bluuebunny/crossref_metadata_2025 huggingface dataset:
Biofilm formation of ica operon‐positive Staphylococcus epidermidis from different sources
Authors: Angeles Argudín Maria , Vanderhaeghen Wannes , Vandendriessche Stien , Vandecandelaere Ilse , Denis Olivier , Coenye Tom , Butaye Patrick
Published: November 2015

Information on the prevalence of biofilm‐related factors (PIA, Bhp, Aap, Embp) in Staphylococcus epidermidis of animal origin is scarce. In this study, 263 S. epidermidis isolates of diverse origin (animal, farmers, patients, and laboratory staff) were investigated for the presence of the ica operon (icaRADBC). The icaRADBC‐positive isolates were further characterized by means of biofilm formation, presence of other biofilm‐related genes, antimicrobial resistance, and population structure. Of all isolates, 28.5% (n = 75) were icaRADBC‐positive, including 16.5% of animal origin, 29.1% farmer isolates, and 44.6% hospital‐associated isolates (including patients and laboratory staff isolates). Most icaRADBC‐positive isolates carried embp (n = 73), aap (n = 57), bhp (n = 22), and IS256 (n = 29). Statistical differences were found between animal and patient isolates for the presence of icaRADBC, bhp, and aap. No statistically significant relation was found between the presence of one or more genes and the level of biofilm formation. Most icaRADBC‐positive isolates belonged to the clonal complex 5 (formerly 2) and most sequence types corresponded to types previously observed in community and nosocomial S. epidermidis populations. Although the prevalence of S. epidermidis in the nasal cavity of bovines and poultry is low, some isolates belong to STs related to ica‐positive clinical strains.
Nuclear, cytoplasmic, and stromal expression of ZEB1 in squamous and small cell carcinoma of the esophagus
Authors: Goscinski Mariusz Adam , Xu Ruiping , Zhou Fuyou , Wang Junsheng , Yang Haijun , Huang Ruixia , Li Yaqing , Larsen Stein Gunnar , Giercksky Karl‐Erik , Nesland Jahn Marthin , Suo Zhenhe
Published: November 2015

Zinc finger E‐box‐binding homeobox 1 (ZEB1) is a transcriptional factor known to repress E‐cadherin promoter and thus induce EMT. Expression of ZEB‐1 has in numerous cancers been associated with aggressive disease and poor clinical outcome. Our aim was to investigate the expression of ZEB1 in esophageal squamous‐ and small‐cell carcinomas. Immunohistochemical staining was performed on tissue sections obtained from 151 patients with esophageal squamous cell carcinoma (ESCC) and 25 patients with primary small‐cell carcinoma of the esophagus (PSCCE). Semi‐quantitative analysis, and thus statistical analysis, has been accomplished on the samples. Immunohistochemistry revealed ZEB1 expression in the cytoplasm (64.9% of cases), in nuclei (11.3% of cases) and in tumor stroma (80.1% of cases) of ESCC. In PSCCE only nuclear staining (88.0% of cases) was observed. Weak cytoplasmic expression of ZEB1 in ESCC was associated with longer survival. Immunohistochemical evaluation of ZEB1 cytoplasmic expression in ESCC may have clinical prognostic value, but further studies are needed to fully understand the function as well as potential clinical and therapeutic implications of ZEB1 expression in cancers.
Differences in sleep disturbances among offspring of parents with and without bipolar disorder: association with conversion to bipolar disorder
Authors: Levenson Jessica C , Axelson David A , Merranko John , Angulo Melina , Goldstein Tina R , Mullin Benjamin C , Goldstein Benjamin I , Brent David A , Diler Rasim , Hickey Mary Beth , Monk Kelly , Sakolsky Dara , Kupfer David J , Birmaher Boris
Published: November 2015

Objectives

Disruptions in sleep and dysregulation in circadian functioning may represent core abnormalities in the pathophysiology of bipolar disorder (BP). However, it is not clear whether these dysfunctions are state or trait markers of BP. This report compared sleep and circadian phenotypes among three groups: offspring of parents with BP diagnosed with BP at intake (BP/OB; n = 47), offspring of parents with BP without BP at intake (non‐BP/OB; n = 386), and offspring of matched control parents who did not have BP (controls; n = 301). We also examined the association of baseline sleep parameters with subsequent development of BP among the non‐BP/OB group.

Methods

Pittsburgh Bipolar Offspring Study youth (ages 6–18 years) and their parents completed assessments every two years pertaining to the child's sleep and circadian phenotypes and current psychopathology. Mixed‐effects models examined differences in baseline sleep and circadian variables among the three groups.

Results

BP/OB offspring who were in a mood episode differed significantly on sleep parameters from the non‐BP/OB and the offspring of controls, such as having inadequate sleep. Mixed logistic regression procedures showed that baseline sleep and circadian variables, such as frequent waking during the night, significantly predicted the development of BP among non‐BP/OB over longitudinal follow‐up.

