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Neurofibromatosis type 1 (NF1) is associated with below average writing achievement. However, little is known about specific aspects of written language impacted by NF1, changes in writing over time, and associations between cognitive aspects of the NF1 phenotype and writing. At three timepoints over six years, children with NF1 and plexiform neurofibromas (PNs) completed Woodcock-Johnson tests of writing mechanics (Spelling, Punctuation & Capitalization, handwriting), written expression of ideas (Writing Samples), writing speed (Writing Fluency), and tests of general cognitive ability, executive function, memory, and attention. Children (N = 76, mean age = 12.8 ± 3.4 years) completed at least one baseline writing subtest. Overall writing scores were in the Average range (M = 93.4, SD = 17.4), but lower than population norms (p = 0.002). Scores were highest on Writing Samples (M = 95.2, SD = 17.3), and lowest for Punctuation & Capitalization (M = 87.9, SD = 18.8, p = 0.034). Writing scores were mostly stable over time. Nonverbal reasoning was related to some tests of writing mechanics and written expression of ideas. Short-term memory and inattention explained additional variance in Writing Samples and Spelling. Poor handwriting was associated with writing content beyond the impact of cognitive factors. Children with NF1 and PNs may benefit from early screening and writing support. Interventions should address the contribution of both cognitive and handwriting difficulties in written language. [ABSTRACT FROM AUTHOR]

Objective: To examine how executive functioning (EF) relates to academic achievement longitudinally in children with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs) and whether age at baseline moderates this relationship. Method: Participants included 88 children with NF1 and PNs (ages 6–18 years old, M = 12.05, SD = 3.62, 50 males) enrolled in a natural history study. Neuropsychological assessments were administered three times over 6 years. EF (working memory, inhibitory control, cognitive flexibility, and attention) was assessed by performance-based (PB) and parent-reported (PR) measures. Multilevel growth modeling was used to examine how EF at baseline related to initial levels and changes in broad math, reading, and writing across time, controlling for demographic variables. Results: The relationship between EF and academic achievement varied across EF and academic domains. Cognitive flexibility (PB) uniquely explained more variances in initial math, reading, and writing scores; working memory (PB) uniquely explained more variances in initial levels of reading and writing. The associations between EF and academic achievement tended to remain consistent across age groups with one exception: Lower initial levels of inhibitory control (PR) were related to a greater decline in reading scores. This pattern was more evident among younger (versus older) children. Conclusions: Findings emphasize the heterogeneous nature of academic development in NF1 and that EF skills could help explain the within-group variability in this population. Routine cognitive/academic monitoring via comprehensive assessments and early targeted treatments consisting of medication and/or systematic cognitive interventions are important to evaluate for improving academic performance in children with NF1 and PNs. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals with neurofibromatosis type 1 (NF1) are vulnerable to socioemotional difficulties. However, we know little about how socioemotional functioning changes across childhood and adolescence and what factors predict the change. The current longitudinal study aims to address this gap by examining how demographic and NF1-disease related factors predict development of socioemotional functioning in a sample of children and adolescents with NF1 and PNs. We found substantial within-group variabilities in socioemotional development with developmental patterns varying across socioemotional domains, reporters of socioemotional functioning, age at baseline, parental education, race/ethnicity, number of NF1-related complications, and visibility of tumors. These findings indicate the need for individualized patient care and interventions that consider each child's unique background and needs. The results also suggest the need for more longitudinal research to further understand how various factors affect socioemotional development in children with NF1 to better inform intervention development and practices. Individuals with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs) have a higher risk for socioemotional problems. The current study aims to identify the socioemotional developmental pattern and its predictors across childhood and adolescence in individuals with NF1 and PNs. Participants included 88 children with NF1 and PNs (aged 6–18 years old, M = 12.05, SD = 3.62, 57% male) in a natural history study. Neuropsychological assessments were administered three times over six years. There are large variabilities in socioemotional development in the study participants. Developmental patterns varied across socioemotional domains, respondent type (parent-report [PR] vs. child-report [CR]), demographic factors, and NF1 disease-related factors. For instance, lower parental education was associated with a greater decline in internalizing problems (PR) but a greater increase in school disconnectedness (CR) over time. Non-White (vs. White) children were more likely to experience increased adaptive skills (PR) but decreased personal adjustment (CR). Children with more visible tumors experienced a greater decrease in school disconnectedness (CR). Children with more NF1 complications experienced a greater decrease in externalizing problems (PR). These findings indicate the necessity of using multi-informants and investigating subdomains of socioemotional functions. They also highlight the importance of developing individualized approaches to patient care and interventions. [ABSTRACT FROM AUTHOR]

