bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy and safety of treating hepatitis C in patients with a diagnosis of schizophrenia
Authors: Mustafa M. Z. , Schofield J. , Mills P. R. , Priest M. , Fox R. , Datta S. , Morris J. , Forrest E. H. , Gillespie R. , Stanley A. J. , Barclay S. T.
Published: February 2014

Treating chronic hepatitis C with pegylated interferon alpha may induce or exacerbate psychiatric illness including depression, mania and aggressive behaviour. There is limited data regarding treatment in the context of chronic schizophrenia. We sought to establish the safety and efficacy of treating patients with schizophrenia. Patient and treatment data, prospectively collected on the Scottish hepatitis C database, were analysed according to the presence or absence of a diagnosis of schizophrenia. Time from referral to treatment, and the proportion of patients commencing treatment in each group, was calculated. Outcomes including sustained viral response rates, reasons for treatment termination and adverse events were compared. Of 5497 patients, 64 (1.2%) had a diagnosis of schizophrenia. Patients with schizophrenia (PWS) were as likely to receive treatment as those without [28/61(46%) vs 1639/4415 (37%) P = 0.19]. Sustained viral response (SVR) rates were higher in PWS [21/25 (84%) vs 788/1453 (54%) P < 0.01]. SVR rates by genotype were similar [4/8 (50%) vs 239/684 (35%) Genotype 1 (P = 0.56), 17/17 (100%) vs 599/742 (81%) non‐Genotype 1 (P = 0.09)]. Adverse events leading to cessation of treatment were comparable [2/25(8%) vs 189/1453 (13%) P: 0.66]. Patients with schizophrenia are good candidates for hepatitis C treatment, with equivalent SVR and treatment discontinuation rates to patients without schizophrenia.
Metamorphosed calcium‐aluminum‐rich inclusions in CK carbonaceous chondrites
Authors: Chaumard Noël , Devouard Bertrand , Bouvier Audrey , Wadhwa Meenakshi
Published: February 2014

CK chondrites are the only group of carbonaceous chondrites with petrologic types ranging from 3 to 6. Although CKs are described as calcium‐aluminum‐rich inclusion (CAI)‐poor objects, the abundance of CAIs in the 18 CK3–6 we analyzed ranges from zero to approximately 16.4%. During thermal metamorphism, some of the fine‐grained CAIs recrystallized as irregular assemblages of plagioclase + Ca‐rich pyroxene ± olivine ± Ca‐poor pyroxene ± magnetite. Coarse‐grained CAIs display zoned spinel, fassaite destabilization, and secondary grossular and spinel. Secondary anorthite, grossular, Ca‐rich pyroxene, and spinel derive from the destabilization of melilite, which is lacking in all CAIs investigated. The Al‐Mg isotopic systematics measured in fine‐ and coarse‐grained CAIs from Tanezrouft (Tnz) 057 was affected by Mg redistribution. The partial equilibration of Al‐Mg isotopic signatures obtained in the core of a coarse‐grained CAI (CG1‐CAI) in Tnz 057 may indicate a lower peak temperature for Mg diffusion of approximately 540–580 °C, while grossular present in the core of this CAI indicates a higher temperature of around 800 °C for the metamorphic event on the parent body of Tnz 057. Excluding metamorphic features, the similarity in nature and abundance of CAIs in CK and CV chondrites confirms that CVs and CKs form a continuous metamorphic series from type 3 to 6.
The essential roles of cytidine diphosphate‐diacylglycerol synthase in bloodstream form Trypanosoma brucei
Authors: Lilley Alison C. , Major Louise , Young Simon , Stark Michael J. R. , Smith Terry K.
Published: February 2014

Lipid metabolism in Trypanosoma brucei, the causative agent of African sleeping sickness, differs from its human host in several fundamental ways. This has lead to the validation of a plethora of novel drug targets, giving hope of novel chemical intervention against this neglected disease. Cytidine diphosphate diacylglycerol (CDP‐DAG) is a central lipid intermediate for several pathways in both prokaryotes and eukaryotes, being produced by CDP‐DAG synthase (CDS). However, nothing is known about the single T. brucei CDS gene (Tb927.7.220/EC 2.7.7.41) or its activity. In this study we show TbCDS is functional by complementation of a non‐viable yeast CDS null strain and that it is essential in the bloodstream form of the parasite via a conditional knockout. The TbCDS conditional knockout showed morphological changes including a cell‐cycle arrest due in part to kinetoplast segregation defects. Biochemical phenotyping of TbCDS conditional knockout showed drastically altered lipid metabolism where reducing levels of phosphatidylinositol detrimentally impacted on glycoylphosphatidylinositol biosynthesis. These studies also suggest that phosphatidylglycerol synthesized via the phosphatidylglycerol‐phosphate synthase is not synthesized from CDP‐DAG, as was previously thought. TbCDS was shown to localized the ER and Golgi, probably to provide CDP‐DAG for the phosphatidylinositol synthases.
Antiphospholipid syndrome in renal transplantation
Authors: Barbour Thomas D , Crosthwaite Amy , Chow Kevin , Finlay Moira J , Better Nathan , Hughes Peter D , Cohney Solomon J
Published: February 2014

