bluuebunny/crossref_metadata_2025 huggingface dataset:
Clarithromycin, a cytochrome P450 inhibitor, can reverse mefloquine resistance in Plasmodium yoelii nigeriensis- infected Swiss mice
Authors: TRIPATHI RENU , PANDEY SWAROOP KUMAR , RIZVI AMBER
Published: July 2011

During the last 2 decades there have been numerous reports of the emergence of mefloquine resistance in Southeast Asia and nearly 50% resistance is reported in Thailand. A World Health Organization report (2001) considers mefloquine as an important component of ACT (artesunate+mefloquine) which is the first line of treatment for the control of uncomplicated/multi-drug resistant (MDR) Plasmodium falciparum malaria. In view of the emergence of resistance towards this drug, it is proposed to develop new drug combinations to prolong the protective life of this drug. Prior studies have suggested that mefloquine resistance can be overcome by a variety of agents such as ketoconazole, cyproheptadine, penfluridol, Icajine and NP30. The present investigation reports that clarithromycin (CLTR), a new macrolide, being a potent inhibitor of Cyt. P450 3A4, can exert significant resistance reversal action against mefloquine resistance of plasmodia. Experiments were carried out to find out the curative dose of CLTR against multi-drug resistant P. yoelii nigeriensis. Mefloquine (MFQ) and clarithromycin (CLTR) combinations have been used for the treatment of this MDR parasite. Different dose combinations of these two drugs were given to the infected mice on day 0 (prophylactic) and day 1 with established infection (therapeutic) to see the combined effect of these combinations against the MDR malaria infection. With a dose of 32 mg/kg MFQ and 225 mg/kg CLTR, 100% cure was observed, while in single drug groups, treated with MFQ or CLTR, the cure was zero and 40% respectively. Therapeutically, MFQ and CLTR combinations 32+300 mg/kg doses cleared the established parasitaemia on day 10. Single treatment with MFQ or CLTR showed considerable suppression of parasitaemia on day 14 but neither was curative. Follow-up of therapeutically treated mice showed enhanced anti-malarial action as reflected by their 100% clearance of parasitaemia. The present study reveals that CLTR is a useful antibiotic to be used as companion drug with mefloquine in order to overcome mefloquine resistance in plasmodia.
Prevalence and co-infection of Toxoplasma gondii and Neospora caninum in Apodemus sylvaticus in an area relatively free of cats
Authors: THOMASSON D. , WRIGHT E. A. , HUGHES J. M. , DODD N. S. , COX A. P. , BOYCE K. , GERWASH O. , ABUSHAHMA M. , LUN Z.-R. , MURPHY R. G. , ROGAN M. T. , HIDE G.
Published: July 2011

The protozoan parasite Toxoplasma gondii is prevalent worldwide and can infect a remarkably wide range of hosts despite felids being the only definitive host. As cats play a major role in transmission to secondary mammalian hosts, the interaction between cats and these hosts should be a major factor determining final prevalence in the secondary host. This study investigates the prevalence of T. gondii in a natural population of Apodemus sylvaticus collected from an area with low cat density (<2·5 cats/km2). A surprisingly high prevalence of 40·78% (95% CI: 34·07%–47·79%) was observed despite this. A comparable level of prevalence was observed in a previously published study using the same approaches where a prevalence of 59% (95% CI: 50·13%–67·87%) was observed in a natural population of Mus domesticus from an area with high cat density (>500 cats/km2). Detection of infected foetuses from pregnant dams in both populations suggests that congenital transmission may enable persistence of infection in the absence of cats. The prevalences of the related parasite, Neospora caninum were found to be low in both populations (A. sylvaticus: 3·39% (95% CI: 0·12%–6·66%); M. domesticus: 3·08% (95% CI: 0·11%–6·05%)). These results suggest that cat density may have a lower than expected effect on final prevalence in these ecosystems.
Morphology and pathology of the ectoparasitic copepod, Nicothoë astaci (‘lobster louse’) in the European lobster, Homarus gammarus
Authors: WOOTTON EMMA C. , POPE EDWARD C. , VOGAN CLAIRE L. , ROBERTS EMILY C. , DAVIES CHARLOTTE E. , ROWLEY ANDREW F.
Published: July 2011

Ectoparasitic copepods have been reported in a wide range of aquatic animals, including crustacean shellfish. However, with the exception of the salmon louse, Lepeophtheirus salmonis, our knowledge of such parasites in commercial species is rudimentary. The current study examines the morphology and pathology of the parasitic copepod, Nicothoë astaci (the ‘lobster louse’) in its host, the European lobster, Homarus gammarus. Lobsters were sampled from waters surrounding Lundy Island (Bristol Channel, UK) and all individuals collected were found to harbour female adult N. astaci in their gills, with a mean of 47·3 parasites/lobster. The majority of N. astaci were found in the basal region of pleurobranch gills. The parasite was found to attach to gill filaments via its oral sucker, maxillae and maxillipeds, and to feed on host haemolymph (blood) through a funnel-like feeding channel. It caused varying degrees of damage to the host gill, including occlusion of gill filaments and disruption to the vascular system in the central axis. Although there was evidence of extensive host response (haemocytic infiltration) to the parasite, it was displaced from the parasite attachment site and thus was observed in the central gill axis below. The region of gill filament immediately underlying the parasite feeding channel was devoid of such activity suggesting that the parasite interferes with the cellular defence and haemostatic mechanisms of the lobster in order to maintain invasion of the host.
Male gametocyte fecundity and sex ratio of a malaria parasite, Plasmodium mexicanum
Authors: NEAL A. T.
Published: July 2011

