bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the relationship between charismatic leadership and the lower-order factors of LMX
Authors: Salvaggio Trent , Kent Thomas W.
Published: January 2017

Purpose

The purpose of this paper is to test the effects of a followers’ perception of charisma to the followers’ perceived quality of each of the four sub-dimensions of LMX quality, and the moderating effect of communication frequency on such a relationship. The study hopes to assess the relationship of the four sub-factors of LMX to charisma and, thereby, to advance the current understanding of relationship-based views of leadership.

Design/methodology/approach

In total, 208 employed adults who are currently residing within the USA completed surveys that assessed charisma, LMX and it’s sub-factors, and communication frequency. The surveys were validated and the relationships between the variables were tested using partial least squares regression.

Findings

Charismatic leadership was shown to have significant effects on all the LMX sub-factors suggesting that charisma is not a simple trait possessed by some leaders. Additionally, the data suggests that there is a significant yet different level of effect of communication frequency on all the LMX sub-factors.

Research limitations/implications

Implications of the research findings are discussed; however, there are some shortcomings in the research. As the variables of communication frequency and LMX quality were rated by the same individual, a limitation to this study exists by way of possible same source bias. A further limitation results from the measurement method utilized to determine communication frequency and its dependence upon the ability of the survey respondent to accurately recall this information free from any type of recall bias (Raphael, 1987). Further study needs to be done into the nature of the moderating effects present on the four lower order factors of LMX. If there are intervening factors that influence the quality of the moderating effects, such as role expectation and role congruence, then the authors may be able to gain further insight into the positive and negative nature of these moderating effects.

Practical implications

The findings suggest that charisma is not a simple, one-dimensional factor and also suggests that the authors need to reconceptualize the ideas of charisma. At a minimum, the authors must rethink how to train people to become leaders.

Originality/value

The study advances the understanding of the relationship between charisma and LMX and its composite factors.
Factors influencing word of mouth behaviour in the restaurant industry
Authors: Jalilvand Mohammad Reza , Salimipour Sirous , Elyasi Mehdi , Mohammadi Mehdi
Published: January 2017

Purpose

Restaurants with limited promotion budgets depend mainly on word of mouth (WOM) among customers. WOM seems particularly important to the marketing of services. This is because services are experiential in nature and difficult to assess before purchase. In the restaurants context there is little research on WOM. The purpose of this paper is to examine the factors that may influence tourists’ WOM about restaurants implying on the critical role of relationship quality.

Design/methodology/approach

A comprehensive literature review is conducted to identify the major factors influencing WOM in the context of restaurant industry. The study utilizes self-administered questionnaire survey and the target population are the customers who have referred to the restaurants of Tehran, Iran. A convenience sampling approach was utilized to collect a sample of 326 customers. A structural equation modeling procedure is applied to the examination of the antecedents of WOM.

Findings

The paper found that food quality, personal interaction quality, physical environment quality, and perceived value influence WOM behavior of customer in an indirect way through relationship quality.

Practical implications

This research conjectured that an understanding of factors that influence the tourist to talk each other about a given restaurant are worthy of additional research. Consequently, the study helps to understand how these factors can provide alternative sources of marketing to attract the long-term economic sustainability of restaurant industry in Iran.

Originality/value

To the authors’ knowledge, this research will be the first attempt to explore influential factors on WOM in restaurant industry focusing on the critical role of relationship quality. It is expected that researchers will find this research a contribution to the WOM literature, particularly in restaurant industry.
Investigating young customers’ retail purchase embarrassment
Authors: Sarkar Juhi Gahlot , Sarkar Abhigyan
Published: January 2017

Purpose

The purpose of this paper is to examine the inter-relationships between product category embarrassment, consumption contexts, individual’s attachment styles, and their combined effects on individual’s preference toward online and physical store channels while buying embarrassing products.

Design/methodology/approach

Experimental design was employed by taking a sample of young adult students.

Findings

The results of this study shows that embarrassing product class and social consumption context can potentially elicit embarrassment. Anxiously attached individuals are more prone to be embarrassed compared to the individuals adopting secure and avoidant attachment styles.

Originality/value

Value of the paper lies in empirically investigating the complex inter-relationships between product class-specific embarrassment, context specific embarrassment, individual’s attachment styles and buying channel selection.
Environmental consciousness and brand equity
Authors: Misra Siddharth , Panda Rajeev Kumar
Published: January 2017

Purpose

The purpose of this paper is to investigate the activities of environmental consciousness from socio-psychographic perspectives and hence evaluates its effect on brand equity through intervening elements of environmental attributes (EAt). It further attempts to research the effect of the environmental performance, environmental communication and environmental positioning in enhancing brand equity. Indian refrigeration industry, particularly the air conditioners and refrigerator brands are chosen to convey and receive the research inputs as their impact on environment is easily interpretable.

Design/methodology/approach

A hypothesized model comprising the environment consciousness and association dimensions with brand equity is framed. In total, 74 expert respondents from four state capital cities of India participated in the survey and the model has been tested in the scope of analytical hierarchy process (AHP).

Findings

The result shows that the EAt and activities can be prioritized and subsequently efficient resource allocation can be done. It also gives theoretical arguments to legitimize the environmental practices.

