Using routinely recorded data in a UK RCT: a comparison to standard prospective data collection methods.

BACKGROUND: Routinely recorded data held in electronic health records can be used to inform the conduct of randomised controlled trials (RCTs). However, limitations with access and accuracy have been identified. OBJECTIVE: Using epilepsy as an exemplar condition, we assessed the attributes and agreement of routinely recorded data compared to data collected using case report forms in a UK RCT assessing antiepileptic drug treatments for individuals newly diagnosed with epilepsy. METHODS: The case study RCT is the Standard and New Antiepileptic Drugs II (SANAD II) trial, a pragmatic, UK multicentre RCT assessing the clinical and cost-effectiveness of antiepileptic drugs as treatments for epilepsy. Ninety-eight of 470 eligible participants provided consent for access to routinely recorded secondary care data that were retrieved from NHS Digital Hospital Episode Statistics (N=71) and primary and secondary care data from The Secure Anonymised Information Linkage Databank (N=27). We assessed data items relevant to the identification of individuals eligible for inclusion in SANAD II, baseline and follow-up visits. The attributes of routinely recorded data were assessed including the degree of missing data. The agreement between routinely recorded data and data collected on case report forms in SANAD II was assessed using calculation of Cohen's kappa for categorical data and construction of Bland-Altman plots for continuous data. RESULTS: There was a significant degree of missing data in the routine record for 15 of the 20 variables assessed, including all clinical variables. Agreement was poor for the majority of comparisons, including the assessments of seizure occurrence and adverse events. For example, only 23/62 (37%) participants had a date of first-ever seizure identified in routine datasets. Agreement was satisfactory for the date of prescription of antiepileptic drugs and episodes of healthcare resource use. CONCLUSIONS: There are currently significant limitations preventing the use of routinely recorded data for participant identification and assessment of clinical outcomes in epilepsy, and potentially other chronic conditions. Further research is urgently required to assess the attributes, agreement, additional benefits, cost-effectiveness and 'optimal mix' of routinely recorded data compared to data collected using standard methods such as case report forms at clinic visits for people with epilepsy. TRIAL REGISTRATION: Standard and New Antiepileptic Drugs II (SANAD II (EudraCT No: 2012-001884-64, registered 05/09/2012; ISRCTN Number: ISRCTN30294119 , registered 03/07/2012)).

Publisher Correction: Dimensionally and environmentally ultra-stable polymer composites reinforced with carbon fibres.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Publisher Correction: Dimensionally and environmentally ultra-stable polymer composites reinforced with carbon fibres.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Dimensionally and environmentally ultra-stable polymer composites reinforced with carbon fibres.

The quest to develop materials that enable the manufacture of dimensionally ultra-stable structures for critical-dimension components in spacecraft has led to much research over many decades and the evolution of carbon fibre reinforced polymer materials. This has resulted in structural designs that feature a near-zero coefficient of thermal expansion. However, the dimensional instabilities that result from moisture ingression and release remain the fundamental vulnerability of the matrix, which restricts many applications. Here, we address this challenge by developing a space-qualifiable physical surface barrier that blends within the mechanical properties of the composite, thus becoming part of the composite itself. The resulting enhanced composite features mechanical integrity and a strength that is superior to the underlying composite, while remaining impervious to moisture and outgassing. We demonstrate production capability for a model-sized component for the Sentinel-5 mission and demonstrate such capability for future European Space Agency (ESA) and National Aeronautics and Space Administration (NASA) programmes such as Copernicus Extension, Earth Explorer and Science Cosmic Visions.

The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum.

Dopamine function is broadly implicated in multiple neuropsychiatric conditions believed to have a genetic basis. Although a few positron emission tomography (PET) studies have investigated the impact of single-nucleotide polymorphisms (SNPs) in the dopamine D2 receptor gene (DRD2) on D2/3 receptor availability (binding potential, BPND), these studies have often been limited by small sample size. Furthermore, the most commonly studied SNP in D2/3 BPND (Taq1A) is not located in the DRD2 gene itself, suggesting that its linkage with other DRD2 SNPs may explain previous PET findings. Here, in the largest PET genetic study to date (n=84), we tested for effects of the C957T and -141C Ins/Del SNPs (located within DRD2) as well as Taq1A on BPND of the high-affinity D2 receptor tracer 18F-Fallypride. In a whole-brain voxelwise analysis, we found a positive linear effect of C957T T allele status on striatal BPND bilaterally. The multilocus genetic scores containing C957T and one or both of the other SNPs produced qualitatively similar striatal results to C957T alone. The number of C957T T alleles predicted BPND in anatomically defined putamen and ventral striatum (but not caudate) regions of interest, suggesting some regional specificity of effects in the striatum. By contrast, no significant effects arose in cortical regions. Taken together, our data support the critical role of C957T in striatal D2/3 receptor availability. This work has implications for a number of psychiatric conditions in which dopamine signaling and variation in C957T status have been implicated, including schizophrenia and substance use disorders.

