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Neural networks in the analysis of episodic growth hormone release.

Pulsatile secretion of growth hormone (GH) has been observed in healthy controls as well as acromegalic patients. In healthy adults, highly regulated secretory pulses of GH occur 4-8 times within 24 h. This episodic pattern of secretion seems to be related to the optimal induction of physiological effects at the peripheral level. In contrast to normal subjects, acromegalic patients demonstrate an irregular pattern of excessive GH release. This pattern of secretion is responsible for many systemic effects, such as the stimulation of connective tissue growth, cardiovascular and cerebrovascular disease, diabetes mellitus and arthritis. Standard methods for the analysis of pulsatile patterns of hormone secretion did not consistently separate the temporal dynamics of GH release in healthy controls and acromegalic patients under various study conditions. Using the cutting edge technology of artificial neural networks for time series prediction, we were able to achieve significant separation of both groups under various conditions by means of the predictability of their GH secretory dynamics. Improving the predictive results by using a more refined system of multiple neural networks acting in parallel (adaptive mixtures of local experts), we found that this system performed a self-organized segmentation of hormone pulsatility. It separated phases of secretory bursts and quiescence without any prior knowledge of the form of a GH pulse or a model of secretion. Comparing the predictive results for the GH dynamics with those for computer-stimulated stochastic processes, we were able to define the irregular pattern of GH secretion in acromegaly as a random autonomous process. The introduction of neural networks to the analysis of dynamic endocrine systems might help to expand the existing analytical approaches beyond counting frequency and amplitude of hormone pulses.

Acromegaly↗

Development of care programmes for cancer. WHO Care Programme Committee.

As part of WHO's programme on model health-care programmes and quality assurance, a series of meetings attended by specialists in cancer care, community medicine and public health, health administrators, epidemiologists, biostatisticians and health economists have looked at ways of improving cancer care. Model health-care programmes, i.e. guidelines on how best to treat a cancer patient with the available resources approved by all concerned parties and adapted to the local needs emerged as a promising method. Drawing on the findings and recommendations of these meetings, this report suggests comprehensive guidelines for the development of care programmes in cancer. Its eight sections cover: objectives; organization; rationale; characteristics; contents; development; evaluation; and the responsibilities of health authorities, cancer registries, cancer centres and WHO in the development and implementation of care programmes. For the health-care administrators and representatives of public health, the discussion on the objectives and rationale of care programmes will be particularly important whereas the detailed and concrete description of their contents and development will interest cancer-care specialists as well as other health-care practitioners. This last section on responsibilities spells out in detail what the concerned parties could do.

Cancer Care Facilities↗

RFLP markers show genetic recombination in Botryotinia fuckeliana (Botrytis cinerea) and transposable elements reveal two sympatric species.

Molecular markers revealed that Botryotinia fuckeliana (the teleomorph of Botrytis cinerea), a haploid, filamentous, heterothallic ascomycete, contained a large amount of intrapopulation genetic variation. The markers were used to determine the mode of reproduction and the population structure of this fungus. We did not detect any differentiation between isolates from different organs, collection dates, varieties of grape, or locations in the Champagne region of France, but two unexpected sympatric populations were identified. One group of isolates (transposa) contained the transposable elements Boty and Flipper; the other (vacuma) did not. These groups differed from one another for all the other markers. RFLP markers showed that there was genetic recombination in both groups of isolates. We conclude that there are two sympatric populations of B. fuckeliana in Champagne. One species (transposa) seems to be local and well adapted, while the other one (vacuma) is presumably a heterogeneous migrant population.

Alleles↗

Analysis of the psychrotolerant property of hormone-sensitive lipase through site-directed mutagenesis.

Mammalian hormone-sensitive lipase (HSL) has given its name to a family of primarily prokaryotic proteins which are structurally related to type B carboxylesterases. In many of these alpha/beta hydrolases, a conserved HG-dipeptide flanks the catalytic pocket. In HSL this dipeptide is followed by two additional glycine residues. Through site-directed mutagenesis, we have investigated the importance of this motif for enzyme activity. Since the presence of multiple glycine residues in a critical region could contribute to cold adaptation by providing local flexibility, we studied the effect of mutating these residues on the psychrotolerant property of HSL. Any double mutation rendered the enzyme completely inactive, without any major effect on the enzyme stability. The partially active single mutants retained the same proportion of activity at reduced temperatures as the wild-type enzyme. These results do not support a role for the HGGG motif in catalysis at low temperatures, but provide further validation of the current three-dimensional model of HSL. Rat HSL was found to be relatively more active than human HSL at low temperatures. This difference was, however, not due to the 12 amino acids which are present in the regulatory module of the rat enzyme but absent in human HSL.

