bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipid droplet distribution of immature canine oocytes in relation to their size and the reproductive stage
Authors: Ariu Federica , Strina Alessandro , Murrone Ombretta , Falchi Laura , Bebbere Daniela , Ledda Sergio , Zedda Maria Teresa , Pau Salvatore , Bogliolo Luisa
Published: September 2015

This study investigated the distribution of lipid droplets (LD) in immature canine oocytes in relation to their size and the reproductive stage. Oocytes were collected from the ovaries of bitches at different estrous stages, divided according to their size (110‐120 µm; >120 µm), and stained with Nile Red to detect lipid droplet distribution. At the follicular phase most of the oocytes displayed a diffuse pattern of LD distribution, whereas at anestrus and luteal phase oocytes showed LD mainly in a peripheral/ perinuclear LD distribution. A significantly higher intensity of LD has been recorded in the oocytes > 120 µm compared to those of smaller size (110 ‐ 120 µm) at all stages of the estrous cycle. At follicular phase, oocytes > 120 µm displayed LD intensity similar to that of oocytes > 120 µm at luteal phase and higher compared to the oocytes of the other groups.
Correlated response of peripheral blood cytokines with selection for reduced mycoplasma pneumonia of swine lesions in Landrace pigs
Authors: Sato Takumi , Okamura Toshihiro , Kojima‐Shibata Chihiro , Kadowaki Hiroshi , Suzuki Eisaku , Uenishi Hirohide , Suzuki Keiichi
Published: October 2015

Mycoplasma pneumonia of swine (MPS) is responsible for significant economic losses in the swine industry. We selected Landrace pigs for reduced MPS pulmonary lesions over five generations, and measured concentrations of the following cytokines: interleukin (IL)‐10, IL‐13, IL‐17, tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ to estimate their correlation with MPS lesions. Sheep red blood cells (SRBC) were injected twice intramuscularly at 70 and 95 kg body weight. Blood serum samples were collected after 1 week of secondary SRBC inoculation and cytokine concentrations were analyzed by ELISA. Genetic parameters and breeding values were estimated. The heritability estimates of IL‐10, IL‐13, IL‐17, TNF‐α and IFN‐γ were 0.20 ± 0.06, 0.12 ± 0.06, 0.27 ± 0.07, 0.20 ± 0.10 and 0.05 ± 0.03, respectively. Genetic correlations of IL‐17 and TNF‐α with pulmonary MPS lesions were high (‐0.86 ± 0.13 and 0.69 ± 0.29, respectively) and those of IFN‐γ and IL‐13 with MPS lesions were moderately negative (‐0.45). Through selection, the breeding values of IL‐17 and IFN‐γ increased substantially and those of TNF‐α decreased. These results suggest that innate and cellular immunity are more important for the suppression of pulmonary lesions in MPS than humoral‐mediated immunity, such as antibody response.
The pharmacokinetic and pharmacodynamic interaction of clopidogrel and cilostazol in relation to CYP2C19 and CYP3A5 genotypes
Authors: Kim Ho‐Sook , Lim Younghae , Oh Minkyung , Ghim Jong‐lyul , Kim Eun‐Young , Kim Dong‐Hyun , Shin Jae‐Gook
Published: October 2015

Aim

The primary objective of the present study was to evaluate the pharmacokinetic and pharmacodynamic interactions between clopidogrel and cilostazol in relation to the CYP2C19 and CYP3A5 genotypes.

Methods

In a randomized, three‐way crossover study, 27 healthy subjects were administered clopidogrel (300 mg), cilostazol (100 mg) or clopidogrel + cilostazol orally. Plasma concentrations of clopidogrel, cilostazol and their active metabolites (clopidogrel thiol metabolite, 3,4‐dehydrocilostazol and 4″‐trans‐hydroxycilostazol), and adenosine diphosphate‐induced platelet aggregation were measured for pharmacokinetic and pharmacodynamic assessment.

Results

The area under the plasma concentration–time curve (AUC) of the active thiol metabolite of clopidogrel was highest in the CYP2C19 extensive metabolizers (EM) and lowest in the poor metabolizers (PM). Cilostazol decreased the thiol metabolite AUC by 29% in the CYP3A5*1/*3 genotype [geometric mean ratio (GMR) 0.71; 90% confidence interval (CI) 0.58, 0.86; P = 0.020] but not in the CYP3A5*3/*3 genotype (GMR 0.93; 90% CI 0.80, 1.10; P = 0.446).

Known effects of the CYP2C19 and CYP3A5 genotypes on the exposure of cilostazol and its metabolites were observed but there was no significant difference in the AUC of cilostazol and 3,4‐dehydrocilostazol between cilostazol and clopidogrel + cilostazol.

The inhibition of platelet aggregation from 4 h to 24 h (IPA4–24) following the administration of clopidogrel alone was highest in the CYP2C19 EM genotype and lowest in the CYP2C19 PM genotype (59.05 ± 18.95 vs. 36.74 ± 13.26, P = 0.023). However, the IPA of the CYP2C19 PM following co‐administration of clopidogrel and cilostazol was comparable with that of the CYP2C19 EM and intermediate metabolizers (IM) only in CYP3A5*3/*3 subjects.

