bluuebunny/crossref_metadata_2025 huggingface dataset:
The haphazard approach to the early detection of asymptomatic renal cancer: results from a contemporary executive health programme
Authors: Feldstein Murray S. , Rhodes Deborah J. , Parker Alex S. , Orford Robert R. , Castle Erik P.
Published: January 2009

OBJECTIVE

To compare the detection of asymptomatic renal cell carcinoma (RCC) in an executive health programme (EHP) that uses traditional methods of screening (history, physical examination and urine analysis) to programmes that screen by renal imaging.

PATIENTS AND METHODS

We retrospectively reviewed case records from patients undergoing executive health examinations at Mayo Clinic between 1 January 2002 and 30 September 2007.

Results

Of 32 310 patients, 18 RCCs were detected; of these, 13 (72%) were detected by the EHP and five (28%) were missed by the initial EHP screening process but subsequently discovered within 4–24 months. Of the 13 detected through the EHP, eight were discovered incidentally, two because of symptoms, and three because of asymptomatic microscopic haematuria (AMH). Of the 13, 12 were classified as early‐stage cancers (Stage I). By contrast, of the five cancers missed by the EHP screening process, two were diagnosed because of the development of symptoms and only one was classified as Stage I. To date, two of these patients whose cancers were undetected by the EHP developed metastasis and one of them has died. Both had been followed in the EHP for years and neither had MH in multiple specimens.

CONCLUSION

Our EHP follows standard policy and relies on a history, physical examination and urine analysis to decide who to evaluate for asymptomatic RCC. This practice missed >70% of the potentially diagnosable cancers. The patients with RCCs that were discovered initially by the EHP fared better than those whose diagnosis was delayed. Our detection rate of four per 10 000 was only a fraction of those reported by programmes using imaging as a screening tool. The logic behind our current approach to the early detection of asymptomatic RCC needs to be reassessed. AMH is coincidental in most cases and patients could forego imaging if they are unsuitable candidates for screening. However, AMH will miss most treatable cancers and is not an appropriate screening test for an early detection programme. In the absence of reliable biomarkers, renal imaging should be the primary screening tool for detecting asymptomatic RCC in informed, clinically suitable individuals enrolled in an early detection programme.
MULTIPLE‐PRIZE CONTESTS – THE OPTIMAL ALLOCATION OF PRIZES
Authors: Sisak Dana
Published: January 2009

Abstract Multiple‐prize contests are important in various fields of economics ranging from rent seeking over labour economics, patent and R&D races to tendering for (governmental) projects. Hence it is crucial to understand the incentive effects of multiple prizes on effort investment. This survey attempts to outline, compare and evaluate the results from the literature. While a first prize always results in a positive incentive to invest effort, second and later prizes lead to ambiguous effects. Depending on the objective function, the characteristics of the individuals and the type of contest a different prize allocation is optimal.
Speaker variability augments phonological processing in early word learning
Authors: Rost Gwyneth C. , McMurray Bob
Published: January 2009

Infants in the early stages of word learning have difficulty learning lexical neighbors (i.e. word pairs that differ by a single phoneme), despite their ability to discriminate the same contrast in a purely auditory task. While prior work has focused on top‐down explanations for this failure (e.g. task demands, lexical competition), none has examined if bottom‐up acoustic‐phonetic factors play a role. We hypothesized that lexical neighbor learning could be improved by incorporating greater acoustic variability in the words being learned, as this may buttress still‐developing phonetic categories, and help infants identify the relevant contrastive dimension. Infants were exposed to pictures accompanied by labels spoken by either a single or multiple speakers. At test, infants in the single‐speaker condition failed to recognize the difference between the two words, while infants who heard multiple speakers discriminated between them.
Ten‐month‐old infants use prior information to identify an actor's goal
Authors: Sommerville Jessica A. , Crane Catharyn C.
Published: January 2009

For adults, prior information about an individual's likely goals, preferences or dispositions plays a powerful role in interpreting ambiguous behavior and predicting and interpreting behavior in novel contexts. Across two studies, we investigated whether 10‐month‐old infants’ ability to identify the goal of an ambiguous action sequence was facilitated by seeing prior instances in which the actor directly pursued and obtained her goal, and whether infants could use this prior information to understand the actor's behavior in a new context. Experiment 1 demonstrated that the goal preview impacted infants’ subsequent action understanding, but only if the preview was delivered in the same room as the subsequent action sequence. Experiment 2 demonstrated that infants’ failure to transfer prior goal information across situations arose from a change in the roomper seand not other features of the task. Our results suggest that infants may use their understanding of simple actions as a leverage point for understanding novel or ambiguous actions, but that their ability to do so is limited to certain types of contextual changes.
Using the ‘protective environment’ framework to analyse children's protection needs in Darfur
Authors: Ager Alastair , Boothby Neil , Bremer Megan
Published: January 2009

