Neural control of the heart: developmental changes in ionic conductances in mammalian intrinsic cardiac neurons

The expression and properties of ionic channels were investigated in dissociated neurons from neonatal and adult rat intracardiac ganglia. Changes in the hyperpolarization-activated and ATP-sensitive K+ conductances during postnatal development and their role in neuronal excitability were examined. The hyperpolarization-activated nonselective cation current, I-h, was observed in all neurons studied and displayed slow time-dependent rectification. An inwardly rectifying K+ current, I-K(I), was present in a population of neurons from adult but not neonatal rats and was sensitive to block by extracellular Ba2+. Using the perforated-patch recording configuration, an ATP-sensitive K+ (K-ATP) conductance was identified in greater than or equal to 50% of intracardiac neurons from adult rats. Levcromakalim evoked membrane hyperpolarization, which was inhibited by the sulphonylurea drugs. glibenclamide and tolbutamide. Exposure to hypoxic conditions also activated a membrane current similar to that induced by levcromakalim and was inhibited by glibenclamide. Changes in the complement of ion channels during postnatal development may underlie observed differences in the function of intracardiac ganglion neurons during maturation. Furthermore, activation of hyperpolarization-activated and KATP channels in mammalian intracardiac neurons may play a role in neural regulation of the mature heart and cardiac function during ischaemia-reperfusion. (C) 2002 Elsevier Science B.V All rights reserved.

The role of growth hormone in fetal development

Studies across several species, particularly the mouse, show that growth hormone (GH, somatotrophin) is an important determinant of litter size, and to a lesser extent, of birth length. GH acts at all stages of development, from ovulation through preimplantation development to the late fetus, with actions on both embryo/fetus and mother contributing to successful fetal development. The fact that these are not more obvious in vivo is likely a result of redundancy of cytokine hormone action, particularly in relation to prolactin, which shares common actions and receptor locations with GH. (C) 2002 Elsevier Science Ltd. All rights reserved.

Temporal and spatial expression of fibroblast growth factor receptor 4 isoforms in murine tissues

Fibroblast growth factor receptors (FGFRs) undergo highly regulated spatial and temporal changes of expression during development. This study describes the use of quantitative reverse transcriptase-polymerase chain reaction and immunochemistry to assess the changes in expression of FGFR4 as compared to its FGFR4-17a and -17b isoforms in mouse tissues, from early embryogenesis through to adulthood. Compared to FGFR4, the expression of the isoforms is more restricted at all developmental stages tested. The reverse transcriptase-polymerase chain reaction demonstrated that FGFR4 is expressed in more tissue types than either of its isoforms: it was found predominantly in lung, liver, brain, skeletal muscle and kidney, whereas the FGFR4-17a form was detected in lung and skeletal muscle, and the FGFR4-17b form only in lung, liver, skeletal muscle and kidney. Immunohistochemistry confirmed strong FGFR4-17b expression in the postnatal lung. When combined, the results suggest that FGFR4 variants play important roles particularly in lung and skeletal muscle development.

Distribution of two splice variants of the glutamate transporter GLT-1 in the developing rat retina

The distributions of a carboxyl terminal splice variant of the glutamate transporter GLT-1, referred to as GLT-1B, and the carboxyl terminus of the originally described variant of GLT-1, referred to hereafter as GLT-1alpha, were examined using specific antisera. GLT-1B was present in the retina at very early developmental stages. Labelling was demonstrable at embryonic day 14, and strong labelling was evident by embryonic day 18. Such labelling was initially restricted to populations of cone photoreceptors, the processes of which extended through the entire thickness of the retina and appeared to make contact with the retinal ganglion cells. During postnatal development the GLT-1B-positive photoreceptor processes retracted to form the outer plexiform layer, and around postnatal day 7, GLT-1B-immunoreactive bipolar cells appeared. The pattern of labelling of bipolar cell processes within the inner plexiform layer changed during postnatal development. Two strata of strongly immunoreactive terminals were initially evident in the inner plexiform layer, but by adulthood these two bands were no longer evident and labelling was restricted to the somata and processes (but not synaptic terminals) of the bipolar cells, as well as the somata, processes, and terminals of cone photoreceptors. By contrast, GLT-1alpha appeared late in postnatal development and was restricted mainly to a population of amacrine cells, although transient labelling was also associated with punctate elements in the outer plexiform layer, which may represent photoreceptor terminals, (C) 2002 Wiley-Liss, Inc.

Differential modes of alaryngeal communication and long-term voice outcomes following pharyngolaryngectomy and laryngectomy

Patterns of vocal rehabilitation for 37 pharyngolaryngectomy patients and 55 total laryngectomy patients over a 5-year period were compared. An electrolarynx (EL) was introduced as the initial communication mode immediately after surgery for 98% of patients, with 30% of pharyngolaryngectomy and 74% of laryngectomy patients subsequently developing tracheoesophageal speech (TES) as their primary mode of communication. Follow-up with 14 of 37 pharyngolaryngectomy patients and 36 of 55 laryngectomy patients was conducted 1-6 years following surgery and revealed that 90% of the pharyngolaryngectomy patients maintained the use of TES in the long term compared to 69% of the laryngectomy group. Long-term outcomes relating to communication disability and handicap did not differ significantly between the two surgical groups, however the laryngectomy patients had significantly higher levels of wellbeing. Across the whole group of patients, statistical comparison revealed that patients using TES had significantly lower levels of disability, handicap and distress than EL users. Considering that lower levels of disability, handicap and distress are associated with TES, and the data supports that suitably selected patients can maintain functional TES in the long term, increased application of this form of communication rehabilitation should be encouraged where viable for the pharyngolaryngectomy population. Copyright (C) 2003 S. Karger AG, Basel.

