scispace - formally typeset
Search or ask a question

Showing papers by "University of Auckland published in 2003"


Journal ArticleDOI
TL;DR: This work summarizes the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks, a software-independent language for describing models common to research in many areas of computational biology.
Abstract: Motivation: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. Results: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. ∗ To whom correspondence should be addressed. Availability: The specification of SBML Level 1 is freely available from http://www.sbml.org/.

3,205 citations


Journal ArticleDOI
01 Feb 2003-Ecology
TL;DR: In this paper, the authors proposed the use of principal coordinate analysis (PCO) followed by either a canonical discriminant analysis (CDA) or a canonical correlation analysis (CCorA) to provide a flexible and meaningful constrained ordination of ecological species abundance data.
Abstract: A flexible method is needed for constrained ordination on the basis of any distance or dissimilarity measure, which will display a cloud of multivariate points by reference to a specific a priori hypothesis. We suggest the use of principal coordinate analysis (PCO, metric MDS), followed by either a canonical discriminant analysis (CDA, when the hypothesis concerns groups) or a canonical correlation analysis (CCorA, when the hypothesis concerns relationships with environmental or other variables), to provide a flexible and meaningful constrained ordination of ecological species abundance data. Called “CAP” for “Canonical Analysis of Principal coordinates,” this method will allow a constrained ordination to be done on the basis of any distance or dissimilarity measure. We describe CAP in detail, including how it can uncover patterns that are masked in an unconstrained MDS ordination. Canonical tests using permutations are also given, and we show how the method can be used (1) to place a new observation into...

2,157 citations


Journal ArticleDOI
TL;DR: The review shows that the burden of stroke is high and is likely to increase in future decades as a result of demographic and epidemiological transitions in populations and further research that uses the best possible methods are urgently needed in other populations of the world.
Abstract: Summary This overview of population-based studies of incidence, prevalence, mortality, and case-fatality of stroke was based on studies from 1990. Incidence (first stroke in an individual's lifetime) and prevalence were computed by age, sex, and stroke type. Age-standardised incidence and prevalence with the corresponding 95% CI were plotted for each study to facilitate comparisons. The review shows that the burden of stroke is high and is likely to increase in future decades as a result of demographic and epidemiological transitions in populations. The main features of stroke epidemiology include modest geographical variation in incidence, prevalence, and case-fatality among the—predominantly white—populations studied so far, and a stabilisation or reversal in the declining secular trends in the pre-1990s rates, especially in older people. However, further research that uses the best possible methods to study the incidence, risk factors, and outcome of stroke are urgently needed in other populations of the world, especially in less developed countries where the risk of stroke is high, lifestyles are changing rapidly, and population restructuring is occurring.

1,802 citations


Journal ArticleDOI
TL;DR: The devised NDBI method was applied to map urban land in the city of Nanjing, eastern China and results at an accuracy of 92.6% indicate that it can be used to fulfil the mapping objective reliably.
Abstract: Remotely sensed imagery is ideally used to monitor and detect land cover changes that occur frequently in urban and peri-urban areas as a consequence of incessant urbanization. It is a lengthy process to convert satellite imagery into land cover map using the existing methods of manual interpretation and parametric image classification digitally. In this paper we propose a new method based on Normalized Difference Built-up Index (NDBI) to automate the process of mapping built-up areas. It takes advantage of the unique spectral response of built-up areas and other land covers. Built-up areas are effectively mapped through arithmetic manipulation of re-coded Normalized Difference Vegetation Index (NDVI) and NDBI images derived from TM imagery. The devised NDBI method was applied to map urban land in the city of Nanjing, eastern China. The mapped results at an accuracy of 92.6% indicate that it can be used to fulfil the mapping objective reliably. Compared with the maximum likelihood classification method, t...

1,690 citations


Journal ArticleDOI
TL;DR: Adiponectin was effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice and could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine.
Abstract: Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.

