bluuebunny/crossref_metadata_2025 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

Aim

Fostamatinib (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.

Method

Three 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.

Results

These 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.

Conclusion

Fostamatinib 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

Connectivity 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.
Innovation Contests: A Review, Classification and Outlook
Authors: Adamczyk Sabrina , Bullinger Angelika C. , Möslein Kathrin M.
Published: November 2012

Innovation contests as a means to realize innovative product or service solutions are growing in popularity among practitioners and researchers. An increasing number of organizations worldwide have adopted innovation contests, not only for innovation purposes, but also for other reasons such as promoting sustainability. At the same time, innovation contests represent a growing research field to scholars from different backgrounds, e.g., economics or information systems. In this article, first, the growing body of literature on innovation contests is reviewed and classified into five research categories: economic perspective, management perspective, education focus, innovation focus and sustainability focus. Second, some design elements of innovation contests that are central for the understanding, design and management of innovation contests are presented based on the current body of literature. Finally, current research gaps are presented and some of the research questions are developed that could be explored to contribute to the body of literature.
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

Not 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

Recent 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.
BRIDGING THE GAP BETWEEN DISTANCE AND GENERALIZATION
Authors: Estruch V. , Ferri C. , Hernández‐Orallo J. , Ramírez‐Quintana M. J.
Published: November 2012

Distance‐based and generalization‐based methods are two families of artificial intelligence techniques that have been successfully used over a wide range of real‐world problems. In the first case, general algorithms can be applied to any data representation by just changing the distance. The metric space sets the search and learning space, which is generally instance‐oriented. In the second case, models can be obtained for a given pattern language, which can be comprehensible. The generality‐ordered space sets the search and learning space, which is generally model‐oriented. However, the concepts of distance and generalization clash in many different ways, especially when knowledge representation is complex (e.g., structured data). This work establishes a framework where these two fields can be integrated in a consistent way. We introduce the concept of distance‐based generalization, which connects all the generalized examples in such a way that all of them are reachable inside the generalization by using straight paths in the metric space. This makes the metric space and the generality‐ordered space coherent (or even dual). Additionally, we also introduce a definition of minimal distance‐based generalization that can be seen as the first formulation of the Minimum Description Length (MDL)/Minimum Message Length (MML) principle in terms of a distance function. We instantiate and develop the framework for the most common data representations and distances, where we show that consistent instances can be found for numerical data, nominal data, sets, lists, tuples, graphs, first‐order atoms, and clauses. As a result, general learning methods that integrate the best from distance‐based and generalization‐based methods can be defined and adapted to any specific problem by appropriately choosing the distance, the pattern language and the generalization operator.
Risk factors for cerebral palsy: current knowledge and future causal inference
Authors: DAY STEVEN M , REYNOLDS ROBERT J
Published: November 2012

This commentary is on the systematic review by McIntyre et al. on
pages 499–508 of this issue.
Constrictive Pericarditis with a Calcific Mass Invading into the Right Ventricular Myocardium
Authors: Ahlgren Bryan , Reece Brett , Salcedo Ernesto , Seres Tamas
Published: November 2012

We present a rare and unique case of calcific constrictive pericarditis with a calcified pericardial mass invading the right ventricular myocardium. Perioperative two‐dimensional and three‐dimensional transesophageal echocardiography revealed the extent and structure of the pericardial mass and led to the repair of the right ventricular free wall as a surgical intervention.
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

Objective

The 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.

Methods

Oral 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].

Results

Despite 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.

Conclusions

Recurrence 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

Intense 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

Background

We investigated whether the prevalence of primary headaches was higher in patients with primary Sjøgren's syndrome (PSS) than in healthy individuals.

Methods

This 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.

Results

Fifty‐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).

Conclusions

In 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

Reasons for performing study

Incisional 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.

Objective

To 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.

Methods

Medical 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.

Results

The 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).

