bluuebunny/crossref_metadata_2025 huggingface dataset:
Serious adverse drug events related to non‐investigational drugs in academic clinical trials: another source of safety data for risk assessment?
Authors: Olivier Pascale , Gimbert Anne , Colin Anne‐Laurène , Salvo Francesco , Becker Madlyne , Marty Valérie , Montastruc Jean‐Louis , Petitpain Nadine
Published: June 2016

Aims

Sponsors of clinical trials have to analyze serious adverse events (SAEs). Both sponsors and investigators determine the relationship between the investigational medicinal product, the investigational device or procedure and SAEs. SAEs related to another cause, such as a non‐investigational medicinal product (NIMP), do not have clear pharmacovigilance reporting requirements. The aim of this study was to evaluate the amount and the nature of NIMP‐related SAEs recorded by three French academic sponsors and to propose pharmacovigilance requirements for these cases.

Methods

This was a retrospective descriptive study including all cases of NIMP‐related SAEs occurring in clinical trials and reported to three academic sponsors between January 2009 and October 2014.

Results

Among 5870 cases of SAEs, 300 (5%) were related to a NIMP in 50 clinical trials. Involved NIMPs were mainly antithrombotics, cytostatics and immunosuppressants. Some of these drugs were currently followed by a risk management plan (e.g. rivoxaban). The most frequent NIMP‐related SAEs were neurological, gastrointestinal and infectious disorders. Seven NIMP‐related SAEs were known as ‘rare’ or ‘very rare’ and two were ‘unlabelled’.

Conclusions

As far as we know, this is the first study to focus about NIMP‐related SAEs occurring in clinical trials. This work highlights the potential high quality source of safety data via NIMP‐related SAE collection. Globally, we propose that NIMP‐related SAEs occurring in clinical trials should systematically be notified to the pharmacovigilance system of the concerned country. Clearer procedures of interactions between safety units of academic sponsors and pharmacovigilance systems are needed to allow an effective recording of NIMP‐related SAEs.
Effects of renal impairment on the pharmacokinetics of orally administered deferiprone
Authors: Fradette Caroline , Pichette Vincent , Sicard Éric , Stilman Anne , Jayashankar Shalini , Tsang Yu Chung , Spino Michael , Tricta Fernando
Published: June 2016

Aims

In light of the growing recognition of renal disease in thalassemia, it is important to understand the impact of renal impairment on the pharmacokinetics of iron chelators. This study evaluated the pharmacokinetics and safety of the iron chelator deferiprone (DFP) in subjects with renal impairment in comparison with healthy volunteers (HVs).

Methods

Thirty‐two subjects were categorized into four groups based on degree of renal impairment: none, mild, moderate or severe, as determined by estimated glomerular filtration rate (eGFR). All subjects received a single oral dose of 33 mg kg−1 DFP, provided serum and urine samples for pharmacokinetic assessment over 24 h and were monitored for safety.

Results

Renal clearance of DFP decreased as renal impairment increased. However, based on Cmax, AUC(0,t) and AUC(0,∞), there were no significant group differences in systemic exposure, because less than 4% of the drug was excreted unchanged in the urine. DFP is extensively metabolized to a renally excreted, pharmacologically inactive metabolite, deferiprone 3‐O‐glucuronide (DFP‐G), which exhibited higher Cmax, AUC(0,t), AUC(0,∞) and longer tmax and t1/2 in the renally impaired groups compared with HVs. The Cmax and AUCs of DFP‐G increased as eGFR decreased. Overall, 75%–95% of the dose was retrieved in urine, either as DFP or DFP‐G, regardless of severity of renal impairment. With respect to safety, DFP was well tolerated.

Conclusions

These data suggest that no adjustment of the DFP dosage regimen in patients with renal impairment is necessary, as there were no significant changes in the systemic exposure to the drug.
Nonparametric Analysis of Competing Risks Data with Event Category Missing at Random
Authors: Gouskova Natalia A. , Lin Feng-Chang , Fine Jason P.
Published: June 2016

In competing risks setup, the data for each subject consist of the event time, censoring indicator, and event category. However, sometimes the information about the event category can be missing, as, for example, in a case when the date of death is known but the cause of death is not available. In such situations, treating subjects with missing event category as censored leads to the underestimation of the hazard functions. We suggest nonparametric estimators for the cumulative cause-specific hazards and the cumulative incidence functions which use the Nadaraya–Watson estimator to obtain the contribution of an event with missing category to each of the cause-specific hazards. We derive the propertied of the proposed estimators. Optimal bandwidth is determined, which minimizes the mean integrated squared errors of the proposed estimators over time. The methodology is illustrated using data on lung infections in patients from the United States Cystic Fibrosis Foundation Patient Registry.
Injunctions as a Legal Weapon in Collective Industrial Disputes in Britain, 2005–2014
Authors: Gall Gregor
Published: June 2016

This article examines the frequency, nature and outcomes of employers seeking injunctions against strikes and industrial action mounted by unions between 2005 and 2014. The number of actual and threatened applications continues to be relatively high compared with the previous period when strike levels were significantly higher, with employers continuing to gain overwhelmingly successful outcomes. Yet, usage is increasingly concentrated in a small number of industrial sectors, suggesting the notion of ‘strike effectiveness’ provides the best means by which to explain their relative frequency and presence. Comparative analysis with Ireland highlights the specificity of the nature of British legal regulation of employers seeking injunctive relief.
Liberalization Only at the Margins? Analysing the Growth of Temporary Work in German Core Manufacturing Sectors
Authors: Benassi Chiara
Published: June 2016