Antiphospholipid syndrome (APS) may occur in isolation or in association with systemic lupus erythematosus (SLE), with the potential to cause renal failure via several distinct pathologies. Renal transplantation in the presence of APS carries a risk of early graft loss from arterial or venous thrombosis, or thrombotic microangiopathy (TMA). Whilst perioperative anticoagulation reduces the risk of large vessel thrombosis, it may result in significant haemorrhage, and its efficacy in preventing post‐transplant TMA is uncertain. Here, we report a patient with end‐stage kidney disease (ESKD) due to lupus nephritis and APS, in whom allograft TMA developed soon after transplantation despite partial anticoagulation. TMA resolved with plasma exchange‐based therapy albeit with some irreversible graft damage and renal impairment. We discuss the differential diagnosis of post‐transplant TMA, and current treatment options.
Conyza canadensis suppresses plant diversity in its nonnative ranges but not at home: a transcontinental comparison
Authors: Shah Manzoor A. , Callaway Ragan M. , Shah Tabasum , Houseman Gregory R. , Pal Robert W. , Xiao Sa , Luo Wenbo , Rosche Christoph , Reshi Zafar A. , Khasa Damase P. , Chen Shuyan
Published: February 2014

The impact of invasive species across their native and nonnative ranges is poorly quantified and this impedes a complete understanding of biological invasions.

We compared the impact of the native North American plant, Conyza canadensis, which is invasive to Eurasia, on species richness at home and in a number of introduced regions through well replicated transcontinental field studies, glasshouse experiments and individual‐based models.

Our results demonstrated mostly negative relationships between C. canadensis abundance and native species richness in nonnative ranges, but either positive or no relationships in its native North American range. In glasshouse experiments, the total biomass of Conyza was suppressed more by species from its native range than by species from regions where it is nonnative, but the effects of Conyza on other species did not show a consistent biogeographical pattern. Finally, individual‐based models led to the exclusion of Conyza from North American scenarios but to high abundances in scenarios with species from the nonnative ranges of Conyza.

We illustrate biogeographical differences in the impact of an invader across regional scales and suggest that inherent differences in one specific aspect of competitive ability, tolerance to the effects of other species, may play some role in these differences.
The mechanism of improved aeration due to gas films on leaves of submerged rice
Authors: VERBOVEN PIETER , PEDERSEN OLE , HO QUANG TRI , NICOLAI BART M. , COLMER TIMOTHY D.
Published: February 2014

Some terrestrial wetland plants, such as rice, have super‐hydrophobic leaf surfaces which retain a gas film when submerged. O2 movement through the diffusive boundary layer (DBL) of floodwater, gas film and stomata into leaf mesophyll was explored by means of a reaction‐diffusion model that was solved in a three‐dimensional leaf anatomy model. The anatomy and dark respiration of leaves of rice (Oryza sativa L.) were measured and used to compute O2 fluxes and partial pressure of O2 (pO2) in the DBL, gas film and leaf when submerged. The effects of floodwater pO2, DBL thickness, cuticle permeability, presence of gas film and stomatal opening were explored. Under O2‐limiting conditions of the bulk water (pO2 < 10 kPa), the gas film significantly increases the O2 flux into submerged leaves regardless of whether stomata are fully or partly open. With a gas film, tissue pO2 substantially increases, even for the slightest stomatal opening, but not when stomata are completely closed. The effect of gas films increases with decreasing cuticle permeability. O2 flux and tissue pO2 decrease with increasing DBL thickness. The present modelling analysis provides a mechanistic understanding of how leaf gas films facilitate O2 entry into submerged plants.
Identifying Children with Autism Spectrum Disorder at 18 Months in a General Population Sample
Authors: Stenberg Nina , Bresnahan Michaeline , Gunnes Nina , Hirtz Deborah , Hornig Mady , Lie Kari Kveim , Lipkin W. Ian , Lord Catherine , Magnus Per , Reichborn‐Kjennerud Ted , Schjølberg Synnve , Surén Pål , Susser Ezra , Svendsen Britt Kveim , von Tetzchner Stephen , Øyen Anne‐Siri , Stoltenberg Camilla
Published: February 2014

Background

Previous research on clinical and high‐risk samples suggests that signs of autism spectrum disorder (ASD) can be detected between 1 and 2 years of age. We investigated signs of ASD at 18 months in a population‐based sample and the association with later ASD diagnosis.

Methods

The study sample includes 52 026 children born 2003 through 2008 and is a subset of children that participated in the Norwegian Mother and Child Cohort (MoBa), a population‐based longitudinal study, and the Autism Birth Cohort (ABC), a sub‐study on ASD. Parents completed all 23 items from the Modified Checklist for Autism in Toddlers (M‐CHAT) at 18 months.

Results

The M‐CHAT 6‐critical‐item criterion and the 23‐item criterion had a specificity of 97.9% and 92.7% and a sensitivity of 20.8% and 34.1%, respectively. In the 173 children diagnosed with ASD to date, 60 children (34.7%) scored above the cut‐off on either of the screening criteria. The items with the highest likelihood ratios were ‘interest in other children’, ‘show objects to others’ and ‘response to name’.