Amino Acid Sequence↗

Expanding the role of the nurse in clinical trials: the nursing summaries.

In order to improve the overall quality of clinical trials, the role of the nurse should be expanded. The minimum requirement to facilitate nurses' participation and the optimal implementation of a clinical research protocol is to provide access to the clinical protocol document itself. However, given the high workload in an oncology unit, there is often little time for the staff to read the entire document. In addition, clinical protocols do not often provide detailed practical instructions for delivering treatment, observing patients, managing toxicities, and treating complications. A nursing summary of the medical protocol is a document that provides a short and easy-to-read selection of protocol-relevant information. It enables nurses to safely and more easily implement the research protocol and improve the care of patients in clinical trials. Master nursing summaries can be prepared centrally by the group responsible for the research protocol, while the unit/wards involved in the research can customize or adapt it to local needs. The potential benefit of implementing nursing summaries is overall improvement of the quality of the study by (a) increasing the reliability of nursing care regarding patients' safety, (b) standardizing monitoring and care of patients, (c) standardizing preventive measures, (d) proposing similar management of complications related to experimental treatments. Moreover, discussing nursing summaries may help evaluate workload related to research, allowing for better planning and allocation of resources.

Antineoplastic Agents↗

Strategic planning system for control of venereal disease: record keeping in a clinic for treatment of sexually transmitted diseases.

A manual data processing system and a computer-based system that was integrated into the operations of a clinic for treatment of sexually transmitted diseases were developed. The automated system can generate routine management reports and cross-tabulate data for special studies. It is flexible and adaptable to other localities but is not a panacea for clinical problems.

Centers for Disease Control and Prevention, U.S.↗

Slow pace of life in tropical sedentary birds: a common-garden experiment on four stonechat populations from different latitudes.

It has been hypothesized that organisms living at different latitudes or in different environments adjust their metabolic activity to the prevailing conditions. However, do differences in energy turnover simply represent a phenotypic adaptation to the local environment, or are they genetically based? To test this, we obtained nestling stonechats (Saxicola torquata) from equatorial Kenya (0 degrees N), Ireland (51.5 degrees N), Austria (47.5 degrees N) and Kazakhstan (51.5 degrees N). Birds were hand-raised and kept in Andechs, Germany. We measured their resting metabolic rates (RMR) and locomotor activity at an age of ca. 14 months (July) and 20 months (January), when birds went through postnuptial moult (July), and neither moulted nor exhibited enlarged gonads or migratory activity (January). RMR was generally higher during moult, but differed among populations: RMR was lowest in the resident Kenyan birds, higher in mostly sedentary Irish birds, and highest in migratory Austrian and Kazakhstan birds. Thus our data demonstrate that even in birds kept from early life under common-garden conditions, the 'pace of life', as indicated by metabolic turnover, is lower in sedentary tropical than in north-temperate migratory individuals of the same species. Such intrinsically low energy expenditure in sedentary tropical birds may have important implications for slow development, delayed senescence and high longevity in many tropical organisms.

Acclimatization↗

Predicting essential genes in fungal genomes.

Essential genes are required for an organism's viability, and the ability to identify these genes in pathogens is crucial to directed drug development. Predicting essential genes through computational methods is appealing because it circumvents expensive and difficult experimental screens. Most such prediction is based on homology mapping to experimentally verified essential genes in model organisms. We present here a different approach, one that relies exclusively on sequence features of a gene to estimate essentiality and offers a promising way to identify essential genes in unstudied or uncultured organisms. We identified 14 characteristic sequence features potentially associated with essentiality, such as localization signals, codon adaptation, GC content, and overall hydrophobicity. Using the well-characterized baker's yeast Saccharomyces cerevisiae, we employed a simple Bayesian framework to measure the correlation of each of these features with essentiality. We then employed the 14 features to learn the parameters of a machine learning classifier capable of predicting essential genes. We trained our classifier on known essential genes in S. cerevisiae and applied it to the closely related and relatively unstudied yeast Saccharomyces mikatae. We assessed predictive success in two ways: First, we compared all of our predictions with those generated by homology mapping between these two species. Second, we verified a subset of our predictions with eight in vivo knockouts in S. mikatae, and we present here the first experimentally confirmed essential genes in this species.