Aim: To describe the cognitive development of children with neurofibromatosis type 1 (NF1) and plexiform neurofibromas, and identify predictors of cognitive development.Method: Participants included 88 children with NF1 and plexiform neurofibromas (50 males, 38 females, aged 6-18y, mean=12y, SD=3y 7mo) on a natural history study at the National Cancer Institute. Neuropsychological assessments (e.g. IQ, academic achievement, attention, and executive functioning) were administered three times over 6 years.Results: Relative to normative peers, the total sample of children with NF1 and plexiform neurofibromas demonstrated significantly lower scores in most cognitive domains and decreasing z-scores over time in math, writing, inhibitory control, and working memory. Children who had parents with (vs without) NF1 were more likely to experience decreased z-scores in performance IQ, reading, writing, attention, and working memory. Higher (vs lower) parental education was related to higher levels of IQ, math, reading, and cognitive flexibility and a slower decrease in math z-scores. Children's sex and the number of NF1 disease-related complications were not related to most cognitive outcomes.Interpretation: Children with NF1 and plexiform neurofibromas are at high risk for cognitive difficulties and declining z-scores in various domains of cognitive functioning over time. The findings highlight the need for a better understanding of the within-group differences in these children and their need for individualized educational plans.What This Paper Adds: Math, writing, inhibitory control, and working memory scores decreased over time. The proportion of children with clinically significant cognitive deficits increased over time. Parental neurofibromatosis type 1 and low education were related to greater cognitive difficulties in children. [ABSTRACT FROM AUTHOR]

A survey of 11 novels featuring a character identified as a clinical psychologist, suggests that fictional psychologists are largely indistinguishable from other psy-professionals and are often unboundaried in their practice. [ABSTRACT FROM AUTHOR]

The question of how to create benign organisational cultures in health care is a topic of particular concern in the UK at the present time. The current study aimed to further understanding of complex health care cultures in the National Health Service (NHS), with a focus on an acute adult in-patient psychiatric ward. The psychoanalytic observational method was used for this purpose. The first author conducted six-hour long observation sessions on the ward at weekly intervals, writing detailed process recordings after each observation to take to a supervision group for discussion. The six presentations of observational material and the responses of the supervision group were audiotaped and transcribed. These data were then analysed thematically. The picture that emerged was of a fragile ward environment in which staff appeared fearful of engagement with patients, there was a sense of confusion regarding roles and decision-making processes, and the nursing team felt burdened by responsibility, isolated and anxious about criticism from outside. Contemporary developments within the social defence paradigm are applied to these findings in the context of the intense pressures currently facing staff in the NHS. [ABSTRACT FROM AUTHOR]

In this article, the author discusses her change of career and her experiences of writing her debut novel "Sugar and Snails" about a transgendered psychologist and writers of literary fiction need to be at least amateur psychologists to get to grips with character complexity.

