bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Analysis of Transcriptome Variation in Uterine Carcinosarcoma and Comparison to Sarcoma and Endometrial Carcinoma
Authors: Davidson Natalie , Lehmann Kjong-Van , Kahles André , Perez Alexander , Rätsch Gunnar
Published: December 2014

Large-scale cancer genomics has made a huge impact onto cancer research. It has allowed the characterization of tumor types in an unprecedented depth. More recent studies target the joint analysis of multiple tumor types to gain insight into similarities and differences on a molecular level. Here we present an analysis of Uterine Carcinosarcoma. The histological similarities to sarcomas and carcinomas warrants an in-depth analysis to Uterine Endometrial Carcinoma as well as Sarcomas and we have used data from The Cancer Genome Atlas to understand transcriptome similarities and differences between these tumor types. We have performed a differential transcriptome analysis of Uterine Carinosarcoma to Uterine samples from GTEx to find genes with tumor specific splicing or expression patterns, which may not only be of interest for a deeper mechanistic understanding of the development and progression of Uterine Carcinosarcoma, but may also be potential tumor markers. Similarities and differences to Sarcomas and Endometrial Carcinomas present new opportunities for the development of new and targeted drug therapies. Finally we have also studied genetic determinants of gene expression and splicing changes and identified germline variants that explain expression and splicing differences between individuals. This analysis demonstrates the opportunities of integrative comparative analysis between multiple tumor types.
The utility of visual estimation of cover for rapid assessment of graminoid abundance in forest and grassland habitats in studies of animal foraging
Authors: Gautam Hansraj , Potdar G. G. , Vidya T.N.C.
Published: December 2014

Questions

To assess the feasibility of using visually-estimated cover in rapid assessment of herbivore food species abundance in the grass layer, we asked the following questions: 1) What is the relationship between total graminoid cover and biomass in forests, and does height improve the prediction of biomass from cover? 2) How does total cover relate to biomass in a grassland habitat? 3) How does elephant food species graminoid cover relate to individual species biomass? 4) How well does species diversity of forest understorey grass layer, calculated from cover data, mirror that calculated from biomass data?

Location

Nagarahole National Park, India.

Methods

We estimated the abundance of graminoids through visual estimation of cover and weighted harvested biomass in forest and grassland plots. In forests, two estimates of total graminoid abundance, total graminoid cover and sum of species covers, were used. In the grassland, only total graminoid abundance was measured. We examined the relationship between cover estimates and biomass, and the additional utility of height in predicting biomass, using multiple regressions and AIC-based model selection. We also assessed similarity in cover- and biomass-based Simpson’s and Shannon-Wiener diversity indices using regressions.

Results

Graminoid cover explained a large portion of variation in total graminoid biomass in forest and grassland habitats. The sum of species covers was better than total cover in estimating total graminoid biomass in the forest. The benefit of including height to estimate total biomass was moderate in forests but substantial in grassland. Cover estimates were good proxies of food species biomass, and the addition of height did not yield better models for most species. Species diversity indices calculated from cover largely matched those based on biomass.

Conclusions

Visual estimation of species cover is a good alternative to biomass harvesting for rapid assessment of abundance of graminoids consumed by generalist herbivores, like elephants.
More Signal, Less Noise: Single-primer Adenylation Method (SAM) for the Efficient Preparation of DNA for Transposon Sequencing (TnSeq)
Authors: Willcocks S , Stabler R , Wren B
Published: December 2014

Transposon Sequencing (TnSeq) is a cutting-edge tool that allows quantitative, genome-wide genetic analysis of a given population in an experimental condition. TnSeq utilises next generation sequencing that is designed to perform optimally when all of the input material is of interest, therefore TnSeq is inefficient since only a small portion of nucleic acid fragments contain the transposon target site for primer annealing. We describe an innovative modification to standard transposon library preparation protocols that provides a significant improvement to the quality of sequencing data recovered.
HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia
Authors: Rai Taranjit Singh , Cole John J. , Nelson David M. , Dikovskaya Dina , Faller William J. , Vizioli Maria Grazia , Hewitt Rachael N. , Anannya Orchi , McBryan Tony , Manoharan Indrani , van Tuyn John , Morrice Nicholas , Pchelintsev Nikolay A. , Ivanov Andre , Brock Claire , Drotar Mark E. , Nixon Colin , Clark William , Sansom Owen J. , Anderson Kurt I. , King Ayala , Blyth Karen , Adams Peter D.
Published: December 2014

Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cellular senescence and associated tumor suppression depend on control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Appropriately for a DNA replication-independent chaperone, HIRA is involved in control of chromatin in nonproliferating senescent cells, although its role is poorly defined. Here, we show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape. Expression of canonical histones is linked to alternative mRNA splicing to eliminate signals that confer mRNA instability in nonproliferating cells. Deposition of newly synthesized histones H3.3 and H4 into chromatin of senescent cells depends on HIRA. HIRA and newly deposited H3.3 colocalize at promoters of expressed genes, partially redistributing between proliferating and senescent cells to parallel changes in expression. In senescent cells, but not proliferating cells, promoters of active genes are exceptionally enriched in H4K16ac, and HIRA is required for retention of H4K16ac. HIRA is also required for retention of H4K16ac in vivo and suppression of oncogene-induced neoplasia. These results show that HIRA controls a specialized, dynamic H4K16ac-decorated chromatin landscape in senescent cells and enforces tumor suppression.
Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization
Authors: Williamson Iain , Berlivet Soizik , Eskeland Ragnhild , Boyle Shelagh , Illingworth Robert S. , Paquette Denis , Dostie Josée , Bickmore Wendy A.
Published: December 2014

