bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits
Authors: Lane Jacqueline M. , Liang Jingjing , Vlasac Irma , Anderson Simon G. , Bechtold David A. , Bowden Jack , Emsley Richard , Gill Shubhroz , Little Max A. , Luik AnneMarie I. , Loudon Andrew , Scheer Frank A.J.L. , Purcell Shaun M. , Kyle Simon D. , Lawlor Deborah A. , Zhu Xiaofeng , Redline Susan , Ray David W. , Rutter Martin K. , Saxena Richa
Published: October 2016

Chronic sleep disturbances, associated with cardio-metabolic diseases, psychiatric disorders and all-cause mortality1,2, affect 25–30% of adults worldwide3. While environmental factors contribute importantly to self-reported habitual sleep duration and disruption, these traits are heritable4–9, and gene identification should improve our understanding of sleep function, mechanisms linking sleep to disease, and development of novel therapies. We report single and multi-trait genome-wide association analyses (GWAS) of self-reported sleep duration, insomnia symptoms including difficulty initiating and/or maintaining sleep, and excessive daytime sleepiness in the UK Biobank (n=112,586), with discovery of loci for insomnia symptoms (nearMEIS1, TMEM132E, CYCL1, TGFBIin females andWDR27in males), excessive daytime sleepiness (nearAR/OPHN1) and a composite sleep trait (nearINADLandHCRTR2), as well as replication of a locus for sleep duration (atPAX-8). Genetic correlation was observed between longer sleep duration and schizophrenia (rG=0.29,p=1.90x10−13) and between increased excessive daytime sleepiness and increased adiposity traits (BMI rG=0.20,p=3.12x10−09; waist circumference rG=0.20,p=2.12x10−07).
Automatic identification of informative regions with epigenomic changes associated to hematopoiesis
Authors: Carrillo-de-Santa-Pau Enrique , Juan David , Pancaldi Vera , Were Felipe , Martin-Subero Ignacio , Rico Daniel , Valencia Alfonso ,   on behalf of The BLUEPRINT Consortium
Published: October 2016

Hematopoiesis is one of the best characterized biological systems but the connection between chromatin changes and lineage differentiation is not yet well understood. We have developed a bioinformatic workflow to generate a chromatin space that allows to classify forty-two human healthy blood epigenomes from the BLUEPRINT, NIH ROADMAP and ENCODE consortia by their cell type. This approach let us to distinguish different cells types based on their epigenomic profiles, thus recapitulating important aspects of human hematopoiesis. The analysis of the orthogonal dimension of the chromatin space identify 32,662 chromatin determinant regions (CDRs), genomic regions with different epigenetic characteristics between the cell types. Functional analysis revealed that these regions are linked with cell identities. The inclusion of leukemia epigenomes in the healthy hematological chromatin sample space gives us insights on the healthy cell types that are more epigenetically similar to the disease samples. Further analysis of tumoral epigenetic alterations in hematopoietic CDRs points to sets of genes that are tightly regulated in leukemic transformations and commonly mutated in other tumors. Our method provides an analytical approach to study the relationship between epigenomic changes and cell lineage differentiation. Method availability:https://github.com/david-juan/ChromDet
Neural differentiation of incorrectly predicted memories
Authors: Kim Ghootae , Norman Kenneth A. , Turk-Browne Nicholas B.
Published: October 2016

When an item is predicted in a particular context but the prediction is violated, memory for that item is weakened (Kim et al., 2014). Here we explore what happens when such previously mispredicted items are later re-encountered. According to prior neural network simulations, this sequence of events - misprediction and subsequent restudy - should lead to differentiation of the item's neural representation from the previous context (on which the misprediction was based). Specifically, misprediction weakens connections in the representation to features shared with the previous context, and restudy allows new features to be incorporated into the representation that are not shared with the previous context. This cycle of misprediction and restudy should have the net effect of moving the item‘s neural representation away from the neural representation of the previous context. We tested this hypothesis using fMRI, by tracking changes in item-specific BOLD activity patterns in the hippocampus, a key structure for representing memories and generating predictions. In left CA2/3/DG, we found greater neural differentiation for items that were repeatedly mispredicted and restudied compared to items from a control condition that was identical except without misprediction. We also measured prediction strength in a trial-by-trial fashion and found that greater misprediction for an item led to more differentiation, further supporting our hypothesis. Thus, the consequences of prediction error go beyond memory weakening: If the mispredicted item is restudied, the brain adaptively differentiates its memory representation to improve the accuracy of subsequent predictions and to shield it from further weakening.

Significance

Competition between overlapping memories leads to weakening of non-target memories over time, making it easier to access target memories. However, a non-target memory in one context might become a target memory in another context. How do such memories get re-strengthened without increasing competition again? Computational models suggest that the brain handles this by reducing neural connections to the previous context and adding connections to new features that were not part of the previous context. The result is neural differentiation away from the previous context. Here provide support for this theory, using fMRI to track neural representations of individual memories in the hippocampus and how they change based on learning.
Energy Conservation as a Measure of Simulation Accuracy
Authors: Eastman Peter , Pande Vijay S.
Published: October 2016