Computational Biology↗

An adaptive Gaussian model for satellite image deblurring.

The deconvolution of blurred and noisy satellite images is an ill-posed inverse problem, which can be regularized within a Bayesian context by using an a priori model of the reconstructed solution. Since real satellite data show spatially variant characteristics, we propose here to use an inhomogeneous model. We use the maximum likelihood estimator (MLE) to estimate its parameters and we show that the MLE computed on the corrupted image is not suitable for image deconvolution because it is not robust to noise. We then show that the estimation is correct only if it is made from the original image. Since this image is unknown, we need to compute an approximation of sufficiently good quality to provide useful estimation results. Such an approximation is provided by a wavelet-based deconvolution algorithm. Thus, a hybrid method is first used to estimate the space-variant parameters from this image and then to compute the regularized solution. The obtained results on high resolution satellite images simultaneously exhibit sharp edges, correctly restored textures, and a high SNR in homogeneous areas, since the proposed technique adapts to the local characteristics of the data.

Algorithms↗

Partition-based vector filtering technique for suppression of noise in digital color images.

A partition-based adaptive vector filter is proposed for the restoration of corrupted digital color images. The novelty of the filter lies in its unique three-stage adaptive estimation. The local image structure is first estimated by a series of center-weighted reference filters. Then the distances between the observed central pixel and estimated references are utilized to classify the local inputs into one of preset structure partition cells. Finally, a weighted filtering operation, indexed by the partition cell, is applied to the estimated references in order to restore the central pixel value. The weighted filtering operation is optimized off-line for each partition cell to achieve the best tradeoff between noise suppression and structure preservation. Recursive filtering operation and recursive weight training are also investigated to further boost the restoration performance. The proposed filter has demonstrated satisfactory results in suppressing many distinct types of noise in natural color images. Noticeable performance gains are demonstrated over other prior-art methods in terms of standard objective measurements, the visual image quality and the computational complexity.

Algorithms↗

Application of the theory of optimal experiments to adaptive electromagnetic-induction sensing of buried targets.

A mobile electromagnetic-induction (EMI) sensor is considered for detection and characterization of buried conducting and/or ferrous targets. The sensor may be placed on a robot and, here, we consider design of an optimal adaptive-search strategy. A frequency-dependent magnetic-dipole model is used to characterize the target at EMI frequencies. The goal of the search is accurate characterization of the dipole-model parameters, denoted bythe vector theta; the target position and orientation are a subset of theta. The sensor position and operating frequency are denoted by the parameter vector p and a measurement is represented by the pair (p, O), where O denotes the observed data. The parametersp are fixed for a given measurement, but, in the context of a sequence of measurements p may be changed adaptively. In a locally optimal sequence of measurements, we desire the optimal sensor parameters, P(N+1) for estimation of theta, based on the previous measurements (p(n), On)n=1,N. The search strategy is based on the theory of optimal experiments, as discussed in detail and demonstrated via several numerical examples.

Algorithms↗

A versatile segmentation procedure.

In this paper, a new method for the segmentation of natural images is proposed. Original images g(x, y) are first regularized by using a self-adaptive implementation of the Mumford-Shah functional so that the two parameters alpha and gamma controlling the smoothness and fidelity, automatically adapt to the local scale and contrast of g(x, y). From the regularized image u(x, y) which is piecewise smooth, it is possible to obtain a piecewise constant image sN(x, y) representing a segmentation of the original image g(x, y). Indeed, sN(X, y) is the union of N closed regions, having a constant grey level, preserving thin bars and trihedral junctions present in the original image g(x, y). If the number N of closed regions is too high, closed regions can be merged by minimizing a functional which depends on a parameter n. When n is set equal to 1, a coarse segmentation is obtained with a few tens of distinct regions. With larger values of n, finer segmentations are obtained with about a hundred distinct regions. Therefore, by selecting the value of n it is possible to obtain segmentations at different resolutions. The proposed method for image segmentation was evaluated in two cases where a ground truth segmentation is available. The proposed procedure for image segmentation is rather versatile and depends on only one parameter n and seems suitable for higher level processing, such as categorization, recognition, and scene understanding.