A Direct Refractory Die Technique for Cast Gold Restorations.

Fabricating accurate cast gold restorations can be challenging for both clinicians and laboratory technicians. Removing the wax pattern from the master die often distorts the pattern, which, in turn, compromises the overall fit and marginal adaptation of the casting. This article demonstrates a laboratory technique in which the final restoration is cast directly on the refractory die without removing the wax pattern. Thus, distortion of the wax pattern is avoided, enabling the production of superbly fitting gold castings for both intracoronal and extracoronal restorations.

Adsorbent 2D and 3D carbon matrices with protected magnetic iron nanoparticles.

We report on the synthesis of two and three dimensional carbonaceous sponges produced directly from graphene oxide (GO) into which functionalized iron nanoparticles can be introduced to render it magnetic. This simple, low cost procedure, wherein an iron polymeric resin precursor is introduced into the carbon framework, results in carbon-based materials with specific surface areas of the order of 93 and 66 m(2) g(-1), compared to approx. 4 m(2) g(-1) for graphite, decorated with ferromagnetic iron nanoparticles giving coercivity fields postulated to be 216 and 98 Oe, values typical for ferrite magnets, for 3.2 and 13.5 wt% Fe respectively. The strongly magnetic iron nanoparticles are robustly anchored to the GO sheets by a layer of residual graphite, on the order of 5 nm, formed during the pyrolysis of the precursor material. The applicability of the carbon sponges is demonstrated in their ability to absorb, store and subsequently elute an organic dye, Rhodamine B, from water as required. It is possible to regenerate the carbon-iron hybrid material after adsorption by eluting the dye with a solvent to which it has a high affinity, such as ethanol. The use of a carbon framework opens the hybrid materials to further chemical functionalization, for enhanced chemical uptake of contaminants, or co-decoration with, for example, silver nanoparticles for bactericidal properties. Such analytical properties, combined with the material's magnetic character, offer solutions for environmental decontamination at land and sea, wastewater purification, solvent extraction, and for the concentration of dilute species.

Biodegradation of roxarsone by a bacterial community of underground water and its toxic impact.

Roxarsone is included in chicken food as anticoccidial and mainly excreted unchanged in faeces. Microorganisms biotransform roxarsone into toxic compounds that leach and contaminate underground waters used for human consumption. This study evaluated roxarsone biotransformation by underground water microorganisms and the toxicity of the resulting compounds. Underground water from an agricultural field was used to prepare microcosms, containing 0.05 mM roxarsone, and cultured under aerobic or anaerobic conditions. Bacterial communities of microcosms were characterized by PCR-DGGE. Roxarsone degradation was measured by HPLC/HG/AAS. Toxicity was evaluated using HUVEC cells and the Toxi-ChromoTest kit. Roxarsone degradation analysis, after 15 days, showed that microcosms of underground water with nutrients degraded 90 and 83.3% of roxarsone under anaerobic and aerobic conditions, respectively. Microcosms without nutrients degraded 50 and 33.1% under anaerobic and aerobic conditions, respectively. Microcosms including nutrients showed more roxarsone conversion into toxic inorganic arsenic species. DGGE analyses showed the presence of Proteobacteria, Firmicutes, Actinobacteria, Planctomycetes and Spirochaetes. Toxicity assays showed that roxarsone biotransformation by underground water microorganisms in all microcosms generated degradation products toxic for eukaryotic and prokaryotic cells. Furthermore, toxicity increased when roxarsone leached though a soil column and was further transformed by the bacterial community present in underground water. Therefore, using underground water from areas where roxarsone containing manure is used as fertilizer might be a health risk.

An agent-based modeling approach for determining corn stover removal rate and transboundary effects.