A major humanitarian concern during the continuing crisis in Darfur, Sudan, has been the protection of children, although there has been little in the way of comprehensive analysis to guide intervention. Founded on a situational analysis conducted between October 2005 and March 2006, this paper documents the significant threats to children's well‐being directly linked to the political conflict. It demonstrates the role of non‐conflict factors in exacerbating these dangers and in promoting additional protection violations, and it uses the ‘protective environment’ framework (UNICEF Sudan, 2006a) to identify systematic features of the current environment that put children at risk. This framework is shown to provide a coherent basis for assessment and planning, prompting broad, multidisciplinary analysis, concentrating on preventive and protective action, and fostering a systemic approach (rather than placing an undue focus on the discrete needs of ‘vulnerable groups’). Constraints on its present utility in emergency settings are also noted.
A tale of two cities: restoring water services in Kabul and Monrovia
Authors: Pinera Jean‐François , Reed Robert A.
Published: January 2009

Kabul and Monrovia, the respective capitals of Afghanistan and Liberia, have recently emerged from long‐lasting armed conflicts. In both cities, a large number of organisations took part in emergency water supply provision and later in the rehabilitation of water systems. Based on field research, this paper establishes a parallel between the operations carried out in the two settings, highlighting similarities and analysing the two most common strategies. The first strategy involves international financial institutions, which fund large‐scale projects focusing on infrastructural rehabilitation and on the institutional development of the water utility, sometimes envisaging private‐sector participation. The second strategy involves humanitarian agencies, which run community‐based projects, in most cases independently of the water utilities, and targeting low‐income areas. Neither of these approaches manages to combine sustainability and universal service. The paper assesses their respective strengths and weaknesses and suggests ways of improving the quality of assistance provided.
Spatial econometric model of natural disaster impacts on human migration in vulnerable regions of Mexico
Authors: Saldaña‐Zorrilla Sergio O. , Sandberg Krister
Published: January 2009

Mexico's vast human and environmental diversity offers an initial framework for comprehending some of the prevailing great disparities between rich and poor. Its socio‐economic constructed vulnerability to climatic events serves to expand this understanding. Based on a spatial econometric model, this paper tests the contribution of natural disasters to stimulating the emigration process in vulnerable regions of Mexico. Besides coping and adaptive capacity, it assesses the effects of economic losses due to disasters as well as the adverse production and trade conditions of the 1990s on emigration rates in 2000 at the municipality level. Weather‐related disasters were responsible for approximately 80 per cent of economic losses in Mexico between 1980 and 2005, mostly in the agricultural sector, which continues to dominate many parts of the country. It is dramatic that this sector generates around only four per cent of gross domestic product but provides a livelihood to about one‐quarter of the national population. It is no wonder, therefore, that most emigration from this country arises in vulnerable rural areas.
Faith‐based aid, globalisation and the humanitarian frontline: an analysis of Western‐based Muslim aid organisations
Authors: De Cordier Bruno
Published: January 2009

This paper focuses on the emergence and modus operandi of Muslim faith‐based aid organisations from the West, particularly those from the United Kingdom. Through case studies of Islamic Relief Worldwide and Muslim Hands, it examines the actual and potential added value generated by these humanitarian players in Muslim‐majority contexts at times when aid actors from or associated with the West are being perceived by some as instrumental to the political agendas of Western powers, or are being confronted with the consequences thereof. The study analyses Muslim faith‐based aid organisations' transnational networks, their implementing partnerships with local faith‐based non‐governmental organisations (NGOs), and their security position within and their access to insecure contexts, drawing on field examples and opinion from Central Asia, Iraq and Pakistan. It thereby argues that there is ground for an expansion of the role of Muslim aid actors, because of the existence of social and political realities in the field that cannot be always effectively tackled by the dominant international development approaches.
WEEKDAY‐ONLY POLLING AND PARTISAN SUPPORT LEVELS: EVIDENCE FROM NEW ZEALAND
Authors: Salmond Rob
Published: January 2009

Some scholars have argued that opinion polls conducted only on weekday evenings are likely to be biased in favour of right‐wing parties, but there is no scholarly consensus on this. This paper presents evidence from New Zealand suggesting that weekday‐only polling consistently increases the reported support levels for right‐wing parties. Polls conducted only on weekdays in New Zealand give estimated support levels for the major right‐leaning party approximately five percentage points higher than do concurrent polls that survey voters both on weekdays and during the weekend. Results for left‐leaning parties are also broadly consistent with this effect.
HIGH‐DIMENSIONAL PARAMETRIC MODELLING OF MULTIVARIATE EXTREME EVENTS
Authors: Stephenson Alec G.
Published: January 2009

Multivariate extreme events are typically modelled using multivariate extreme value distributions. Unfortunately, there exists no finite parametrization for the class of multivariate extreme value distributions. One common approach is to model extreme events using some flexible parametric subclass. This approach has been limited to only two or three dimensions, primarily because suitably flexible high‐dimensional parametric models have prohibitively complex density functions. We present an approach that allows a number of popular flexible models to be used in arbitrarily high dimensions. The approach easily handles missing and censored data, and can be employed when modelling componentwise maxima and multivariate threshold exceedances. The approach is based on a representation using conditionally independent marginal components, conditioning on positive stable random variables. We use Bayesian inference, where the conditioning variables are treated as auxiliary variables within Markov chain Monte Carlo simulations. We demonstrate these methods with an application to sea‐levels, using data collected at 10 sites on the east coast of England.
MULTIPLE‐RECORD SYSTEMS ESTIMATION USING LATENT CLASS MODELS
Authors: Wang Yan , Thandrayen Joanne
Published: January 2009