Conclusion

Even though one‐third of the children who later received an ASD diagnosis were identified through M‐CHAT items, the majority scored below cut‐off on the screening criteria at 18 months. The results imply that it might not be possible to detect all children with ASD at this age.
Income Risk in 30 Countries
Authors: Nichols Austin , Rehm Philipp
Published: February 2014

We present a measure of income risk that decomposes income dynamics into long‐run inequality, volatility (inter‐temporal variability around individual‐specific growth rates), and mobility risk (variation in individual‐specific growth rates). We measure these income risk components in panel data from 30 rich democracies. We use this comprehensive collection of panel data to analyze long‐terms trends in income dynamics for four countries (Canada, Germany, Great Britain, and the United States), and cross‐national patterns of income dynamics for an additional 26 countries. We find that tax and transfer systems lower income risk, but less so in the United States than in other comparable countries. We find that higher incomes tend to grow faster and to be more volatile than lower incomes. We find that the United States is exceptional in its level of, and increase in, each type of income risk. Various other measures of mobility are positively correlated with mobility risk.
Extending Integrated Nested Laplace Approximation to a Class of Near‐Gaussian Latent Models
Authors: Martins Thiago G. , Rue Håvard
Published: February 2014

This work extends the integrated nested Laplace approximation (INLA) method to latent models outside the scope of latent Gaussian models, where independent components of the latent field can have a near‐Gaussian distribution. The proposed methodology is an essential component of a bigger project that aims to extend the R package INLA in order to allow the user to add flexibility and challenge the Gaussian assumptions of some of the model components in a straightforward and intuitive way. Our approach is applied to two examples, and the results are compared with that obtained by Markov chain Monte Carlo, showing similar accuracy with only a small fraction of computational time. Implementation of the proposed extension is available in the R‐INLA package.
Computing Critical Values of Exact Tests by Incorporating Monte Carlo Simulations Combined with Statistical Tables
Authors: Vexler Albert , Kim Young Min , Yu Jihnhee , Lazar Nicole A. , Hutson Alan D.
Published: February 2014

Various exact tests for statistical inference are available for powerful and accurate decision rules provided that corresponding critical values are tabulated or evaluated via Monte Carlo methods. This article introduces a novel hybrid method for computingp‐values of exact tests by combining Monte Carlo simulations and statistical tables generateda priori. To use the data from Monte Carlo generations and tabulated critical values jointly, we employ kernel density estimation within Bayesian‐type procedures. Thep‐values are linked to the posterior means of quantiles. In this framework, we present relevant information from the Monte Carlo experiments via likelihood‐type functions, whereas tabulated critical values are used to reflect prior distributions. The local maximum likelihood technique is employed to compute functional forms of prior distributions from statistical tables. Empirical likelihood functions are proposed to replace parametric likelihood functions within the structure of the posterior mean calculations to provide a Bayesian‐type procedure with a distribution‐free set of assumptions. We derive the asymptotic properties of the proposed nonparametric posterior means of quantiles process. Using the theoretical propositions, we calculate the minimum number of needed Monte Carlo resamples for desired level of accuracy on the basis of distances between actual data characteristics (e.g. sample sizes) and characteristics of data used to present corresponding critical values in a table. The proposed approach makes practical applications of exact tests simple and rapid. Implementations of the proposed technique are easily carried out via the recently developedSTATAand R statistical packages.
Muscle conduction velocity, strength, neural activity, and morphological changes after eccentric and concentric training
Authors: Cadore E. L. , González‐Izal M. , Pallarés J. G. , Rodriguez‐Falces J. , Häkkinen K. , Kraemer W. J. , Pinto R. S. , Izquierdo M.
Published: February 2014

This study compared the effects of concentric and eccentric training on neuromuscular adaptations in young subjects. Twenty‐two men and women were assigned to one of two groups: concentric (CON, n = 11) and eccentric (ECC, n = 11) training. Training consisted of 6 weeks of isokinetic exercise, performed twice weekly, starting with two sets of eight repetitions, and progressing to five sets of 10 repetitions. Subjects were tested in strength variables [concentric, eccentric, and isometric peak torque (PT), and rate of force development (RFD)], muscle conduction velocity (CV), neuromuscular activity, vastus lateralis (VL) muscle thickness, and echo intensity as determined by ultrasonography. There were similar increases in the concentric and eccentric PTs in both the CON and ECC groups (P < 0.01), but only the ECC group showed an increase in isometric PT (P < 0.001). Similarly, both groups exhibited increased VL muscle thickness, CV, and RFD, and reduced VL echo intensity (P < 0.05). Significant correlations were observed among the relative changes in the neuromuscular outcomes and training variables (e.g., total work, average PT) (r = 0.68–0.75, P < 0.05). The results showed that both training types similarly improved dynamic PT, CV, RFD, and muscle thickness and quality during the early weeks of training.
Changing epidemiology of maternal mortality in rural India: time to reset strategies for MDG‐5
Authors: Shah Pankaj , Shah Shobha , Kutty Raman V. , Modi Dhiren
Published: February 2014

Objective

To understand changes in epidemiology of maternal mortality in rural India in the context of increasing institutional deliveries and implementation of community‐based interventions that can inform policies to reach MDG‐5.

Methods

This study is a secondary analysis of prospectively collected community‐based data of every pregnancy and its outcomes from 2002 to 2011 in a rural, tribal area of Gujarat, India as part of safe‐motherhood programme implemented by voluntary organisation, SEWA Rural. The programme consisted of community‐based interventions supported by a first referral unit, and promotion of institutional deliveries. For every maternal death, a verbal autopsy was conducted. The incidence rates for maternal mortality according to place, cause and timing of maternal deaths in relation to pregnancy were computed. Annual incidence rate ratios (IRR) and 95% confidence intervals, adjusted for caste and maternal education, were estimated using Poisson regression to test for linear trend in reduction in mortality during the study period.