Energy conservation is widely used as a measure of accuracy for molecular simulations. When reporting rates of energy drift, researchers usually assume it is linear in the simulation length, temperature, and system size. We study these assumptions and find that all three are incorrect. Energy drift is too complicated to characterize with a single number, and a more sophisticated analysis is needed to identify the effects of systematic versus random drift, and of integration error versus numerical error. We further argue that energy conservation is not a reliable measure of accuracy. Having small overall drift on long time scales is not a sufficient condition, and in some cases not a necessary condition, for a simulation to produce meaningful results.
Mechanochemical synthesis and crystal structure of a 1:2 co-crystal of 1,3,6,8-tetraazatricyclo[4.3.1.13,8]undecane (TATU) and 4-chloro-3,5-dimethylphenol
Authors: Rivera Augusto , Rojas Jicli José , Sadat-Bernal John , Ríos-Motta Jaime , Bolte Michael
Published: October 2016

Solvent-free treatment of 1,3,6,8-tetraazatricyclo[4.3.1.13,8]undecano (TATU) with 4-chloro-3,5-dimethylphenol led to the formation of the title co-crystal, C7H14N4·2C8H9ClO. The asymmetric unit contains one aminal cage molecule and two phenol molecules linked via two O—H...N hydrogen bonds. In the aminal cage, the N–CH2–CH2–N unit is slightly distorted from a syn periplanar geometry. Aromatic π–π stacking between the benzene rings from two different neighbouring phenol molecules [centroid–centroid distance = 4.0570 (11) Å] consolidates the crystal packing.
Channels with ordered water and bipyridine molecules in the porous coordination polymer {[Cu(SiF6)(C10H8N2)2]·2C10N2H8·5H2O}
n
Authors: Aubert Emmanuel , Doudouh Abdelatif , Peluso Paola , Mamane Victor
Published: October 2016

The coordination polymer {[Cu(SiF6)(C10H8N2)2]·2C10H8N2·5H2O}
n
, systematic name: poly[[bis(μ2-4,4′-bipyridine)(μ2-hexafluoridosilicato)copper(II)] 4,4′-bipyridine disolvate pentahydrate], contains pores which are filled with water and 4,4′-bipyridine molecules. As a result of the presence of these ordered species, the framework changes its symmetry from P4/mmm to P21/c. The 4,4′-bipyridine guest molecules form chains inside the 6.5 × 6.9 Å pores parallel to [100] in which the molecules interact through π–π stacking. Ordered water molecules form infinite hydrogen-bonded chains inside a second pore system (1.6 × 5.3 Å free aperture) perpendicular to the 4,4′-bipyridine channels.
Crystal structure of 9-(dibromomethyl)-1,1-difluoro-3,7-dimethyl-1H-[1,3,5,2]oxadiazaborinino[3,4-a][1,8]naphthyridin-11-ium-1-uide
Authors: Wang Bang Zhong , Zhou Jun Ping , Zhou Yong , Luo Jian Song , Chi Shao Ming
Published: October 2016

The molecule of the title 1,8-naphthyridine-BF2 derivative, C12H10BBr2F2N3O, is located on a mirror plane running parallel to the entire ring system and the attached methyl C atoms. Individual molecules are stacked along the b-axis direction. The cohesion in the crystal structure is accomplished by C—H...F hydrogen bonds and additional off-set π–π interactions [centroid-to-centroid distance = 3.6392 (9) Å, slippage 0.472 Å], leading to the formation of a three-dimensional supramolecular network.
Crystal structures of 2′-benzoyl-1′-(4-methylphenyl)-1,1′,2,2′,5′,6′,7′,7a′-octahydrospiro[indole-3,3′-pyrrolizin]-2-one and 2′-(4-bromobenzoyl)-1′-(2-chlorophenyl)-1,1′,2,2′,5′,6′,7′,7a′-octahydrospiro[indole-3,3′-pyrrolizin]-2-one
Authors: Chandrarekha M. , Srinivasan N. , Kottala Vijaya P. , Siva A. , Krishnakumar R. V.
Published: October 2016

The two title compounds, C28H26N2O2, (I), and C27H22BrClN2O2, (II), differ in their substituents, viz.4-methylphenyl and benzoyl rings in (I) replaced by 2-chlorophenyl and 4- bromobenzoyl, respectively, in (II). A significant difference between the two molecules is found in the deviation of the benzoyl O atom from the least-squares plane of the ring to which it is attached [0.593 (4) and 0.131 (3) Å, respectively], a fact which may be attributed to the different participation of the benzoyl O atoms as acceptors in their intermolecular C—H...O interactions. The chemical modifications in (I) and (II) do not seem to affect the type nor strength of the intermolecular N—H...N and C—H...O hydrogen bonds responsible for the two crystal structures, such that the aggregation of molecules appears similar in spite of the molecular changes.
Crystal structure of 2,4-di-tert-butyl-6-(hydroxymethyl)phenol
Authors: Aranburu Leiva Ane I. , Benjamin Sophie L. , Langley Stuart K. , Mewis Ryan E.
Published: October 2016

The title compound, C15H24O2, is an example of a phenol-based pendant-arm precursor. In the molecule, the phenol hydroxy group participates in an intramolecular O—H...O hydrogen bond with the pendant alcohol group, forming an S(6) ring. This ring adopts a half-chair conformation. In the crystal, O—H...O hydrogen bonds connect molecules related by the 31 screw axes, forming chains along the c axis. The C—C—O angles for the hydroxy groups are different as a result of the type of hybridization for the C atoms that are involved in these angles. The C—C—O angle for the phenol hydroxy group is 119.21 (13)°, while the angle within the pendant alcohol is 111.99 (13)°. The bond length involving the phenolic oxygen is 1.3820 (19) Å, which contrasts with that of the alcoholic oxygen which is 1.447 (2) Å. The former is conjugated with the aromatic ring and so leads to the observed shorter bond length.
Crystal structure and Hirshfeld surface analysis of 1-carboxy-2-(3,4-dihydroxyphenyl)ethan-1-aminium chloride 2-ammonio-3-(3,4-dihydroxyphenyl)propanoate: a new polymorph of L-dopa HCl and isotypic with its bromide counterpart
Authors: Kathiravan Perumal , Balakrishnan Thangavelu , Venkatesan Perumal , Ramamurthi Kandasamy , Percino María Judith , Thamotharan Subbiah
Published: October 2016

