Linkage of Paget disease of bone to a novel region on human chromosome 18q23

Paget disease of bone (PDB) is characterized by increased osteoclast activity and localized abnormal bone remodeling. PDB has a significant genetic component, with evidence of linkage to chromosomes 6p21.3 (PDB1) and 18q21-22 (PDB2) in some pedigrees. There is evidence of genetic heterogeneity, with other pedigrees showing negative linkage to these regions. TNFRSF11A, a gene that is essential for osteoclast formation and that encodes receptor activator of nuclear factor-kappa B (RANK), has been mapped to the PDB2 region. TNFRSF11A mutations that segregate in pedigrees with either familial expansile osteolysis or familial PDB have been identified; however, linkage studies and mutation screening have excluded the involvement of RANK in the majority of patients with PDB. We have excluded linkage, both to PDB1 and to PDB2, in a large multigenerational pedigree with multiple family members affected by PDB. We have conducted a genomewide scan of this pedigree, followed by fine mapping and multipoint analysis in regions of interest. The peak two-point LOD scores from the genomewide scan were 2.75, at D7S507, and 1.76, at D18S70. Multipoint and haplotype analysis of markers flanking D7S507 did not support linkage to this region. Haplotype analysis of markers flanking D18S70 demonstrated a haplotype segregating with PDB in a large subpedigree. This subpedigree had a significantly lower age at diagnosis than the rest of the pedigree (51.2 +/- 8.5 vs. 64.2 +/- 9.7 years; P = .0012). Linkage analysis of this subpedigree demonstrated a peak two-point LOD score of 4.23, at marker D18S1390 (theta = 0), and a peak multipoint LOD score of 4.71, at marker D18S70. Our data are consistent with genetic heterogeneity within the pedigree and indicate that 18q23 harbors a novel susceptibility gene for PDB.

Noninvasive measurement of cerebral bioimpedance for detection of cerebral edema in the neonatal piglet

The association of sustained cerebral edema with poor neurological outcome following hypoxia-ischaemia in the neonate suggests that measurement of cerebral edema may allow early prediction of outcome in these infants. Direct measurements of cerebral impedance have been widely used in animal studies to monitor cerebral edema, but such invasive measurements are not possible in the human neonate. This study investigated the ability of noninvasive cerebral impedance measurements to detect cerebral edema following hypoxia-ischaemia. One-day-old piglets were anaesthetized, intubated and ventilated. Hypoxia was induced by reducing the inspired oxygen concentration to 4-6% O-2. Noninvasive cerebral bioimpedance was measured using gel electrodes attached to the scalp. Cerebral bioimpedance was also measured directly by insertion of two silver-silver chloride electrodes subdurally. Noninvasive and invasive measurements were made before, during and after hypoxia. Whole body impedance was measured to assess overall fluid movements. Intracranial pressure was measured continuously via a catheter inserted subdurally, as an index of cerebral edema. There was good agreement between noninvasive and invasive measurements of cerebral impedance although externally obtained responses were attenuated. Noninvasive measurements were also well correlated with intracranial pressure. Whole body impedance changes did not account for increases in noninvasively measured cerebral impedance. Results suggest that noninvasive cerebral impedance measurements do reflect intracranial events, and are able to detect cerebral edema following hypoxia-ischaemia in the neonate. (C) 2002 Elsevier Science B.V. All rights reserved.

Fas ligand and tumour counter-attack in colorectal cancer stratified according to microsatellite instability status