Practical implications

On the other hand, clients have numerous options, and a competitive advantage may not be maintained. Regardless of the fact that clients are environmentally conscious of a given refrigeration brand at the present time that they are utilizing, they may observe that they are much more charmed with a competitors’ enhanced environmental dimensions. All methods that take a try at an enhanced brand equity must be continually determined by environmental consciousness. The above can be accomplished if the evaluations of competitors by the clients are known. The AHP-ECBE technique depicted in this study accordingly helps refrigeration organization to devise and keep up a pertinent, focused plan for persistent improvements in environmental dimensions. It offers a “greater image” in brand equity administration.

Originality/value

If legitimately done in a generalized way, environmental activities like eco-literacy, interpersonal influence and value orientation can impact EAt and contribute in building brand equity.
The changing contribution of top‐down and bottom‐up limitation of mesopredators during 220 years of land use and climate change
Authors: Pasanen‐Mortensen Marianne , Elmhagen Bodil , Lindén Harto , Bergström Roger , Wallgren Märtha , van der Velde Ype , Cousins Sara A.O.
Published: January 2017

Apex predators may buffer bottom‐up driven ecosystem change, as top‐down suppression may dampen herbivore and mesopredator responses to increased resource availability. However, theory suggests that for this buffering capacity to be realized, the equilibrium abundance of apex predators must increase. This raises the question: will apex predators maintain herbivore/mesopredator limitation, if bottom‐up change relaxes resource constraints?

Here, we explore changes in mesopredator (red fox Vulpes vulpes) abundance over 220 years in response to eradication and recovery of an apex predator (Eurasian lynx Lynx lynx), and changes in land use and climate which are linked to resource availability.

A three‐step approach was used. First, recent data from Finland and Sweden were modelled to estimate linear effects of lynx density, land use and winter temperature on fox density. Second, lynx density, land use and winter temperature was estimated in a 22 650 km2 focal area in boreal and boreo‐nemoral Sweden in the years 1830, 1920, 2010 and 2050. Third, the models and estimates were used to project historic and future fox densities in the focal area.

Projected fox density was lowest in 1830 when lynx density was high, winters cold and the proportion of cropland low. Fox density peaked in 1920 due to lynx eradication, a mesopredator release boosted by favourable bottom‐up changes – milder winters and cropland expansion. By 2010, lynx recolonization had reduced fox density, but it remained higher than in 1830, partly due to the bottom‐up changes. Comparing 1830 to 2010, the contribution of top‐down limitation decreased, while environment enrichment relaxed bottom‐up limitation. Future scenarios indicated that by 2050, lynx density would have to increase by 79% to compensate for a projected climate‐driven increase in fox density.

We highlight that although top‐down limitation in theory can buffer bottom‐up change, this requires compensatory changes in apex predator abundance. Hence apex predator recolonization/recovery to historical levels would not be sufficient to compensate for widespread changes in climate and land use, which have relaxed the resource constraints for many herbivores and mesopredators. Variation in bottom‐up conditions may also contribute to context dependence in apex predator effects.
Warmer temperatures reduce the influence of an important keystone predator
Authors: Bonaviri Chiara , Graham Michael , Gianguzza Paola , Shears Nick T.
Published: January 2017

Predator–prey interactions may be strongly influenced by temperature variations in marine ecosystems. Consequently, climate change may alter the importance of predators with repercussions for ecosystem functioning and structure.

In North‐eastern Pacific kelp forests, the starfish Pycnopodia helianthoides is known to be an important predator of the purple sea urchin Strongylocentrotus purpuratus. Here we investigated the influence of water temperature on this predator–prey interaction by: (i) assessing the spatial distribution and temporal dynamics of both species across a temperature gradient in the northern Channel Islands, California, and (ii) investigating how the feeding rate of P. helianthoides on S. purpuratus is affected by temperature in laboratory tests.

On average, at sites where mean annual temperatures were <14 °C, P. helianthoides were common, S. purpuratus was rare and kelp was persistent, whereas where mean annual temperatures exceeded 14 °C, P. helianthoides and kelp were rare and S. purpuratus abundant. Temperature was found to be the primary environmental factor influencing P. helianthoides abundance, and in turn P. helianthoides was the primary determinant of S. purpuratus abundance. In the laboratory, temperatures >16 °C (equivalent to summer temperatures at sites where P. helianthoides were rare) reduced predation rates regardless of predator and prey sizes, although larger sea urchins were consumed only by large starfishes.

These results clearly demonstrate that the effect of P. helianthoides on S. purpuratus is strongly mediated by temperature, and that the local abundance and predation rate of P. helianthoides on sea urchins will likely decrease with future warming. A reduction in top‐down control on sea urchins, combined with other expected impacts of climate change on kelp, poses significant risks for the persistence of kelp forests in the future.
Towards a trait‐based ecology of wetland vegetation
Authors: Moor Helen , Rydin Håkan , Hylander Kristoffer , Nilsson Mats B. , Lindborg Regina , Norberg Jon
Published: January 2017

Functional traits mechanistically capture plant responses to environmental gradients as well as plant effects on ecosystem functioning. Yet most trait‐based theory stems from terrestrial systems and extension to other habitats can provide new insights.

