Targeted density electrode placement achieves high concordance with traditional high-density EEG for electrical source imaging in epilepsy.

OBJECTIVE: High-density (HD) electroencephalography (EEG) is increasingly used in presurgical epilepsy evaluation, but it is demanding in time and resources. To overcome these issues, we compared EEG source imaging (ESI) solutions with a targeted density and HD-EEG montage. METHODS: HD-EEGs from patients undergoing presurgical evaluation were analyzed. A low-density recording was created by selecting the 25 electrodes of a standard montage from the 83 electrodes of the HD-EEG and adding 8-11 electrodes around the electrode with the highest amplitude interictal epileptiform discharges. The ESI solution from this "targeted" montage was compared to that from the HD-EEG using the distance between peak vertices, sublobar concordance and a qualitative similarity measure. RESULTS: Fifty-eight foci of forty-three patients were included. The median distance between the peak vertices of the two montages was 13.2 mm, irrespective of focus' location. Tangential generators (n = 5/58) showed a higher distance than radial generators (p = 0.04). We found sublobar concordance in 54/58 of the foci (93%). Map similarity, assessed by an epileptologist, had a median score of 4/5. CONCLUSIONS: ESI solutions obtained from a targeted density montage show high concordance with those calculated from HD-EEG. SIGNIFICANCE: Requiring significantly fewer electrodes, targeted density EEG allows obtaining similar ESI solutions as traditional HD-EEG montage.

Neurocognitive basis of model-based decision making and its metacontrol in childhood.

Human behavior is supported by both goal-directed (model-based) and habitual (model-free) decision-making, each differing in its flexibility, accuracy, and computational cost. The arbitration between habitual and goal-directed systems is thought to be regulated by a process known as metacontrol. However, how these systems emerge and develop remains poorly understood. Recently, we found that while children between 5 and 11 years displayed robust signatures of model-based decision-making, which increased during this developmental period, there were substantial individual differences in the display of metacontrol. Here, we inspect the neurocognitive basis of model-based decision-making and metacontrol in childhood and focus this investigation on executive functions, fluid reasoning, and brain structure. A total of 69 participants between the ages of 6-13 completed a two-step decision-making task and an extensive behavioral test battery. A subset of 44 participants also completed a structural magnetic resonance imaging scan. We find that individual differences in metacontrol are specifically associated with performance on an inhibition task and individual differences in thickness of dorsolateral prefrontal, temporal, and superior-parietal cortices. These brain regions likely reflect the involvement of cognitive processes crucial to metacontrol, such as cognitive control and contextual processing.

A comprehensive phylogeny helps clarify the evolutionary history of host breadth and lure response in the Australian Dacini fruit flies (Diptera: Tephritidae).

The tribe Dacini (Diptera: Tephritidae) contains over 930 recognised species and has been widely studied due to the economic importance of some taxa, such as the Oriental fruit fly Bactrocera dorsalis. Despite the attention this group has received, very few phylogenetic reconstructions have comprehensively sampled taxa from a single biogeographic region, thereby limiting our capacity to address more targeted evolutionary questions. To study the evolution of diet breadth and male lure response, two key traits fundamental to understanding dacine diversity and the biology of pest taxa, we analysed 273 individuals representing 144 described species from Australia (80% continental coverage), the Pacific, and select close relatives from South-east Asia to estimate a dated molecular phylogenetic reconstruction of the Dacini. We utilised seven loci with a combined total of 4,332 nucleotides, to estimate both Bayesian and Maximum Likelihood phylogenies of the tribe. Consistent with other molecular phylogenies of the tribe, there was a high level of disagreement between the placement of species in the phylogeny and their current subgeneric and species-complex level taxonomies. The Australian fauna exhibit high levels of endemism, with radiations of both exclusively Australian clades, and clades that originate elsewhere (e.g. the Bactrocera dorsalis species group). Bidirectional movement of species has occurred between Papua New Guinea and Australia, with evidence for multiple incursions over evolutionary time. The Bactrocera aglaiae species group emerged sister to all other Bactrocera species examined. Divergence time estimates were âˆ¼ 30 my younger than previously reported for this group, with the tribe diverging from its most recent common ancestor âˆ¼ 43 mya. Ancestral trait reconstruction and tests for trait phylogenetic signal revealed a strong signal for the evolution of male lure response across the tree, with cue-lure/raspberry ketone lure response the ancestral trait. Methyl eugenol response has arisen on multiple, independent occasions. The evolution of host breadth exhibited a weaker signal; yet, basal groups were more likely to be host specialists. Both the evolution of lure response and host fruit use provide predictive information for the outbreak management of understudied pest fruit flies for which direct inference of these features may be lacking. Our results, which parallel those of earlier research into the closely-related African Dacus spp., demonstrate how geographically focussed taxon coverage allows Dacini phylogenetics to more explicitly test evolutionary hypotheses, thereby progressing our understanding of the evolution of this highly diverse and recently-radiated group of flies.

