bluuebunny/crossref_metadata_2025 huggingface dataset:
Success rate of informed consent acquisition and factors influencing participation in a multicenter randomized controlled trial of laparoscopic versus open surgery for stage II/III colon cancer in Japan (JCOG0404)
Authors: Etoh Tsuyoshi , Inomata Masafumi , Watanabe Masahiko , Konishi Fumio , Kawamura Yutaka , Ueda Yoshitake , Toujigamori Manabu , Shiroshita Hidefumi , Katayama Hiroshi , Kitano Seigo
Published: July 2015

Introduction

Successful completion of randomized controlled trials (RCT) is dependent on informed consent (IC) acquisition from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed IC acquisition.

Methods

A 30‐institute RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage II/III colon cancer (JCOG0404: UMIN‐CTR C000000105). The success rate of obtaining IC, which was supported by a DVD that helped patients understand this trial, was evaluated in eight periods between October 2004 and March 2009. In addition, reasons for failed IC acquisition were identified from questionnaires.

Results

A total of 1767 patients were informed of their eligibility for the trial, and 1057 (60%) were randomly assigned to either the laparoscopic surgery (n = 529) or open surgery (n = 528) group. The success rate of IC acquisition ranged from 50% to 62% in eight periods. The most common reasons for failed IC acquisition were anxiety/unhappiness about the randomization, patients' preference for one form of surgery, and strong recommendations from referring doctors or relatives.

Conclusions

With the assistance of a DVD, high success rates of IC acquisition were obtained for an RCT of laparoscopic versus open surgery for stage II/III colon cancers. To obtain such a rate, investigators should make efforts to inform patients, their relatives, and referring doctors about the medical contributions a surgical RCT can make.
Human hepatocyte assessment of imatinib drug–drug interactions – complexities in clinical translation
Authors: Beumer Jan H. , Pillai Venkateswaran C. , Parise Robert A. , Christner Susan M. , Kiesel Brian F. , Rudek Michelle A. , Venkataramanan Raman
Published: July 2015

Aim

Inducers and inhibitors of CYP3A, such as ritonavir and efavirenz, may be used as part of the highly active antiretroviral therapy (HAART) to treat HIV patients. HIV patients with chronic myeloid leukemia or gastrointestinal stromal tumour may need imatinib, a CYP3A4 substrate with known exposure response–relationships. Administration of imatinib to patients on ritonavir or efavirenz may result in altered imatinib exposure leading to increased toxicity or failure of therapy, respectively. We used primary human hepatocyte cultures to evaluate the magnitude of interaction between imatinib and ritonavir/efavirenz.

Methods

Hepatocytes were pre‐treated with vehicle, ritonavir, ketoconazole, efavirenz or rifampicin, and the metabolism of imatinib was characterized over time. Concentrations of imatinib and metabolite were quantitated in combined lysate and medium, using LC‐MS.

Results

The predicted changes in imatinib CLoral (95% CI) with ketoconazole, ritonavir, rifampicin and efavirenz were 4.0‐fold (0, 9.2) lower, 2.8‐fold (0.04, 5.5) lower, 2.9‐fold (2.2, 3.5) higher and 2.0‐fold (0.42, 3.5) higher, respectively. These predictions were in good agreement with clinical single dose drug–drug interaction studies, but not with reports of imatinib interactions at steady‐state. Alterations in metabolism were similar after acute or chronic imatinib exposure.

Conclusions

In vitro human hepatocytes predicted increased clearance of imatinib with inducers and decreased clearance with inhibitors of CYP enzymes. The impact of HAART on imatinib may depend on whether it is being initiated or has already been dosed chronically in patients. Therapeutic drug monitoring may have a role in optimizing imatinib therapy in this patient population.
Retrospective Likelihood-Based Methods for Analyzing Case-Cohort Genetic Association Studies
Authors: Shen Yuanyuan , Cai Tianxi , Chen Yu , Yang Ying , Chen Jinbo
Published: July 2015

The case cohort (CCH) design is a cost-effective design for assessing genetic susceptibility with time-to-event data especially when the event rate is low. In this work, we propose a powerful pseudo-score test for assessing the association between a single nucleotide polymorphism (SNP) and the event time under the CCH design. The pseudo-score is derived from a pseudo-likelihood which is an estimated retrospective likelihood that treats the SNP genotype as the dependent variable and time-to-event outcome and other covariates as independent variables. It exploits the fact that the genetic variable is often distributed independent of covariates or only related to a low-dimensional subset. Estimates of hazard ratio parameters for association can be obtained by maximizing the pseudo-likelihood. A unique advantage of our method is that it allows the censoring distribution to depend on covariates that are only measured for the CCH sample while not requiring the knowledge of follow-up or covariate information on subjects not selected into the CCH sample. In addition to these flexibilities, the proposed method has high relative efficiency compared with commonly used alternative approaches. We study large sample properties of this method and assess its finite sample performance using both simulated and real data examples.
Monitoring others’ errors: The role of the motor system in early childhood and adulthood
Authors: Meyer Marlene , Braukmann Ricarda , Stapel Janny C. , Bekkering Harold , Hunnius Sabine
Published: July 2015