The Panama Canal region is susceptible to non-native species introductions due to the heavy international shipping traffic through the area. Ascidian introductions are occurring worldwide but little is known about introductions at the Panama Canal. Surveys were conducted in 2002, 2008, and 2009 within the Pacific and Atlantic entrances to the canal. We found a high diversity of ascidians on both sides of the canal, dominated by non-native species; six species occurred at both Pacific and Atlantic Panama sites. This is the first report of Polyandrocarpa anguinea and P. sagamiensis in Atlantic Panama waters and Ascidia incrassata, Ascidia sydneiensis, Botrylloides nigrum, Botryllus planus, Didemnum perlucidum, Diplosoma listerianum, Microcosmus exasperatus, Polyandrocarpa zorritensis, Polyclinum constellatum, Symplegma brakenhielmi, Symplegma rubra, and Trididemnum orbiculatum in Pacific Panama waters. The canal may serve as a major invasion corridor for ascidians and should be monitored over time. [ABSTRACT FROM AUTHOR]

Little is known about the ascidian fauna of Pacific Panama. Ascidian surveys were conducted in the southern Gulf of Chiriquí on the Pacific coast of Panama in January 2008 and 2009. Surveys along linear transects at 2-3 m depth (snorkel, 2008) and 5 and 12 m depth (SCUBA, 2009) were conducted at multiple sites within a chain of islands extending out from the mainland. Twelve different ascidian taxa were observed with mean densities of up to ∼17 ascidians·m-2. The most abundant species was Rhopalaea birkelandi. Two of the most abundant taxa (Ascidia sp., Pyura sp.) appear to represent previously undescribed species. Several species of didemnids were also abundant. Ascidians were most abundant near the coast of the mainland and were less abundant near the islands farthest offshore. These data on Panamanian ascidian communities provide a baseline of local biodiversity against which it will be possible to determine whether the communities change over time, if additional species become introduced to the region, or if native Panamanian species become invasive in other parts of the world. [ABSTRACT FROM AUTHOR]

Abstract: Autoantibody production is associated with a variety of ocular disorders, including autoimmune retinopathy (AIR) and age-related macular degeneration (AMD). A breakdown of immunologic tolerance (ocular immune privilege), including the blood–retinal barrier, anti-immune and anti-inflammatory proteins, and anterior chamber-associated immune deviation may play important roles in these disorders. Although the exact triggers for ocular autoimmunity are unknown, autoimmune targeting of retinal tissue is clearly associated with and may contribute to the pathogenesis of both AIR and AMD. Autoantibody production has long been associated with AIR, a collection of disorders that includes cancer-associated retinopathy, melanoma-associated retinopathy and non-paraneoplastic autoimmune retinopathy. A growing body of evidence indicates that AMD pathogenesis, too, involves ocular inflammation and autoimmunity. Identification and quantification of autoantibodies produced in patients with AIR and AMD may assist with diagnosis, prognosis, and choice of treatments. Animal models that allow investigation of ocular autoimmunity will also be needed to better understand the disease processes and to develop novel therapies. In this review we discuss ocular immune privilege and potential mechanisms of autoimmunity in the eye. We describe how autoimmunity relates to the pathogenesis of AIR and AMD. We explain how the antigen microarray technique is used to detect autoantibodies in patient serum samples, and discuss how current animal models for AMD can be used to investigate autoimmune pathogenesis. Finally, we outline unanswered questions and exciting areas of future study related to autoimmune retinal degeneration. [Copyright &y& Elsevier]

Abstract: Blood vessels, either in insufficient numbers or in excess, contribute to the pathogenesis of many diseases. Agents that stimulate angiogenesis can improve blood flow in patients with ischemic diseases, whereas anti-angiogenic agents are used to treat disorders ranging from macular degeneration to cancer. In this review I describe in vitro assays that can be used to assess the activity of agents that affect angiogenesis. Means of quantifying endothelial cell matrix degradation, migration, proliferation, apoptosis and morphogenesis are discussed, as are embryoid body, aortic ring and metatarsal assays of vessel outgrowth. Strengths and limitations of these techniques are also addressed. [Copyright &y& Elsevier]