The title molecular salt, C9H12NO4
+·Cl−·C9H11NO4, is isotypic with that of the bromide counterpart [Kathiravan et al. (2016). Acta Cryst. E72, 1544–1548]. The title salt is a second monoclinic polymorph of the L-dopa HCl structure reported earlier in the monoclinic space group P21 [Jandacek & Earle (1971). Acta Cryst. B27, 841–845; Mostad & Rømming (1974). Acta Chemica Scand. B28, 1161–1168]. In the title compound, monoclinic space group I2, one of the dopa molecules has a positive charge with a protonated α-amino group and the α-carboxylic acid group uncharged, while the second dopa molecule has a neutral charge, the α-amino group is protonated and the α-carboxylic acid is deprotonated. In the previously reported form, a single dopa molecule is observed in which the α-amino group is protonated and the α-carboxylic acid group is uncharged. The invariant and variations of various types of intermolecular interactions present in these two forms of dopa HCl structures are discussed with the aid of two-dimensional fingerprint plots.
Zwitterionic 4-carboxy-2-(pyridinium-2-yl)-1H-imidazole-5-carboxylate
Authors: Zhang Kanglong , Qi Xiaojin , Yuan Bingnian
Published: October 2016

The title compound, C10H7N3O4, is zwitterionic, with one carboxyl group deprotonated and the pyridyl group protonated. The pyridine ring is close to coplanar with the imidazole ring, making a dihedral angle of 2.79 (8)°, this conformation being maintained by the presence of an intramolecular O—H...O hydrogen bond. In the crystal, two sets of N—H...O hydrogen bonds link the molecules through three conjoined cyclic hydrogen-bonding interactions, with two R
1
2(7) and one R
2
2(10) motifs, forming centrosymmetric cyclic dimers. These are linked through C—H...O hydrogen bonds, giving a supramolecular chain structure extending along the b-axis direction.
Marketing in B2B organisations: as it is; as it should be – a commentary for change
Authors: McDonald Malcolm
Published: October 2016

Purpose

There are many challenges facing senior marketing people, and this commentary paper, based on the author’s consultancy experience, teaching expertise and observations of the business-to-business (B2B) environment, aims to address the causal relationship between marketing expenditure and results, which is holding back marketers from inclusion in the boardroom.

Design/methodology/approach

This paper includes a contextual analysis with questions and answers, giving supporting examples and facts.

Findings

B2B marketers have work extensively to earn a place in the boardroom. The author remains optimistic that given the increasing number of chartered marketers (marketing executives qualified to practice via the Chartered Institute of Marketing) and marketing MSc programmes, B2B marketers will eventually earn the right become the main drivers of corporate strategy, as is the case in the best companies in the world.

Originality/value

The paper brings valuable insight into enhancing marketing accountability and to provide a better position to marketers in the boardroom.
Does cultural intelligence matter?
Authors: Collins Kathy S. , Duyar Ibrahim , Pearson Carolyn L.
Published: October 2016

Purpose

The purpose of this study was to examine whether the levels of cultural intelligence (CQ) of principals and teachers influence Latino students’ achievement. The study first tested the applicability of Ang and Van Dyne’s (2008) Cultural Intelligence Questionnaire (CQS) for the measurement of principals and teachers’ CQ levels by construct validating this instrument. Later, it investigated whether the CQ levels of principals and teachers explain the achievement levels of Latino students in mathematics and language arts.

Design/methodology/approach

A naturalistic relational research design was used to study the relationships between the study variables. Participants included a cluster random sample of 86 principals and 311 teachers in a southern state. The convergent validation was used to establish the construct validity of the CQS by correlating CQS subscale scores with several measures of principal and teacher multicultural exposure. A series of hierarchical multiple regression analyses were conducted to investigate the association between the principal and teacher CQS subscale scores and the Latino student achievement scores on state standardized tests.

Findings

The four-factor structure of the CQS scale was found to be valid in the educational settings. Principals’ level of CQ significantly predicted Latino students’ achievement scores of eight grade math and eight grade language arts. On the contrary to the expectations, there was no evidence to suggest that teacher-level CQ as measured by the CQS is predictive of Latino student achievement. Further analyses showed that multicultural exposures of teachers, such as being multilingual and visiting other countries, significantly predicted Latino students’ language arts performance.

Originality/value

This study has policy and research implications toward understanding and eliminating achievement gaps of Latino student populations. It sheds empirical light on whether this gap can be explained with the multicultural intelligence levels of principals and teachers, the two most influential actors in schools. By construct validating CQS, the study methodologically contributed to the pertinent educational research, which lacks instruments for the measurement of CQ levels of educational workforce.
Aspiration to enrol children in Islamic studies: a case of academicians
Authors: Islam Tazul , Zayed Tareq M.
Published: October 2016

Purpose

A preliminary observation reveals that children of Islamic studies (IS) academicians do not choose IS as their career discipline. In view of this, this paper aims to explore the dimensions of parental attitudes, behaviours, perceptions and aspirations in seeing a future in IS for their children.