Although important for gene regulation, most studies of genome organization use either fluorescence in situ hybridization (FISH) or chromosome conformation capture (3C) methods. FISH directly visualizes the spatial relationship of sequences but is usually applied to a few loci at a time. The frequency at which sequences are ligated together by formaldehyde cross-linking can be measured genome-wide by 3C methods, with higher frequencies thought to reflect shorter distances. FISH and 3C should therefore give the same views of genome organization, but this has not been tested extensively. We investigated the murine HoxD locus with 3C carbon copy (5C) and FISH in different developmental and activity states and in the presence or absence of epigenetic regulators. We identified situations in which the two data sets are concordant but found other conditions under which chromatin topographies extrapolated from 5C or FISH data are not compatible. We suggest that products captured by 3C do not always reflect spatial proximity, with ligation occurring between sequences located hundreds of nanometers apart, influenced by nuclear environment and chromatin composition. We conclude that results obtained at high resolution with either 3C methods or FISH alone must be interpreted with caution and that views about genome organization should be validated by independent methods.
Molecular characterization of the skin fungal microbiome in patients with psoriasis
Authors: Takemoto Akemi , Cho Otomi , Morohoshi Yuka , Sugita Takashi , Muto Masahiko
Published: December 2014

The skin surface is colonized by a wide variety of fungi and bacteria. While many of these organisms, including Malassezia, Candida, Streptococcus and Staphylococcus species, are associated with provocation and/or exacerbation of psoriasis, a detailed analysis of the cutaneous fungal microbiome in psoriatic patients has yet to be performed. To identify the disease‐specific fungal microbiota on psoriatic scale samples, fungal rRNA gene sequences from 12 psoriatic patients and 12 healthy controls were analyzed by pyrosequencing. A total of 317 806 high‐quality sequences were obtained, representing 142 genera. Malassezia species were the most abundant sequences in both populations (46.9 ± 14.0% in psoriasis vs 76.0 ± 14.6% for healthy controls). Principal coordinate analysis revealed that the fungal microbiomes were independent. Although an association between the cutaneous fungal microbiome and psoriasis has yet to be established, our data indicate that the microbiome in patients with psoriasis is independent of that in healthy controls.
Alien and native plant species play different roles in plant community structure
Authors: Bernard‐Verdier Maud , Hulme Philip E.
Published: December 2014

Although impacts of alien plants on species richness are widely reported, it remains unclear how common such effects might be and whether they differ from those due to native species. To date, too few studies have examined the impacts of a wide enough spectrum of native and alien species to address the importance of geographic origin on the richness of plant communities.

We investigated how total plant species richness, as well as its separate alien and native components, varied with the abundance of 115 alien and 146 native plant species across Banks Peninsula in New Zealand. Using null models, we tested whether significant correlations between the abundance of each focal species and species richness were more frequent than expected by chance. Examination of the differences in the relationships with species abundance found for native and alien richness can shed light as to whether alien species might be acting as drivers of biodiversity change or passengers responding to external environmental factors.

Significant relationships were rarely found for total richness due to contrasting trends of native and alien richness with species abundance. In contrast to natives, an increase in the abundance of an alien species revealed more frequent negative relationships with native richness and positive correlations with alien richness.

The relationship with species abundance found for native and alien components of richness differed between grasslands and woodlands. While we found putative support for negative impacts on native richness for several alien species in grasslands, the similar negative correlations in woodlands were more likely to reflect the shade intolerance of alien grasses where native species richness was high.

Synthesis. Our analyses reveal that widespread alien and native species play different roles in the plant communities in which they co‐occur. Separately analysing the relationship with species abundance for alien and native components of richness can help distinguish between situations where aliens may be acting as the primary drivers in plant community changes or simply passengers. This is an essential first step in designing further experimental studies to determine the underlying ecological processes and potential ecosystem impacts of alien species.
Practical consequences of calcium addition to and removal from milk and milk products
Authors: Deeth Hilton C , Lewis Michael J
Published: December 2014

Calcium in milk is significant for both its nutritive value and its key role in many functional properties of milk and milk products. Manipulating its concentration, particularly of the ionic form, alters the properties of the products and facilitates or hinders certain processing operations. Stability to thermal treatment is the major property affected, but several others such as gelation, coagulation and foaming are influenced by either adding or removing calcium. This article reviews the manipulation of the calcium content of several products and its practical consequences for dairy processing.
Insects as a model system for aging studies
Authors: Lee Hye‐Yeon , Lee Shin‐Hae , Min Kyung‐Jin
Published: December 2014

