bluuebunny/crossref_metadata_2025 huggingface dataset:
Employment Protection Reform, Enforcement in Collective Agreements and Worker Flows
Authors: Heyman Fredrik , Skedinger Per
Published: September 2016

We analyze a reform of notice periods for employer‐initiated separations in Sweden, which reduced the notice periods for newly hired older workers substantially but implied minor or no changes in the advance notices for younger workers. The reform was initiated at different times depending on collective agreement. These circumstances provide ample opportunity for the identification of its effects. Our findings indicate heterogeneous effects on hirings and separations across collective agreements.
Arguing Sanctions. On the EU's Response to the Crisis in Ukraine
Authors: Sjursen Helene , Rosén Guri
Published: September 2016

Despite diverging perspectives and interests, the EU's Member States have forged a common response to the Russia–Ukraine crisis. How can this be? In this article, we suggest that in order to explain the Member States' ability to reach agreement in this case, we must take into account the normative force of the arguments presented in favour of a common response. We find that neither a concern for security (as would be expected from a realist perspective) nor the institutionalization of a norm of cohesion (which would be the constructivist expectation) triggered the collective response. Instead, agreement was established due to concurrence over a fundamental breach of the Ukrainians' right to self‐determination. This finding is significant in theoretical terms in that it confirms that norms may trump interests. It does not, however, allow for definite conclusions with regard to the robustness of integration in EU foreign policy.
Fracture Resistance of Premolars Restored Either with Short Fiber or Polyethylene Woven Fiber‐Reinforced Composite
Authors: Gürel Mügem Asli , Helvacioğlu Kivanç Bağdagül , Ekıcı Adil , Alaçam Tayfun
Published: September 2016

Objective

To compare the fracture resistance of endodontically treated maxillary premolars with one remaining cavity wall restored either with short fiber‐reinforced composite or polyethylene woven fiber‐reinforced composite.

Materials and Methods

Forty‐eight maxillary premolars were endodontically treated and randomly assigned to four groups (n = 12). Palatal cusp was removed, buccal wall was remained. In groups 1 to 3, standardized cavities were prepared in the palatal canal entrances. In group 1, short fiber‐reinforced composite was used for restoration both of deep cavity and coronal part. In group 2, short fiber‐reinforced composite was placed inside the deep cavity and core part of the restoration. Coronal restoration was restored by using conventional filler composite. In group 3, both deep cavities and coronal parts were built up by using conventional filler composite. In group 4, post space was prepared in the palatal canal. Polyethylene woven fiber‐reinforced composite post then was placed into post space and the coronal part was restored by using conventional filler composite. Specimens were placed into a universal testing machine. The fracture loads were recorded and analyzed statistically using one‐way ANOVA (α = 0.05). Fracture patterns were analyzed by using Chi‐square test (α = 0.05).

Results

No statistically significant difference was found in fracture strength (p > 0.05). Group 1 exhibited the highest and group 4 exhibited the lowest incidence of restorable fracture (p < 0.05).

Conclusions

The restoration of severely weakened premolar teeth with the use of short fiber‐reinforced composite might have advantages over conventional filler composite or polyethylene woven fiber‐reinforced composite techniques.

Clinical Significance

The results of this in vitro study will be helpful to understand reinforced composite materials for restoring endodontically treated maxillary premolars. (J Esthet Restor Dent 28:412–418, 2016)
Kinesin‐14 is Important for Chromosome Segregation During Mitosis and Meiosis in the Ciliate Tetrahymena thermophila
Authors: Kushida Yasuharu , Takaine Masak , Nakano Kentaro , Sugai Toshiro , Vasudevan Krishna Kumar , Guha Mayukh , Jiang Yu‐Yang , Gaertig Jacek , Numata Osamu
Published: September 2016

Ciliates such as Tetrahymena thermophila have two distinct nuclei within one cell: the micronucleus that undergoes mitosis and meiosis and the macronucleus that undergoes amitosis, a type of nuclear division that does not involve a bipolar spindle, but still relies on intranuclear microtubules. Ciliates provide an opportunity for the discovery of factors that specifically contribute to chromosome segregation based on a bipolar spindle, by identification of factors that affect the micronuclear but not the macronuclear division. Kinesin‐14 is a conserved minus‐end directed microtubule motor that cross‐links microtubules and contributes to the bipolar spindle sizing and organization. Here, we use homologous DNA recombination to knock out genes that encode kinesin‐14 orthologues (KIN141, KIN142) in Tetrahymena. A loss of KIN141 led to severe defects in the chromosome segregation during both mitosis and meiosis but did not affect amitosis. A loss of KIN141 altered the shape of the meiotic spindle in a way consistent with the KIN141's contribution to the organization of the spindle poles. EGFP‐tagged KIN141 preferentially accumulated at the spindle poles during the meiotic prophase and metaphase I. Thus, in ciliates, kinesin‐14 is important for nuclear divisions that involve a bipolar spindle.
Characterization of circular RNAs landscape in multiple system atrophy brain
Authors: Chen Bei Jun , Mills James D. , Takenaka Konii , Bliim Nicola , Halliday Glenda M. , Janitz Michael
Published: September 2016

Circular RNAs (circRNAs) have been recently identified as a naturally occurring family of widespread and diverse endogenous non‐coding RNAs that may regulate gene expression in mammals. They are unusually stable RNA molecules with cell type‐ or developmental stage‐specific expression patterns. However, the role of circRNAs in pathology of complex disease is entirely unknown. Here, we report the specific circular transcriptome in the multiple system atrophy (MSA) brain as determined by RNA sequencing. Five circRNAs, namely IQCK, MAP4K3, EFCAB11, DTNA, and MCTP1, were identified and validated as specifically over‐expressed in MSA frontal cortex. The expression levels of linear transcripts were not significantly altered and thus did not follow the pattern of their circular counterparts. Further analysis of expression of five MSA‐specific circRNAs revealed their over‐expression in the white matter of the MSA cortical tissue. Together, this is the first report describing perturbation of circular transcriptome in α‐synucleinopathies.

