bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundPrevious 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.MethodsThe 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.ResultsThe 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’.ConclusionEven 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.
Extending Integrated Nested Laplace Approximation to a Class of Near‐Gaussian Latent Models
Authors: Martins Thiago G. , Rue Håvard 
Published: February 2014

ABSTRACTThis 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

ABSTRACTVarious 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.
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

AbstractObjectiveTo 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.MethodsThis 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.ResultsThirty‐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.ConclusionGains 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

SummaryKnowledge 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

SummaryWe 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

AbstractBaboons 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.
AbstractDopamine 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

AbstractThe 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.
AbstractSpinal 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.