Competing Timescales Lead to Oscillations in Shear-Thickening Suspensions.

Competing timescales generate novelty. Here, we show that a coupling between the timescales imposed by instrument inertia and the formation of interparticle frictional contacts in shear-thickening suspensions leads to highly asymmetric shear-rate oscillations. Experiments tuning the presence of oscillations by varying the two timescales support our model. The observed oscillations give access to a shear-jamming portion of the flow curve that is forbidden in conventional rheometry. Moreover, the oscillation frequency allows us to quantify an intrinsic relaxation time for particle contacts. The coupling of fast contact network dynamics to a slower system variable should be generic to many other areas of dense suspension flow, with instrument inertia providing a paradigmatic example.

Factors associated with ambulatory care sensitive emergency department visits for South Carolina Medicaid members with intellectual disability.

INTRODUCTION: Ambulatory care sensitive conditions (ACSCs) can be seen as failure of access or management in primary care settings. Identifying factors associated with ACSCs for individuals with an Intellectual Disability (ID) provide insight into potential interventions. METHOD: To assess the association between emergency department (ED) ACSC visits and a number of demographic and health characteristics of South Carolina Medicaid members with ID. A retrospective cohort of adults with ID was followed from 2001 to 2011. Using ICD-9-CM codes, four ID subgroups, totalling 14 650 members, were studied. RESULTS: There were 106 919 ED visits, with 21 214 visits (19.8%) classified as ACSC. Of those, 82.9% were treated and released from EDs with costs averaging $578 per visit. People with mild and unspecified ID averaged greater than one ED visit per member year. Those with Down syndrome and other genetic cause ID had the lowest rates of ED visits but the highest percentage of ACSC ED visits that resulted in inpatient hospitalisation (26.6% vs. an average of 16.8% for other subgroups). When compared with other residential types, those residing at home with no health support services had the highest ED visit rate and were most likely to be discharged back to the community following an ED visit (85.2%). Adults residing in a nursing home had lower rates of ED visits but were most likely to be admitted to the hospital (38.9%) following an ED visit. Epilepsy and convulsions were the leading cause (29.6%) of ACSC ED visits across all subgroups and residential settings. CONCLUSION: Prevention of ACSC ED visits may be possible by targeting adults with ID who live at home without health support services.

Cognitive ability, social desirability, body mass index and socioeconomic status as correlates of fourth-grade children's dietary-reporting accuracy.