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Platelet‐rich plasma and hyaluronic acid – an efficient biostimulation method for face rejuvenation
Authors: Ulusal Betul Gozel
Published: September 2016

Background

Cosmetic applications of platelet‐rich plasma (PRP) are new, and reports are scarce and dispersed in the literature. There are a variety of commercially available kits and injection techniques, and the number and intervals of injections vary. New investigations should focus on developing a standardized procedure for PRP preparation and application methods to augment its efficacy and potency.

Objectives

In this report, we aim to provide data and commentary to assist and add to current guidelines.

Methods

A series of 94 female patients with varying degrees of facial aging signs were treated with PRP and hyaluronic acid (HA). Mean age was 53.0 ± 5.6. The mean injection number was 3.6 ± 2.0. Platelet‐poor and platelet‐ rich plasma parts were mixed with 0.5 cc %3.5 hyaluronic acid and 0.5 cc procaine and injected with a 30G, 13‐mm needle into deep dermis and hypodermis. Patients were asked to rate their personal satisfaction with their skin texture, pigmentation, and sagging. In addition, the overall results were rated by three independent physicians and the patients themselves. The outcomes were peer‐reviewed, and correlations between the degree of the aesthetic scores and the number of injections were explored.

Results

There was a statistically significant difference in general appearance, skin firmness‐sagging and skin texture according to the patients’ before and after applications of PRP. A statistically significant correlation was found between the number of injections and overall satisfaction.

Conclusions

Compared to the baseline, the PRP and HA injections provided clinically visible and statistically significant improvement on facial skin. The improvements were more remarkable as the injection numbers increased.
Hair removal‐related injuries in the United States, 1991–2014
Authors: Swain Thomas A , Tully Albert Scott , Redford Travis , McGwin Gerald
Published: September 2016

Background

Hair removal practices have changed in frequency and location on the body. Previous research on hair removal injuries has focused on a specific body region, age, or gender.

Objective

This study sought to take a broader perspective of hair removal‐associated injuries in the United States which sought treatment at emergency departments.

Methods

Data from the National Electronic Injury Surveillance System (NEISS) from 1991 to 2014 were used to identify hair removal‐related injuries. Incidence rates were determined for the overall population and stratified by gender and age category using US Census Bureau population estimates.

Results

From 1991 to 2014, there were an estimated 292 053 hair removal‐associated injuries in the United States. The overall incidence rate was highest in 2013 (9/100 000). Those aged 65+ had the highest incidence from 1991 to 2010 with those aged 19–34 having the highest rate starting in 2011. When stratified by body region injured, males had highest injury rates to the face and females had highest rates to the lower limbs. Starting in 2010, those aged 19–34 had higher incidence particularly for pubic and trunk regions.

Conclusion

The incidence of hair removal‐associated injuries seen by emergency departments increased nearly ninefold between 1991 and 2013. Due to the increased incidence among 19‐ to 34‐year‐olds, caution should be taken particularly for this age group when undergoing depilatory practices. Overall, individuals should practice safe and acceptable usage of hair removal products to reduce the risk of injury.
Potential health hazards of eating red meat
Authors: Wolk A.
Published: September 2016

Red meat (beef, veal, pork, lamb and mutton) consumption contributes several important nutrients to the diet, for example essential amino acids, vitamins (including B12) and minerals (including iron and zinc). Processed red meat (ham, sausages, bacon, frankfurters, salami, etc.) undergoes treatment (curing, smoking, salting or the use of chemical preservatives and additives) to improve its shelf life and/or taste. During recent decades, consumption of red meat has been increasing globally, especially in developing countries. At the same time, there has been growing evidence that high consumption of red meat, especially of processed meat, may be associated with an increased risk of several major chronic diseases. Here, a comprehensive summary is provided of the accumulated evidence based on prospective cohort studies regarding the potential adverse health effects of red meat consumption on major chronic diseases, such as diabetes, coronary heart disease, heart failure, stroke and cancer at several sites, and mortality. Risk estimates from pooled analyses and meta‐analyses are presented together with recently published findings. Based on at least six cohorts, summary results for the consumption of unprocessed red meat of 100 g day−1 varied from nonsignificant to statistically significantly increased risk (11% for stroke and for breast cancer, 15% for cardiovascular mortality, 17% for colorectal and 19% for advanced prostate cancer); for the consumption of 50 g day−1 processed meat, the risks were statistically significantly increased for most of the studied diseases (4% for total prostate cancer, 8% for cancer mortality, 9% for breast, 18% for colorectal and 19% for pancreatic cancer, 13% for stroke, 22% for total and 24% for cardiovascular mortality and 32% for diabetes). Potential biological mechanisms underlying the observed risks and the environmental impact of red meat production are also discussed. The evidence‐based integrated message is that it is plausible to conclude that high consumption of red meat, and especially processed meat, is associated with an increased risk of several major chronic diseases and preterm mortality. Production of red meat involves an environmental burden. Therefore, some European countries have already integrated these two issues, human health and the ‘health of the planet’, into new dietary guidelines and recommended limiting consumption of red meat.
Stressors alter intercellular communication and exosome profile of nasopharyngeal carcinoma cells
Authors: Harmati Maria , Tarnai Zsofia , Decsi Gabor , Kormondi Sandor , Szegletes Zsolt , Janovak Laszlo , Dekany Imre , Saydam Okay , Gyukity‐Sebestyen Edina , Dobra Gabriella , Nagy Istvan , Nagy Katalin , Buzas Krisztina
Published: September 2016