Design/methodology/approach

Fifteen interviews were conducted to explore the attitude of IS academicians. Findings led us to hypothesize that perceived social recognition explains the maximum variance. Later, 126 academicians were surveyed.

Findings

Results of regression analysis rejected the null hypothesis. The parental attitude of IS academicians, their engagement and perceived social recognition significantly predicted their aspiration in enrolling their children in IS. The regression model explained 64 per cent of total variance accounted for IS academicians’ career aspirations for their children. This study suggests investigating the socio-cultural and geographical impact on the career aspirations of IS academicians for their children.

Originality/value

The findings and results of the study can contribute to educational counselling to guide the counsellors. Further study on this issue may reveal whether IS academicians have plans to modify the curriculum or change their socio-economic status. It should also be examined whether they are doing so as a part of their implicit or explicit strategy.
Does anthropomorphism influence customers’ switching intentions in the self-service technology failure context?
Authors: Fan Alei , Wu Luorong (Laurie) , Mattila Anna S.
Published: October 2016

Purpose

To enhance customer experiences, firms are increasingly adding human-like features to their self-service technology (SST) machines. To that end, the purpose of the present study is to examine customer interactions with an anthropomorphic machine in a service failure context. Specifically, the authors investigate the joint effects of machine voice, an individual’s sense of power and the presence of other customers in influencing customers’ switching intentions following an SST failure.

Design/methodology/approach

In this study, the authors used a quasi-experimental design in which they manipulated voice type (anthropomorphic vs robotic) and the presence of other customers (present vs absent) in video-based scenarios while measuring customers’ sense of power. The scenarios reflected a service failure experience with a self-service kiosk at an airport. The authors tested the hypotheses using PROCESS analyses with the Johnson–Neyman technique.

Findings

Consumer reactions to SST failures vary depending on the degree of anthropomorphism associated with an SST machine, an individual’s sense of power and the presence of other customers.

Research limitations/implications

Field inquiry and an investigation in other SST contexts or of other anthropomorphic features are needed to generalize the findings.

Practical implications

Service providers targeting powerful consumers should consider the social presence of others when incorporating anthropomorphic features into their SST facilities.

Originality/value

This study is the first to examine consumer responses to service failures in an anthropomorphic SST context.
Consumer search and satisfaction with mental health services
Authors: Larson Lindsay R.L. , Bock Dora Elizabeth
Published: October 2016

Purpose

Recent evidence on consumer decision-making suggests that highly complex choice scenarios lead consumers to use simplistic decision heuristics, often resulting in suboptimal decision-making. This study aims to investigate the relationships among consumers’ primary information source, patient satisfaction and patient well-being, specifically focused on the search for mental health professionals. The selection of a mental health provider is of interest, because practitioners work from a highly diverse set of theoretical bases, may hold a wide range of different credentials and provide drastically different therapeutic approaches, therefore making the selection complex and difficult for consumers to self-navigate.

Design/methodology/approach

Three studies were undertaken, with data sampling from both patients of mental health services and practitioners.

Findings

Consumers selecting a provider based on self-performed searches, rather than receiving external input (referrals from physicians, relatives or friends), report lower satisfaction with their mental health provider. In turn, patient satisfaction positively impacts patient well-being. Practitioner data corroborate these findings, revealing that a large percentage of patients stem from a self-performed internet search, though mental health providers recognize that external referrals are likely to lead to better outcomes.

Originality/value

The results reveal the importance of understanding the consumer search and, particularly, the use of the internet as a search tool. The results present several implications for service providers, including the need to identify patients’ primary source utilized within an information search, as it can adversely impact patient satisfaction.
Organization and Reporting of Public Financial Accounts: Insights and Policy Implications from the Singapore Budget
Authors: Kwan Chang Yee , Bali Azad Singh , Asher Mukul G.
Published: October 2016

This paper analyses the Singapore government budget's organization and reporting structure, and draws lessons and policy implications for improving public financial management practices. The paper finds that Singapore's fiscal marksmanship record has been poor with consistent underestimates of revenue and overestimates of expenditure. Second, subtle divergences from international reporting standards limit the information available and constrain the budget's analytical usefulness in international comparisons. Third, current reporting conventions of the budget fail to provide an adequate representation of the government's fiscal position. Fourth, revised estimates of budgetary balances in line with international reporting standards show a considerable increase in the fiscal space available. The policy implications of these findings are discussed, as well as some reporting changes which can help improve the fiscal marksmanship record, increase public sector transparency and accountability, and facilitate better quality discourse among all stakeholders on public financial management.
Applications of Wine Pomace in the Food Industry: Approaches and Functions
Authors: García‐Lomillo Javier , González‐SanJosé María Luisa
Published: October 2016

Winemaking generates large amounts of wine pomace, also called grape pomace. This by‐product has attracted the attention of food scientists and the food industry, due to its high content in nutrients and bioactive compounds. This review mainly focuses on the different published approaches to the use of wine pomace and its functions in the food industry. Traditionally, wine pomace has been used to obtain wine alcohol, food colorings, and grape seed oil. More recently, research has focused in the production of other value‐added products, such as extracts of bioactive compounds, mainly phenols, recovery of tartaric acid, and the making of flours. The most common functions associated with wine pomace products are their use as antioxidants, followed by their use as fortifying, coloring, and antimicrobial agents. These products have mainly been applied to the preparation of meat and fish products and to, a lesser extent, cereal products.
Impacts of Scarification and Degermination on the Expansion Characteristics of Select Quinoa Varieties during Extrusion Processing
Authors: Aluwi Nicole A. , Gu Bon‐Jae , Dhumal Gaurav S. , Medina‐Meza Ilce G. , Murphy Kevin M. , Ganjyal Girish M.
Published: October 2016

