bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foxp3+ regulatory T cells, immune stimulation and host defence against infection
Authors: Rowe Jared H. , Ertelt James M. , Way Sing Sing 
Published: December 2011

SummaryThe immune system is intricately regulated allowing potent effectors to expand and become rapidly mobilized after infection, while simultaneously silencing potentially detrimental responses that averts immune‐mediated damage to host tissues. This relies in large part on the delicate interplay between immune suppressive regulatory CD4+ T (Treg) cells and immune effectors that without active suppression by Treg cells cause systemic and organ‐specific autoimmunity. Although these beneficial roles have been classically described as counterbalanced by impaired host defence against infection, newfound protective roles for Treg cells against specific viral pathogens (e.g. herpes simplex virus 2, lymphocytic choriomeningitis virus, West Nile virus) have been uncovered using transgenic mice that allow in vivo Treg‐cell ablation based on Foxp3 expression. In turn, Foxp3+ Treg cells also provide protection against some parasitic (Plasmodium sp., Toxoplasma gondii) and fungal (Candida albicans) pathogens. By contrast, for bacterial and mycobacterial infections (e.g. Listeria monocytogenes, Salmonella enterica, Mycobacterium tuberculosis), experimental manipulation of Foxp3+ cells continues to indicate detrimental roles for Treg cells in host defence. This variance is probably related to functional plasticity in Treg cell suppression that shifts discordantly following infection with different types of pathogens. Furthermore, the efficiency whereby Treg cells silence immune activation coupled with the plasticity in Foxp3+ cell activity suggest that overriding Treg‐mediated suppression represents a prerequisite ‘signal zero’ that together with other stimulation signals [T‐cell receptor (signal 1), co‐stimulation (signal 2), inflammatory cytokines (signal 3)] are essential for T‐cell activation in vivo. Herein, the importance of Foxp3+ Treg cells in host defence against infection, and the significance of infection‐induced shifts in Treg‐cell suppression are summarized.
Cryptic lineages and Pleistocene population expansion in a Brazilian Cerrado frog
Authors: PRADO CYNTHIA P. A. , HADDAD CÉLIO F. B. , ZAMUDIO KELLY R. 
Published: December 2011

AbstractDiversification of South American species endemic to open habitats has been attributed to both Tertiary events and Pleistocene climatic fluctuations. Nonetheless, phylogeographical studies of taxa in these regions are few, precluding generalizations about the timing and processes leading to differentiation and speciation. We inferred population structure of Hypsiboas albopunctatus, a frog widely distributed in the Brazilian Cerrado. Three geographically distinct lineages were recovered in our phylogeny. The Chapada dos Guimarães (CG) clade was the first to diverge from other populations and contains multiple haplotypes from a single population in western Cerrado, probably representing a cryptic species. The southeast clade (SE) includes populations along the southeastern limit of the range within the historical distribution of the Brazilian Atlantic forest. Finally, the Central Cerrado (CC) group includes haplotypes from the interior of Brazil that are paraphyletic relative to the SE clade. Analyses of historical demography indicate significant population expansion in the CC and SE populations, likely associated with colonization of newly formed open habitats. The divergence of populations in the CG clade occurred in the late Miocene, concordant with the uplift of the central Brazilian plateau. Divergence of the SE clade from the CC occurred during the mid‐Pleistocene. Thus, both Tertiary geological events and Pleistocene climatic fluctuations promoted divergences among lineages. Our study reveals a complex history of diversification in the Cerrado, a morphoclimatic domain highly threatened because of anthropogenic habitat alteration. We identified surprisingly deep divergences in a widely distributed frog, indicating that the Cerrado is not a barrier‐free habitat and that its diversity is likely underestimated.
Evaluation of preharvest sprouting traits in a collection of spring wheat germplasm using genotype and genotype × environment interaction model
Authors: Rasul Golam , Humphreys Gavin D. , Wu Jixiang , Brûlé‐Babel Anita , Fofana Bourlaye , Glover Karl D. 
Published: December 2011

With 10 tablesAbstractPreharvest sprouting (PHS) can greatly affect the consistent production of high‐quality spring wheat (Triticum aestivum L.) in many regions worldwide including Western Canada. A worldwide collection of red‐ and white‐seeded spring wheat genotypes with different levels of sprouting response were characterized for three PHS traits: falling number, germination index and sprouting index in three different environments in Manitoba, Canada. The data sets were analysed by the genotype and genotype × environment interaction model. Variance components were estimated, genotypic and their interaction effects with environments were predicted by using one of mixed linear model approaches: minimum norm quadratic unbiased estimation approach. Genotypic variance expressed as proportion to the phenotypic variance was higher compared to genotype × environment (G × E) interaction effects for all three PHS traits, suggesting that these genotypes can be used to develop high level of PHS‐resistant cultivars regardless of environment. Strong correlations between PHS traits across environments suggest that all three traits are repeatable and reliable methods to determine PHS response in spring wheat depending on sample types (spike, grain or flour). Predicted genotypic effects, G × E interaction effects and the linear discriminant analysis revealed that white‐seeded genotypes ‘AUS1408’, ‘SC8019‐R1’ and Kanata, and red‐seeded genotypes ‘AC Domain’, ‘AC Majestic’ and ‘Red RL4137’ would be useful PHS‐resistant donors in spring wheat cultivar development programmes.
Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: A pilot study of four patients
Authors: Foster Rachael S , Bint Lewis J , Halbert Anne R 
Published: December 2011

