected cases was 14 (70%). The median Gleason score was 6.5 (range 6–8). Cancer‐detected rates of the systematic and targeted biopsy cores were 6.7 and 31.8%, respectively (P < 0.0001). In six patients who underwent radical prostatectomy, the geographic locations and pathological grades of clinically significant cancers and index lesions corresponded to the pathological results of the targeted biopsies.

Conclusion

Prostate cancers detected by targeted biopsies with manually controlled targeted biopsy using real‐time multiparametric magnetic resonance imaging and transrectal ultrasound fusion imaging have significantly higher grades and longer length compared with those detected by systematic biopsies. Further studies and comparison with the pathological findings of whole‐gland specimens have the potential to determine the role of this biopsy methodology in patients selected for focal therapy and those under active surveillance.
Eighteen‐Month‐Olds, but not 14‐Month‐Olds, Use Social Context to Bind Action Sequences
Authors: Fawcett Christine , Gredebäck Gustaf
Published: October 2014

We demonstrate that 18‐month‐olds, but not 14‐month‐olds, can anticipate others' actions based on an interpretation of shared goals that bind together individual actions into a collaborative sequence. After viewing a sequence of actions performed by two people who socially interact, 18‐month‐olds bound together the socially engaged actors' actions such that they later expected the actors to share the same final goal. Eighteen‐month‐olds who saw nonsocially engaged actors did not have this expectation and neither did 14‐month‐olds when viewing either socially or nonsocially engaged actors. The results are discussed in light of the possibility that experience in collaborations could be necessary for understanding collaboration from a third‐person perspective.
Fabrication of a Novel Calcium Carbonate Composite Ceramic as Bone Substitute
Authors: He Fupo , Yang Fanwen , Zhu Jixiang , Peng Ye , Tian Xiumei , Chen Xiaoming
Published: October 2014

The coral, whose main composition is aragonite‐type calcium carbonate, has been widely used as bone substitute in clinic. However, the study on calcium carbonate bioceramic has not been largely reported due to difficulty in sintering calcium carbonate which is liable to evidently decompose at low temperature. In this study, a novel calcium carbonate composite ceramic was fabricated by sintering fast at a low temperature. A degradable, biocompatible phosphate‐based glass (PG) which grew liquid at a low temperature was added as sintering agent in the sintering process. The sintering schedule was explored by thermal analysis. The phase composition, microstructure, compressive strength, and biocompatibility of calcium carbonate composite ceramics were evaluated. The results revealed that the optimum holding time at the sintering temperature was 20 min. The obtained calcium carbonate composite ceramics did not produce calcium oxide but new compounds according to phase analysis. The compressive strength of calcium carbonate composite ceramics correspondingly increased with growing addition of PG ranging from 10 to 50 wt%. The cell proliferation on the calcium carbonate composite ceramic was not compromised but augmented compared to the neat calcium carbonate ceramic without adding PG as sintering agent. The novel calcium carbonate composite ceramic is a promising bone substitute for bone defects.
Effects of CuO Addition on Electrical Properties of 0.6BiFeO3–0.4(Bi0.5K0.5)TiO3 Lead‐Free Piezoelectric Ceramics
Authors: Hagiwara Manabu , Fujihara Shinobu
Published: October 2014

0.6BiFeO3–0.4(Bi0.5K0.5)TiO3 (0.6BF–0.4BKT) ceramic samples with 0.0–4.0 mol% CuO were prepared by the solid‐state reaction. The CuO addition aided the densification of the samples and slightly increased the lattice constant. The relaxor‐like defuse dielectric peak of 0.6BF–0.4BKT became sharper with increasing the CuO content. Polarization–electric field curve of the undoped 0.6BF–0.4BKT was a pinched loop in the as‐sintered state, while that was a square hysteresis with a large remanent polarization of 48 μC/cm2 after the thermal quenching, demonstrating a strong domain wall pinning due to defect dipoles. We found that the CuO addition up to 2.0 mol% facilitates the polarization switching in the as‐sintered samples to increase the remanent polarization and the piezoelectric d33 coefficient. The results of the structural and electrical investigations suggested that the copper ion acts as a donor in 0.6BF–0.4BKT by compensating the potassium vacancy created by the evaporation of K2O during the calcination and sintering processes.
Dielectric Relaxation in Zr‐Doped SrTiO3 Ceramics Sintered in N2 with Giant Permittivity and Low Dielectric Loss
Authors: Wang Zhijian , Cao Minghe , Zhang Qi , Hao Hua , Yao Zhonghua , Wang Zhihao , Song Zhe , Zhang Yiming , Hu Wei , Liu Hanxing
Published: October 2014