Blood vessel growth is critical for embryonic development and contributes to pathologies including cancer and diabetic retinopathy. A growing body of evidence suggests that signaling via the Wnt/β-catenin pathway contributes to angiogenesis, and that paracrine Wnt signaling might alter endothelial cell function. To test the hypothesis that Wnt signaling promotes endothelial cell proliferation and vessel growth, we treated bovine aortic endothelial cells with Wnt1, Wnt2 and Wnt5a derived from coculture with Wnt-expressing fibroblasts. Endothelial cells cultured in the presence of Wnt1 displayed increased Wnt/β-catenin signaling, proliferation and capillary stability in vitro. Wnt5a, which primarily signals via an alternate Wnt pathway, the Wnt/Ca++ pathway, decreased both cell number and capillary length. Wnt2, which in other cell types activates the Wnt/β-catenin pathway, did not activate signaling, affect cell number or increase capillary length. These results suggest that Wnt/β-catenin and Wnt/Ca++ signals might have opposing effects on angiogenesis. [ABSTRACT FROM AUTHOR]

Perceptions of the value of work for people with severe and enduring mental health problems have changed frequently over the last two decades. With the new social inclusion agenda manifest in the Disability Discrimination Act and in the NHS modernization agenda, work is once again in vogue. There is a need for a way of evaluating work which draws on its potential contribution to psychological well-being as well as its provision of a valued social role and which is less susceptible to fluctuations in health and social policy. Jahoda's work on the psychosocial functions of work provides such a framework and this study sets out to explore its utility among workers who are severely disabled by mental health problems. Twelve of the psychosocial functions of work were rated by 50 people attending two sheltered work placements according to how important they were perceived to he and the extent to which the functions were fulfilled through their attendance. Satisfaction of the psychosocial functions through work was compared with their satisfaction through other aspects of the respondents' lives, till functions were perceived as important, hut self-confidence/self-esteem was rated as more important than most of the others. Structure to the day, self-confidence and social contact were better satisfied through work than were decision making, practising old skills and having goals to aim for. In general, the results showed that the functions were fulfilled better by work than by other aspects of the respondents' lives. The study supports the notion that work is of value in the rehabilitation of people with severe and enduring mental health problems and offers a possible framework for the further exploration of this theme, both within mental health services and the community at large. [ABSTRACT FROM AUTHOR]

Research has shown that quality of life (QOL) among people with severe and enduring mental health problems is better if they live in the community rather than in hospital. In the course of a study to replicate this result in one particular service, comparisons were made between different QOL measures in their suitability for routine clinical use. Forty-five hospital and community residents each took part in four out of six QOL assessments: the Life Experience Checklist (Ager, 1990) in user and keyworker report forms; the Quality of Life Questionnaire (Bigelow, McFarland & Olson, 1991); the Quality of Life Interview (Lehman, 1983); Values Satisfaction (Hartley, 1988) and Five Accomplishments (developed specifically for the study). Measures were also taken of adaptive behaviours and psychiatric symptomatology, as well as the practicalities of completion. The expected difference between hospital and community residents was found for three of the six measures (LEC-keyworker, Bigelow and Five Accomplishments), which were also strongly correlated with psychiatric symptomatology and adaptive behaviour scores. The measures differed considerably in the numbers of failures to complete, the percentage of missing data and the amount of face-to-face contact with service users required. The correlations between subscale scores on the different measures were generally low. The study raises questions about the robustness of the QOL construct, and its use as an outcome measure in mental health. [ABSTRACT FROM AUTHOR]

Regular observations were made of a group of residents and staff on a long stay psychiatric ward and in the early months following their move to the community. During the period before the move, staff and residents colluded to prevent residents` active involvement in the preparations. Immediately following the move, staff seemed unsure of their roles and value, and residents expressed continued uncertainty about their identity as psychiatric patients versus members of the community. The results were interpreted in terms of the threat that transition from hospital to community represents to the defensive social structures developed by each group to cope with the anxieties inherent in their position. For the residents, this threat is to their already ambiguous identities as neither "mad" nor "normal". For the staff, it means greater intimacy with the residents and raises expectations of improvement that may not be fulfilled. [ABSTRACT FROM AUTHOR]