Conclusions

While lifetime diagnostic status accounted for differences among the groups in sleep and circadian disturbances, psychopathology explained the differences even further. Additionally, sleep disturbance may be a prognostic indicator of the development of BP in high‐risk youth. Future studies are required to further disentangle whether sleep and circadian disruption are state or trait features of BP.
Glass ceilings or glass doors? The role of firms in male‐female wage disparities
Authors: Javdani Mohsen
Published: November 2015

I use Canadian linked employer‐employee data to examine whether women face a glass ceiling in the labour market. I also measure the extent to which the glass ceiling comes about because women are segregated into lower‐paying firms, or because they are segregated into lower‐paying jobs within firms. I find clear evidence that women experience a glass ceiling that is driven by their disproportionate sorting across firm types (glass doors) rather than within firms. I find no evidence that these results are supply‐driven. However, my results are consistent with predictions of an efficiency wage model where high‐paying firms discriminate against females.
QSAR Models Guided by Molecular Dynamics Applied to Human Glucokinase Activators
Authors: de Assis Tamiris Maria , Gajo Giovanna Cardoso , de Assis Letícia Cristina , Garcia Letícia Santos , Silva Daniela Rodrigues , Ramalho Teodorico Castro , da Cunha Elaine Fontes Ferreira
Published: November 2015

In this study, quantitative structure–activity relationship studies which make use of molecular dynamics trajectories were performed on a set of 54 glucokinase protein activators. The conformations obtained by molecular dynamics simulation were superimposed according to the twelve alignments tested in a virtual three‐dimensional box comprised of 2 Å cells. The models were generated by the technique that combines genetic algorithms and partial least squares. The best alignment models generated with a determination coefficient (r2) between 0.674 and 0.743 and cross‐validation (q2) between 0.509 and 0.610, indicating good predictive capacity. The 4D‐QSAR models developed in this study suggest novel molecular regions to be explored in the search for better glucokinase activators.
Parental decision‐making on utilisation of out‐of‐home respite in children's palliative care: findings of qualitative case study research ‐ a proposed new model
Authors: Ling J. , Payne S. , Connaire K. , McCarron M.
Published: November 2015

Background

Respite in children's palliative care aims to provide a break for family's from the routine of caring. Parental decision‐making regarding the utilisation of out‐of‐home respite is dependent on many interlinking factors including the child's age, diagnosis, geographical location and the family's capacity to meet their child's care needs. A proposed model for out‐of‐home respite has been developed based on the findings of qualitative case study research.

Methods

Utilising multiple, longitudinal, qualitative case study design, the respite needs and experiences of parents caring for a child with a life‐limiting condition were explored. Multiple, in‐depth interviews were undertaken with the parents identified by a hospital‐based children's palliative care team. Data were analysed using thematic analysis. Each individual case consists of a whole study. Cross‐case comparison was also conducted.

Results

Nine families were recruited and followed for two years. A total of 19 in‐depth interviews were conducted with mothers and fathers (one or both) caring for a child with a life‐limiting condition in Ireland. Each family reported vastly different needs and experiences of respite from their own unique perspective. Cross‐case comparison showed that for all parents utilising respite care, regardless of their child's age and condition, home was the location of choice. Many interlinking factors influencing these decisions included: past experience of in‐patient care, and trust and confidence in care providers. Issues were raised regarding the impact of care provision in the home on family life, siblings and the concept of home.

Conclusion

Respite is an essential element of children's palliative care. Utilisation of out‐of‐home respite is heavily dependent on a number of interlinked and intertwined factors. The proposed model of care offers an opportunity to identify how these decisions are made and may ultimately assist in identifying the elements of responsive and family‐focused respite that are important to families of children with life‐limiting conditions.
No data, no problem, no action: parenting programs in low‐income countries. Making the social–emotional outcomes more visible
Authors: Tinajero A. R. , Cohen N. J. , Ametorwo S.
Published: November 2015

Background

Parenting programs are delivered in many low income countries in an effort to address the effects of insufficient cognitive stimulation, major social–emotional risk factors related to inadequate caregiver sensitivity and responsiveness, maternal depression, violence and biological risk factors. However, the outcomes of these programs are often untested because of methodological limitations in the existing evaluation tools available for cross‐cultural research, and especially those related to social–emotional development and functioning.

Method

This study takes an approach that involves organizing data from focus groups collected following caregiver participation in a parenting program, Learning Through Play (LTP) delivered in 11 low income countries. The LTP program has as its aim to increase parent knowledge and influence parental practice regarding the essential components of early development of children aged birth to 6 years. The purpose of systematically organizing focus group data was to illustrate a means by which program developers worldwide can discuss outcomes of program participation, particularly in social–emotional domains that have been overlooked in past studies on parenting programs.