Drawing on workers’ surveys and workplace interviews, this article investigates the growth of temporary work in German manufacturing sectors since the 1980s. Findings partly confirm a ‘dualization’ scenario as workers without industry‐specific vocational training are more likely to be on a temporary contract than skilled workers, and the gap has widened over time. However, also skilled workers have become increasingly vulnerable to casualization due to job routine and the erosion of industrial relations. Evidence confirms the crucial role of institutions in supporting the linkage between specific skills and employment stability, and suggests that the liberalization of the employment relationship has the potential to advance also in the core of the German economy.
Dental implants in the elderly population: a systematic review and meta‐analysis
Authors: Srinivasan Murali , Meyer Simon , Mombelli Andrea , Müller Frauke
Published: June 2016

Objective

This systematic review was conducted to evaluate the outcome of dental implant therapy in elderly patients (≥65 years).

Material and Methods

Online database and hand searches were systematically performed to identify studies reporting on dental implants placed in the partially/completely edentulous jaws of elderly patients. Only prospective studies reporting on regular‐diameter (≥3 mm), micro‐rough surface implants were included in this review. Two investigators performed the search and data extraction. An inter‐investigator reliability was verified using kappa statistics (κ). A meta‐analysis was performed on implant survival rates, while the mean peri‐implant marginal bone level changes (PI‐MBL), technical/mechanical complications, and biological complications were reported descriptively.

Results

The systematic search yielded 2221 publications, of which 11 studies were included for statistical analyses. The calculated κ for the various parameters extracted was κ = 0.818–1.000. A meta‐analysis was performed on the post‐loading implant survival rates at 1, 3, 5, and 10 years. The random‐effects model revealed an overall 1‐year implant survival of 97.7% (95% CI: 95.8, 98.8; I2 = 0.00%, P = 0.968; n = 11 studies). The model further revealed an overall implant survival of 96.3% (95% CI: 92.8, 98.1; I2 = 0.00%, P = 0.618; n = 6 studies), 96.2% (95% CI: 93.0, 97.9; I2 = 0.00%, P = 0.850; n = 7 studies), and 91.2% (95% CI: 83.4, 95.6; I2 = 0.00%, P = 0.381; n = 3 studies) for 3, 5, and 10 years, respectively. The reported 1‐year average PI‐MBL ranged between 0.1 and 0.3 mm, while the reported 5‐ and 10‐year PI‐MBL were 0.7 and 1.5 mm, respectively. Information obtained pertaining to the technical and biological complications in the included studies was inadequate for statistical analysis. The frequent technical/mechanical complications reported were abutment screw loosening, fracture of the overdenture prostheses, activation of retentive clips, ceramic chipping, and fractures. The common biological complication reported included peri‐implant mucositis, mucosal enlargement, bone loss, pain, and implant loss.

Conclusions

This review provides robust evidence favoring dental implant therapy in elderly patients as a predictable long‐term treatment option, in terms of implant survival, clinically acceptable PI‐MBL changes, and minimal complications. Therefore, age alone should not be a limiting factor for dental implant therapy.
Skin disease symptoms and related risk factors among young workers in high‐risk jobs
Authors: Aktas Emine , Esin M. Nihal
Published: June 2016

Background

Occupational skin diseases are the one of the most frequent diseases in many industrialized countries. The studies about skin disease (SD) on young workers were limited.

Objectives

In this study, we aim to evaluate the prevalence of SD symptoms and related risk factors among young workers in high‐risk occupations.

Methods

This cross‐sectional study was undertaken between 2011 and 2012 in two vocational training centres. We included 455 young workers who were working as hairdressers, jewellers, or car mechanics. Data were collected with the Nordic Occupational Skin Questionnaire, which was adapted to Turkish for young workers.

Results

The average age of the young workers was 17.9 ± 1.7 years. Of the 455 young workers, 52.7% were female and 47.3% were male. During the previous 12 months, the prevalences of the total SD symptoms, hand/forearm eczema symptoms and urticaria symptoms were 49.7%, 44.4%, and 13.4%, respectively. Those who worked as car mechanics were 5.8 times more likely [odds ratio (OR) 5.81, 95%CI: 2.58–13.10) to have a dry skin type, 2.9 times more likely (OR 2.86, 95%CI: 1.72–4.75) to work for >12 h daily, 2.6 times more likely (OR 2.59, 95%CI: 1.25–5.35) to have worked for >5 years, and 3.0 times more likely (OR 3.05, 95%CI: 1.14–8.14) to have SD symptoms.