SrTiZrxO3 (x = 0, 0.002, 0.006, 0.01, and 0.014) ceramics with a weak temperature‐dependent giant permittivity (>104) and a very low dielectric loss (<0.01) were fabricated using the conventional solid‐state reaction method by sintering them in N2 at 1500°C. With increasing Zr content, the permittivity decreased from approximately 48 000 to 18 000 and the dielectric loss decreased from approximately 0.005 to 0.003. According to the XRD, XPS, and ac conductivity analysis, the dielectric properties of pure SrTiO3 ceramics sintered in N2 were due to the existence of the giant defect dipoles generated by the fully ionized oxygen vacancies and Ti3+ ions, while the dielectric properties of SrTiZrxO3 (x > 0) ceramics were also influenced by the defect dipoles (). The giant permittivity and low dielectric loss phenomenon could be explained by giant defect dipoles related to oxygen vacancies.
The Influence of Cation Additives on Grain‐Boundary Mobility in Yttrium Aluminum Garnet (YAG)
Authors: Zamir Shlomit
Published: October 2014

Pure yttrium aluminum garnet (YAG) nano‐powders, doped with 1.4 at.% of La2O3, ZrO2, MgO, Nb2O5, and SiO2, were vacuum sintered to full density and subjected to grain growth at 1700°C, for up to 15 h. The YAG intrinsic grain‐boundary (GB) mobility, determined from the pure fully dense YAG specimens, was 2.9 × 10−16 [m3·N−1·s−1]. All dopants, except for La2O3, increased the GB mobility compared to pure YAG (La2O3 didn't cause any significant change in YAG's GB mobility). All GBs were found to be free of secondary phases or intergranular films. These findings differ from numerous publications where dopants were found to either inhibit grain growth by solute drag, or to enhance grain growth due to liquid phase sintering. It was found that the GB mobility systematically increased with the decrease in the dopant cation radius. Moreover, it seems that vacancy population plays an important role in determining the GB mobility of YAG.
Imaging for metastatic disease in patients with newly diagnosed breast cancer: are doctor's perceptions in keeping with the guidelines?
Authors: Simos Demetrios , Hutton Brian , Graham Ian D. , Arnaout Angel , Caudrelier Jean‐Michel , Clemons Mark
Published: October 2014

Rationale, aims and objectives

Despite multiple guidelines advocating against routine radiological evaluation for metastases in women with early stage breast cancer, imaging is still frequently overused. The objective of this study was to assess doctor's views on imaging guidelines, and an attempt to establish why personal and local clinical practice patterns regarding imaging may differ from current guidelines.

Methods

Canadian doctors who treat breast cancer were invited by email to complete an online survey developed by members of the research team.

Results

Responses were received from 173 physicians (26% response rate). Most (82%) indicated awareness of at least one published imaging guideline. Sixty per cent indicated that they had read the recommendations of the 2012 American Society of Clinical Oncology ‘Top 5’ list for choosing wisely in oncology imaging and, of those, 81% agreed with it. However, most indicated that this recommendation has not influenced them to order less imaging. Over 95% of doctors identified suspicious history, physical examination findings and inflammatory breast cancer as important factors for performing imaging. The majority did not feel that patient demand, fear of litigation or ease of access to imaging influenced their ordering for imaging.

Conclusions

The majority of breast cancer doctors are aware of and generally agree that guidelines pertaining to staging imaging for early breast cancer are reflective of evidence. Despite this, adherence is variable and factors such as local practice patterns and disease biology may play a role. Alternative strategies, beyond simply publishing recommendations, are therefore required if there is to be a sustained change in doctor behaviour.
Uniform presentation of process evaluation results facilitates the evaluation of complex interventions: development of a graph
Authors: Bakker Franka C. , Persoon Anke , Schoon Yvonne , Olde Rikkert Marcel G. M.
Published: October 2014

Rationale, aims and objectives

Process evaluation is a highly essential element for the increasing number of studies regarding multi‐component interventions. Yet, researchers are challenged to collect and present appropriate process outcomes in such way that it is easy and valuable to be used by other researchers and policy makers in interpreting and comparing intervention effects because of the absence of standards for conducting and publishing process evaluation. This article describes the development of a method to concisely summarize the results of process evaluations of complex multi‐component interventions.

Methods

Development of a graph with the aim to facilitate the reporting of process evaluation's results, based on a narrative review of the literature for process measures used in complex interventions for elderly people.