Previous research demonstrates that from early in life, our cortical sensorimotor areas are activated both when performing and when observing actions (mirroring). Recent findings suggest that the adult motor system is also involved in detecting others’ rule violations. Yet, how this translates to everyday action errors (e.g., accidentally dropping something) and how error‐sensitive motor activity for others’ actions emerges are still unknown. In this study, we examined the role of the motor system in error monitoring. Participants observed successful and unsuccessful pincer grasp actions while their electroencephalography was registered. We tested infants (8‐ and 14‐month‐olds) at different stages of learning the pincer grasp and adults as advanced graspers. Power in Alpha‐ and Beta‐frequencies was analysed to assess motor and visual processing. Adults showed enhanced motor activity when observing erroneous actions. However, neither 8‐ nor 14‐month‐olds displayed this error sensitivity, despite showing motor activity for both actions. All groups did show similar visual activity, that is more Alpha‐suppression, when observing correct actions. Thus, while correct and erroneous actions were processed as visually distinct in all age groups, only the adults’ motor system was sensitive to action correctness. Functionality of different brain oscillations in the development of error monitoring and mirroring is discussed.
The Role of Early Emotion Impairments in the Development of Persistent Antisocial Behavior
Authors: van Goozen Stephanie H. M.
Published: July 2015

Antisocial behavior that begins in childhood predicts chronic and serious antisocial behavior in adulthood. Antisocial children are impaired in how they perceive, experience, and regulate emotion, particularly fear and sadness, and the neurobiological systems that process aversive emotional information, particularly the stress response systems in the paralimbic system, are compromised. As a result, children may have a difficult temperament, impaired cognitive abilities, or different levels of emotional reactivity. These characteristics, in turn, increase the risk that children have poor social relationships and make decisions that increase the likelihood that their antisocial behavior becomes stable and pervasive. In this article, I clarify the role of emotion impairments in children's antisocial behavior. I also argue that investigating these emotional functions can help identify which children are more likely to persist in behaving antisocially and guide the development of new interventions.
The morning and late‐night salivary cortisol ranges for healthy women may be used in pregnancy
Authors: Ambroziak Urszula , Kondracka Agnieszka , Bartoszewicz Zbigniew , Krasnodębska‐Kiljańska Małgorzata , Bednarczuk Tomasz
Published: July 2015

Objectives

The diagnosis of adrenal dysfunction in pregnancy and in women taking oral contraceptives remains a diagnostic challenge. Salivary cortisol seems to be a useful tool for the diagnosis of Cushing's syndrome and adrenal insufficiency. However, the changes in salivary cortisol concentration in healthy pregnancy are not clearly defined.

Design

The aim of our study was to compare diurnal changes in salivary cortisol in healthy pregnant women, healthy controls and women on oral contraceptives.

Patients

The study groups consisted of (i) 41 healthy pregnant women, (ii) 42 healthy women and (iii) 12 healthy women on oral contraceptives.

Measurements

Serum and salivary cortisol in the morning and salivary late‐night cortisol were measured with Roche ECLIA cortisol test (Elecsys 2010) in each trimester and postpartum.

Results

Despite the elevation of morning serum cortisol in the second and third trimesters of pregnancy, the morning salivary values as well as late‐night salivary cortisol throughout all trimesters were not significantly different from control values (P > 0·5). In the postpartum period, the morning and late‐night salivary cortisol values were significantly lower than in late pregnancy. The morning and late‐night salivary cortisol values in women on contraceptives were also not different from those in the healthy women group.

Conclusion

The results of our study suggest that reference values for salivary cortisol established for a healthy adult population can be used for pregnant women and women on oral contraceptives in the initial diagnostic testing for Cushing's syndrome and adrenal insufficiency.
The impact of poor sampling of polymorphism on cladistic analysis
Authors: Watanabe Akinobu
Published: July 2015

Despite its ubiquity in the natural world, polymorphism is commonly disregarded or poorly sampled in phylogenetic analyses due to deliberate sampling strategy, inadequate sampling effort and limited specimen availability. Poor sampling of intraspecific variation engenders differential sampling of morphs within polymorphic species, which could generate conflicting tree topologies by altering the character‐based affinity among taxa. To assess the potential magnitude of this impact, Polymorphic Entry Replacement Data Analysis (PERDA) was developed as a new script for the TNT phylogenetic program. This script simulates poor sampling of polymorphic taxa on a matrix of discrete characters by iteratively replacing each polymorphic state (e.g. [01]) with a randomly selected single state included in the original polymorphic coding (e.g. 0 or 1). The trees recovered from these subsampled data sets provide a distribution of tree distances, which indicates the level of incongruent trees resulting from different combinations of single states. Performing PERDA on empirical data sets shows alarming frequencies and magnitudes of conflicting tree topologies, demonstrating that poor sampling within polymorphic taxa could yield highly incompatible trees in many data sets. This troubling outcome undermines phylogenetic inferences based on data with poor intraspecific sampling, which is typical for palaeontological studies. With trees obtained from subsampled data sets, PERDA also generates a metaconsensus tree revealing interspecific relationships that become ambiguous due to documented levels of intraspecific variation. These collapsed clades point to taxa for which evidence should be sought to justify their taxonomic classification.
Surpassing the Target: How a Recruitment Campaign Transformed the Participant Accrual Trajectory in the Epilepsy Phenome/Genome Project
Authors: McGovern Kathleen , Freyer Karn Catharine , Fox Kristen ,   EPGP Investigators
Published: July 2015