Evolutionary theory predicts that the sex ratio of Plasmodium gametocytes will be determined by the number of gametes produced per male gametocyte (male fecundity), parasite clonal diversity and any factor that reduces male gametes' ability to find and combine with female gametes. Despite the importance of male gametocyte fecundity for sex ratio theory as applied to malaria parasites, few data are available on gamete production by male gametocytes. In this study, exflagellating gametes, a measure of male fecundity, were counted for 866 gametocytes from 26 natural infections of the lizard malaria parasite, Plasmodium mexicanum. The maximum male fecundity observed was 8, but most gametocytes produced 2–3 gametes, a value consistent with the typical sex ratio observed for P. mexicanum. Male gametocytes in infections with higher gametocytaemia had lower fecundity. Male fecundity was not correlated with gametocyte size, but differed among infections, suggesting genetic variation for fecundity. Fecundity and sex ratio were correlated (more female gametocytes with higher fecundity) as predicted by theory. Results agree with evolutionary theory, but also suggest a possible tradeoff between production time and fecundity, which could explain the low fecundity of this species, the variation among infections, and the correlation with gametocytaemia.
Asymptotic analysis of the eigenvalues of an elliptic problem in an anisotropic thin multidomain
Authors: Gaudiello Antonio , Sili Ali
Published: July 2011

We study, via an asymptotic analysis, an elliptic eigenvalue problem in a 1D–1D multidomain and in a 1D–2D multidomain filled with anisotropic material. The corresponding isotropic cases were considered in a previous work by Gaudiello and Sili.
Non-existence of radial backward self-similar blow-up solutions with sign change
Authors: Mizoguchi Noriko
Published: July 2011

We consider a Cauchy problem for a semilinear heat equation

with p > 1. If u(x, t) = (T − t)−1/(p−1)ϕ((T − t)−1/2x) for x ∈ ℝN and t ∈ [0, T),

where ϕ ∈ L∞(ℝN) is a solution not identically equal to zero of

then u is called a backward self-similar solution blowing up at t = T. We show that, for all p > 1, there exists no radial sign-changing solution of (E) which belongs to L∞(ℝN). This implies the non-existence of radial backward self-similar solution with sign change blowing up in finite time.
k-quasi-convexity reduces to quasi-convexity
Authors: Cagnetti Filippo
Published: July 2011

The relation between quasi-convexity and k-quasi-convexity, k ≥ 2, is investigated. It is shown that every smooth strictly k-quasi-convex integrand with p-growth at infinity, p > 1, is the restriction to kth-order symmetric tensors of a quasi-convex function with the same growth. When the smoothness condition is dropped, it is possible to prove an approximation result. As a consequence, lower semicontinuity results for kth-order variational problems are deduced as corollaries of well-known first-order theorems. This generalizes a previous work by Dal Maso et al., in which the case where k = 2 was treated.
Non-existence of global solutions for a class of wave equations with nonlinear damping and source terms
Authors: Wu Shun-Tang
Published: July 2011

An initial–boundary-value problem for a class of wave equations with nonlinear damping and source terms in a bounded domain is considered. We establish the non-existence result of global solutions with the initial energy controlled above by a critical value via the method introduced in a work by Autuori et al. in 2010. This improves the 2009 result of Liu and Wang.
Rearrangements of affine subspaces in vector spaces over finite fields
Authors: Carbery Anthony , Wilheim Daniel
Published: July 2011

We consider the Lp norms of sums of characteristic functions of affine subspaces of a vector space V over a finite field under certain restrictions on p, dim V and the dimensions of the subspaces involved. We investigate the conditions under which these norms are increased when the affine subspaces are replaced by their parallel translates passing through 0. Applications to extremal configurations for Kakeya maximal-type inequalities are given and open questions are raised.
Lq-almost solvability of inelastic models of monotone type
Authors: Nesenenko Sergiy
Published: July 2011

It is well known that the loss of the coerciveness for governing monotone nonlinearities in evolution equations/inclusions can lead to the problem having no solution for given data, and the rule for choosing appropriate data has to be prescribed. Allowing constitutive functions in the evolution relations for elasto-/visco-plastic models of monotone type to be non-coercive, we first give a new (relaxed) meaning to the solvability of the systems of equations under consideration and then we define criteria for choosing admissible data, which guarantees the solvability in the defined sense. Realizing this strategy, a slight extension of the well-developed monotone-operator method to our needs is performed. The theory is applied to some well-known models in elasto-/visco-plasticity. The relations between the standard notion of the solvability and defined one are investigated.
On generalized geometric domain-wall models
Authors: Zhang Ruifeng , Wang Xiaojing
Published: July 2011

We study domain walls that are topological solitons in one dimension. We present an existence theory for the solutions of the basic governing equations of some extended geometrically constrained domain-wall models. When the cross-section and potential density are both even, we establish the existence of an odd domain-wall solution realizing the phase-transition process between two adjacent domain phases. When the cross-section satisfies a certain integrability condition, we prove that a domain-wall solution always exists that links two arbitrarily designated domain phases.
Normalizing the development of cortisol regulation in maltreated infants through preventive interventions
Authors: Cicchetti Dante , Rogosch Fred A. , Toth Sheree L. , Sturge-Apple Melissa L.
Published: July 2011