Extrusion of 2 quinoa varieties, Cherry Vanilla and Black (scarified and unscarified) and a mixed quinoa variety, Bolivian Royal (scarified and degermed) were studied for their extrusion characteristics. A corotating twin‐screw extruder with a 3 mm round die was used. Feed moisture contents of 15%, 20%, and 25% (wet basis) were studied. The extruder barrel temperature was kept constant at 140 °C and screw speeds were varied from 100, 150, and 200 revolutions per minutes. Process responses (specific mechanical energy, back pressure, and torque) and product responses (expansion ratio, unit density, and water absorption index/water solubility index) were evaluated. The degermed Bolivian Royal showed the highest expansion in comparison to all other varieties, attributed to its significantly low levels of fat, fiber, and protein. The scarified Cherry Vanilla resulted in the lowest expansion ratio. This was attributed to the increase in the protein content from the removal of the outer layer. The results indicate that all the varieties performed differently in the extrusion process due to their modification processes as well as the individual variety characteristics.
Analysis of cell‐free fetal DNA in maternal blood for detection of trisomy 21, 18 and 13 in a general pregnant population and in a high risk population – a systematic review and meta‐analysis
Authors: Iwarsson Erik , Jacobsson Bo , Dagerhamn Jessica , Davidson Thomas , Bernabé Eduardo , Heibert Arnlind Marianne
Published: October 2016

Introduction

The aim of this study was to review the performance of non‐invasive prenatal testing (NIPT) for detection of trisomy 21, 18 and 13 (T21, T18 and T13) in a general pregnant population as well as to update the data on high‐risk pregnancies.

Material and methods

Systematic review and meta‐analysis. PubMed, Embase and the Cochrane Library were searched. Methodological quality was rated using QUADAS and scientific evidence using GRADE. Summary measures of diagnostic accuracy were calculated using a bivariate random‐effects model.

Results

In a general pregnant population, there is moderate evidence that the pooled sensitivity is 0.993 (95% CI 0.955–0.999) and specificity was 0.999 (95% CI 0.998–0.999) for the analysis of T21. Pooled sensitivity and specificity for T13 and T18 was not calculated in this population due to the low number of studies. In a high‐risk pregnant population, there is moderate evidence that the pooled sensitivities for T21 and T18 are 0.998 (95% CI 0.981–0.999) and 0.977 (95% CI 0.958–0.987) respectively, and low evidence that the pooled sensitivity for T13 is 0.975 (95% CI 0.819–0.997). The pooled specificity for all three trisomies is 0.999 (95% CI 0.998–0.999).

Conclusions

This is the first meta‐analysis using GRADE that shows that NIPT performs well as a screen for trisomy 21 in a general pregnant population. Although the false positive rate is low compared with first trimester combined screening, women should still be advised to confirm a positive result by invasive testing if termination of pregnancy is under consideration.
Pharmacokinetics and pharmacodynamics of a new highly concentrated intranasal midazolam formulation for conscious sedation
Authors: Schrier Lenneke , Zuiker Rob , Merkus Frans W. H. M. , Klaassen Erica S. , Guan Zheng , Tuk Bert , van Gerven Joop M. A. , van der Geest Ronald , Groeneveld Geert Jan
Published: October 2016

Aim

To evaluate the pharmacokinetics, pharmacodynamics, nasal tolerance and effects on sedation of a highly concentrated aqueous intranasal midazolam formulation (Nazolam) and to compare these to intravenous midazolam.

Methods

In this four‐way crossover, double‐blind, double‐dummy, randomized, placebo‐controlled study, 16 subjects received 2.5 mg Nazolam, 5.0 mg Nazolam, 2.5 mg intravenous midazolam or placebo on different occasions. Pharmacokinetics of midazolam and α‐hydroxy‐midazolam were characterized and related to outcome variables for sedation (saccadic peak velocity, the Bond and Lader visual analogue scale for sedation, the simple reaction time task and the observer's assessment of alertness/sedation). Nasal tolerance was evaluated through subject reporting, and ear, nose and throat examination.

Results

Nazolam bioavailability was 75%. Maximal plasma concentrations of 31 ng ml−1 (CV, 42.3%) were reached after 11 min (2.5 mg Nazolam), and of 66 ng ml−1 (coefficient of variability, 31.5%) after 14 min (5.0 mg Nazolam). Nazolam displayed a significant effect on OAA/S scores. Sedation onset (based on SPV change) occurred 1 ± 0.7 min after administration of 2.5 mg intravenous midazolam, 7 ± 4.4 min after 2.5 mg Nazolam, and 4 ± 1.8 min after 5 mg Nazolam. Sedation duration was 118 ± 95.6 min for 2.5 mg intravenous midazolam, 76 ± 80.4 min for 2.5 mg Nazolam, and 145 ± 104.9 min for 5.0 mg Nazolam. Nazolam did not lead to nasal mucosa damage.

Conclusions

This study demonstrates the nasal tolerance, safety and efficacy of Nazolam. When considering the preparation time needed for obtaining venous access, conscious sedation can be achieved in the same time span as needed for intravenous midazolam. Nazolam may offer important advantages in conscious sedation.
Mentalization and depressive symptoms in a clinical sample of adolescents and young adults
Authors: Belvederi Murri Martino , Ferrigno Gabriella , Penati Simona , Muzio Caterina , Piccinini Giulia , Innamorati Marco , Ricci Federica , Pompili Maurizio , Amore Mario
Published: October 2016

Background

Increasing evidence supports that mentalization deficits may have a role in the genesis of young age depression; however, few studies examined this issue in clinical populations.