Clinicians are increasingly being required to take on additional management duties in today's National Health Service. The framework of social defences provides one way of understanding the role-conflict for these clinician-managers. It is proposed that clinicians cope with the anxieties of health-care work by projecting unacceptable aspects of themselves into managers and that managers develop defensive social structures involving projection into clinicians. The current NHS culture and the associated increased anxiety exacerbates the reliance on these defensive structures. This makes collaboration between clinicians and managers particularly difficult, and results in increased anxiety for those who occupy the dual role. [ABSTRACT FROM PUBLISHER]

Purpose: To determine the toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of cediranib administered orally, once daily, continuously in children and adolescents with solid tumors., Patients and Methods: Children and adolescents with refractory solid tumors, excluding primary brain tumors, were eligible. DLT at the starting dose of 12 mg/m(2)/d resulted in de-escalation to 8 mg/m(2)/d and subsequent re-escalation to 12 and 17 mg/m(2)/d. Pharmacokinetic and pharmacodynamic studies were performed during cycle 1. Response was evaluated using WHO criteria., Results: Sixteen patients (median age, 15 years; range, 8 to 18 years) were evaluable for toxicity. DLTs (grade 3 nausea, vomiting, fatigue in one; hypertension and prolonged corrected QT interval in another) occurred in patients initially enrolled at 12 mg/m(2)/d. Subsequently, 8 mg/m(2)/d was well tolerated in three patients. An additional seven patients were enrolled at 12 mg/m(2)/d; one had DLT (grade 3 diarrhea). At 17 mg/m(2)/d, two of four patients had DLTs (grade 3 nausea; intolerable grade 2 fatigue). Non-dose-limiting toxicities included left ventricular dysfunction, elevated thyroid stimulating hormone, palmar-plantar erythrodysesthesia, weight loss, and headache. The MTD of cediranib was 12 mg/m(2)/d (adult fixed dose equivalent, 20 mg). At 12 mg/m(2)/d, the median area under the plasma concentration-time curve extrapolated to infinity (AUC(0-∞)) was 900 ng·h/mL, which is similar to adults receiving 20 mg. Objective responses were observed in patients with Ewing sarcoma, synovial sarcoma, and osteosarcoma., Conclusion: The recommended monotherapy dose of cediranib for children with extracranial solid tumors is 12 mg/m(2)/d administered orally, once daily, continuously. A phase II study is in development.

Purpose: Ixabepilone is a microtubule-stabilizing agent with activity in adult solid tumors and in pediatric tumor xenograft models that are resistant to paclitaxel. The maximum tolerated dose on the daily-for-5-days i.v. schedule was 6 mg/m(2)/dose in adults and 8 mg/m(2)/dose in children, and the primary dose-limiting toxicity (DLT) was neutropenia. This study aimed to determine the response rate to ixabepilone in six solid tumor strata in children and young adults., Experimental Design: We conducted a phase II trial of ixabepilone (8 mg/m(2)/dose for 5 days every 21 days) using a two-stage design in taxane-naïve children and young adults with treatment-refractory, measurable rhabdomyosarcoma, Ewing sarcoma family tumors, osteosarcoma, synovial sarcoma, or malignant peripheral nerve sheath tumor, neuroblastoma, and Wilms tumor., Results: Sixty-one eligible patients (36 male) were enrolled. Median (range) age was 13 years (range, 3-36). Fifty-nine patients were fully evaluable for toxicity and response. DLTs, most commonly myelosuppression, occurred in 11 patients (15% incidence in 3-18 years old and 33% in 19-36 years old; P = 0.2) during cycle 1. The median (range) number of cycles was 2 (range, 1-38). No partial or complete responses (response evaluation criteria in solid tumors) were observed. Seven patients received >or=3 cycles, and two had prolonged stable disease (Wilms' tumor, 38 cycles; synovial sarcoma, 8 cycles)., Conclusions: Ixabepilone at 8 mg/m(2)/dose daily for 5 days was tolerable in children and adolescents, but did not show evidence of clinical activity in the childhood solid tumors studied.