1,239 citations


Journal ArticleDOI
TL;DR: Exercise is the most effective means of alleviating pain during DOMS, however the analgesic effect is also temporary, and athletes who must train on a daily basis should be encouraged to reduce the intensity and duration of exercise for 1–2 days following intense DOMS-inducing exercise.
Abstract: Delayed onset muscle soreness (DOMS) is a familiar experience for the elite or novice athlete. Symptoms can range from muscle tenderness to severe debilitating pain. The mechanisms, treatment strategies, and impact on athletic performance remain uncertain, despite the high incidence of DOMS. DOMS is most prevalent at the beginning of the sporting season when athletes are returning to training following a period of reduced activity. DOMS is also common when athletes are first introduced to certain types of activities regardless of the time of year. Eccentric activities induce micro-injury at a greater frequency and severity than other types of muscle actions. The intensity and duration of exercise are also important factors in DOMS onset. Up to six hypothesised theories have been proposed for the mechanism of DOMS, namely: lactic acid, muscle spasm, connective tissue damage, muscle damage, inflammation and the enzyme efflux theories. However, an integration of two or more theories is likely to explain muscle soreness. DOMS can affect athletic performance by causing a reduction in joint range of motion, shock attenuation and peak torque. Alterations in muscle sequencing and recruitment patterns may also occur, causing unaccustomed stress to be placed on muscle ligaments and tendons. These compensatory mechanisms may increase the risk of further injury if a premature return to sport is attempted. A number of treatment strategies have been introduced to help alleviate the severity of DOMS and to restore the maximal function of the muscles as rapidly as possible. Nonsteroidal anti-inflammatory drugs have demonstrated dosage-dependent effects that may also be influenced by the time of administration. Similarly, massage has shown varying results that may be attributed to the time of massage application and the type of massage technique used. Cryotherapy, stretching, homeopathy, ultrasound and electrical current modalities have demonstrated no effect on the alleviation of muscle soreness or other DOMS symptoms. Exercise is the most effective means of alleviating pain during DOMS, however the analgesic effect is also temporary. Athletes who must train on a daily basis should be encouraged to reduce the intensity and duration of exercise for 1–2 days following intense DOMS-inducing exercise. Alternatively, exercises targeting less affected body parts should be encouraged in order to allow the most affected muscle groups to recover. Eccentric exercises or novel activities should be introduced progressively over a period of 1 or 2 weeks at the beginning of, or during, the sporting season in order to reduce the level of physical impairment and/or training disruption. There are still many unanswered questions relating to DOMS, and many potential areas for future research.

1,121 citations


Journal ArticleDOI
27 Nov 2003-Nature
TL;DR: An analysis of a matrix of 87 languages with 2,449 lexical items produced an estimated age range for the initial Indo-European divergence of between 7,800 and 9,800 years bp, in striking agreement with the Anatolian hypothesis.
Abstract: Languages, like genes, provide vital clues about human history1,2. The origin of the Indo-European language family is “the most intensively studied, yet still most recalcitrant, problem of historical linguistics”3. Numerous genetic studies of Indo-European origins have also produced inconclusive results4,5,6. Here we analyse linguistic data using computational methods derived from evolutionary biology. We test two theories of Indo-European origin: the ‘Kurgan expansion’ and the ‘Anatolian farming’ hypotheses. The Kurgan theory centres on possible archaeological evidence for an expansion into Europe and the Near East by Kurgan horsemen beginning in the sixth millennium BP7,8. In contrast, the Anatolian theory claims that Indo-European languages expanded with the spread of agriculture from Anatolia around 8,000–9,500 years bp9. In striking agreement with the Anatolian hypothesis, our analysis of a matrix of 87 languages with 2,449 lexical items produced an estimated age range for the initial Indo-European divergence of between 7,800 and 9,800 years bp. These results were robust to changes in coding procedures, calibration points, rooting of the trees and priors in the bayesian analysis.