Results and conclusion

The findings from this study suggest that qualitative outcome data can be organized to make the social–emotional outcomes of participation in parenting programs more visible.
Situating Children's Voices: Considering the Context When Conducting Research with Young Children
Authors: Khoja Nazeeha
Published: November 2015

I problematise my own concept of children's voices in research by reflecting on certain practices in a study that I conducted in a kindergarten classroom in a city in Saudi Arabia. I examine the cultural and social contexts of my research by drawing on my experience of obtaining children's assent or dissent, my assumptions regarding the possibility of reducing power differentials, and finally, my understanding of the ways children voice their feelings and views. I conclude that voices manifest themselves in multiple ways that extend beyond visual or verbal media. Voices are constructed socially and are shaped culturally to reflect norms regarding how individuals should express their views and feelings within a particular setting and time.
Predictive factors for recurrence of cryptoglandular fistulae characterized by preoperative three‐dimensional endoanal ultrasound
Authors: Visscher A. P. , Schuur D. , Slooff R. A. E. , Meijerink W. J. H. J. , Deen‐Molenaar C. B. H. , Felt‐Bersma R. J. F.
Published: November 2015

Aim

Precise information regarding the location of an anal fistula and its relationship to adjacent structures is necessary for selecting the best surgical strategy. Retrospective and cross‐sectional studies were performed to determine predictive factors for recurrence of anal fistula from preoperative examination by three‐dimensional endoanal ultrasound (3D‐EAUS).

Method

Patients in our tertiary centre and in a private centre specialized in proctology undergoing preoperative 3D‐EAUS for cryptoglandular anal fistulae between 2002 and 2012 were included. A questionnaire was sent in September 2013 to assess the patient's condition with regard to recurrence. Variables checked for association with recurrence were gender, type of centre, previous fistula surgery, secondary track formation and classification of the fistula.

Results

There were 143 patients of whom 96 had a low fistula treated by fistulotomy, 28 a high fistula treated by fistulectomy and 19 a high fistula treated by fistulectomy combined with a mucosal advancement flap. The median duration of follow‐up was 26 (2–118) months. The fistula recurred in 40 (27%) patients. Independent risk factors included the presence of secondary track formation [hazard ratio 2.4 (95% CI 1.2–51), P = 0.016] and previous fistula surgery [hazard ratio 1.2 (95% CI 1.0–4.6), P = 0.041]. Agreement between the 3D‐EAUS examination and the evaluation under anaesthesia regarding the site of the internal opening, classification of the fistula and the presence of secondary tracks was 97%, 98% and 78%.

Conclusion

The identification of secondary tracks by preoperative 3D‐EAUS examination was the strongest independent risk factor for recurrence. This stresses the importance of preoperative 3D‐EAUS in mapping the pathological anatomy of the fistula and a thorough search for secondary track formation during surgery.
Systematic review of guidelines for the assessment and management of high‐grade anal intraepithelial neoplasia (AIN II/III)
Authors: Alam N. N. , White D. A. , Narang S. K. , Daniels I. R. , Smart N. J.
Published: November 2015

Aim

There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare international/national society guidelines currently available in the literature on the management, treatment and surveillance of AIN III. We also aimed to assess the quality of the studies used to compile the guidelines and to clarify the terminology used in histological assessment.

Method

An electronic search of PubMed and Embase was performed using the search terms ‘anal intraepithelial neoplasia’, ‘AIN’, ‘anal cancer’, ‘guidelines’, ‘surveillance’ and ‘management’. Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1 January 2000 to 31 December 2014 assessing the treatment, surveillance or management of patients with AIN related to human papilloma virus were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence‐based Medicine 2011 Levels of Evidence.

Results

The database search identified 5159 articles and two further guidelines were sourced from official body guidelines. After inclusion criteria were applied, 28 full‐text papers were reviewed. Twenty‐five of these were excluded, leaving three guidelines for inclusion in the systematic review: those published by the Association of Coloproctology of Great Britain and Ireland, the American Society of Colon and Rectal Surgeons and the Italian Society of Colorectal Surgery. No guidelines were identified on the management of AIN III from human papilloma virus associations and societies. All three guidelines agree that a high index of clinical suspicion is essential for diagnosing AIN with a disease‐specific history, physical examination, digital rectal examination and anal cytology. There is interchange of terminology from high‐grade AIN (HGAIN) (which incorporates AIN II/III) and AIN III in the literature leading to confusion in therapy use. Treatment varies from immunomodulation and photodynamic therapy to targeted destruction of areas of HGAIN/AIN II/III using infrared coagulation, electrocautery, cryotherapy or surgical excision but with little consensus between the guidelines. Recommendations on surveillance strategies are similarly discordant, ranging from 6‐monthly physical examination to annual anoscopy ± biopsy. Over 50% of the recommendations are based on Level 3 or Level 4 evidence and many were compiled using studies that were more than 10 years old.