Conclusions

The additive antiplatelet effect of cilostazol plus clopidogrel is maximized in subjects with both the CYP2C19 PM and CYP3A5*3/*3 genotypes because of a lack of change of clopidogrel thiol metabolite exposure in CYP3A5*3/*3 as well as the highest cilostazol IPA in CYP2C19 PM and CYP3A5*3/*3 subjects.
From Planning to Market: A Framework for Cuba
Authors: FONT MAURICIO , JANCSICS DAVID
Published: October 2015

The measures introduced by Raúl Castro since 2008 and the most recent US–Cuba policy change indicate that Cuba is shifting from a planned and highly centralised state socialist economic model toward one in which economic actors and markets become main drivers of the economy. The examples of Asian and Central and Eastern European socialist countries suggest four distinguished pathways for such transition. The question is which one may provide a feasible model for Cuba. Based on the country's economic and population structure, this study places the Cuban case within the framework of socialist economic transitions and explores some policy implications.
Synthesis, Biological Evaluation, and Molecular Docking of (R)‐2‐((8‐(3‐aminopiperidin‐1‐yl)‐3‐methyl‐7‐(3‐methylbut‐2‐en‐1‐yl)‐2,6‐dioxo‐2,3,6,7‐tetrahydro‐1H‐purin‐1‐yl)methyl)benzonitrile as Dipeptidyl Peptidase IV Inhibitors
Authors: Ran Yan , Pei Heying , Shao Mingfeng , Chen Lijuan
Published: October 2015

Type 2 diabetes (T2D) is classified as a major metabolic disorder, which has affected approximately 194 million people worldwide. DPP‐IV inhibitors as a new therapy have shown several advantages over traditional antidiabetic drugs. Based on the similar binding modes of Alogliptin and Linagliptin, molecular operation was conducted via combining pharmacophore hybridization with structural optimization between the two market drugs and racemic compounds 40 and 43 were reported as DPP‐IV inhibitors in our previous studies. But the majority of DPP‐IV inhibitors have developed into a small molecule with certain conformation; in this study, we described the synthesis, biological evaluation, and molecular docking of corresponding enantiomers of compounds 40 and 43. The most potent inhibitor is (R)‐40 (IC50 = 23.5 nm, F = 74.67%, T1/2 = 4 h), which exhibited moderate antihyperglycemic activity as compared to the standard antidiabetic drug Linagliptin in OGTT. In addition, compound (R)‐40 effectively improved the pathological state of DIO mice. Molecular docking studies clarified the favorable binding affinity between compound (R)‐40 and DPP‐IV active site. Thus, compound (R)‐40 would be entitled to further development as a drug candidate on the basis of the suitable pharmacokinetic (PK) and desirable pharmacodynamic (PD) profiles.
Sexual function and depressive symptoms in young women with thyroid autoimmunity and subclinical hypothyroidism
Authors: Krysiak Robert , Drosdzol‐Cop Agnieszka , Skrzypulec‐Plinta Violetta , Okopien Bogusław
Published: October 2015

Objective

The results of few studies conducted to date suggest an increased prevalence of sexual dysfunction in patients with thyroid disorders.

Design

The aim of this study was to compare female sexual function and depressive symptoms between women with autoimmune thyroid disease and with mild thyroid failure.

Patients

The study included four groups of young women: euthyroid women with Hashimoto's thyroiditis (Group 1), women with nonautoimmune subclinical hypothyroidism (Group 2), women with autoimmune subclinical hypothyroidism (Group 3) and healthy euthyroid females without thyroid autoimmunity (Group 4).

Measurements

Beyond measuring serum hormone levels and thyroid antibody titres, all enrolled women completed questionnaires evaluating female sexual function (Female Sexual Function Index – FSFI) and the presence and severity of depressive symptoms (Beck Depression Inventory‐Second Edition – BDI‐II).

Results

The mean total FSFI score was lower in women with autoimmune hypothyroidism than in the remaining groups of women, as well as lower in Groups 1 and 2 than in Group 4. Compared to Group 4, three domains (sexual desire, lubrication and sexual satisfaction) were lower in Group 1, four domains (desire, arousal, lubrication and dyspareunia) in Group 2 and all FSFI domain scores in Group 3. The total BDI‐II score was higher in Groups 1 and 2 than in Group 4, as well as higher in Group 3 than in the other groups of women.

Conclusions

The obtained results suggest that both thyroid autoimmunity and mild thyroid failure, particularly if they occur together, may negatively affect female sexual function and depressive symptoms.
Association between left ventricular mass, androgens, adiposity and insulin resistance in girls with precocious pubarche: a case–control study
Authors: Satler Fabíola , Vieira Raquel do Amaral , Firpo Cora , Spritzer Poli Mara
Published: October 2015

Objective

Precocious pubarche (PP) has been linked to higher prevalence of metabolic disturbances and polycystic ovary syndrome (PCOS). The aim of the study was to assess echocardiographic parameters in PP girls and to analyse their relationship with androgens and insulin resistance (IR).

Design

Case–control study.

Patients

Thirty‐five PP girls and 35 healthy age‐matched controls.

Measurements

Clinical, hormonal and metabolic profiles, echocardiography, body composition and oral glucose tolerance test.

Results

Chronological age (10·04 ± 2·6 years in PP vs 10·13 ± 2·56 years in controls, P = 0·227), and pubertal stage at the time of the study were similar between the groups. PP girls had higher free androgen index (FAI) [1·39 (0·48–3·64) vs 1·06 (0·39–1·7), P = 0·005] and QUICKI (0·58 ± 0·08 vs 0·63 ± 0·12, P = 0·021). However, HOMA‐IR was not significantly different between the groups [2·79 (1·84–4·05) vs 2·15 (1·09–3·23), P = 0·085]. After adjusting for total body fat, left ventricular mass (LVM) was higher in the PP group (97·31 ± 33·37 vs 81·25 ± 19·06 g, P = 0·017) as well as A′ wave (5·66 ± 1·34 vs 5·09 ± 0·98 cm/s, P = 0·025), a measurement of diastolic function. FAI and total body fat were independent predictors of higher LVM and together with HOMA‐IR contributed 72% of LVM variability in the PP group.