Capture–recapture methods (also referred to as ‘multiple‐record systems’) have been widely used in enumerating human populations in the fields of epidemiology and public health. In this article, we introduce latent class models into multiple‐record systems to account for unobserved heterogeneity in the population. Two approaches, the full and the conditional likelihood, are proposed to estimate the unknown population abundance. We also suggest rules to diagnose identifiability of the proposed latent class models. The methodologies are illustrated by two real examples: the first is to count the undercount of homelessness in the Adelaide central business district, and the second concerns the incidence of diabetes in a small Italian town.
From Vision to Action: Fostering Peaceful Coexistence and the Common Good in a Pluralistic Society through Teacher Education
Authors: DeMulder Elizabeth K. , Ndura‐Ouédraogo Elavie , Stribling Stacia M.
Published: January 2009

This article examines the role of education and the responsibilities of teachers and teacher educators in working for social justice and peace. It describes a nontraditional professional development master's program designed to empower practicing teachers to become active contributors in the quest for social justice and to speak for the common good in their increasingly diverse schools and society. In the context of continuing intolerance and violence in schools and society, the program offers a model for preparing educators with the knowledge, skills, dispositions, and commitments necessary to engage in transformative social action. The article draws on teachers’ written feedback responses to examine the impact of particular curricular experiences and cumulative influences on teachers’ struggles for awareness of human diversity issues and commitments to transformative social action in their own classrooms.
Learned Piety: Education for Justice and the Common Good in Jesuit Secondary Education
Authors: Scibilia Dominic P. , Giamario Patrick , Rogers Michael
Published: January 2009

One of the five essential outcomes of Jesuit secondary education focuses on the development of a student's social consciousness for the purpose of preparing an individual who contributes to the common good. An educational meritocracy, such as the academic structure at St. Peter's Preparatory School in New Jersey, tends to center learning on how to recognize what a teacher wants a student to see, know, and judge for the sake of academic self‐interest rather than directing efforts toward the Jesuit pedagogical vision of learned piety. We assert that education for justice must move beyond education as seeing and reporting to involve students in a critical social analysis that encourages participation in making justice and realizing the common good.
Understanding Peace Consciousness and Its Language: Unfinishedness
Authors: Bryzzheva Lyudmila
Published: January 2009

This article will attempt to elucidate the concept of the language of peace as a medium through which people can express their peace consciousness. First, peace consciousness is explored in some depth. It is suggested that unfinishedness, dialogicality, and interdependence are aspects of human nature that should be honored to achieve peace consciousness. This article then reviews unfinishedness and the ways it may translate into corresponding verbal and non‐verbal elements of the language of peace such as modal verbs and adjuncts, the future‐oriented conditional/suppositional mood, ellipses and question marks, the softening of Extreme Case Formulations, and living silence.
Non-Linear Oil Price Dynamics: A Tale of Heterogeneous Speculators?
Authors: Reitz Stefan , Slopek Ulf
Published: January 2009

While some of the recent surges in oil prices can be attributed to a robust global demand at a time of tight production capacities, commentators occasionally also blame the impact of speculators for part of the price pressure. We propose an empirical oil market model with heterogeneous speculators. Whereas trend-extrapolating chartists may tend to destabilize the market, fundamentalists exercise a stabilizing effect on the price dynamics. Using monthly data for West Texas Intermediate oil prices, our STR-GARCH estimates indicate that oil price cycles may indeed emerge due to the non-linear interplay between different trader types.
Did the Hartz Reforms Speed-Up the Matching Process? A Macro- Evaluation Using Empirical Matching Functions
Authors: Fahr René , Sunde Uwe
Published: January 2009

Starting in January 2003, Germany implemented the first two so-called Hartz reforms, followed by the third and fourth packages of Hartz reforms in January 2004 and January 2005, respectively. The aim of these reforms was to accelerate labor market flows and reduce unemployment duration.Without attempting to evaluate the specific components of these Hartz reforms, this paper provides a first attempt to evaluate the overall effectiveness of the first two reform waves, Hartz I/II and III, in speeding up the matching process between unemployed and vacant jobs. The analysis is conceptually rooted in the flow-based view underlying the reforms, estimating the structural features of the matching process. The results indicate that the reforms indeed had an impact in making the labor market more dynamic and accelerating the matching process.
Does German Development Aid Promote German Exports?
Authors: Martínez-Zarzoso Inmaculada , Klasen Stephan , Nowak-Lehmann D. Felicitas , Larch Mario
Published: January 2009