Conclusion

Despite concordance regarding diagnosis, there is significant variation in the guidelines over recommendations on the treatment and surveillance of patients with HGAIN/AIN II/III. All three sets of guidelines are based on low level, outdated evidence originating from the 1980s and 1990s.
When does social learning become cultural learning?
Authors: Heyes Cecilia
Published: November 2015

Developmental research on selective social learning, or ‘social learning strategies’, is currently a rich source of information about when children copy behaviour, and who they prefer to copy. It also has the potential to tell us when and how human social learning becomes cultural learning; i.e. mediated by psychological mechanisms that are specialized, genetically or culturally, to promote cultural inheritance. However, this review article argues that, to realize its potential, research on the development of selective social learning needs more clearly to distinguish functional from mechanistic explanation; to achieve integration with research on attention and learning in adult humans and ‘dumb’ animals; and to recognize that psychological mechanisms can be specialized, not only by genetic evolution, but also by associative learning and cultural evolution.
Survey on multisensory feedback virtual reality dental training systems
Authors: Wang D. , Li T. , Zhang Y. , Hou J.
Published: November 2015

Compared with traditional dental training methods, virtual reality training systems integrated with multisensory feedback possess potentials advantages. However, there exist many technical challenges in developing a satisfactory simulator. In this manuscript, we systematically survey several current dental training systems to identify the gaps between the capabilities of these systems and the clinical training requirements. After briefly summarising the components, functions and unique features of each system, we discuss the technical challenges behind these systems including the software, hardware and user evaluation methods. Finally, the clinical requirements of an ideal dental training system are proposed. Future research/development areas are identified based on an analysis of the gaps between current systems and clinical training requirements.
Effectiveness of Jigsaw learning compared to lecture‐based learning in dental education
Authors: Sagsoz O. , Karatas O. , Turel V. , Yildiz M. , Kaya E.
Published: November 2015

Aim

The objective of this study was to evaluate the success levels of students using the Jigsaw learning method in dental education.

Method

Fifty students with similar grade point average (GPA) scores were selected and randomly assigned into one of two groups (n = 25). A pretest concerning ‘adhesion and bonding agents in dentistry’ was administered to all students before classes. The Jigsaw learning method was applied to the experimental group for 3 weeks. At the same time, the control group was taking classes using the lecture‐based learning method. At the end of the 3 weeks, all students were retested (post‐test) on the subject. A retention test was administered 3 weeks after the post‐test. Mean scores were calculated for each test for the experimental and control groups, and the data obtained were analysed using the independent samples t‐test.

Results

No significant difference was determined between the Jigsaw and lecture‐based methods at pretest or post‐test. The highest mean test score was observed in the post‐test with the Jigsaw method. In the retention test, success with the Jigsaw method was significantly higher than that with the lecture‐based method.

Conclusion

The Jigsaw method is as effective as the lecture‐based method.
LPL gene expression is associated with poor prognosis in CLL and closely related to NOTCH1 mutations
Authors: Kristensen Louise , Kristensen Thomas , Abildgaard Niels , Royo Cristina , Frederiksen Mikael , Mourits‐Andersen Torben , Campo Elias , Møller Michael Boe
Published: November 2015

Introduction

Chronic lymphocytic leukemia is a heterogeneous yet incurable disease. Whole‐genome and whole‐exome sequencing studies have revealed recurrently occurring somatic mutations in some genes. Several other prognostic markers have previously been tested for their prognostic value in CLL. LPL is among these markers.

Aim

To evaluate LPL gene expression together with the well‐established prognostic markers of CLL and investigate correlations with more recently identified prognostic markers, NOTCH1 and TP53 mutations.

Methods

On 149 patients, LPL gene expression was analyzed by real‐time RT‐PCR. Exon 34 of NOTCH1 was PCR‐amplified and directly sequenced.

Results

LPL gene expression could be measured as a categorical variable (LPL+/LPL‐) and was associated with time to treatment (P < 0.001) and overall survival (P = 0.007). In patients otherwise classified as having a good prognosis according to established and new prognostic markers, 3 of 4 patients, who received treatment within 24 months after diagnosis, were LPL+ (P = 0.03). There was a strong correlation between NOTCH1 mutation and LPL+ (P = 0.005). The unfavorable prognosis of LPL+ was maintained in CLL with wild‐type NOTCH1.

Conclusions

NOTCH1 mutations are tightly associated with LPL gene expression. LPL expression is independently associated with poor outcome in CLL and can be measured as a categorical variable.
Alteration of SLP2‐like immunolabeling in mitochondria signifies early cellular damage in developing and adult mouse brain
Authors: Morozov Yury M. , Sun Yu‐Yo , Kuan Chia‐Yi , Rakic Pasko
Published: November 2015

Mitochondria play a critical role in various pathways of regulated cell death. Here we propose a novel method for detection of initial derangement of mitochondria in degenerating and dying neuronal cells. The method is based on our recent finding that antibodies directed against the cannabinoid type 1 receptor (CB1) also bind the mitochondrial stomatin‐like protein 2 (SLP2) that belongs to an inner mitochondrial membrane protein complex. It is well established that SLP2 regulates mitochondrial biogenesis and respiratory functions. We now show that anti‐CB1 antibodies recognize conformational epitopes but not the linear amino acid sequence of SLP2. In addition we found that anti‐CB1 serum mostly labels swollen mitochondria with early or advanced stages of pathology in mouse brain while other proteins of the complex may mask epitopes of SLP2 in the normal mitochondria. Although neurons and endothelial cells in healthy brains contain occasional immunopositive mitochondria detectable with anti‐CB1 serum, their numbers increase significantly after hypoxic insults in parallel with signs of cellular damage. Moreover, use of electron microscopy suggests relocation of SLP2 from its normal functional position in the inner mitochondrial membrane into the mitochondrial matrix in pathological cells. Thus, SLP2‐like immunolabeling serves as an in situ histochemical target detecting early derangement of mitochondria. Anti‐CB1 serum is crucial for this purpose because available anti‐SLP2 antibodies do not provide selective labeling of mitochondria in the fixed tissue. This new method of detecting mitochondrial dysfunction can benefit the in vitro research of human diseases and developmental disorders by enabling analysis in live animal models.
Individual and sex‐related differences in pain and relief responsiveness are associated with differences in resting‐state functional networks in healthy volunteers
Authors: Galli Giulia , Santarnecchi Emiliano , Feurra Matteo , Bonifazi Marco , Rossi Simone , Paulus Martin P. , Rossi Alessandro
Published: November 2015