Background

Head and neck cancers comprise the sixth most common cancer type worldwide. One of the most remarkable malignancies of the head and neck is the cancer of the nasopharynx, with a strong metastatic tendency already in the early stage. Besides the conventional pathways of metastasis formation, the information content of exosomes produced by the cancer cells may play a key role in metastatic transformation. The aim of this study was to investigate how stressors alter the characteristic of tumor derived exosomes.

Methods

In our experimental model, we compared the quantity and content of exosomes produced by a nasopharyngeal carcinoma cell line (5‐8F) under conventional (chemotherapy) and alternative (Ag–TiO2‐catalyzed reactive oxygen species generation) cytostatic treatment. After isolation, exosomes were identified by atomic force microscopy and quantified with Nanosight NS500 device. MicroRNA content of them was analyzed using SOLiD 5500xl technology. The sequences were annotated in CLC Genomics Workbench version 5.5.1.

Results

Beyond the classic chemotherapeutic agent (doxorubicin), Ag–TiO2 in a photo‐catalytic process also showed cytostatic activity. Tumor cell damage induced by the cytostatic treatments significantly altered the number of released exosomes and led to the predominance of tumor suppressors in the exosomal miRNA profile.

Conclusions

Our results suggest that the intercellular communication between tumor cells and surrounding stroma cells can be altered by microenvironment which increased quantity of exosomes and diversity of miRNAs in this study. Imbalance of oncogenic and tumor suppressor miRNAs caused by cytostatic treatments may influence the antiproliferative and metastasis inhibitory effect of cytostatic agents.
Obstructive Sleep Apnea Management: An Overview of the Literature
Authors: AlRumaih Hamad S. , Baba Nadim Z. , AlShehri Abdulkareem , AlHelal Abdulaziz , Al‐Humaidan Abdulkareem
Published: September 2016

Purpose

Different approaches have been proposed to treat obstructive sleep apnea (OSA). This article reviews a synopsis of the available literature regarding the management of OSA.

Methods

A comprehensive review of the literature on the management of OSA began with a search of English‐language peer‐reviewed manuscripts using PubMed and MEDLINE. The focus was on clinical research articles published between 1996 and 2016. A search of relevant dental journals was also completed.

Results

OSA can be managed through behavior management, continuous positive airway pressure (CPAP), oral appliances, and other therapies. Clinicians may select treatment modalities based on the severity of clinical presentation and the patient's symptoms.

Conclusion

Studies showed an enhancement in the quality of life in many patients who have been treated with oral appliances, and patients in general prefer oral appliances over CPAP therapy or any other treatments for OSA because of its convenience.
In Vitro Effectiveness of a Terpenic Denture Cleanser on Old Biofilm Surfaces
Authors: Martínez Alejandra , Catalán Alfonso , Rojas Ninón , Torres Viviana , Acuña Mónica
Published: September 2016

Purpose

To assess the effects of terpenic denture cleanser on denture biofilm removal using scanning electron microscopy (SEM).

Materials and Methods

The internal surface biofilm of four maxillary dentures was elucidated with Caristop‐revelador Dual Tone, and 40 blue‐stained specimens (0.6 cm × 0.4 cm × 2 mm) were obtained. These specimens were randomly assigned to one of the following four groups of 10 specimens each: control, Eci Clean, Fitty Dent, and terpenic denture cleanser. The period of immersion in each solution was 12 hours. Biofilm removal was evaluated using SEM, and morphologically varying areas of the SEM images were quantified with Imaris software. The data were analyzed using Kolmogorov‐Smirnov, t‐tests, ANOVA, and Tamhane's tests (p = 0.05).

Results

Data revealed that terpenic denture cleanser removed significantly more biofilm than any other treatment examined in this study. The t‐tests revealed significant differences in the clean area that resulted from the use of the terpenic cleanser compared with the clean area that resulted from the use of Eci Clean (p = 0.013). Fitty Dent was the least effective and left dirty acrylic resin. The average areas with few removed layers were 59.3%, 43.3%, and 9.5% in Fitty Dent, Eci Clean, and terpenic cleanser groups, respectively. Tamhane's tests indicated that the Eci Clean and Fitty Dent groups were significantly different from the 0.5% terpenic cleanser group (p = 0.008).