Results

Thirty‐two thousand eight hundred and ninety‐three pregnancies, 29 817 live births and 80 maternal deaths were recorded. Maternal mortality ratio improved from 607 (19 deaths) in 2002–2003 to 161 (five deaths) in 2010–2011. The institutional delivery rate increased from 23% to 65%. The trend of falling maternal deaths was significant over time, with an annual reduction of 17% (adjusted IRR 0.83 CI 0.75–0.91, P‐value <0.001). There were significant reductions in adjusted incidence rate of maternal deaths due to direct causes, during intrapartum and post‐partum periods, and those which occurred at home. However, reductions in incidence of maternal deaths due to indirect causes, at hospital and during antepartum period were not statistically significant. Most maternal deaths are now occurring at hospitals and due to indirect causes.

Conclusion

Gains in institutional deliveries and community‐based interventions resulting in fewer maternal deaths due to direct causes should be maintained. However, it would be essential to now prioritise management of indirect causes of maternal mortality during pregnancy at community and hospitals for further reduction in maternal deaths to achieve MDG‐5.
Gibberellins inhibit adventitious rooting in hybrid aspen and Arabidopsis by affecting auxin transport
Authors: Mauriat Mélanie , Petterle Anna , Bellini Catherine , Moritz Thomas
Published: February 2014

Knowledge of processes involved in adventitious rooting is important to improve both fundamental understanding of plant physiology and the propagation of numerous plants. Hybrid aspen (Populus tremula × tremuloïdes) plants overexpressing a key gibberellin (GA) biosynthesis gene (AtGA20ox1) grow rapidly but have poor rooting efficiency, which restricts their clonal propagation. Therefore, we investigated the molecular basis of adventitious rooting in Populus and the model plant Arabidopsis. The production of adventitious roots (ARs) in tree cuttings is initiated from the basal stem region, and involves the interplay of several endogenous and exogenous factors. The roles of several hormones in this process have been characterized, but the effects of GAs have not been fully investigated. Here, we show that a GA treatment negatively affects the numbers of ARs produced by wild‐type hybrid aspen cuttings. Furthermore, both hybrid aspen plants and intact Arabidopsis seedlings overexpressing AtGA20ox1, PttGID1.1 or PttGID1.3 genes (with a 35S promoter) produce few ARs, although ARs develop from the basal stem region of hybrid aspen and the hypocotyl of Arabidopsis. In Arabidopsis, auxin and strigolactones are known to affect AR formation. Our data show that the inhibitory effect of GA treatment on adventitious rooting is not mediated by perturbation of the auxin signalling pathway, or of the strigolactone biosynthetic and signalling pathways. Instead, GAs appear to act by perturbing polar auxin transport, in particular auxin efflux in hybrid aspen, and both efflux and influx in Arabidopsis.
Functional interplay between protein kinase CK2 and salicylic acid sustains PIN transcriptional expression and root development
Authors: Armengot Laia , Marquès‐Bueno María Mar , Soria‐Garcia Angel , Müller Maren , Munné‐Bosch Sergi , Martínez María Carmen
Published: February 2014

We have previously reported that CK2‐defective Arabidopsis thaliana plants (CK2mut plants) were impaired severely in root development and auxin polar transport, and exhibited transcriptional misregulation of auxin‐efflux transporters (Plant J., 67, 2011a, 169). In this work we show that CK2mut roots accumulate high levels of salicylic acid (SA) and that the gene that encodes isochorismate synthase (SID2) is overexpressed, strongly suggesting that CK2 activity is required for SA biosynthesis via the shikimate pathway. Moreover, SA activates transcription of CK2‐encoding genes and, thus, SA and CK2 appear to be part of an autoregulatory feed‐back loop to fine‐tune each other's activities. We also show that exogenous SA and constitutive high SA levels in cpr mutants reproduce the CK2mut root phenotypes (decrease of root length and of number of lateral roots), whereas inhibition of CK2 activity in SA‐defective and SA‐signalling mutants lead to less severe phenotypes, suggesting that the CK2mut root phenotypes are SA‐mediated effects. Moreover, exogenous SA mediates transcriptional repression of most of PIN‐FORMED (PIN) genes, which is the opposite effect observed in CK2mut roots. These results prompted us to propose a model in which CK2 acts as a link between SA homeostasis and transcriptional regulation of auxin‐efflux transporters. We also show that CK2 overexpression in Arabidopsis has neither impact on SA biosynthesis nor on auxin transport, but it improves the Arabidopsis root system. Thus, unlike the outcome in mammals, an excess of CK2 in plant cells does not produce neoplasia, but it might be advantageous for plant fitness.
COMPARISON OF NONCONTRAST COMPUTED TOMOGRAPHY AND HIGH‐FIELD MAGNETIC RESONANCE IMAGING IN THE EVALUATION OF GREAT DANES WITH CERVICAL SPONDYLOMYELOPATHY
Authors: Martin‐Vaquero Paula , da Costa Ronaldo C. , Drost Wm Tod
Published: February 2014