Methods

Outpatients aged 14–21, suffering from various psychiatric disorders, were assessed using the Mentalization Questionnaire (MZQ), the Beck Depression Inventory (BDI), and the Childhood Trauma Questionnaire (CTQ), using data from age‐matched healthy students for comparison. The relationship between CTQ, MZQ, and BDI scores was examined at the cross‐sectional level, including mediation analyses, and longitudinally, in a subsample who underwent a psychotherapy intervention.

Results

Of 83 subjects, 33 (39.8%) had mentalization levels that were 1 standard deviation below those of comparison subjects. In the whole sample, the levels of mentalization were inversely associated with BDI (r = −.68, p < .001) and CTQ scores (r = −.30, p = .006). Moreover, MZQ scores mediated a large part of the effect of childhood trauma on depression (total effect: 10.6, 95% CI: 5.3, 15.9; direct effect: 6.5, 95% CI: 2.1, 10.8; indirect effect: 4.1, 95% CI: 1.5, 7.4). This effect was almost entirely explained by the Affect Regulation subscale. In patients re‐evaluated after four sessions (n = 37), the decrease in BDI scores correlated with the increase in MZQ scores (r = .40, p = .02).

Conclusions

In a juvenile clinical sample, deficits of mentalization abilities were associated with the severity of depression and explained part of the depressogenic effects of childhood trauma.
The Norms of Popular Peers Moderate Friendship Dynamics of Adolescent Aggression
Authors: Laninga‐Wijnen Lydia , Harakeh Zeena , Steglich Christian , Dijkstra Jan K. , Veenstra René , Vollebergh Wilma
Published: October 2016

This study examined whether peer norms for aggression within the classroom impact friendship selection, maintenance, and socialization processes related to aggression across the 1st year of secondary school (N = 1,134 students from 51 classes, Mage = 12.66). As hypothesized, longitudinal social network analyses indicated that friendship selection and influence processes related to aggression depended on the popularity norm within the classroom (i.e., the class‐level association between popularity and aggression) rather than the descriptive norm (aggregated average of aggressive behavior). Hence, only in classes where the valence of aggression is high (because it is positively associated with popularity), adolescents tend to select their friends based on similarity in aggression and adopt the aggressive behavior of their friends.
The inheritance of juvenile onset primary open angle glaucoma
Authors: Gupta V. , Somarajan B.I. , Gupta S. , Chaurasia A.K. , Kumar S. , Dutta P. , Gupta V. , Sharma A. , Tayo B.O. , Nischal K.
Published: October 2016

Juvenile onset open angle glaucoma (JOAG) affects patients before 40 years of age, who present with high intraocular pressure and deep steep cupping of the optic nerve head. While it was considered to be inherited in an autosomal dominant fashion, recent studies have shown an autosomal recessive pattern as well as sporadic occurrence of the disease in several families. In this review, we analyze the genetic basis of the disease along with common mutations and their association with JOAG. We also analyzed the inheritance patterns in a large group of unrelated JOAG patients (n = 336) from Northern India wherein the prevalence of familial occurrence was assessed and segregation analysis performed, to determine the mode of inheritance.
Improvement in the prediction of exercise‐induced elevation of left ventricular filling pressure in patients with normal left ventricular ejection fraction
Authors: Meluzin Jaroslav , Starek Zdenek , Kulik Tomas , Jez Jiri , Lehar Frantisek , Tomandl Josef , Dusek Ladislav , Wolf Jiri , Leinveber Pavel , Novak Miroslav
Published: October 2016

Background

Noninvasive diagnosis of exercise‐induced elevation of left ventricular filling pressure is difficult and remains unsatisfactory. The aim of this study was to assess the accuracy of the ratio of early diastolic transmitral (E) to mitral annular (e′) velocity and to determine new parameters or parameter combinations with the ability to predict exercise‐induced left atrial pressure (LAP) elevation.

Methods and results

Eighty patients with paroxysmal atrial fibrillation (AF) referred for catheter AF ablation underwent simultaneous exercise echocardiography and direct invasive LAP measurements, as well as a resting and postexercise biomarker analysis. Exercise E/e′ ≥8.85 predicted exercise LAP ≥20 mm Hg with 61.5% sensitivity and 88.9% specificity (area under the curve [AUC], 0.76). Of all of the individual parameters tested, the best prediction was achieved with exercise E/s′ (s′=peak systolic mitral annular velocity) ≥8.75 (sensitivity, 88.5%; specificity, 64.8%; positive predictive value, 54.8%; negative predictive value, 92.1%; AUC, 0.84). However, the combination of exercise E/A (A = late diastolic transmitral flow velocity) ≥1.22 + exercise E/e′ ≥8.85 + exercise s′≤11.05 cm/s provided the most precise prediction of exercise LAP elevation (sensitivity, 84.6%; specificity, 79.6%; positive predictive value, 66.7%; negative predictive value, 91.5%; AUC, 0.90).