Wetlands differ from terrestrial systems in conditions (e.g. soil water saturation, anoxia, pH extremes), plant adaptations (e.g. aerenchyma, clonality, ubiquity of bryophytes) and important processes (e.g. denitrification, peat accumulation, methane emission). Wetland plant adaptations and trait (co‐)variation can be situated along major plant trait trade‐off axes (e.g. the resource economics spectrum), but soil saturation represents a complex stress gradient beyond a simple extension of commonly studied water availability gradients.

Traits that affect ecosystem functioning overlap with patterns in terrestrial systems. But wetland‐specific traits that mediate plant effects on soil redox conditions, microbial communities and on water flow, as well as trait spectra of mosses, vary among wetland types.

Synthesis. With increasing availability of quantitative plant traits a trait‐based ecology of wetlands is emerging, with the potential to advance process‐based understanding and prediction. We provide an interactive cause‐and‐effect framework that may guide research efforts to disentangle the multiple interacting processes involved in scaling from environmental conditions to ecosystem functioning via plant communities.
The ectomycorrhizal basidiomycete Hebeloma cylindrosporum undergoes early waves of transcriptional reprogramming prior to symbiotic structures differentiation
Authors: Doré Jeanne , Kohler Annegret , Dubost Audrey , Hundley Hope , Singan Vasanth , Peng Yi , Kuo Alan , Grigoriev Igor V. , Martin Francis , Marmeisse Roland , Gay Gilles
Published: January 2017

To clarify the early molecular interaction between ectomycorrhizal partners, we performed a RNA‐Seq study of transcriptome reprogramming of the basidiomycete Hebeloma cylindrosporum before symbiotic structure differentiation with Pinus pinaster. Mycorrhiza transcriptome was studied for comparison. By reference to asymbiotic mycelium, 47 and 46 genes were specifically upregulated over fivefold (p ≤ 0.05) upon rhizosphere colonization and root adhesion respectively. Other 45 were upregulated throughout the symbiotic interaction, from rhizosphere colonization to differentiated mycorrhizas, whereas 274 were specifically upregulated in mycorrhizas. Although exoproteome represents 5.6% of H. cylindrosporum proteome, 38.5% of the genes upregulated upon pre‐infectious root colonization encoded extracellular proteins. The proportion decreased to 23.5% in mycorrhizas. At all studied time points, mycorrhiza‐induced small secreted proteins (MiSSPs), representing potential effectors, were over‐represented among upregulated genes. This was also the case for carbohydrate‐active enzymes (CAZymes). Several CAZymes were upregulated at all studied stages of the interaction. Consistent with a role in fungal morphogenesis and symbiotic interface differentiation, CAZymes over‐expressed before and upon root attachment targeted fungal and both fungal and plant polysaccharides respectively. Different hydrophobins were upregulated upon early root adhesion, in mycorrhizas or throughout interaction. The functional classification of genes upregulated only in mycorrhizas pointed to intense metabolic activity and nutritional exchanges.
Moderately elevated blood pressure during pregnancy and odds of hypertension later in life: the POUCHmoms longitudinal study
Authors: Dunietz GL , Strutz KL , Holzman C , Tian Y , Todem D , Bullen BL , Catov JM
Published: January 2017

Objective

Hypertensive disorders in pregnancy signal an increased risk of cardiovascular disease for women. However, future hypertension risk among pregnant women with moderately elevated blood pressure (BP) is unknown. We examined associations among moderately elevated BP or hypertensive disorders during pregnancy and later prehypertension or hypertension.

Design

Longitudinal cohort study.

Setting

Five communities in Michigan, USA.

Sample

Data are from pregnant women enrolled in the Pregnancy Outcomes and Community Health Study. We included 667 women with gestational BP measurements who participated in the POUCHmoms Study follow‐up 7–15 years later.

Methods

Moderately elevated BP was defined as two measures of systolic BP ≥ 120 mmHg or diastolic BP ≥80 mmHg among women without a hypertensive disorder. Weighted multinomial logistic regression models estimated odds of prehypertension or hypertension at follow‐up, adjusted for maternal confounders and time to follow‐up.

Main outcome measures

Prehypertension or hypertension.

Results

Women meeting the moderately elevated BP criteria (64%) had significantly higher odds of hypertension at follow‐up (adjusted odds ratio 2.6; 95% confidence interval 1.2–5.5). These increased odds were observed for moderately elevated BP first identified before or after 20 weeks of gestation, and for elevated systolic BP alone or combined with elevated diastolic BP.

Conclusions

Moderately elevated BP in pregnancy may be a risk factor for future hypertension. Pregnancy offers an opportunity to identify women at risk for hypertension who may not have been identified otherwise.

