bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, in healthy human subjects following single and multiple oral dosing in three phase I studies
Authors: Baluom Muhammad , Grossbard Elliott B. , Mant Tim , Lau David T. W. 
Published: November 2012

AimFostamatinib (R788) is an orally dosed prodrug designed to deliver the active metabolite R940406 (R406), a spleen tyrosine kinase (SYK) inhibitor, for the treatment of rheumatoid arthritis. The objectives were to evaluate the human pharmacokinetic properties of fostamatinib and R406.MethodThree clinical studies were conducted in healthy subjects: (A) A single ascending dose study for R406 with doses ranging from 80–600 mg, (B) a single‐ and multiple‐dose study of fostamatinib in aqueous suspension, with single doses ranging from 80–400 mg and multiple doses at 160 mg twice daily and (C) a study comparing suspension and tablet of fostamatinib, with the latter tested in both fed and fasted states.ResultsThese studies demonstrated that when administered as a solution, R406 was rapidly absorbed. Increases in exposure were observed with doses up to 400 mg. A terminal half‐life of 12–21 h was observed. Similar R406 exposure could be achieved with fostamatinib suspension and steady‐state was achieved after 3–4 days following twice daily administration. Fostamatinib tablet and suspension exhibited similar R406 exposure. Upon co‐administration with food, a delay in peak time and lower peak concentrations of R406 were observed but at the same time the overall exposure did not change.ConclusionFostamatinib demonstrates rapid and extensive conversion to R406, an inhibitor of SYK. Solid dosage forms of fostamatinib overcome the challenge of low aqueous solubility of R406. The PK profile of R406 could potentially allow once daily or twice daily oral administration of fostamatinib.
Individual dispersal, landscape connectivity and ecological networks
Authors: Baguette Michel , Blanchet Simon , Legrand Delphine , Stevens Virginie M. , Turlure Camille 
Published: November 2012

ABSTRACTConnectivity is classically considered an emergent property of landscapes encapsulating individuals' flows across space. However, its operational use requires a precise understanding of why and how organisms disperse. Such movements, and hence landscape connectivity, will obviously vary according to both organism properties and landscape features. We review whether landscape connectivity estimates could gain in both precision and generality by incorporating three fundamental outcomes of dispersal theory. Firstly, dispersal is a multi‐causal process; its restriction to an ‘escape reaction’ to environmental unsuitability is an oversimplification, as dispersing individuals can leave excellent quality habitat patches or stay in poor‐quality habitats according to the relative costs and benefits of dispersal and philopatry. Secondly, species, populations and individuals do not always react similarly to those cues that trigger dispersal, which sometimes results in contrasting dispersal strategies. Finally, dispersal is a major component of fitness and is thus under strong selective pressures, which could generate rapid adaptations of dispersal strategies. Such evolutionary responses will entail spatiotemporal variation in landscape connectivity. We thus strongly recommend the use of genetic tools to: (i) assess gene flow intensity and direction among populations in a given landscape; and (ii) accurately estimate landscape features impacting gene flow, and hence landscape connectivity. Such approaches will provide the basic data for planning corridors or stepping stones aiming at (re)connecting local populations of a given species in a given landscape. This strategy is clearly species‐ and landscape‐specific. But we suggest that the ecological network in a given landscape could be designed by stacking up such linkages designed for several species living in different ecosystems. This procedure relies on the use of umbrella species that are representative of other species living in the same ecosystem.
When Narcissus Was a Boy: Origins, Nature, and Consequences of Childhood Narcissism
Authors: Thomaes Sander , Brummelman Eddie , Reijntjes Albert , Bushman Brad J. 
Published: November 2012

AbstractNot all positive self‐views are alike. Developmental researchers increasingly recognize that it is important to distinguish between accurate, well‐balanced positive self‐views and inflated, narcissistic positive self‐views. Narcissism refers to a sense of grandiosity and a strong need to be seen and admired by others. This article reviews current empirical knowledge of narcissistic traits in youths and discusses future challenges and opportunities for this rapidly developing field. Narcissism can be identified from late childhood and has similar manifestations and consequences among youths as it has among adults. Future research will need to uncover the origins and early development of narcissism. The study of childhood narcissism promises to contribute to a more accurate and comprehensive understanding of the development of the self and the consequences of the self.
The Early Ontogeny of Social Norms
Authors: Rakoczy Hannes , Schmidt Marco F. H. 
Published: November 2012