As the human lifespan has increased dramatically in recent decades, the amount of aging research has correspondingly increased. To investigate mechanisms of aging, an efficient model system is required. Although mammalian animal models are essential for aging studies, they are sometimes inappropriate due to their long lifespans and high maintenance costs. In this regard, insects can be effective alternative model systems for aging studies, as insects have a relatively short lifespan and cost less to maintain. Many species of insects have been used as model systems for aging studies, especially fruit flies, silkworm moths and several social insects. Fruit flies are most commonly used for aging studies due to the wide availability of abundant resources such as mutant stocks, databases and genetic tools. Silkworm moths are also good tools for studying aging at the tissue level due to their relatively large size. Last, social insects such as ants and bees are good for investigating lifespan determinants, as their lifespans significantly differ according to caste despite a constant genotype among the population. In this review, we discuss the current status and future prospects of aging research using insect model systems.
Risk of tuberculosis, serious infection and lymphoma with disease‐modifying biologic drugs in rheumatoid arthritis patients in Taiwan
Authors: Chiu Ying‐Ming , Lang Hui‐Chu , Lin Hsiao‐Yi , Yang Ming‐Ta , Fang Chi‐Hui , Yang Ya‐Wen , Schabert Vernon F. , Tang Boxiong
Published: December 2014

Aim

To determine the risk of adverse events in rheumatoid arthritis (RA) patients treated with biological disease‐modifying anti‐rheumatic drugs (bDMARD) versus traditional DMARDs (tDMARD).

Method

This retrospective study used Taiwan's National Health Insurance Research Database to capture data for adult patients diagnosed with RA between 1 January 1999 and 31 December 2009 and treated with tDMARD or bDMARD. The endpoints were patients with cases of an inpatient serious bacterial infection (SBI), diagnosis of tuberculosis (TB) or lymphoma. Within the bDMARD cohort, individual bDMARDS with adequate data were also compared (adalimumab and etanercept). Propensity‐score matching was used to adjust for significant (P ≤ 0.05) patient characteristics. Incidence rate ratios (IRR) of SBI/TB/lymphoma cases versus non‐cases were adjusted for exposure time (rate per 100 000 patient‐years) and 95% confidence intervals were constructed to assess whether IRRs differed from 1.0.

Results

Of 34 947 potential patients, 7888 tDMARD, 3459 bDMARD (including 1492 etanercept and 746 adalimumab) patients were matched for analysis. A total of 2150 cases were identified and of these 1711 were SBI, 406 as TB and 33 as lymphoma. For all cases except SBI, the IRR (95% CI) was higher for bDMARD versus tDMARD (SBI 1.04 [0.89–1.19]; TB 2.67 [2.12–3.34]; lymphoma 3.24 [1.37–7.06]). Excepting lymphoma, IRR was higher for adalimumab versus etanercept (SBI 1.83 [1.19–2.77]; TB 2.35 [1.29–4.15]; lymphoma 1.49 [0.03–18.66]).

Conclusions

There was a higher risk for specified infections and lymphoma with bDMARD versus tDMARD and adalimumab versus etanercept.
Association of mortality with out‐of‐hours admission in patients with perforated peptic ulcer
Authors: KNUDSEN N. V. , MØLLER M. H. ,   THE DANISH CLINICAL REGISTER OF EMERGENCY SURGERY
Published: December 2014

Background

Perforated peptic ulcer is a serious emergency surgical condition. The aim of the present nationwide cohort study was to evaluate the association between mortality and out‐of‐hours admission in patients surgically treated for perforated peptic ulcer.

Methods

All Danish patients surgically treated for benign gastric or duodenal perforated peptic ulcer in Denmark between September 1, 2011 and August 31, 2013 were included. Patients were identified through The Danish Clinical Register of Emergency Surgery. The association between 90‐day mortality and time and day of admission and surgery was assessed by crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs).

Results

A total of 726 patients were included. Median age was 69.5 years (range 18.2–101.7), and 569 of the 726 patients (78.4%) had at least one coexisting disease. Adjusted ORs and 95% CIs between 90‐day mortality and admission in daytime vs. nighttime and weekday vs. weekend were 1.0 (0.7–1.5) and 1.2 (0.8–1.8), respectively. Adjusted ORs with 95% CI between surgery in daytime vs. nighttime and weekday vs. weekend were 0.9 (0.6–1.3) and 1.2 (0.8–1.8), respectively. Sensitivity analysis was consistent with the primary analysis. The overall 90‐day mortality rate was 25.6% (186/726).