Results

Seventeen articles of process evaluations alongside effect studies of complex interventions were reviewed. From these articles, it was found that process evaluations should address whether the intervention (1) was implemented successfully; (2) was evaluated properly; and (3) can be continued in the future. A flow chart based on the essential components of an adequate process evaluation was developed. A simplified but highly informative figure reporting a summary of the results of the process evaluation is proposed and its use is explained by administering the figure to two studies including a process and effect evaluation of a complex intervention.

Conclusion

A graphical approach – which includes the core results of process evaluation and can be used directly in reporting effectiveness studies – will help researchers and policy makers to interpret and compare effects of complex multi‐component interventions.
Amelioration of trinitrobenzene sulfonic acid‐induced colitis in mice by liquiritigenin
Authors: Min Joon Ki , Lee Chi Hoon , Jang Se‐Eun , Park Jae‐Woo , Lim Sung‐Jig , Kim Dong‐Hyun , Bae Hyunsu , Kim Hyo‐Jong , Cha Jae Myung
Published: October 2014

Background and Aim

The anti‐inflammatory effects of liquiritigenin, a major flavonoid isolated from Glycyrrhizae uralensis, have been reported in many inflammation models. However, its protective effects have not been reported in a colitis model. This study investigated the anti‐inflammatory effect and mechanism of liquiritigenin for trinitrobenzene sulfonic acid (TNBS)‐induced colitis in mice.

Methods

Male mice imprinting control regions (ICR) were randomly divided into five groups: normal, TNBS‐induced colitis, colitis treated with liquiritigenin at low dose (10 mg/kg) and high dose (20 mg/kg), or mesalazine (10 mg/kg). TNBS colitis induction was performed except for in the normal group, and they were treated with liquiritigenin or mesalazine except control group. The treatment effect was measured after three days treatment, by body weight, colon length, macroscopic score, histological score, levels of cytokines (tumor necrosis factor‐α, interleukin [IL]‐1β, IL‐6, and IL‐10) in colon tissue as well as the nuclear factor kappa‐light‐chain‐enhancer pathway of activated B cells (NF‐κB) activation.

Results

Mice treated with high‐dose liquiritigenin showed significant body weight gain, inhibition of colon shortening, protective effect on histological damages, and myeloperoxidase activity of colon tissue compared with the control group. Furthermore, mice treated with high‐dose liquiritigenin experienced significantly suppressed tumor necrosis factor‐α, IL‐1β, and IL‐6 as well as enhanced IL‐10 expression (all P < 0.05). High‐dose liquiritigenin treatment group showed significant decreases in TNBS‐induced phosphorylation of IKKβ, p65, and IκB‐α.

Conclusion

Liquiritigenin may ameliorate TNBS‐induced colitis in mice by suppressing expression of pro‐inflammatory cytokines through NF‐κB pathway.
Why Do Firms Enter a New Product Market? A Two‐Dimensional Framework for Market Entry Motivation and Behavior
Authors: Kim Namwoon , Min Sungwook , Chaiy Seoil
Published: October 2014

What are the energetic forces that induce established firms to enter new product markets? While most previous research has explained the economic profits expected from a new product market as firms' distinctive motivation for market entry, some recent studies also emphasize interfirm competition and benchmarking activities as another important factor that motivates firms' new market entry. To explain the established firms' diverse new product market entry behaviors, this study presents a two‐dimensional scheme of entry motivation in terms of the degrees oftarget market profit focusandcompetitor focus. The first dimension captures the economic motivation of firms' new market entry that ranges from focusing on the direct expected profits from the target market to considering more strategic/indirect benefit incentives. The second dimension captures the degree of firms' external motivation for entry affected by competitors that ranges from independent entry decisions to fully competitor‐oriented entry decisions.

Using multiple‐industry survey data, the current study empirically verifies that these two entry motivation dimensions explain a great portion of actual firms' new product market entry behaviors and that they are independent of each other. Subsequently, this study validates that firms' operational size and their environmental factors like perceived technological uncertainty and competitive intensity upon new market entry affect the degrees of the two dimensions of firms' new product market entry motivation. More specifically, large firms less emphasize target‐market profits than small firms, and when perceived technological uncertainty is high, potential market entrants become less target market profit focused but more competitor focused. Under a highly competitive new market condition, firms focus on both target‐market profits and competitors.