Purpose: To determine the toxicity profile, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) of ABT-751 administered orally once daily for 21 days, repeated every 28 days in a pediatric population., Experimental Design: Patients who were < or = 18 years with relapsed or refractory solid tumors and who were able to swallow capsules were eligible. The starting dose was 75 mg/m(2)/d (n = 3) and was escalated to 100 (n = 6), 130 (n = 5), and 165 (n = 3) mg/m(2)/d in cohorts of three to six patients. The MTD was determined from DLTs occurring during the first treatment cycle., Results: Nineteen children (median age, 13 years; range, 5-18 years) were enrolled, and 17 were evaluable for toxicity. Diagnoses included neuroblastoma (n = 9), sarcomas (n = 9), and other solid tumors (n = 1). DLTs included fatigue, sensory neuropathy, transient hypertension, neutropenia, thrombocytopenia, nausea, vomiting, dehydration, abdominal pain, and constipation. The MTD of ABT-751 administered daily for 21 days every 28 days was 100 mg/m(2)/d. Non-DLT at the MTD included bone marrow suppression, gastrointestinal toxicities (anorexia, abdominal pain, nausea, vomiting, and constipation), and sensory and motor neuropathies. The median number of cycles administered was one (range, one to five). Tolerance of repeated treatment cycles was poor., Conclusion: Fatigue, hematologic, and gastrointestinal toxicities limited the tolerability of ABT-751 administered to children on the once daily for 21 days every 28 days schedule. The MTD in children with solid tumors (100 mg/m(2)/d daily for 21 days) was similar to the recommended dose in adults with solid tumors (200 mg fixed dose) receiving the same dosing schedule.

A growing body of evidence implicates Wnt signaling in the control of angiogenesis. To better understand the role of the Wnt/beta-catenin pathway in endothelial cells (EC), we examined endogenous signaling activity and signaling component expression in vascular cells. We observed stabilization of cytosolic beta-catenin and activation of a T-cell factor (TCF) -luciferase promoter, hallmarks of canonical Wnt signaling activity, in cultured EC. This activity was increased in subconfluent EC, which are known to display characteristics of angiogenic EC, compared with confluent EC, which have a more differentiated phenotype. Endogenous TCF activity was inhibited by transfection with a secreted inhibitor of canonical Wnt signaling. A systematic analysis of Wnt, Fzd, SFRP, and Dkk gene expression in human EC (cultured and freshly isolated), smooth muscle cells (cultured), and aorta demonstrated that numerous Wnt signaling components are expressed by vascular cells. We conclude that Wnt signaling components are expressed and active in cultured EC., ((c) 2006 Wiley-Liss, Inc.)

Purpose: To determine the toxicity profile, dose-limiting toxicities, and maximum tolerated dose of ABT-751 administered orally once daily for 7 days, repeated every 21 days., Experimental Design: Patients who were 40% higher than the maximum tolerated dose in adults receiving the same dosing schedule.

This paper is based upon our experience as a psychosocial team working on the paediatric heart/heart-lung (H/HLT) programme for the last 10 years. During this time more than 350 children have been assessed, 240 have been put onto an active waiting list and 160 have had transplants. The essence of this paper is a detailed description of the multidisciplinary and comprehensive approach to children who are being considered for heart or heart-lung transplantation, and their families. The key issues of which we have become aware are: creating a therapeutic alliance; listening to and involving the children; involving the wider network; understanding the family's illness narrative and their individual belief systems, including issues of culture, ethnicity and spirituality; acknowledging and addressing the power imbalance between the child/family and professional. (Int J Psych Clin Pract 2000; 4:93-99).