Algorithms↗

Phenology of the tick, Ixodes ricinus, in its southern distribution range (central Spain).

The abundance, seasonal activity patterns and development rates of the tick Ixodes ricinus (L.) (Acari: Ixodidae), as well as microclimate features of the site of study, are described for a 9-year-long study (1994-2002) in north-central Spain. According to drag captures, larvae had a unimodal activity pattern, with a maximum observed around July-August, whereas nymphs displayed a bimodal pattern (May-June and August-September) with strong dominance of spring activity. An inversion of this pattern, with larger autumn peak, was observed in years with humid summers. Adults showed a small spring peak and a large autumn one. In the later years of the study, a small increase in the adult spring peak of activity was noticed, correlated with mild winters. Over the entire period of study, a clear increase in the total tick abundance was detected. Statistically significant differences between years were observed for some climate variables (saturation deficit, winter temperatures and number of days with temperatures above 6 degrees C), but a consistent and constant pattern of change was not observed in any climate variable. Temperature requirements for developing stages showed a sharp decrease in weeks 35-51 (eggs) and 38-50 (larvae and nymphs), a feature attributed to the presence of the morphogenetic diapause, beginning around September. Development rates obtained under quasi-natural conditions were almost twice those reported for other sites, suggesting an adaptation of this local, largely isolated I. ricinus population. According to drag captures and field-obtained development rates, interchange of nymphs between the two cohorts is common in this site, and seems to be influenced by the winter temperature and the date of larval engorgement.

Animals↗

Problems with criteria and quality control in the registration of coronary events in the MONICA study.

This paper discusses the practical difficulties experienced in registering and coding coronary events. The populations being monitored for fatal and non-fatal coronary events in the World Health Organization MONICA study are too large for surveillance of individuals. Routine medical and medico-legal sources have to be used to indentify potential events, which are then coded and categorized according to standard criteria. Methods are dependent on, and have to be adapted to the local system of medical care. Non-fatal cases in hospital are identified and registered either through their admission, "hot pursuit", or through their discharge, "cold pursuit". Each method has its own advantages and disadvantages. Local legal and ethical constraints are also responsible for differences between MONICA Collaborating Centres. Adequacy of investigation of events, and the availability and completeness of medical records are major determinants of the ease and quality of registration. Changes in medical care could cause spurious changes in event rates, and so potential biases need to be monitored and allowed for.

Coronary Disease↗

Measuring information strategies in oncology - developing an information satisfaction questionnaire.

The benefits of providing accurate and culturally sensitive information for patients are now undisputable and information strategies are generally being adopted nationally. Measuring their benefits and adapting strategies to local needs is now a new challenge. Although questionnaires to measure global satisfaction are available, no concise tool has previously existed to specifically measure the information aspects of care. The aims of this study are: to establish which aspects of information were most important to the patients during their cancer pathway; to develop a robust single-page questionnaire that is sensitive to patient priorities to measure and compare satisfaction between patient groups; and to audit information provision within routine clinical practice. Seventy-seven consecutive patients were asked to complete a priority list of which aspects of information were most important to them during their recent cancer care. A total of 303 answers were categorized into five final categories of equal weighting. The data were combined with demographic issues to produce a robust one-page questionnaire which has been adopted formally by the West Anglia Cancer Network. One hundred consecutive patients were then audited to highlight the information shortcomings of a busy community oncology department and the findings are reforming information services. We recommend the use of this practical audit tool in routine clinical practice, which can be downloaded free from cancernet.co.uk in seven languages.

Adult↗

Leptin and ghrelin expression in adipose tissues and serum levels in gastric banding patients.