793 citations


Journal ArticleDOI
TL;DR: This paper published a Journal Article in The Econometrics Journal Volume 6 Issue 1 Page 217 Page 217 - June 2003======http://www.1368-423X.00108
Abstract: Now published as a Journal Article in The Econometrics Journal Volume 6 Issue 1 Page 217 - June 2003 doi:10.1111/1368-423X.00108

780 citations


Journal ArticleDOI
TL;DR: The conceptual and methodological issues for quantifying the population health effects of individual or groups of risk factors in various levels of causality using knowledge from different scientific disciplines are discussed.
Abstract: Reliable and comparable analysis of risks to health is key for preventing disease and injury. Causal attribution of morbidity and mortality to risk factors has traditionally been conducted in the context of methodological traditions of individual risk factors, often in a limited number of settings, restricting comparability.In this paper, we discuss the conceptual and methodological issues for quantifying the population health effects of individual or groups of risk factors in various levels of causality using knowledge from different scientific disciplines. The issues include: comparing the burden of disease due to the observed exposure distribution in a population with the burden from a hypothetical distribution or series of distributions, rather than a single reference level such as non-exposed; considering the multiple stages in the causal network of interactions among risk factor(s) and disease outcome to allow making inferences about some combinations of risk factors for which epidemiological studies have not been conducted, including the joint effects of multiple risk factors; calculating the health loss due to risk factor(s) as a time-indexed "stream" of disease burden due to a time-indexed "stream" of exposure, including consideration of discounting; and the sources of uncertainty.

778 citations


Journal ArticleDOI
TL;DR: It is shown that myostatin, a TGF-β member, signals satellite cell quiescence and also negatively regulates satellite cell self-renewal.
Abstract: Satellite cells are quiescent muscle stem cells that promote postnatal muscle growth and repair. Here we show that myostatin, a TGF-β member, signals satellite cell quiescence and also negatively regulates satellite cell self-renewal. BrdU labeling in vivo revealed that, among the Myostatin-deficient satellite cells, higher numbers of satellite cells are activated as compared with wild type. In contrast, addition of Myostatin to myofiber explant cultures inhibits satellite cell activation. Cell cycle analysis confirms that Myostatin up-regulated p21, a Cdk inhibitor, and decreased the levels and activity of Cdk2 protein in satellite cells. Hence, Myostatin negatively regulates the G1 to S progression and thus maintains the quiescent status of satellite cells. Immunohistochemical analysis with CD34 antibodies indicates that there is an increased number of satellite cells per unit length of freshly isolated Mstn−/− muscle fibers. Determination of proliferation rate suggests that this elevation in satellite cell number could be due to increased self-renewal and delayed expression of the differentiation gene (myogenin) in Mstn−/− adult myoblasts. Taken together, these results suggest that Myostatin is a potent negative regulator of satellite cell activation and thus signals the quiescence of satellite cells.

777 citations


Journal ArticleDOI
TL;DR: Systemic administration of [Ser(2)]exendin(1–9) in wild-type animals prevents kainate-induced apoptosis of hippocampal neurons and represents a promising new target for both cognitive-enhancing and neuroprotective agents.
Abstract: Glucagon-like peptide-1 (GLP-1) is a gut peptide that, together with its receptor, GLP-1R, is expressed in the brain. Here we show that intracerebroventricular (i.c.v.) GLP-1 and [Ser(2)]exendin(1-9) (HSEGTFTSD; homologous to a conserved domain in the glucagon/GLP-1 family) enhance associative and spatial learning through GLP-1R. [Ser(2)]exendin(1-9), but not GLP-1, is also active when administered peripherally. GLP-1R-deficient mice have a phenotype characterized by a learning deficit that is restored after hippocampal Glp1r gene transfer. In addition, rats overexpressing GLP-1R in the hippocampus show improved learning and memory. GLP-1R-deficient mice also have enhanced seizure severity and neuronal injury after kainate administration, with an intermediate phenotype in heterozygotes and phenotypic correction after Glp1r gene transfer in hippocampal somatic cells. Systemic administration of [Ser(2)]exendin(1-9) in wild-type animals prevents kainate-induced apoptosis of hippocampal neurons. Brain GLP-1R represents a promising new target for both cognitive-enhancing and neuroprotective agents.

Journal ArticleDOI
TL;DR: In this paper, the authors provide firms with a scale for measuring the quality of these intangible relationships between service firms and their customers, and test this scale against the related, yet dissimilar scale for service quality to determine whether the relationship quality (RQ) scale adds any further explanation of behavioral intentions.
Abstract: Increasingly, firms are recognizing the value of establishing close relationships with their customers as a means of retaining existing customers. Also, firms are realizing that the intangible aspects of a relationship are not easily duplicated by competition, thus providing a sustainable competitive advantage to the firm. In this paper, we provide firms with a scale for measuring the quality of these intangible relationships between service firms and their customers. We then test this scale against the related, yet dissimilar scale for service quality to determine whether the relationship quality (RQ) scale adds any further explanation of behavioral intentions. Our results indicate that relationship quality is a distinct construct from service quality and that RQ is a better predictor of behavioral intentions than service quality.