Conclusion

No statistically significant adjusted association between 90‐day mortality and out‐of‐hours admission was found in patients surgically treated for perforated peptic ulcer.
Self‐efficacy mediates the effects of topiramate and GRIK1 genotype on drinking
Authors: Kranzler Henry R. , Armeli Stephen , Wetherill Reagan , Feinn Richard , Tennen Howard , Gelernter Joel , Covault Jonathan , Pond Timothy
Published: December 2014

Previous studies indicate that topiramate reduces alcohol use among problem drinkers, with one study showing that the effect was moderated by a polymorphism (rs2832407) in GRIK1, the gene encoding the GluK1 kainate subunit. We examined whether the interactive effect of medication and genotype (1) altered the association between daily self‐efficacy and later‐day drinking; and (2) had an indirect effect on drinking via self‐efficacy. In a 12‐week, placebo‐controlled trial of topiramate, we used daily interactive voice response technology to measure self‐efficacy (i.e. confidence in avoiding heavy drinking later in the day) and drinking behavior in 122 European‐American heavy drinkers. Topiramate's effects on both self‐efficacy and drinking level were moderated by rs2832407. C‐allele homozygotes treated with topiramate showed higher levels of self‐efficacy and lower levels of nighttime drinking across the 12‐week trial. Further, the interactive effect of topiramate and genotype on mean nighttime drinking levels was mediated by mean levels of self‐efficacy. By modeling topiramate's effects on nighttime drinking across multiple levels of analysis, we found that self‐efficacy, a key psychologic construct, mediated the effect of topiramate, which was moderated by rs2832407 genotype. Thus, it may be possible to use an individualized assessment (i.e. genotype) to select treatment to optimize the reduction in heavy drinking and thereby provide a personalized treatment approach.
Comparative analysis of corneal measurements obtained from a Scheimpflug camera and an integrated Placido‐optical coherence tomography device in normal and keratoconic eyes
Authors: Viswanathan Deepa , Kumar Nikhil L. , Males John J. , Graham Stuart L.
Published: December 2014

Purpose

To assess the agreement between a Scheimpflug camera (Pentacam) and a combined Placido‐optical coherence tomography device (Visante OMNI) in measuring corneal curvature, thickness and elevation values in normal and keratoconic eyes.

Methods

Corneal measurements of 110 normal eyes (one eye per subject) and 70 keratoconic eyes were obtained from both devices and compared. Agreement was determined using the Bland–Altman analysis 95% limits of agreement (LoA).

Results

The Pentacam measured significantly greater keratometry readings in the flattest (K1) and steepest meridians (K2) in normal and keratoconic eyes. The 95% LoA in normal eyes were −0.32 to 0.59 dioptres (D) (K1) and −0.41 to 0.74 D (K2). In keratoconic eyes, the 95% LoA were −1.35 to 1.92 D (K1) and −1.38 to 1.99 D (K2). The Pentacam recorded significantly higher central corneal thickness (CCT) values in both groups of eyes. The 95% LoA were −4.31 to 39.89 microns (μ) and −12.92 to 41.35 μ in normal and keratoconic eyes, respectively. Pentacam anterior and posterior corneal elevations were significantly greater in both groups of eyes. The devices demonstrated excellent repeatability and reproducibility for corneal curvature and thickness but not elevation measurements.

Conclusions

The Pentacam measured significantly greater corneal curvature, thickness and elevation values compared to the Visante OMNI in normal and keratoconic eyes. The devices agree moderately for anterior corneal elevations in normal eyes and do not appear to be interchangeable for corneal measurements in clinical practice.
Stand management to reduce fire risk promotes understorey plant diversity and biomass in a semi‐aridPinus halepensisplantation
Authors: Jiménez María N. , Spotswood Erica N. , Cañadas Eva M. , Navarro Francisco B.
Published: December 2014

Questions

How do thinning and understorey management practices (ploughing, clearing) to reduce fire risk affect plant species composition, diversity and biomass within pine plantations on previous croplands? Do managed pine plantations promote changes in plant succession compared to unplanted areas (old fields) towards restoration goals including holm oak forest or other alternative land‐use types?

Location

Altiplano del Conejo, Guadix‐Baza Basin,SEIberian Peninsula, Spain.

Methods

We evaluated plant species composition, diversity, cover and biomass in the understorey of a semi‐arid 10‐yr‐old afforestation area ofPinus halepensisthrough a manipulative experiment in which four different thinning regimes (T0 treatment: control plots; T100, T75, T60 and T48 treatments: 100%, 75%, 60%, and 48% of mean basal area removed, respectively), and two understorey vegetation treatments (clearing, ploughing) were applied, simulating stand practices to reduce fire risk. Sampling was performed annually for 5 yr (from 2006 to 2010). For comparison, four other land‐use types (rain‐fed cereal crops, old fields, alpha grass steppes and holm oak forests) were sampled to quantify understorey vegetation community composition and diversity.

Results

Afforestation plots were compositionally distinct from each other within 5 yr, mainly as a result of canopy thinning and to a lesser extent, vegetation treatments. Total species richness was highest in the low to medium densities of pines, where richness approached that found in native communities. However, afforestation plots were most similar in diversity, life‐form type and composition to abandoned agricultural fields, and large differences were found between afforestation plots, native forests and alpha grass steppes.