Based on the analysis of new market entry motivation dimensions, the current study proposes a new typology of established firms' market entry behaviors. The suggested typology represents the four different types of new product market entrants and examines specific characteristics and entry strategies for each type of potential entrants. This entry‐motivation framework should provide a deeper understanding of the backgrounds of entry behaviors and assist firms in developing appropriate entry strategies and in advantageously responding to rival firms' actions with regard to entry.
Who Knows What inNPDTeams: Communication Context, Mode, and Task Contingencies
Authors: Tang Fangcheng , Mu Jifeng , Thomas Ellen
Published: October 2014

The use of cross‐functional teams in new product development (NPD) benefits firms in many ways. One benefit is the diverse knowledge team members bring to the project, but that benefit can only be appreciated if team members fully utilize and integrate the differentiated expertise of members. As reliance on cross‐functionalNPDteams grows, however, firms struggle to exploit the full potential of functionally diverse groups, the biggest obstacle being integrating team members' varied knowledge, expertise, and abilities. Therefore, understanding how information is integrated and used is a primary concern for both practitioners and researchers. Databases and other forms of hard data are methods team members can use to effectively share and integrate knowledge; another method based on social cognition is transactive memory systems (TMS).TMSindicates who will learn what and from whom. The notion is that knowledge is distributed among people in the group, and to make effective use of it, individuals need to know who knows what and who knows who knows what.

Grounded in the knowledge‐based theory of the firm, this study investigates the influence of different communication contexts and modes onTMSunder differentNPDtask environments (i.e., exploitation and exploration) in cross‐functionalNPDteams. A theoretical model is developed and empirically tested using data collected from 272 ongoingNPDteams of 128Chinese high‐tech companies. Findings suggest that when teams face tasks defined by exploration, informal communication and face‐to‐face communication are positively associated withTMS, whereas for tasks defined by exploitation, formal communication and computer‐mediated communication are positively related withTMS. Additionally, this study found thatTMSis positively related toNPDperformance both in terms of project performance and in terms of market performance. Based on these findings, theoretical and managerial implications are drawn regarding resource deployment that encourages the development of effectiveTMSleading to successfulNPDprojects.
Joining Forces or Going It Alone? On the Interplay among External Collaboration Partner Types, Interfirm Governance Modes, and Internal R&D
Authors: Gesing Judith , Antons David , Piening Erk P. , Rese Mario , Salge Torsten Oliver
Published: October 2014

This paper adds to the emerging literature stream advocating a contingency view on open innovation. Drawing on the relational view of the firm, this study sheds light on the complex interplay among collaboration partner types (market‐ and science‐focused innovation partners), governance modes (informal, self‐enforcing and formal, contractual collaboration governance), and internal research and development(R&D). More specifically, it is proposed that the use of governance modes tailored to both the characteristics of each innovation partner type and the specific innovation objectives pursued by the focal firm (incremental and radical new product development) can increase the payoff from innovation collaboration. Moreover, appropriate collaboration governance is expected to reduce the focal firm's vulnerability to possible negative side effects often assumed to be associated with the simultaneous pursuit of external collaboration and internal R&D, among which most notably the not‐invented‐here (NIH) syndrome. Cross‐industry evidence from 2502 German firms underlines the critical role of collaboration governance—a contingency factor that is at the heart of the relational view, yet has remained surprisingly absent from the open innovation debate so far.
In the Eye of the Beholder? The Effect of Product Appearance on Shareholder Value
Authors: Bornemann Torsten , Schöler Lisa , Homburg Christian
Published: October 2014

In times of convergence with regard to product functionality and performance, the appearance of a product constitutes an important source of competitive advantage. Astonishingly, only a few studies have empirically examined the relationship between design‐related aspects and firm value. Moreover, existing studies predominantly use accounting‐based and/or subjective performance measures. Against this background, the present work assesses the contribution of the three most important product design dimensions (i.e., aesthetic, ergonomic, and symbolic value) to the creation of firm value in the context of the automotive and consumer electronics industry. To do so, we examine stock market reactions to the unveiling of a new product's appearance to the public using event study methodology. In particular, we combine perceptual data at the consumer level with stock market data to examine how target consumers' perceptions of the aforementioned design dimensions are related to abnormal returns following the unveiling of a new product. Results reveal that ergonomic value is positively related to abnormal returns, while aesthetic value only exerts a significant positive effect on abnormal returns if the product also exhibits a certain degree of functional product advantage. Finally, symbolic value exerts a negative influence on stock market reactions. These findings have important implications for the allocation of design‐related investments to aesthetic, ergonomic, and symbolic design features.
Balancing the Two Knowledge Dimensions in Innovation Efforts: An Empirical Examination among Pharmaceutical Firms
Authors: Xu Shichun
Published: October 2014