Tweetable abstract

Moderately elevated blood pressure in pregnancy may be associated with hypertension later in life.
Gene expression profiles of the Southern house mosquito Culex quinquefasciatus during exposure to permethrin
Authors: Reid William R. , Zhang Lee , Gong Youhui , Li Ting , Liu Nannan
Published: January 2017

Insecticide resistance is a major obstacle to the management of disease‐vectoring mosquitoes worldwide. The genetic changes and detoxification genes involved in insecticide resistance have been extensively studied in populations of insecticide‐resistant mosquitoes, however few studies have focused on the resistance genes upregulated upon insecticide exposure and the possible regulation pathways involved in insecticide resistance. To characterize the changes in gene expression during insecticide exposure, and to investigate the possible connection of known regulation pathways with insecticide resistance, we conducted RNA‐Seq analysis of a highly permethrin‐resistant strain of Culex quinquefasciatus following permethrin exposure. Gene expression profiles revealed a total of 224 upregulated and 146 downregulated genes when compared to a blank acetone carrier treated control, respectively, suggesting that there were multiple, but specific genes involved in permethrin resistance. Functional enrichment analysis showed that the upregulated genes contained multiple detoxification genes including a glutathione S‐transferase and multiple cytochrome P450 genes, as well as several immune‐related genes, while the downregulated genes consisted primarily of proteases and carbohydrate metabolism and transport. Further analysis showed that permethrin exposure resulted in a decrease in the expression of serum storage proteins and likely represented a delay in the development of the fourth instar possibly due to a decrease in feeding. This effect was more pronounced in an insecticide‐resistant strain than in an insecticide‐susceptible strain and may represent a behavioral mechanism of insecticide resistance in Culex mosquitoes.
Development of a voided urine assay for detecting prostate cancer non‐invasively: a pilot study
Authors: Trabulsi Edouard J. , Tripathi Sushil K. , Gomella Leonard , Solomides Charalambos , Wickstrom Eric , Thakur Mathew L.
Published: January 2017

Objective

To validate a hypothesis that prostate cancer can be detected non‐invasively by a simple and reliable assay by targeting genomic VPAC receptors expressed on malignant prostate cancer cells shed in voided urine.

Patients/Subjects and Methods

VPAC receptors were targeted with a specific biomolecule, TP4303, developed in our laboratory. With an Institutional Review Board exempt approval of use of de‐identified discarded samples, an aliquot of urine collected as a standard of care, from patients presenting to the urology clinic (207 patients, 176 men and 31 women, aged ≥21 years) was cytospun. The cells were fixed and treated with TP4303 and 4,6‐diamidino‐2‐phenylindole (DAPI). The cells were then observed under a microscope and cells with TP4303 orange fluorescence around the blue (DAPI) nucleus were considered ‘malignant’ and those only with a blue nucleus were regarded as ‘normal’. VPAC presence was validated using receptor blocking assay and cell malignancy was confirmed by prostate cancer gene profile examination.

Results

The urine specimens were labelled only with gender and presenting diagnosis, with no personal health identifiers or other clinical data. The assay detected VPAC positive cells in 98.6% of the men with a prostate cancer diagnosis (141), and none of the 10 men with benign prostatic hyperplasia. Of the 56 ‘normal’ patients, 62.5% (35 patients, 10 men and 25 women) were negative for VPAC cells; 19.6% (11, 11 men and no women) had VPAC positive cells; and 17.8% (10, four men and six women) were uninterpretable due to excessive crystals in the urine. Although data are limited, the sensitivity of the assay was 99.3% with a confidence interval (CI) of 96.1–100% and the specificity was 100% with a CI of 69.2–100%. Receptor blocking assay and fluorescence‐activated cell sorting (FACS) analyses demonstrated the presence of VPAC receptors and gene profiling examinations confirmed that the cells expressing VPAC receptors were malignant prostate cancer cells.

Conclusion

These preliminary data are highly encouraging and warrant further evaluation of the assay to serve as a simple and reliable tool to detect prostate cancer non‐invasively.
Cetuximab strongly enhances immune cell infiltration into liver metastatic sites in colorectal cancer
Authors: Inoue Yuka , Hazama Shoichi , Suzuki Nobuaki , Tokumitsu Yukio , Kanekiyo Shinsuke , Tomochika Shinobu , Tsunedomi Ryouichi , Tokuhisa Yoshihiro , Iida Michihisa , Sakamoto Kazuhiko , Takeda Shigeru , Ueno Tomio , Yoshino Shigefumi , Nagano Hiroaki
Published: January 2017

Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody‐dependent cell‐mediated cytotoxicity via immune cells, and a new immune‐related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy. The inflammatory cells in the liver metastatic sites were assessed by hematoxylin–eosin staining, focusing on the invasive margin. The overall inflammatory reaction and number of lymphoid cells were assessed with a four‐point scoring system. We then assessed immune cell infiltration (CD3, CD8 and CD56) in 15 liver metastatic sites. Hematoxylin–eosin staining demonstrated more inflammatory cells in the chemotherapy with cetuximab group than in the other groups (P < 0.001). Of note, inflammatory cells were found in intratumoral areas, and the destruction of cancer cell foci was observed in the chemotherapy with cetuximab group. Moreover, a higher infiltration of CD3+ (P = 0.003), CD8+ (P = 0.003) and CD56+ (P = 0.001) cells was observed in the chemotherapy with cetuximab group than in the other groups. These results suggest that cetuximab might have an immune‐enhancing effect. As such, the immune‐related mechanism of action of cetuximab may enhance the efficacy of combination therapy, such as chemotherapy and immunotherapy using therapeutic peptides.
Crucial role of carbonic anhydrase IX in tumorigenicity of xenotransplanted adult T‐cell leukemia‐derived cells
Authors: Nasu Kentaro , Yamaguchi Kazunori , Takanashi Tomoka , Tamai Keiichi , Sato Ikuro , Ine Shoji , Sasaki Osamu , Satoh Kennichi , Tanaka Nobuyuki , Tanaka Yuetsu , Fukushima Takuya , Harigae Hideo , Sugamura Kazuo
Published: January 2017