Journal ArticleDOI
TL;DR: In this paper, a method of generalized discriminant analysis based on a dissimilarity matrix to test for differences in a priori groups of multivariate observations is described. But the results of the analysis are not as robust to changes in the distributions of the original variables, unlike the distribution of the multi-response permutation test statistics which have been considered by other workers for testing differences among groups.
Abstract: Summary This paper describes a method of generalized discriminant analysis based on a dissimilarity matrix to test for differences in a priori groups of multivariate observations. Use of classical multidimensional scaling produces a low-dimensional representation of the data for which Euclidean distances approximate the original dissimilarities. The resulting scores are then analysed using discriminant analysis, giving tests based on the canonical correlations. The asymptotic distributions of these statistics under permutations of the observations are shown to be invariant to changes in the distributions of the original variables, unlike the distributions of the multi-response permutation test statistics which have been considered by other workers for testing differences among groups. This canonical method is applied to multivariate fish assemblage data, with Monte Carlo simulations to make power comparisons and to compare theoretical results and empirical distributions. The paper proposes classification based on distances. Error rates are estimated using cross-validation.

Journal ArticleDOI
TL;DR: A review of the use of cultural indices in accounting research can be found in this article, where the authors identify problems such as: (i) the assumption of equating nation with culture, (ii) the difficulties of, and limitations on, a quantification of culture represented by cultural dimensions and matrices; and (iii) the status of the observer outside the culture.
Abstract: The continuation of accounting research utilising Hofstede’s cultural indices suggests an absence of sufficient consideration for the reasons behind the rejection of such a universalist approach in anthropology and sociology. These reasons include the assumption of equating nation with culture and the difficulty, and limitations on an understanding of culture by means of numeric indices and matrices. Alternative approaches for research on national differences in accounting are suggested. # 2002 Elsevier Science Ltd. All rights reserved. In 1967, employees in an organization, IBM, were asked to complete an attitude survey. IBM had organized incidental surveys of parts of its organization since 1950, but it was decided to standardize an international survey in order to provide a management tool for organization development. This survey process repeated until 1973, resulting in 117,000 responses from88,000 employees in 66 countries. The results of this data led the head of the international teamconducting the survey, Geert Hofstede, to develop cultural indices. These indices provided four dimensions of national culture for each one of the countries surveyed. Twenty years later, accounting research is one of numerous disciplines which utilize Hofstede’s classification and quantification of cultural differences. This study acknowledges the variety of applications of Hofstede’s Culture’s Consequences— International Differences in Work-Related Values (1980) (hereafter referred to as Culture’s Consequences) in accounting research, and then examines the development of ideas about culture and its quantification by Hofstede, and the theoretical bases for Hofstede’s cultural measurements. This review identifies problems such as: (i) the assumption of equating nation with culture (ii) the difficulties of, and limitations on, a quantification of culture represented by cultural dimensions and matrices; and (iii) the status of the observer outside the culture. Possible alternative and multiple explanations of national differences in accounting systems are also described. A further problemis a general lack of confidence in the assumption of stability of cultural differences, considering the twenty years since the 1980 publication of Culture’s Consequences. Cultural diffusion and the dynamism of both national and ethnic shifts may be problematic where reification and indexation of culture is concerned. The outcome of this examination suggests that the manner in which Hofstede established the dimensions of culture, and the subsequent reification of ‘‘culture’’ as a variable in cross-national studies in accounting research, led to a misleading