Conclusions

The 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 relevance

A 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

Frank 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

This 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.
An assessment of gene‐by‐environment interactions in developmental dyslexia‐related phenotypes
Authors: Mascheretti S. , Bureau A. , Battaglia M. , Simone D. , Quadrelli E. , Croteau J. , Cellino M. R. , Giorda R. , Beri S. , Maziade M. , Marino C.
Published: November 2012

While the genetic and environmental contributions to developmental dyslexia (DD) have been studied extensively, the effects of identified genetic risk susceptibility and of specified environmental hazardous factors have usually been investigated separately. We assessed potential gene‐by‐environment (GxE) interactions onDD‐related reading, spelling and memory phenotypes. The presence ofGxEeffects were investigated for theDYX1C1,DCDC2,KIAA0319andROBO1genes, and for seven specified environmental moderators in 165 nuclear families in which at least one member hadDD, by implementing a general test forGxEinteraction in sib‐pair‐based association analysis of quantitative traits. Our results support a diathesis‐stress model for both reading and memory composites:GxEeffects were found between some specified environmental moderators (i.e. maternal smoke during pregnancy, birth weight and socio‐economic status) and theDYX1C1‐1259C/G marker. We have provided initial evidence that the joint analysis of identified genetic risk susceptibility and measured putative risk factors can be exploited in the study of the etiology ofDDand reading‐related neuropsychological phenotypes, and may assist in identifying/preventing the occurrence ofDD.
Sensation‐seeking genes and physical activity in youth
Authors: Wilkinson A. V. , Gabriel K. P. , Wang J. , Bondy M. L. , Dong Q. , Wu X. , Shete S. , Spitz M. R.
Published: November 2012

Many studies examining genetic influences on physical activity (PA) have evaluated the impact of single nucleotide polymorphisms (SNPs) related to the development of lifestyle‐related chronic diseases, under the hypothesis that they would be associated with PA. However, PA is a multidetermined behavior and associated with a multitude of health consequences. Thus, examining a broader range of candidate genes associated with a broader range of PA correlates may provide new insights into the genetic underpinnings of PA. In this study, we focus on one such correlate – sensation‐seeking behavior. Participants (N = 1130 Mexican origin youth) provided a saliva sample and data on PA and sensation‐seeking tendencies in 2008–2009. Participants were genotyped for 630 functional and tagging variants in the dopamine, serotonin and cannabinoid pathways. Overall 30% of participants (males – 37.6% and females – 22.0%) reported ≥60 min of PA on 5 of 7 days. After adjusting for gender, age and population stratification, and applying the Bayesian False Discovery Probability approach for assessing noteworthiness, four gene variants were significantly associated with PA. In a multivariable model, being male, having higher sensation‐seeking tendencies and at least one copy of the minor allele for SNPs in angiotensin I‐converting enzyme gene [ACE; rs8066276 odds ratio (OR) = 1.44; P = 0.012] and tryptophan hydroxylase 2 gene (TPH2; rs11615016 OR = 1.73; P = 0.021) were associated with increased likelihood of meeting PA recommendations. Participants with at least one copy of the minor allele for SNPs in synaptosomal‐associated protein 25 gene (SNAP25; rs363035 OR = 0.53; P = 0.005) and cannabinoid receptor 1 gene (CNR1; rs6454672 OR = 0.62; P = 0.022) have decreased likelihood of meeting PA recommendations. Our findings extend current knowledge of the complex relationship between PA and possible genetic underpinnings.
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

Small 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

Aim

The 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.

Methods

Twenty 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.

Results

Although 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.

Conclusion

Although 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

Human 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.
How Contexts of Reception Matter: Comparing Peruvian Migrants’ Economic Trajectories in Japan and the US
Authors: Takenaka Ayumi , Paerregaard Karsten
Published: November 2012

This paper examines how Peruvian migrants fare economically in two historically and culturally distinct host countries, Japan and the US, drawing upon a survey and interviews conducted in both countries. Peruvian migrants surveyed share similar socio‐economic backgrounds and migrated to both countries for similar reasons roughly around the same time. Yet, over time, they achieved more occupational upward mobility in the US than in Japan. Japan has not done quite as well as the US in providing immigrants with occupational opportunities due to its less diversified immigrant labor market, limited entrepreneurship opportunities, and restricted modes of immigrant incorporation. Does it mean, however, that Peruvian migrants are less successful in Japan than the US? Although occupational mobility is a commonly used measure of social mobility, the definitions and meanings of “success” are context‐dependent. Peruvians in the US do experience more occupational mobility, but diverge more greatly in economic achievement amongst themselves. In Japan, on the other hand, while they experience little occupational mobility, they have had more economic equality with relatively stable and high wages. The paper examines Peruvian migrants’ distinct economic trajectories over time, focusing on their occupational mobility. We conclude that occupational mobility matters, not necessarily because it accompanies higher income, but because it shapes migrants’ aspirations. In the context where immigrants’ destinations have become more diverse in the world, the paper provides insights into how immigrants “make it” and what it means to “make it” in recent destinations, such as Japan, in comparison to more traditional immigrant countries, such as the US.
Internal Migration of Ethno‐national Minorities: The Case of Arabs in Israel
Authors: Cohen Nir , Czamanski Daniel , Hefetz Amir
Published: November 2012