Conclusion

The terpenic denture cleanser was effective in removing denture biofilm.
Utility‐based quality of life in mothers of children with behaviour problems: A population‐based study
Authors: Le Ha ND , Gulenc Alisha , Gold Lisa , Sarkadi Anna , Ukoumunne Obioha C , Bayer Jordana , Wake Melissa , Hiscock Harriet
Published: September 2016

Aim

To examine the relationship between mothers’ health‐related quality of life (HRQoL) and child behaviour problems at age 2 years. To investigate whether the relationship between maternal HRQoL and child behaviour problems is independent of maternal mental health.

Methods

Cross‐sectional survey nested within a population‐level, cluster randomised trial, which aims to prevent early child behaviour problems. One hundred and sixty mothers of 2‐year‐old children, in nine local government areas in Victoria, Australia. HRQoL was measured using the Assessment of Quality of Life 6D and child behaviour was measured using the child behaviour checklist (CBCL/1.5–5 years). Maternal mental health was measured using the Depression Anxiety Stress Scale. Data were collected at child age 2 years; demographic data were collected at child age 8 months.

Results

HRQoL was lower for mothers with children that had borderline/clinical behaviour problems compared to those with children without problems (mean difference −0.14, 95% confidence interval (CI): −0.16 to −0.12, P < 0.001). The finding did not markedly change when adjusting for household income, financial security, child gender, child temperament and intervention group status at child age 8 months (mean difference −0.12, 95% CI: −0.15 to −0.09, P < 0.001), but did attenuate when additionally adjusting for concurrent maternal mental health (mean difference −0.03, 95% CI: −0.05 to −0.02, P < 0.001).

Conclusions

Child behaviour problems were associated with lower maternal HRQoL. Child behaviour problems prevention programmes could consider this association with maternal HRQoL and be designed to improve and report both mothers’ and their child's health and wellbeing.
Determinants of developmental progress in pre‐schoolers referred for neuro‐developmental diagnosis
Authors: Milne Susan , McDonald Jenny , Kayrouz Norma
Published: September 2016

Aim

To determine factors associated with change in developmental progress in pre‐schoolers referred to a developmental clinic.

Methods

Of 360 pre‐schoolers referred to a Child Assessment clinic for neuro‐developmental diagnosis before 3.6 years, 190 (53%) were reassessed prior to school entry and recruited to this study. They were assessed with the Bayley Scales of Infant and Toddler Development (3rd edn) before 3.5 years and the Griffiths Mental Development Scales before school entry. The influence of medical and environmental variables on improvement or deterioration in scores (±0.5 SD) was examined using logistic regression.

Results

Consistent scores were present in 51.6% of children, and associated with environmental variables. Children with stable scores were more likely to live in a suburb of social advantage (OR = 3.2; 95%CI = 1.37–7.64, P = 0.008) or to come from families dependent on welfare or public housing (OR=4.8; 95%CI = 2.19–10.49, P < 0.001). Improvement was seen in 18.1% of children; they were more likely to have commenced therapy after the first assessment (OR = 2.4; 95%CI = 1.05–5.58, P = 0.038). Deterioration of scores was seen in 30% of children. Children with a mild delay on initial assessment were less likely to deteriorate (OR = 2.9; 95%CI = 1.16–7.04, P = 0.022), while lower scores were more likely in children with neuro‐motor disabilities (OR = 10.8; 95%CI = 2.64–44.58, P < 0.001), and chromosomal variations of both known and unknown significance (OR = 4.4; 95%CI = 1.54–12.76, P = 0.006).

Conclusions

Socio‐economic advantage and disadvantage are associated with stable scores, but introducing intervention is associated with improved scores. Deterioration is most likely in children with chromosomal variations or neuro‐motor disabilities, and regular reassessment of these children is recommended.
Emotion Regulation and Coping Strategies in Pedagogical Students with Different Attachment Styles
Authors: Prosen Simona , Vitulić Helena Smrtnik
Published: September 2016

Abstract: Emotion regulation (ER) and coping strategies were compared in 242 pedagogical students from the Faculty of Education, University of Ljubljana, with different attachment styles: secure (51.3%), fearful (31.9%), preoccupied (14.2%), and dismissive (2.7%). The students’ ages ranged from 18 to 24 years (
M
 = 19.02;
SD
 = .92), and the majority were female (95.0%). They completed three questionnaires assessing their attachment styles and their use of ER and coping strategies. It was determined that the students used the majority of ER and coping strategies sometimes. Somewhat different patterns in the use of ER and coping strategies were, however, present in each attachment‐based group. Significant differences between these groups appeared in their use of the ER strategies of social support, suppression, and comfort eating, and in the coping strategies of seeking social support and escaping or avoiding stressful situations.
Capromorelin increases food consumption, body weight, growth hormone, and sustained insulin‐like growth factor 1 concentrations when administered to healthy adult Beagle dogs
Authors: Zollers B. , Rhodes L. , Smith R. G.
Published: September 2016