This paper uses a static and dynamic gravity model of trade to investigate the link between German development aid and exports from Germany to the recipient countries. The findings indicate that, in the long run, German aid is associated with an increase in exports of goods that is larger than the aid flow, with a point estimate of 140% of the aid given. In addition, the evolution of the estimated coefficients over time shows an effect that is consistently positive but that oscillates over time. Interestingly, after a decrease in the 1990s, the estimated coefficients of the effect of aid on trade show a steady increase in the period between 2001 and 2005. The paper distinguishes among recipient countries and finds that the return on aid measured by German exports is higher for aid to countries considered ‘strategic aid recipients’ by the German government.We also find some evidence that aid given by other EU members reduces German exports.
The Relationship between Components of the Behavioural Phenotype in Prader‐Willi Syndrome
Authors: Oliver Chris , Woodcock Kate A. , Humphreys Glyn W.
Published: January 2009

Background  Repetitive questions and temper outbursts form part of the behavioural phenotype of Prader‐Willi syndrome (PWS). We investigated the phenomenology of temper outbursts in PWS and their relationship with other PWS behavioural characteristics.

Method  Four individuals with PWS were observed (5–10 h), during a number of experimental and natural environment challenges, some of which were expected to trigger temper outbursts. Individual behaviours including crying, ignoring, arguing, questioning, stereotypy, frowning and posture changes were recorded and subjected to lag sequential analysis.

Results  All participants were significantly more likely to show repetitive questioning before more challenging behaviours such as crying, arguing or ignoring requests. Precursor behaviours such as frowning and stereotypical behaviour were identified in three participants.

Conclusions  Temper outbursts in PWS may be associated with other PWS behavioural phenotypic characteristics such as repetitive questions and ‘stubbornness’. A progression of behaviours may lead up to the most challenging temper outburst behaviours. This may have important implications for effective coping strategies.
Frequency of Use and Characteristics of People with Intellectual Disabilities Subject to Physical Interventions
Authors: McGill Peter , Murphy Glynis , Kelly‐Pike Amanda
Published: January 2009

Background  The use of physical intervention (PI) with people with intellectual disabilities continues to cause concern. This study sought to clarify the frequency and circumstances of PI use and gather data on the characteristics of individuals subject to PI.

Method  Data on individuals subject to PI were gathered by postal questionnaire completed by service providers from three samples: people who (i) had attended a PI conference and/or purchased a PI policy document; (ii) operated in a specific geographical area of England and (iii) operated specialist assessment and treatment settings for children/adults with intellectual disabilities throughout the UK.

Results  Frequent PI use was reported. Restraint was most commonly reported – monthly or more frequently with most individuals. Overall, those receiving PI were more likely to be young, male, not legally restricted and identified as having an autistic spectrum disorder than those who did not receive PI.

Conclusions  The relatively frequent use of PI is consistent with routine rather than last resort use. Such use carries risk of physical and psychological damage. Service providers should systematically reduce the frequency of use of PI.
Predictors of Restrictive Reactive Strategy Use in People with Challenging Behaviour
Authors: Allen David , Lowe Kathy , Brophy Sam , Moore Kate
Published: January 2009

Background  Intrusive reactive strategies (physical restraint, emergency medication and seclusion) are frequently used procedures in the management of challenging behaviour. The present study identifies predictors for reactive strategy use in an attempt to more clearly delineate at risk service users.

Method  Eight hundred and thirty‐nine agencies and service settings in a large area of South Wales were screened to identify children and adults with challenging behaviour against a number of defined operational criteria. Full data were available for 901 participants. Univariate and multivariate statistics were employed to identify predictors for reactive strategy use.

Results  The individuals most at risk of the use of reactive strategies were those who were subject to formal detention under the Mental Health Act (restraint and sedation), had more severe challenging behaviour (seclusion), showed destructive behaviour (restraint and seclusion) were placed out of area (seclusion) and had behavioural plans in place for specific topographies (restraint and sedation).

Conclusions  Individual differences such as challenging behaviour and service practices, such as detention under the Mental Health Act, predicted the use of restrictive procedures. The identification of those service users most at risk of reactive strategy use may enable the specific targeting of therapeutic interventions that may reduce or eliminate their use.
Mindful Staff Can Reduce the Use of Physical Restraints When Providing Care to Individuals with Intellectual Disabilities
Authors: Singh Nirbhay N. , Lancioni Giulio E. , Winton Alan S. W. , Singh Ashvind N. , Adkins Angela D. , Singh Judy
Published: January 2009

Background  The use of physical restraints has generated immense controversy in the delivery of services to individuals with intellectual disabilities. The current zeitgeist is that effective positive approaches obviate the need for using physical restraints. In a multiple baseline design, we sought to assess how training staff members in mindfulness affected their use of physical restraints for aggressive and destructive behaviours of individuals with intellectual disabilities.

Methods  Twenty‐three members of staff working in four group homes participated in a 12‐week mindfulness‐training programme. Objective data were collected on the number of incidents, staff observations of incidents, staff verbal redirections, restraints used, Stat medications administered, staff injuries and peer injuries. Data were collected during baseline, mindfulness training and mindfulness practice phases.

Results  As mindfulness training progressed, the use of restraints decreased, with almost no use being recorded by the end of the study. Any use of physical restraints was correlated with new admissions and on‐call staff who had not received training in mindfulness. Stat medications administered also decreased and staff and peer injuries were close to zero levels during the latter stages of mindfulness practice.