AbstractRecent research has produced new insights into the early development of social cognition and social learning. Even very young children learn and understand social activities as governed by conventional norms that (a) are arbitrary and shared by the community, (b) have normative force and apply to all participants, and (c) are valid in context‐relative ways. Importantly, such understanding is revealed both in the fact that children themselves follow the norms, and in the fact that they actively enforce them toward third parties. Human social cognition thus has a fundamental normative dimension that begins early. This norm psychology plausibly evolved due to its role in stabilizing group coordination and cooperation, and is one of the foundations of what is uniquely human social learning and culture.
Acute and Chronic Effects of Smoking on Myocardial Function in Healthy Heavy Smokers: A Study of Doppler Flow, Doppler Tissue Velocity, and Two‐Dimensional Speckle Tracking Echocardiography
Authors: Farsalinos Konstantinos , Tsiapras Dimitrios , Kyrzopoulos Stamatis , Voudris Vassilis 
Published: November 2012

Background: The purpose of the study was to evaluate the acute and chronic effect of smoking on left ventricular function in healthy heavy smokers by conventional Doppler flow, tissue Doppler, and two‐dimensional speckle tracking echocardiography (2D‐STE). Methods: Echocardiograms were performed in 42 healthy heavy (>20 cigarettes/day) smokers (age 34 ± 5 years), before (group SM‐1), 15 minutes (SM‐2) and 30 minutes (SM‐3) after starting smoking 2 cigarettes. Nonsmokers (n = 41, age 33 ± 4 years) served as controls. Transmitral flow, isovolumetric relaxation time (IVRT), and myocardial performance index (MPI) were measured. Tissue velocity measurements were averaged from lateral and septal mitral annulus. Longitudinal strain (GS), systolic (SRs), early diastolic (SRe), late diastolic (SRa), and isovolumetric relaxation (SRivr) strain rate were measured. The percent change in strain from end‐systole to the first one‐third of diastole (SI‐DI = [(GS − strain at one‐third diastole)/GS] × 100) was also measured. Results: IVRT and MPI were increased and early diastolic mitral annular velocity was decreased in SM‐2; they returned to baseline in SM‐3. There was no difference in GS and SRs. SRe and SRivr were reduced in SM‐1 (P < 0.05), and remained significantly reduced in SM‐2 and SM‐3. SI‐DI was lower in SM‐1 (P = 0.011) and was further reduced in SM‐2 and SM‐3 (P < 0.001). Conclusion: Acute and chronic smoking inhalation has adverse effects on myocardial function in healthy heavy smokers. 2D‐STE is able to detect both baseline differences and late acute effects of smoking.
The impact of recurrent gestational diabetes on maternal metabolic and cardiovascular risk factors
Authors: Winhofer Yvonne , Tura Andrea , Prikoszovich Thomas , Winzer Christine , Schneider Barbara , Pacini Giovanni , Luger Anton , Kautzky‐Willer Alexandra 
Published: November 2012

AbstractObjectiveThe development of overt diabetes in women with prior gestational diabetes mellitus (priorGDM) has been linked to several risk factors including age, obesity and insulin therapy during pregnancy; the role of recurrent GDM as a further risk factor remains unclear. As studies examining detailed metabolic consequences of recurrent GDM are missing and the role of recurrent GDM on cardiovascular risk is unknown, our aim was to investigate the impact of recurrent GDM (within 5 years after an index pregnancy) on metabolic and cardiovascular parameters.MethodsOral and intravenous glucose tolerance tests as well as assessment of cardiovascular risk factors were performed at baseline (6 months after index pregnancy) and 5 years thereafter in 21 prior GDM with recurrent GDM (recGDM), 41 prior GDM with no additional pregnancy (nonrecGDM) and 10 healthy controls [CON].ResultsDespite weight gain in recGDM (2·3 ± 5·1 vs. −1·3 ± 6·7 kg, P < 0·04), glucose tolerance, insulin sensitivity and secretion did not differ compared with nonrecGDM at baseline and follow‐up. Furthermore, recGDM did not exhibit increased cardiovascular risk factors. Metabolic deterioration in (19% of) the total priorGDM group was associated with decreased insulin sensitivity (OGIS:367·4 ± 89·6 vs. 436·4 ± 75·5 mL/min*m², P = 0·01), hyperinsulinaemia (TIS:37·9 ± 9·7 vs. 28·0 ± 10·2 nM, P < 0·006) and postchallenge hyperglycaemia at 5 years postpartum.ConclusionsRecurrence of gestational diabetes was not associated with deterioration of glucose metabolism, insulin sensitivity and secretion nor with increased cardiovascular risk. Consequently, priorGDM should not be recommended to refrain from subsequent pregnancies, but be encouraged to regain and maintain normal body weight after delivery and regularly undergo OGTTs to early detect metabolic deterioration.
Lateral hypothalamic involvement in feeding elicited from the ventral pallidum
Authors: Stratford Thomas R. , Wirtshafter David 
Published: November 2012