Conclusions

This study demonstrates that plant species composition in the understorey of pine plantations on former cropland can respond rapidly to common management practices intended to reduce fire risk. In particular, tree thinning increases both understorey plant diversity and biomass, but does not lead to recruitment of species that are typical of native forests. Rates of native forest succession appear to be slow in this semi‐arid Mediterranean ecosystem. Current pine plantation management practices, while useful for increasing understorey biomass and plant diversity will need to be coupled with additional restoration techniques (e.g. seeding and transplants) to recover species composition and structure of native forests.
Pharmacokinetics of serelaxin in patients with hepatic impairment: a single‐dose, open‐label, parallel group study
Authors: Kobalava Zhanna , Villevalde Svetlana , Kotovskaya Yulia , Hinrichsen Holger , Petersen‐Sylla Marc , Zaehringer Andreas , Pang Yinuo , Rajman Iris , Canadi Jasna , Dahlke Marion , Lloyd Peter , Halabi Atef
Published: December 2014

Aims

Serelaxin is a recombinant form of human relaxin‐2 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin.

Methods

This was an open‐label, parallel group study (NCT01433458) comparing the PK of serelaxin following a single 24 h intravenous (i.v.) infusion (30 μg kg−1 day−1) between patients with mild, moderate or severe hepatic impairment (Child–Pugh class A, B, C) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non‐compartmental PK parameters [including area under the serum concentration–time curve AUC(0–48 h) and AUC(0–∞) and serum concentration at 24 h post‐dose (C24h)] were compared between each hepatic impairment group and healthy controls.

Results

A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady‐state at 12–24 h and then declined following completion of infusion, with a mean terminal half‐life of 7–8 h. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment‐related antibodies developed during this study.

Conclusions

The PK and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48 h i.v. infusion in patients with hepatic impairment.
The Adverse Effects of Sorafenib in Patients with Advanced Cancers
Authors: Li Ye , Gao Zu‐Hua , Qu Xian‐Jun
Published: December 2014

Sorafenib is the first multi‐kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well‐differentiated radioiodine‐resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non‐receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in long‐term efficacy and low incidence of life‐threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment‐related toxicities include diarrhoea, fatigue, hand–foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers.
Effectiveness of hexaminolevulinate fluorescence cystoscopy for the diagnosis of non‐muscle‐invasive bladder cancer in daily clinical practice: a Spanish multicentre observational study
Authors: Palou Juan , Hernández Carlos , Solsona Eduardo , Abascal Ramon , Burgués Juan P. , Rioja Carlos , Cabrera José A. , Gutiérrez Carlos , Rodríguez Oscar , Iborra Inmaculada , Herranz Felipe , Abascal José M. , Conde Guillermo , Oliva José
Published: December 2014

Objective

To assess the sensitivity and specificity of blue‐light cystoscopy (BLC) with hexaminolevulinate as an adjunct to white‐light cystoscopy (WLC) vs WLC alone for the detection of non‐muscle‐invasive bladder cancer (NMIBC), in routine clinical practice in Spain.

Patients and Method

An intra‐patient comparative, multicentre, prospective, observational study. Adults with suspected or documented primary or recurrent NMIBC at eight Spanish centres were included in the study. All patients were examined with WLC followed by BLC with hexaminolevulinate. We evaluated the detection rate of bladder cancer lesions by WLC and BLC with hexaminolevulinate, overall and by tumour stage and compared with histological examination of the biopsied lesions. Sensitivity and specificity was calculated.

Results

In all, 1 569 lesions were identified from 283 patients: 621 were tumour lesions according to histology and 948 were false‐positives. Of the 621 tumour lesions, 475 were detected by WLC (sensitivity 76.5%, 95% confidence interval [CI] 73.2–79.8) and 579 were detected by BLC (sensitivity 93.2%, 95% CI 91.0–95.1; P < 0.001). There was a significant improvement in the sensitivity in the detection of all types of NMIBC lesions with BLC compared with WLC. Of 219 patients with tumours, 188 had NMIBC [highest grade: carcinoma in situ (CIS), n = 36; Ta, n = 87; T1, n = 65). CIS lesions were identified more with BLC (n = 27) than with WLC [n = 19; sensitivity: BLC 75.0% (95% CI 57.8–87.9) vs WLC 52.8% (95% CI 35.5–69.6); P = 0.021]. Results varied across centres.

Conclusions

This study shows that improvement in diagnosis of NMIBC, mainly CIS and Ta tumours, obtained with BLC with hexaminolevulinate as an adjunct to WLC vs WLC alone can be shown in routine clinical practice.
Review: Adoption, fostering, and the needs of looked‐after and adopted children
Authors: Fisher Philip A.
Published: December 2014

Background

This review of the literature examines adoption, fostering, and the needs of looked‐after and adopted children. Three domains of research about looked‐after children are examined.

Findings

There is extensive evidence that early adverse experiences affect psychological and neurobiological development in looked‐after and adopted children. There is also evidence that some looked‐after and adopted children show remarkable resilience in the face of adversity; intervention research provides evidence of the ability to reduce risks and promote positive outcomes in this population. The intervention studies have revealed not only the potential for improved behavioral trajectories but also the plasticity of neurobiological systems affected by early stress.