Recent scholarship emphasizes differences among ethnic groups' internal migration patterns. Yet, with few exceptions, research has focused on the Anglo‐American world, neglecting experiences from other regions. This paper is part of a larger research project that studies mobility among the Arab minority in Israel and its driving forces. In this paper we examine patterns of internal migration by analysing the propensity to migrate as well as migrants' individual and social characteristics. First, we survey the theoretical backdrop that is suggested by recent geographic literature on internal migration among ethnic and racial minorities, including native groups. Second, we contextualize the group studied, providing necessary background information on the political, socio‐economic and demographic conditions of Arabs in Israel. We briefly discuss attributes that are – or have been – potential hindering factors to Arab mobility in the Jewish state. Finally, we analyse 1995 national census data at the micro scale and provide a basis for future explanations of the phenomenon. We conclude by outlying some future directions in the study of internal migration of minorities in Israel.
Migration at a Time of Global Economic Crisis: The Situation in Spain
Authors: Domínguez‐Mujica Josefina , Guerra‐Talavera Raquel , Parreño‐Castellano Juan Manuel
Published: November 2012

In this paper, we offer an initial assessment of the impact of the economic crisis on Spain's migration flows. After a period of intensive economic growth and the ensuing immigratory appeal (1995–2007), Spain has been hit hard by the recession. This has modified the trends that had so far characterized foreign immigration in Spain. The impact of the economic recession has been particularly severe in the case of immigrant workers and, consequently, from an institutional point of view, the Spanish government has adopted various measures to restrict the arrival of new immigrants: it has reduced work permit quotas and it has modified the Foreign Residents Law, toughening residence permit requirements. It has also tried to encourage voluntary returns with a programme devised to provide assistance to immigrants originating from countries with which Spain has social security agreements. The response to this programme has, however, been very limited. Immigration flows have continued and rates of return have stayed low, although new trends are also detectable, such as a decrease in the number of irregular arrivals and a rise in informal employment, as well as differences in the impact of unemployment according to nationality and gender. This reveals the complexity of migration processes beyond the supply and demand of labour and the political will to regulate human mobility. Consequently, immigration patterns in Spain reveal the degree of complexity reached by human mobility, which has increased beyond the logic of the labour market and the government's attempts at regulating migration flows by means of institutional measures. The immigrants' hope of raising their standard of living and the socio‐economic differences between source and receiving countries, even at a time of severe economic crisis, do still serve as explanations for current migration networks, one of the key points in the current debate on international migration.
Differing responses of cortisol to oCRF during endonasal and oral treatment with DDAVP
Authors: CARRARO A. , GIUSTI M. , PORCELLA E. , SESSAREGO P. , DiSEM G. GIORDANO
Published: November 2012

Abstract. Arginine vasopressin (AVP) exerts a potentiating effect on the responses of cortisol and ACTH to ovine CRF (oCRF). A stimulation test using AVP plus oCRF to assess ACTH reserve has been proposed. In central diabetes insipidus, long‐term substitution therapy is commonly undertaken with desmopressin (DDAVP), an analogue of the natural hormone which has a greater antidiuretic action but whose effects on the ACTH‐cortisol axis are still controversial. The aim of our study was to evaluate the variations in the responses of ACTH and cortisol to oCRF in various phases of the treatment of central diabetes insipidus: no treatment, endonasal treatment with DDAVP solution and oral treatment with DDAVP in tablet form. Seven patients suffering from central diabetes insipidus underwent testing with oCRF during the various phases of treatment. In the absence of DDAVP treatment, normal responses were registered for cortisol (basal 164·1 ± 29·4 ng ml−1, peak 396·1 ± 37·9 ng ml−1; P < 0·05) and ACTH (basal 20·4 ± 3·9 pg ml−1, peak 86·3 ± 20·9 pg ml−1; P < 0·05) in all patients. During oral treatment with DDAVP, no variation in cortisol response to oCRF was seen. By contrast, when DDAVP was administered endonasally, a significant reduction in cortisol responsiveness to oCRF (secretory area: 2429 ± 548 ng ml−1 120 min) was noted in comparison with that found during the other two tests (no treatment: 3070 ± 704 ng ml−1 120 min; oral DDAVP: 3419 ± 650 ng ml−1 120 min; P < 0·05) performed. There is no clear explanation for this phenomenon, but an interesting hypothesis is that DDAVP acts as a weak agonist which exerts only a slight stimulatory effect on the corticotropic hypophyseal cells but which is able to compete with the natural hormone for receptor binding.
Induction of oxygen free radical generation in human monocytes by lipoprotein(a)
Authors: HANSEN P. RIIS , KHARAZMI A. , JAUHIAINEN M. , EHNHOLM C.
Published: November 2012