This study's objective was to determine the effects in dogs of oral capromorelin, a ghrelin agonist, at different doses for 7 days on food consumption, body weight and serum concentrations of growth hormone (GH), insulin‐like growth factor 1 (IGF‐1), and cortisol. Adult Beagles (n = 6) were dosed with placebo BID, capromorelin at 3.0 mg/kg SID, 4.5 mg/kg SID, or 3.0 mg/kg BID. Food consumption, body weight, serum capromorelin, GH, IGF‐1, and cortisol were measured at intervals on days 1, 4, 7, and 9. Capromorelin increased food consumption and body weight compared to placebo and caused increased serum GH, which returned to the baseline by 8 h postdose. The magnitude of the GH increase was less on days 4 and 7 compared to Day 1. IGF‐1 concentrations increased on Day 1 in capromorelin‐treated dogs and this increase was sustained through Day 7. Serum cortisol increased postdosing and returned to the baseline concentrations by 8 h. The magnitude of the increase was less on days 4 and 7 compared to Day 1. A dose of 3 mg/kg was chosen for further study in dogs based on this dose causing increased food consumption and sustained IGF‐1 serum concentrations that may increase lean muscle mass when administered over extended periods.
Identification of novel OCT4 genetic variant associated with the risk of chronic hepatitis B in a Korean population
Authors: Shin Joong‐Gon , Cheong Hyun Sub , Lee Kwanghyun , Ju Bong‐Gun , Lee Jeong‐Hoon , Yu Su Jong , Yoon Jung‐Hwan , Cheong Jae Youn , Cho Sung Won , Park Neung Hwa , Namgoong Suhg , Kim Lyoung Hyo , Kim Yoon Jun , Shin Hyoung Doo
Published: September 2016

Background & Aims

Hepatitis B viral infection is a serious risk factor for chronic hepatitis B (CHB), cirrhosis and hepatocellular carcinoma. Recently, several genome‐wide association studies (GWASs) have been conducted to identify important genetic variant associated with the risk of CHB. In our previous GWAS, TCF19 was identified as one of the susceptibility genes for CHB risk (P=4.2×10−9 at rs1419881). In order to discover possible additional causal variants around TCF19, we performed an association study by genotyping single nucleotide polymorphisms (SNPs) in OCT4, a nearby gene to TCF19.

Methods

Nineteen OCT4 genetic variants were selected and genotyped in 3902 subjects (1046 CHB patients and 2856 population controls).

Results

Logistic regression analysis revealed that OCT4 rs1265163 showed the most significant association signal for the risk of CHB (OR=1.46, P=4.78×10−12). Linkage disequilibrium and conditional analysis confirmed rs1265163 in OCT4 as a novel genetic marker for CHB susceptibility. The genetic risk scores (GRSs) were calculated to visualize the combined genetic effects of all known CHB‐associated loci, including OCT4 rs1265163, which had been identified in this study. Individuals with higher cumulative GRSs showed significantly increased ORs. The luciferase activity of rs885952, a tagging SNP of rs1265163, showed that OCT4 promoter activity was significantly different between the wild‐type and SNP mutant form (P<.05).

Conclusions

This follow‐up study to our previous GWAS identified a possible causal genetic variant associated with the risk of CHB, and findings from this study may prove useful in the understanding of genetic susceptibility to CHB.
Material Connections: “The Smithsonian Effect” in Anthropological Cataloguing
Authors: Greene Candace S.
Published: September 2016

Museum curators led development of the discipline of anthropology in the late nineteenth century, and at the same time developed foundational systems for cataloguing cultural materials. Although entering and accessing catalogue information now relies on keyboards rather than inkwells, the earliest systems continue to influence our understanding of objects. Among the most influential of the early systems was that of the Smithsonian's United States National Museum (USNM), with its first anthropological catalogue entry dating to 1859. Analysis of the material culture of the ubiquitous catalogue books of American museums both before and after the establishment of the USNM system reveals its wide and lasting impact. This system normalized certain fields as essential and disciplined data accordingly, resisting alternate ideas about information offered by donors and by later developments in anthropology. While many museums have now moved through successive generations of information management systems, the effect of early data choices has seldom been examined.
How petals change their spots: cis‐regulatory re‐wiring in Clarkia (Onagraceae)
Authors: Martins Talline R. , Jiang Peng , Rausher Mark D.
Published: September 2016

A long‐standing question in evolutionary developmental biology is how new traits evolve. Although most floral pigmentation studies have focused on how pigment intensity and composition diversify, few, if any, have explored how a pattern element can shift position. In the present study, we examine the genetic changes underlying shifts in the position of petal spots in Clarkia.

Comparative transcriptome analyses were used to identify potential candidate genes responsible for spot formation. Co‐segregation analyses in F2 individuals segregating for different spot positions, quantitative PCR, and pyrosequencing, were used to confirm the role of the candidate gene in determining spot position. Transient expression assays were used to identify the expression domain of different alleles.

An R2R3Myb transcription factor (CgMyb1) activated spot formation, and different alleles of CgMyb1 were expressed in different domains, leading to spot formation in different petal locations. Reporter assays revealed that promoters from different alleles determine different locations of expression.