Conclusions

Exercise E/e′, when used as a sole parameter, was not sufficiently reliable to predict exercise‐induced elevation of LAP. The application of a multivariate‐adjusted combination of parameters appeared to be the preferable approach for the noninvasive prediction of exercise LAP elevation.
Leukemic infiltration presenting as myocardial hypertrophy after complete remission of acute myeloid leukemia
Authors: Jung Mi‐Hyang , Lee Youn‐Ho , Lee Kyo‐Young , Jung Hae Ok , Youn Ho‐Joong
Published: October 2016

Here, we report a rare case of isolated leukemic infiltrate of the myocardium (extramedullary involvement) presenting as restrictive cardiomyopathy in a patient in complete remission of acute myeloid leukemia. It was evaluated with multimodality imaging studies (echocardiography and cardiac MRI) and further confirmed by pathology. The present case highlights the importance of maintaining a high degree of clinical suspicion when evaluating patients with progressive ventricular hypertrophy of unknown cause, including recognition of the potential involvement by recurrent hematologic malignancy.
Surgical treatment of polymicrogyria‐related epilepsy
Authors: Cossu Massimo , Pelliccia Veronica , Gozzo Francesca , Casaceli Giuseppe , Francione Stefano , Nobili Lino , Mai Roberto , Castana Laura , Sartori Ivana , Cardinale Francesco , Lo Russo Giorgio , Tassi Laura
Published: October 2016

Objective

The role of resective surgery in the treatment of polymicrogyria (PMG)–related focal epilepsy is uncertain. Our aim was to retrospectively evaluate the seizure outcome in a consecutive series of patients with PMG‐related epilepsy who received, or did not receive, surgical treatment, and to outline the clinical characteristics of patients who underwent surgery.

Methods

We evaluated 64 patients with epilepsy associated with magnetic resonance imaging (MRI)–documented PMG. After presurgical evaluation, 32 patients were excluded from surgical treatment and 32 were offered surgery, which was declined by 8 patients. Seizure outcome was assessed in the 40 nonsurgical and 24 surgical patients.

Results

Of 40 nonsurgical patients, 8 (20%) were seizure‐free after a mean follow‐up of 91.7 ± (standard deviation) 59.5 months. None of the eight patients who declined surgical treatment was seizure‐free (mean follow‐up: 74.3 ± 60.6 months). These seizure outcomes differ significantly (p = 0.000005 and p = 0.0003, respectively) from that of the 24 surgical patients, 18 of whom (66.7%) were Engel's class I postoperatively (mean follow‐up: 66.5 ± 54.0 months). Of the eight patients excluded from surgery for seizure control at first visit, two had seizure recurrence at last contact. At last contact, antiepileptic drugs (AEDs) had been withdrawn in 6 of 24 surgical and in one of 40 nonsurgical cases (p = 0.0092).

Significance

The present study indicates that, at least in a subset of adequately selected patients with PMG‐related epilepsy, surgery may provide excellent seizure outcomes. Furthermore, it suggests that surgery is superior to AEDs for achieving seizure freedom in these cases.
Olfactory symptoms reported by migraineurs with and without auras
Authors: Fornazieri Marco Aurélio , Neto Anibal Rodrigues , de Rezende Pinna Fabio , Gobbi Porto Fabio Henrique , de Lima Navarro Paulo , Voegels Richard Louis , Doty Richard L.
Published: October 2016

Objective

Olfaction‐related symptoms accompany migraine attacks and some, such as osmophobia, may be useful in differentiating migraine from other types of headaches. However, the types and frequencies of olfactory symptoms associated with migraine have not been well characterized. The goal of this study was to better characterize the olfactory symptoms of migraine.

Methods

A cross‐sectional study was devised. One hundred and thirteen patients who met the International Classification of Headache Disorders II criteria for migraine were administered a new 65‐item questionnaire specifically focused on olfaction‐related experiences (eg, odor‐related triggers, osmophobia, cacosmia, phantosmia, olfactory hallucinations, olfactory hypersensitivity, and self‐perceived olfactory function). Visual analog scale ratings and frequencies were computed and compared between migraineurs with and without auras using t‐tests and chi‐square analyses.

Results

While osmophobia was present in 95.5% of the patients, the prevalence of other olfaction‐related symptoms was much lower (interictal olfactory hypersensitivity [IOH], 14.1%; olfactory hallucinations, 6.2%; phantosmia, 4.4%; cacosmia/euosmia, 2.6%). Migraine was commonly triggered by odors (90.2%), with perfume being the most common trigger (95.1%), followed by cleaning products (81.3%), cigarette smoke (71.5%), and motor vehicle exhaust (70.5%). No significant differences in symptom frequencies were apparent between migraineurs with or without auras (P > .40). Interestingly, patients with IOH reported being less likely to experience osmophobia and odor‐triggered crisis than did those without this symptom (respective percentages: 75% vs. 99% and 69% vs. 94%, P ≤ .002). Osmophobia and odor triggered headache were associated with a mild decrease in self‐reported olfactory acuity.

Conclusion

Odor‐related disturbances were common symptoms of the 113 migraineurs, with nearly all reporting osmophobia. Perfume odor was the most common trigger for the migraine. The reported symptoms did not differ between patients with and without auras. Patients who experienced IOH appeared to fundamentally differ from those who did not experience IOH in terms of the incidence of osmophobia and odor‐triggered crisis. Subjects who reported experiencing osmophobia and odor‐triggered headache reported having worse olfactory acuity.
Microscopic gastrointestinal stromal tumours: a clinical and molecular study of 13 cases
Authors: Anderson William , O'Sullivan Brendan , Hughes Frances , Swift Claire , Smith Matthew , Deshmukh Nayneeta , Taniere Philippe
Published: October 2016

Aims

Recent literature suggests that clinically silent, microscopic gastrointestinal stromal tumours (micro‐GISTs) are common incidental findings. The aim of this study was to examine the histological, immunohistochemical and molecular characteristics of these tumours, which we have defined as measuring ≤20 mm, in order to determine whether the rate and spectrum of mutations are similar to those of clinically symptomatic gastrointestinal stromal tumours (GISTs).