Conclusion

In this study with PP girls, greater LVM, associated with higher androgen levels, IR and total body fat, occurred early in pubertal development.
Insulin resistance and composite indices of femoral neck strength in Asians: the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV)
Authors: Ahn Seong Hee , Kim Hyeonmok , Kim Beom‐Jun , Lee Seung Hun , Koh Jung‐Min
Published: October 2015

Objective

Fracture risk in type 2 diabetes mellitus with insulin resistance is increased, despite relatively preserved bone mineral density (BMD). In this study, we investigated the relationship between insulin resistance and composite indices of femoral neck strength in Koreans.

Design

A population‐based, cross‐sectional study from the Korea National Health and Nutrition Examination Survey

Participants

About 1243 men and 1433 women

Measurements

Insulin resistance was evaluated using the homoeostasis model assessment‐estimated insulin resistance (HOMA‐IR) index. Femoral neck width and axis length were measured from hip dual‐energy X‐ray absorptiometry scans and combined with BMD, weight and height to calculate composite indices of femoral neck strength relative to load: compression (CSI), bending (BSI) and impact strength indices (ISI).

Results

HOMA‐IR showed an inverse relationship with CSI, BSI and ISI in both genders before and after adjusting for confounders (P < 0·001–0·029). CSI was more strongly associated with HOMA‐IR than BSI and/or ISI in both genders (P < 0·001–0·013). When men were stratified according to HOMA‐IR quartiles, all strength indices decreased as the quartile increased, after adjusting for all potential confounders (P for trend <0·001–0·001), whereas CSI and ISI did in women (P for trend = 0·012 and 0·002, respectively). Fasting insulin levels, but not glucose levels, were negatively associated with all strength indices regardless of confounders (P < 0·001–0·044).

Conclusions

Insulin resistance is associated with low femoral neck strength, particularly against the compressive load. These findings suggest a better approach to evaluate bone health in insulin‐resistant individuals.
Gender‐Related Violence and Young People: An Overview of Italian, Irish, Spanish, UK and EU Legislation
Authors: Alldred Pam , Biglia Barbara
Published: October 2015

Do laws regarding violence against or sexual exploitation of young people recognise gendered and other power dynamics? Cross‐national comparison of legal texts can illustrate the benefits of framing issues of violence/gender/youth in certain ways and offer critical reflection on particular legal frameworks or cultural understandings. This policy review is based on an analysis of select laws regarding gender‐related violence (GRV) as relates to young people in Italy, Ireland, Spain and the UK. Here, GRV is defined as sexist, sexualising or norm‐driven bullying, harassment, discrimination or violence whoever is targeted. It therefore includes gender, sexuality and sex‐gender normativities, as well as violence against women and girls. A tension emerges between granting young people agency and recognising the multiple, intersecting power relations that might limit and shape that agency. This article draws out the implications for the UK in particular, highlighting the absence of preventative measures and the need for a broader approach to combat GRV.
Protein biomarkers and microbial profiles in peri‐implantitis
Authors: Wang Hom‐Lay , Garaicoa‐Pazmino Carlos , Collins Amy , Ong Hwen‐Sei , Chudri Rini , Giannobile William V.
Published: October 2015

Objectives

The aim of the present investigation was to determine the profile of peri‐implant crevicular fluid (PICF) biomarkers combined with microbial profiles from implants with healthy peri‐implant tissues and peri‐implantitis to assess real‐time disease activity.

Material and methods

Sixty‐eight patients were included in this cross‐sectional study. They were divided into two groups: 34 patients with at least one healthy implant (control) and 34 with at least one peri‐implantitis affected implant (test). Total DNA content and qPCR analysis for periodontal bacteria obtained from subgingival plaque samples (Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) and a PICF analysis for IL‐1β, VEGF, MMP‐8, TIMP‐2, and OPG were performed. The individual and combined diagnostic ability of each biomarker for peri‐implantitis and target bacterial species were analyzed.

Results

The mean concentration of IL‐1β (44.6 vs. 135.8 pg/ml; P < 0.001), TIMP‐2 (5488.3 vs. 9771.8 pg/ml; P = 0.001), VEGF (59.1 vs. 129.0 pg/ml; P = 0.012), and OPG (66.5 vs. 111.7 pg/ml; P = 0.050) was increased in the peri‐implantitis patients. The mean expression of MMP‐8 (6029.2 vs. 5943.1 pg/ml; P = 0.454) and did not reveal a meaningful difference among groups. Total bacterial DNA of selected microorganisms was associated with a threefold or greater increase in peri‐implantitis although no statistical significant difference. The ability to diagnose diseased sites was enhanced by T. denticola combined with IL‐1β, VEGF, and TIMP‐2 PICF levels.