Journal ArticleDOI
TL;DR: The panel dynamic ordinary least square (DOLS) estimator of a homogeneous cointegration vector for a balanced panel of N individuals observed over T time periods was studied in this article.
Abstract: We study the panel dynamic ordinary least square (DOLS) estimator of a homogeneous cointegration vector for a balanced panel of N individuals observed over T time periods. Allowable heterogeneity across individuals include individual-specific time trends, individual-specific fixed effects and time-specific effects. The estimator is fully parametric, computationally convenient, and more precise than the single equation estimator. For fixed N as T fi 1, the estimator converges to a function of Brownian motions and the Wald statistic for testing a set of s linear constraints has a limiting v 2 (s) distribution. The estimator also has a Gaussian sequential limit distribution that is obtained first by letting T fi 1 and then letting N fi 1. In a series of Monte-Carlo experiments, we find that the asymptotic distribution theory provides a reasonably close approximation to the exact finite sample distribution. We use panel DOLS to estimate coefficients of the long-run money demand function from a panel of 19 countries with annual observations that span from 1957 to 1996. The estimated income elasticity is 1.08 (asymptotic s.e. ¼ 0.26) and the estimated interest rate semi-elasticity is )0.02 (asymptotic s.e. ¼ 0.01).

Journal ArticleDOI
TL;DR: Non-personal health interventions, including government action to stimulate a reduction in the salt content of processed foods, are cost-effective ways to limit cardiovascular disease and could avert over 21 million DALYs per year worldwide.

Journal ArticleDOI
TL;DR: HIF-1 is an essential component in changing the transcriptional repertoire of tissues as oxygen levels drop, and could prove to be a very important target for drug development, as treatments evolve for diseases, such as cancer, heart disease and stroke, in which hypoxia is a central aspect.
Abstract: Sensing and responding to fluxes in oxygen tension is perhaps the single most important variable in physiology, and animal tissues have developed a number of essential mechanisms to cope with the stress of low physiological oxygen levels, or hypoxia. Among these coping mechanisms is the response mediated by the hypoxia-inducible transcription factor, or HIF-1. HIF-1 is an essential component in changing the transcriptional repertoire of tissues as oxygen levels drop, and could prove to be a very important target for drug development, as treatments evolve for diseases, such as cancer, heart disease and stroke, in which hypoxia is a central aspect.

Journal ArticleDOI
12 Apr 2003-BMJ
TL;DR: Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months without evidence of adverse effects.
Abstract: Objective: To assess the long term effectiveness of the “green prescription” programme, a clinician based initiative in general practice that provides counselling on physical activity. Design: Cluster randomised controlled trial. Practices were randomised before systematic screening and recruitment of patients. Setting: 42 rural and urban general practices in one region of New Zealand. Subjects: All sedentary 40–79 year old patients visiting their general practitioner during the study9s recruitment period. Intervention: General practitioners were prompted by the patient to give oral and written advice on physical activity during usual consultations. Exercise specialists continued support by telephone and post. Control patients received usual care. Main outcome measures: Change in physical activity, quality of life (as measured by the “short form 36” (SF-36) questionnaire), cardiovascular risk (Framingham and D9Agostino equations), and blood pressure over a 12 month period. Results: 74% (117/159) of general practitioners and 66% (878/1322) of screened eligible patients participated in the study. The follow up rate was 85% (750/878). Mean total energy expenditure increased by 9.4 kcal/kg/week (P=0.001) and leisure exercise by 2.7 kcal/kg/week (P=0.02) or 34 minutes/week more in the intervention group than in the control group (P=0.04). The proportion of the intervention group undertaking 2.5 hours/week of leisure exercise increased by 9.72% (P=0.003) more than in the control group (number needed to treat=10.3). SF-36 measures of self rated “general health,” “role physical,” “vitality,” and “bodily pain” improved significantly more in the intervention group (P Conclusion: Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months. What is already known on this topic Counselling patients in general practice on exercise has resulted in gains in physical fitness and activity, but no health benefits have been found What this study adds Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months without evidence of adverse effects The intervention may reduce blood pressure by an average of 1–2 mm Hg over 12 months No changes in the risk of coronary heart disease were observed The intervention is sustainable in usual general practice Prompting practice staff to deliver the intervention may have increased its effectiveness

Journal ArticleDOI
01 Apr 2003-Placenta
TL;DR: Patterns of expression of cytokines in the foetal membranes and decidua suggest that inflammatory activation occurs modestly with term labour, but much more robustly in preterm delivery, particularly in the presence of intrauterine infection.