Core outcome domains for chronic pain clinical trials: IMMPACT recommendations

Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. Methods. Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia. governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. Conclusions. There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy. (C) 2003 International Association for the Study of Pain.

Etiology of ovarian failure in blepharophimosis ptosis epicanthus inversus syndrome: FOXL2 is a conserved, early-acting gene in vertebrate ovarian development

Blepharophimosis ptosis epicanthus inversus syndrome (BPES) is a human disorder caused by mutations in the forkhead transcription factor gene FOXL2 and is characterized by facial dysmorphology combined in some cases with ovarian failure. To better understand the role of FOXL2 in the etiology of ovarian failure in BPES, we examined its expression in embryonic ovaries of mice, chickens, and red-eared slider turtles, representatives of three phylogenetically distant vertebrate groups that have different mechanisms of sex determination. Expression of Foxl2 was detected in early ovaries of all three species around the time of sex determination and was associated with both somatic and germ cell populations in mice. Expression was sexually dimorphic in all cases. Sequence analysis of turtle and chicken FoxL2 orthologues indicated an unusually high degree of structural conservation during evolution. FoxL2 was found to be autosomal in chickens, and therefore unlikely to represent the dominant ovarian-determining gene that has been postulated to exist as a possible explanation for female heterogamety in birds. Our observations suggest that BPES may result from early abnormalities in regulating the development of the fetal ovary, rather than premature degeneration of the postnatal or adult ovary. Further, our results suggest that FOXL2 is a highly conserved early regulator of vertebrate ovarian development.

Hyperinsulinism and overgrowth without obesity

We report a 5 year old girl with postnatal overgrowth (height velocity >97th centile), hyperinsulinaemia, and increased insulin-like growth factor 1 for age, without evidence of bioactive or immunoreactive growth hormone excess or pituitary abnormality. Although her overgrowth may be a result of hyperinsulinism, her serum contains a factor (neither insulin nor IGF-1) which is able to stimulate the proliferation of lymphocyte precursors, and this could also account for the overgrowth. Over the course of two years observation she has developed acanthosis nigricans and diabetes mellitus.

Nutritional effects on neuron numbers

Undemutrition during early life is known to cause deficits and distortions of brain structure although it has remained uncertain whether or not this includes a diminution of the total numbers of neurons. Estimates of numerical density (e.g. number of cells per microscopic field, or number of cells per unit area of section, or number of cells per unit volume of tissue) are extremely difficult to interpret and do not provide estimates of total numbers of cells. However, advances in stereological techniques have made it possible to obtain unbiased estimates of total numbers of cells in well defined biological structures. These methods have been utilised in studies to determine the effects of varying periods of undernutrition during early life on the numbers of neurons in various regions of the rat brain. The regions examined so far have included the cerebellum, the dentate gyrus, the olfactory bulbs and the cerebral cortex. The only region to show, unequivocally, that a period of undernutrition during early life causes a deficit in the number of neurons was the dentate gyrus. These findings are discussed in the context of other morphological and functional deficits present in undernourished animals.

A experiência de mulheres e a decisão pelo aborto provocado em uma região do Espírito Santo, Brasil

O escopo deste trabalho buscou compreender as percepções de mulheres que passaram pela decisão do aborto provocadona Microrregião de São Mateus (norte do estado do Espírito Santo, Brasil), a partir do percurso e das interações que se sustentaram nesse processo. Foram realizadas entrevistas com roteiro semiestruturado com sete mulheres sobre essa experiência no ambiente domiciliar dos sujeitos do presente estudo. Os dados foram colhidos em entrevistas abertas e foram analisados à luz do referencial teórico de autores que discorrem acerca do tema e também acerca da ciência bioética.O estudo apresenta seis categorias: O aborto na perspectiva da decisão íntima; o aborto como fonte de revelações de sentimentos; o contemplar peremptório da atitude;técnicas empregadas na intencionalidade e no ato de abortar; sustentando a decisão pelas relações comunitárias; e conteúdos e confidências femininas. A experiência das mulheres foi marcada poruma diversidade de sentimentos, como tristeza, culpa, arrependimento, desespero e dor emocional, todavia, também, pelo alívio com o fim da gravidez e do risco de morte. Angústia adicional foi condicionadaa partir da percepção de fatores contribuintes da decisão, como falta de condições financeiras, falta de apoio da família ou do parceiro e instabilidade no relacionamento com parceiro. Este estudo também sinalizou que o caráter cultural e histórico da gestação, no sentido da norma social, faz-se presente nas mulheres que vivenciam o aborto provocado; demonstrou que as mulheres do presente estudo encontram-se à margem das políticas públicas e de saúde; assinalou que os programas de planejamento familiar ou de saúde reprodutiva deveriam ser estruturados de forma a ajudar também a lidar com problemas de destituição social, econômica e educacional dessa população vulnerada, no sentido de que essas mulheres ultrapassem a proteção social básica e sejam amparadas por serviços de saúde, que constituam espaços equânimes de escuta, orientação e resolução.