Conclusion

The present data suggest that the increased levels of the selected PICF‐derived biomarkers of periodontal tissue inflammation, matrix degradation/regulation, and alveolar bone turnover/resorption combined with site‐specific microbial profiles may be associated with peri‐implantitis and could have potential as predictors of peri‐implant diseases.
Growth, development, and life‐history strategies in an unpredictable environment: case study of a rare hoverfly Blera fallax (Diptera, Syrphidae)
Authors: ROTHERAY ELLEN L. , GOULSON DAVE , BUSSIÈRE LUC F.
Published: October 2015

1. Development in organisms can vary in response to fluctuating environments. In holometabolous insects, variation in adult phenotypic traits is strongly influenced by growth conditions experienced by larvae. The main aim of this study was to assess how much environmental insight can be gained from analysis of the phenotypic changes in an insect's life history parameters in response to realistic food limitations.

2. This investigation was motivated by a need for more information about the developmental requirements of the endangered pine hoverfly Blera fallax (Linnaeus) (Diptera, Syrphidae) in Scotland. Blera fallax depends on a scarce and often ephemeral habitat, rot holes of Scots pine Pinus sylvestris L. stumps. We studied how rearing conditions affected growth in captive larvae, and compared these responses with a wild population.

3. The growth curve observed in the field was similar to that in resource‐limited, lab conditions, suggesting that resources are limiting in nature. The effects of resource availability on development time and body size depended on sex. Adult females were larger but had more variable size at maturity compared with males. In contrast, males typically were not smaller in resource‐limited conditions, but rather continued to develop for another year. Between 2% and 20% of larvae extended development over 2 years regardless of growth conditions, perhaps indicating a semivoltine strategy to circumvent extinction during years with a low breeding success.

4. These results identify life history traits that may be important for other saproxylic Diptera in rot holes, and organisms that experience food restrictions during growth.
A consensus review on the development of palliative care for patients with chronic and progressive neurological disease
Authors: Oliver D. J. , Borasio G. D. , Caraceni A. , de Visser M. , Grisold W. , Lorenzl S. , Veronese S. , Voltz R.
Published: October 2015

Background and purpose

The European Association of Palliative Care Taskforce, in collaboration with the Scientific Panel on Palliative Care in Neurology of the European Federation of Neurological Societies (now the European Academy of Neurology), aimed to undertake a review of the literature to establish an evidence‐based consensus for palliative and end of life care for patients with progressive neurological disease, and their families.

Methods

A search of the literature yielded 942 articles on this area. These were reviewed by two investigators to determine the main areas and the subsections. A draft list of papers supporting the evidence for each area was circulated to the other authors in an iterative process leading to the agreed recommendations.

Results

Overall there is limited evidence to support the recommendations but there is increasing evidence that palliative care and a multidisciplinary approach to care do lead to improved symptoms (Level B) and quality of life of patients and their families (Level C). The main areas in which consensus was found and recommendations could be made are in the early integration of palliative care (Level C), involvement of the wider multidisciplinary team (Level B), communication with patients and families including advance care planning (Level C), symptom management (Level B), end of life care (Level C), carer support and training (Level C), and education for all professionals involved in the care of these patients and families (Good Practice Point).

Conclusions

The care of patients with progressive neurological disease and their families continues to improve and develop. There is a pressing need for increased collaboration between neurology and palliative care.
European Roe Deer Increase Vigilance When Faced with Immediate Predation Risk by Eurasian Lynx
Authors: Eccard Jana A. , Meißner Jessica K. , Heurich Marco
Published: October 2015

Prey animals must balance antipredatory behaviour with foraging behaviour. According to the risk allocation hypothesis, prey increase antipredatory behaviour and reduce foraging activity during pulses of high risk, but with continuous risk, other activities must continue and antipredatory behaviour decreases despite the risk. We studied the impact of lynx presence on the vigilance behaviour of wild roe deer under conditions of (i) a pulsed elevated risk by experimentally spreading lynx urine as an olfactory cue, and (ii) continuous risk by comparing an area where lynx was eradicated 160 years ago to an area where lynx has been re‐introduced 30 years ago. Roe deer were extremely vigilant in response to the predator olfactory cue; however, roe deer vigilance did not differ measurably among areas with or without potential lynx presence. Deer were more vigilant before sunset than during the night at both study areas, probably due to long‐term adaptation of roe deer to human hunting during daytime. Vigilance decreased from August to September even though activity of lynx increases in autumn, which may be a result either of increased foraging due to decrease in food quality in autumn, or of changes in social organization of the deer. Our results suggested that the degree of vigilance depends on environmental cues. We found that roe deer respond to lynx urine despite a long absence of lynx in the ecosystem. Our results support the risk allocation hypothesis for responses to pulses of high risk but not for responses to continuous elevated levels of risk.
The Oxidative Cost of Acoustic Signals: Examining Steroid Versus Aerobic Activity Hypotheses in a Wild Bird
Authors: Baldo Sarah , Mennill Daniel J. , Guindre‐Parker Sarah , Gilchrist Hugh Grant , Love Oliver P.
Published: October 2015