BACKGROUND: To determine how leptin and ghrelin are expressed in the adipose tissues of obese adults undergoing gastric banding (LAGB), and to correlate tissue expression with serum concentrations and parameters of the metabolic syndrome. MATERIALS AND METHODS: A cross-sectional analysis of 92 patients: 61 obese patients with a body mass index (BMI) 49.2 +/- 1 kg m(-2) received LAGB, 20 patients underwent band exchange (BMI, 36.6 +/- 1.4 kg m(-2)) and 11 adult patients (BMI, 24.3 +/- 0.6 kg m(-2)) with fundoplication served as controls. Clinical data such as BMI and blood pressure were evaluated along with subcutaneous and visceral adipose tissue gene expression and fasting levels of leptin and ghrelin. Tissue transcripts were measured using real-time PCR, serum protein concentrations radio-immunologically. RESULTS: Leptin gene expression was highest in the primary LAGB group and more pronounced in subcutaneous fat in both sexes (P < 0.0001). Serum leptin concentrations were highest in the LAGB group (P < 0.001), whereby women exhibited higher serum levels than men. Leptin concentrations correlated positively to expression in subcutaneous fat (P < 0.0001), and leptin expression was also correlated to BMI and systolic blood pressure. We detected ghrelin gene expression in both types of fat. The ghrelin mRNA amounts in adipose tissues were similar in both sexes and comparable within groups; serum concentrations were lower in patients with primary LAGB than in controls (P < 0.05). CONCLUSIONS: Human adipose tissue expression of leptin is weight-course dependent and ghrelin is constitutional. Serum levels of leptin, but not of ghrelin, are indicative of an adaptive pattern of local gene expression in obese subjects undergoing weight reduction.

Adipose Tissue↗

Morphological and molecular comparison of host-derived populations of parasitic Psoroptes mites.

Infestation by parasitic Psoroptes mites (Acari: Psoroptidae) is an important cause of economic loss and welfare problems in livestock in many areas of the world. At least five species within this genus have been recognized, based on the host infested, the infestation site and differences in length of the opisthosomal setae of adult male mites. Here the integrity of these species is considered by subjecting populations of mites from a range of host species and geographical locations to simultaneous morphological and molecular genetic analyses. Morphological analysis showed that there were significant differences in shape and size between mite populations from different hosts, and that length of the outer opisthosomal setae in males and the homologous seta in females were the most important distinguishing character in adults. However, considerable variation in outer opisthosomal seta length was evident within and between populations of mites, and differences were not clearly related to host-species or geographical origin and did not support the accepted species differences. Molecular characterization using sequence data from the mitochondrial second internal transcribed spacer (ITS-2) region and microsatellite markers found little or no consistent host-related variation between the mite population samples. The results suggest that there is no case for considering the Psoroptes mites from the different hosts examined as separate species and that the morphological variation observed therefore may represent phenotypic adaptation to the local microenvironment on particular species of host.

Animal Structures↗

Microsatellite analysis of the phylogeography, Pleistocene history and secondary contact hypotheses for the killifish, Fundulus heteroclitus.

The mummichog, Fundulus heteroclitus, exhibits extensive latitudinal clinal variation in a number of physiological and biochemical traits, coupled with phylogeographical patterns at mitochondrial and nuclear DNA loci that suggest a complicated history of spatially variable selection and secondary intergradation. This species continues to serve as a model for understanding local and regional adaptation to variable environments. Resolving the influences of historical processes on the distribution of genetic variation within and among extant populations of F. heteroclitus is crucial to a better understanding of how populations evolve in the context of contemporary environments. In this study, we analysed geographical patterns of genetic variation at eight microsatellite loci among 15 populations of F. heteroclitus distributed throughout the North American range of the species from Nova Scotia to Georgia. Genetic variation in Northern populations was lower than in Southern populations and was strongly correlated with latitude throughout the species range. The most common Northern alleles at all eight loci exhibited concordant latitudinal clinal patterns, and the existence of an abrupt transition zone in allele frequencies between Northern and Southern populations was similar to that observed for mitochondrial DNA and allozyme loci. A significant pattern of isolation by distance was observed both within and between northern and southern regions. This pattern was unexpected, particularly for northern populations, given the recent colonization history of post-Pleistocene habitats, and was inconsistent with either a recent northward population expansion or a geographically restricted northern Pleistocene refugium. The data provided no evidence for recent population bottlenecks, and estimates of historical effective population sizes suggest that post-Pleistocene populations have been large throughout the species distribution. These results suggest that F. heteroclitus was broadly distributed throughout most of its current range during the last glacial event and that the abrupt transition in allele frequencies that separate Northern and Southern populations may reflect regional disequilibrium conditions associated with the post-Pleistocene colonization history of habitats in that region.

Animal Migration↗