Conclusions  Data from this initial study suggest that staff training in mindfulness is potentially beneficial to both staff and the individuals with intellectual disabilities, particularly in reducing the use of physical restraints and Stat medication for aggressive and destructive behaviours.
The Clinical Management and Prevention of Pica: A Retrospective Follow‐Up of 41 Individuals with Intellectual Disabilities and Pica
Authors: Williams Don E. , Kirkpatrick‐Sanchez Sharon , Enzinna Christie , Dunn Jacqueline , Borden‐Karasack Deborah
Published: January 2009

Background  Pica is a very dangerous form of self‐injurious behaviour because one occurrence can be lethal. Dealing successfully with dangerous pica in a large institution requires a high level of administrative support. It cannot be relegated to each psychologist to write a programme. A written behaviour programme is only one component of long‐term treatment.

Method  This study describes an intervention for people with intellectual disabilities and pica that included comprehensive management of the environment as well as behaviour treatment over a 9‐year period.

Results  Over a 9‐year period, nine surgeries for pica‐related incidents occurred prior to intervention; over the 9 years of intervention, pica surgeries were eliminated. Eighty‐five percent of participants experienced a 75–100% reduction in pica. Sixteen participants still had restrictive procedures including oral hygiene, overcorrection, contingent personal restraint, contingent mechanical restraint and visual screening with goggles. All continuous mechanical restraint that had been used in baseline was eliminated.

Conclusion  People with intellectual disabilities and dangerous pica can be protected on a long‐term basis from serious harm if proper management and clinical interventions are both employed. Although restrictive interventions were used on a long‐term basis, they were contingent upon a pica incident or pica attempts, which occurred much lower than in baseline sessions. Resident rights were protected throughout the intervention.
The Effects of an Action Plan, Staff Training, Management Support and Monitoring on Restraint Use and Costs of Work‐Related Injuries
Authors: Sanders Kim
Published: January 2009

Background  Dignity and respect are at the foundation of good care and effective treatment planning and are guiding service principles. The use of physical restraints is contrary to treatment with dignity and respect. Because of the numerous risks to clients and employees associated with the use of physical restraints, an innovative plan was implemented to minimize the use.

Method  Information was gathered to obtain a clear understanding of the employees’ feelings about the initiative to minimize physical restraint. Training was provided regarding philosophical issues as well as how to utilize a new tool/procedure to keep everyone safe during aggressive outbursts. Presence by the management team was increased to support employees and encourage newly trained techniques. Finally, a formal system of processing was put in place to learn from each restraint in order to prevent the situation in the future.

Results  The Winchester Region reduced the use of physical restraint by 99.4% and client‐induced employee injuries by 37.7%.

Conclusions  We drastically reduced physical restraints, staff injuries and created a safer place to work.
The contribution of callous‐unemotional traits and conduct problems to bullying in early adolescence
Authors: Viding Essi , Simmonds Elizabeth , Petrides K.V. , Frederickson Norah
Published: January 2009

Background:  Although a lot is known about the association of conduct problems with bullying, less attention has been paid to co‐occurring traits, such as callous‐unemotional (CU) traits that might additionally contribute to the risk of engaging in bullying. This study investigated the contribution of CU traits to direct and indirect bullying, alongside the contributions made by conduct problems and gender.

Methods:  Seven hundred and four 11–13‐year‐olds completed self‐report measures of callous‐emotional traits and psychopathology, including conduct problems. Peer‐report measures of direct and indirect bullying were collected from classmates.

Results:  Higher levels of CU traits were associated with higher levels of direct bullying, over and above the association between bullying and conduct problems. Conduct problems and CU traits interacted in the prediction of both direct and indirect bullying. In line with previous research, males were more likely to engage in direct and females in indirect bullying.

Conclusions:  This study highlights the importance of viewing CU traits and conduct problems, not only as related phenomena, but also as distinct entities in mediating the underlying susceptibility of children to bully others directly. Furthermore, a combination of these traits appears to be a particularly potent risk factor for both direct and indirect bullying. Implications for intervention are discussed, in particular the concern that lack of empathy and insensitivity to punishment in those with CU traits may also make them particularly resistant to current forms of bullying intervention.
Children’s experiences with chat support and telephone support
Authors: Fukkink Ruben G. , Hermanns Jo M.A.
Published: January 2009

Background:  In line with the wider trend of offering support via the Internet, many counseling and referral services for children have introduced online chat, often in addition to a traditional telephone service.

Methods:  A comparative study was conducted between the telephone service and the confidential one‐on‐one online chat service of the Dutch Kindertelefoon. The design included a concise pretest and a posttest (n = 902). The study also comprised a follow‐up test (n = 213), which included the Strengths and Difficulties Questionnaire.

Results:  Children experienced a higher sense of well‐being and a reduced severity of their problems after consulting the Kindertelefoon. The results were slightly more favorable for the chat service than for the telephone service. The follow‐up survey showed that many of the children who contact the Kindertelefoon suffer from relatively severe emotional problems.