Vertebrate vocalizations are widespread secondary sexual signals used for mate attraction and territory defence, and variation in signal quality is often condition dependent and impacts reproductive outcomes. Although vocal signal performance is known to reflect various aspects of male quality, few studies have examined the underlying mechanisms mediating its costs and hence its honesty. Using a population of Arctic‐breeding snow buntings (Plectrophenax nivalis), we compared the ‘Oxidation Handicap Hypothesis’, which predicts that testosterone‐induced increases in oxidative stress provide a direct mechanistic basis for ensuring the honesty of many secondary sexual signals, to the ‘Aerobic Activity Hypothesis, which predicts that it is the aerobic activity involved with signal production (i.e. vocal performance or defending a large territory) and not testosterone directly that links signal quality and oxidative stress. Males singing at faster rates had higher levels of both reactive oxygen metabolites and non‐enzymatic antioxidant capacity in the plasma (i.e. without an increase in overall oxidative stress), enabling certain males to produce high‐quality signals while also mitigating the costs of an associated increase in oxidative stress. However, these results were completely independent of plasma testosterone levels, supporting the role of aerobic performance in directly affecting oxidative stress. Although song performance was not linked to reproductive parameters in our data set, our research is the first to test these competing hypotheses in a behavioural trait and results suggest that oxidative stress may be an underlying physiological cost preventing low‐quality individuals from producing high‐quality signals.
Sequence and structure‐based prediction of fructosyltransferase activity for functional subclassification of fungal GH32 enzymes
Authors: Trollope Kim M. , van Wyk Niël , Kotjomela Momo A. , Volschenk Heinrich
Published: October 2015

Sucrolytic enzymes catalyse sucrose hydrolysis or the synthesis of fructooligosaccharides (FOSs), a prebiotic in human and animal nutrition. FOS synthesis capacity differs between sucrolytic enzymes. Amino‐acid‐sequence‐based classification of FOS synthesizing enzymes would greatly facilitate the in silico identification of novel catalysts, as large amounts of sequence data lie untapped. The development of a bioinformatics tool to rapidly distinguish between high‐level FOSs synthesizing predominantly sucrose hydrolysing enzymes from fungal genomic data is presented. Sequence comparison of functionally characterized enzymes displaying low‐ and high‐level FOS synthesis revealed conserved motifs unique to each group. New light is shed on the sequence context of active site residues in three previously identified conserved motifs. We characterized two enzymes predicted to possess low‐ and high‐level FOS synthesis activities based on their conserved motif sequences. FOS data for the enzymes confirmed our successful prediction of their FOS synthesis capacity. Structural comparison of enzymes displaying low‐ and high‐level FOS synthesis identified steric hindrance between nystose and a long loop region present only in low‐level FOS synthesizers. This loop is proposed to limit the synthesis of FOS species with higher degrees of polymerization, a phenomenon observed among enzymes displaying low‐level FOS synthesis. Conserved sequence motifs surrounding catalytic residues and a distant structural determinant were identifiers of FOS synthesis capacity and allow for functional annotation of sucrolytic enzymes directly from amino acid sequence. The tool presented may also be useful to study the structure–function relationships of β‐fructofuranosidases by identifying mutations present in a group of closely related enzymes displaying similar function.
Loss of thermal refugia near equatorial range limits
Authors: Lima Fernando P. , Gomes Filipa , Seabra Rui , Wethey David S. , Seabra Maria I. , Cruz Teresa , Santos António M. , Hilbish Thomas J.
Published: October 2015

This study examines the importance of thermal refugia along the majority of the geographical range of a key intertidal species (Patella vulgata Linnaeus, 1758) on the Atlantic coast of Europe. We asked whether differences between sun‐exposed and shaded microhabitats were responsible for differences in physiological stress and ecological performance and examined the availability of refugia near equatorial range limits. Thermal differences between sun‐exposed and shaded microhabitats are consistently associated with differences in physiological performance, and the frequency of occurrence of high temperatures is most probably limiting the maximum population densities supported at any given place. Topographical complexity provides thermal refugia throughout most of the distribution range, although towards the equatorial edges the magnitude of the amelioration provided by shaded microhabitats is largely reduced. Importantly, the limiting effects of temperature, rather than being related to latitude, seem to be tightly associated with microsite variability, which therefore is likely to have profound effects on the way local populations (and consequently species) respond to climatic changes.
Principal–Agent Analysis and Pathological Delegation: The (Almost) Untold Story
Authors: Sobol Mor
Published: October 2015

Principal–agent (PA) has come a long way since it was introduced to the political science sphere. Nowadays, PA has established itself as an institutional midrange theoretical framework that encompasses various methodological as well as theoretical approaches. This article argues, however, that scholars still assume, a priori, that the agent is an opportunistic and disloyal actor. This article seeks to question this theoretical assumption by demonstrating how principals could be as much problematic as their agents, a phenomenon that it terms “pathological delegation.” In so doing, it offers a first analysis of the small strand of the literature that examines problems embedded in the principals' side as well as provides new empirical evidence in the context of the European Neighbourhood Policy. Finally, the article posits that scholars should not treat pathological delegation as an anomaly but rather attempt to integrate, test, and develop new theoretical assumptions on this phenomenon.
Progression through Academic Ranks: A Longitudinal Examination of Internal Promotion Drivers
Authors: Dobele Angela R. , Rundle‐Theile Sharyn
Published: October 2015

The last 20 years have brought major workload changes for academics globally, with the feeling that an academic in today's global higher education industry has three full‐time jobs (research, teaching and service). Following recent Government reforms, the Australian higher education sector has been forced to redefine itself in a more commercial context. The need to research workloads over time is recommended owing to changes as a result of growth, internationalisation and increasing competition. This longitudinal study comprises 5 years of observable teaching and research workloads capturing the teaching and research output of more than 85 individuals in two Australian university business faculties. Our results reinforce the axiom ‘publish or perish’ as it is the number of research papers published which increases the chances of internal promotion. Other observed workload characteristics, number of courses taught, number of students, research income and the number of research grants awarded, did not increase the likelihood of internal promotion. Suggestions for policy reforms and further research are identified.
Clinicopathological analysis of programmed cell death 1 and programmed cell death ligand 1 expression in the tumour microenvironments of diffuse large B cell lymphomas
Authors: Kwon Dohee , Kim Sehui , Kim Pil‐Jong , Go Heounjeong , Nam Soo Jeong , Paik Jin Ho , Kim Young A , Kim Tae Min , Heo Dae Seog , Kim Chul Woo , Jeon Yoon Kyung
Published: October 2015

Aims

To investigate the clinicopathological characteristics of programmed cell death ligand 1 (PD‐L1) and programmed cell death 1 (PD‐1) expression in the tumour microenvironments of diffuse large B cell lymphoma (DLBCL).