Journal ArticleDOI
04 Sep 2003-Nature
TL;DR: An evolutionary transition that occurs in experimental populations of Pseudomonas fluorescens propagated in a spatially heterogeneous environment is described to show that transitions to higher orders of complexity are readily achievable, provide insights into the selective conditions, and facilitate experimental analysis of the evolution of individuality.
Abstract: A fundamental problem in biology is the evolutionary transition from single cells to multicellular life forms. During this transition the unit of selection shifts from individual cells to groups of cooperating cells. Although there is much theory, there are few empirical studies. Here we describe an evolutionary transition that occurs in experimental populations of Pseudomonas fluorescens propagated in a spatially heterogeneous environment. Cooperating groups are formed by over-production of an adhesive polymer, which causes the interests of individuals to align with those of the group. The costs and benefits of cooperation, plus evolutionary susceptibility to defecting genotypes, were analysed to determine conformation to theory. Cooperation was costly to individuals, but beneficial to the group. Defecting genotypes evolved in populations founded by the cooperating type and were fitter in the presence of this type than in its absence. In the short term, defectors sabotaged the viability of the group; but these findings nevertheless show that transitions to higher orders of complexity are readily achievable, provide insights into the selective conditions, and facilitate experimental analysis of the evolution of individuality.

Journal ArticleDOI
TL;DR: Removal of major risk factors would not only increase healthy life expectancy in every region, but also reduce some of the differences between regions.

Journal ArticleDOI
TL;DR: The distribution of MC4‐R mRNA in the adult rat central nervous system is consistent with the proposed roles of central melanocortin systems in feeding and autonomic regulation.
Abstract: The melanocortin 4 receptor (MC4-R) plays a pivotal role in maintaining energy homeostasis in rodents and humans. For example, MC4-R deletion or mutation results in obesity, hyperphagia, and insulin resistance. Additionally, subsets of leptin-induced autonomic responses can be blocked by melanocortin receptor antagonism, suggesting that MC4-R-expressing neurons are downstream targets of leptin. However, the critical autonomic control sites expressing MC4-Rs are still unclear. In the present study, we systematically examined the distribution of MC4-R mRNA in the adult rat central nervous system, including the spinal cord, by using in situ hybridization histochemistry (ISHH) with a novel cRNA probe. Autonomic control sites expressing MC4-R mRNA in the hypothalamus included the anteroventral periventricular, ventromedial preoptic, median preoptic, paraventricular, dorsomedial, and arcuate nuclei. The subfornical organ, dorsal hypothalamic, perifornical, and posterior hypothalamic areas were also observed to express MC4-R mRNA. Within extrahypothalamic autonomic control sites, MC4-R-specific hybridization was evident in the infralimbic and insular cortices, bed nucleus of the stria terminalis, central nucleus of the amygdala, periaqueductal gray, lateral parabrachial nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus (DMV), and intermediolateral nucleus of the spinal cord (IML). By using dual-label ISHH, we confirmed that the cells expressing MC4-R mRNA in the IML and DMV were autonomic preganglionic neurons as cells in both sites coexpressed choline acetyltransferase mRNA. The distribution of MC4-R mRNA is consistent with the proposed roles of central melanocortin systems in feeding and autonomic regulation.

Journal ArticleDOI
TL;DR: Evidence is provided of increased progenitor cell proliferation and neurogenesis in the diseased adult human brain and further indicate the regenerative potential of the human brain.
Abstract: Neurogenesis has recently been observed in the adult human brain, suggesting the possibility of endogenous neural repair. However, the augmentation of neurogenesis in the adult human brain in response to neuronal cell loss has not been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the subependymal layer (SEL) adjacent to the caudate nucleus in the human brain in response to neurodegeneration of the caudate nucleus in Huntington's disease (HD). Postmortem control and HD human brain tissue were examined by using the cell cycle marker proliferating cell nuclear antigen (PCNA), the neuronal marker βIII-tubulin, and the glial cell marker glial fibrillary acidic protein (GFAP). We observed a significant increase in cell proliferation in the SEL in HD compared with control brains. Within the HD group, the degree of cell proliferation increased with pathological severity and increasing CAG repeats in the HD gene. Most importantly, PCNA+ cells were shown to coexpress βIII-tubulin or GFAP, demonstrating the generation of neurons and glial cells in the SEL of the diseased human brain. Our results provide evidence of increased progenitor cell proliferation and neurogenesis in the diseased adult human brain and further indicate the regenerative potential of the human brain.