Abstract. The mechanism behind the association of elevated plasma lipoprotein(a) [Lp(a)] levels with atherosclerotic disease is unknown. In the present study, Lp(a) induced generation of oxygen free radicals by monocytes from selected healthy individuals in vitro. This observation may provide a link between Lp(a) and generation of oxidized LDL, which can promote multiple atherogenic cellular responses.
Serial changes in serum vitamin K1, triglyceride, cholesterol, osteocalcin and 25‐hydroxyvitamin D3 in patients after hip replacement for fractured neck of femur or osteoarthritis
Authors: ROBERTS N. B. , HOLDING J. D. , WALSH H. P. J. , KLENERMAN L. , HELLIWELL T. , KING D. , SHEARER M.
Published: November 2012

Abstract. Serum vitamin K1 concentrations were measured at presentation (just before surgery) and then at weekly intervals for 3 weeks in two groups of elderly patients requiring either hemiarthroplasty for fractured neck of femur (FON, n= 13) or total hip replacement for osteoarthritis of the hip (OA, n= 16). In comparison with healthy elderly volunteers (n= 25), serum vitamin K1 concentrations were significantly lower in both groups at presentation, and fell significantly within 24 h after surgery to concentrations approaching non‐detectable, subsequently returning to pre‐operative values within 3 weeks. Serum vitamin K1 tended to be lower in the fracture group both before and after operation, although calculation of a vitamin K1–triglyceride ratio reduced the apparent difference as triglyceride concentrations were lower in the fracture group. Osteocalcin concentrations were similar and fell significantly after operation in both groups, returning to pre‐operative levels within 7 days. No differences in the two forms of osteocalcin (carboxylated and undercarboxylated) were observed either before or after operation in either group. 25‐Hydroxyvitamin D3 concentrations were not significantly different between the two groups at any time. Vitamin K1 status may be lower than desirable in certain groups of the elderly population, and supplementation should be considered as prophylactic therapy.
Assessment of sleep‐disordered breathing using a non‐contact bio‐motion sensor
Authors: Zaffaroni Alberto , Kent Brian , O'Hare Emer , Heneghan Conor , Boyle Patricia , O'Connell Geraldine , Pallin Michael , de Chazal Philip , McNicholas Walter T.
Published: November 2012

Obstructive sleep apnoea is a highly prevalent but under‐diagnosed disorder. The gold standard for diagnosis of obstructive sleep apnoea is inpatient polysomnography. This is resource intensive and inconvenient for the patient, and the development of ambulatory diagnostic modalities has been identified as a key research priority. SleepMinder (BiancaMed, NovaUCD, Ireland) is a novel, non‐contact, bedside sensor, which uses radio‐waves to measure respiration and movement. Previous studies have shown it to be effective in measuring sleep and respiration. We sought to assess its utility in the diagnosis of obstructive sleep apnoea. SleepMinder and polysomnographic assessment of sleep‐disordered breathing were performed simultaneously on consecutive subjects recruited prospectively from our sleep clinic. We assessed the diagnostic accuracy of SleepMinder in identifying obstructive sleep apnoea, and how SleepMinder assessment of the apnoea–hypopnoea index correlated with polysomnography. Seventy‐four subjects were recruited. The apnoea–hypopnoea index as measured by SleepMinder correlated strongly with polysomnographic measurement (r = 0.90; P ≤ 0.0001). When a diagnostic threshold of moderate–severe (apnoea–hypopnoea index ≥15 events h−1) obstructive sleep apnoea was used, SleepMinder displayed a sensitivity of 90%, a specificity of 92% and an accuracy of 91% in the diagnosis of sleep‐disordered breathing. The area under the curve for the receiver operator characteristic was 0.97. SleepMinder correctly classified obstructive sleep apnoea severity in the majority of cases, with only one case different from equivalent polysomnography by more than one diagnostic class. We conclude that in an unselected clinical population undergoing investigation for suspected obstructive sleep apnoea, SleepMinder measurement of sleep‐disordered breathing correlates significantly with polysomnography.
War 2008 das neue 1929? Richtige und falsche Vergleiche zwischen der Großen Depression der 1930er Jahre und der Großen Rezession von 2008
Authors: Ritschl Albrecht
Published: November 2012