ABSTRACTTuberous sclerosis complex (TSC) is an autosomal dominant genodermatosis characterised by the development of hamartomatous tumours in multiple organs including the brain, skin, kidneys, heart and lungs. Facial angiofibromas are the most visible and unsightly of the cutaneous manifestations of TSC, often resulting in stigmatisation for both the affected individuals and their families. Current treatments include vascular laser, ablative lasers and other destructive techniques such as shave excision and electrodessication. For the best outcome these treatments have to be repeated throughout childhood and teenage years, necessitating multiple general anaesthetics. We report a pilot study of topical rapamycin in four children with TSC and facial angiofibromas. Two patients were trialled on 0.1% rapamycin in petrolatum and the other two patients with 0.1% rapamycin solution (Rapamune) applied topically. Both preparations were rapidly and equally effective, however the 0.1% in petrolatum was much better tolerated. Younger patients with smaller angiofibromas had the best response with near complete clearance. Both preparations were more cost effective than pulsed dye laser under general anaesthesia. Although larger studies are needed, this treatment shows a potential to be a first‐line management for facial angiofibromas in TSC and appears safe to start in early childhood.
Anti‐neutrophil cytoplasmic antibody‐associated systemic vasculitis: nature or nurture?
Authors: Gatenby P. A. 
Published: December 2011

AbstractThis review examines the environmental and genetic contributions to the anti‐neutrophil cytoplasmic antibody‐associated systemic vasculitides. The dominant environmental risk factors appear to be silica exposure for all three syndromes, and vitamin D deficiency is strongly suggested by the latitude and ultraviolet radiation gradient observed for Wegener's granulomatosis and Churg–Strauss syndrome. Genetic factors are generally not very strong, consistent with the rarity of these conditions in children. However, multiple genetic factors, each with a relatively small effect, may combine to create a state of susceptibility towards autoimmunity. With infection as a triggering agent, it is possible to synthesise a pathogenetic hypothesis that accounts for both environmental and genetic effects in regard to both necrotising vasculitis and granuloma formation.
Congenital heart disease‐associated pulmonary arterial hypertension: preliminary results from a novel registry
Authors: Rose M. L. , Strange G. , King I. , Arnup S. , Vidmar S. , O'Donnell C. , Kermeen F. , Grigg L. , Weintraub R. G. , Celermajer D. S. 
Published: December 2011

AbstractBackground/Aims:  Pulmonary arterial hypertension (PAH) frequently accompanies childhood congenital heart disease (CHD) and may persist into adult life. The advent of specific PAH therapies for PAH prompted formation of a national Australian and New Zealand registry in 2010 to document the incidence, demographics, presentation and outcomes for these patients.Methods:  This multicentre, prospective, web‐based registry enrols patients with CHD‐associated PAH being followed in a tertiary centre. The inclusion criteria stipulated patient age ≥16 years, a measured mean pulmonary arterial pressure >25 mmHg at rest or echocardiographical evidence of PAH or a diagnosis of Eisenmenger syndrome, and followed since 1 January 2000. A single observer collected standardised data during a series of site visits.Results:  Of the first 50 patients enrolled, 30 (60%) were female. The mean age (standard deviation (SD)) at the time of PAH diagnosis or confirmation in an adult centre was 27.23 (10.07) years, and 32 (64%) patients are currently aged >30 years. Fourteen (28%) patients were in World Health Organization Functional Class II and 36 (72%) in Class III at the time of diagnosis. Forty‐seven of 50 (94%) had congenital systemic‐pulmonary shunts, and 36 (72%) never underwent intervention. Thirteen (26%) had Down syndrome. Confirmation of PAH by recent cardiac catheterisation was available in 30 (60%) subjects. During follow up, a total of 32 (64%) patients received a PAH‐specific therapy.Conclusions:  CHD associated with PAH in adult life has resulted in a new population with unique needs. This registry will allow documentation of clinical course and long‐term outcomes for these patients.
Pharmacokinetics and safety of Intragam 10 NF, the next generation 10% liquid intravenous immunoglobulin, in patients with primary antibody deficiencies
Authors: Bleasel K. , Heddle R. , Hissaria P. , Stirling R. , Stone C. , Maher D. 
Published: December 2011