Carbonic anhydrase IX (CA9) is a membrane‐associated carbonic anhydrase that regulates cellular pH, is upregulated in various solid tumors, and is considered to be a therapeutic target. Here, we describe the essential role of CA9 in the tumorigenicity of cells derived from human adult T‐cell leukemia/lymphoma (ATL). We previously established the highly tumorigenic ST1‐N6 subline from the ATL‐derived ST1 cell line by serial xenotransplantation in NOG mice. In the present study, we first show that CA9 expression is strongly enhanced in ST1‐N6 cells. We then sorted ST1 cells by high or low CA9 expression and established ST1‐CA9high and ST1‐CA9low sublines. ST1‐CA9high cells, like ST1‐N6 cells, were more strongly tumorigenic than ST1‐CA9low or parental ST1 cells when injected into NOG mice. Knockdown of CA9 with shRNAs suppressed the ability of ST1‐CA9high cells to initiate tumors, and the tumorigenicity of ST1 cells was significantly enhanced by introducing wild‐type CA9 or a CA9 mutant with deletion of an intracytoplasmic domain. However, a CA9 with point mutations in the catalytic site did not increase the tumorigenicity of ST1 cells. Furthermore, we detected a small population of CA9+CD25+ cells in lymph nodes of ATL patients. These findings suggest that CA9, and particularly its carbonic anhydrase activity, promotes the tumorigenicity of ATL‐derived cells and may be involved in malignant development of lymphoma‐type ATL.
Erythropoietic protoporphyria a clinical and molecular study from Lebanon: Ferrochelatase a potential tumor suppressor gene in colon cancer
Authors: Kadara H. , Nemer G. , Safi R. , Rebeiz N. , Daou L. , Delbani D. , Btadini W. , Abbas O. , Tofaili M. , Bitar F. , Kibbi A.G. , Shimomura Y. , Kurban M.
Published: January 2017

Erythropoietic protoporphyria (EPP) is a rare cutaneous and systemic disease caused by mutations in the ferrochelatase gene (FECH). The molecular underpinnings of EPP in Middle Eastern populations and relative to other ethnic groups secondary to increased consanguinity are unknown. To understand the molecular pathogenesis of Middle Eastern EPP, we surveyed clinicopathological and molecular features in 6 large consanguineous families from Lebanon and Syria presenting with cutaneous and systemic features consistent with EPP. We observed 30% increased liver disease and 20% elevated end‐stage liver complications in our EPP cohort compared to EPP patients previously reported elsewhere. In addition, Middle Eastern EPP patients in our cohort exhibited uniquely an increased incidence of colon cancer. Sequence analysis revealed 2 novel non‐synonymous FECH mutations in the studied families designated p.M294T and p.I230M. In addition, FECH activity was significantly decreased (6%) in fibroblasts obtained from sun‐exposed sites in a patient with p.M294T mutation, whereas in sharp contrast, protected sites from the same patient exhibited 54% activity for the gene. We also found that sun‐exposed fibroblasts, relative to sun‐protected and control fibroblasts, exhibited suppressed growth and atypical morphology in vitro, and that these effects were alleviated when the cells were co‐cultured with sun‐protected fibroblasts. Our findings on the increased incidence of colon cancer in EPP patients prompted us to survey FECH expression patterns in cancer. Using publicly available microarray datasets we found that FECH mRNA was largely significantly decreased in colon adenocarcinomas relative to normal colon tissues. Our findings suggest that families with autosomal recessive EPP should be screened more extensively for systemic involvement including liver diseases and colon cancer, and point to a previously unknown yet plausible tumor suppressor role for FECH in colon malignancy.
Bilateral multifocal upper extremity atypical granular cell tumors presenting as long‐standing right wrist and left hand masses in a 15‐year‐old African‐American female
Authors: R. DeWall Michael , Montgomery Corey O. , Gardner Jerad M.
Published: January 2017

Granular cell tumor (GrCT) is a benign nerve sheath tumor. Atypical and malignant variants of GrCT are rare but have been well described. We report a case of multifocal symmetric atypical GrCT in the bilateral hand/wrists of a 15‐year‐old African‐American female. The initial clinical impression for both masses was favored to be ganglion cysts. Ultrasound findings of both masses revealed hypoechoic soft tissue lesions with some internal echogenicity favoring complex cysts. On excision, both masses were histologically circumscribed, lobulated and attached to tendon. Large epithelioid cells with abundant granular eosinophilic cytoplasm arranged in syncytial cords and trabeculae percolated through collagen. Many cells had pleomorphism and/or prominent nucleoli. Mitotic figures, spindling, high nuclear‐to‐cytoplasmic ratio and necrosis were absent. Both masses showed diffuse S100 protein but negative desmin and pancytokeratin expression. Ki‐67 index was 1% to 2%. p53 was positive in 5% to 10% of nuclei. Both masses met criteria for atypical (but not malignant) GrCT. Our case shows that atypical GrCT may be not only multifocal but also symmetric. We speculate that migration of defective neural crest stem cells along both upper limb buds during embryogenesis may have allowed these essentially identical tumors to arise in similar locations bilaterally simultaneously.
Efficacy and safety of fixed‐dose combination therapy, alogliptin plus metformin, in Asian patients with type 2 diabetes: A phase 3 trial
Authors: Ji Linong , Li Ling , Kuang Jian , Yang Tao , Kim Dong‐Jun , Kadir Azidah A. , Huang Chien‐Ning , Lee Douglas
Published: January 2017