AbstractIntense feeding can be elicited by injections of theGABAAreceptor antagonist bicuculline into the medial ventral pallidum (VPm), a basal forebrain structure anatomically interposed between two other feeding‐related brain regions, the nucleus accumbens shell and the lateral hypothalamus (LH). To determine whether theVPm effects changes in feeding behavior through actions on theLH, we examined feeding following unilateral injections of bicuculline into theVPm made either ipsilateral or contralateral to a unilateral excitotoxic lesion of theLHin nondeprived rats. We found that lesions of theLHsignificantly attenuated feeding induced from the ipsilateralVPm, as compared to sham‐operated controls. In striking contrast, unilateralLHlesions significantly potentiated the feeding response elicited by injections of bicuculline into the contralateralVPm. The ‘ipsilateral–contralateral disruption’ design we used makes it extremely unlikely that our findings could have resulted from nonspecific effects of the lesions. These results suggest that theLHis causally involved in mediating the ingestive effects produced by activation of theVPm, and provide an important insight into the functional circuitry by which basal forebrain structures control food intake in mammals.
Headache in primary Sjøgren's syndrome: a population‐based retrospective cohort study
Authors: Tjensvoll A. B. , Harboe E. , Gøransson L. G. , Beyer M. K. , Greve O. J. , Kvaløy J. T. , Omdal R. 
Published: November 2012

BackgroundWe investigated whether the prevalence of primary headaches was higher in patients with primary Sjøgren's syndrome (PSS) than in healthy individuals.MethodsThis retrospective cohort study included 71 patients with PSS (patients) based on the American European Consensus Classification criteria, and 71 age‐ and gender‐matched healthy subjects (controls). Headaches were classified according to the International Classification of Headache Disorders. We measured depression with the Beck Depression Inventory, and fatigue with the Fatigue Severity Scale.ResultsFifty‐one patients and 42 controls had headaches in the previous 12 months (71.8% vs. 59.2%, P = 0.10). Thirty‐eight patients and 28 controls had tension type headaches (TTHs) (53.5% vs. 39.4%, P = 0.12). Eight patients (11.3%) and one control had chronic TTHs (P = 0.05). Migraines and migraines with aura were equally prevalent in patients (26.8% and 11.3%, respectively) and controls (28.2% and 15.5%, respectively; P = 0.61).ConclusionsIn general, patients did not have more migraines or headaches than controls. However, patients had more chronic TTHs than controls. Chronic TTHs were not associated with PSS‐related autoantibodies, fatigue, depression, abnormalities on magnetic resonance imaging or abnormalities in the cerebrospinal fluid. Patients with PSS did, however, have higher depression and fatigue scores than controls.
Effect of a stent bandage on the likelihood of incisional infection following exploratory coeliotomy for colic in horses: A comparative retrospective study
Authors: Tnibar A. , Grubbe Lin K. , Thurøe Nielsen K. , Christophersen M. T. , Lindegaard C. , Martinussen T. , Ekstrøm C. T. 
Published: November 2012