Longitudinal effects of child maltreatment on cortisol regulation in infants from age 1 to 3 years were investigated in the context of a randomized preventive intervention trial. Thirteen-month-old infants from maltreating families (N= 91) and their mothers were randomly assigned to one of three intervention conditions: child–parent psychotherapy, psychoeducational parenting intervention, and a control group involving standard community services (CS). A fourth group of infants from nonmaltreating families (N= 52) and their mothers comprised a nonmaltreated comparison (NC) group. The two active interventions were combined into one maltreated intervention (MI) group for statistical analyses. Saliva samples were obtained from children at 10:00 a.m. before beginning a laboratory observation session with their mothers when the children were 13 months of age (preintervention), 19 months (midintervention), 26 months (postintervention), and 38 months (1-year postintervention follow-up). At the initial assessment, no significant differences among groups in morning cortisol were observed. Latent growth curve analyses examined trajectories of cortisol regulation over time. Beginning at midintervention, divergence was found among the groups. Whereas the MI group remained indistinguishable from the NC group across time, the CS group progressively evinced lower levels of morning cortisol, statistically differing from the MI and NC groups. Results highlight the value of psychosocial interventions for early child maltreatment in normalizing biological regulatory processes.
The impact of allostatic load on maternal sympathovagal functioning in stressful child contexts: Implications for problematic parenting
Authors: Sturge-Apple Melissa L. , Skibo Michael A. , Rogosch Fred A. , Ignjatovic Zeljko , Heinzelman Wendi
Published: July 2011

The present study applies an allostatic load framework to an examination of the relationship between maternal psychosocial risk factors and maladaptive parenting behaviors. Specifically, the implications of low socioeconomic status and maternal depressive symptoms for maternal sympathovagal functioning during young children's distress were examined, as well as whether that functioning was, in turn, associated with maternal insensitivity, hostility, intrusiveness, and disengagement during mother–child dyadic interaction. Consistent with an allostatic framework, three patterns of sympathovagal functioning were expected to emerge: normative arousal, hyperarousal, and hypoarousal profiles. Furthermore, meaningful associations between maternal psychosocial risk factors, maladaptive parenting behaviors, and the three profiles of sympathovagal functioning were anticipated. Participants included 153 mother–toddler dyads recruited proportionately from lower and middle socioeconomic status backgrounds. Mothers’ sympathovagal response to their child's distress was assessed during the Strange Situation paradigm, and mothers’ parenting behavior was assessed during a dyadic free-play interaction. As hypothesized, normative arousal, hyperarousal, and hypoarousal profiles of maternal sympathovagal functioning were identified. Maternal depressive symptomatology predicted the hyperarousal profile, whereas socioeconomic adversity predicted hypoarousal. Moreover, allostatic load profiles were differentially associated with problematic parenting behaviors. These findings underscore the role of physiological dysregulation as a mechanism in the relationship between proximal risk factors and actual maladaptive parenting behaviors.
Allostasis and allostatic load in the context of poverty in early childhood
Authors: Blair Clancy , Raver C. Cybele , Granger Douglas , Mills-Koonce Roger , Hibel Leah ,   The Family Life Project Key Investigators
Published: July 2011

This paper examined the relation of early environmental adversity associated with poverty to child resting or basal level of cortisol in a prospective longitudinal sample of 1135 children seen at 7, 15, 24, 35, and 48 months of age. We found main effects for poor housing quality, African American ethnicity, and low positive caregiving behavior in which each was uniquely associated with an overall higher level of cortisol from age 7 to 48 months. We also found that two aspects of the early environment in the context of poverty, adult exits from the home and perceived economic insufficiency, were related to salivary cortisol in a time-dependent manner. The effect for the first of these, exits from the home, was consistent with the principle of allostatic load in which the effects of adversity on stress physiology accumulate over time. The effect for perceived economic insufficiency was one in which insufficiency was associated with higher levels of cortisol in infancy but with a typical but steeper decline in cortisol with age at subsequent time points.
Maternal responsiveness moderates the relationship between allostatic load and working memory
Authors: Doan Stacey N. , Evans Gary W.
Published: July 2011

A substantial amount of research has demonstrated the deleterious effects of chronic stress on memory. However, much less is known about protective factors. In the current study we test the role of maternal responsiveness in buffering the effects of childhood allostatic load on subsequent adolescent working memory. Allostatic load is a marker of cumulative stress on the body that is caused by mobilization of multiple physiological systems in response to chronic environmental demands. Results of the study suggest that allostatic load negatively affects working memory, but that this effect is significantly attenuated in children with responsive mothers.
Hypocortisolism as a potential marker of allostatic load in children: Associations with family risk and internalizing disorders
Authors: Badanes Lisa S. , Watamura Sarah Enos , Hankin Benjamin L.
Published: July 2011

Although the majority of research attention to the hypothalamic–pituitary–adrenal (HPA) axis in stress-related disorders and as a marker of allostatic load has focused on overactivation of this stress system, theory and data clearly indicate that underactivation is also an important type of dysregulation. In the current study we focused on low cortisol, exploring a constellation of risk factors including stress exposure, maternal depression, and attenuated basal and stress reactive cortisol in two samples of children. The first sample was comprised of 110 preschoolers living in high-stress environments. Cortisol was assessed across the day at home and at child care as well as across two stress paradigms. These data were used to classify whether children's HPA axis activity was attenuated. Serious family financial strain, maternal depression, and attenuated cortisol all made unique contributions in models predicting current clinical levels of internalizing symptoms as rated by mothers and teachers. The second sample was 166 third, sixth, and ninth graders studied five times across a 1-year period. Maternal and child depression were determined through structured clinical interviews, and stress exposure was assessed via checklist and interview techniques with the child and parent. Cortisol was assessed multiple times across a lab visit at Time 1, and these data were combined into a single continuous measure. Cortisol concentrations across the lab visit interacted with stress exposure across the year such that children with lower average cortisol at Time 1 and increased stress across the 12 months showed elevated levels of internalizing symptoms. Based on these and related data we propose that prior to puberty low cortisol may be an important marker of allostatic load, particularly for risk of depression and anxiety.
Social encounters in daily life and 2-year changes in metabolic risk factors in young women
Authors: Ross Kharah , Martin Tara , Chen Edith , Miller Gregory E.
Published: July 2011