Expression of membrane-bound Fas ligand (FasL) by colorectal cancer cells may allow the development of an immune-privileged site by eliminating incoming tumour-infiltrating lymphocytes (TILs) in a Fas-mediated counter-attack. Sporadic colorectal cancer can be subdivided into three groups based on the level of DNA microsatellite instability (NISI). High-level NISI (NISI-High) is characterized by the presence of TILs and a favourable prognosis, while microsatellite-stable (MSS) cancers are TIL-deficient and low-level MSI (MSI-Low) is associated with an intermediate TIL density. The purpose of this study was to establish the relationship between MSI status and FasL expression in primary colorectal adenocarcinoma. Using immunohistochemistry and a selected series of 101 cancers previously classified as 31 MSI-High, 30 NISI-Low, and 40 MISS, the present study sought to confirm the hypothesis that increased TIL density in MSI-High cancers is associated with low or absent membrane-bound FasL expression, while increased FasL in MSS cancers allows the killing of host TILs. TUNEL/CD3 double staining was also used to determine whether MSS cancers contain higher numbers of apoptotic TILs in vivo than MSI-High or MSI-Low cancers. Contrary to the initial hypothesis, it was found that MSI-High cancers were associated with higher FasL expression (p = 0.04) and a stronger intensity of FasL staining (p = 0.007). In addition, mucinous carcinomas were independently characterized by increased FasL expression (p = 0.03) and staining intensity (p = 0.0005). Higher FasL expression and staining intensity did not correlate with reduced TIL density or increased numbers of apoptotic TILs. However, consistent with the hypothesis that curtailment of the host anti-tumour immune response contributes to the poor prognosis in MSS cancers, it was found that apoptotic TILs were most abundant in MSS carcinomas and metastatic Dukes' stage C or D tumours (p = 0.004; p = 0.046 respectively). This study therefore suggests that MSS colorectal cancers are killing incoming TILs in an effective tumour counter-attack, but apparently not via membrane-bound FasL. Copyright (C) 2003 John Wiley Sons, Ltd.

Writing the body of the mother: Narrative moments in Tsushima Yuko, Ariyoshi Sawako and Enchi Fumiko

This discussion argues the transformative potential inherent in the corporeal experience of motherhood as represented in selected textual moments of Japanese narrative. Narratives that address the experiences of the body of the mother are informed and given substance by an intense physicality, and thus have the potential to contest processes of social inscription in addition to suggesting alternative possibilities for all readers, not just those occupying an embodied maternal space. The discussion features brief events from the work of three writers who have written as mothers: Tsushima Y(u)macrko, Ariyoshi Sawako and Enchi Fumiko. In Yama o hashiru onna (1980; translated as Woman Running in the Mountains, 1991), Tsushima Y(u)macrko invites the reader to consider the embodied response to light of Takiko, a young pregnant woman. Emiko, the protagonist of Hishoku (Without Colour, 1967) by Ariyoshi Sawako, is the Japanese wife of an African American and has just given birth to a child. The daughter protagonist in Enchi Fumiko's 'Kami' ('Hair', 1957) operates a hairdressing business that is viable only with her mother's unpaid labour. The narratives are read through a matrix of post-structuralist theories of embodiment, drawing on the work of writers such as Julia Kristeva, Luce Irigaray and Elizabeth Grosz.

Quality of Life and Colorectal Cancer: a Review

Objectives: To describe what is known of quality of life for colorectal cancer patients, to review what has been done in the Australian setting and to identify emerging directions for future research to address current gaps in knowledge. Method: A literature search (using Medline, PsychInfo, CINAHL and Sociological Abstracts) was conducted and 41 articles identified for review. Results: Three key areas relating to quality of life in colorectal cancer patients emerged from the literature review: the definition and measurement of quality of life; predictors of quality of life; and the relationship of quality of life to survival. Results of existing studies are inconsistent in relation to quality of life over time and its relationship to survival. Small sample sizes and methodological limitations make interpretation difficult. Conclusions: There is a need for large-scale, longitudinal, population-based studies describing the quality of life experienced by colorectal cancer patients and its determinants. Measurement and simultaneous adjustment for potential confounding factors would productively advance knowledge in this area, as would an analysis of the economic cost of morbidity to the community and an assessment of the cost effectiveness of proposed interventions. Implications: As the Australian population ages, the prevalence of colorectal cancer within the community will increase. This burden of disease presents as a priority area for public health research. An improved understanding of quality of life and its predictors will inform the development and design of supportive interventions for those affected by the disease.

Graduate entry to medical studies: thoughts from 'down under' (editorial)

This invited editorial, reflecting on expectations of changing to graduate entry, eg enhanced maturity in the student cohort with greater self-sufficiency and taking of responsibility for learning in the context of adoption of a problem-based learning model, examines experiences of early post-change years and raises questions for contemplation by medical schools considering graduate entry.

Ger??ncia de recursos humanos no setor p??blico: li????es da reforma em pa??ses desenvolvidos

Texto que analisa aspectos diversos relativos aos Recursos Humanos do Servi??o P??blico nos pa??ses industrializados, visando contribuir para a solu????o dos dilemas enfrentados pelos pa??ses em desenvolvimento nos seus atuais processos de reforma do Estado.

Semin??rio internacional sobre educa????o a dist??ncia

Semin??rio internacional sobre educa????o a dist??ncia, realizado na ENAP em 09 de julho de 2007.