Conclusion

The results indicate that young workers in high‐risk jobs have a high frequency of skin symptoms. These results could provide a basis for occupational health professionals to plan prevention programmes for young workers.
ECOOP: Applying Dynamic Coalition Formation to the Power Regulation Problem in Smart Grids
Authors: Mihailescu Radu‐Casian , Ossowski Sascha , Klusch Matthias
Published: June 2016

In this work, we focus on one particular area of the smart grid, namely, the challenges faced by distribution network operators in securing the balance between supply and demand in the intraday market, as a growing number of load‐controllable devices and small‐scale, intermittent generators coming from renewables are expected to pervade the system. We introduce a multiagent design to facilitate coordinating the various actors in the grid. The underpinning of our approach consists of an online cooperation scheme, ECOOP, where agents learn a prediction model regarding potential coalition partners and so can respond in an agile manner to situations that are occurring in the grid, by means of negotiating and formulating speculative solutions, with respect to the estimated behavior of the system. We provide a computational characterization for our solution in terms of complexity, as well as an empirical analysis against real consumption data sets, based on the macro‐model of the Australian energy market, showing a performance improvement of about 17%.
A Reform That Includes Eco‐Justice
Authors: Gebara Ivone
Published: June 2016

This article argues that in order to think seriously about an eco‐reformation, we must take the experience of daily life as central to theology. Too often reformations begin with trying to apply traditional theologies and scriptures to contemporary contexts; this is akin to cutting and pasting abstract ideas and scriptures written in other times and cultures onto the present. Instead, the daily, lived experiences of Christians living through periods of climate change should be the basis of the eco‐reformation that is needed. Such a method is able to look at theology and scripture as possible ecological problems in need of new interpretations from within the context of a changing climate.
The Pastoral Challenge of the Environmental Crisis: Environmental Anxiety and Lutheran Eco‐Reformation
Authors: Pihkala Panu
Published: June 2016

Plans for a Lutheran “eco‐reformation” are complicated by the polarization of views related to environmental issues. I argue that there is a special reason to take the agenda of eco‐reformation seriously: a widespread and often unconscious environmental anxiety, which posits a pastoral and existential challenge that must be addressed by the churches. I contextualize the challenge of eco‐reformation in the historical context of Lutheran eco‐theology. Finally, I briefly discuss two key themes for Lutheran eco‐theology: God's presence in nature and the theology of the cross.
Host plant preference and offspring performance of a leaf‐mining moth, Caloptilia fraxinella, on two Fraxinus species
Authors: Wist Tyler J. , Evenden Maya L.
Published: June 2016

The preference‐performance or ‘mother‐knows‐best’ hypothesis states that female insects choose to oviposit on a host plant that increases the performance of their offspring. This positive link between host plant choice and larval performance is especially important for leaf miners with non‐motile larvae that are entirely dependent upon the oviposition choice of the female for host plant location. Preference and performance of the ash leaf coneroller, Caloptilia fraxinella (Ely) (Lepidoptera: Gracillariidae), a specialist on ash trees, Fraxinus spp. (Oleaceae), were tested in a series of laboratory and field experiments. Female C. fraxinella were exposed to two closely related hosts, black ash, Fraxinus nigra Marshall, and green ash, Fraxinus pennsylvanica Marshall var. subintegerrima (Vahl), in oviposition choice and wind tunnel flight experiments to determine which host is most attractive for oviposition. Caloptilia fraxinella females were inconsistent in host choice, yet performance of larvae was greater on green than black ash. In preference studies, C. fraxinella preferred to oviposit on black ash when leaflets were removed from the tree, but preferred intact green ash over black ash seedlings for oviposition and host location in a wind tunnel. In the field, however, more C. fraxinella visited black ash var. ‘Fallgold’ at leaf flush than green ash at the same sites. Age of the ash leaflet also influences oviposition in this leaf miner and females preferred new over old leaflets for oviposition. Performance of C. fraxinella larvae was evaluated in field and laboratory experiments and was greater on green ash than on black ash in both experiments based on larval survival and development time parameters. The stronger oviposition and host location preference in the field for black ash were not linked to enhanced performance of offspring, as green ash was the superior host, supporting higher larval survival and faster development. A stronger host location preference in the wind tunnel for green ash over black ash, however, suggests that under certain circumstances with this moth species, ‘mother (may) know best’.
SCN8A encephalopathy: Research progress and prospects
Authors: Meisler Miriam H. , Helman Guy , Hammer Michael F. , Fureman Brandy E. , Gaillard William D. , Goldin Alan L. , Hirose Shinichi , Ishii Atsushi , Kroner Barbara L. , Lossin Christoph , Mefford Heather C. , Parent Jack M. , Patel Manoj , Schreiber John , Stewart Randall , Whittemore Vicky , Wilcox Karen , Wagnon Jacy L , Pearl Phillip L. , Vanderver Adeline , Scheffer Ingrid E.
Published: June 2016

On April 21, 2015, the first SCN8A Encephalopathy Research Group convened in Washington, DC, to assess current research into clinical and pathogenic features of the disorder and prepare an agenda for future research collaborations. The group comprised clinical and basic scientists and representatives of patient advocacy groups. SCN8A encephalopathy is a rare disorder caused by de novo missense mutations of the sodium channel gene SCN8A, which encodes the neuronal sodium channel Nav1.6. Since the initial description in 2012, approximately 140 affected individuals have been reported in publications or by SCN8A family groups. As a result, an understanding of the severe impact of SCN8A mutations is beginning to emerge. Defining a genetic epilepsy syndrome goes beyond identification of molecular etiology. Topics discussed at this meeting included (1) comparison between mutations of SCN8A and the SCN1A mutations in Dravet syndrome, (2) biophysical properties of the Nav1.6 channel, (3) electrophysiologic effects of patient mutations on channel properties, (4) cell and animal models of SCN8A encephalopathy, (5) drug screening strategies, (6) the phenotypic spectrum of SCN8A encephalopathy, and (7) efforts to develop a bioregistry. A panel discussion of gaps in bioregistry, biobanking, and clinical outcomes data was followed by a planning session for improved integration of clinical and basic science research. Although SCN8A encephalopathy was identified only recently, there has been rapid progress in functional analysis and phenotypic classification. The focus is now shifting from identification of the underlying molecular cause to the development of strategies for drug screening and prioritized patient care.
Improving the prevention of alien plant invasion in the EPPO region: the need to focus on highly invasive plants with (still) limited distribution – examples from Israel
Authors: Dufour‐Dror J. M.
Published: June 2016