Participant recruitment challenges pervade the majority of publicly funded clinical trials. However, little is known about methods for enhancing participant accrual. The Epilepsy Phenome/Genome Project (EPGP), a multicenter study funded by the National Institute of Neurological Disorders and Stroke (NINDS), aimed to enroll a total of 5,250 participants to better understand the genetic causes and phenotypic manifestations of epilepsy. However, similar to other trials, EPGP encountered recruitment challenges, and by the end of its first year, net enrollment was only 48% of the target for that time. To address this, EPGP established a National Participant Recruitment Campaign and began implementing and tracking the enrollment outcomes of a variety of proven and relatively novel recruitment methods. At the conclusion of the project, EPGP had successfully enrolled a total of 5,445 participants, thus surpassing its enrollment target. Data pertaining to EPGP's National Participant Recruitment Campaign was analyzed retrospectively, and the results are reported here, so that other multicenter trials may consider these methods in their recruitment planning and potentially avoid the costly repercussions of participant accrual issues.
Evaluating the Development, Implementation and Dissemination of a Multisite Card Study in the WWAMI Region Practice and Research Network
Authors: Cole Allison , Keppel Gina A. , Linares Adriana , Alto William , Kriegsman William , Reed Alex , Holmes John , Mohanachandran Mathini , Baldwin Laura‐Mae
Published: July 2015

Background

Practice‐based research networks (PBRNs) promote the conduct of research in real‐world settings by engaging primary care clinicians as champion research collaborators. Card studies are brief surveys administered to patients or clinicians at the point of care. The objective of this paper is to describe the design and evaluation of a card study methodology that the WWAMI Region Practice and Research Network (WPRN) used to develop research partnerships across multiple member sites.

Methods

We used a collaborative model to develop, implement and disseminate the results of a network‐wide card study to assess patient preferences for weight loss in primary care. After the card study data collection was completed, we conducted individual and focus group interviews and a brief survey of participating practice champions.

Results

Increased research engagement and personal and professional developments were the primary motivators for participating in the development of the card study. Increasing research activity at practices and learning information about patients were motivators for implementing the study. Their participation resulted in champions reporting increased confidence in collaborating on research projects as well as the development of new clinical services for patients.

Discussion

This collaborative model positively influenced research capacity in the WPRN and may be a useful strategy for helping PBRNs conducted translational research.
What guides invasion success? Ecological correlates of arrival, establishment and spread of Red Sea bivalves in the Mediterranean Sea
Authors: Nawrot Rafał , Chattopadhyay Devapriya , Zuschin Martin
Published: July 2015

Aim

The opening of the Suez Canal in 1869 re‐established the direct link between long‐separated biogeographic realms, allowing hundreds of marine species to spread from the Red Sea to the Mediterranean. We use marine bivalves to relate species‐level attributes to successful transition through successive stages of the invasion process.

Location

Mediterranean and Red Sea.

Methods

We compiled data on taxonomic composition, body size, life habit and geographic distribution of the Red Sea bivalve fauna from published literature, museum collections and our own field surveys. Using multimodel inference, we examined selectivity of the Lessepsian invasion and identify traits that distinguish successful species at three major stages of invasion: arrival, establishment and spread.

Results

The upper limit of bathymetric range and occurrence outside the tropical zone in other regions are the strongest predictors of successful transition through the Suez Canal. Establishment in the Mediterranean is positively correlated with earlier arrival and association with hard‐bottom habitats. Preference for hard substrates together with large body size is the primary factor distinguishing invasive aliens representing a significant threat to recipient ecosystems from other established species.

Main conclusions

The relative strength of abiotic and biotic filters changes along the course of the invasion: environmental affinity and climate match constrain the pool of potential invaders, while the establishment in the new region and invasive status depend on the habitat preferences and life history traits of aliens, affecting their interactions with resident species. Our results together with previous studies suggest that the eastern Mediterranean rocky shores are more susceptible to the establishment of Lessepsian species, many of which may induce strong pressure on recipient communities as ecosystems engineers and competitors of native species.
Optimizing post‐polypectomy surveillance: A practical guide for the endoscopist
Authors: Bogie Roel , Sanduleanu Silvia
Published: July 2015

Several gastrointestinal societies strongly recommend colonoscopy surveillance after endoscopic and surgical resection of colorectal neoplasms. Common denominators to these recommendations include: high‐quality baseline colonoscopy before inclusion in a surveillance program; risk stratification based on clinicopathological profiles to guide surveillance intervals; and endoscopist responsibility for providing surveillance advice. Considerable variability also exists between guidelines (i.e. regarding risk classification and surveillance intervals). In this review, we examine key factors for quality of post‐polypectomy surveillance practice, in particular bowel preparation, endoscopic findings at baseline examination and adherence to surveillance recommendations. Frequently asked questions by the practising endoscopist are addressed.
Clinical patterns of dystonia and choreoathetosis in participants with dyskinetic cerebral palsy
Authors: Monbaliu Elegast , de Cock Paul , Ortibus Els , Heyrman Lieve , Klingels Katrijn , Feys Hilde
Published: July 2015

Aim

The aim of the study was to map clinical patterns of dystonia and choreoathetosis and to assess the relation between functional classifications and basal ganglia and thalamus lesions in participants with dyskinetic cerebral palsy (CP).