AbstractBackground and aims:  Intragam® 10 NF is the next generation 10% intravenous immunoglobulin with three pathogen reduction steps and a noncarbohydrate stabiliser. This open label, cross‐over study in patients with primary immunodeficiency was designed to evaluate whether Intragam 10 NF differed in its pharmacokinetics (PK) compared with Intragam P and to assess Intragam 10 NF safety and tolerability.Methods:  Nineteen primary immunodeficiency patients were administered one cycle of their existing Intragam P dose (0.2–0.8 g/kg 3–4 weekly), followed by seven cycles of Intragam 10 NF administered at the same dosing schedule as Intragam P. The primary objective was to compare serum immunoglobulin G (IgG) trough levels. Secondary endpoints were PK variables, safety and tolerability.Results:  There was no significant within‐patient difference in the average trough immunoglobulin G concentration between Intragam P and Intragam 10 NF (8.76 g/L, 8.55 g/L respectively) (geometrical mean ratio 1.034; 95% confidence interval 0.996–1.073; P = 0.079). Mean PK parameters for both products were similar, with all 95% confidence interval encompassing 1.0 except for time to maximum concentration. Time to maximum concentration occurred earlier with Intragam 10 NF compared with Intragam P, with a shorter infusion time (mean 1.75 h vs 2.52 h respectively; P < 0.05). Headache was the most frequent treatment‐related event following both products. There were no study withdrawals, deaths, or notable changes in laboratory values or vital signs.Conclusion:  Intragam 10 NF was well tolerated and exhibited similar PK to Intragam P, with the advantage of a 45 min shorter infusion time.
Postoperative analgesia via transversus abdominis plane (TAP) catheter for small weight children‐our initial experience
Authors: Visoiu Mihaela , Boretsky Karen R. , Goyal Gagandeep , Cladis Franklyn P. , Cassara Antonio 
Published: December 2011

SummaryPain management in small infants and children is challenging. We report the use of unilateral transversus abdominis plane (TAP) catheters for analgesia following single‐sided open lower abdominal surgery when epidural analgesia was undesirable in a series of six low‐weight children. Data collection was done via a retrospective chart review. All catheters attempted were successfully placed with resultant low pain scores and the minimal use of rescue analgesic medications. No complications were reported related to these catheters. TAP catheters, although technically challenging, are feasible for the provision of analgesia for surgeries involving the lower abdominal wall in very small patients.
Glacier‐bed geomorphic processes and hydrologic conditions relevant to nuclear waste disposal
Authors: IVERSON N. , PERSON M. 
Published: December 2011

AbstractCharacterizing glaciotectonic deformation, glacial erosion and sedimentation, and basal hydrologic conditions of ice sheets is vital for selecting sites for nuclear waste repositories at high latitudes. Glaciotectonic deformation is enhanced by excess pore pressures that commonly persist near ice sheet margins. Depths of such deformation can extend locally to a few tens of meters, with depths up to approximately 300 m in exceptional cases. Rates of glacial erosion are highly variable (0.05–15 mm a−1), but rates <1 mm a−1 are expected in tectonically quiescent regions. Total erosion probably not exceeding several tens of meters is expected during a glacial cycle, although locally erosion could be greater. Consolidation of glacial sediments that is less than expected from independent estimates of glacier thickness indicates that heads at the bases of past ice sheets were usually within 30% of the floatation value. This conclusion is reinforced by direct measurements of water pressure beneath portions of the West Antarctic ice sheet, which indicate average heads <7 m below floatation. Landforms of the Laurentide and Scandinavian ice sheets and recent observations in Greenland indicate that high seasonal discharges of surface water are conducted to the bed, despite thick ice at subfreezing temperatures. Therefore, in models of subglacial groundwater flow used to assess sites for nuclear waste repositories, a flux upper boundary condition based on water input from only basal melting will be far more uncertain than applying a hydraulic head at the upper boundary set equal to a large fraction of the floatation value.
The mutual prospective influence of child and parental post‐traumatic stress symptoms in pediatric patients
Authors: Landolt Markus A. , Ystrom Eivind , Sennhauser Felix H. , Gnehm Hanspeter E. , Vollrath Margarete E. 
Published: December 2011