Comparative analysis between statistical and artificial intelligence models in business failure prediction

A growing number of predicting corporate failure models has emerged since 60s. Economic and social consequences of business failure can be dramatic, thus it is not surprise that the issue has been of growing interest in academic research as well as in business context. The main purpose of this study is to compare the predictive ability of five developed models based on three statistical techniques (Discriminant Analysis, Logit and Probit) and two models based on Artificial Intelligence (Neural Networks and Rough Sets). The five models were employed to a dataset of 420 non-bankrupt firms and 125 bankrupt firms belonging to the textile and clothing industry, over the period 2003–09. Results show that all the models performed well, with an overall correct classification level higher than 90%, and a type II error always less than 2%. The type I error increases as we move away from the year prior to failure. Our models contribute to the discussion of corporate financial distress causes. Moreover it can be used to assist decisions of creditors, investors and auditors. Additionally, this research can be of great contribution to devisers of national economic policies that aim to reduce industrial unemployment.

Survival Analysis Employed in Predicting Corporate Failure: A Forecasting Model Proposal

In face of the current economic and financial environment, predicting corporate bankruptcy is arguably a phenomenon of increasing interest to investors, creditors, borrowing firms, and governments alike. Within the strand of literature focused on bankruptcy forecasting we can find diverse types of research employing a wide variety of techniques, but only a few researchers have used survival analysis for the examination of this issue. We propose a model for the prediction of corporate bankruptcy based on survival analysis, a technique which stands on its own merits. In this research, the hazard rate is the probability of ‘‘bankruptcy’’ as of time t, conditional upon having survived until time t. Many hazard models are applied in a context where the running of time naturally affects the hazard rate. The model employed in this paper uses the time of survival or the hazard risk as dependent variable, considering the unsuccessful companies as censured observations.

Comparative Analysis between Statistical and Artificial Intelligence Models in Business Failure Prediction

A growing number of predicting corporate failure models has emerged since 60s. Economic and social consequences of business failure can be dramatic, thus it is not surprise that the issue has been of growing interest in academic research as well as in business context. The main purpose of this study is to compare the predictive ability of five developed models based on three statistical techniques (Discriminant Analysis, Logit and Probit) and two models based on Artificial Intelligence (Neural Networks and Rough Sets). The five models were employed to a dataset of 420 non-bankrupt firms and 125 bankrupt firms belonging to the textile and clothing industry, over the period 2003–09. Results show that all the models performed well, with an overall correct classification level higher than 90%, and a type II error always less than 2%. The type I error increases as we move away from the year prior to failure. Our models contribute to the discussion of corporate financial distress causes. Moreover it can be used to assist decisions of creditors, investors and auditors. Additionally, this research can be of great contribution to devisers of national economic policies that aim to reduce industrial unemployment.

Comportamento dinâmico da rede eléctrica da ilha de São Vicente em Cabo Verde: estabilidade de tensão

Neste trabalho é efectuado, não só o diagnóstico em regime permanente, mas também o estudo, simulação e análise do comportamento dinâmico da rede eléctrica da ilha de São Vicente em Cabo Verde. Os estudos de estabilidade transitória desempenham um importante papel, tanto no planeamento como na operação dos sistemas de potência. Tais estudos são realizados, em grande parte, através de simulação digital no domínio do tempo, utilizando integração numérica para resolver as equações não-lineares que modelam a dinâmica do sistema e dependem da existência de registos reais de perturbação (ex: osciloperturbografia). O objectivo do trabalho será também verificar a aplicabilidade dos requisitos técnicos que as unidades geradoras devem ter, no que concerne ao controlo de tensão, estabelecidos na futura regulamentação europeia desenvolvida pela ENTSO-E (European Network Transmission System Operator for Electricity). De entre os requisitos analisou-se a capacidade das máquinas existentes suportarem cavas de tensão decorrentes de curto-circuitos trifásicos simétricos, Fault Ride Through, no ponto de ligação à rede. Identificaram-se para o efeito os factores que influenciam a estabilidade desta rede, em regime perturbado nomeadamente: (i) duração do defeito, (ii) caracterização da carga, com e sem a presença do sistema de controlo de tensão (AVR) em unidades de geração síncronas. Na ausência de registos reais sobre o comportamento do sistema, conclui-se que este é sensível à elasticidade das cargas em particular do tipo potência constante, existindo risco de perda de estabilidade, neste caso, para defeitos superiores a 5ms sem AVR. A existência de AVR nesta rede afigura-se como indispensável para garantir estabilidade de tensão sendo contudo necessário proceder a uma correcta parametrização.