This study investigates the relationships between the two knowledge dimensions (knowledge breadth and knowledge depth) and two types of innovations (radical innovation and incremental innovation). While existing literature identifies knowledge in general as an important driver of innovation, the exact relationships between knowledge breadth/depth and incremental/radical innovations are not clear. Drawing from the knowledge‐based view, this study advances the understanding of the relationships between knowledge dimensions and types of innovations by hypothesizing a nonlinear relationship between knowledge breadth and radical innovation as well as a nonlinear relationship between knowledge depth and incremental innovation. Furthermore, the moderating effects of the interaction between knowledge breadth and knowledge depth on the above‐mentioned relationships are also examined. Due to the different natures of the two types of innovations, it is hypothesized that knowledge depth positively moderates the relationship between knowledge breadth and radical innovation while knowledge breadth negatively moderates the relationship between knowledge depth and incremental innovation. To empirically test the hypotheses, secondary data from multiple sources were collected on 64 pharmaceutical firms over 15 years. Due to the panel data structure and observed dispersion issues in the dependent variables, negative binomial random effects models were formulated to test the hypotheses. The statistical results largely support the proposed hypotheses. The results demonstrate that while knowledge breadth positively contributes to the development of radical innovations and knowledge depth positively contributes to the development of incremental innovations, both relationships are subject to diminishing returns. Furthermore, while the finding did support the negative moderating effect of the knowledge breadth on incremental innovation, the positive moderating effect of knowledge depth on radical innovation is not supported. While the effect is not explicitly hypothesized, knowledge breadth seems to have a direct impact on incremental innovation as well.
Integration of Finance with Marketing and R&D in New Product Development: The Role of Project Stage
Authors: Hempelmann Franziska , Engelen Andreas
Published: October 2014

While the interfaces of marketing, research and development (R&D), and manufacturing in product development have been extensively studied, no large‐scale empirical study has focused on finance's role in the product development team. The present research investigates the role of finance in cross‐functional product development teams, thereby extending existing research on cross‐functional integration in product development. A set of hypotheses is tested with a survey of 389 project team leaders and top management team members from companies in the United States, Australia, New Zealand, Germany, and Austria. The findings suggest that the integration of finance in cross‐functional teams positively impacts project performance and that the importance of the finance interface depends on the project development stage and the innovativeness of the product developed. The results indicate that the R&D–finance interface is most critical at the early stage of a project, while the marketing–finance interface is most important at the late stage, and that the integration between R&D and finance is especially useful in the development of less innovative products.
When Research Meets Development: Antecedents and Implications of Transfer Speed
Authors: Du Jingshu , Leten Bart , Vanhaverbeke Wim , Lopez‐Vega Henry
Published: October 2014

This paper focuses on the organization of new product development in large,R&D‐intensive firms. In these firms, research and development activities are often separated. Research is conducted in dedicated research projects at specialized research labs. Once research results are achieved by research projects, they are transferred to business units for further development and commercialization. We investigate the speed whereby research projects transfer their first research results to business units (hereafter:transfer speed). In particular, we analyze the antecedents and performance implications of transfer speed. Based on data of 503 research projects from aEuropeanR&Dintensive manufacturing firm, our results suggest that a fast transfer speed (as measured by the time it takes for a research project to develop and transfer its first research result to business units) is associated with a better research performance (as measured by the total number of transfers the research project generates). Moreover, we find that different types of externalR&Dpartners—science‐based and market‐based partners—play distinct roles in speeding up project first research transfers. While market‐based partnerships (i.e., customers and suppliers) generally contribute to a faster transfer of first research results, science‐based partnerships (i.e., universities and research institutions) only speed up first research transfers of technologically very complex projects. Our results also show that early patent filings by research projects accelerate first research transfers.
Bootstrap Joint Prediction Regions
Authors: Wolf Michael , Wunderli Dan
Published: October 2014

Many statistical applications require the forecast of a random variable of interest over several periods into the future. The sequence of individual forecasts, one period at a time, is called a path forecast, where the term path refers to the sequence of individual future realizations of the random variable. The problem of constructing a corresponding joint prediction region has been rather neglected in the literature so far: such a region is supposed to contain the entire future path with a prespecified probability. We develop bootstrap methods to construct joint prediction regions. The resulting regions are proven to be asymptotically consistent under a mild high‐level assumption. We compare the finite‐sample performance of our joint prediction regions with some previous proposals via Monte Carlo simulations. An empirical application to a real data set is also provided.
Big spleens and hypersplenism: fix it or forget it?
Authors: Boyer Thomas D. , Habib Shahid
Published: October 2014