Prevention (of invasion) is the most efficient strategy to control invasive alien plants (IAPs). This requires that potentially invasive plant taxa not yet introduced into regions where they could become invasive are identified as early as possible. Therefore, alongside the best known and already widespread IAPs it is crucial to highlight highly invasive plant taxa whose distribution is still limited. It becomes even more important to consider those taxa when some are recommended as ornamental/useful species outside their native range. This paper provides six examples of IAPs whose invasiveness has been established but which are still restricted to a single EPPO country (Israel). While horizon‐scanning studies have produced valuable alert lists, mainly for temperate Europe, EPPO pest risk analyses have focused on IAPs that are widespread outside the EPPO region. Therefore it is suggested that more attention is given to IAPs that pose a threat to Mediterranean, semiarid and arid areas within the EPPO region but that so far have remained largely unnoticed because of their present limited distribution. Awareness of these species must be urgently raised before they spread to new EPPO countries. The elaboration of a database compiling information about IAPs characterized by a restricted distribution in each EPPO country is discussed. The examples presented in this paper are most relevant to EPPO countries with a dry (Mediterranean, semiarid and arid) climate.
A Review of the Research in Emotionally Focused Therapy for Couples
Authors: Wiebe Stephanie A. , Johnson Susan M.
Published: June 2016

Emotionally Focused Therapy for Couples (EFT) is a brief evidence‐based couple therapy based in attachment theory. Since the development of EFT, efficacy and effectiveness research has accumulated to address a range of couple concerns. EFT meets or exceeds the guidelines for classification as an evidence‐based couple therapy outlined for couple and family research. Furthermore, EFT researchers have examined the process of change and predictors of outcome in EFT. Future research in EFT will continue to examine the process of change in EFT and test the efficacy and effectiveness of EFT in new applications and for couples of diverse backgrounds and concerns.
Changes in pediatric waist circumference percentiles despite reported pediatric weight stabilization in the United States
Authors: Fernández J. R. , Bohan Brown M. , López‐Alarcón M. , Dawson J. A. , Guo F. , Redden D. T. , Allison D. B.
Published: June 2016

Background

Obesity is a global health concern but the United States has reported a leveling in obesity rates in the pediatric population.

Objective

To provide updated waist circumference (WC) percentile values, identify differences across time and discuss differences within the context of reported weight stabilization in a nationally representative sample of American children.

Methods

Percentiles for WC in self‐identified African Americans (AA), European Americans (EA) and Mexican Americans (MA) were obtained from 2009–2014 National Health and Nutrition Examination Survey data (NHANES2014). Descriptive trends across time in 10th, 25th, 50th, 75th and 90th percentile WC distributions were identified by comparing NHANES2012 with previously reported NHANESIII (1988–1994).

Results

WC increased in a monotonic fashion in AA, EA and MA boys and girls. When compared with NHANESIII data, a clear left shift of percentile categories was observed such that values that used to be in the 90th percentile are now in the 85th percentile. Differences in WC were observed in EA and MA boys during a reported period of weight stabilization.

Conclusion and Relevance

WC has changed in the US pediatric population across time, even during times of reported weight stabilization, particularly among children of diverse racial/ethnic backgrounds.
The concurrent and longitudinal associations of temperament and nutritional risk factors in early childhood
Authors: van den Heuvel M. , Chen Y. , Abdullah K. , Maguire J. L. , Parkin P. C. , Birken C. S. ,   on behalf of the TARGet Kids! Collaboration
Published: June 2016

Background

Early childhood temperament is increasingly recognized as an important attribute that may impact screen time use, outdoor play and childhood obesity. The relationship between temperament and nutrition in preschool children is less clear.

Objective

The objective of the study is to investigate if temperament dimensions (negative affectivity, effortful control and surgency) in early childhood are associated with nutritional risk factors.

Methods

Six hundred seventy‐eight children were followed (mean age at baseline visit 3.1 years; mean time to follow‐up 16.5 months). Parents reported on child temperament and nutritional risk factors during regularly scheduled well‐child clinic visits.

Results

A mixed effect model demonstrated a significant association between higher negative affectivity (1.03; 95% CI 0.69 to 1.37) and higher effortful control (−0.88; 95% CI −1.27 to −0.49) on concurrent nutritional risk, independent of covariates. Multivariate linear regression analysis identified that higher effortful control, and not negative affectivity, was significantly associated with a decrease in nutritional risk (−0.67; 95% CI −1.10 to −0.24) over time, independent of covariates. There was no relationship identified between surgency and nutritional risk.