The evolutionary shift in spot position is due to one or more cis‐regulatory changes in the promoter of CgMyb1, indicating that shifts in pattern element position can be caused by changes in a single gene, and that cis‐regulatory rewiring can be used to alter the relative position of an existing character.
Neurophysiology and new techniques to assess esophageal sensory function: an update
Authors: Brock Christina , McCallum Richard W. , Gyawali C. Prakash , Farmer Adam D. , Frøkjær Jens Brøndum , McMahon Barry P. , Drewes Asbjørn Mohr
Published: September 2016

This review aims to discuss the neurophysiology of the esophagus and new methods to assess esophageal nociception. Pain and other symptoms can be caused by diseases in the mucosa or muscular or sphincter dysfunction, together with abnormal pain processing, either in the peripheral or central nervous systems. Therefore, we present new techniques in the assessment of esophageal function and the potential role of the mucosal barrier in the generation and propagation of pain. We discuss the assessment and role of esophageal sphincters in nociception, as well as imaging and electrophysiological techniques, with examples of their use in understanding the sensory system following noxious stimuli to the esophagus. Additionally, we discuss the mechanisms behind functional diseases of the esophagus. We conclude that the new methods have identified many of the mechanisms behind malfunction of the mucosa, disturbances of muscular and sphincter functions, and the central response to different stimuli. Taken together, this has increased our understanding of esophageal disorders and may lead to new treatment modalities.
Correlating eligibility criteria generalizability and adverse events using Big Data for patients and clinical trials
Authors: Sen Anando , Ryan Patrick B. , Goldstein Andrew , Chakrabarti Shreya , Wang Shuang , Koski Eileen , Weng Chunhua
Published: September 2016

Randomized controlled trials can benefit from proactive assessment of how well their participant selection strategies during the design of eligibility criteria can influence the study generalizability. In this paper, we present a quantitative metric called generalizability index for study traits 2.0 (GIST 2.0) to assess the a priori generalizability (based on population representativeness) of a clinical trial by accounting for the dependencies among multiple eligibility criteria. The metric was evaluated on 16 sepsis trials identified from ClinicalTrials.gov, with their adverse event reports extracted from the trial results sections. The correlation between GIST scores and adverse events was analyzed. We found that the GIST 2.0 score was significantly correlated with total adverse events and serious adverse events (weighted correlation coefficients of 0.825 and 0.709, respectively, with P < 0.01). This study exemplifies the promising use of Big Data in electronic health records and ClinicalTrials.gov for optimizing eligibility criteria design for clinical studies.
Contemporary variations of immune responsiveness during range expansion of two invasive rodents in Senegal
Authors: Diagne Christophe , Gilot‐Fromont Emmanuelle , Cornet Stéphane , Husse Laëtitia , Doucouré Souleymane , Dalecky Ambroise , Bâ Khalilou , Kane Mamadou , Niang Youssoupha , Diallo Mamoudou , Sow Aliou , Fossati‐Gaschignard Odile , Piry Sylvain , Artige Emmanuelle , Sembène Mbacké , Brouat Carine , Charbonnel Nathalie
Published: September 2016

Biological invasions provide unique opportunities for studying life history trait changes over contemporary time scales. As spatial spread may be related to changes in parasite communities, several hypotheses (such as the evolution of increased competitive ability (EICA) or EICA‐refined hypotheses) suggest immune changes in invasive species along invasion gradients. Although native hosts may be subject to similar changes in parasite selection pressures, their immune responses have been rarely investigated in invasion contexts. In this study, we evaluated immune variations for invasive house mice Mus musculus domesticus, invasive black rats Rattus rattus and native rodents Mastomys erythroleucus and Mastomys natalensis along well‐characterised invasion gradients in Senegal. We focused on antibody‐mediated (natural antibodies and complement) and inflammatory (haptoglobin) responses. One invasion route was considered for each invasive species, and environmental conditions were recorded. Natural‐antibody mediated responses increased between sites of long‐established invasion and recently invaded sites only in house mice. Both invasive species exhibited higher inflammatory responses at the invasion front than in sites of long‐established invasion. The immune responses of native species did not change with the presence of invasive species. These patterns of immune variations do not support the EICA and EICA refined hypotheses, and they rather suggest a higher risk of exposure to parasites on the invasion front. Altogether, these results provide a first basis to further assess the role of immune changes in invasion success.
Acro‐Dermato‐Ungual‐Lacrimal‐Tooth Syndrome: An Uncommon Member of the Ectodermal Dysplasias
Authors: Whittington Adam , Stein Sarah , Kenner‐Bell Brandi
Published: September 2016

Acro‐dermato‐ungual‐lacrimal‐tooth (ADULT) syndrome is a rare form of autosomal dominant ectodermal dysplasia due to mutations in the TP63 gene, a locus that has also been implicated in other syndromic forms of ectodermal dysplasia. It shares many phenotypic characteristics with other TP63 gene mutation syndromes, often making an accurate diagnosis difficult. Long‐term management and follow‐up of the various sequelae of ectodermal dysplasia require an accurate diagnosis. We report a familial case of ADULT syndrome in a daughter, mother, and son and provide a brief review of the clinical characteristics of this syndrome.
Tuberous Sclerosis Complex Associated with Vascular Anomalies or Overgrowth
Authors: Jenkins David , McCuaig Catherine , Drolet Beth A. , Siegel Dawn , Adams Susan , Lawson John A. , Wargon Orli
Published: September 2016

Background

Dysregulation of the mammalian target of rapamycin pathway is the underlying pathogenic mechanism in tuberous sclerosis complex (TSC). Other syndromes caused by genetic alterations in this pathway frequently manifest as vascular anomalies or asymmetric overgrowth. Rarely, these features have been documented in TSC.

Objective

To collate cases of TSC with vascular anomaly or overgrowth that have been published and to assemble additional recent cases, as this finding has been underreported.

Methods

TSC cases from three pediatric dermatology referral centers on two continents were reviewed to identify individuals noted to have hemihypertrophy or vascular anomalies.