Methods

In this cross‐sectional study, 55 participants with dyskinetic CP (mean age 14y 6mo, SD 4y 1mo; range 6–22y) were assessed with the Dyskinesia Impairment Scale and classified with the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS).

Results

Dystonia and choreoathetosis are simultaneously present. Median levels of dystonia (70.2%) were significantly higher than levels of choreoathetosis (26.7%) and both were significantly higher during activity than at rest (both p<0.01). High correlations were found between dystonia levels and GMFCS level (Spearman's rank correlation coefficient, rS=0.70; 95% confidence interval [CI] 0.53–0.81; p<0.01) and MACS (rS=0.65; 95% CI 0.47–0.81; p<0.01), and fair correlation with CFCS (rs=0.36; 95% CI=0.11–0.57; p<0.05). No significant correlation was found between choreoathetosis levels and motor classifications. Finally, higher choreoathetosis levels were found in participants with pure thalamus and basal ganglia lesions (p=0.03) than mixed lesions, but not for dystonia (p=0.41).

Interpretation

Dystonia and choreoathetosis increase during activity. However, dystonia predominates and seems to have a larger impact on functional abilities. Our findings further suggest that choreoathetosis seems to be more linked to pure thalamus and basal ganglia lesions than dystonia.
Magnetic stimulation and movement‐related cortical activity for acute stroke with hemiparesis
Authors: Matsuura A. , Onoda K. , Oguro H. , Yamaguchi S.
Published: July 2015

Background and purpose

This double‐blind, randomized, placebo‐controlled study investigated the beneficial effects of repetitive transcranial magnetic stimulation (rTMS) to patients with motor paresis in acute subcortical stroke on functional recovery and electrophysiological measures.

Methods

Twenty patients with acute stroke were randomized into real rTMS (n = 10) or sham (n = 10) groups. Patients received five daily sessions of rTMS with 1200 pulses at 1 Hz for 20 min or sham stimulation over the contralesional motor cortex. Movement‐related cortical potential MRCP, consisting of the Bereitschaftpotential, negative slope (NS′) and motor potential (MP), was recorded during self‐paced wrist extension of the affected limb associated with assessment of the Fugl−Meyer assessment (FMA) of the upper extremity, the pegboard test and the grip strength before and after the rTMS session.

Results

Real rTMS improved the FMA and pegboard test scores compared to the sham group in the affected hand. This improvement was associated with increases in the MP and NS′ over the front‐central sites in the ipsilesional hemisphere, whereas the sham group did not show significant changes in MRCP components by rTMS.

Conclusions

Our findings suggest that low‐frequency rTMS to the contralesional motor cortex facilitates functional recovery of paretic limbs in acute stroke patients through enhancing the the neuronal activity of ipsilesional motor and pre‐motor areas.
Epilepsia partialis continua responsive to neocortical electrical stimulation
Authors: Valentin Antonio , Ughratdar Ismail , Cheserem Beverly , Morris Robert , Selway Richard , Alarcon Gonzalo
Published: July 2015

Epilepsia partialis continua (EPC), defined as a syndrome of continuous focal jerking, is a rare form of focal status epilepticus that usually affects a distal limb, and when prolonged, can produce long‐lasting deficits in limb function. Substantial electrophysiologic evidence links the origin ofEPCto the motor cortex; thus surgical resection carries the risk of significant handicap. We present two patients with focal, drug‐resistantEPC, who were admitted for intracranial video‐electroencephalography monitoring to elucidate the location of the epileptogenic focus and identification of eloquent motor cortex with functional mapping. In both cases, the focus resided at or near eloquent motor cortex and therefore precluded resective surgery. Chronic cortical stimulation delivered through subdural strips at the seizure focus (continuous stimulation at 60–130 Hz, 2–3 mA) resulted in >90% reduction in seizures and abolition of theEPCafter a follow‐up of 22 months in both patients. Following permanent implantation of cortical stimulators, no adverse effects were noted.EPCrestarted when intensity was reduced or batteries depleted. Battery replacement restored previous improvement. This two‐case report opens up avenues for the treatment of this debilitating condition.
Extending the phenotypic spectrum of RBFOX1 deletions: Sporadic focal epilepsy
Authors: Lal Dennis , Pernhorst Katharina , Klein Karl Martin , Reif Philipp , Tozzi Rossana , Toliat Mohammad R. , Winterer Georg , Neubauer Bernd , Nürnberg Peter , Rosenow Felix , Becker Felicitas , Lerche Holger , Kunz Wolfram S. , Kurki Mitja I. , Hoffmann Per , Becker Albert J. , Perucca Emilio , Zara Federico , Sander Thomas , Weber Yvonne G.
Published: July 2015