Bioenergy production involves different agents with potentially different objectives, and an agent's decision often has transboundary impacts on other agents along the bioenergy value chain. Understanding and estimating the transboundary impacts is essential to portraying the interactions among the different agents and in the search for the optimal configuration of the bioenergy value chain. We develop an agent-based model to mimic the decision making by feedstock producers and feedstock-to-biofuel conversion plant operators and propose multipliers (i.e., ratios of economic values accruing to different segments and associated agents in the value chain) for assessing the transboundary impacts. Our approach is generic and thus applicable to a variety of bioenergy production systems at different sites and geographic scales. We apply it to the case of producing ethanol using corn stover in Iowa, USA. The results from the case study indicate that stover removal rate is site specific and varies considerably with soil type, as well as other factors, such as stover price and harvesting cost. In addition, ethanol production using corn stover in the study region would have strong positive ripple effects, with the values of multipliers varying with greenhouse gas price and national energy security premium. The relatively high multiplier values suggest that a large portion of the value associated with corn stover ethanol production would accrue to the downstream end of the value chain instead of stover producers.

Effects of considering greenhouse gas consequences on fertilizer use in loblolly pine plantations.

Fertilizer use, widely practiced in forest plantation management to stimulate tree growth, contributes to greenhouse gas (GHG) emissions. We explore how accounting for GHG consequences affects optimal fertilizer application rates of commercial forest plantations. A generic model that maximizes the equivalent annual net benefit of timber production and GHG balance is developed and applied to loblolly pine (Pinus taeda L.) plantations in the southern United States. We find that fertilizer use still is a viable practice for managing loblolly pine plantations in the region although fertilizer application rate should be reduced when GHG consequences are valued. A greater reduction in fertilizer application rate is recommended where wood is used for paper production because life cycle GHG emissions of paper products are much higher than those of solid wood or bioenergy products. A higher fertilizer rate should be applied when forest residues are used for the production of bioenergy that offsets GHG emissions from consuming fossil fuels.

The influence of hydrology and waterway distance on population structure of Chinook salmon Oncorhynchus tshawytscha in a large river.

Adult Chinook salmon Oncorhynchus tshawytscha navigate in river systems using olfactory cues that may be influenced by hydrologic factors such as flow and the number, size and spatial distribution of tributaries. Thus, river hydrology may influence both homing success and the level of straying (gene flow), which in turn influences population structure. In this study, two methods of multivariate analysis were used to examine the extent to which four indicators of hydrology and waterway distance explained population structure of O. tshawytscha in the Yukon River. A partial Mantel test showed that the indicators of hydrology were positively associated with broad-scale (Yukon basin) population structure, when controlling for the influence of waterway distance. Multivariate multiple regression showed that waterway distance, supplemented with the number and flow of major drainage basins, explained more variation in broad-scale population structure than any single indicator. At an intermediate spatial scale, indicators of hydrology did not appear to influence population structure after accounting for waterway distance. These results suggest that habitat changes in the Yukon River, which alter hydrology, may influence the basin-wide pattern of population structure in O. tshawytscha. Further research is warranted on the role of hydrology in concert with waterway distance in influencing population structure in Pacific salmon.

Increased GABAergic activity in the region of the pedunculopontine and deep mesencephalic reticular nuclei reduces REM sleep and impairs learning in rats.

Newly formed memories are initially fragile and require consolidation to be transformed into an enduring state. Memory consolidation may occur during increased postlearning REM sleep. REM deprivation during these periods (termed REM sleep windows [RSWs]) impairs subsequent performance. The pedunculopontine nucleus (PPT) and adjacent deep mesencephalic reticular nuclei (DpMe) have been implicated in the generation of REM sleep. Following 24-hr baseline recording, rats were trained on the 2-way avoidance task for 50 trials/day over 2 days and retested on Day 3. EEG was recorded 22 hr after training on training Days 1 and 2. Rats were injected with the GABAB agonist baclofen or saline into the PPT/DpMe region at 0300 to coincide with the start of a known RSW. Based on shuttle performance, saline rats were assigned post hoc to a learning group (LG) that avoided the footshock at least 60% at retest or nonlearning group (NLG) that performed below this criterion. Baclofen-injected rats were not assigned post hoc into separate groups as all rats performed below the learning criterion. PPN/DpMe infusions of the inhibitory GABAB agonist baclofen decreased REM and impaired subsequent memory performance. Normal GABAergic transmission in the PPN/DpMe may be necessary for REM to occur and for the consolidation of incentive learning.

Too much of a good thing? Elevated baseline sleep spindles predict poor avoidance performance in rats.