Pain processing is associated with neural activity in a number of widespread brain regions. Here, we investigated whether functional connectivity at rest between these brain regions is associated with individual and sex‐related differences in thermal pain and relief responsiveness. Twenty healthy volunteers (ten females) were scanned with functional magnetic resonance imaging in resting conditions. Half an hour after scanning, we administered thermal pain on the back of their right hand and collected pain and relief ratings in two separate runs of twelve stimuli each. Across the whole group, mean pain ratings were associated with decreased connectivity at rest between brain regions belonging to the default mode and the visual resting‐state network. In men, pain measures correlated with increased connectivity within the visual resting‐state network. In women, in contrast, decreased connectivity between this network and parietal and prefrontal brain regions implicated in affective cognitive control were associated with both pain and relief ratings. Our findings indicate that the well documented individual variability and sex differences in pain sensitivity may be explained, at least in part, by network dynamics at rest in these brain regions.
Areas V1 and V2 show microsaccade‐related 3–4‐Hz covariation in gamma power and frequency
Authors: Lowet E. , Roberts M. J. , Bosman C. A. , Fries P. , De Weerd P.
Published: November 2015

Neuronal gamma‐band synchronization (25–80 Hz) in visual cortex appears sustained and stable during prolonged visual stimulation when investigated with conventional averages across trials. However, recent studies in macaque visual cortex have used single‐trial analyses to show that both power and frequency of gamma oscillations exhibit substantial moment‐by‐moment variation. This has raised the question of whether these apparently random variations might limit the functional role of gamma‐band synchronization for neural processing. Here, we studied the moment‐by‐moment variation in gamma oscillation power and frequency, as well as inter‐areal gamma synchronization, by simultaneously recording local field potentials in V1 and V2 of two macaque monkeys. We additionally analyzed electrocorticographic V1 data from a third monkey. Our analyses confirm that gamma‐band synchronization is not stationary and sustained but undergoes moment‐by‐moment variations in power and frequency. However, those variations are neither random and nor a possible obstacle to neural communication. Instead, the gamma power and frequency variations are highly structured, shared between areas and shaped by a microsaccade‐related 3–4‐Hz theta rhythm. Our findings provide experimental support for the suggestion that cross‐frequency coupling might structure and facilitate the information flow between brain regions.
Origins of multisynaptic projections from the basal ganglia to the forelimb region of the ventral premotor cortex in macaque monkeys
Authors: Ishida Hiroaki , Inoue Ken‐ichi , Takada Masahiko , Hoshi Eiji
Published: November 2015

The ventral premotor cortex (PMv), occupying the ventral aspect of area 6 in the frontal lobe, has been implicated in action planning and execution based on visual signals. Although the PMv has been characterized by cortico‐cortical connections with specific subregions of the parietal and prefrontal cortical areas, a topographical input/output organization between the PMv and the basal ganglia (BG) still remains elusive. In the present study, retrograde transneuronal labelling with the rabies virus was employed to identify the origins of multisynaptic projections from the BG to the PMv. The virus was injected into the forelimb region of the PMv, identified in the ventral aspect of the genu of the arcuate sulcus, in macaque monkeys. The survival time after the virus injection was set to allow either the second‐ or third‐order neuron labelling across two or three synapses. The second‐order neurons were observed in the ventral portion (primary motor territory) and the caudodorsal portion (higher‐order motor territory) of the internal segment of the globus pallidus. Subsequently, the third‐order neurons were distributed in the putamen caudal to the anterior commissure, including both the primary and the higher‐order motor territories, and in the ventral striatum (limbic territory). In addition, they were found in the dorsolateral portion (motor territory) and ventromedial portion (limbic territory) of the subthalamic nucleus, and in the external segment of the globus pallidus including both the limbic and motor territories. These findings indicate that the PMv receives diverse signals from the primary motor, higher‐order motor and limbic territories of the BG.
Tonically active NMDA receptors – a signalling mechanism critical for interneuronal excitability in the CA1 stratum radiatum
Authors: Riebe Ilse , Seth Henrik , Culley Georgia , Dósa Zita , Radi Shayma , Strand Karin , Fröjd Victoria , Hanse Eric
Published: November 2015