Background:  Previous studies found notable rates of post‐traumatic stress symptoms (PTSS) and post‐traumatic stress disorder (PTSD) in pediatric patients and their parents and suggest a significant association between child and parent PTSS. However, little is known about mutual influences between child and parental PTSS over time. This study prospectively examined the presence of PTSS and PTSD and the mutual influence of child and parental PTSS in a large sample of pediatric patients with different medical conditions.Methods:  A total of 287 children (aged 6.5–16 years) and their mothers (n = 239) and fathers (n = 221) were assessed at 5–6 weeks and 1 year after an accident or a new diagnosis of cancer or diabetes mellitus type 1 in the child.Results:  At the first assessment 11.1% and at the second assessment 10.2% of the children had moderate to severe PTSS. At 5–6 weeks 29.3% of mothers and 18.6% of fathers met criteria for PTSD. At 1 year the rates were 14.6% for mothers and 7.9% for fathers. There were considerable differences of PTSS among different medical diagnostic groups in children and parents. Mothers were more vulnerable than fathers. Structural equation analysis revealed that initially high PTSS in mothers and fathers were longitudinally related to poorer recovery from PTSS in the child. Cross‐lagged effects from the child to the parents and from one parent to the other were not significant.Conclusions:  This study highlights the long‐term influence of parental PTSS on the child’s recovery after trauma and calls for a family systems approach and for early interventions in the treatment of traumatized pediatric patients.
New targets for antiviral therapy of chronic hepatitis C
Authors: Bühler Sandra , Bartenschlager Ralf 
Published: December 2011

AbstractUntil recently, chronic hepatitis C caused by persistent infection with the hepatitis C virus (HCV) has been treated with a combination of pegylated interferon‐alpha (PEG‐IFNα) and ribavirin (RBV). This situation has changed with the development of two drugs targeting the NS3/4A protease, approved for combination therapy with PEG‐IFNα/RBV for patients infected with genotype 1 viruses. Moreover, two additional viral proteins, the RNA‐dependent RNA polymerase (residing in NS5B) and the NS5A protein have emerged as promising drug targets and a large number of antivirals targeting these proteins are at different stages of clinical development. Although this progress is very promising, it is not clear whether these new compounds will suffice to eradicate the virus in an infected individual, ideally by using a PEG‐IFNα/RBV‐free regimen, or whether additional compounds targeting other factors that promote HCV replication are required. In this respect, host cell factors have emerged as a promising alternative. They reduce the risk of development of antiviral resistance and they increase the chance for broad‐spectrum activity, ideally covering all HCV genotypes. Work in the last few years has identified several host cell factors used by HCV for productive replication. These include, amongst others, cyclophilins, especially cyclophilinA (cypA), microRNA‐122 (miR‐122) or phosphatidylinositol‐4‐kinase III alpha. For instance, cypA inhibitors have shown to be effective in combination therapy with PEG‐IFN/RBV in increasing the sustained viral response (SVR) rate significantly compared to PEG‐IFN/RBV. This review briefly summarizes recent advances in the development of novel antivirals against HCV.
Barriers to hepatitis C treatment
Authors: McGowan Christopher E. , Fried Michael W. 
Published: December 2011

AbstractDespite the availability of highly effective therapy for hepatitis C virus (HCV) infection, few patients receive treatment. Barriers arising at multiple levels, from diagnosis to specialist referral, may impede the delivery of hepatitis C care. At the patient level, lack of awareness, fear of side effects, poor adherence and comorbid conditions may prevent treatment. For providers, limited knowledge, lack of availability and communication difficulties may be problematic. At the government and payer level, a lack of promotion, surveillance and funding may interfere. Each of these barriers needs to be addressed if wider implementation of antiviral therapy is to be achieved.
Space‐Time Data fusion Under Error in Computer Model Output: An Application to Modeling Air Quality
Authors: Berrocal Veronica J. , Gelfand Alan E. , Holland David M. 
Published: December 2011

Summary We provide methods that can be used to obtain more accurate environmental exposure assessment. In particular, we propose two modeling approaches to combine monitoring data at point level with numerical model output at grid cell level, yielding improved prediction of ambient exposure at point level. Extending our earlier downscaler model (Berrocal, V. J., Gelfand, A. E., and Holland, D. M. (2010b). A spatio‐temporal downscaler for outputs from numerical models. Journal of Agricultural, Biological and Environmental Statistics 15, 176–197), these new models are intended to address two potential concerns with the model output. One recognizes that there may be useful information in the outputs for grid cells that are neighbors of the one in which the location lies. The second acknowledges potential spatial misalignment between a station and its putatively associated grid cell.The first model is a Gaussian Markov random field smoothed downscaler that relates monitoring station data and computer model output via the introduction of a latent Gaussian Markov random field linked to both sources of data. The second model is a smoothed downscaler with spatially varying random weights defined through a latent Gaussian process and an exponential kernel function, that yields, at each site, a new variable on which the monitoring station data is regressed with a spatial linear model. We applied both methods to daily ozone concentration data for the Eastern US during the summer months of June, July and August 2001, obtaining, respectively, a 5% and a 15% predictive gain in overall predictive mean square error over our earlier downscaler model (Berrocal et al., 2010b). Perhaps more importantly, the predictive gain is greater at hold‐out sites that are far from monitoring sites.