Sleep spindles may be involved in synaptic plasticity. Learning-dependent increases in spindles have been observed in both humans and rats. In humans, the innate (i.e., baseline) number of spindles correlate with measures of academic potential such as Intelligence Quotient (IQ) tests. The present study investigated if spindles predict whether rats are able to learn to make avoidance responses in the two-way shuttle task. Baseline recordings were taken continuously for 24h prior to training on the two-way shuttle task for 50trials/day for two days followed by a 25 trial re-test on the third day. At re-test, rats were categorized into learners (n=16) or non-learners (n=21). Groups did not differ in baseline duration of rapid eye movement sleep, slow wave sleep, wake or spindle density. For combined groups, spindle density in the 21 to 24-hour period but not at any other period during baseline was negatively correlated with shuttle task performance at re-test. Conversely, the learning-related change in spindle density in the 21 to 24-hour period, but not at any other time after the first training session was positively correlated with shuttle task performance. Rats in the non-learning condition have a higher number of spindles at baseline, which is unaffected by training. On the other hand, learning rats have fewer spindles at baseline, but have a learning-related increase in spindles. Extreme spindle activity and high spindle density have been observed in humans with learning disabilities. Results suggest that while spindles may be involved in memory consolidation, in some cases, high levels of spindles prior to training may be maladaptive.

Differentiating salmon populations at broad and fine geographical scales with microsatellites and single nucleotide polymorphisms.

Single nucleotide polymorphisms (SNPs) are appealing genetic markers due to several beneficial attributes, but uncertainty remains about how many of these bi-allelic markers are necessary to have sufficient power to differentiate populations, a task now generally accomplished with highly polymorphic microsatellite markers. In this study, we tested the utility of 37 SNPs and 13 microsatellites for differentiating 29 broadly distributed populations of Chinook salmon (n = 2783). Information content of all loci was determined by In and G'(ST), and the top 12 markers ranked by In were microsatellites, but the 6 highest, and 7 of the top 10 G'(ST) ranked markers, were SNPs. The mean ratio of random SNPs to random microsatellites ranged from 3.9 to 4.1, but this ratio was consistently reduced when only the most informative loci were included. Individual assignment test accuracy was higher for microsatellites (73.1%) than SNPs (66.6%), and pooling all 50 markers provided the highest accuracy (83.2%). When marker types were combined, as few as 15 of the top ranked loci provided higher assignment accuracy than either microsatellites or SNPs alone. Neighbour-joining dendrograms revealed similar clustering patterns and pairwise tests of population differentiation had nearly identical results with each suite of markers. Statistical tests and simulations indicated that closely related populations were better differentiated by microsatellites than SNPs. Our results indicate that both types of markers are likely to be useful in population genetics studies and that, in some cases, a combination of SNPs and microsatellites may be the most effective suite of loci.

Sleep spindles and learning potential.

The number of sleep spindles remains relatively stable within individuals from night to night. However, there is little explanation for the large interindividual differences in spindles. The authors investigated the relationship between spindles and intelligence quotient (IQ) in 3 separate studies. The number of spindles and sigma power were positively correlated with performance IQ (PIQ), but not verbal IQ (VIQ). The perceptual/analytical skills measured by the PIQ Picture Completion subscale accounted for most of the interindividual differences in spindles. Furthermore, there was a relationship between the rapid eye movements (REMs) of REM sleep and VIQ in individuals with higher IQ scores. A similar pattern was observed between spindles and PIQ. It was hypothesized that high-IQ individuals have more spindles that can support more complex cortical networks underlying perceptual/analytical abilities.

Comparative in vitro evaluation of two provisional restorative materials.

STATEMENT OF PROBLEM: Provisional crowns traditionally have been associated with problems such as poor occlusion, contour, fit, and finish. Fabrication procedures should be uncomplicated and predictable within a realistic time frame. PURPOSE: The purpose of this study was to compare the quality of provisional restorations fabricated by dental students from 2 different materials (bis-acryl composite resin and PMMA) and identify the advantages and disadvantages associated with each material. MATERIAL AND METHODS: This study evaluated the occlusion, contour, marginal adaptation, and finish of 222 provisional crowns fabricated by 2 groups (A and B) of dental students. One bis-acryl composite resin material (Integrity) and 2 PMMA resins (C&B Resin and Snap) were evaluated. RESULTS: For group A, Integrity was statistically superior (P<.05) to C&B Resin in all 4 categories for anterior provisional crowns. For posterior provisional crowns, Integrity proved superior in the categories of contour and marginal adaptation, but no significant differences were established for occlusion and finish. For group B, Integrity was statistically superior to Snap in the categories of occlusion, contour, and marginal adaptation, whereas there was no statistical difference in finish. When all 4 categories were analyzed, Integrity was found to be statistically superior. CONCLUSION: Bis-acryl composite resin (Integrity) was significantly superior to PMMA (C&B Resin and Snap) as a provisional restorative material.