Conclusion

Three‐year‐old children with higher effortful control had reduced nutritional risk at 5 years of age. Future nutritional risk prevention strategies may benefit from interventions to increase effortful control in early childhood.
Interdisciplinary Research inSCM: Through the Lens of the Behavioral Theory of the Firm
Authors: Sanders Nada R. , Fugate Brian S. , Zacharia Zach G.
Published: June 2016

To accelerate research discoveries—those required to address paramount challenges facing business today—researchers from diverse disciplines must work together. Interdisciplinary research (IDR) is a research that involves bringing together perspectives from two or more disciplines in an integrative manner to address complex and multifaceted supply chain management (SCM) problems.IDRis needed to address contemporary business challenges. We look atSCMresearch through the lens of the Behavioral Theory of the Firm (BTF) drawing parallels in research evolution and noting similar antecedents in theoretical development. We point to the advancesBTFhas offered to organizational theory built onIDRand consider the possibilities forSCM. We make a case for methodological diversity in supporting this research, further paralleling lessons fromBTF. Last, we describe the state ofIDRinSCMtoday, discuss the objective of this special issue, and showcase the five contributing papers.
From Vagrancy Heterotopias to the Proximity of Homelessness. A Historical Ethnography of the State's Moral Dilemmas in the Management of Unease
Authors: Trovão Susana
Published: June 2016

This paper discusses the tension between the criminal justice system and the welfare state as expressed through practices focused on populations who are perceived as being ‘at risk’ and constituting ‘a danger’ to society, therefore challenging the national governance of social precariousness and public (in)security. The analysis of a paradigmatic institution of Portuguese Fascism has brought to light how the contradictions between the long‐term subjectivation of vagrancy processes and the uses of anti‐vagrancy policies promoted by the dictatorial state to arrest and punish a significant part of his citizens may justify the moral dilemmas underlying the current Portuguese State's response to homelessness and urban marginality.
Identity, accent aim, and motivation in second language users: New Scottish Gaelic speakers’ use of phonetic variation
Authors: Nance Claire , McLeod Wilson , O'Rourke Bernadette , Dunmore Stuart
Published: June 2016

This paper examines the use of phonetic variation in word‐final rhotics among nineteen adult new speakers of Scottish Gaelic, i.e. speakers who did not acquire the language through intergenerational transmission. Our speakers learned Gaelic as adults and are now highly advanced users of the language. We consider variation in their rhotic productions compared to the productions of six older, traditional speakers. Previous approaches to variation in second language users have either focussed on how variable production will eventually result in native‐like ‘target’ forms (Type 1 study), or have investigated the extent to which second language users reproduce patterns of variation similar to ‘native speakers’ (Type 2 study). We additionally draw on sociocultural approaches to Second Language Acquisition and apply notions of accent aim, identity construction, and learning motivation in order to fully explore the data. In doing so, we advocate a ‘Type 3’ approach to variation in second language users.
Gender, interaction and intonational variation: The discourse functions of High Rising Terminals in London
Authors: Levon Erez
Published: June 2016

In this paper, I examine the different conversational and interactional functions that High Rising Terminals (HRT) fulfil among young, White, middle‐class speakers of London English. Data are drawn from sixteen small‐group interviews with forty‐two individuals (28 women and 14 men) aged 18–25. From this corpus, 7351 declarative Intonation Phrases were extracted, and auditorily coded for the presence/absence ofHRTas well as for a variety of social, interactional and pragmatic factors. I combine quantitative and qualitative methods to demonstrate that while all of the speakers investigated useHRTto accomplish relational work in conversation, the specific interactional strategies that the feature is recruited to perform differ markedly across genders. I consider the ramifications of this finding for our understanding of ‘politeness’ as a gendered practice, and illustrate the importance of examining a variable likeHRTin its discourse‐functional context.
Ovalbumin expression in the oviduct magnum of hens is related to the rate of egg laying and shows distinct stress‐type‐specific responses
Authors: Zhao J. P. , Zhang Q. , Jiao H. C. , Wang X. J. , Jiang M. J. , Luo H. , Lin H.
Published: June 2016

Three trials were performed to evaluate the association of ovalbumin (OVA) abundance in the oviduct magnum with egg production and the underlying regulatory mechanism by glucocorticoids. In trial 1, twenty Hy‐Line Brown layers (56–60 weeks of age) with different combinations (n = 5/combination) of laying rate (high or low) and egg weight (high or low) were selected from an initial group of 300. An upregulated expression of magnum OVA was observed (p < 0.05) in hens with higher laying rate, regardless of egg weight. In trial 2, eighty Hy‐Line Brown layers (80–90 weeks of age) were subjected to the forced moulting (n = 8). The abundance of OVA transcript and protein in the magnum was significantly decreased during moulting (p < 0.01), and the same was true for laying rate (p < 0.01) and serum oestrogen (p < 0.05). In trial 3, forty‐five 56‐week‐old Hy‐Line Brown layers were kept individually (n = 15) in the following conditions for 10 days: constant optimal ambient temperature at 23 °C and ad libitum feeding, high ambient temperature at 32 °C for 6 h/day (10:00–16:00) and ad libitum feeding (32AL), and constant optimal ambient temperature at 23 °C and pair‐fed to the 32AL hens. In spite of elevated corticosterone in circulation, OVA synthesis, blood oestrogen and laying rate were not affected by heat exposure (p > 0.05). These results allow concluding that OVA expression in the oviduct magnum of hens is related to the rate of egg laying and shows distinct stress‐type‐specific responses.
Effects of dietary supplementation of bacteriophages against enterotoxigenic Escherichia coli (ETEC) K88 on clinical symptoms of post‐weaning pigs challenged with the ETEC pathogen
Authors: Lee C. Y. , Kim S. J. , Park B. C. , Han J. H.
Published: June 2016