Conclusion

Foster and adopted children face many challenges, but scientific knowledge also provides reason for hope and information about how to maximize positive outcomes.
Evaluation of the influence exerted by different dental specialty backgrounds and measuring instrument reproducibility on esthetic aspects of maxillary implant‐supported single crown
Authors: Vaidya Samriddhi , Ho Yu Lau Elaine , Hao Jie , Lang Niklaus P. , Mattheos Nikos
Published: December 2014

Objective

To evaluate the influence exerted by different dental specialty backgrounds as well as the validity and reproducibility of the Pink Esthetic Score/White Esthetic Score (PES/WES) and the modified Implant Crown Aesthetic Index (mod‐ICAI) on the assessment of esthetic aspects of maxillary implants supported single‐tooth prosthesis.

Material and methods

A total of fourteen examiners (Two orthodontists, two prosthodontists, two oral surgeons, two periodontists, two dental technicians, two dental assistants, and two postgraduate students in Implant Dentistry evaluated 20 photographs of single‐implant‐supported crowns and five photographs of unrestored teeth of esthetic zone in a two part study. The examiners assessed the photographs with each index (Pink Esthetic Score/White Esthetic Score and modified Implant Crown Aesthetic Index), twice with a week's interval. Orders of photographs were rearranged in the second assessment.

Results

Kruskal–Wallis test results showed significant differences among all the six specialties (P ≤ 0.001). DAs and periodontists had significantly better ratings than other specialties with both indices. Prosthodontists had the lowest mean rank scores regardless of the index. Interobserver agreement was also lowest between the two prosthodontists (4–28%), rest of the groups had low‐to‐moderate agreement (20–80%) when limited allowance was accepted. With mod‐ICAI, more interobserver agreement was noted within the specialty group than with PES/WES.

Conclusions

The PES/WES and the modified ICAI can be reliable estimates of esthetic outcomes. The assessor degree of specialization affected the esthetic evaluation with both the PES/WES and the modified ICAI. DAs and periodontists were identified to provide more favorable ratings than other specialties while prosthodontists were most critical in this study. With modified ICAI, more interobserver agreement within specialty resulted. The interexaminer agreement may be increased if more tolerance of 1–2 points is considered.
Early reconstruction of the leaking ileal pouch‐anal anastomosis: a novel solution to an old problem
Authors: Gardenbroek T. J. , Musters G. D. , Buskens C. J. , Ponsioen C. Y. , D'Haens G. R. A. M. , Dijkgraaf M. G. W. , Tanis P. J. , Bemelman W. A.
Published: December 2014

Aim

The study aimed to determine the effectiveness and direct medical costs of early surgical closure of the anastomotic defect after a short course of Endo‐sponge® therapy of the presacral cavity, compared with conventional treatment in patients with anastomotic leakage after ileal pouch‐anal anastomosis (IPAA).

Method

Patients with anastomotic leakage after IPAA undergoing early surgical closure of the anastomotic defect after a short Endo‐sponge® treatment were prospectively followed and compared with a consecutive cohort of patients with an anastomotic leak treated by creation of a loop ileostomy and occasional drainage of the presacral cavity.

Results

A total of 15 patients were treated with early surgical closure and 29 were treated conventionally. In the early surgical closure group, the Endo‐sponge® treatment was continued for a median of 12 days [interquartile range (IQR) 7–15 days] with a median of 3 (IQR 2–4) Endo‐sponge® changes. Secondary anastomotic healing was achieved in all patients (n = 15) in the early surgical closure group compared with 52% (n = 16) in the conventional treatment group (P = 0.003). Closure of the anastomotic defect was achieved after a median of 48 (25–103) days in the early surgical closure group compared with 70 (IQR 49–175) days in the conventional treatment group (P = 0.013). A functional pouch was seen in 93% and 86% of the patients in each group. There was no significant difference in direct medical cost.

Conclusion

Early surgical closure after a short period of Endo‐sponge® treatment is highly effective in treating anastomotic leakage after IPAA without increasing cost.
Assessing Antecedents of Socially Responsible Supplier Selection in Three Global Supply Chain Contexts
Authors: Griffis Stanley E. , Autry Chad W. , Thornton LaDonna M. , Brik Anis ben
Published: December 2014

A number of highly publicized, controversial lapses in social responsibility within global supply chains have forced managers and scholars to reexamine long‐held perspectives on supplier selection. Extending Carter and Jennings’ department‐level study of purchasing social responsibility, our research assesses the role of supply managers’ ethical intentions and three key antecedents that drive socially responsible supplier selection. Comparing evidence from firms operating in China, the United States, and the United Arab Emirates, we identify three key drivers of supply managers’ ethical intentions and examine both their direct and indirect impacts on socially responsible supplier selection. We find differential support for the predictor relationships on supply manager ethical intentions across national contexts and mediated versus nonmediated models. These observations bear important implications for firms conducting global supply management.
Learning to Pray
Authors: Beck Joan
Published: December 2014

Joan Beck writes a personal account of how her life of prayer has developed since graduating from seminary in 1978. She tells how, through prayer, the Holy Spirit enlivened the presence of Christ in her as she learned to listen more than talk and weathered dry spells of no response. She hopes that by including reports and resources from her own journey, readers will be moved to reflect upon and share what they have learned through prayer.
Formation for the Whole Church: A New/Old Vision of Theological Education in the 21st Century
Authors: Stache Kristine
Published: December 2014