Partial deletions of the RBFOX1 gene encoding the neuronal splicing regulator have been reported in a range of neurodevelopmental diseases including idiopathic/genetic generalized epilepsy (IGE/GGE), childhood focal epilepsy, and self‐limited childhood benign epilepsy with centrotemporal spikes (BECTS, rolandic epilepsy), and autism. The protein regulates alternative splicing of many neuronal transcripts involved in the homeostatic control of neuronal excitability. Herein, we examined whether structural deletions affecting RBFOX1 exons confer susceptibility to common forms of juvenile and adult focal epilepsy syndromes. We screened 807 unrelated patients with sporadic focal epilepsy, and we identified seven hemizygous exonic RBFOX1 deletions in patients with sporadic focal epilepsy (0.9%) in comparison to one deletion found in 1,502 controls. The phenotypes of the patients carrying RBFOX1 deletions comprise magnetic resonance imaging (MRI)–negative epilepsy of unknown etiology with frontal and temporal origin (n = 5) and two patients with temporal lobe epilepsy with hippocampal sclerosis. The epilepsies were largely pharmacoresistant but not associated with intellectual disability. Our study extends the phenotypic spectrum of RBFOX1 deletions as a risk factor for focal epilepsy and suggests that exonic RBFOX1 deletions are involved in the broad spectrum of focal and generalized epilepsies.
Social behavior in a genetic model of dopamine dysfunction at different neurodevelopmental time points
Authors: Kabitzke P. A. , Simpson E. H. , Kandel E. R. , Balsam P. D.
Published: July 2015

Impairments in social behavior characterize many neurodevelopmental psychiatric disorders. In fact, the temporal emergence and trajectory of these deficits can define the disorder, specify their treatment and signal their prognosis. The sophistication of mouse models with neurobiological endophenotypes of many aspects of psychiatric diseases has increased in recent years, with the necessity to evaluate social behavior in these models. We adapted an assay for the multimodal characterization of social behavior at different development time points (juvenile, adolescent and adult) in control mice in different social contexts (specifically, different sex pairings). Although social context did not affect social behavior in juvenile mice, it did have an effect on the quantity and type of social interaction as well as ultrasonic vocalizations in both adolescence and adulthood. We compared social development in control mice to a transgenic mouse model of the increase in postsynaptic striatal D2R activity observed in patients with schizophrenia (D2R‐OE mice). Genotypic differences in social interactions emerged in adolescence and appeared to become more pronounced in adulthood. That vocalizations emitted from dyads with a D2R‐OE subject were negatively correlated with active social behavior while vocalizations from control dyads were positively correlated with both active and passive social behavior also suggest social deficits. These data show that striatal dopamine dysfunction plays an important role in the development of social behavior and mouse models such as the one studied here provide an opportunity for screening potential therapeutics at different developmental time points.
Fell–Muir Lecture: Heparan sulphate and the art of cell regulation: a polymer chain conducts the protein orchestra
Authors: Gallagher John
Published: July 2015

Heparan sulphate (HS) sits at the interface of the cell and the extracellular matrix. It is a member of the glycosaminoglycan family of anionic polysaccharides with unique structural features designed for protein interaction and regulation. Its client proteins include soluble effectors (e.g. growth factors, morphogens, chemokines), membrane receptors and cell adhesion proteins such as fibronectin, fibrillin and various types of collagen. The protein‐binding properties of HS, together with its strategic positioning in the pericellular domain, are indicative of key roles in mediating the flow of regulatory signals between cells and their microenvironment. The control of transmembrane signalling is a fundamental element in the complex biology of HS. It seems likely that, in some way, HS orchestrates diverse signalling pathways to facilitate information processing inside the cell. A dictionary definition of an orchestra is ‘a large group of musicians who play together on various instruments …’ to paraphrase, the HS orchestra is ‘a large group of proteins that play together on various receptors’. HS conducts this orchestra to ensure that proteins hit the right notes on their receptors but, in the manner of a true conductor, does it also set ‘the musical pulse’ and create rhythm and harmony attractive to the cell? This is too big a question to answer but fun to think about as you read this review.
Variations in the phytosterol and tocopherol compositions and the oxidative stability in seed oils from four safflower (Carthamus tinctorius L) varieties grown in north‐eastern Morocco
Authors: Ben Moumen Abdessamad , Mansouri Farid , Richard Gaetan , Fauconnier Marie‐Laure , Sindic Marianne , Nabloussi Abdelghani , Elamrani Ahmed , Serghini Caid Hana
Published: July 2015

Phytosterol and tocopherol contents and oxidative stability were evaluated from seeds oils of four safflower (Carthamus tinctorius L) varieties originating from Spain (Rancho), India (Sharda) and Morocco (Cartamar and Cartafri), which were cultivated at the experimental station in Oujda (a semi‐arid region of eastern Morocco). Total phytosterols ranged from 3640 to 4140 mg kg−1. GC analysis allowed the identification of nine compounds, of which β‐sitosterol was the major component. Total tocopherols ranged from 461.56 to 499.68 mg kg−1. HPLC analysis allowed the identification of three compounds, α‐tocopherol (99.45%–98.84%), β‐tocopherol (0.94%–0.5%) and γ‐tocopherol (0.21%–0.01%). Oxidative stability study showed that Sharda had the lowest induction period of 2.3 h compared with 7.18, 7 and 6.67 h for Cartafri, Rancho and Cartamar, respectively. Likewise, we established a positive correlation between the oxidative stability and γ‐tocopherol; however, this difference was not significant.
A biased random‐key genetic algorithm for single‐round divisible load scheduling
Authors: Brandão Julliany S. , Noronha Thiago F. , Resende Mauricio G. C. , Ribeiro Celso C.
Published: July 2015