The present study was performed to investigate the effects of dietary supplementation of bacteriophages (phages) against enterotoxigenic Escherichia coli (ETEC) K88 as a therapy against the ETEC infection in post‐weaning pigs. Two groups of post‐weaning pigs aged 35 days, eight animals per group, were challenged with 3.0 × 1010 colony forming units of ETEC K88, a third group given the vehicle. The unchallenged group and one challenged group were fed a basal nursery diet for 14 days while the remaining challenged group was fed the basal diet supplemented with 1.0 × 107 plaque forming units of the phage per kg. Average daily gain (ADG), goblet cell density and villous height:crypt depth (VH:CD) ratio in the intestine were less in the challenged group than in the unchallenged group within the animals fed the basal diet (p < 0.05); the reverse was true for rectal temperature, faecal consistency score (FCS), E. coli adhesion score (EAS) in the intestine, serum interleukin‐8 (IL‐8) and tumour necrosis factor‐α (TNF‐α) concentrations and digesta pH in the stomach, caecum and colon. The ETEC infection symptom within the challenged animals was alleviated by the dietary phage supplementation (p < 0.05) in ADG, FCS, EAS in the jejunum, serum TNF‐α concentration, digesta pH in the colon, goblet cell density in the ileum and colon and VH:CD ratio in the ileum. Moreover, the infection symptom tended to be alleviated (p < 0.10) by the phage supplementation in rectal temperature, EAS in the ileum and caecum, and VH:CD ratio in the duodenum and jejunum. However, EAS in the colon, digesta pH in the stomach and caecum, and goblet cell density in the jejunum did not change due to the dietary phage. Overall, results indicate that the phage therapy is effective for alleviation of acute ETEC K88 infection in post‐weaning pigs.
Influence of dietary slow‐release urea on growth performance, organ development and serum biochemical parameters of mutton sheep
Authors: Ji S. K. , Zhang F. , Sun Y. K. , Deng K. D. , Wang B. , Tu Y. , Zhang N. F. , Jiang C. G. , Wang S. Q. , Diao Q. Y.
Published: June 2016

Eighty Dorper × thin‐tailed Han cross‐bred non‐castrated male lambs [mean body weight (BW), 25.87 ± 1.06 kg] were randomly allocated to one of five different concentrations of slow‐release urea (urea phosphate, UP). The feed consisted of an equal amount of concentrate diet and roughage; the concentrate feed was formulated to be isoenergetic and isonitrogenic and contained 0%, 1%, 2%, 4% and 8% UP (UP0.0, UP1.0, UP2.0, UP4.0 and UP8.0, respectively) as a replacement for soya bean meal. Feed intake, BW, average daily gain (ADG), feed utilisation efficiency (FUE), absolute and relative organ weights and biochemical and histopathological parameters were measured. Feed intake, BW, ADG and FUE significantly decreased in the group receiving UP8.0 (p < 0.05), but no difference was found among the other groups (p > 0.05). Quadratic equations were developed between the UP dosage in the concentrate feed and ADG or FUE (r2 = 0.973 for ADG and r2 = 0.761 for FUE) to determine the appropriate dosage of UP given the desire to maximise either ADG or FUE, the appropriate dosage (feed concentration) was calculated as 2.01% UP to achieve the greatest ADG or 2.13% UP to achieve the best FUE. The relative weight of the liver (% BW) in the UP2.0 groups was significantly greater than that of UP0.0 (p < 0.05), and the relative weight of the intestine in the UP8.0 was significantly greater than that of UP0.0 (p < 0.05); the relative weight of the carcass, heart, spleen, lung, kidney, rumen, reticulum, omasum and abomasum did not differ among treatments (p > 0.05). The UP8.0 treatment significantly increased serum phosphorus levels (p < 0.05) and decreased the levels of alkaline phosphatase, glucose and calcium (Ca) compared with the lower UP dosage (p < 0.05). No histopathological differences were found in either hepatic tissues or renal tissues among treatments. Dietary UP as a replacement for soya bean in concentrate feeds for mutton sheep should not exceed 4%, as higher dosing may cause malnutrition and mineral disorders.
Multi‐centre retrospective study of long‐term outcomes following traumatic elbow luxation in 37 dogs
Authors: Sajik D. , Meeson R. L. , Kulendra N. , Jordan C. J. , James D. , Calvo I. , Farrell M. , Kulendra E.
Published: June 2016

OBJECTIVES

Limited guidelines exist regarding the optimal treatment of traumatic canine elbow luxation, and there is a lack of information on long‐term functional outcome. Here we report reduction and stabilisation techniques for a series of traumatic elbow luxations and describe clinical outcome plus long‐term questionnaire‐based follow‐up.

METHODS

Retrospective review of canine traumatic elbow luxations (2006 to 2013) treated at five referral centres. Data recorded included signalment, luxation aetiology, time to reduction, reduction technique, surgical procedure, post‐reduction care and complications. Questionnaire follow‐up was attempted for all cases with owners completing the Canine Brief Pain Inventory.

RESULTS

Thirty‐seven dogs were included. The most frequent cause of luxation was road traffic accident (n=22). Twenty cases were treated surgically. Seven dogs suffered major postoperative complications: reluxation (n=6), infection requiring implant removal (n=1). Four of the six reluxations occurred in dogs that had other orthopaedic injuries. Twenty‐two owners completed the Canine Brief Pain Inventory questionnaire: there were 13 excellent, 6 very good, 1 good and 2 fair outcomes. Outcome was not associated with the reduction technique.