Hypersplenism is a common manifestation of portal hypertension in the cirrhotic. More than half of cirrhotics will have low platelet counts, but neutropenia is much less common. Despite being common in the cirrhotic population, the presence of hypersplenism is of little clinical consequence. The presence of hypersplenism suggests more advanced liver disease and an increase in risk of complications, but there is no data showing that correcting the hypersplenism improves patient survival. In most series, the most common indications for treating the hypersplenism is to increase platelet and white blood cell counts to allow for use of drugs that suppress the bone marrow such as interferon alpha and chemotherapeutic agents. There are several approaches used to treat hypersplenism. Portosystemic shunts are of questionable benefit. Splenectomy, either open or laparoscopically, is the most effective but is associated with a significant risk of portal vein thrombosis. Partial splenic artery embolization and radiofrequency ablation are effective methods for treating hypersplenism, but counts tend to fall back to baseline long‐term. Pharmacological agents are also effective in increasing platelet counts. Development of direct acting antivirals against hepatitis C will eliminate the most common indication for treatment. We lack controlled trials designed to determine if treating the hypersplenism has benefits other than raising the platelet and white blood cell counts. In the absence of such studies, hypersplenism in most patients should be considered a laboratory abnormality and not treated, in other words forget it.
Gene flow between nascent species: geographic, genotypic and phenotypic differentiation within and between Aquilegia formosa and A. pubescens
Authors: Noutsos C. , Borevitz J. O. , Hodges S. A.
Published: October 2014

Speciation can be described as a reduction, and the eventual cessation, in the ability to interbreed. Thus, determining how gene flow differs within and between nascent species can illuminate the relative stage the taxa have attained in the speciation process. Aquilegia formosa and A. pubescens are fully intercompatible, yet occur in different habitats and have flowers specialized for pollination by hummingbirds and hawkmoths, respectively. Using 79 SNP loci, we genotyped nearly 1000 individuals from populations of both species in close proximity to each other and from putative hybrid zones. The species shared all but one SNP polymorphism, and on average, allele frequencies differed by only 0.14. However, the species were clearly differentiated using Structure, and admixed individuals were primarily identified at putative hybrid zones. PopGraph identified a highly integrated network among all populations, but populations of each species and hybrid zones occupied distinct regions in the network. Using either conditional graph distance (cGD) or Fst/(1‐Fst), we found significant isolation by distance (IBD) among populations. Within species, IBD was strong, indicating high historic gene flow. IBD extended approximately 100 km in A. pubescens and 30 km in A. formosa. However, IBD between the species was very weak and extended only a few km beyond hybrid zones, suggesting little recent gene flow. The extensive sharing of SNP polymorphisms between these species suggests that they are very early in the speciation process while the low signal of IBD suggests that they have largely ceased gene exchange.
Identification of clinical target areas in the brainstem of prion‐infected mice
Authors: Mirabile Ilaria , Jat Parmjit S. , Brandner Sebastian , Collinge John
Published: October 2014

Aims

While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas.

Method

We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset).

Results

We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre‐Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem.

Conclusions

Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre‐Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic Creutzfeldt–Jakob disease, we suggest that these nuclei represent key clinical target areas in prion diseases.
When do grazers accelerate or decelerate soil carbon and nitrogen cycling in tundra? A test of theory on grazing effects in fertile and infertile habitats
Authors: Stark Sari , Männistö Minna K. , Eskelinen Anu
Published: October 2014

It is generally predicted that grazers enhance soil microbial activity and nutrient availability and promote soil bacteria in fertile ecosystems, but retard microbial activity and nutrient availability and promote soil fungi in infertile ecosystems. We tested these predictions in tundra by comparing grazing effects between fertile and infertile habitats and with/without nutrient manipulation by fertilization. Grazing decreased soil N content in fertile and in fertilized plots in infertile habitats while increased it in infertile tundra habitats, which directly opposed our prediction. We conclude that this unpredicted outcome probably resulted from nutrient transport between habitats. Also contrasting with our hypothesis, grazing increased fungal rather than bacterial abundance in fertilized plots at both habitats. In support with predictions, grazing increased microbial activity for soil C decomposition in fertile but decreased it in infertile habitats. The effect of grazing on soil C decomposition followed same patterns as grazer‐induced changes in the activity of β‐glucosidase, which is an extracellular enzyme synthesized by soil microorganisms for degrading soil cellulose. We suggest that the theoretical framework on grazer–soil interactions should incorporate microbial potential for extracellular enzyme production (‘microscale’ grazer effects) and nutrient translocation by grazers among habitats (‘macroscale’ grazer effects) as important mechanisms by which grazers influence soil processes and nutrient availability for plants at contrasting levels of habitat fertility.
Optimizing Paced Ventricular Function in Patients with and without Repaired Congenital Heart Disease by Contractility‐Guided Lead Implant
Authors: KARPAWICH PETER P. , SINGH HARINDER , ZELIN KATHLEEN
Published: October 2014

Background

This study evaluates the concept of optimizing ventricular pacing in regard to functional cardiac response. Lead implant based on physiologic variables of contractility at various sites was performed in patients with and without congenital heart disease (CHD). Since right ventricular apical pacing may adversely alter contractility and myocellular function, septal and outflow tract pacing have been advocated. However, there are few studies in the young and essentially none in those with CHD.