In contrast to tonic extrasynaptic γ‐aminobutyric acid (GABA)A receptor‐mediated signalling, the physiological significance of tonic extrasynaptic N‐methyl‐d‐aspartate (NMDA) receptor (NMDAR)‐mediated signalling remains uncertain. In this study, reversible open‐channel blockers of NMDARs, memantine and phencyclidine (PCP) were used as tools to examine tonic NMDAR‐mediated signalling in rat hippocampal slices. Memantine in concentrations up to 10 μm had no effect on synaptically evoked NMDAR‐mediated responses in pyramidal neurons or GABAergic interneurons. On the other hand, 10 μm memantine reduced tonic NMDAR‐mediated currents in GABAergic interneurons by approximately 50%. These tonic NMDAR‐mediated currents in interneurons contributed significantly to the excitability of the interneurons as 10 μm memantine reduced the disynaptic inhibitory postsynaptic current in pyramidal cells by about 50%. Moreover, 10 μm memantine, but also PCP in concentrations ≤ 1 μm, increased the magnitude of the population spike, likely because of disinhibition. The relatively higher impact of tonic NMDAR‐mediated signalling in interneurons was at least partly explained by the expression of GluN2D‐containing NMDARs, which was not observed in mature pyramidal cells. The current results are consistent with the idea that low doses of readily reversible NMDAR open‐channel blockers preferentially inhibit tonically active extrasynaptic NMDARs, and they suggest that tonically active NMDARs contribute more prominently to the intrinsic excitation in GABAergic interneurons than in pyramidal cells. It is proposed that this specific difference between interneurons and pyramidal cells can explain the disinhibition caused by the Alzheimer's disease medication memantine.
Shank–cortactin interactions control actin dynamics to maintain flexibility of neuronal spines and synapses
Authors: MacGillavry Harold D. , Kerr Justin M. , Kassner Josh , Frost Nicholas A. , Blanpied Thomas A.
Published: November 2015

The family of Shank scaffolding molecules (comprising Shank1, 2 and 3) are core components of the postsynaptic density (PSD) in neuronal synapses. Shanks link surface receptors to other scaffolding molecules within the PSD, as well as to the actin cytoskeleton. However, determining the function of Shank proteins in neurons has been complicated because the different Shank isoforms share a very high degree of sequence and domain homology. Therefore, to control Shank content while minimizing potential compensatory effects, a miRNA‐based knockdown strategy was developed to reduce the expression of all synaptically targeted Shank isoforms simultaneously in rat hippocampal neurons. Using this approach, a strong (>75%) reduction in total Shank protein levels was achieved at individual dendritic spines, prompting an approximately 40% decrease in mushroom spine density. Furthermore, Shank knockdown reduced spine actin levels and increased sensitivity to the actin depolymerizing agent Latrunculin A. A SHANK2 mutant lacking the proline‐rich cortactin‐binding motif (SHANK2‐ΔPRO) was unable to rescue these defects. Furthermore, Shank knockdown reduced cortactin levels in spines and increased the mobility of spine cortactin as measured by single‐molecule tracking photoactivated localization microscopy, suggesting that Shank proteins recruit and stabilize cortactin at the synapse. Furthermore, it was found that Shank knockdown significantly reduced spontaneous remodelling of synapse morphology that could not be rescued by the SHANK2‐ΔPRO mutant. It was concluded that Shank proteins are key intermediates between the synapse and the spine interior that, via cortactin, permit the actin cytoskeleton to dynamically regulate synapse morphology and function.
Delimiting Coefficient α from Internal Consistency and Unidimensionality
Authors: Sijtsma Klaas
Published: November 2015

I discuss the contribution by Davenport, Davison, Liou, & Love (2015) in which they relate reliability represented by coefficient α to formal definitions of internal consistency and unidimensionality, both proposed by Cronbach (1951). I argue that coefficient α is a lower bound to reliability and that concepts of internal consistency and unidimensionality, however defined, belong to the realm of validity, viz. the issue of what the test measures. Internal consistency and unidimensionality may play a role in the construction of tests when the theory of the attribute for which the test is constructed implies that the items be internally consistent or unidimensional. I also offer examples of attributes that do not imply internal consistency or unidimensionality, thus limiting these concepts' usefulness in practical applications.
Evaluation of Dimensionality in the Assessment of Internal Consistency Reliability: Coefficient Alpha and Omega Coefficients
Authors: Green Samuel B. , Yang Yanyun
Published: November 2015

In the lead article, Davenport, Davison, Liou, & Love demonstrate the relationship among homogeneity, internal consistency, and coefficient alpha, and also distinguish among them. These distinctions are important because too often coefficient alpha—a reliability coefficient—is interpreted as an index of homogeneity or internal consistency. We argue that factor analysis should be conducted before calculating internal consistency estimates of reliability. If factor analysis indicates the assumptions underlying coefficient alpha are met, then it can be reported as a reliability coefficient. However, to the extent that items are multidimensional, alternative internal consistency reliability coefficients should be computed based on the parameter estimates of the factor model. Assuming a bifactor model evidenced good fit, and the measure was designed to assess a single construct, omega hierarchical—the proportion of variance of the total scores due to the general factor—should be presented. Omega—the proportion of variance of the total scores due to all factors—also should be reported in that it represents a more traditional view of reliability, although it is computed within a factor analytic framework. By presenting both these coefficients and potentially other omega coefficients, the reliability results are less likely to be misinterpreted.
Forebrain‐independent generation of hyperthermic convulsions in infant rats
Authors: Pospelov Alexey S. , Yukin Alexey Y. , Blumberg Mark S. , Puskarjov Martin , Kaila Kai
Published: November 2015