SummaryReasons for performing studyIncisional infections are common in horses after colic surgery. There is a clinical impression that the use of a stent bandage reduces the prevalence of such infections.ObjectiveTo determine the effect of a stent bandage on the likelihood of incisional infection after ventral midline exploratory coeliotomy. It was hypothesised that the use of a stent bandage would reduce the likelihood of incisional infection.MethodsMedical records of horses that underwent exploratory coeliotomy for colic betweenJanuary 2005 andSeptember 2011 were reviewed. Inclusion criteria were animals that had one ventral midline coeliotomy and had survived at least 10 days after surgery. Horses were categorised into 2 groups:no‐stent group and stent group. The following data were collected for each case: age, sex, weight, heart rate, packed cell volume, primary lesion, performance of an enterotomy or intestinal resection, surgical classification, use of local antimicrobials, duration of surgery, intra‐abdominal administration of sodium carboxymethylcellulose, intravenous administration of lidocaine, surgeon, use of a stent bandage, duration of stent use, and use of a belly band. Factors associated with the outcome measure ‘wound infection’ vs. ‘no wound infection’ were analysed using a generalised linear mixed model for logistic regression with surgeon as a random effect.ResultsThe inclusion criteria were met in 130 horses: 55 were assigned to the no‐stent group and 75 to the stent group. In the no‐stent group, 12 (21.8%) horses developed incisional infections, whereas only 2 horses (2.7%) in the stent group had incisional infections. In the stent group, no incisional infections were observed during the last 20 months of the study. Statistical analysis showed that only the effect of the use of a stent bandage was significant (P = 0.005).ConclusionsThe prevalence of incisional infections when a stent bandage was used was 2.7%, a finding that compared favourably to information in the literature. Use of a stent bandage significantly reduced the likelihood of incisional infections.Potential relevanceA stent bandage would reduce the likelihood of incisional infection in horses undergoing exploratory coeliotomy for colic.
Towards a more balanced view of marine ecosystems
Authors: Greene Charles H. 
Published: November 2012

AbstractFrank et al. (Nature, 477, 2011, 86) hypothesize that the slow recovery of the Scotian Shelf ecosystem to its structure prior to the early 1990s is a result of the oscillatory, runaway consumption dynamics of the forage fish complex. Their hypothesis is based on the underlying assumptions that this ecosystem's dynamics are governed by top‐down forcing, predator–prey role reversals, and a trophic cascade extending from demersal predatory fish, especially cod, down to the level of nutrients (Science, 308, 2005, 1621; Nature, 477, 2011, 86). Greene and Pershing (Science, 315, 2007, 1084) called into question the underlying assumption of an extended trophic cascade. They argued that while top‐down forcing can be important at higher trophic levels in many Northwest Atlantic Shelf ecosystems, its impacts on zooplankton, phytoplankton, and nutrients are minor or nonexistent. Instead, they argued that lower trophic‐level dynamics in these ecosystems are governed by climate‐associated, bottom‐up forcing. Observations over the past three decades (Greene et al. Ecology, 89, (Suppl 11), 2008, S24; MERCINA Oceanography, 25, 2012, 208.) are consistent with predictions from the climate‐forcing hypothesis proposed by Greene and Pershing (Science, 315, 2007, 1084), while those from the past decade (MERCINA, Oceanography, 25, 2012, 208) demonstrate that the trophic cascade hypothesis as proposed by Frank et al. (Science, 308, 2005, 1621) should be rejected. A closer examination of these observations also calls into question the hypothesis of ecosystem recovery in the Northwest Atlantic being governed by the oscillatory, runaway consumption dynamics of the forage fish complex.
Setting the record straight on drivers of changing ecosystem states
Authors: Frank Kenneth T. , Petrie Brian , Fisher Jonathan A.D. , Leggett William C. 
Published: November 2012

AbstractThis short communication is a response to the critique by Greene (2012), who puts forward the argument that the dynamics of northwest Atlantic continental shelf ecosystems are strongly influenced by changes in Arctic climate, as indexed by surface salinity. The argument, in its essence, discounts any indirect effects from over‐exploitation of top predators on lower trophic levels in northwest Atlantic ecosystems. Frank et al. (Science 308, 2005, 1621; Nature 477, 2011, 86) reported the existence of cascading trophic interactions with particular emphasis on the eastern Scotian Shelf. Greene argues that the events occurring in the Gulf of Maine/Georges Bank region are representative of all Northwest Atlantic shelf systems, despite previous research (Frank et al. Trends Ecol. Evol. 22, 2007, 236; Petrie et al. Fish. Oceanogr. 18, 2009, 83) that has shown a differential pattern of forcing ranging from top‐down in species‐poor, cold water systems to bottom‐up in warmer, more species‐rich systems, including Georges Bank.
Nonlinear effects of climate on boreal rodent dynamics: mild winters do not negate high‐amplitude cycles
Authors: Korpela Katri , Delgado Maria , Henttonen Heikki , Korpimäki Erkki , Koskela Esa , Ovaskainen Otso , Pietiäinen Hannu , Sundell Janne , Yoccoz Nigel G , Huitu Otso 
Published: November 2012