A divisible load is an amount W of computational work that can be arbitrarily divided into chunks and distributed among a set P of worker processors to be processed in parallel. Divisible load applications occur in many fields of science and engineering. They can be parallelized in a master‐worker fashion, but they pose several scheduling challenges. The divisible load scheduling problem consists in (a) selecting a subset of active workers, (b) defining the order in which the chunks will be transmitted to each of them, and (c) deciding the amount of load that will be transmitted to each worker , with , so as to minimize the makespan, i.e., the total elapsed time since the master began to send data to the first worker, until the last worker stops its computations. In this work, we propose a biased random‐key genetic algorithm for solving the divisible load scheduling problem. Computational results show that the proposed heuristic outperforms the best heuristic in the literature.
The Impact of Independence on Regulatory Outcomes: the Case of EU Competition Policy
Authors: Guidi Mattia
Published: July 2015

Independent regulatory agencies are created in order to enhance the stability and credibility of economic regulation, and to improve policy implementation. So far, most research in political science has focused on explaining the reasons for independence, while less attention has been paid to analysing the consequences of independence. Aiming to start filling this gap, this article seeks to test if (and to what extent) independence makes a difference in competition policy enforcement. Original data on formal independence of national competition agencies in EU Member States from 1993 to 2009 are employed to test if different degrees of independence (and changes in independence over time) affect foreign direct investment and consumer prices. The results indicate that the formal independence of a competition agency does not have any significant impact on either indicator, thus questioning the assumption that independence yields better regulatory performance.
Judicialized Law‐Making and Opportunistic Enforcement: Explaining the EU's Challenge of National Defence Offsets
Authors: Weiss Moritz , Blauberger Michael
Published: July 2015

This article seeks to explain how the European Union (EU) – by challenging national defence offsets – managed to move into a highly sensitive policy area under formerly exclusive Member State competence. Whereas major accounts of integration depict defence policy as a least likely case, our process‐tracing analysis shows that the EU's recent challenge of defence offsets was a case of supranational self‐empowerment. We theorize two consecutive strategies of judicial politics, which the Commission employed at different policy stages to overcome opposition from Member States and defence firms against domestic policy change: judicialized law‐making and opportunistic enforcement. Both strategies depend on three scope conditions: expansive case law of the European Court of Justice (ECJ), its fit with policy priorities of the Commission and a credible threat of follow‐up litigation.
Optimization of Leavening Agents in Extruded Gluten‐Free Brewer's Rice Hard Pretzel Using Response Surface Methodology
Authors: Paykary Maryam , Karim Roselina , Saari Nazamid , Sulaiman Rabiha , Shekarforoush Elhamalsadat , Aghazadeh Mona
Published: July 2015

Celiac is the second most important issue in food sensitivities. The only treatment for celiac is a lifetime avoidance of consuming gluten. As pretzels are one of the most popular snacks in the world, making gluten‐free pretzels is a market need. To produce gluten‐free products, it is important to optimize the ingredients of the formulation. This research focused on optimization of the leavening agents of the most popular commercial hard pretzel formulation in which wheat flour is replaced with brewer's rice flour. This research also attempts to explain the effect of leavening agents in products containing no matrix molecules such as gluten. Response surface methodology via the central composite design was used to optimize the effects of yeast and bicarbonate of soda on the hardness (cutting strength), fracturability (brittleness), surface color, lateral expansion, expansion ratio, specific length, density (bulk, particle, material), porosity (open, close, total), water absorption index, water solubility index, water holding capacity, oil absorption index and oil holding capacity of gluten‐free hard pretzel. The optimized results indicated that the gluten‐free pretzel requires 8.05g yeast and 2.59g bicarbonate of soda for every 500g of brewer's rice flour.

Practical Applications

The study investigated the effect of leavening agents (yeast and sodium bicarbonate) which are critical ingredients affecting the quality characteristics, consumer preference and palatability of gluten‐free hard pretzel when typical soft wheat flour was replaced with a gluten‐free flour like rice or brewer's rice flour. The result guides the gluten‐free industries on the importance of using the suitable amount of leavening agents for production of acceptable physicochemical and textural properties of not only hard pretzel, but also for other low moisture cereal products as well. The findings also introduce the usage of brewer's rice, a by‐product of rice milling industry as one of the ingredients for the production of value‐added products for all consumers' especially the celiac sufferers who need to find more reasonable price products compared to gluten ones.
The Impact of Demand and Supplier on Wine's Supply Chain Performance
Authors: García‐Alcaraz Jorge Luis , Alvarado‐Iniesta Alejandro , Blanco‐Fernández Julio , Maldonado‐Macías Aide Aracely , Jiménez‐Macías Emilio , Saenz‐Díez Muro Juan Carlos
Published: July 2015

The wine industry is one of the most important income sources in the autonomous community of La Rioja in Spain, and this report is aimed to identify and measure the effect of the latent variables such as Demand, Suppliers, Quality and delivery time on Financial profits for wineries. Latent variables were integrated by the observed variables, and a questionnaire was given to 64 wineries in La Rioja, Spain. A descriptive analysis appears for indicators and latent variables were related using structural equation modeling. The results indicate that there is not a direct effect between an efficient Demand forecasting and Suppliers on the Financial profits for wineries, but there are indirect effects through a Quality and delivery time, the most important variable being analyzed. Managers in wineries must focus their attention on Quality and delivery time to costumers, while having a direct relationship with suppliers.