The Great Recession of 2008 hit the international economy harder than any other peacetime recession since the Great Contraction after 1929. Soon enough, analogies with the Great Depression were presented, and conclusions were drawn regarding the political response to the slump. This paper is an attempt to sort out real and false analogies and to present conclusions for policy. Its main hypothesis is that the Great Recession resembles the final phase of the Great Contraction between 1931 and 1933, characterized by a fast spreading global financial crisis and the breakdown of the international Gold Standard. The same is also true of the political responses to the banking problems occurring in both crises. The analogy seems less robust for the initial phase of the Great Depression after 1929. The monetary policy response to the Great Recession largely seems to be informed by the monetary interpretation of the Great Depression, but less so by the lessons from the interwar financial crises. As in the Great Depression, policy appears to be on a learning curve, moving away from a mostly monetary response toward mitigating counterpart risk and minimizing interbank contagion.
Symptoms of Delirium Occurring Before and After Episodes of Delirium in Older Long‐Term Care Residents
Authors: Cole Martin G. , McCusker Jane , Voyer Philippe , Monette Johanne , Champoux Nathalie , Ciampi Antonio , Vu Minh , Dyachenko Alina , Belzile Eric
Published: November 2012

Objective

To describe Confusion Assessment Method (CAM) core symptoms of delirium occurring before and after incident episodes of delirium in older long‐term care (LTC) residents. A secondary objective was to describe the mean number of symptoms before and after episodes by dementia status.

Design

Secondary analysis of data collected for a prospective cohort study of delirium, with repeated weekly assessments for up to 6 months.

Setting

Seven LTC facilities in Montreal and Quebec City, Canada.

Participants

Forty‐one older LTC residents who had at least one CAM‐defined incident episode of delirium.

Measurements

The Mini‐Mental State Examination (MMSE), CAM, Delirium Index (DI), Hierarchic Dementia Scale, Barthel Index, and Cornell Scale for Depression were completed at baseline. The MMSE, CAM, and DI were repeated weekly for 6 months. The frequency, mean number, type, and duration of CAM core symptoms of delirium occurring before and after incident episodes were examined using descriptive statistics, frequency analysis, and survival analysis.

Results

CAM core symptoms of delirium preceded 38 (92.7%) episodes of delirium for many weeks; core symptoms followed 37 (90.2%) episodes for many weeks. Symptoms of inattention and disorganized thinking occurred most commonly. The mean number of symptoms was higher in residents with dementia but not significantly so.

Conclusion

CAM core symptoms of delirium were frequent and protracted before and after most incident episodes of delirium in LTC residents with and without dementia. If replicated, these findings have potentially important implications for clinical practice and research in LTC settings.
Brand, Citationality, Performativity
Authors: Nakassis Constantine V.
Published: November 2012

ABSTRACT This article provides a semiotic account of the performativity of the brand. It argues that the brand's performativity is a function of its citationality: the ways in which (fractions of) brands are reanimated, or cited, while being reflexively marked as reanimations or citations. First the article argues that the intelligibility and coherence of brands turns on the calibration of a number of gaps in the brand's form: between brand tokens, brand types, and a brand ontology. Such calibration is achieved through moments of citing brand type and brand ontology. The article then discusses three forms of brand citationality that exceed the brand by situating themselves in, and exploiting, these gaps: brand counterfeits, “remixes,” and simulations. The article concludes by discussing the relation between citationality and performativity, arguing that the performativity of brand turns on the (meta‐)semiotics of citationality and the excesses it continually generates.