Research shows that poor social ties increase risks of morbidity and mortality from cardiovascular disease (CVD). However, little is known about the nature of everyday social encounters that give rise to this association, or when in the course of development they begin to shape disease-relevant biological processes. In this study, 122 adolescent females recorded the qualities of their everyday social interactions using electronic diaries. At the same time we measured components of the metabolic syndrome, a precursor to CVD that includes central adiposity, high blood pressure, insulin resistance, and lipid dysregulation. Metabolic symptoms were reassessed 12 and 24 months later. Hierarchical linear modeling revealed an association between negative social interactions and metabolic symptom trajectories. To the extent that participants had more intense negative social encounters in daily life, they showed increasing scores on a composite indicator of metabolic risk over 2 years. This association was independent of a variety of potential confounders, and persisted when symptoms of depression and broader personality traits were controlled. There was no association between positive social encounters and metabolic risk trajectories. These findings suggest that even in otherwise healthy adolescents, abrasive social encounters may accelerate the progression of early stages of CVD.
Neuropsychologische Modelle von Autismus-Spektrum-Störungen
Authors: Dziobek Isabel , Bölte Sven
Published: July 2011

Fragestellung: Der Artikel gibt einen Überblick über die Modelle der Theory of Mind (ToM), Exekutivfunktionen (EF) und Zentralen Kohärenz (ZK), welche die neuropsychologischen Auffälligkeiten bei Menschen mit Autismus-Spektrum Störungen (ASS) treffend zu beschreiben vermögen. Methodik: In einem selektiven Review werden Ergebnisse behavioraler und funktionell-bildgebender Arbeiten zu den sozial-kognitiven, emotionalen und exekutiven Funktionen sowie der lokal-orientierten Wahrnehmung bei ASS berichtet. Ergebnisse: Beeinträchtigungen in ToM und EF sowie Besonderheiten in ZK sind vielfach replizierte Phänomene bei ASS. Vor allem soziale Wahrnehmungsprobleme und ToM haben einen hohen Erklärungswert für die klinische Symptomatik von ASS. Cerebrale Aktivierungsmuster unterscheiden sich bei Menschen mit und ohne ASS für ToM, EF und ZK. Als übergeordnetes neurales Erklärungsmodell scheint sich verringerte Konnektivität rekrutierter kortikaler Netzwerke gegen das Konzept einzelner betroffener Gehirnareale durchzusetzen. Schlussfolgerungen: Für ein besseres Verständnis der komplexen Zusammenhänge bei ASS ist eine zukünftige Integration klinischer, neuropsychologischer, funktionell-bildgebender und molekulargenetischer Befunde essenziell. Schwächen bei ToM und EF sowie Stärken in den Bereichen detail-orientierte Wahrnehmung sollten bei der individuellen Interventionsplanung verstärkt Eingang finden.
Komorbiditäten bei Autismus-Spektrum-Erkrankungen
Authors: Sinzig Judith , Lehmkuhl Gerd
Published: July 2011

Zahlreiche körperliche und psychopathologische Störungsbilder treten häufig bei Autismus-Spektrum-Erkrankungen auf. Derzeit wird diskutiert, ob zusätzlich auftretende psychopathologische Symptome eine eigene kategoriale komorbide Störung darstellen und als solche diagnostiziert werden dürfen oder ob sie als Teil der autistischen Störung zu verstehen sind. Anhand der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) wird ausgehend vom aktuellen Forschungsstand und eigener Forschungsergebnisse beispielhaft dargestellt, welche Voraussetzung für eine komorbide Störung erfüllt sein sollten und welche Bedingungen sich aufgrund neurobiologischer Ergebnisse aus dem Bereich der Molekularbiologie, Neuropsychologie und Bildgebung für Ätiologie, Früherkennung, pharmakologische und psychotherapeutische Behandlung, Verlauf und den kategorialen Klassifikationsansatz ergeben.
Genetische Analysen zur Identifizierung molekularer Mechanismen bei Autismus-Spektrum-Störungen
Authors: Chiocchetti Andreas , Klauck Sabine M.
Published: July 2011

Autismus-Spektrum-Störungen (ASS) sind neuronale Entwicklungsstörungen mit Auswirkung auf Kommunikation, Sprachentwicklung und Verhalten. Der komplexe Phänotyp und die starke klinische Heterogenität lassen bei erhöhter Disposition von ASS unter Geschwistern auf einen multifaktoriellen genetischen Hintergrund schließen. Neben einzelnen seltenen Mutationen werden auch Genkopie-Varianten und Einzelnukleotid-Polymorphismen immer mehr als Risikofaktoren in Betracht gezogen. Zur Identifizierung zentraler Schlüsselmechanismen werden im Rahmen von Konsortien Kopplungsanalysen und genomweite Assoziationsstudien durchgeführt. Außer polygenen bzw. genetisch komplexen Modellen, denen ASS zugrunde liegt, gibt es auch monogenetisch bedingte Formen. Dabei kommt es durch Aberrationen an einzelnen Genen zu einem autistischen Phänotyp, wie z. B. beim Fragilen-X-Syndrom. Knockout-Tiermodelle für monogenetischen Autismus wie FMRP–/– oder für neurodegenerative Erkrankungen wie MeCP2–/– werden häufig zur Untersuchung der molekularen Mechanismen herangezogen, welche bei ASS gestört sein könnten. Hier geben wir einen Einblick in den Stand der aktuellen Forschung im Bereich der Genomanalyse und beschreiben die wichtigsten Mausmodelle im Hinblick auf die Erkenntnisse bei poly- und monogenetischem Autismus. Grundsätzlich kann man erkennen, dass die meisten assoziierten Genomregionen und Gene im Zusammenhang mit der Ausbildung des synaptischen Spalts, der korrekten Sekretion von Oberflächenmolekülen oder der Translation stehen. Dies lässt vermuten, dass der Phänotyp bei ASS vorrangig durch eine Störung der translationsabhängigen Zell-Zell-Konnektivität und synaptischen Plastizität hervorgerufen wird.
Selbst- und Fremdbeurteilung der Empathie bei Jugendlichen mit Autismus
Authors: Greimel Ellen , Schulte-Rüther Martin , Kamp-Becker Inge , Remschmidt Helmut , Herpertz-Dahlmann Beate , Konrad Kerstin
Published: July 2011