Conclusions:  Both the telephone and the web‐based support improved the children’s well‐being and decreased their perceived burden of problem. The results of this study underline the need for closer cooperation between child helplines and mental health and child welfare services.
Prosocial development from childhood to adolescence: a multi‐informant perspective with Canadian and Italian longitudinal studies
Authors: Nantel‐Vivier Amélie , Kokko Katja , Caprara Gian Vittorio , Pastorelli Concetta , Gerbino Maria Grazia , Paciello Marinella , Côté Sylvana , Pihl Robert O. , Vitaro Frank , Tremblay Richard E.
Published: January 2009

Objectives:  To longitudinally describe prosocial behaviour development from childhood to adolescence, using multiple informants within Canadian and Italian samples.

Method:  Participants in Study 1 were 1037 boys from low socioeconomic status (SES) areas in Montreal, Canada, for whom yearly teacher and mother reports were obtained between the ages of 10 and 15. Participants in Study 2 were 472 children (209 girls) from Genzano, Italy, for whom yearly self and teacher reports were obtained between the ages of 10 and 14. Developmental trajectories were estimated from ratings by each informant to identify subgroups of children following distinct courses of prosocial development.

Results:  In Study 1, three trajectory groups (low/declining 53%, high/declining 16%, high/steep declining 31%) were identified from teacher ratings, while five trajectories (low/stable 7%, low/declining 19%, moderate/stable 41%, high/declining 24%, high/stable 9%) were identified from mother ratings. Small but significant associations were observed between mother and teacher ratings. In Study 2, three trajectory groups (low/stable 9%, moderate/stable 50%, high/stable 42%) were identified from self‐ratings, while four trajectory groups (low/stable 8%, moderate/declining 48%, high/declining 37%, increasing 7%) were identified from teacher ratings. Small but significant associations were observed between self‐ and teacher ratings.

Conclusions:  The present studies investigated levels of prosocial behaviours from childhood to adolescence, using a multi‐informant, cross‐cultural perspective. All but one of the developmental trajectories identified were characterised by stable or declining levels of prosocial behaviours. Further research longitudinally investigating prosociality across developmental periods is needed to clarify prosocial behaviour development over time.
Interplay of genes and early mother–child relationship in the development of self‐regulation from toddler to preschool age
Authors: Kochanska Grazyna , Philibert Robert A. , Barry Robin A.
Published: January 2009

Background:  A broad capacity for deliberate self‐regulation plays a key role in emotion regulation. This longitudinal investigation from infancy to preschool age examines genotype by environment (G × E) interaction in the development of self‐regulation, using molecular measures of children’s genotypes and observed measures of the quality of early mother–child relationship, as reflected in attachment organization in infancy.

Methods:  In 89 children, we assessed the polymorphism in the serotonin transporter gene (5‐HTTLPR, ss/sl vs. ll allele status), security of attachment to mothers at 15 months in the Strange Situation, and children’s ability for self‐regulation at 25, 38, and 52 months, using behavioral batteries of tasks that called for deliberately suppressing a dominant response and performing instead a sub‐dominant response.

Results:  There was a robust G × E interaction between genetic risk and the quality of early relationship. Among children who carried a short 5‐HTTLPR allele (ss/sl ), those who were insecurely attached developed poor regulatory capacities, but those who were securely attached developed as good regulatory capacities as children who were homozygotic for the long allele (ll ). There was no effect of security for ll homozygotes.

Conclusions:  Those findings, consistent with diathesis‐stress model, bridge research on self‐regulation in typically developing children with research on non‐human primates and research on psychopathology. They also indicate that a secure attachment relationship can serve as a protective factor in the presence of risk conferred by a genotype.
Environmental regulation of leaf colour in red 35S:PAP1 Arabidopsis thaliana
Authors: Rowan Daryl D. , Cao Mingshu , Lin‐Wang Kui , Cooney Janine M. , Jensen Dwayne J. , Austin Paul T. , Hunt Martin B. , Norling Cara , Hellens Roger P. , Schaffer Robert J. , Allan Andrew C.
Published: January 2009

DOI: 10.1111/j.1469-8137.2009.02771.xCommentary p 1
Brevican distinctively assembles extracellular components at the large diameter nodes of Ranvier in the CNS
Authors: Bekku Yoko , Rauch Uwe , Ninomiya Yoshifumi , Oohashi Toshitaka
Published: January 2009

Brevican is known to be an abundant extracellular matrix component in the adult brain and a structural constituent of perineuronal nets. We herein show that brevican, tenascin‐R (TN‐R) and phosphacan are present at the nodes of Ranvier on myelinated axons with a particularly large diameter in the central nervous system. A brevican deficiency resulted in a reorganization of the nodal matrices, which was characterized by the shift of TN‐R, and concomitantly phosphacan, from an axonal diameter‐dependent association with nodes to an axonal diameter independent association. Supported by the co‐immunoprecipitation results, these observations indicate that the presence of TN‐R and phosphacan at nodes is normally brevican‐dependent, while in the absence of brevican these molecules can also be recruited by versican V2. The versican V2 and Bral1 distribution was not affected, thus indicating a brevican‐independent role of these two molecules for establishing hyaluronan‐binding matrices at the nodes. Our results revealed that brevican plays a crucial role in determining the specialization of the hyaluronan‐binding nodal matrix assemblies in large diameter nodes.
Identification of a minimal segment of complexin II essential for preferential distribution in axons
Authors: Kataoka Masakazu , Sekiguchi Mariko , Takahashi Masami
Published: January 2009