Glacial biogeography of North American coho salmon (Oncorhynchus kisutch).

To study the glacial biogeography of coho we examined 20 microsatellite loci and mitochondrial DNA D-loop sequence in samples from Alaska to California. Microsatellite data divided our samples among five biogeographic regions: (1) Alaska and northern coastal British Columbia; (2) the Queen Charlotte Islands; (3) the mainland coast of British Columbia and northern Washington State; (4) the Thompson River; and (5) Oregon and California. The D-loop sequence data suggested three geographical regions: (1) Oregon and California; (2) the Thompson River; and (3) all the other sites north of the southern ice margin. Microsatellite data revealed no difference in the number of alleles in different regions, but mitochondrial DNA data revealed a cline of decreasing diversity from south to north. We suggest that the two signals presented by these different marker types illuminate two time frames in the history of this species. Endemic microsatellite diversity in Alaska and on the Queen Charlotte Islands provides evidence in favour of Fraser Glaciation refugia in these regions. The loss of mitochondrial variation from south to north suggests that one of the earlier, more extensive, Pleistocene glaciations eliminated coho from its northern range.

Platelet noradrenaline and adrenaline efflux in hypercholesterolaemia: studies in platelet-rich plasma.

Collagen-induced (5-80 microg/ml) efflux of free noradrenaline (NA) and adrenaline (Ad) from platelets in platelet-rich plasma was compared in normal human subjects and heterozygous familial hypercholesterolaemic (FH) patients. Stimulated release of NA and Ad to the plasma (platelet-poor; PPP) increased in a dose-dependent fashion in both normal and FH groups. Under resting conditions (0 microg/ml collagen) PPP NA concentrations were increased in hypercholesterolaemics by 38% (non-significant). The absolute amounts of NA released on stimulation with 5 microg/ml and 10 microg/ml collagen (i.e. the differences between resting and stimulated release) were reduced in hypercholesterolaemics by 45% (p<0.01) and 38% (p<0.02), respectively. Collagen EC50 values for NA and Ad release were increased in hypercholesterolaemics by 118% (p<0.001) and 141% (p<0.05). Combining the data for the normal and FH groups revealed that the collagen EC50 values for NA release correlated positively with plasma total cholesterol (p<0.02) and low-density lipoprotein (p<0.02). These data provide additional evidence for catecholaminergic abnormalities in hypercholesterolaemia.

Alexithymia and impoverished dream content: evidence from rapid eye movement sleep awakenings.

OBJECTIVE: Despite the repeated suggestion in the literature of an association between impoverished dream processes and alexithymia, little systematic research has been conducted. METHODS: Eight nonclinical adults scoring in the alexithymia range and eight nonclinical adults scoring in the nonalexithymia range on a measure of alexithymia were awakened for dream reports during their second, third, and fourth rapid eye movement periods on the second of two consecutive polygraphically monitored nights in a sleep laboratory. RESULTS: The alexithymic and nonalexithymic groups did not differ in the number of dreams reported or the number of words used in the description of their dreams. The two groups also did not differ in their self-reports of the emotional valence associated with their dream experiences. In contrast, the dream reports of the alexithymic group were rated as less fantastic than the dream reports of the nonalexithymic group. CONCLUSIONS: These findings provide additional evidence that alexithymia involves restricted imaginative processes.

Interhemispheric transfer deficit in alexithymia: an experimental study.

OBJECTIVE: Previous research has demonstrated an association between alexithymia and a deficit in interhemispheric communication in Vietnam combat veterans with posttraumatic stress disorder. The purpose of this study was to evaluate this association in a nonclinical sample. METHODS: The efficiency of interhemispheric transfer was assessed in 14 alexithymic and 15 nonalexithymic right-handed, male, undergraduate university students using a tactile finger localization task. RESULTS: The nonalexithymic subjects were significantly more efficient at transferring information between the cerebral hemispheres than the alexithymic subjects. CONCLUSIONS: This finding provides further evidence of an interhemispheric transfer deficit in alexithymia and suggests that an alexithymic cognitive style reflects poor integration of the information processing of the two cerebral hemispheres.