Fragestellung: Ein Empathiedefizit wird häufig als ein zentrales Charakteristikum autistischer Störungen beschrieben. Bislang ist unzureichend erforscht, wie Jugendliche mit Autismus ihre Empathiefähigkeiten selbst einschätzen bzw. wie diese Fähigkeiten von ihren Eltern beurteilt werden. Ziel der Studie war, affektive Aspekte der Empathie bei gesunden Jugendlichen und Jugendlichen mit Autismus sowohl im Selbsturteil als auch im Fremdurteil der Eltern zu erfassen. Methodik: An der Studie nahmen 18 Jungen mit Autismus sowie 18 gesunde Jungen im Alter von 12–17 Jahren teil. Für die Selbstbeurteilung empathischer Fähigkeiten wurde eine deutsche Übersetzung des Bryant Index of Empathy eingesetzt. Elternbeurteilungen der Empathie wurden mittels einer deutschen Fassung des Griffith Empathy Measure eingeholt. Beide Fragebögen erfassen schwerpunktmäßig affektive Komponenten der Empathie und sind inhaltlich miteinander vergleichbar. Ergebnisse: Während sich zwischen der Autismus- und der Kontrollgruppe keine Unterschiede im Selbsturteil zeigten, wurden Jugendliche mit Autismus von ihren Eltern als weniger empathisch eingestuft als gesunde Jugendliche. Schlussfolgerungen: Die Diskrepanz zwischen unbeeinträchtigter Empathie im Selbsturteil und Empathiedefiziten im Fremdurteil bei Jugendlichen mit Autismus könnte darauf zurückzuführen sein, dass die Betroffenen zwar nach innen gerichtete empathische Reaktionen zeigen, diese aber nicht wirksam nach außen vermitteln. Zum anderen könnten die Unterschiede möglicherweise in einer eingeschränkten Introspektionsfähigkeit von Menschen mit Autismus begründet sein.
Health-Related Quality of Life in Children and Adolescents with Autism Spectrum Disorder
Authors: Kamp-Becker Inge , Schröder Johanna , Muehlan Holger , Remschmidt Helmut , Becker Katja , Bachmann Christian J.
Published: July 2011

Objective: This study evaluates self- and proxy-reported health-related quality of life (HRQOL) in children and adolescents with autism spectrum disorders (ASD). The study also compares HRQOL in ASD patients with a healthy control sample and a psychiatric reference sample. Method: 42 children and adolescents (39 male, mean age: 12.7 ± 2.6 years, mean IQ: 100.5 ± 20.7) with the diagnosis of autism spectrum disorder (ASD) and their parents completed the Inventory for the Assessment of Quality of Life in Children and Adolescents (ILK). Results: Mean ILK LQ 0–28 scores were 20.6 (± 4.6) (self-report version) and 18.2 (± 4.0) (proxy version). Compared to a reference sample, mean ILK scores from the ASD sample were at the 47th percentile (self-report) and the 33rd percentile (proxy). Compared to children and adolescents with psychiatric disorders, self-reported ILK scores correlated with the 69th percentile, and proxy-reported ILK scores correlated with the 67th percentile. Self-reported HRQOL was significantly higher than proxy-reported HRQOL. No significant correlation was found between HRQOL and age, IQ, or autistic symptoms. Conclusions: HRQOL in children and adolescents with ASD seems to be better than in other psychiatric disorders, but lower than in healthy controls.
Familienkohärenz und Resilienz bei Eltern von Kindern mit intellektueller Behinderung
Authors: Doege Daniela , Aschenbrenner Regina M. , Nassal Angela , Holtz Karl-Ludwig , Retzlaff Rüdiger
Published: July 2011

Zusammenfassung. Das Familien-Kohärenzgefühl (FSOC) gilt als wichtige salutogene Ressource für Familien, die durch die intellektuelle Behinderung eines Kindes einer anhaltenden Belastung und erschwerten Lebensumständen ausgesetzt sind. In einer Studie mit 327 Familien von Kindern mit intellektueller Behinderung wurden das Familien-Kohärenzgefühl, die Familienfunktionen, selbstberichteter Stress und das Bewältigungsverhalten untersucht. Zusätzlich wurden Maße für die praktischen, kognitiven und sozialen Kompetenzen und Verhaltensauffälligkeiten mit dem Heidelberger Kompetenzinventar erhoben. Bezüglich der Reliabilität und Validität erwies sich die deutsche Fassung des FSOC-Fragebogens als vergleichbar mit der Originalfassung von Antonovsky. Faktoranalysen ergaben, dass die Unterskalen Verstehbarkeit, Handhabbarkeit und Sinnhaftigkeit interkorreliert sind und damit nicht getrennt voneinander interpretiert werden dürfen. In Regressionsanalysen zeigte sich das FSOC als stärkster Prädiktor von elterlichem Stress. Die Ergebnisse dieser Studie bestätigen die Bedeutung von Familienprozessen für die Adaptation an das Leben mit der intellektuellen Behinderung eines Kindes und sprechen für eine weitere Untersuchung des Konzeptes der Familien-Kohärenz.
Mittelfristige Effekte des Präventionsprogramms EFFEKT-E für emotional belastete Mütter und ihre Kinder unter besonderer Berücksichtigung psychosozialer Risikofaktoren
Authors: Kötter Charlotte , Stemmler Mark , Lösel Friedrich , Bühler Anneke , Jaursch Stefanie
Published: July 2011