This study evaluated the efficacy and safety of 26 weeks of twice‐daily (BID) alogliptin + metformin fixed‐dose combination (FDC) therapy in Asian patients with type 2 diabetes. Patients aged 18 to 75 years with hemoglobin A1c (HbA1c) of 7.5% to 10.0% after ≥2 months of diet and exercise and a 4‐week placebo run‐in were enrolled. Eligible patients were randomized (1:1:1:1) to placebo, alogliptin 12.5 mg BID, metformin 500 mg BID or alogliptin 12.5 mg plus metformin 500 mg FDC BID. The primary endpoint was change in HbA1c from baseline to end of treatment (Week 26). In total, 647 patients were randomized. The least‐squares mean change in HbA1c from baseline to Week 26 was −0.19% with placebo, −0.86% with alogliptin, −1.04% with metformin and −1.53% with alogliptin + metformin FDC. Alogliptin + metformin FDC was significantly more effective (
P
 < .0001) in lowering HbA1c than either alogliptin or metformin alone. The safety profile of alogliptin + metformin FDC was similar to that of the individual components alogliptin and metformin. The study demonstrated that treatment with alogliptin + metformin FDC BID resulted in better glycaemic control than either monotherapy and was well tolerated in Asian patients with type 2 diabetes.
Soluble transferrin receptor and risk of type 2 diabetes in the obese and nonobese
Authors: Fernández‐Cao José C. , Arija Victoria , Aranda Núria , Basora Josep , Diez‐Espino Javier , Estruch Ramón , Fitó Montse , Corella Dolores , Salas‐Salvadó Jordi
Published: January 2017

Background

Studies evaluating the relationship between soluble transferrin receptor (sTfR), a biomarker inversely related to body iron stores, and risk of type 2 diabetes mellitus (T2DM) are scarce and inconclusive. Furthermore, sTfR concentrations have been observed to be significantly higher in obese than in nonobese individuals. Therefore, the aim of this study was to assess the relationship between sTfR and the risk of T2DM in obese and nonobese subjects.

Design

A nested case–control study of 153 cases of newly diagnosed diabetic subjects, 73 obese and 80 nonobese, and 306 individually matched controls, 138 obese and 166 nonobese, who did not develop T2DM for a median 6‐year follow‐up (interquartile range: 3·9–6·5) was conducted using data from the PREvention with MEDiterranean Diet (PREDIMED) cohort (http://www.controlled-trials.com/ISRCTN35739639). Cases and controls were matched for age (≤ 67 vs. > 67 years), gender, dietary intervention group and BMI (≤ 27 vs. > 27 kg/m2).

Results

Waist circumference is the main determinant of sTfR concentrations in the whole sample (β = 0·476, P < 0·001), in the obese (β = 0·802, P < 0·001) and the nonobese (β = 0·455, P = 0·003). Furthermore, sTfR is directly associated with the risk of T2DM in obese individuals (OR = 2·79; 95% CI: 1·35–5·77, P = 0·005) and inversely associated in nonobese individuals (OR = 0·40; 95% CI: 0·20–0·79, P = 0·015).

Conclusions

The association between sTfR levels and risk of T2DM in a population at high cardiovascular risk depend on the presence or absence of obesity. While in nonobese subjects elevated sTfR levels are associated with a decreased risk of developing T2DM, in obese subjects the risk increases. This suggests that obesity alters the relationship between sTfR and T2DM incidence.
Knowledge and its Objects: Revisiting the Bounds of Sense
Authors: Cassam Quassim
Published: January 2017

The Kantian project of investigating the necessary structure of experience presupposes answers to three questions: what is the purpose of such an investigation, what is the source of necessary features of experience, and by what means is it possible to establish the necessary structure of experience? This paper is a critical examination of Strawson's answers to these questions in The Bounds of Sense and his later work. The realism that is implicit in The Bounds of Sense is much more explicit in Strawson's later work but relies on problematic assumptions about the relationship between epistemology and metaphysics.
Binding and processing of β‐lactam antibiotics by the transpeptidase LdtMt2 from Mycobacterium tuberculosis
Authors: Steiner Eva Maria , Schneider Gunter , Schnell Robert
Published: January 2017

β‐lactam antibiotics represent a novel direction in the chemotherapy of tuberculosis that brings the peptidoglycan layer of the complex mycobacterial cell wall in focus as a therapeutic target. Peptidoglycan stability in Mycobacterium tuberculosis, especially during infection, relies on the nonconventional peptide cross‐links formed by l,d‐transpeptidases. These enzymes are known to be inhibited by β‐lactams, primarily carbapenems, leading to a stable covalent modification at the enzyme active site. A panel of 16 β‐lactam antibiotics was characterized by inhibition kinetics, mass spectrometry, and x‐ray crystallography to identify efficient compounds and study their action on the essential transpeptidase, LdtMt2. Members of the carbapenem class displayed fast binding kinetics, but faropenem, a penem type compound showed a three to four time higher rate in the adduct formation. In three cases, mass spectrometry indicated that carbapenems may undergo decarboxylation, while faropenem decomposition following the acylation step results in a small 87 Da β‐OH‐butyryl adduct bound at the catalytic cysteine residue. The crystal structure of LdtMt2 at 1.54 Å resolution with this fragment bound revealed that the protein adopts a closed conformation that shields the thioester bond from the solvent, which is in line with the high stability of this dead‐end complex observed also in biochemical assays.