Results

We report five additional cases of TSC associated with vascular anomalies or overgrowth that contribute to our understanding of some of the pathways and treatments involved in vascular anomalies.

Conclusion

Hemihypertrophy and vascular anomalies may be more frequent in the setting of TSC than previously appreciated. A common pathogenetic mechanism may tie these manifestations together.
Acute antibody‐mediated rejection in ABO‐compatible pediatric liver transplant recipients: case series and review of the literature
Authors: Wozniak Laura J. , Naini Bita V. , Hickey Michelle J. , Bhattacharyya Sarathi , Reed Elaine F. , Busuttil Ronald W. , Farmer Douglas G. , Vargas Jorge H. , Venick Robert S. , McDiarmid Sue V.
Published: September 2016

Acute AMR is well reported following ABO‐incompatible LTx. However, it remains uncommon in ABO‐compatible LTx. It typically presents with graft dysfunction ≤2 weeks post‐LTx and is often associated with graft loss. We report the clinical presentation, treatment regimen, and outcome of six pediatric LTx recipients diagnosed with early acute AMR based on (i) clinical signs of graft dysfunction, (ii) histopathology indicative of acute injury ± C4d staining, and (iii) presence of HLA DSA. All patients developed elevated ALT and GGT ≤ 45 days post‐LTx. All showed HLA class I (n=4) and/or II (n=6) DSA (peak MFI 6153–11 910). Four had de novo DSA, and two had preformed DSA. Five were initially diagnosed with ACR refractory to steroid therapy. Four exhibited resolution of graft dysfunction with AMR therapy. Two had refractory AMR—one was re‐transplanted; the other was treated with eculizumab and showed improvement in graft function but later died due to a tracheostomy complication. Our case series suggests that AMR following ABO‐compatible LTx may be under‐diagnosed. The presentation can be variable, and treatment should be individualized. Eculizumab may be an option for refractory AMR. Ultimately, future multicenter studies are needed to better define diagnostic criteria, characterize optimal treatment, and assess long‐term outcomes following liver AMR.
‘Fuller's Internal Morality of Law’
Authors: Rundle Kristen
Published: September 2016

Teased out through a playful tale about a king who failed in eight ways to make law, Lon L. Fuller's eight principles of the ‘internal morality of law’ became an important contribution to legal philosophy and rule of law theory alike. Moreover, it was Fuller's claim that his principles were not just internal to the enterprise of law, but also ‘moral’ in character, that precipitated a particular kind of ‘natural law versus legal positivism’ contest that continues among legal philosophers today. But as a recent revival of interest in Fuller's thought indicates, his scholarly agenda around the idea of ‘the internal morality of law’ was wider still and deserves revisiting for the range of avenues of inquiry it opens up.
Renal epithelioid angiomyolipoma: Histopathologic review, immunohistochemical evaluation and prognostic significance
Authors: Park Jeong Hwan , Lee Cheol , Suh Ja Hee , Kim Gilhyang , Song Boram , Moon Kyung Chul
Published: September 2016

Epithelioid angiomyolipoma (EAML) is considered to be a potentially malignant tumor and requires a differential diagnosis from renal cell carcinoma. In this study, we assessed the clinicopathologic features of renal EAML and evaluated the prognostic significance. Among 78 angiomyolipoma (AML) patients, a total of 5 EAMLs were identified, accounting for 6.4% of the total AML cases. The mean age was 41.4 years, and the average tumor size was 12.7 cm in diameter. Association of tuberous sclerosis complex was identified in two cases. One EAML case showed malignant behavior with local recurrence and distant metastasis. The malignant EAML had a larger tumor size, a higher percentage of epithelioid component and atypical epithelioid cells, ≥2 mitoses per 10 high power fields with atypical mitosis, necrosis, extrarenal extension, and carcinoma‐like growth pattern. Furthermore, the malignant case revealed p53 immunoreactivity and decreased membranous E‐cadherin expression. Pathologic evaluation of adverse prognostic factors will be helpful for risk stratification and prognosis estimation of EAML patients.
Bayesian D-Optimal Choice Designs for Mixtures
Authors: Ruseckaite Aiste , Goos Peter , Fok Dennis
Published: September 2016

Consumer products and services can often be described as mixtures of ingredients. Examples are the mixture of ingredients in a cocktail and the mixture of different components of travel time (e.g. in-vehicle and out-of-vehicle travel time) in a transportation setting. Choice experiments may help to determine how the respondent's choice of a product or service is affected by the combination of ingredients. In such experiments, individuals are confronted with sets of hypothetical products or services and they are asked to choose the most preferred product or service from each set. However, there are no studies on the optimal design of choice experiments involving mixtures. We propose a method for generating optimal designs for such choice experiments and demonstrate the large increase in statistical efficiency that can be obtained by using an optimal design.
Bullying: Definition, Types, Causes, Consequences and Intervention
Authors: Smith Peter K
Published: September 2016