Journal ArticleDOI
TL;DR: It is argued that language evolved from manual gestures, gradually incorporating vocal elements, and may be traced through changes in the function of Broca's area, the code for both the production of manual reaching movements and the perception of the same movements performed by others.
Abstract: The strong predominance of right-handedness appears to be a uniquely human characteristic, whereas the left-cerebral dominance for vocalization occurs in many species, including frogs, birds, and mammals. Right-handedness may have arisen because of an association between manual gestures and vocalization in the evolution of language. I argue that language evolved from manual gestures, gradually incorporating vocal elements. The transition may be traced through changes in the function of Broca's area. Its homologue in monkeys has nothing to do with vocal control, but contains the so-called “mirror neurons,” the code for both the production of manual reaching movements and the perception of the same movements performed by others. This system is bilateral in monkeys, but predominantly left-hemispheric in humans, and in humans is involved with vocalization as well as manual actions. There is evidence that Broca's area is enlarged on the left side in Homo habilis, suggesting that a link between gesture and vocalization may go back at least two million years, although other evidence suggests that speech may not have become fully autonomous until Homo sapiens appeared some 170,000 years ago, or perhaps even later. The removal of manual gesture as a necessary component of language may explain the rapid advance of technology, allowing late migrations of Homo sapiens from Africa to replace all other hominids in other parts of the world, including the Neanderthals in Europe and Homo erectus in Asia. Nevertheless, the long association of vocalization with manual gesture left us a legacy of right-handedness.

Journal ArticleDOI
TL;DR: The Physiome Project will provide a framework for modelling the human body, using computational methods that incorporate biochemical, biophysical and anatomical information on cells, tissues and organs.
Abstract: The Physiome Project will provide a framework for modelling the human body, using computational methods that incorporate biochemical, biophysical and anatomical information on cells, tissues and organs. The main project goals are to use computational modelling to analyse integrative biological function and to provide a system for hypothesis testing.

Journal ArticleDOI
TL;DR: First year of practice is an important confidence-building phase for nurses and yet many new graduates are exposed to horizontal violence, which may negatively impact on this process, and underscore a priority for the development of effective prevention programmes.
Abstract: Background. Interpersonal conflict among nurses (traditionally called ‘horizontal violence’ or ‘bullying’) is a significant issue confronting the nursing profession. However, there is a dearth of research focusing on horizontal violence experienced by new graduate nurses. Aims. In order to assess the priority for preventive intervention programmes, the aims of this study were to determine the prevalence of horizontal violence experienced by nurses in their first year of practice; to describe the characteristics of the most distressing incidents experienced; to determine the consequences, and measure the psychological impact, of such events; and to determine the adequacy of training received to manage horizontal violence. Method. An anonymous survey was mailed to nurses in New Zealand who had registered in the year prior to November 2000 (n = 1169) and 551 completed questionnaires were returned (response rate 47%). Information was requested on the type and frequency of interpersonal conflict; a description of the most distressing event experienced; the consequences of the behaviour; and training to manage such events. The Impact of Event Scale was used to measure the level of distress experienced. Results. Many new graduates experienced horizontal violence across all clinical settings. Absenteeism from work, the high number of respondents who considered leaving nursing, and scores on the Impact of Event Scale all indicated the serious impact of interpersonal conflict. Nearly half of the events described were not reported, only 12% of those who described a distressing incident received formal debriefing, and the majority of respondents had no training to manage the behaviour. Conclusions. First year of practice is an important confidence-building phase for nurses and yet many new graduates are exposed to horizontal violence, which may negatively impact on this process. The findings underscore a priority for the development of effective prevention programmes. Adequate reporting mechanisms and supportive services should also be readily available for those exposed to the behaviour.