CLINICAL SIGNIFICANCE

Initial closed reduction, followed by surgical stabilisation if unsuccessful, results in good‐to‐excellent outcomes in the majority of traumatic canine elbow luxations. Reluxation was the most common major complication and there was a higher incidence of reluxation in patients with multiple orthopaedic injuries.
Genome‐wide set of SNPs reveals evidence for two glacial refugia and admixture from postglacial recolonization in an alpine ungulate
Authors: Sim Zijian , Hall Jocelyn C. , Jex Bill , Hegel Troy M. , Coltman David W.
Published: June 2016

Past glaciation events have played a major role in shaping the genetic diversity and distribution of wild sheep in North America. The advancement of glaciers can isolate populations in ice‐free refugia, where they can survive until the recession of ice sheets. The major Beringian refugium is thought to have held thinhorn sheep (Ovis dalli) populations during times of glacial advance. While isolation in the major refugium can account for much of the genetic and morphological diversity seen in extant thinhorn sheep populations, mounting evidence suggests the persistence of populations in smaller minor refugia. We investigated the refugial origins of thinhorn sheep using ~10 000 SNPs obtained via a cross‐species application of the domestic sheep ovine HD BeadChip to genotype 52 thinhorn sheep and five bighorn sheep (O. canadensis) samples. Phylogenetic inference revealed a distinct lineage of thinhorn sheep inhabiting British Columbia, which is consistent with the survival of a group of thinhorn sheep in a minor refugium separate from the Beringian refugium. Isolation in separate glacial refugia probably mediated the evolution of the two thinhorn sheep subspecies, the white Dall's sheep (O. d. dalli), which persisted in Beringia, and the dark Stone's sheep (O. d. stonei), which utilized the minor refugium. We also found the first genetic evidence for admixture between sheep from different glacial refugia in south‐central Yukon as a consequence of post glacial expansion and recolonization. These results show that glaciation events can have a major role in the evolution of species inhabiting previously glaciated habitats and the need to look beyond established refugia when examining the evolutionary history of such species.
Homologues of CsLOB1 in citrus function as disease susceptibility genes in citrus canker
Authors: Zhang Junli , Huguet ‐Tapia Jose Carlos , Hu Yang , Jones Jeffrey , Wang Nian , Liu Sanzhen , White Frank F.
Published: June 2016

The lateral organ boundary domain (LBD) genes encode a group of plant‐specific proteins that function as transcription factors in the regulation of plant growth and development. Citrus sinensis lateral organ boundary 1 (CsLOB1) is a member of the LBD family and functions as a disease susceptibility gene in citrus bacterial canker (CBC). Thirty‐four LBD members have been identified from the Citrus sinensis genome. We assessed the potential for additional members of LBD genes in citrus to function as surrogates for CsLOB1 in CBC, and compared host gene expression on induction of different LBD genes. Using custom‐designed transcription activator‐like (TAL) effectors, two members of the same clade as CsLOB1, named CsLOB2 and CsLOB3, were found to be capable of functioning similarly to CsLOB1 in CBC. RNA sequencing and quantitative reverse transcription‐polymerase chain reaction analyses revealed a set of cell wall metabolic genes that are associated with CsLOB1, CsLOB2 and CsLOB3 expression and may represent downstream genes involved in CBC.
Prolonged esophageal acid exposures induce synaptic downscaling of cortical membrane AMPA receptor subunits in rats
Authors: Banerjee B. , Medda B. K. , Zhang J. , Tuchscherer V. , Babygirija R. , Kannampalli P. , Sengupta J. N. , Shaker R.
Published: June 2016

Background

We recently reported the involvement of AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid) receptor subunit upregulation and phosphorylation in the rostral cingulate cortex (rCC) as the underlying mechanism of acute esophageal acid‐induced cortical sensitization. Based on these findings, we proposed to investigate whether prolonged esophageal acid exposures in rats exhibit homeostatic synaptic scaling through downregulation of AMPA receptor expression in rCC neurons. We intended to study further whether this compensatory mechanism is impaired when rats are pre‐exposed to repeated esophageal acid exposures neonatally during neuronal development.

Methods

Two different esophageal acid exposure protocols in rats were used. Since AMPA receptor trafficking and channel conductance depend on CaMKIIα‐mediated phosphorylation of AMPA receptor subunits, we examined the effect of esophageal acid on CaMKIIα activation and AMPA receptor expression in synaptoneurosomes and membrane preparations from rCCs.

Key Results

In cortical membrane preparations, GluA1 and pGluA1Ser831 expression were significantly downregulated following prolonged acid exposures in adult rats; this was accompanied by the significant downregulation of cortical membrane pCaMKIIα expression. No change in GluA1 and pGluA1Ser831 expression was observed in rCC membrane preparations in rats pre‐exposed to acid neonatally followed by adult rechallenge.