Febrile seizures are the most common type of convulsive events in children. It is generally assumed that the generalization of these seizures is a result of brainstem invasion by the initial limbic seizure activity. Using precollicular transection in 13‐day‐old rats to isolate the forebrain from the brainstem, we demonstrate that the forebrain is not required for generation of tonic–clonic convulsions induced by hyperthermia or kainate. Compared with sham‐operated littermate controls, latency to onset of convulsions in both models was significantly shorter in pups that had undergone precollicular transection, indicating suppression of the brainstem seizure network by the forebrain in the intact animal. We have shown previously that febrile seizures are precipitated by hyperthermia‐induced respiratory alkalosis. Here, we show that triggering of hyperthermia‐induced hyperventilation and consequent convulsions in transected animals are blocked by diazepam. The present data suggest that the role of endogenous brainstem activity in triggering tonic–clonic seizures should be re‐evaluated in standard experimental models of limbic seizures. Our work sheds new light on the mechanisms that generate febrile seizures in children and, therefore, on how they might be treated.
Couples Relationship Education and Couples Therapy: Healthy Marriage or Strange Bedfellows?
Authors: Markman Howard J. , Ritchie Lane L.
Published: November 2015

This paper focuses on issues sparked by the Couples Relationship Education (CRE) field moving toward a more clinical model to meet the needs of an increasing number of distressed couples coming to CRE programs. We review the concerns raised and recommendations made by Bradford, Hawkins, and Acker (2015), most of which push CRE toward a more clinical model. We address these recommendations and make suggestions for best practices that preserve the prevention/education model underlying research‐based CRE. The three main issues are couple screening, leader training, and service delivery models. Our suggested best practices include: conducting minimal screening including the assessment of dangerous levels of couple violence, training leaders with key skills to handle issues raised by distressed couples as well as other couples who may place additional burdens on leaders, providing referrals and choices of programs available to participants at intake and throughout the CRE program, and adding (rather than integrating) clinical services to CRE services for couples who desire additional intervention. Finally, throughout the paper, we review other key issues in the CRE field and make recommendations made for future research and practice.
Informed Trading in Corporate Bonds Prior to Earnings Announcements
Authors: Wei Jason , Zhou Xing
Published: November 2015

This paper examines the information content of corporate bond trading prior to earnings announcements using data from both NAIC and TRACE. We find that the direction of pre‐announcement bond trading is closely related to earnings surprises. This link is most evident prior to negative news and in high‐yield bonds. Further, abnormal bond trading during the pre‐announcement period can help predict both earnings surprises and post‐announcement bond returns. Such predictive ability of bond trading largely originates from institutional‐sized trades and is concentrated in the issuer's most actively traded bond. Finally, even after accounting for transactions costs, informed bond trading can generate significant net profits, especially prior to the release of bad news.
Deficiencies in the health care system contribute to a high rate of late HIV diagnosis in Sweden
Authors: Brännström J , Svedhem Johansson V , Marrone G , Wendahl S , Yilmaz A , Blaxhult A , Sönnerborg A
Published: November 2015

Objectives

The aim of the study was to identify factors in HIV‐infected patients and the health care system which contribute to late diagnosis.

Methods

All patients who were newly diagnosed with HIV infection at 12 clinics in Sweden over a period of 2.5 years (n = 575) were included in the study, corresponding to three‐quarters of newly diagnosed HIV infections in the country. The patients were classified as non‐late presenters or late presenters (LPs), defined as those with a CD4 count < 350 cells/μL or AIDS. LPs were subdivided into those without and those with advanced HIV disease, which was defined as a CD4 count < 200 cells/μL or AIDS. Demographics, missed AIDS and HIV‐associated symptoms in the preceding 3 years, immigration date, and health examination at immigration were recorded.

Results

Fifty‐eight per cent of the patients were LPs, of whom 66% had advanced disease. Age > 30 years, origin in sub‐Saharan Africa or Eastern Europe/Asia/the Pacific region, and country of transmission being in sub‐Saharan Africa or unknown were associated with late presentation. Half of the patients of non‐Swedish origin had lived for more than 1 year in Sweden at diagnosis and 66% had a missed HIV testing opportunity at immigration. Twenty‐seven per cent of all patients had presented for health care with AIDS‐ and/or HIV‐associated conditions without having an HIV test. Sixteen per cent had a history of symptoms without seeking care.