Practical Applications

Winery managers must make an effort to have a fast prediction of variants in the forecast and adjust the order to suppliers and production process so that the supply chain can be more agile and with quality and timely deliveries with the final result being the company's financial profit. An agile supply chain with quality products seems to be insignificant for managers in wineries.
Optimization of Cryogenic Grinding Process for Cassia (Cinnamomum loureirii Nees L.)
Authors: Ghodki Bhupendra M , Goswami T.K.
Published: July 2015

The cryogenic grinding conditions for cassia powder were optimized with four independent variables, viz., feed rate (2–10 kg/h), grinding temperature (−130 to 30C), peripheral speed (7.77–18.13 m/s) and moisture content (6–14% d.b.) using central composite design (CCD) and response surface methodology (RSM). The optimization was targeted to obtain the cassia powder with a lower particle size (μm), together with a minimum color difference (ΔE*) and specific energy consumption values (kJ/kg), while retaining maximum volatile oil content (mL/100 g) in the sample. The numerical optimization suggested that the cryo‐grinding of the sample of 9.1% moisture content with the feed rate of 2 kg/h would be the optimum (desirability value of 0.91) at −97C of grinding temperature and 10.5 m/s peripheral speed, respectively. The optimized condition was validated further at the nearest possible condition within the domain. At the optimized cryo‐grinding condition, the final particle size of 60 μm containing 2.9 mL/100 g volatile oil and the specific energy consumption of 31.3 kJ/kg was obtained. In addition, the corresponding color difference in the optimized sample was minimal (ΔE* < 3).

Practical Applications

The results of this study will enable the spice industry to apply the cryogenic grinding process specifically for cassia powder. The optimized condition obtained from this study is capable of producing the cassia powder with desirable particle size together with a minimal loss in its characteristic flavor.
MicroRNA‐18a modulates P53 expression by targeting IRF2 in gastric cancer patients
Authors: Chen Yan‐Jie , Wu Hao , Zhu Ji‐Min , Li Xiao‐Dan , Luo Si‐Wei , Dong Ling , Liu Tao‐Tao , Shen Xi‐Zhong
Published: July 2015

Background and Aim:

MicroRNA‐18a (miR‐18a) has been reported to be upregulated in gastric cancer (GC) tissues compared with normal gastric tissues. However, little is known about its prognostic value and biological roles.

Methods:

In this study, miR‐18a expression in gastric adenocarcinoma (GAC) tissues and adjacent non‐tumor tissues was validated by in situ hybridization, and the predictive values of miR‐18a were explored. The biological roles of miR‐18a and the underlying signal pathway were investigated in GC cell lines.

Results:

Overexpressed intra‐tumoral miR‐18a was associated with poor survival rate and was an independent prognostic factor for overall survival rate (P < 0.001) in GC patients. Forced expression of miR‐18a remarkably enhanced cell proliferation, migration, and invasion in GC cells, while inhibition of miR‐18a caused the opposite effects. Further study showed that miR‐18a suppressed the expression of interferon regulatory factor 2 (IRF2) by directly binding to its 3′‐untranslated region. Moreover, miR‐18a expression levels are inversely correlated with IRF2 in human GC tissues. Western blot showed that forced expression of miR‐18a could not only downregulate the expression of IRF2, but also inhibit the expression of P53, suggesting that IRF2 might play as a tumor suppressor by regulating P53 signaling in GC.

Conclusion:

miR‐18a modulated P53 expression by directly targeting IRF2 and had a high predictive value for prognosis of GAC patients. These results may lead to identification of therapeutic candidates of GC.
Tracking workforce diversity in dentistry: importance, methods, and challenges
Authors: Mertz Elizabeth , Wides Cynthia , Cooke Alexis , Gates Paul E.
Published: July 2015

Objectives

The objectives of this paper are to describe sources of data on underrepresented minority (URM) dental providers and to perform a structured critique of primary survey research on African American (AA), Hispanic/Latino (HL), and American Indian/Alaska Native (AI/AN) dentists.

Methods

A national sample survey was conducted between October 2012 and March 2013, and secondary datasets were assessed for comparability. The survey used 21 sampling frames, with censuses of AI/AN and nonurban dentists, and assessed demographics, education, practice history, patient population, volunteerism, experiences with discrimination, and opinions on issues in dentistry. The survey was developed with constituent input, pilot‐tested, and distributed online and through US mail with three reminder postcards, phone, and email follow‐up. Continuing education credit and entry to a prize drawing were provided for participation.

Results

Existing data sources cannot answer critical research questions about URM dentists. Using best practices, the survey received a 34 percent adjusted response rate. Selection likelihood and measurable response bias were adjusted for using base and poststratification weights.