Methods and results

Tumour tissues from 126 DLBCL patients were immunostained for PD‐L1 and PD‐1. The expression of PD‐L1 by tumour cells and/or tumour‐infiltrating immune cells (mainly macrophages) was evaluated, and the number of tumour‐infiltrating PD‐1+ cells was assessed. PD‐L1 expression in tumour cells was observed in 61.1% of DLBCLs, with a weak intensity in 29.4%, moderate intensity in 21.4% and strong intensity in 10.3% of cases. Strong PD‐L1 expression in tumour cells was associated significantly with the presence of B symptoms (adjusted P = 0.005) and Epstein–Barr virus (EBV) infection (adjusted P = 0.015), and tended to be higher in activated B cell‐like immunophenotype (16.7%) than germinal centre B cell‐like immunophenotype (2.5%) (adjusted P = 0.271). DLBCLs with PD‐L1 expression in tumour cells/macrophages showed similar clinicopathological characteristics. The quantity of PD‐1+ tumour‐infiltrating lymphocytes correlated positively with the level of PD‐L1 expression in tumour cells (P = 0.042) or in tumour cells/macrophages (P = 0.03). Increased infiltration of PD‐1+ cells was associated with prolonged progression‐free survival (P = 0.005) and overall survival (P = 0.026) in DLBCL patients treated with rituximab‐cyclophosphamide, doxorubicin, vincristine, prednisone (R‐CHOP), whereas PD‐L1 expression had no prognostic significance.

Conclusions

PD‐L1 and PD‐1 were expressed variably in DLBCLs by tumour cells and tumour‐infiltrating immune cells and might be potential therapeutic targets using PD‐1/PD‐L1 blockade.
MYC/BCL6 double‐hit lymphoma (DHL): a tumour associated with an aggressive clinical course and poor prognosis
Authors: Li Shaoying , Desai Parth , Lin Pei , Yin C Cameron , Tang Guilin , Wang Xuan J , Konoplev Sergej N , Khoury Joseph D , Bueso‐Ramos Carlos E , Medeiros L Jeffrey
Published: October 2015

Aims

Large B cell lymphomas with MYC and BCL6/3q27 rearrangements, designated MYC/BCL6 DHL, are uncommon. Our aim was to better characterize this group of tumours.

Methods and results

We studied the clinicopathological features and outcome of 13 patients with MYC/BCL6 DHL and compared this group to a group of 83 MYC/BCL2 DHL patients. There were eight men and five women, with a median age of 63 years. Eleven tumours were classified as diffuse large B cell lymphomas (DLBCL) and two were B cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCLU). Immunohistochemical analysis showed that these tumours were positive for BCL6 (100%), BCL2 (eight of 10; 80%) and CD10 (eight of 10; 80%). Nine of 12 (75%) cases had a germinal centre B cell (GCB) immunophenotype; in one case data were incomplete. All patients were treated with chemotherapy. The clinicopathological features of MYC/BCL6 DHL were similar to MYC/BCL2 DHL, except that MYC/BCL6 DHL had a GCB immunophenotype less often. Patients with MYC/BCL6 DHL had a poor overall survival, similar to patients with MYC/BCL2 DHL (P = 0.32).

Conclusions

MYC/BCL6 DHL is an aggressive B cell lymphoma and patients often have an aggressive clinical course and poor prognosis, similar to patients with MYC/BCL2 DHL.
FoxP3‐positive T cell lymphoma arising in non‐HTLV1 carrier: clinicopathological analysis of 11 cases of PTCL‐NOS and 2 cases of mycosis fungoides
Authors: Satou Akira , Asano Naoko , Kato Seiichi , Katsuya Hiroo , Ishitsuka Kenji , Elsayed Ahmed A , Nakamura Shigeo
Published: October 2015

Aims

Forkhead box protein 3‐positive (FoxP3+) T cell lymphoma, in the absence of human T cell lymphotrophic virus type 1 (HTLV‐1) infection, is rare and its clinicopathological characteristics still remain unclear. The aim of this study was to elucidate its characteristics.

Methods and results

We describe here 11 cases of peripheral T cell lymphoma not otherwise specified (PTCL‐NOS) and two cases of mycosis fingoides (MF) which were positive for FoxP3. The median age of the 11 PTCL‐NOS cases was 65 years (range: 48–80 years), and all the patients were male. Eight patients (80%) showed stages III/IV disease, and six (60%) were categorized as high–intermediate/high‐risk groups according to the International Prognostic Index. Two cases of MF were 57‐ and 59‐year‐old males. Both cases were categorized as stage IA, according to International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. Immunohistochemically, all the cases were negative for cytotoxic molecule marker, and nine (75%) were αβ T cell type. Scattered Epstein–Barr virus (EBV)‐infected cells were detected in four cases of PTCL‐NOS, implying the reactivation of EBV caused by the immunodeficient status of the patients.