Conclusions

Deficiencies in the health care system with missed HIV testing opportunities contribute to the high proportion of late presenters in Sweden, especially among migrants. With increased testing at immigration and further incorporation of “indicator‐guided” testing in general practice, most patients could be diagnosed earlier.
Consistency of passerine embryo development and the use of embryonic staging in studies of hatching failure
Authors: Hemmings Nicola , Birkhead Tim R.
Published: November 2015

Hatching failure is widespread in birds, and is usually the result of embryo death rather than infertility. Embryo death can result from both intrinsic and extrinsic factors, some of which may vary across the developmental period. Determining the point at which an embryo died during development may therefore help us to understand the underlying cause of death. Here we describe simple criteria that can be used by field ornithologists to establish the developmental stage of dead embryos found in unhatched passerine eggs, and explain how this can be used to estimate the date of embryo death. We compared the pattern of embryo development over the incubation period for three species, the Zebra FinchTaeniopygia guttata, Blue TitCyanistes caeruleusand Great TitParus major. We also compared rates of Zebra Finch embryo development under artificial and standard (parental) incubation. Embryo development rates were remarkably similar across the three species and between Zebra Finch embryos under artificial and natural incubation conditions. We therefore suggest that the pattern of embryo development in the Zebra Finch may provide a model for other small passerines with similar incubation periods, but acknowledge that further interspecific comparisons are required before this model is considered more widely applicable. By estimating embryo death dates using our approach, ornithologists will be able to determine temporal patterns of embryo mortality in relation to extrinsic environmental conditions. This approach may shed light on how extrinsic factors such as climate and parental behaviour influence embryo survival in wild birds.
Apically extruded debris during root canal preparation using Vortex Blue, K3XF, ProTaper Next and Reciproc instruments
Authors: Topçuoğlu H. S. , Zan R. , Akpek F. , Topçuoğlu G. , Ulusan Ö. , Aktı A. , Düzgün S. , Ağırnaslıgil M.
Published: November 2015

Aim

To assess the amount of debris extruded apically during root canal preparation using various nickel–titanium instrumentation systems.

Methodology

Sixty extracted single‐rooted mandibular premolar human teeth were randomly assigned to four groups (n = 15 teeth for each group). The canals were then instrumented with the following instrument systems: Vortex Blue (VB; Dentsply Tulsa Dental, Tulsa, OK, USA), K3XF (SybronEndo, Orange, CA, USA), Reciproc (VDW, Munich, Germany) and ProTaper Next (PTN; Dentsply Maillefer, Ballaigues, Switzerland). Apically extruded debris during instrumentation was collected into pre‐weighed Eppendorf tubes. The Eppendorf tubes were then stored in an incubator at 70 °C for 5 days. The weight of the dry extruded debris was established by subtracting the pre‐instrumentation and post‐instrumentation weight of the Eppendorf tubes for each group. The data were analysed using one‐way analysis of variance (anova) and Tukey's post hoc tests.

Results

Vortex Blue and PTN files were associated with significantly less apically extruded debris than the K3XF and Reciproc files (P < 0.05), but there was no significant difference between the VB and PTN files or between the K3XF and Reciproc files (P > 0.05).

Conclusions

All instruments were associated with apical extrusion of debris. VB and PTN files were associated with less debris extrusion compared to the other systems.
Dislodgement resistance of calcium silicate‐based materials from root canals with varying thickness of dentine
Authors: Ulusoy Ö. İ. , Paltun Y. N. , Güven N. , Çelik B.
Published: November 2015

Aim

To evaluate the dislodgement resistance of DiaRoot BioAggregate and Biodentine from canals in roots with varying amounts of remaining dentine thickness.

Methodology

A total of 90 maxillary incisor teeth with similar dimensions were used. The teeth were extracted for periodontal reasons from adult subjects aged between 52 and 61 years. They were decoronated at the cemento‐enamel junction. Simulated internal cavities with a depth of 3 mm were performed by widening the canals on the coronal thirds of the roots, leaving varying amounts of remaining dentine thickness. The canals were enlarged progressively using round diamond burs until the desired dentine wall thickness was obtained. The samples were divided into three main groups (n = 30 each) according to the dentine thickness as follows: group 1: dentine thickness of 0.75 mm, group 2: dentine thickness of 1.50 mm and group 3: dentine thickness of 2.25 mm. Then, these main groups were further divided into two subgroups (n = 15 each) according to the filling material (DiaRoot BioAggregate or Biodentine). Horizontal root slices of 1 mm were obtained from each specimen. Vertical loading was applied to the filling materials at a cross‐head speed of 1 mm min−1 using a universal testing machine. The force that led to dislodgement of the filling was recorded in Newtons. The resistance to dislodgement was calculated in megapascals (MPa) by dividing the load in Newtons by the area of the bonded interface. The data were statistically analysed with two‐way anova with Tukey's honestly significant difference (HSD) test.

Results

Biodentine had significantly higher resistance to dislodgement than DiaRoot BioAggregate (P < 0.001). The specimens with thinner remaining dentine had lower dislodgement resistance compared to those with dentine thicknesses of 1.50 and 2.25 mm (P < 0.001). The lowest mean value for dislodgement resistance was obtained from the DiaRoot BioAggregate group with 0.75 mm dentine thickness (2.72 ± 0.90 MPa).

Conclusion

The dislodgement resistance of Biodentine and DiaRoot BioAggregate from root dentine was influenced by remaining dentine thickness, which determines dentinal tubular density.