Computed tomography (CT) provides excellent bony detail, whereas magnetic resonance (MR) imaging is superior in evaluating the neural structures. The purpose of this prospective study was to assess interobserver and intermethod agreement in the evaluation of cervical vertebral column morphology and lesion severity in Great Danes with cervical spondylomyelopathy by use of noncontrast CT and high‐field MR imaging. Fifteen client‐owned affected Great Danes were enrolled. All dogs underwent noncontrast CT under sedation and MR imaging under general anesthesia of the cervical vertebral column. Three observers independently evaluated the images to determine the main site of spinal cord compression, direction and cause of the compression, articular process joint characteristics, and presence of foraminal stenosis. Overall intermethod agreement, intermethod agreement for each observer, overall interobserver agreement, and interobserver agreement between pairs of observers were calculated by use of kappa (κ) statistics. The highest overall intermethod agreements were obtained for the main site of compression and direction of compression with substantial agreements (κ = 0.65 and 0.62, respectively), whereas the lowest was obtained for right‐sided foraminal stenosis (κ = 0.39, fair agreement). For both imaging techniques, the highest and lowest interobserver agreements were recorded for the main site of compression and degree of articular joint proliferation, respectively. While different observers frequently agree on the main site of compression using both imaging techniques, there is considerable variation between modalities and among observers when assessing articular process characteristics and foraminal stenosis. Caution should be exerted when comparing image interpretations from multiple observers.
Are there advantages in the use of specific pathogen‐free baboons in pig organ xenotransplantation models?
Authors: Zhou Huidong , Iwase Hayato , Wolf Roman F. , Ekser Burcin , Ezzelarab Mohamed , Hara Hidetaka , White Gary , Cooper David K.C.
Published: February 2014

Baboons have natural antibodies against pig antigens. We have investigated whether there are differences in anti‐non‐Gal pig antibody levels between baboons maintained under specific pathogen‐free (SPF) conditions and those housed under conventional conditions (non‐SPF) that might be associated with improved outcome after pig‐to‐baboon organ transplantation. Baboons (n = 40) were housed indoors (SPF n = 8) or in indoor/outdoor pens (non‐SPF n = 32) in colonies of similar size and structure. Non‐SPF colonies harbor a number of pathogens common to non‐human primate species, whereas many of these pathogens have been eliminated from the SPF colony. Complete blood cell counts (CBC), blood chemistry, and anti‐non‐Gal IgM and IgG levels were monitored. There were no significant differences in CBC or blood chemistry between SPF and non‐SPF baboons. Anti‐non‐Gal IgM levels were significantly lower in the SPF baboons than in the non‐SPF baboons (MFI 7.1 vs. 8.8, P < 0.05). One SPF and two non‐SPF baboons had an MFI >20; if these three baboons are omitted, the mean MFIs were 4.8 (SPF) vs. 7.5 (non‐SPF) (P < 0.05). Anti‐non‐Gal IgG was minimal in both groups (MFI 1.0 vs. 1.0). As their levels of anti‐non‐Gal IgM are lower, baboons maintained under SPF conditions may be beneficial for xenotransplantation studies as the initial binding of anti‐pig IgM to an α1,3‐galactosyltransferase gene‐knockout pig organ may be less, thus resulting in less complement and/or endothelial cell activation. However, even under identical SPF conditions, an occasional baboon will express a high level of anti‐non‐Gal IgM, the reason for which remains uncertain.
Intrinsic vascular dopamine – a key modulator of hypoxia‐induced vasodilatation in splanchnic vessels
Authors: Pfeil Uwe , Kuncova Jitka , Brüggmann Doerthe , Paddenberg Renate , Rafiq Amir , Henrich Michael , Weigand Markus A. , Schlüter Klaus‐Dieter , Mewe Marco , Middendorff Ralf , Slavikova Jana , Kummer Wolfgang
Published: February 2014

Key points

Dopamine is a member of the catecholamine family and a precursor in the biosynthetic pathway of adrenaline and noradrenaline, which acts as an independent neurotransmitter in the sympathetic nervous system and as a paracrine hormone.

We found that the arterial wall of systemic vessels itself, i.e. the endothelial cells and the underlying tissue, produces a substantial pool of dopamine.

This intrinsic vascular dopamine is released upon stimulation by decreasing oxygen concentrations, causing a dilatation of the blood vessel, thereby increasing blood flow and subsequently oxygenation of the tissue.

This study identifies dopamine as a novel non‐neuronal intrinsic vasodilator in the arterial wall, crucially involved in ‐driven modulation of vascular tone and maintenance of tissue oxygenation under conditions where reduced oxygen supply may cause severe damage to body systems as in stroke, heart infarction and pulmonary hypertension.

Dopamine not only is a precursor of the catecholamines noradrenaline and adrenaline but also serves as an independent neurotransmitter and paracrine hormone. It plays an important role in the pathogenesis of hypertension and is a potent vasodilator in many mammalian systemic arteries, strongly suggesting an endogenous source of dopamine in the vascular wall. Here we demonstrated dopamine, noradrenaline and adrenaline in rat aorta and superior mesenteric arteries (SMA) by radioimmunoassay. Chemical sympathectomy with 6‐hydroxydopamine showed a significant reduction of noradrenaline and adrenaline, while dopamine levels remained unaffected. Isolated endothelial cells were able to synthesize and release dopamine upon cAMP stimulation. Consistent with these data, mRNAs coding for catecholamine synthesizing enzymes, i.e. tyrosine hydroxylase (TH), aromatic l‐amino acid decarboxylase, and dopamine‐β‐hydroxylase were detected by RT‐PCR in cultured endothelial cells from SMA. TH protein was detected by immunohistochemisty and Western blot. Exposure of endothelial cells to hypoxia (1% O2) increased TH mRNA. Vascular smooth muscle cells partially expressed catecholaminergic traits. A physiological role of endogenous vascular dopamine was shown in SMA, where D1 dopamine receptor blockade abrogated hypoxic vasodilatation. Experiments on SMA with endothelial denudation revealed a significant contribution of the endothelium, although subendothelial dopamine release dominated. From these results we conclude that endothelial cells and cells of the underlying vascular wall synthesize and release dopamine in an oxygen‐regulated manner. In the splanchnic vasculature, this intrinsic non‐neuronal dopamine is the dominating vasodilator released upon lowering of oxygen tension.
Glucocorticoids and renal Na+ transport: implications for hypertension and salt sensitivity
Authors: Hunter Robert W. , Ivy Jessica R. , Bailey Matthew A.
Published: February 2014