Bullying is repetitive aggressive behaviour with an imbalance of power. Research, especially on school bullying, has increased massively in the last decade, fuelled in part by the rise of cyberbullying. Prevalence rates vary greatly. This is in part because of measurement issues, but some persons, and groups, are more at risk of involvement. Victims suffer from bullying, but some of those who perpetrate bullying can be socially skilled and get at least short‐term benefits from their behaviour. Individual, family, school class, school and broader country factors can influence the chances of involvement. Beyond individual coping strategies, there have been many anti‐bullying interventions developed over the last 30 years. Meta‐analyses of these programmes show that they have had some success. Further progress is needed in establishing the most effective components and in tackling cyberbullying.
Cyclin‐dependent kinase activity enhances phosphatidylcholine biosynthesis in Arabidopsis by repressing phosphatidic acid phosphohydrolase activity
Authors: Craddock Christian P. , Adams Nicolette , Kroon Johan T.M. , Bryant Fiona M. , Hussey Patrick J. , Kurup Smita , Eastmond Peter J.
Published: September 2016

Coordination of endomembrane biogenesis with cell cycle progression is considered to be important in maintaining cell function during growth and development. We previously showed that the disruption of PHOSPHATIDIC ACID PHOSPHOHYDROLASE (PAH) activity in Arabidopsis thaliana stimulates biosynthesis of the major phospholipid phosphatidylcholine (PC) and causes expansion of the endoplasmic reticulum. Here we show that PC biosynthesis is repressed by disruption of the core cell cycle regulator CYCLIN‐DEPENDENT KINASE A;1 (CDKA;1) and that this repression is reliant on PAH. Furthermore, we show that cyclin‐dependent kinases (CDKs) phosphorylate PAH1 at serine 162, which reduces both its activity and membrane association. Expression of a CDK‐insensitive version of PAH1 with a serine 162 to alanine substitution represses PC biosynthesis and also reduces the rate of cell division in early leaf development. Together our findings reveal a physiologically important mechanism that couples the rate of phospholipid biosynthesis and endomembrane biogenesis to cell cycle progression in Arabidopsis.
Overexpression of a flower‐specific aerolysin‐like protein from the dioecious plant Rumex acetosa alters flower development and induces male sterility in transgenic tobacco
Authors: Manzano Susana , Megías Zoraida , Martínez Cecilia , García Alicia , Aguado Encarnación , Chileh Tarik , López‐Alonso Diego , García‐Maroto Federico , Kejnovský Eduard , Široký Jiří , Kubát Zdeněk , Králová Tereza , Vyskot Boris , Jamilena Manuel
Published: September 2016

Sex determination in Rumex acetosa, a dioecious plant with a complex XY1Y2 sex chromosome system (females are XX and males are XY1Y2), is not controlled by an active Y chromosome but depends on the ratio between the number of X chromosomes and autosomes. To gain insight into the molecular mechanisms of sex determination, we generated a subtracted cDNA library enriched in genes specifically or predominantly expressed in female floral buds in early stages of development, when sex determination mechanisms come into play. In the present paper, we report the molecular and functional characterization of FEM32, a gene encoding a protein that shares a common architecture with proteins in different plants, animals, bacteria and fungi of the aerolysin superfamily; many of these function as β pore‐forming toxins. The expression analysis, assessed by northern blot, RT‐PCR and in situ hybridization, demonstrates that this gene is specifically expressed in flowers in both early and late stages of development, although its transcripts accumulate much more in female flowers than in male flowers. The ectopic expression of FEM32 under both the constitutive promoter 35S and the flower‐specific promoter AP3 in transgenic tobacco showed no obvious alteration in vegetative development but was able to alter floral organ growth and pollen fertility. The 35S::FEM32 and AP3::FEM32 transgenic lines showed a reduction in stamen development and pollen viability, as well as a diminution in fruit set, fruit development and seed production. Compared with other floral organs, pistil development was, however, enhanced in plants overexpressing FEM32. According to these effects, it is likely that FEM32 functions in Rumex by arresting stamen and pollen development during female flower development. The aerolysin‐like pore‐forming proteins of eukaryotes are mainly involved in defence mechanisms against bacteria, fungi and insects and are also involved in apoptosis and programmed cell death (PCD), a mechanism that could explain the role of FEM32 in Rumex sex determination.
Structural variability of plant photosystem II megacomplexes in thylakoid membranes
Authors: Nosek Lukáš , Semchonok Dmitry , Boekema Egbert J. , Ilík Petr , Kouřil Roman
Published: September 2016

Plant photosystem II (PSII) is organized into large supercomplexes with variable levels of membrane‐bound light‐harvesting proteins (LHCIIs). The largest stable form of the PSII supercomplex involves four LHCII trimers, which are specifically connected to the PSII core dimer via monomeric antenna proteins. The PSII supercomplexes can further interact in the thylakoid membrane, forming PSII megacomplexes. So far, only megacomplexes consisting of two PSII supercomplexes associated in parallel have been observed. Here we show that the forms of PSII megacomplexes can be much more variable. We performed single particle electron microscopy (EM) analysis of PSII megacomplexes isolated from Arabidopsis thaliana using clear‐native polyacrylamide gel electrophoresis. Extensive image analysis of a large data set revealed that besides the known PSII megacomplexes, there are distinct groups of megacomplexes with non‐parallel association of supercomplexes. In some of them, we have found additional LHCII trimers, which appear to stabilize the non‐parallel assemblies. We also performed EM analysis of the PSII supercomplexes on the level of whole grana membranes and successfully identified several types of megacomplexes, including those with non‐parallel supercomplexes, which strongly supports their natural origin. Our data demonstrate a remarkable ability of plant PSII to form various larger assemblies, which may control photochemical usage of absorbed light energy in plants in a changing environment.