Conclusions & Inferences

This study along with our previous findings suggests that synaptic AMPA receptor subunits expression and phosphorylation may be involved bidirectionally in both esophageal acid‐induced neuronal sensitization and acid‐dependent homeostatic plasticity in cortical neurons. The impairment of homeostatic compensatory mechanism as observed following early‐in‐life acid exposure could be the underlying mechanism of heightening cortical sensitization and esophageal hypersensitivity in patients with gastroesophageal reflux disease.
Neogene sloth assemblages (Mammalia,Pilosa) of theCocinetasBasin (LaGuajira,Colombia): implications for theGreatAmericanBioticInterchange
Authors: Amson Eli , Carrillo Juan D. , Jaramillo Carlos
Published: June 2016

We describe sloth assemblages from theCocinetasBasin (LaGuajira peninsula,Colombia), found in theNeogeneCastilletes andWare formations, located in northernmostSouthAmerica, documenting otherwise poorly known biotas. The tentative referral of a specimen to a small megatherioid sloth,Hyperleptus?, from the early–middleMioceneCastilletesFormation, suggests affinities of this fauna with the distantSantaCruzFormation and documents a large latitudinal distribution for this taxon. The latePlioceneWareFormation is much more diverse, with five distinct taxa representing every family of ‘ground sloths’. This diversity is also remarkable at the ecological level, with sloths spanning over two orders of magnitude of body mass and probably having different feeding strategies. Being only a few hundred kilometres away from theIsthmus ofPanama, and a few hundred thousand years older than the classically recognized first main pulse of theGreatAmericanBiotic interchange (GABI1), theWareFormation furthermore documents an important fauna for the understanding of this major event inNeogene palaeobiogeography. The sloths for which unambiguous affinities were recovered are not closely related to the early immigrants found inNorthAmerica beforeGABI1.
Development of gene‐based markers for the Turnip mosaic virus resistance gene retr02 in Brassica rapa
Authors: Li Guo‐Liang , Qian Wei , Zhang Shu‐Jiang , Zhang Shi‐Fan , Li Fei , Zhang Hui , Wu Jian , Wang Xiao‐Wu , Sun Ri‐Fei
Published: June 2016

Turnip mosaic virus (TuMV) is responsible for a serious disease that affects the production of Chinese cabbage. Previous studies have cloned a series of TuMV resistance genes and developed molecular markers. In this study, a derived cleaved amplified polymorphism sequence (dCAPS) marker and a Kompetitive Allele Specific PCR (KASP) marker were developed based on a single recessive gene, retr02, which confers broad‐spectrum TuMV resistance in Chinese cabbage by means of an additional G at the junction of exon 1 and intron 1. The two markers were able to detect the retr02 allele in Chinese cabbage accessions used in breeding programmes. Compared with the dCAPS marker, the KASP marker was flexible, cost‐effective and quick to process, which is likely to be beneficial in establishing high‐throughput assays for marker‐assisted selection.
Diffuse Reflectance Spectroscopy Versus Mexameter® MX18 Measurements of Melanin and Erythema in an African Population
Authors: Wright Caradee Y. , Karsten Aletta E. , Wilkes Marcus , Singh Ann , du Plessis Johan , Albers Patricia N. , Karsten Petrus A.
Published: June 2016

Melanin provides protection against excess exposure to solar ultraviolet radiation (UVR) and related adverse health effects. Diffuse reflectance spectroscopy (DRS) can be used to calculate cutaneous melanin and erythema, but this is complex and has been mostly used for light‐to‐medium pigmented skin. Handheld reflectance spectrophotometers, such as the Mexameter® MX18, can also be used. We compared DRS‐calculated melanin and erythema values with Mexameter melanin and erythema index values to understand how these techniques/measurements correlate in an African population of predominantly deeply pigmented skin. Five hundred and three participants comprised 68.5% self‐identified Black African, 9.9% Indian/Asian, 18.4% White and 2.9% Colored. The majority of Black African (45%), Indian/Asian (34%) and Colored (53%) participants self‐identified their skin as being “brown.” Measured melanin levels increased with darker self‐reported skin color. DRS‐calculated and Mexameter melanin values demonstrated a positive correlation (Spearman rho = 0.87, P < 0.001). The results from both instruments showed erythema values were strongly correlated with their own melanin values. This finding is considered spurious and may result from the complexity of separating brown and red pigment when using narrowband reflectance techniques. Further work is needed to understand melanin, erythema and color in Black skin given sun‐related health risks in vulnerable groups in Africa.
Fungal endophyte protects Atractylodes lancea from root rot caused by Fusarium oxysporum
Authors: Ren C.‐G. , Chen F. , Dai C.‐C.
Published: June 2016

Endophytic fungi, which stimulate a variety of defence reactions in host plants without causing visible disease symptoms, have been isolated from almost every plant. However, beneficial interactions between fungal endophytes and pathogens from the same habitat remain largely unknown. An inoculation of Atractylodes lancea plantlets with Gilmaniella sp. AL12 (AL12) prior to infection with Fusarium oxysporum prevented the necrotization of root tissues and plant growth retardation commonly associated with fusarium root rot. Quantification of F. oxysporum infections using real‐time PCR revealed a correlation between root rot symptoms and the relative amount of fungal DNA. Pretreatment with AL12 reduced the accumulation of reactive oxygen species stimulated by F. oxysporum. An in vitro analysis of their interactions under axenic culture conditions showed AL12 could inhibit F. oxysporum growth. Additionally, F. oxysporum infections were shown to decrease salicylic acid (SA) production compared with control plantlets. SA biosynthesis inhibitors, 2‐aminoindan‐2‐phosphonic acid and paclobutrazol, abolished the inhibition of F. oxysporum growth in A. lancea even after inoculation with AL12. The results indicated that the fungal endophyte protected A. lancea not only by direct antibiosis, but also by reversing the F. oxysporum‐mediated suppression of SA production.