The clinical manifestations of glucocorticoid excess include central obesity, hyperglycaemia, dyslipidaemia, electrolyte abnormalities and hypertension. A century on from Cushing's original case study, these cardinal features are prevalent in industrialized nations. Hypertension is the major modifiable risk factor for cardiovascular and renal disease and reflects underlying abnormalities of Na+ homeostasis. Aldosterone is a master regulator of renal Na+ transport but here we argue that glucocorticoids are also influential, particularly during moderate excess. The hypothalamic–pituitary–adrenal axis can affect renal Na+ homeostasis on multiple levels, systemically by increasing mineralocorticoid synthesis and locally by actions on both the mineralocorticoid and glucocorticoid receptors, both of which are expressed in the kidney. The kidney also expresses both of the 11β‐hydroxysteroid dehydrogenase (11βHSD) enzymes. The intrarenal generation of active glucocorticoid by 11βHSD1 stimulates Na+ reabsorption; failure to downregulate the enzyme during adaption to high dietary salt causes salt‐sensitive hypertension. The deactivation of glucocorticoid by 11βHSD2 underpins the regulatory dominance for Na+ transport of mineralocorticoids and defines the ‘aldosterone‐sensitive distal nephron’. In summary, glucocorticoids can stimulate renal transport processes conventionally attributed to the renin–angiotensin–aldosterone system. Importantly, Na+ and volume homeostasis do not exert negative feedback on the hypothalamic–pituitary–adrenal axis. These actions are therefore clinically relevant and may contribute to the pathogenesis of hypertension in conditions associated with elevated glucocorticoid levels, such as the metabolic syndrome and chronic stress.
Passive hind‐limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury
Authors: West Christopher R. , Crawford Mark A. , Poormasjedi‐Meibod Malihe‐Sadat , Currie Katharine D. , Fallavollita Andre , Yuen Violet , McNeill John H. , Krassioukov Andrei V.
Published: February 2014

Key points

Using a wide array of experimental approaches, we demonstrate for the first time that spinal cord injury is associated with a rapid and sustained impairment in cardiac structure and function that is present as early as 1 week post‐injury.

We provide novel data demonstrating that spinal cord injury elicits an altered Starling curve and myocardial fibrosis. The latter of these may be secondary to an up‐regulation of transforming growth factor beta‐1 and mothers against decapentaplegic homolog 3 mRNA, both of which form part of a well‐known fibrotic signalling pathway.

Passive hind‐limb cycling averts the spinal cord injury‐induced impairments in cardiac structure and function, prevents myocardial fibrosis and improves blood lipid profiles.

Passive lower‐limb cycling represents an elegant, cost‐effective and widely accessible therapeutic strategy that may reduce the clinical cardiovascular burden imposed by spinal cord injury and other neurological disorders.

Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio‐metabolic responses to SCI and to establish whether passive hind‐limb cycling elicits a cardio‐protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind‐limb cycling (SCI‐EX; 2 × 30 min day−1, 5 days week−1 for 4 weeks beginning 6 days post‐SCI). On day 32, cardio‐metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI‐EX) underwent in vivo echocardiography and basal haemodynamic assessments pre‐SCI and at days 7, 14 and 32 post‐SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up‐regulation of transforming growth factor beta‐1 (TGFβ1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI‐EX, the initial reduction in left ventricular dimensions and function at day 7 post‐SCI was completely reversed by day 32 post‐SCI, and there were no differences in myocardial contractility between SCI‐EX and CON. Collagen deposition was similar between SCI‐EX and CON. TGFβ1 and Smad3 were down‐regulated in SCI‐EX. Blood lipid profiles were improved in SCI‐EX versus SCI. We provide compelling novel evidence that passive hind‐limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI.
Neuropeptide Y acts in the paraventricular nucleus to suppress sympathetic nerve activity and its baroreflex regulation
Authors: Cassaglia Priscila A. , Shi Zhigang , Li Baoxin , Reis Wagner L. , Clute‐Reinig Nicholas M. , Stern Javier E. , Brooks Virginia L.
Published: February 2014

Key points

Neuropeptide Y (NPY) acts in the brain to decrease sympathetic nerve activity (SNA); however, the specific site is unknown.

We identify the paraventricular nucleus of the hypothalamus (PVN) as a site of action, since nanoinjection of NPY into the PVN dose‐dependently decreases SNA, whereas PVN injection of NPY Y1 and Y5 receptor antagonists increases SNA.

NPY may directly inhibit PVN presympathetic neurons, since these neurons express Y1 receptors and, in patch‐clamp experiments, are inhibited by NPY.

Our data also indicate that identified PVN presympathetic neurons that are inhibited by NPY are also excited by α‐melanocyte‐stimulating hormone.