Database

Structural data are available in Protein Data Bank under the accession numbers 5LB1 and 5LBG.
Large extents of intensive land use limit community reorganization during climate warming
Authors: Oliver Tom H. , Gillings Simon , Pearce‐Higgins James W. , Brereton Tom , Crick Humphrey Q. P. , Duffield Simon J. , Morecroft Michael D. , Roy David B.
Published: January 2017

Climate change is increasingly altering the composition of ecological communities, in combination with other environmental pressures such as high‐intensity land use. Pressures are expected to interact in their effects, but the extent to which intensive human land use constrains community responses to climate change is currently unclear. A generic indicator of climate change impact, the community temperature index (CTI), has previously been used to suggest that both bird and butterflies are successfully ‘tracking’ climate change. Here, we assessed community changes at over 600 English bird or butterfly monitoring sites over three decades and tested how the surrounding land has influenced these changes. We partitioned community changes into warm‐ and cold‐associated assemblages and found that English bird communities have not reorganized successfully in response to climate change. CTI increases for birds are primarily attributable to the loss of cold‐associated species, whilst for butterflies, warm‐associated species have tended to increase. Importantly, the area of intensively managed land use around monitoring sites appears to influence these community changes, with large extents of intensively managed land limiting ‘adaptive’ community reorganization in response to climate change. Specifically, high‐intensity land use appears to exacerbate declines in cold‐adapted bird and butterfly species, and prevent increases in warm‐associated birds. This has broad implications for managing landscapes to promote climate change adaptation.
National implementation of a mental health service model: A survey of Crisis Resolution Teams in England
Authors: Lloyd‐Evans Brynmor , Paterson Bethan , Onyett Steve , Brown Ellie , Istead Hannah , Gray Richard , Henderson Claire , Johnson Sonia
Published: January 2017

In response to pressures on mental health inpatient beds and a perceived ‘crisis in acute care’, Crisis Resolution Teams (CRTs), acute home treatment services, were implemented nationally in England following the NHS Plan in the year 2000: an unprecedentedly prescriptive policy mandate for three new types of functional community mental health team. We examined the effects of this mandate on implementation of the CRT service model. Two hundred and eighteen CRTs were mapped in England, including services in all 65 mental health administrative regions. Eighty‐eight percent (n = 192) of CRT managers in England participated in an online survey. CRT service organization and delivery was highly variable. Nurses were the only professional group employed in all CRT staff teams. Almost no teams adhered fully to government implementation guidance. CRT managers identified several aspects of CRT service delivery as desirable but not routinely provided. A national policy mandate and government guidance and standards have proved insufficient to ensure CRT implementation as planned. Development and testing of resources to support implementation and monitoring of a complex mental health intervention is required.
A comparison of approaches for stratifying on the propensity score to reduce bias
Authors: Linden Ariel
Published: January 2017

Rationale, aims, and objectives

Stratification is a popular propensity score (PS) adjustment technique. It has been shown that stratifying the PS into 5 quantiles can remove over 90% of the bias due to the covariates used to generate the PS. Because of this finding, many investigators partition their data into 5 quantiles of the PS without examining whether a more robust solution (one that increases covariate balance while potentially reducing bias in the outcome analysis) can be found for their data. Two approaches (referred to herein as PSCORE and PSTRATA) obtain the optimal stratification solution by repeatedly dividing the data into strata until balance is achieved between treatment and control groups on the PS. These algorithms differ in how they partition the data, and it is not known which is better, or if either is better than a 5‐quantile default approach, for reducing bias in treatment effect estimates.

Method

Monte Carlo simulations and empirical data are used to assess whether PS strata defined by PSCORE, PSTRATA, or 5 quantiles is best at reducing bias in treatment effect estimates, when used within a marginal mean weighting framework (MMWS). These estimates are further compared to results derived using inverse probability of treatment weights (IPTW).

Results

PSTRATA was slightly better than PSCORE in balancing covariates and reducing bias, while both approaches outperformed the 5‐quantile approach. Overall MMWS using any stratification method outperformed IPTW.