BACKGROUND/OBJECTIVES: To investigate the relationship of reporting accuracy in 24-h dietary recalls to child-respondent characteristics-cognitive ability, social desirability, body mass index (BMI) percentile and socioeconomic status (SES). SUBJECTS/METHODS: Fourth-grade children (mean age 10.1 years) were observed eating two school meals and interviewed about dietary intake for 24 h that included those meals. (Eight multiple-pass interview protocols operationalized the conditions of an experiment that crossed two retention intervals-short and long-with four prompts (ways of eliciting reports in the first pass)). Academic achievement-test scores indexed cognitive ability; social desirability was assessed by questionnaire; height and weight were measured to calculate BMI; nutrition-assistance program eligibility information was obtained to index SES. Reported intake was compared to observed intake to calculate measures of reporting accuracy for school meals at the food-item (omission rate; intrusion rate) and energy (correspondence rate; inflation ratio) levels. Complete data were available for 425 of 480 validation-study participants. RESULTS: Controlling for manipulated variables and other measured respondent characteristics, for one or more of the outcome variables, reporting accuracy increased with cognitive ability (omission rate, intrusion rate, correspondence rate, P<0.001), decreased with social desirability (correspondence rate, P<0.0004), decreased with BMI percentile (correspondence rate, P=0.001) and was better by higher- than by lower-SES children (intrusion rate, P=0.001). Some of these effects were moderated by interactions with retention interval and sex. CONCLUSIONS: Children's dietary-reporting accuracy is systematically related to such respondent characteristics as cognitive ability, social desirability, BMI percentile and SES.

Use of state administrative data sources to study adolescents and young adults with rare conditions.

BACKGROUND: Effective care of young people with rare conditions requires ongoing coordinated medical treatment as well as educational and social support services. However, information on treatment is often lacking due to limited data. South Carolina has a repository of comprehensive health and human service data with which individuals may be tracked across the data systems of multiple state agencies and organizations. OBJECTIVE: To develop a method for studying health care of young persons with rare conditions using this repository. METHODS: We identified individuals aged 15 to 24 years diagnosed during 2000-2010 with Fragile X syndrome (FXS), spina bifida (SB), or muscular dystrophy (MD) using a series of algorithms. ICD-9-CM codes were used to initially identify the cohort from medical billing data. Demographics, medical care, employment, education, and socioeconomic status data were then extracted from linked administrative sources. RESULTS: We identified 1,040 individuals with these rare conditions: 125 with FXS, 695 with SB, and 220 with MD. The vast majority of the cases (95%) were identified in the Medicaid database. Half of the cohort was male, with a higher percentage in the FXS and MD groups. Sixty-two percent of the cohort was enrolled in the last year of high school. Over half of the cohort received support services from the state's disability and special-needs agency; 16% received food assistance. Thirty-eight percent were employed at some point during the study period. Forty-nine individuals with SB and 56 with MD died during the study period. CONCLUSIONS: We used a linked statewide data system to study rare conditions. Strengths include the diversity of information, rigorous identification strategies, and access to longitudinal data. Despite limitations inherent to administrative data, we found that linked state data systems are valuable resources for investigating important public health questions on rare conditions.

Accuracy of children's school-breakfast reports and school-lunch reports (in 24-h dietary recalls) differs by retention interval.

BACKGROUND/OBJECTIVES: Validation-study data were analyzed to investigate the effect of retention interval (time between the to-be-reported meal and interview) on accuracy of children's school-breakfast reports and school-lunch reports in 24-h recalls, and to compare accuracy of children's school-breakfast reports for two breakfast locations (classroom; cafeteria). SUBJECTS/METHODS: Each of 374 fourth-grade children was interviewed to obtain a 24-h recall using one of six conditions from crossing two target periods (prior 24 h; previous day) with three interview times (morning; afternoon; evening). Each condition had 62 or 64 children (half boys). A recall's target period included one school breakfast and one school lunch, for which the child had been observed. Food-item variables (observed number; reported number; omission rate; intrusion rate) and energy variables (observed; reported; report rate; correspondence rate; inflation ratio) were calculated for each child for school breakfast and school lunch separately. RESULTS: Accuracy for school-breakfast reports and school-lunch reports was inversely related to retention interval. Specifically, as indicated by smaller omission rates, smaller intrusion rates, larger correspondence rates and smaller inflation ratios, accuracy for school-breakfast reports was best for prior-24-h recalls in the morning, and accuracy for school-lunch reports was best for prior-24-h recalls in the afternoon. For neither school meal was a significant sex effect found for any variable. For school-breakfast reports, there was no significant school-breakfast location effect for any variable. CONCLUSIONS: By shortening the retention interval, accuracy can be improved for school-breakfast reports and school-lunch reports in children's 24-h recalls.