Conclusions

The survey design was consistent with best practices, and our response analytics provide high confidence that the survey produced data representative of the URM dentist population. Enhanced study design, content, and response rates of existing survey efforts would be needed to provide a more robust body of knowledge on URM providers, perspectives, and practices.
Barriers and Facilitators to Substance Use Treatment in the Rural South: A Qualitative Study
Authors: Browne Teri , Priester Mary Ann , Clone Stephanie , Iachini Aidyn , DeHart Dana , Hock Robert
Published: July 2015

Purpose

Little qualitative research has examined factors associated with care in substance abuse treatment agencies in Southeastern rural communities. This study explored client‐ and agency stakeholder‐perceived barriers and facilitators to substance use treatment delivery in southeastern rural communities.

Methods

Group and individual interviews were conducted with 40 key stakeholders and 40 clients at 9 substance abuse agencies serving rural communities in a southeastern state. Qualitative thematic analysis was used to identify perceived barriers and facilitators to substance abuse services in rural communities.

Findings

Four primary themes emerged from the client and stakeholder interviews as both barriers and facilitators: availability of services for individuals with substance use disorders; access to the current technology for client services and agency functioning; cost of services; and stigma.

Conclusions

This study identifies novel barriers and facilitators to substance use care in the rural South and highlights essential areas for consideration when developing and implementing substance use care in this geographic region. These findings can be used as guidelines to provide better care to individuals with substance use disorders living in rural communities.
Validating an Elicited Imitation Task as a Measure of Implicit Knowledge: Comparisons With Other Validation Studies
Authors: Spada Nina , Shiu Julie Li‐Ju , Tomita Yasuyo
Published: July 2015

This study builds on research investigating the construct validity of elicited imitation (EI) as a measure of implicit second language (L2) grammatical knowledge. It differs from previous studies in that the EI task focuses on a single grammatical feature and time on task is strictly controlled. Seventy‐three EFL learners and 20 native English speakers completed the EI and four other tests hypothesized as measures of implicit or explicit L2 knowledge. Factor analytic results indicated that learners’ EI scores loaded on the factor labeled implicit L2 knowledge, confirming previous findings. Results from other tests and methodological issues concerning EI design and use suggest that the construct validation of EI as a measure of implicit L2 grammatical knowledge awaits further investigation.
Biased introgression of mitochondrial and nuclear genes: a comparison of diploid and haplodiploid systems
Authors: Patten Manus M. , Carioscia Sara A. , Linnen Catherine R.
Published: July 2015

Hybridization between recently diverged species, even if infrequent, can lead to the introgression of genes from one species into another. The rates of mitochondrial and nuclear introgression often differ, with some taxa showing biases for mitochondrial introgression and others for nuclear introgression. Several hypotheses exist to explain such biases, including adaptive introgression, sex differences in dispersal rates, sex‐specific prezygotic isolation and sex‐specific fitness of hybrids (e.g. Haldane's rule). We derive a simple population genetic model that permits an analysis of sex‐specific demographic and fitness parameters and measures the relative rates of mitochondrial and nuclear introgression between hybridizing pairs. We do this separately for diploid and haplodiploid species. For diploid taxa, we recover results consistent with previous hypotheses: an excess of one sex among the hybridizing migrants or sex‐specific prezygotic isolation causes a bias for one type of marker or the other; when Haldane's rule is obeyed, we find a mitochondrial bias inXYsystems and a nuclear bias inZWsystems. For haplodiploid taxa, the model reveals that owing to their unique transmission genetics, they are seemingly assured of strong mitochondrial biases in introgression rates, unlike diploid taxa, where the relative fitness of male and female hybrids can tip the bias in either direction. This heretofore overlooked aspect of hybridization in haplodiploids provides what is perhaps the most likely explanation for differential introgression of mitochondrial and nuclear markers and raises concerns about the use of mitochondrialDNAbarcodes for species delimitation in these taxa.
In Vivo Capillary Loop Hemoglobin Spectroscopy in Labial, Sublingual, and Periodontal Tissues
Authors: Townsend David , D'Aiuto Francesco , Deanfield John
Published: July 2015

Objective

Reproducible estimates of hemoglobin absorption spectra from human capillaroscopy images of arterioles, capillaries, and venules in sublingual and labial mucosa in vivo and venules in the tissues lining the periodontal pocket.

Method

By reducing the size of both the imaging lens and the light guide to a maximum 1 mm diameter and opposing them with a gap of 600 μm we have been able to transmit light through the loop of tissues which moves into the gap between the lens and light guide when these are placed in contact with the labial and sublingual oral mucosa. This allows in vivo transillumination of the microvessels supplying the mucosa.

Results

Images from five volunteers showed similar patterns and the ratio of optical densities at 410 nm and 430 nm had a range from 2.5 at 90–100% saturation to 0.5 at zero % saturation. Measured optical density ratios ranged from 0.5 to 1.6 ± 0.1 in the afferent arm of the capillary loops and 0.5 to 1.1 ± 0.1 in the efferent arm of the capillary loops.

Conclusion

In vivo spectroscopic hemoglobin optical density ratios in oral mucosal microvessels show a qualitatively consistent result within the expected in vitro parameters.