Methods and results

Thirteen micro‐GISTs identified as incidental findings in patients undergoing management of concomitant disease were tested for KIT/PDGFRA mutations. Ten micro‐GISTs (77%) were located in the stomach, two (15%) in the duodenum, and one (8%) in the rectum. The mean tumour size was 9.3 mm (range 2–19 mm). All tumours were well‐circumscribed lesions showing a predominantly spindle‐cell morphology and a very low mitotic rate. Twelve of 13 (92%) tumours carried mutations in either KIT (83%) or PDGFRA (17%), a rate higher than in other published series. A high mutation rate (80%) was also seen in lesions measuring ≤5 mm.

Conclusions

Our results suggest that KIT/PDGFRA mutation is a very common early event in GIST development, that tumour size does not reliably predict the presence of mutation, and that one or more subsequent mutations are required for clinical manifestation.
Trait‐driven responses of grassland butterflies to habitat quality and matrix composition in mosaic agricultural landscapes
Authors: van Halder Inge , Thierry Mélanie , Villemey Anne , Ouin Annie , Archaux Frédéric , Barbaro Luc , Balent Gérard , Benot Marie‐Lise
Published: October 2016

The relative importance of local‐ and landscape‐scale factors on butterfly diversity can depend on the quality, management intensity and landscape context of habitat patches. This study aims to disentangle these local and landscape effects on taxonomic and functional composition of butterfly communities within mosaic agricultural landscapes.

We sampled butterflies in 144 grasslands and 142 linear elements (road verges and herbaceous strips between crops) in three regions in France. We analysed how local and landscape variables affected butterfly species richness, community composition and community‐weighted mean traits.

Local habitat variables explained more variation in butterfly richness and community composition than landscape‐scale variables, both in grasslands and linear elements. Floristic composition was the most important predictor of butterfly community composition. In sites with tall vegetation and low biomass removal, butterfly communities were more dominated by species with long larval development, low fecundity and low mobility.

Landscape variables were proportionally more influential in linear elements than in grasslands. Increasing landscape heterogeneity, by favouring agricultural mosaics with semi‐natural grasslands and woodlands, appeared to be beneficial for butterflies, especially for specialist species.

Agri‐environmental schemes aiming at preserving butterfly diversity should thus primarily provide incentives to conserve or restore grasslands with low management intensity, while promoting at the same time landscape heterogeneity.
Histological lymphovascular invasion is associated with nodal involvement, recurrence, and survival in patients with cutaneous malignant melanoma
Authors: Tas Faruk , Erturk Kayhan
Published: October 2016

Background

Invasion of the lymphatic or vascular vessels by the primary tumor is considered a sign of aggressive disease that leads to metastases to the regional lymph nodes and to distant sites. Although lymphovascular invasion (LVI) is one of the major characteristics of a primary melanoma tumor, its prognostic significance remains controversial.

Objective

The objective of this study was to determine the clinical significance of LVI in melanoma patients.

Methods

Outcomes in 705 patients with cutaneous melanoma were investigated retrospectively.

Results

The median age of the patients was 52 years (range: 16–104 years). Of the 705 patients, 624 (88.5%) did not have LVI and 81 (11.5%) patients did. Melanoma patients with LVI more frequently had nodular pathology (P = 0.001), invasion to an advanced Clark level (P = 0.000), greater Breslow thickness (P = 0.000), a high mitotic rate (P = 0.018), ulceration (P = 0.000), neurotropism (P = 0.000), lymph node involvement (P = 0.000), multiple lymph node involvement (P = 0.008), recurrent disease (P = 0.003), and metastatic disease (P = 0.008) than those without LVI. However, LVI was not significantly associated with age, gender, anatomic localization, tumor‐infiltrating lymphocytes, vertical growth phase, a pre‐existing melanocytic nevus, or type of distant metastasis. Lymphovascular invasion was significantly associated with both recurrence‐free (P = 0.000) and overall (P = 0.000) survival. On multivariate analyses, although LVI was not independently associated with RFS (P = 0.134), it retained its significance for overall survival (P = 0.000).

Conclusions

Lymphovascular invasion has significant prognostic impact on nodal involvement, recurrence, and overall survival in cutaneous melanoma.
Enzyme‐assisted solvent extraction for extraction of blueberry anthocyanins and separation using resin adsorption combined with extraction technologies
Authors: Xu Qing , Zhou Yuanjing , Wu Yuxiang , Jia Qiang , Gao Guilong , Nie Fei
Published: October 2016

Blueberry anthocyanins are the major active ingredients of blueberry with a variety of biological activities. The scale extraction and separation of blueberry anthocyanins could contribute to their application in drugs, cosmetics, food additives and so on. In this study, using combined technologies to high‐efficient extraction and separation of blueberry anthocyanins was developed. Under the optimum extraction conditions of first 0.3% cellulose and pectinase with 2:1 (m/m) at 37 °C for 4 h and then 1% citric acid‐acidified 75% (v/v) ethanol at 37 °C for 6 h, as high as 25% extraction rate of blueberry anthocyanins was obtained. By ethyl acetate extraction in triplicate and then D101 resin column chromatography, up to 49.6% purity of blueberry anthocyanins was obtained based on UV–vis analysis. The scale‐up extraction and separation of blueberry anthocyanins were carried out. This method was simple but effective, and easy scalable at industrial purpose.