Journal ArticleDOI
13 Nov 2003-BMJ
TL;DR: Two verbally asked questions for screening for depression would detect most cases of depression in general practice, and have the advantage of brevity.
Abstract: Objective To determine the diagnostic accuracy of two verbally asked questions for screening for depression. Design Cross sectional criterion standard validation study. Setting 15 general practices in New Zealand. Participants 421 consecutive patients not taking psychotropic drugs. Main outcome measures Sensitivity, specificity, and likelihood ratios of the two questions compared with the computerised composite international diagnostic interview. Results The two screening questions showed a sensitivity and specificity of 97% (95% confidence interval, 83% to 99%) and 67% (62% to 72%), respectively. The likelihood ratio for a positive test was 2.9 (2.5 to 3.4) and the likelihood ratio for a negative test was 0.05 (0.01 to 0.35). Overall, 37% (157/421) of the patients screened positive for depression. Conclusion Two verbally asked questions for screening for depression would detect most cases of depression in general practice. The questions have the advantage of brevity. As treatment is more likely when doctors make the diagnosis, these questions may have even greater utility.

Journal ArticleDOI
TL;DR: A broad class of exact self-similar solutions to the nonlinear Schrödinger equation (NLSE) with distributed dispersion, nonlinearity, and gain or loss has been found and the stability of these solutions has been confirmed by numerical simulations of the NLSE.
Abstract: A broad class of exact self-similar solutions to the nonlinear Schrodinger equation (NLSE) with distributed dispersion, nonlinearity, and gain or loss has been found. Appropriate solitary wave solutions applying to propagation in optical fibers and optical fiber amplifiers with these distributed parameters have also been studied. These solutions exist for physically realistic dispersion and nonlinearity profiles in a fiber with anomalous group velocity dispersion. They correspond either to compressing or spreading solitary pulses which maintain a linear chirp or to chirped oscillatory solutions. The stability of these solutions has been confirmed by numerical simulations of the NLSE.

Journal ArticleDOI
TL;DR: To determine the effectiveness of vitamin D and home‐based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge.
Abstract: OBJECTIVES: To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge. DESIGN: Multicenter, randomized, controlled trial with a factorial design. SETTING: Five hospitals in Auckland, New Zealand, and Sydney, Australia. PARTICIPANTS: Two hundred forty-three frail older people. INTERVENTIONS: Patients were randomized to receive a single dose of vitamin D (calciferol, 300,000 IU) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits. MEASUREMENTS: The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months. Physical performance and self-rated function were secondary endpoints. Assessments took place in the participants' homes at 3 and 6 months after randomization and were performed by blinded assessors. RESULTS: There was no effect of either intervention on physical health or falls, but patients in the exercise group were at increased risk of musculoskeletal injury (risk ratio = 3.6, 95% confidence interval = 1.5-8.0). Vitamin D supplementation did not improve physical performance, even in those who were vitamin D deficient (<12 ng/mL) at baseline. CONCLUSION: Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization. There was no effect of vitamin D on physical performance, and the exercises increased the risk of musculoskeletal injury. These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people.

Journal ArticleDOI
TL;DR: Investigation of the hypotheses that childhood sexual and physical abuse are related to hallucinations, delusions, and thought disorder in adults and that those relationships are greater in those who have suffered abuse during adulthood as well as childhood found that child abuse was a significant predictor of auditory and tactile hallucinations, even in the absence of adult abuse.
Abstract: In light of recent studies indicating a relationship between child abuse and the positive symptoms of schizophrenia, this study investigated the hypotheses that childhood sexual and physical abuse are related to hallucinations, delusions, and thought disorder in adults, and that those relationships are greater in those who have suffered abuse during adulthood as well as childhood. In 200 community mental-health-centre clients, the clinically evaluated symptomatology of the 92 clients whose files documented sexual or physical abuse at some point in their lives was compared with that of the 108 for whom no abuse was documented. In the 60 patients for whom child abuse was documented, hallucinations (including all six subtypes), but not delusions, thought disorder or negative symptoms, were significantly more common than in the non-abused group. Adult sexual assault was related to hallucinations, delusions, and thought disorder. In linear regression analysis, a combination of child abuse and adult abuse predicted hallucinations, delusions, and thought disorder. However, child abuse was a significant predictor of auditory and tactile hallucinations, even in the absence of adult abuse. Possible psychological and neurobiological pathways from abuse to symptoms are discussed, along with research and clinical implications.