This article offers a proposal for a vision of theological education beyond the boundaries of training and teaching for traditional professional ministry roles. Particular attention will be given to the idea of education as formation and the shared role academic institutions have with congregations. Implications for reshaping definitions of student and faculty will be explored.
Beyond Biblical Literacy: Developing Readerly Readers in Teaching Biblical Studies
Authors: Stack‐Nelson Judith
Published: December 2014

Theological education in biblical studies often has focused on information, but it needs to emphasize developing skills and sensibilities in students that will produce confident, imaginative, and attentive readers. To form readers with a disciplined imagination—what we are calling “readerly readers”—educators need to inculcate skills and sensibilities that will enable students to interact with the text as a living voice, rather than as an object to be mastered, and to allow the text to provoke difficult, profound, or long‐term questions.
Nurturing Faith for Action: Theological Education and Global Responsibility
Authors: Rosencrans Kendra
Published: December 2014

Ghana hopes to parlay the financial promises of oil recovery into a better life for its people. If Ghana succeeds, it would be a model for the developing world. But Ghana's capacity to overcome poverty and support human dignity will be stronger if the rest of us who also hold that value commit more truly to it. As people of faith, as leaders of institutions, as educators, we face substantive questions about how our own actions, business decisions, and consumptive practices contribute to the larger issues of oil, consumerism, and planetary health. A course that asks not just Christian scholars and clergy, but leaders of theological institutions, church bodies, businesses, and others, to consider an ethical, paradigmatic shift toward a whole‐world ethic of well‐being is in order.
Coming In? Or Going Out? A Few Thoughts on Theological Education
Authors: Haemig Mary Jane
Published: December 2014

Much of theological education and church life has been based on the assumption that people will come to church. Instead, the church needs to look at how it can go out to those who do not come. Careful consideration needs to be given to the traits of leaders needed for this task and the ethos of the education best suited to helping them move out. The past provides some models that may be useful for Lutherans today.
Academic Theology Centered on Practical Theology
Authors: Iversen Hans Raun
Published: December 2014

This article argues that there are considerable advantages for society, university, theology and the church to conduct theological research and education of pastors at a secular state university like the University of Copenhagen. The disadvantage is foremost that learning from a practice‐theory‐practice model is not found in theological education at the secular university. In the case of Denmark, this is, however, more due to the theology and set up of the church than to the university, where it is commonplace to integrate practice in academic studies.
From Mission Theology Towards an Intercultural Theology—The German Way
Authors: Reppenhagen Martin
Published: December 2014

The rather young theological discipline of missiology is in a process of transition. Against the backdrop of a shift in gravity of the global church's geographical centre, and considering the rising number of contextual theologies and Christianities, as well as a continuously bad reputation of mission in the Western world, the discourse has shifted and is focusing on the term “intercultural theology.” Will “intercultural theology” replace “missiology,” and how important is the issue of mission in this debate?
Theological Education in a New Missional Era: A Personal Journey with Seven Theses
Authors: Rooms Nigel
Published: December 2014

The author's personal journey in discovering, developing, researching and practicing adult theological education in the church is rehearsed, pointing out key learning moments along the way. Out of this praxis seven theses are offered that set an agenda for theological education in the new missional era in which the church finds itself.
What Do the Theologically Educated Look Like?
Authors: Harrison Mike
Published: December 2014

What do the theologically educated look like? Nine outcomes of a theological education are suggested that respond to this question, outcomes particularly pertinent to the contemporary cultural setting and mission challenge of Western Europe. These outcomes are compared with the nine learning outcomes that the Church of England uses at the present time to assess candidates for ordained ministry. In the light of this comparison some broad recommendations are made for future emphases in theological education.
In Memoriam: Wolfhart Pannenberg (1928–2014)
Authors: Peters Ted
Published: December 2014

Prompted by the September 4, 2014 passing of a Continental titan of Protestant systematic theology, this article summarizes the life and thought of Wolfhart Pannenberg. A brief review is offered of his conversion from atheism to the Christian faith, student studies, and faculty positions along with his corpus of writings. An in‐depth analysis is offered of Pannenberg's key theological commitments to creation, eschatology, Christology, Trinity, retroactive ontology, prolepsis, anthropology, and the relationship between time and eternity. The scale and complexity and subtlety of Pannenberg's worldview renders it vulnerable to charges of incoherence; but few can doubt the masterful achievement of the gift of this person's life—a gift from God—to the world of Christian theology.
Theological Education at the Crossroads
Authors: Ladd Nick
Published: December 2014

Theological education and ministerial training must prepare people for a post‐Christendom context. Moving on from the subject‐object dualism of modernity, where ministry is seen as a professional task done to and for others, this article proposes that attending to the subjectivity of others is necessary for the formation of mature community, and for genuine missional engagement. It proposes a contextualised training in which students learn theologically reflective practice from the heart of Christian community.
Circulating cardiac biomarkers and postoperative atrial fibrillation in the OPERA trial
Authors: Masson Serge , Wu Jason H. Y. , Simon Caterina , Barlera Simona , Marchioli Roberto , Mariani Javier , Macchia Alejandro , Lombardi Federico , Vago Tarcisio , Aleksova Aneta , Dreas Lorella , Favaloro Roberto R. , Hershson Alejandro R. , Puskas John D. , Dozza Luca , Silletta Maria G. , Tognoni Gianni , Mozaffarian Dariush , Latini Roberto ,   the OPERA Investigators
Published: December 2014

Background

Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and predicts increased morbidity and mortality. Identification of patients at high risk of POAF with the help of circulating biomarkers may enable early preventive treatment but data are limited, especially in contemporary surgical patients.