These results identify endogenous PVN NPY as a novel and potent inhibitory neuromodulator that may contribute to changes in SNA that occur in states associated with altered energy balance, such as obesity and pregnancy.

Neuropeptide Y (NPY), a brain neuromodulator that has been strongly implicated in the regulation of energy balance, also acts centrally to inhibit sympathetic nerve activity (SNA); however, the site and mechanism of action are unknown. In chloralose‐anaesthetized female rats, nanoinjection of NPY into the paraventricular nucleus of the hypothalamus (PVN) dose‐dependently suppressed lumbar SNA (LSNA) and its baroreflex regulation, and these effects were blocked by prior inhibition of NPY Y1 or Y5 receptors. Moreover, PVN injection of Y1 and Y5 receptor antagonists in otherwise untreated rats increased basal and baroreflex control of LSNA, indicating that endogenous NPY tonically inhibits PVN presympathetic neurons. The sympathoexcitation following blockade of PVN NPY inhibition was eliminated by prior PVN nanoinjection of the melanocortin 3/4 receptor inhibitor SHU9119. Moreover, presympathetic neurons, identified immunohistochemically using cholera toxin b neuronal tract tracing from the rostral ventrolateral medulla (RVLM), express NPY Y1 receptor immunoreactivity, and patch‐clamp recordings revealed that both NPY and α‑melanocyte‐stimulating hormone (α‐MSH) inhibit and stimulate, respectively, PVN–RVLM neurons. Collectively, these data suggest that PVN NPY inputs converge with α‐MSH to influence presympathetic neurons. Together these results identify endogenous NPY as a novel and potent inhibitory neuromodulator within the PVN that may contribute to changes in SNA that occur in states associated with altered energy balance, such as obesity and pregnancy.
Dietary pre‐exposure of rats to fish oil does not enhance myocardial efficiency of isolated working hearts or their left ventricular trabeculae
Authors: Goo Soyeon , Han June‐Chiew , Nisbet Linley A. , LeGrice Ian J. , Taberner Andrew J. , Loiselle Denis S.
Published: February 2014

Key points

Dietary fish oil has been found to have protective effects against cardiovascular disease, particularly in its role as an anti‐arrhythmic agent.

An additional mechanism proposed for the putative cardio‐protective effect is enhanced efficiency of metabolic energy usage by the heart.

We tested whether dietary supplementation of fish oil enhances cardiac efficiency or otherwise improves mechano‐energetic performance. Experiments were performed at two distinct physiological levels (whole organ and isolated tissues) employing two independent metabolic indices (oxygen consumption and heat production), respectively.

Feeding rats with either a fish oil‐enriched or a saturated fatty acid‐enriched diet did not alter the efficiency of either the isolated whole heart or its left ventricular trabeculae.

Numerous epidemiological studies, supported by clinical and experimental findings, have suggested beneficial effects of dietary fish or fish oil supplementation on cardiovascular health. One such experimental study showed a profound (100%) increase in myocardial efficiency (i.e. the ratio of work output to metabolic energy input) of the isolated whole heart, achieved by a corresponding decrease in the rate of myocardial oxygen consumption. However, a number of other investigations have returned null results on the latter energetic index. Such conflicting findings have motivated us to undertake a re‐examination. To that effect, we investigated the effects of dietary fatty acid supplementation on myocardial mechano‑energetics, with our primary focus on cardiac efficiency. We used both isolated hearts and isolated left ventricular trabeculae of rats fed with one of three distinct diets: reference (REF), fish oil‐supplemented (FO) or saturated fat‐supplemented (SFA). For all three groups, and at both spatial levels, we supplied 10 mm glucose as the exogenous metabolic substrate. In the working heart experiments, we found no difference in the average mechanical efficiency among the three dietary groups: 14.8 ± 1.1% (REF), 13.9 ± 0.6% (FO) and 13.6 ± 0.7% (SFA). Likewise, we observed no difference in peak mechanical efficiency of left ventricular trabeculae among the REF, FO and SFA groups: 13.3 ± 1.4, 11.2 ± 2.2 and 12.5 ± 1.5%, respectively. We conclude that there is no effect of a period of pre‐exposure to a diet supplemented with either fish oil or saturated fatty acids on the efficiency of the myocardium at either spatial level: tissue or whole heart.
Used Nuclear Fuel/Depleted Uranium: Is it a Waste or a Resource?
Authors: Kok Kenneth D.
Published: February 2014

The purpose of this paper is to examine the energy and economic value of used nuclear fuel and depleted uranium. In the USA these materials are considered to be wastes. As such they are candidates for permanent disposal. The disposal of these materials in a manner that isolates them from human contact is a scientific, engineering, economic and political problem. Isolation can be defined requiring no potential human contact during a stated period of time due to failed containment. The period of isolation is expected to be in excess of one million years.

The uranium in the used fuel and the depleted uranium left over from the enrichment process represent about 99.5 percent of the uranium that was removed from the ground by mining uranium ores. If these materials can be utilized they would not be considered to be wastes. In addition they would carry a positive economic value. The value of these materials, based on the energy that can be extracted from the uranium, exceeds $100 trillion. Based on this the conclusion is that the material is a very valuable resource and definitely is not a waste.
Waste Management Strategy for Cost Effective and Environmentally Friendly NPP Decommissioning
Authors: Lidar Per , Bergh Niklas , Larsson Arne , Hedin Gunnar
Published: February 2014

Decommissioning of nuclear power plants generates large volumes of radioactive or potentially radioactive waste. The proper management of the dismantling waste plays an important role for the time needed for the dismantling phase and thus is critical to the decommissioning cost.