Parceria p??blico-privada: compreendendo o modelo brasileiro

A necessidade de viabilizar investimentos p??blicos em um contexto de restri????o fiscal impulsionou governos de diversos pa??ses a buscar na parceria com o setor privado a alternativa para a realiza????o de obras e servi??os p??blicos. A experi??ncia paradigm??tica do Reino Unido em programas de parceria p??blico-privada (PPP) norteou a implanta????o de iniciativas semelhantes mundo afora. No Brasil, a aprova????o, em dezembro de 2004, da lei que disciplina as normas para contrata????o de PPP deu in??cio a um processo que passar?? pela defini????o dos projetos priorit??rios e que culminar?? na consolida????o das parcerias como mais um instrumento para a viabiliza????o de obras e servi??os p??blicos de que o pa??s necessita. Esse artigo tem por objetivo elucidar o modelo brasileiro de parcerias p??blico-privadas. Ap??s uma contextualiza????o inicial, s??o discutidos os fundamentos que balizam a implanta????o de um programa de PPP e apresentadas algumas caracter??sticas gerais dos contratos. Por fim, s??o expostos os pontos centrais da lei brasileira.

??tica na administra????o p??blica

Esse texto ?? fruto do semin??rio ?????tica na Administra????o P??blica???, realizado na ENAP em 28 de setembro de 2004.

1?? Semin??rio Internacional sobre Educa????o a Dist??ncia para a Rede Escolas de Governo

Organizado em junho de 2007 pela ENAP, o Semin??rio Internacional sobre Educa????o a Dist??ncia reuniu em Bras??lia/DF, 72 participantes de 35 diferentes institui????es, sendo 28 do Brasil e sete internacionais. Com o objetivo de propiciar espa??o de aprendizagem sobre o tema e de privilegiar a troca de conhecimentos e experi??ncias entre os participantes, abordou os seguintes conte??dos: Panorama sobre Educa????o a Dist??ncia, Tend??ncias, desafios e necessidades das institui????es participantes, Constru????o de uma proposta de a????o comum. O Semin??rio Internacional sobre Educa????o a Dist??ncia mostrou a import??ncia de a????es sistematizadas para a democratiza????o das oportunidades de capacita????o para o servidor p??blico, como a utiliza????o das tecnologias da informa????o e da comunica????o no enfrentamento dos desafios relacionados ao aumento da efic??cia das institui????es que trabalham com forma????o e aperfei??oamento profissional. Nesse evento surgiu a proposta de continuidade de discuss??es com a realiza????o dos eventos nacionais e anuais com o objetivo de socializar conhecimentos e pr??ticas sobre essa tem??tica.

Seletividade de produtos naturais comerciais a Trichogramma pretiosum (Riley, 1879) (Hymenoptera: Trichogrammatidae)

A seletividade de produtos naturais a parasitoides é pouco conhecida. Em vista disso, este trabalho teve por objetivo avaliar a seletividade de produtos naturais comerciais a Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae). Os produtos utilizados foram Baicao®, Orobor® e Topneem®, nas concentrações recomendadas pelos fabricantes, e pulverizados sobre cartelas contendo ovos esterilizados de Anagasta kuehniella Zeller (Lepidoptera: Pyralidae). Teste com chance de escolha para parasitismo foi realizado, confinando-se uma fêmea de T. pretiosum com duas cartelas, uma pulverizada com o produto e outra considerada testemunha, avaliando-se a percentagem de parasitismo. O teste sem chance de escolha consistiu na pulverização dos tratamentos, em cartelas, previamente ou posteriormente ao parasitismo. Em ambos os testes, avaliaram-se o número de ovos parasitados, a percentagem de emergência e a longevidade de adultos. No teste com chance de escolha, os produtos Topneem® e Baicao® provocaram redução do parasitismo de T. pretiosum. No teste sem chance de escolha, Baicao®, pulverizado previamente sobre cartelas contendo ovos de A. kuehniella, interferiu negativamente na emergência de T. pretiosum. Houve redução do número de ovos parasitados quando Baicao® foi pulverizado no tratamento pré-parasitismo. Orobor® é seletivo a T. pretiosum nas condições de realização do experimento e não afetou negativamente os parâmetros avaliados. Baicao® não foi seletivo para T. pretiosum, afetou a maioria dos parâmetros avaliados e foi classificado como levemente nocivo quanto à toxicidade aos adultos do parasitoide, em condições de laboratório.