Complexin II (CPLX2) is a soluble pre‐synaptic protein believed to regulate neurotransmitter release from pre‐synaptic terminals. CPLX2 is localized in pre‐synaptic terminals in mature brain, but the mechanism of selective localization remains unclear. Here we identified an essential segment of CPLX2 for preferential axonal distribution. Myc‐tagged CPLX2 was expressed in cultured rat hippocampal neurons and its distribution between axons and dendrites was compared by immunocytochemistry and image analysis. Fluorescence signals were detected in both axons and dendrites; however, their respective distribution varied significantly. Despite the fact that signal intensity decreased almost linearly from the base to the tip of the dendrite, a substantial level was sustained along the axon, even at a position near the tip. Image analyses using a series of mutants indicated that the deletion of 19 amino acid residues, G71‐P89, within the ‘central core’ for binding to soluble N‐ethylmaleimide sensitive factor attachment protein receptor proteins resulted in the loss of preferential axonal distribution. The enhanced green fluorescent protein derivative fused with the G71‐P89 fragment exhibited a similar localization to that of wild type CPLX2, indicating that the G71‐P89 region of CPLX2 is essential and sufficient for preferential axonal distribution.
Pleiotropic effects of spastin on neurite growth depending on expression levels
Authors: Riano Elena , Martignoni Monica , Mancuso Giuseppe , Cartelli Daniele , Crippa Francesca , Toldo Irene , Siciliano Gabriele , Di Bella Daniela , Taroni Franco , Bassi Maria Teresa , Cappelletti Graziella , Rugarli Elena I.
Published: January 2009

Hereditary spastic paraplegia (HSP) is characterized by weakness and spasticity of the lower limbs, owing to degeneration of corticospinal axons. The most common form is due to heterozygous mutations in the SPG4 gene, encoding spastin, a microtubule (MT)‐severing protein. Here, we show that neurite growth in immortalized and primary neurons responds in pleiotropic ways to changes in spastin levels. Spastin depletion alters the development of primary hippocampal neurons leading to abnormal neuron morphology, dystrophic neurites, and axonal growth defects. By live imaging with End‐Binding Protein 3‐Fluorescent Green Protein (EB3‐GFP), a MT plus‐end tracking protein, we ascertained that the assembly rate of MTs is reduced when spastin is down‐regulated. Spastin over‐expression at high levels strongly suppresses neurite maintenance, while slight spastin up‐regulation using an endogenous promoter enhances neurite branching and elongation. Spastin severing activity is exerted preferentially on stable acetylated and detyrosinated MTs. We further show that SPG4 nonsense or splice site mutations found in hereditary spastic paraplegia patients result in reduced spastin levels, supporting haploinsufficiency as the molecular cause of the disease. Our study reveals that SPG4 is a dosage‐sensitive gene, and broadens the understanding of the role of spastin in neurite growth and MT dynamics.
GDNF control of the glutamatergic cortico‐striatal pathway requires tonic activation of adenosine A2Areceptors
Authors: Gomes Catarina A. R. V. , Simões Patrícia F. , Canas Paula M. , Quiroz César , Sebastião Ana M. , Ferré Sergi , Cunha Rodrigo A. , Ribeiro Joaquim A.
Published: January 2009

Glial cell line‐derived neurotrophic factor (GDNF) affords neuroprotection in Parkinson’s disease in accordance with its ability to bolster nigrostriatal innervation. We previously found that GDNF facilitates dopamine release in a manner dependent on adenosine A2Areceptor activation. As motor dysfunction also involves modifications of striatal glutamatergic innervation, we now tested if GDNF and its receptor system, Ret (rearranged during transfection) and GDNF family receptor α1 controlled the cortico‐striatal glutamatergic pathway in an A2Areceptor‐dependent manner. GDNF (10 ng/mL) enhanced (by ≈13%) glutamate release from rat striatal nerve endings, an effect potentiated (up to ≈30%) by the A2Areceptor agonist CGS 21680 (10 nM) and prevented by the A2Areceptor antagonist, SCH 58261 (50 nM). Triple immunocytochemical studies revealed that Ret and GDNF family receptor α1 were located in 50% of rat striatal glutamatergic terminals (immunopositive for vesicular glutamate transporters‐1/2), where they were found to be co‐located with A2Areceptors. Activation of the glutamatergic system uponin vivoelectrical stimulation of the rat cortico‐striatal input induced striatal Ret phosphorylation that was prevented by pre‐treatment with the A2Areceptor antagonist, MSX‐3 (3 mg/kg). The results provide the first functional and morphological evidence that GDNF controls cortico‐striatal glutamatergic pathways in a manner largely dependent on the co‐activation of adenosine A2Areceptors.
The basal flux of Akt in the mitochondria is mediated by heat shock protein 90
Authors: Barksdale Keri A. , Bijur Gautam N.
Published: January 2009