Conclusions

FoxP3+ PTCL‐NOS constitute a minor phenotypical subtype with poor prognosis and EBV reactivation in some. Conversely, two cases of MF showed an indolent clinical course which was different from previously reported cutaneous T cell lymphoma (CTCL) cases.
Prevalence of oesophageal epidermoid metaplasia in 1048 consecutive patients and 58 patients with squamous neoplasms
Authors: Cottreau Jonathan , Gruchy Steven , Kamionek Michal , Lauwers Gregory Y , Arnason Thomas
Published: October 2015

Aims

Oesophageal epidermoid metaplasia is defined by a dense granular layer with overlying hyperorthokeratosis, resembling the epidermis of skin. A possible association between epidermoid metaplasia, squamous dysplasia and squamous cell carcinoma has been proposed. The aim of this study was to compare the prevalence of epidermoid metaplasia in patients with oesophageal squamous neoplasms with that in a control cohort.

Methods and results

Medical records and slides from 1048 consecutive oesophageal biopsies and resections for any indication and 58 patients with oesophageal squamous neoplasms were reviewed. Two cases (0.19%) of epidermoid metaplasia were identified in the 1048‐patient control group. The prevalence of epidermoid metaplasia was significantly higher (P< 0.05) in the 58 patients with oesophageal squamous neoplasms, two of whom (3.5%) had concurrent epidermoid metaplasia (odds ratio 18.1, 95% confidence interval 2.5–131). One case was associated with a verrucous carcinoma and the other with a well‐differentiated, superficial (pT1), exophytic squamous cell carcinoma. No patients had epidermoid metaplasia in a biopsy prior to the diagnosis of squamous neoplasia.

Conclusions

The increased prevalence of epidermoid metaplasia observed in patients with squamous neoplasms provides some additional support for the proposed association. The hypothesis that epidermoid metaplasia is a precursor to squamous neoplasms remains unproven.
Influence of therapeutic cancer radiation on the bond strength of an epoxy‐ or an MTA‐based sealer to root dentine
Authors: Martins C. V. , Leoni G. B. , Oliveira H. F. , Arid J. , Queiroz A. M. , Silva L. A. B. , Sousa‐Neto M. D.
Published: October 2015

Aim

To evaluate the influence of radiation on root canal sealer push‐out bond strength to dentine and sealer/dentine interface in teeth filled with AH Plus (Dentsply Ind. Com. Ltda, Petrópolis, RJ, Brazil) and MTA Fillapex (Angelus Ind. Prod. Odontológicos S/A, Londrina, PR, Brazil).

Methodology

Thirty‐two maxillary canines were selected and randomly assigned to 2 groups (n = 16): one group was not irradiated, and the other was subjected to a cumulative radiation dose of 60 Gy. Root canals were prepared with the Reciproc system (VDW GmbH, Munich, Germany), and each group was divided into 2 subgroups (n = 8) according to the sealer – AH Plus or MTA Fillapex – using the single‐cone filling technique. Then, 1‐mm‐thick dentine slices were obtained from each root third for the push‐out test to evaluate sealer bond strength to dentine and for scanning electron microscopy (SEM) to examine the sealer/dentine interface. Failure mode after debonding was determined with a stereomicroscope at ×25 magnification. Bond strength data were analysed by two‐way anova with a split‐plot design and post hoc Tukey's test (α = 0.05).

Results

Significantly lower bond strength (P < 0.0001) was obtained after irradiation (0.71 ± 0.20 versus 0.97 ± 0.29 MPa) and in specimens filled with MTA Fillapex (0.70 ± 0.18 MPa) compared with AH Plus (1.00 ± 0.27 MPa). Percentage of adhesive failures increased after radiation in all root thirds in the teeth filled with AH Plus. SEM revealed more gap‐containing regions and fewer tags at the sealer/dentine interface in irradiated specimens, with more tag formation and fewer gaps with AH Plus sealer.

Conclusions

Radiation was associated with a decrease in the push‐out bond strength of sealers to intraradicular dentine and formation of more gaps and fewer tags at the sealer/dentine interface regardless of the sealer.
Mechanical properties of ProTaper Gold nickel‐titanium rotary instruments
Authors: Elnaghy A. M. , Elsaka S. E.
Published: October 2015

Aim

To evaluate and compare the resistance to cyclic fatigue and torsional stress, flexibility and surface microhardness of ProTaper Gold (PTG; Dentsply, Tulsa Dental Specialties, Tulsa, OK, USA) system with ProTaper Universal (PTU; Dentsply Maillefer, Ballaigues, Switzerland).

Methodology

PTG and PTU instruments were rotated in simulated canals and the number of cycles to failure was recorded to assess their cyclic fatigue resistance. Torsional strength was measured using a torsiometer after fixing firmly the apical 3 mm of the instrument. A scanning electron microscope was used to characterize the topographic features of the fracture surfaces of the broken instruments. The instruments were tested for bending resistance using cantilever‐bending test. Vickers microhardness was measured on the cross section of instruments with 300 g load and 15 s dwell time. Data were analysed statistically using independent t‐tests. Statistical significance was set at P < 0.05.

Results

PTG instruments had a significantly higher resistance to cyclic fatigue and flexibility than PTU (P < 0.001). The fractured cross‐sectional surfaces revealed typical features of cyclic fractures, including crack origins, fatigue zones and overload fast fracture zones. On the other hand, PTU instruments were associated with higher resistance to torsional stress and microhardness than PTG instruments (P < 0.001). After torsional tests, the fractured cross‐sectional surfaces revealed skewed dimples near the centre of the fracture surfaces and circular abrasion streaks.