Zusammenfassung. Kinder (subklinisch) depressiver Mütter haben ein erhöhtes Risiko, Verhaltensauffälligkeiten auszubilden. Einige der Faktoren der Transmission liegen direkt in der Interaktion, wie das Erziehungsverhalten. Weitere Risikofaktoren wie Alleinerziehendenstatus oder geringe soziale Unterstützung können die Auswirkungen auf die Kinder noch verstärken. Da Erlebens- und Verhaltensprobleme häufig bereits im Vorschulalter auftreten, sollten Präventionsprogramme möglichst früh ansetzen. Dem folgt die vorliegende Studie, die in 13 Mutter-Kind-Kliniken durchgeführt wurde. Geprüft wurde, ob Kinder von emotional und sozial belasteten Müttern von einem Präventionsprogramm (EFFEKT-E) profitieren, das einen Erziehungskurs für Mütter und ein soziales Kompetenztraining für Kinder umfasst. Dazu wurden 194 Mütter mit 4- bis 7-jährigen Kindern in der Kontrollgruppe und 169 Mütter in der Interventionsgruppe in einem Vortest-Nachtest-Design untersucht. Abhängige Variablen waren kindliche Erlebens- und Verhaltensprobleme sowie das mütterliche Erziehungsverhalten und Kompetenzerleben. Neben allgemeinen Effekten wurden eventuelle Moderatoreffekte von mütterlichen Risikofaktoren geprüft. Es zeigten sich positive kurzfristige Effekte auf das kindliche Problemverhalten. Mittelfristige positive Effekte gab es bei der elterlichen Kompetenzeinschätzung (Sechs-Monats-Follow-up). Dies galt insbesondere für Mütter, die eine hohe soziale Unterstützung erlebten. Die Ergebnisse werden unter methodischen und praktischen Gesichtspunkten diskutiert.
Localized bedrock aquifer distribution explains discharge from a headwater catchment
Authors: Kosugi Ken'ichirou , Fujimoto Masamitsu , Katsura Shin'ya , Kato Hiroyuki , Sando Yoshiki , Mizuyama Takahisa
Published: July 2011

Understanding a discharge hydrograph is one of the leading interests in catchment hydrology. Recent research has provided credible information on the importance of bedrock groundwater on discharge hydrographs from headwater catchments. However, intensive monitoring of bedrock groundwater is rare in mountains with steep topography. Hence, how bedrock groundwater controls discharge from a steep headwater catchment is in dispute. In this study, we conducted long‐term hydrological observations using densely located bedrock wells in a headwater catchment underlain by granitic bedrock. The catchment has steep topography affected by diastrophic activities. Results showed a fairly regionalized distribution of bedrock aquifers within a scale of tens of meters, consisting of upper, middle, and lower aquifers, instead of a gradual and continuous decline in water level from ridge to valley bottom. This was presumably attributable to the unique bedrock structure; fault lines developed in the watershed worked to form divides between the bedrock aquifers. Spatial expanse of each aquifer and the interaction among aquifers were key factors to explain gentle and considerable variations in the base flow discharge and triple‐peak discharge responses of the observed hydrograph. A simple model was developed to simulate the discharge hydrograph, which computed each of the contributions from the soil mantle groundwater, from the lower aquifer, and from the middle aquifer to the discharge. The modeling results generally succeeded in reproducing the observed hydrograph. Thus, this study demonstrated that understanding regionalized bedrock aquifer distribution is pivotal for explaining discharge hydrograph from headwater catchments that have been affected by diastrophic activities.
Global food security and the governance of modern biotechnologies
Authors: Tait Joyce , Barker Guy
Published: July 2011

Food security has become a serious issue for governments around the world. Europe stands to have a key role, but the European Union will need to change its policies on plant biotechnology to do so.
Regulatory RNAs and beyond
Authors: Hammann Christian , Hartmann Roland K , Helm Mark , Klostermeier Dagmar , Marchfelder Anita , Suess Beatrix , Vörtler Stefan
Published: July 2011

The dynamic regulation of biological processes by RNA has emerged as an important field in recent years, and was the topic of the 62nd Mosbacher Colloquium of the German Society for Biochemistry and Molecular Biology, held in April 2011.
Docking interactions of the JNK scaffold protein WDR62
Authors: Cohen-Katsenelson Ksenya , Wasserman Tanya , Khateb Samer , Whitmarsh Alan J. , Aronheim Ami
Published: July 2011