A novel antagonist of prostaglandin D2 blocks the locomotion of eosinophils and basophils.

BACKGROUND: Chemoattractant receptor homologous molecule of Th2 cells (CRTH2) has been shown to mediate the chemotaxis of eosinophils, basophils and Th2-type T lymphocytes. The major mast cell product prostaglandin (PG) D(2) is considered to be the principal ligand of CRTH2. MATERIALS AND METHODS: We developed a novel CRTH2 antagonist, AZ11665362 [2,5-dimethyl-3-(8-methylquinolin-4-yl)-1H-indole-1-yl]acetic acid, and characterized its efficacy in binding assay in HEK293 cells, eosinophil and basophil shape change assay and migration assay, platelet aggregation and eosinophil release from guinea pig bone marrow. The effects were compared with ramatroban, the sole CRTH2 antagonist clinically available to date. RESULTS: AZ11665362 bound with high affinity to human and guinea pig CRTH2 expressed in HEK293 cells and antagonized eosinophil and basophil shape change responses to PGD(2). AZ11665362 was without effect on the PGD(2)-induced inhibition of platelet aggregation. In contrast, AZ11665362 effectively inhibited the in vitro migration of human eosinophils and basophils towards PGD(2). The release of eosinophils from the isolated perfused hind limb of the guinea pig was potently stimulated by PGD(2), and this effect was prevented by AZ11665362. In all assays tested, AZ11665362 was at least 10 times more potent than ramatroban. CONCLUSIONS: AZ11665362 is a potent CRTH2 antagonist that is capable of blocking the migration of eosinophils and basophils, and the rapid mobilization of eosinophils from bone marrow. AZ11665362 might hence be useful for the treatment of allergic diseases.

Contact-induced crystallinity for high-performance soluble acene-based transistors and circuits.

The use of organic materials presents a tremendous opportunity to significantly impact the functionality and pervasiveness of large-area electronics. Commercialization of this technology requires reduction in manufacturing costs by exploiting inexpensive low-temperature deposition and patterning techniques, which typically lead to lower device performance. We report a low-cost approach to control the microstructure of solution-cast acene-based organic thin films through modification of interfacial chemistry. Chemically and selectively tailoring the source/drain contact interface is a novel route to initiating the crystallization of soluble organic semiconductors, leading to the growth on opposing contacts of crystalline films that extend into the transistor channel. This selective crystallization enables us to fabricate high-performance organic thin-film transistors and circuits, and to deterministically study the influence of the microstructure on the device characteristics. By connecting device fabrication to molecular design, we demonstrate that rapid film processing under ambient room conditions and high performance are not mutually exclusive.

A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst.

BACKGROUND: Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) has been revealed to be a novel receptor for prostaglandin (PG) D(2), which is a major mast cell product released during the allergic response. The aim of this study was to analyze the effects of a newly developed small molecule antagonist of CRTH2, Cay10471, on eosinophil function with respect to recruitment, respiratory burst and degranulation. METHODS: Chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils were determined using microBoyden chambers. Eosinophil release from bone marrow was investigated in the in situ perfused guinea pig hind limb preparation. Respiratory burst and degranulation were measured by flow cytometry. RESULTS: Cay10471 bound with high affinity to recombinant human and guinea pig CRTH2, but not DP, receptors. The antagonist prevented the PGD(2)-induced release of eosinophils from guinea pig bone marrow, and inhibited the chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils. Pretreatment with PGD(2) primed eosinophils for chemotaxis towards eotaxin, and this effect was prevented by Cay10471. In contrast, PGD(2) inhibited the C5a-induced up-regulation of CD63, a cellular marker of degranulation, in a Cay10471-sensitive manner. Finally, Cay10471 abolished the respiratory burst of eosinophils upon stimulation by PGD(2). CONCLUSION: These data further emphasize the importance of CRTH2 in eosinophil function and show that Cay10471 is a highly potent and selective antagonist of PGD(2)-induced eosinophil responses. Cay10471 might hence be a useful compound for the treatment of allergic diseases.