Conclusions

The PTG instrument had improved resistance to cyclic fatigue and flexibility compared with PTU. PTU instruments had improved resistance to torsional stress and microhardness compared with PTG.
Establishment of a specific cell death induction system in Bombyx mori by a transgene with the conserved apoptotic regulator, mouse Bcl‐2‐associated X protein (mouse Bax)
Authors: Sumitani M. , Sakurai T. , Kasashima K. , Kobayashi S. , Uchino K. , Kanzaki R. , Tamura T. , Sezutsu H.
Published: October 2015

The induction of apoptosis in vivo is a useful tool for investigating the functions and importance of particular tissues. B‐cell leukaemia/lymphoma 2‐associated X protein (Bax) functions as a pro‐apoptotic factor and induces apoptosis in several organisms. The Bax‐mediated apoptotic system is widely conserved from Caenorhabditis elegans to humans. In order to establish a tissue‐specific cell death system in the domestic silkworm, Bombyx mori, we constructed a transgenic silkworm that overexpressed mouse Bax (mBax) in particular tissues by the Gal4‐upstream activation sequence system. We found that the expression of mBax induced specific cell death in the silk gland, fat body and sensory cells. Fragmentation of genomic DNA was observed in the fat body, which expressed mBax, thereby supporting apoptotic cell death in this tissue. Using this system, we also demonstrated that specific cell death in sensory cells attenuated the response to the sex pheromone bombykol. These results show that we successfully established a tissue‐specific cell death system in vivo that enabled specific deficiencies in particular tissues. The inducible cell death system may provide useful means for industrial applications of the silkworm and possible utilization for other species.
Direct costs of acute respiratory infections in a pediatric long‐term care facility
Authors: Murray Meghan T. , Heitkemper Elizabeth , Jackson Olivia , Neu Natalie , Stone Patricia , Cohen Bevin , Saiman Lisa , Hutcheon Gordon , Larson Elaine L.
Published: October 2015

Acute respiratory tract infections (ARI) are a major burden in pediatric long‐term care. We analyzed the financial impact of ARI in 2012–2013. Costs associated with ARI during the respiratory viral season were ten times greater than during the non‐respiratory viral season, $31 224 and $3242 per 1000 patient‐days, respectively (P < 0·001). ARI are burdensome for pediatric long‐term care facilities not only because of the associated morbidity and mortality, but also due to the great financial costs of prevention.
Leaving school: a comparison of the worries held by adolescents with and without intellectual disabilities
Authors: Young R. , Dagnan D. , Jahoda A.
Published: September 2015

Background

Leaving school is an important time for adolescents, with increasing autonomy and developing adult identities. The present study sought to shed light on the content and emotional impact of worries amongst adolescents with and without intellectual disabilities (IDs) at this time of change.

Methods

Twenty‐five adolescents with mild to moderate IDs and 27 adolescents without IDs, aged 15 to 18 years, took part in the study. Participants' worries were elicited using a structured interview. The levels of rumination and distress related to their most salient worries were also examined, along with their self‐reported levels of anxiety.

Results

Content analysis of the interviews identified differences between the worries of the two groups of participants, with the adolescents with IDs expressing more general worries about failure and personal threat. Level of distress about worries was positively correlated with anxiety in both groups. The adolescents with IDs were significantly more anxious than their non‐disabled peers.

Conclusions

The differences between the groups' worries may be linked to differences in life experience and expectations. Consideration should be given to the specific worries of adolescents at the stage of leaving school. Doing so may allow solutions for their concerns to be identified, thus easing distress and leading to a less stressful transition.
Children with PIMD in interaction with peers with PIMD or siblings
Authors: Nijs S. , Vlaskamp C. , Maes B.
Published: September 2015

Background

The complex disabilities of children with profound intellectual and multiple disabilities (PIMD) impede their presentation of peer directed behaviours. Interactions with typically developing peers have been observed to be more frequent than those with peers with PIMD. The typically developing peers with whom people with PIMD have frequent contact are their siblings. In this study, the amount of peer directed behaviours was compared between an interaction with a sibling and an interaction with a peer with PIMD. In addition, the attention directing strategies of the siblings, and how these affect the presentation of peer directed behaviours, were examined.

Method

Thirteen children and young people with PIMD, who had a typically developing sibling, were identified. For each of these thirteen children, a peer with PIMD and a sibling were selected. The child with PIMD was observed together with a peer with PIMD and together with a sibling. In both conditions, video observations were conducted. A coding scheme for the peer directed behaviours of the children and young people with PIMD and a coding scheme for the attention directing behaviours of the siblings were used. Descriptive, comparative and sequential analyses were conducted.

Results

Significantly, more peer directed behaviours of the children with PIMD were observed in the condition with the sibling (30.76%) compared with that of the condition with the peer with PIMD (13.73%). The siblings presented attention directing behaviours in 30% of the time; the most frequently used was nonverbal behaviour. When the siblings presented a combination of verbal and nonverbal attention directing behaviours, they elicited multiple peer directed behaviours in the children and young people with PIMD.

Conclusions

Persons with PIMD interact more with their siblings compared with their peers with PIMD. Interacting with siblings may probably be more motivating and encouraging. Presenting a combination of verbal and nonverbal behaviours attracts more attention of the persons with PIMD.