JNK (c-Jun N-terminal kinase) is part of a MAPK (mitogen-activated protein kinase) signalling cascade. Scaffold proteins simultaneously associate with various components of the MAPK signalling pathway and play a crucial role in signal transmission and MAPK regulation. WDR62 (WD repeat domain 62) is a JNK scaffold protein. Recessive mutations within WDR62 result in severe cerebral cortical malformation. In the present study we demonstrate the association of WDR62 with endogenous and overexpressed proteins of both JNK2 and the JNK2-activating kinase MKK7 (MAPK kinase 7). Association of WDR62 with JNK2 and MKK7 occurs via direct protein–protein interactions. We mapped the docking domain of WDR62 responsible for the association with JNK. WDR62 interacts with all JNK isoforms through a D domain motif located at the C-terminus. A WDR62 mutant lacking the putative JNK-binding domain fails to activate and recruit JNK to cellular granules. Furthermore, a synthetic peptide composed of the WDR62 docking domain inhibits JNK2 activity in vitro. WDR62 association with JNK2 requires both the JNK CD and ED domains, and the binding requisite is distinct from that of the previously described JNK2 association with JIP1 (JNK-interacting protein 1). Next, we characterized the association between WDR62 and MKK7. WDR62 associates directly with the MKK7β1 isoform independently of JNK binding, but fails to interact with MKK7α1. Furthermore, MKK7β1 recruits a protein phosphatase that dephosphorylates WDR62. Interestingly, a premature termination mutation in WDR62 that results in severe brain developmental defects does not abrogate WDR62 association with either JNK or MKK7. Therefore such mutations represent a loss of WDR62 function independent of JNK signalling.
Inhibition of the chlorinating activity of myeloperoxidase by tempol: revisiting the kinetics and mechanisms
Authors: Queiroz Raphael F. , Vaz Sandra M. , Augusto Ohara
Published: July 2011

The nitroxide tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) reduces tissue injury in animal models of inflammation by mechanisms that are not completely understood. MPO (myeloperoxidase), which plays a fundamental role in oxidant production by neutrophils, is an important target for anti-inflammatory action. By amplifying the oxidative potential of H2O2, MPO produces hypochlorous acid and radicals through the oxidizing intermediates MPO-I [MPO-porphyrin•+-Fe(IV)=O] and MPO-II [MPO-porphyrin-Fe(IV)=O]. Previously, we reported that tempol reacts with MPO-I and MPO-II with second-order rate constants similar to those of tyrosine. However, we noticed that tempol inhibits the chlorinating activity of MPO, in contrast with tyrosine. Thus we studied the inhibition of MPO-mediated taurine chlorination by tempol at pH 7.4 and re-determined the kinetic constants of the reactions of tempol with MPO-I (k=3.5×105 M−1·s−1) and MPO-II, the kinetics of which indicated a binding interaction (K=2.0×10−5 M; k=3.6×10−2 s−1). Also, we showed that tempol reacts extremely slowly with hypochlorous acid (k=0.29 and 0.054 M−1·s−1 at pH 5.4 and 7.4 respectively). The results demonstrated that tempol acts mostly as a reversible inhibitor of MPO by trapping it as MPO-II and the MPO-II–tempol complex, which are not within the chlorinating cycle. After turnover, a minor fraction of MPO is irreversibly inactivated, probably due to its reaction with the oxammonium cation resulting from tempol oxidation. Kinetic modelling indicated that taurine reacts with enzyme-bound hypochlorous acid. Our investigation complements a comprehensive study reported while the present study was underway [Rees, Bottle, Fairfull-Smith, Malle, Whitelock and Davies (2009) Biochem. J. 421, 79–86].
Diurnal variability in orthostatic tachycardia: implications for the postural tachycardia syndrome
Authors: Brewster Jordan A. , Garland Emily M. , Biaggioni Italo , Black Bonnie K. , Ling John F. , Shibao Cyndya A. , Robertson David , Raj Satish R.
Published: July 2011

Patients with POTS (postural tachycardia syndrome) have excessive orthostatic tachycardia (>30 beats/min) when standing from a supine position. HR (heart rate) and BP (blood pressure) are known to exhibit diurnal variability, but the role of diurnal variability in orthostatic changes of HR and BP is not known. In the present study, we tested the hypothesis that there is diurnal variation of orthostatic HR and BP in patients with POTS and healthy controls. Patients with POTS (n=54) and healthy volunteers (n=26) were admitted to the Clinical Research Center. Supine and standing (5 min) HR and BP were obtained in the evening on the day of admission and in the following morning. Overall, standing HR was significantly higher in the morning (102±3 beats/min) than in the evening (93±2 beats/min; P<0.001). Standing HR was higher in the morning in both POTS patients (108±4 beats/min in the morning compared with 100±3 beats/min in the evening; P=0.012) and controls (89±3 beats/min in the morning compared with 80±2 beats/min in the evening; P=0.005) when analysed separately. There was no diurnal variability in orthostatic BP in POTS. A greater number of subjects met the POTS HR criterion in the morning compared with the evening (P=0.008). There was significant diurnal variability in orthostatic tachycardia, with a great orthostatic tachycardia in the morning compared with the evening in both patients with POTS and healthy subjects. Given the importance of orthostatic tachycardia in diagnosing POTS, this diurnal variability should be considered in the clinic as it may affect the diagnosis of POTS.
Exaggerated natriuresis during clamping of systemic NO supply in healthy young men
Authors: Simonsen Jane A. , Rasmussen Mona S. , Vach Werner , Høilund-Carlsen Poul F. , Bie Peter
Published: July 2011