Anodic oxidation of ifosfamide and cyclophosphamide: a biomimetic metabolism model of the oxazaphosphorinane anticancer drugs.

The electrochemical oxidation of anticancer drugs ifosfamide and cyclophosphamide produced in high yield methoxylated analogues of the key hydroxy-metabolites of these oxazaphosphorine prodrugs. The cytotoxicity of these compounds was evaluated, and found to be as high as the hydroxy-metabolite.

A gene associated with filamentous growth in Ophiostoma novo-ulmi has RNA-binding motifs and is similar to a yeast gene involved in mRNA splicing.

The COL1 gene was isolated from Ophiostoma novo-ulmi using the techniques of insertional mutagenesis and plasmid rescue. Sequence analyses suggest that the COL1 gene encodes a unique protein of 826 amino acids with consensus-type RNA-binding domains, most similar to a putative protein from Schizosaccharomyces pombe which resembles the C-terminus of the Saccharomyces cerevisiae U4/U6 splicing factor PRP24. Disruption of the COL1 gene produced the yeast-like col1 mutant. The inability of the mutant to synthesize the COL1 gene product was confirmed by transcript analysis. Transformation of the col1 mutant with the COL1 gene restored the wild phenotype and production of the 4.0-kb mRNA. The results from this study demonstrate that the COL1 RNA-binding protein is associated with filamentous growth in O. novo-ulmi.

Deletion of the trichodiene synthase gene of Fusarium venenatum: two systems for repeated gene deletions.

The trichodiene synthase (tri5) gene of Fusarium venenatum was cloned from a genomic library. Vectors were created in which the tri5 coding sequence was replaced with the Neurospora crassa nitrate reductase (nit3) gene and with the Aspergillus nidulans acetamidase (amdS) gene flanked by direct repeats. The first vector was utilized to transform a nitrate reductase (niaD) mutant of F. venenatum to prototrophy, and the second vector was utilized to confer acetamide utilization to the wild-type strain. Several of the transformants lost the capacity to produce the trichothecene diacetoxyscirpenol and were shown by hybridization analysis to have gene replacements at the tri5 locus. The nit3 gene was removed by retransformation with a tri5 deletion fragment and selection on chlorate. The amdS gene was shown to excise spontaneously via the flanking direct repeats when spores were plated onto fluoroacetamide.

Influence of local environment on incorporation of ceramic for lumbar fusion. Comparison of laminar and intertransverse sites in a canine model.

OBJECTIVES: To evaluate bone growth into macroporous ceramic in a canine model in terms of the effect at the lumbar spine site (lamina versus transverse process site) and the depth of the area within the ceramic block (peripheral or central areas). SUMMARY OF BACKGROUND DATA: Previous comparative studies have assessed that the efficacy of bone graft substitutes for spine fusion depends on their physicochemical properties and on the mechanical environment, but rarely on the grafting site at the lumbar spine level. METHODS: Posterior and lateral arthrodesis using pedicular instrumentation was performed at L2, L3, and L4 with a parallelepipedic ceramic block in an experimental group of dogs. A second group of dogs was fused with only autogenous bone graft to compare the fusion stiffness obtained with this material with the stiffness obtained with ceramic. Dogs were studied for 9 months. A biomechanical test and histomorphometric analysis were conducted. RESULTS: With the biomechanical test, no significant differences were found between ceramic and autogenous bone. The percentage of newly formed bone was higher (P < 0.0001) at the lamina (26.52 +/- 6.45%) than at the transverse process site (17.33 +/- 2.54%). For both locations, the highest amount of newly formed bone was observed in the area of close contact between ceramic and bone, and the lowest was observed in central areas (24.6 +/- 5.9% for the laminar site, 14.79 +/- 1.75% for the transverse process site). CONCLUSION: This animal study, which replicated the human procedure in posterolateral lumbar fusion, showed a significant difference of ceramic incorporation between laminar and intertransverse sites. This histomorphometric analysis also confirmed the relationship between bone in-growth and ceramic thickness and ceramic contact area with bone.