An efficient and thorough process for inventorying, characterization and categorization of the waste provides a sound basis for the planning process. As part of comprehensive decommissioning studies for Nordic NPPs, Westinghouse has developed the decommissioning inventories that have been used for estimations of the duration of specific work packages and the corresponding costs. As part of creating the design basis for a national repository for decommissioning waste, the total production of different categories of waste packages has also been predicted. Studsvik has developed a risk based concept for categorization and handling of the generated waste using six different categories with a span from extremely small risk for radiological contamination to high level waste. The two companies have recently joined their skills in the area of decommissioning on selected market in a consortium named ndcon to further strengthen the proposed process.

Depending on the risk for radiological contamination or the radiological properties and other properties of importance for waste management, treatment routes are proposed with well-defined and proven methods for on-site or off-site treatment, activity determination and conditioning. The system is based on a graded approach philosophy aiming for high confidence and sustainability, aiming for re-use and recycling where found applicable.

The objective is to establish a process where all dismantled material has a pre-determined treatment route. These routes should through measurements, categorization, treatment, conditioning, intermediate storage and final disposal be designed to provide a steady, un-disturbed flow of material to avoid interruptions. Bottle-necks in the process causes increased space requirements and will have negative impact on the project schedule, which increases not only the cost but also the dose exposure to personnel. For these reasons it is critical to create a process that transfers material into conditioned waste ready for disposal as quickly as possible.

To a certain extent the decommissioning program should be led by the waste management process. With the objective to reduce time for handling of dismantled material at site and to efficiently and environmental-friendly use waste management methods (clearance for re-use followed by clearance for recycling), the costs for the plant decommissioning could be reduced as well as time needed for performing the decommissioning project. Also, risks for delays would be reduced with a well-defined handling scheme which limits surprises. Delays are a major cost driver for decommissioning projects.
γ Dose Rate Estimation and Operation Management Suggestions for Decommissioning the Reactor Pressure Vessel of HTR-PM
Authors: Fang Sheng , Li Hong , Cao Jianzhu , Li Wenqian , Xie Feng , Tong Jiejuan
Published: February 2014

China is now designing and constructing a high temperature gas cooled reactor-pebble bed module (HTR-PM). In order to investigate the future decommissioning approach and evaluate possible radiation dose, gamma dose rate near the reactor pressure vessel was calculated for different cooling durations using QAD-CGA program. The source term of this calculation was provided by KORIGEN program. Based on the calculated results, the spatial distribution and temporal changes of gamma dose rate near reactor pressure vessel was systematically analyzed. A suggestion on planning decommissioning operation of reactor pressure vessel of HTR-PM was given based on calculated dose rate and the Chinese Standard GB18871-2002.
Impact of Recent Developments on the Status of Commercial Nuclear Power and Reactor Decommissioning in the United States
Authors: Devgun Jas S.
Published: February 2014

This paper examines the impact of three recent developments on the commercial nuclear power in the United States. These developments include: Yucca Mountain closure and issues related to SNF; actions in response to Fukushima Diaiichi accident, and; energy economics. All of these have had a significant impact on the commercial nuclear power, its future, as well as the reactor decommissioning scene in the US.
Building Flexibility Into the Design of a Pilot Plant for the Immobilisation of Pu Containing Residues and Wastes
Authors: Scales C. R. , Maddrell E. R. , Hobbs J. , Stephen R. , Moricca S. , Stewart M. W. A.
Published: February 2014

NNL and ANSTO on behalf of Sellafield Ltd have developed a process for the immobilisation of a range of Pu containing wastes and residues. Following the inactive demonstration of the technology the project is now focusing on the design of an active pilot plant capable of validating the technology and ultimately immobilising a waste inventory containing around 100kg plutonium. The diverse wastes from which it is uneconomic to recover Pu, require a flexible process with a wide product envelope capable of producing a wasteform suitable for disposal in a UK repository. Ceramics, glass ceramics and metal encapsulated wasteforms can be delivered by the process line which incorporates size reduction and heat treatment techniques with the aim of feeding a hot isostatic pressing process designed to deliver the highly durable wasteforms. Following a demonstration of feasibility, flowsheet development is progressing to support the design which has the aim of a fully flexible facility based in NNL’s Central Laboratory on the Sellafield site. Optimisation of the size reduction, mixing and blending operations is being carried out using UO2 as a surrogate for PuO2. This work is supporting the potential of using an enhanced glass ceramic formulation in place of the full ceramic with the aim of simplifying glove box operations. Heat treatment and subsequent HIPing strategies are being explored in order to eliminate any carbon from the feeds without increasing the valence state of the uranium present in some of the inventory which can result in an unwanted increase in wasteform volumes. The HIP and ancillary systems are being specifically designed to meet the requirements of the Sellafield site and within the constraints of the NNL Central Laboratory. The HIP is being configured to produce consolidated product cans consistent with the requirements of ongoing storage and disposal. With the aim of one cycle per day, the facility will deliver its mission of immobilising the identified waste and residues inventory within 3 years. During that period it will also be used to demonstrate the potential of this technology to deliver the immobilisation of a proportion of the UK plutonium stockpile that may not be suitable for use as MOx fuel should that decision be taken.