Conclusions

Investigators should routinely use stratification approaches that obtain the optimal stratification solution, rather than simply partitioning the data into 5 quantiles of the PS. Moreover, MMWS (in conjunction with an optimal stratification approach) should be considered as an alternative to IPTW in studies that use PS weights.
Prevalence, geographic distribution and phenotypic differences of Piscirickettsia salmonis EM‐90‐like isolates
Authors: Saavedra J , Hernandez N , Osses A , Castillo A , Cancino A , Grothusen H , Navas E , Henriquez P , Bohle H , Bustamante F , Bustos P , Mancilla M
Published: January 2017

Early reports accounted for two main genotypes of Piscirickettsia salmonis, a fish pathogen and causative agent of piscirickettsiosis, placing the single isolate EM‐90 apart from the prototypic LF‐89 and related isolates. In this study, we provide evidence that, contrary to what has been supposed, the EM‐90‐like isolates are highly prevalent and disseminated across Chilean marine farms. Molecular analysis of 507 P. salmonis field isolates derived from main rearing areas, diverse hosts and collected over 6 years, revealed that nearly 50% of the entire collection were indeed typed as EM‐90‐like. Interestingly, these isolates showed a marked host preference, being recovered exclusively from Atlantic salmon (Salmo salar) samples. Although both strains produce undistinguishable pathological outcomes, differences regarding growth kinetics and susceptibility to the antibiotics and bactericidal action of serum could be identified. In sum, our results allow to conclude that the EM‐90‐like isolates represent an epidemiologically relevant group in the current situation of piscirickettsiosis. Based on the consistency between genotype and phenotype exhibited by this strain, we point out the need for genotypic studies that may be as important for the Chilean salmon industry as the continuous surveillance of antimicrobial susceptibility patterns.
Uncovering iron regulation with species‐specific transcriptome patterns in Atlantic and coho salmon during a Caligus rogercresseyi infestation
Authors: Valenzuela‐Muñoz V , Boltaña S , Gallardo‐Escárate C
Published: January 2017

Salmon species cultured in Chile evidence different levels of susceptibility to the sea louse Caligus rogercresseyi. These differences have mainly been associated with specific immune responses. Moreover, iron regulation seems to be an important mechanism to confer immunity during the host infestation. This response called nutritional immunity has been described in bacterial infections, despite that no comprehensive studies involving in marine ectoparasites infestation have been reported. With this aim, we analysed the transcriptome profiles of Atlantic and coho salmon infected with C. rogercresseyi to evidence modulation of the iron metabolism as a proxy of nutritional immune responses. Whole transcriptome sequencing was performed in samples of skin and head kidney from Atlantic and coho salmon infected with sea lice. RNA‐seq analyses revealed significant upregulation of transcripts in both salmon species at 7 and 14 dpi in skin and head kidney, respectively. However, iron regulation transcripts were differentially modulated, evidencing species‐specific expression profiles. Genes related to heme degradation and iron transport such as hepcidin, transferrin and haptoglobin were primary upregulated in Atlantic salmon; meanwhile, in coho salmon, genes associated with heme biosynthesis were strongly transcribed. In summary, Atlantic salmon, which are more susceptible to infestation, presented molecular mechanisms to deplete cellular iron availability, suggesting putative mechanisms of nutritional immunity. In contrast, resistant coho salmon were less affected by sea lice, mainly activating pro‐inflammatory mechanisms to cope with infestation.
THE INNOVATION‐EMPLOYMENT NEXUS: A CRITICAL SURVEY OF THEORY AND EMPIRICS
Authors: Calvino Flavio , Virgillito Maria Enrica
Published: January 2017

Understanding whether technical change is beneficial or detrimental for employment is at the center of the policy debate, especially in phases of economic recession. So far, the effects of innovation – in its manifold declinations and intrinsic complexity – on labor demand have proven to be not unequivocal. This essay critically reviews the role of technical change in shaping employment dynamics at different levels of aggregation. First, it disentangles theoretically the role of different compensation mechanisms through which employment adjusts after an innovation is introduced. Second, it critically presents the most recent empirical evidence on the topic, with a focus on methods and limitations. Finally, it provides an attempt to conceptualize a number of stylized facts and empirical regularities on the innovation‐employment nexus.
Oral tactile sensitivity and masticatory performance are impaired in stroke patients
Authors: Schimmel M. , Voegeli G. , Duvernay E. , Leemann B. , Müller F.
Published: January 2017

Oro‐facial impairment following stroke frequently involves reduced chewing performance, that is oral phase dysphagia. The aim was to investigate the sensitivity of oral tissues following stroke and its potential impact on masticatory function. Therefore, hospitalised post‐stroke patients were recruited and compared to healthy controls. Outcome measures comprised masticatory performance employing a colour‐mixing ability, that is a bolus‐kneading test, maximum lip‐ and bite force and the one‐point and two‐point tactile thresholds. Food hoarding and prevalence of dry mouth were evaluated with ordinal scales. Twenty‐seven stroke patients (age 64·3 ± 14·1 years) and 27 healthy controls (age 60·8 ± 14·3 years, P = 0·254) participated in this study. The groups had similar numbers of occluding units. Stroke patients reported more frequently dry mouth sensations and food hoarding. The intra‐oral tactile sensitivity on the contra‐lesional side was significantly lower in stroke patients compared to controls (0·0001 < P < 0·0002), and significant intra‐group side differences were found only in the stroke group (0·0001 < P < 0·0010). For the lip, both sides were less sensitive in the stroke group compared with controls. The experiments confirmed lower masticatory performance and lip force in the stroke group, but the bite force was similar compared to healthy controls. Oral sensitivity was correlated with masticatory performance when a global correlation model was applied. A stroke may affect the sensitivity of the intra‐oral tissues contra‐lesionally, thus potentially affecting chewing function. Rehabilitation should therefore not only focus on motor impairment, but equally stimulate the sensitivity of the oral tissues, employing dry ice application or similar specific treatments.