Akt is a known client protein of heat shock protein 90 (HSP90). We have found that HSP90 is responsible for Akt accumulation in the mitochondria in unstimulated cells. Treatment of SH‐SY5Y neuroblastoma cells and human embryonic kidney cells with the HSP90 inhibitors novobiocin and geldanamycin caused substantial decreases in the level of Akt in the mitochondria without affecting the level of Akt in the cytosol. Moreover, intracerebroventricular injection of novobiocin into mice brains decreased Akt levels in cortical mitochondria. Knockdown of HSP90 expression with short interfering RNA also caused a significant decrease in Akt levels in the mitochondria without affecting total Akt levels. Using a mitochondrial import assay it was found that Akt is transported into the mitochondria. Furthermore, it was found that the mitochondrial import of Akt was independent of Akt activation as both an unmodified Akt and constitutively active mutant Akt; both readily accumulated in the mitochondria in an HSP90‐dependent manner. Interestingly, incubation of isolated mitochondria with constitutively active Akt caused visible alterations in mitochondrial morphology, including pronounced remodeling of the mitochondrial matrix. This effect was blocked when Akt was mostly excluded from the mitochondria with novobiocin treatment. These results indicate that the level of Akt in the mitochondria is dependent on HSP90 chaperoning activity and that Akt import can cause dynamic changes in mitochondrial configuration.
Role of the ERK/MSK1 signalling pathway in chromatin remodelling and brain responses to drugs of abuse
Authors: Brami‐Cherrier Karen , Roze Emmanuel , Girault Jean‐Antoine , Betuing Sandrine , Caboche Jocelyne
Published: January 2009

Drugs of abuse induce neuroadaptations through regulation of gene expression. Although much attention has focused on transcription factor activities, new concepts have recently emerged on the role of chromatin remodelling as a prerequisite for regulation of gene expression in neurons. Thus, for transcription to occur, chromatin must be decondensed, a dynamic process that depends on post‐translational modifications of histones. We review here these modifications with a particular emphasis on the role of histone H3 phosphorylation at the promoter of specific genes, including c‐fos and c‐jun. We trace the signalling pathways involved in H3 phosphorylation and provide evidence for a role of mitogen and stress‐activated protein kinase‐1 (MSK1) downstream from the MAPK/extracellular‐signal regulated kinase (ERK) cascade. In response to cocaine, MSK1 controls an early phase of histone H3 phosphorylation at the c‐fos promoter in striatal neurons. MSK1 action may be potentiated by the concomitant inhibition of protein phosphatase 1 by nuclear translocation of dopamine‐ and cAMP‐regulated phosphoprotein Mr = 32 000. H3 phosphorylation by MSK1 is critically involved in c‐fos transcription, and cocaine‐induced locomotor sensitization. Thus, ERK plays a dual role in gene regulation and drug addiction by direct activation of transcription factors and by chromatin remodelling.
The interplay between inorganic phosphate and amino acids determines zinc solubility in brain slices
Authors: Rumschik Sean M. , Nydegger Irma , Zhao Jinfu , Kay Alan R.
Published: January 2009

Inorganic phosphate (Pi) is an important polyanion needed for ATP synthesis and bone formation. As it is found at millimolar levels in plasma, it is usually incorporated as a constituent of artificial CSF formulations for maintaining brain slices. In this paper, we show that Pi limits the extracellular zinc concentration by inducing metal precipitation. We present data suggesting that amino acids like histidine may counteract the Pi‐induced zinc precipitation by the formation of soluble zinc complexes. We propose that the interplay between Pi and amino acids in the extracellular space may influence the availability of metals for cellular uptake.
Helicobacter pylori eradication: role of individual therapy constituents and therapy duration
Authors: Qasim Asghar , O’Morain Colm A. , O’Connor Humphrey J.
Published: January 2009

Treatment of Helicobacter pylori (H. pylori) infection has become a key factor in the management of dyspepsia and is the treatment of choice for peptic ulcer disease. First‐line eradication regimens combining a proton pump inhibitor (PPI) with clarithromycin and amoxicillin or metronidazole are considered most effective when given for a minimum period of 1 week. Eradication regimens of shorter duration have shown promising results but clinical experience remains limited. Pharmacological properties such as bioavailability and plasma concentrations of individual PPIs differ between individuals but it remains unclear whether these differences impact on the efficacy of eradication therapy and are influenced by renal or hepatic impairment. Bioavailability of PPIs also differs and is impacted on by factors including intragastric pH, metabolic pathways, potency on an mg‐for‐mg basis and intrinsic antibacterial activity. Several significant pharmacokinetic differences between the PPIs do not seem to influence overall H. pylori eradication rates for first‐line triple therapy. However, comparison of factors including pharmacokinetics and treatment duration may prove important in achieving successful eradication with second‐ and third‐line treatments. Based on the factors which influence therapy outcome, we suggest an algorithm for the use of H. pylori eradication therapies.