Methods

A total of 113 consecutive patients with and without repaired CHD, aged two to 51 (median 16), some with preexisting epicardial pacemakers, underwent transvenous pacemaker implant using standard sensing/pacing indices plus measurements of pressures, QRS, and contractility responses at each of five predefined potential ventricular implant sites: apex, inflow‐, low‐, mid‐, and infundibular/outflow‐septal with each patient serving as his/her own control. Implant was at the site of best contractility with active‐fixation, low‐threshold steroid‐eluting leads.

Results

Measured contractility indices varied up to 31% (mean 12%) between sites per patient. Septal regions (mid‐, inflow‐, and low‐) were associated with the most optimal and right ventricular epicardial showed the worst contractility (P < 0.05) responses. Apex was optimal in some CHD patients. Threshold and sensing were comparable up to 11 years (mean 7) postimplant regardless of septal site.

Conclusion

There is no single “sweet spot” for optimal ventricular pacing, and the best implant sites are patient and CHD variable. Current lead designs ensure chronic stability/performance regardless of site. Proactive contractility‐guided pacing implant can optimize chronic paced ventricular function.
Phosphorus recycling in photorespiration maintains high photosynthetic capacity in woody species
Authors: ELLSWORTH DAVID S. , CROUS KRISTINE Y. , LAMBERS HANS , COOKE JULIA
Published: October 2014

Leaf photosynthetic CO2 responses can provide insight into how major nutrients, such as phosphorus (P), constrain leaf CO2 assimilation rates (Anet). However, triose‐phosphate limitations are rarely employed in the classic photosynthesis model and it is uncertain as to what extent these limitations occur in field situations. In contrast to predictions from biochemical theory of photosynthesis, we found consistent evidence in the field of lower Anet in high [CO2] and low [O2] than at ambient [O2]. For 10 species of trees and shrubs across a range of soil P availability in Australia, none of them showed a positive response of Anet at saturating [CO2] (i.e. Amax) to 2 kPa O2. Three species showed >20% reductions in Amax in low [O2], a phenomenon potentially explained by orthophosphate (Pi) savings during photorespiration. These species, with largest photosynthetic capacity and Pi > 2 mmol P m−2, rely the most on additional Pi made available from photorespiration rather than species growing in P‐impoverished soils. The results suggest that rarely used adjustments to a biochemical photosynthesis model are useful for predicting Amax and give insight into the biochemical limitations of photosynthesis rates at a range of leaf P concentrations. Phosphate limitations to photosynthetic capacity are likely more common in the field than previously considered.
Single‐center experience in pediatric renal transplantation using thymoglobulin induction and steroid minimization
Authors: Warejko Jillian K. , Hmiel S. Paul
Published: October 2014

Our center has offered thymoglobulin induction with steroid minimization to our pediatric renal transplant patients for the last 10 yr. Steroid minimization or avoidance has shown favorable results in survival, kidney function, and growth in previous studies of pediatric patients. We report our experience with this protocol over the past 10 yr with respect to patient/graft survival, acute rejection episodes, renal function, linear growth, bone density, cardiovascular risk factors, and opportunistic infections. A retrospective chart review was performed for pediatric renal transplant patients on the steroid‐minimized protocol between January 2002 and December 2011 on an intention to treat basis. Patient demographics, height, weight, serum creatinine, iGFR, biopsies, and survival data were collected. Height and weight z‐scores were calculated with EpiInfo 7, using the CDC 2000 growth charts. Survival was calculated using Kaplan–Meier analysis. eGFR was calculated using the original and modified Schwartz equations. Forty‐four pediatric patients were identified, aged 13 months to 19 yr. Five‐yr survival was 95.5% for males and 94.4% for females. Only five patients had biopsy‐proven ACR, two of which were at more than 12 months post‐transplantation. Height delta z‐scores from transplant to one, three, and five yr were 0.34, 0.38, and 0.79, respectively. Weight delta z‐scores from transplant to one, three, and five yr were 0.87, 0.79, and 0.84, respectively. Mean original Schwartz eGFR was 84.3 ± 15.8 mL/min/1.73 m2, modified Schwartz eGFR was 59.3 ± 11.5 mL/min/1.73 m2, and iGFR was 64.2 ± 8.5 mL/min/1.73 m2 at three yr. Of 18 subjects who had a bone density exam, none had a z‐score less than −2 on DEXA exam at one‐yr post‐transplantation. Fifty‐one percent of patients were on antihypertensives at the time of transplant compared with 43% at one‐yr post‐transplantation. Three yr post‐transplantation, the average LDL was <100 mg/dL, and average total cholesterol was <200 mg/dL. There were no clinical episodes of EBV or CMV infection. A steroid‐minimized protocol with thymoglobulin induction is safe and provides favorable improvement in linear growth, stable graft function, stable or improved cardiovascular risk factors, and normal bone density in pediatric renal transplant patients.
Assessing Characteristic Scales Using Wavelets
Authors: Keim Michael J. , Percival Donald B.
Published: October 2014