NO (nitric oxide) may be involved in fluid homoeostasis. We hypothesized that increases in NO synthesis contribute to acute, saline-induced natriuresis, which, therefore, should be blunted when NO availability is stabilized. Young men were studied during simultaneous infusions of L-NAME [NG-nitro-L-arginine methyl ester; bolus of 750 μg·kg−1 of body weight and 8.3 μg·min−1·kg−1 of body weight] and SNP (sodium nitroprusside), the latter at a rate preventing L-NAME from increasing total peripheral resistance (‘NO-clamping’). Slow volume expansion (saline, 20 μmol of NaCl·min−1·kg−1 of body weight for 3 h) was performed with and without concomitant NO-clamping. NO-clamping itself decreased RPF (renal plasma flow; P~0.02) and tended to decrease arterial blood pressure [MABP (mean arterial blood pressure)]. Volume expansion markedly decreased the plasma levels of renin, AngII (angiotensin II) and aldosterone (all P<0.001), while MABP (oscillometry), heart rate, cardiac output (impedance cardiography), RPF (by p-aminohippurate), GFR [glomerular filtration rate; by using 51Cr-labelled EDTA] and plasma [Na+] and [K+] remained constant. Volume expansion increased sodium excretion (P<0.02) at constant filtered load, but more so during NO-clamping than during control (+184% compared with 52%; P<0.0001). Urinary nitrate/nitrite excretion increased during volume expansion; plasma cGMP and plasma vasopressin were unchanged. The results demonstrate that NO-clamping augments sodium excretion in response to volume expansion at constant MABP and GFR, reduced RPF and decreased renin system activity, a response termed hypernatriuresis. The results indicate that mediator(s) other than MABP, RPF, GFR and renin system activity contribute significantly to the homoeostatic response to saline loading, but the specific mechanisms of hypernatriuresis remain obscure.
A compact post-acceleration scheme for laser-generated protons
Authors: Antici P. , Migliorati M. , Mostacci A. , Picardi L. , Palumbo L. , Ronsivalle C.
Published: July 2011

Protons generated by irradiating a thin metal foil with a high-intensitylaser have shown to posses interesting characteristics in terms of energy, emittance, current, and pulse duration. Therefore, in the near future, they might become a competitive source with respect to conventional proton sources. Previous theoretical, numerical, and experimental studies have already demonstrated efficient coupling between laser-accelerated proton beams with traditional radio frequency (RF)-based particle accelerators. These hybrid proton accelerators benefit from both the excellent properties of the laser-based source and the flexibility, reliability, and know-how of beam handling as provided by RF-based accelerator structures. In this paper, state of the art experimental results of laser-accelerated proton beams are used as input for a numerical study using compact and innovative conventional accelerator structures designed for medical applications. Results show that this compact hybrid accelerator allows even more efficient capture and acceleration of the laser-generated proton beam.
Passive acoustic diagnostics of an atmospheric pressure linear field jet including analysis in the time-frequency domain
Authors: O’Connor N. , Daniels S.
Published: July 2011

This study presents the results of passive acoustic diagnostics of an atmospheric pressure linear field jet source operating inflowing helium. Variations of the electrical, optical and acoustic parameters of the source are monitored with respect to changing gas flow rate [0.5–7 liters per minute (lpm)] and applied voltage amplitude (3.5–7 kV). It was found that the jet length and coupled power were maximized when the jet flow was laminar. Flow mode transitions (buoyant, laminar and turbulent) associated with the jet Richardson number could easily be distinguished acoustically through their unique wavelet scalograms. Each scalogram can also be explained through qualitative correlation with the discharge electrical parameters. As the jet became turbulent, low frequency oscillation (c. 180 Hz) bursts were present in the time-frequency trace which were compared to an empirical relation for the Richardson number in the case of flow induced oscillations. It was found that the frequency value correlated well with the frequency of 200 Hz determined from literature. Anomalous sparking events were detected which manifested as almost constant magnitude, broadband acoustic transients in the time-frequency domain. Comparisons between the average acoustic output power and the average dissipated power from the discharge at two different flow rates (4 lpm and 2 lpm) reveal an approximately equal linear trend for a fixed microphone-discharge placement while in the laminar flow regime. Due to the increased turbulence induced noise, however, no such linear correlation could be drawn. Finally, optical emission spectra from the discharge at a point 8 mm downstream of the plume exit were taken and correlations drawn for each flow regime.
The third-order nonlinear optical coefficients of Si, Ge, and Si1−xGex in the midwave and longwave infrared
Authors: Hon Nick K. , Soref Richard , Jalali Bahram
Published: July 2011

Using a combination of semiconductor theory and experimental results from the scientific literature, we have compiled and plotted the key third-order nonlinear optical coefficients of bulk crystalline Si and Ge as a function of wavelength (1.5−6.7 μm for Si and 2–14.7 μm for Ge). The real part of third-order nonlinear dielectric susceptibility (χ(3)′), the two-photon absorption coefficient (βTPA), and the Raman gain coefficient (gR), have been investigated. Theoretical predictions were used to curve-fit the experimental data. For a spectral range in which no experimental data exists, we estimate and fill in the missing knowledge. Generally, these coefficient-values appear quite useful for a host of device applications, both Si and Ge offer large χ(3)′ and gR with Ge offering the stronger nonlinearity. In addition, we use the same theory to predict the third-order nonlinear optical coefficients of Si1−xGex alloy. By alloying Si and Ge, device designers can gain flexibility in tuning desired optical coefficients in between the two fundamental components based upon their application requirements.
Effects of metal contacts and dopants on the performance of ZnO-based memristive devices
Authors: Qiu Julia , Shih Andy , Zhou Wendi , Mi Zetian , Shih Ishiang
Published: July 2011

We have performed a detailed investigation of the fabrication and switching characteristics of ZnO-based memristive devices. The effects of doping and various metal contacts have been studied. It is observed that, with the use of Al metal contacts and ZnO:Al layers, relatively high ROFF/RON ratios of 200 can be achieved. Much improved device stability and reproducibility, on the other hand, can be realized by using either nominally undoped or Mg-doped ZnO memristive layers. The experimental results may be well explained by an oxygen vacancy formation and migration model. The present work represents an important step in realizing high performance ZnO-based memristive devices for future nonvolatile memory applications.