AbstractSmall rodents are key species in many ecosystems. In boreal and subarctic environments, their importance is heightened by pronounced multiannual population cycles. Alarmingly, the previously regular rodent cycles appear to be collapsing simultaneously in many areas. Climate change, particularly decreasing snow quality or quantity in winter, is hypothesized as a causal factor, but the evidence is contradictory. Reliable analysis of population dynamics and the influence of climate thereon necessitate spatially and temporally extensive data. We combined data on vole abundances and climate, collected at 33 locations throughout Finland from 1970 to 2011, to test the hypothesis that warming winters are causing a disappearance of multiannual vole cycles. We predicted that vole population dynamics exhibit geographic and temporal variation associated with variation in climate; reduced cyclicity should be observed when and where winter weather has become milder. We found that the temporal patterns in cyclicity varied between climatically different regions: a transient reduction in cycle amplitude in the coldest region, low‐amplitude cycles or irregular dynamics in the climatically intermediate regions, and strengthening cyclicity in the warmest region. Our results did not support the hypothesis that mild winters are uniformly leading to irregular dynamics in boreal vole populations. Long and cold winters were neither a prerequisite for high‐amplitude multiannual cycles, nor were mild winters with reduced snow cover associated with reduced winter growth rates. Population dynamics correlated more strongly with growing season than with winter conditions. Cyclicity was weakened by increasing growing season temperatures in the cold, but strengthened in the warm regions. High‐amplitude multiannual vole cycles emerge in two climatic regimes: a winter‐driven cycle in cold, and a summer‐driven cycle in warm climates. Finally, we show that geographic climatic gradients alone may not reliably predict biological responses to climate change.
Exploratory study on telaprevir given every 8 h at 500 mg or 750 mg with peginterferon‐alpha‐2b and ribavirin in hepatitis C patients
Authors: Suzuki Fumitaka , Suzuki Yoshiyuki , Sezaki Hitomi , Akuta Norio , Seko Yuya , Kawamura Yusuke , Hosaka Tetsuya , Kobayashi Masahiro , Saito Satoshi , Arase Yasuji , Ikeda Kenji , Mineta Rie , Watahiki Sachiyo , Kobayashi Mariko , Nakayasu Yoshiyuki , Tsuda Hidetaka , Aoki Keiji , Yamada Ichimaro , Kumada Hiromitsu 
Published: November 2012

AimThe aims of this study are to assess the antiviral effects, safety and telaprevir (TVR) pharmacokinetics in two cohorts given TVR every 8 h (q8h) at doses of 500 mg and 750 mg with peginterferon‐α‐2b and ribavirin in chronic hepatitis C patients.MethodsTwenty chronic hepatitis C (HCV) patients with genotype 1b in high viral loads were randomly assigned to two TVR‐based regimens of 750 mg q8h (group A) and 500 mg q8h (group B) in combination with peginterferon‐α‐2b and ribavirin for 12 weeks.ResultsAlthough the difference was not statistically significant other than trough concentration (Ctrough) at week 4, the parameters of maximum concentration (Cmax), the area under the concentration time curve (AUC0–∞) and Ctrough tended to be higher in group A than those in group B. The antiviral effects were similar in the two groups (sustained virological response rates [SVR], 40% in group A, 50% in group B). The discontinuation rates by anemia were 30% in group A and 20% in group B. Serum creatinine concentrations were lower in group B than those in group A.ConclusionAlthough the exposure to TVR tended to be lower in 500 mg q8h than that in 750 mg q8h, the SVR rates in both groups were similar. The result suggests that the 500 mg q8h dose may be one option for treatment. In addition, the present findings indicate that the development of adverse events which increase with a TVR‐based regimen, specifically anemia and creatinine, could be avoided by dose adjustment of TVR.
A novel HLA‐B allele, B*58:01:12, detected in a Taiwanese volunteer bone marrow stem cell donor using sequence‐based typing method
Authors: Yang K. L. , Lee S. K. , Kao R. H. , Lin C. L. , Lin P. Y. 
Published: November 2012

SummaryHuman leukocyte antigen‐B*58:01:12, a novel rare allele of HLA‐B*58:01 variant, was found in a Taiwanese volunteer bone marrow donor by SBT (sequence‐based typing) method. The DNA sequence of B*58:01:12 is identical to the sequence of B*58:01:01 in exons 2, 3 and 4 except at nucleotide position 483 where nucleotide C is substituted by T (at codon 137; GACGAT). Due to the silent point mutation, the amino acid sequence of B*58:01:12 is identical to the sequence of B*58:01:01. The HLA haplotype in association with B*58:01:12 may be deduced as A*33:03‐B*58:01:12‐DRB1*03:01. The discovery of B*58:01:12 adds further polymorphism of B*58:01 in Taiwanese population.