Methods

Plasma concentrations of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity cardiac troponin T (hs‐cTnT) were measured at enrolment, on the morning of cardiac surgery, at end surgery, and 2 days postsurgery in 562 patients undergoing cardiac surgery, randomized to perioperative supplementation with oral fish oil or placebo in the Omega‐3 Fatty Acids for Prevention of Post‐Operative Atrial Fibrillation trial (OPERA). The primary endpoint was incident POAF lasting ≥ 30 s, centrally adjudicated and confirmed electrocardiographically.

Results

Higher levels of NT‐proBNP and hs‐cTnT before surgery were associated with older age, renal or cardiac dysfunction and EuroSCORE. NT‐proBNP peaked on postoperative day 2 (2172 [1238–3758] ng/L, median [Q1–Q3]), while hs‐cTnT peaked at the end of surgery (373 [188–660] ng/L). Fish oil supplementation did not alter the time course of the cardiac biomarkers (P > 0·05). Concentrations of NT‐proBNP or hs‐cTnT, on the morning of surgery, or changes in their level between morning of surgery and postsurgery, were not significantly associated with POAF after adjustment for clinical and surgical characteristics.

Conclusion

Among patients undergoing cardiac surgery, NT‐proBNP and hs‐cTnT are related to clinical and surgical characteristics, have different perioperative time courses but are not independently associated with risk of POAF.
Comparison of Recharge Estimation Methods During a Wet Period in a Karst Aquifer
Authors: Guardiola‐Albert Carolina , Martos‐Rosillo Sergio , Pardo‐Igúzquiza Eulogio , Durán Valsero Juan José , Pedrera Antonio , Jiménez‐Gavilán Pablo , Liñán Baena Cristina
Published: December 2014

Management of water resources, implying their appropriate protection, calls for a sound evaluation of recharge. Such assessment is very complex in karst aquifers. Most methods are developed for application to detrital aquifers, without taking into account the extraordinary heterogeneity of porosity and permeability of karst systems. It is commonly recommended to estimate recharge using multiple methods; however, differences inherent to the diverse methods make it difficult to clarify the accuracy of each result. In this study, recharge was estimated in a karst aquifer working in a natural regime, in a Mediterranean‐type climate, in the western part of the Sierra de las Nieves (southern Spain). Mediterranean climate regions are characterized by high inter‐annual rainfall variability featuring long dry periods and short intense wet periods, the latter constituting the most important contribution to aquifer water input. This paper aims to identify the methods that provide the most plausible range of recharge rate during wet periods. Six methods were tested: the classical method of Thornthwaite‐Mather, the Visual Balan code, the chloride balance method, and spatially distributed methods such as APLIS, a novel spatiotemporal estimation of recharge, and ZOODRM. The results help determine valid methods for application in the rest of the unit of study and in similar karst aquifers.
Mechanisms of pre‐B‐cell receptor checkpoint control and its oncogenic subversion in acute lymphoblastic leukemia
Authors: Buchner Maike , Swaminathan Srividya , Chen Zhengshan , Müschen Markus
Published: December 2014

Pre‐B cells within the bone marrow represent the normal counterpart for most acute lymphoblastic leukemia (ALL). During normal early B‐cell development, survival and proliferation signals are dominated by cytokines, particularly interleukin‐7 (IL‐7) for murine developing B cells. With expression of a functional pre‐B‐cell receptor (BCR), cytokine signaling is attenuated and the tonic/autonomous pre‐BCR signaling pathway provides proliferation as well as differentiation signals. In this review, we first describe checkpoint mechanisms during normal B‐cell development and then discuss how genetic lesions in these pathways function as oncogenic mimicries and allow transformed pre‐B cells to bypass checkpoint control. We focus on cytokine receptor signaling that is mimicked by activating lesions in receptor subunits or downstream mediators as well as aberrant activation of non‐B lymphoid cytokine receptors. Furthermore, we describe the molecular switch from cytokine receptor to pre‐BCR signaling, how this pathway is of particular importance for certain ALL subtypes, and how pre‐BCR signaling is engaged by genetic lesions, such as BCR‐ABL1. We discuss the transcriptional control mechanisms downstream of both cytokine‐ and pre‐BCR signaling and how normal checkpoint control mechanisms are circumvented in pre‐B ALL. Finally, we highlight new therapeutic concepts for targeted inhibition of oncogenic cytokine or pre‐BCR signaling pathways.