Providing incentives to control health care costs and remain competitive in the marketplace: a pilot study.

Few marketplaces in the United States have been subject to as much scrutiny, and undergone as much transformation in the 1990s, as has health care. Even based on the slowest growth rates experienced in the 1980s and 1990s, the United States is projected to be spending $3,140,221 per minute on health care by the year 2000. The purpose of this study was to examine how coordination between providers of medical care, and working with their customers (i.e., payors) might reduce costs without compromising quality. Providing incentives to these groups of businesses that form the health systems can be a means for achieving both individual health system objectives. Because of the importance of pharmacists in health care delivery systems, they were considered an excellent group for testing and measuring the impact of incentive programs. The study involved a before and after six month period involving dispensing patterns through a pharmacy benefit manager. Incentives were provided to pharmacies based on percent improvement in generic substitution rates and formulary compliance. A network of 342 independent pharmacies, with their dispensing patterns monitored through a pharmacy benefit manager under its contract program. The results of the study were that generic substitution rates rose from the pre-trial period of 68.5% to 73.7% in the first three months of the trial period, and to 75.6% in the second three months of the trial period. The overall increase in substitution was from 68.5% in the base period to 74.7% over six months. These differences were statistically significant at the 0.05 level. Estimated savings to health plans on an annualized basis would be approximately $3.4 million, and the payout per conversion to pharmacies was $3.23. While not measured directly, no adverse clinical effects were reported due to substitutions. Thus, an incentive system to reward those health care providers can effectively control expenses to achieve mutually desirable goals of all parties. If properly structured, the providers, health systems of which they are a part, and payors can benefit. Using an incentive program like the one designed for this study, health systems may be able to be more competitive in marketing their services to payors.

Macroporous biphasic calcium phosphate ceramics: influence of five synthesis parameters on compressive strength.

Compressive strength measurements were conducted on 32 macroporous biphasic calcium phosphate (MBCP) samples to evaluate the influences and interactions of five synthesis factors: chemical composition, percentage of macropores, mean size of macropores, isostatic compaction pressure, and sintering temperature. These parameters were varied simultaneously between two limit levels. Experiments used a factorial design method (FDM) allowing optimization of the number of samples as well as statistical analysis of results. FDM showed that compressive strength, in a defined experimental area, can be described by a first-order polynomial equation in which the percentage of macroporosity and sintering temperature are the major influences. This study leads up to an isoresponse line diagram that will allow the manufacture of some classes of MBCP with fitted compressive strength.

Fusarium graminearum A 3/5 as a novel host for heterologous protein production.

We describe a novel fungal expression system which utilizes the Quorn myco-protein fungus Fusarium graminearum A 3/5. A transformation system was developed for F. graminearum and was used to introduce the coding and regulatory regions of a trypsin gene from Fusarium oxysporum. The protein was efficiently expressed, processed and secreted by the recombinant host strain. In addition, the promoter and terminator of the F. oxysporum trypsin gene have been successfully utilized to drive the expression of a cellulase gene from Scytalidium thermophilum and a lipase gene from Thermomyces lanuginosus in F. graminearum.