Characteristic scale is a notion that pervades the geophysical sciences, but it has no widely accepted precise definition. Motivated by the facts that the wavelet transform decomposes a time series into coefficients that are associated with different scales and that the variance of these coefficients (the so-called wavelet variance) decomposes the variance of the time series across scales, the paper proposes a definition for characteristic scale in terms of peaks in plots of the wavelet variance versus scale. After presenting basic theory for wavelet-based characteristic scales, a natural estimator for these scales is considered. Large sample theory for this estimator permits the construction of confidence intervals for a true unknown characteristic scale. Computer experiments are presented that demonstrate the efficacy of the large sample theory for finite sample sizes. Characteristic scale estimates are calculated for medium multiyear Arctic sea ice, global temperature records, coherent structures in river flows and the Madden–Julian oscillation in an atmospheric time series.
The Interpersonal Theory of Suicide Applied to Male Prisoners
Authors: Mandracchia Jon T. , Smith Phillip N.
Published: October 2014

The interpersonal theory of suicide proposes that severe suicide ideation is caused by the combination of thwarted belongingness (TB) and perceived burdensomeness (PB), yet few studies have actually examined their interaction. Further, no studies have examined this proposal in male prisoners, a particularly at‐risk group. To address this gap, the current study surveyed 399 male prisoners. TB and PB interacted to predict suicide ideation while controlling for depression and hopelessness. High levels of both TB and PB were associated with more severe suicide ideation. The interpersonal theory may aid in the detection, prevention, and treatment of suicide risk in prisoners.
Bilateral lenticular Encephalitozoon cuniculi infection in a snow leopard (Panthera uncia)
Authors: Scurrell Emma Jane , Holding Ellen , Hopper Jane , Denk Daniela , Fuchs‐Baumgartinger Andrea , Silbermayr Katja , Nell Barbara
Published: October 2014

Bilateral phacoclastic uveitis caused by lenticular infection with Encephalitozoon cuniculi is described in a snow leopard. The diagnosis was made on histopathological and immunohistological examination of both eyes submitted after postmortem examination. There was a positive antibody titer for E. cuniculi (1:320). Polymerase chain reaction (PCR) and sequence analysis of formalin‐fixed, paraffin‐embedded ocular tissue detected the DNA of E. cuniculi, strain III. No other systemic lesions attributable to the E. cuniculi infection were identified.
Limbal squamous cell carcinoma inHaflinger horses
Authors: Lassaline Mary , Cranford Taryn L. , Latimer Claire A. , Bellone Rebecca R.
Published: October 2014

Objective

To describe the prevalence ofLSCCin Haflinger horses and to analyze affected horses' pedigrees investigating the genetic mode of inheritance.

Animals

Fifteen horses met inclusion criterion of (i) being of the Haflinger breed, as confirmed by North American Haflinger Registry pedigree and (ii) being diagnosed withLSCC, as confirmed by clinical examination by a veterinary ophthalmologist or by histopathology. Pedigrees could not be obtained for four additional horses diagnosed withLSCCthat had been identified as Haflingers.

Procedure

Retrospective medical record review of all 19 horses was used to determine patient sex and age at diagnosis. The four‐generation pedigrees available for 15 of the horses were used to perform pedigree analysis.

Results

Average age of 19 Haflingers at diagnosis withLSCCwas 8.7 years. Eleven were males and eight were females. Thirteen of 15 affected horses for whom pedigrees were available shared a common ancestor within five generations, and all 15 shared a common ancestor from the A stallion line in the breed pedigree. Pedigree analysis identified a common sire of two of the affected male horses. Clinical examination of this sire that had no history ofLSCCshowed no current clinical signs ofLSCC, suggesting an autosomal recessive mode of inheritance.

Conclusions

Haflingers may be over‐represented amongst horses withLSCCand may be diagnosed at a younger age than other breeds. Affected Haflingers appear closely related, suggesting a possible heritable basis forLSCC. The genetic basis forLSCCwill be investigated further by aGWASapproach.