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PubMed2006

Quantitative genetics of speciation: additive and non-additive genetic differentiation between Drosophila madeirensis and Drosophila subobscura.

The role of dominance and epistasis in population divergence has been an issue of much debate ever since the neoDarwinian synthesis. One of the best ways to dissect the several genetic components affecting the genetic architecture of populations is line cross analysis. Here we present a study comparing generation means of several life history-traits in two closely related Drosophila species: Drosophila subobscura, D. madeirensis as well as their F1 and F2 hybrids. This study aims to determine the relative contributions of additive and non-additive genetic parameters to the differentiation of life-history traits between these two species. The results indicate that both negative dominance and epistatic effects are very important in the differentiation of most traits. We end with considerations about the relevance of these findings for the understanding of the role of non-additive effects in speciation.

Animals↗

PubMed2001

Two dimensional non equilibrium pH gel electrophoresis mapping of cytosolic protein changes caused by dietary protein depletion in mouse liver.

Two-dimensional non-equilibrium pH gel electrophoresis (2D-NEPHGE) analysis was used to evaluate the effects of dietary protein depletion on the protein composition of mouse liver cytosol. Analysing the cytosol from both normal and protein depleted liver, the position in gels of more than three hundred protein spots was determined. After 5 days of protein depletion, about 20% of the spots either increased or decreased more than 2 fold. Five spots of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were recognised by specific antibodies. The glutathione S-transferase (GSTs) subunits Ybl, Yc and Yf were identified by the simultaneous analysis of both glutathione-binding cytosolic proteins and the corresponding standards. As estimated by internal optical density (IOD) of spots, the changes caused by protein depletion in GAPDH and GST subunit contents were similar to those obtained by other methods. By means of mass spectrometric analysis of tryptic peptides generated from spots and/or comparison of two-dimensional gel electrophoretic patterns, carbonic anhydrase III (CAIII), Cu, Zn superoxide dismutase (CuZnSOD) and a cytochrome P450 cytosolic protein (cyt P450) were identified. These three proteins, as well as GSTs, are related with intracellular detoxification and free radical scavenging systems. Their contents were regulated by dietary protein restriction in a manner indicative of diminished liver defence against oxidising agents.

Animals↗

PubMed1987

Fetal heart variability indices and the accuracy of variability measurements.

Several indices of fetal heart rate variability, including short-term variability (STV) and long-term variability (LTV) were analyzed. All the STV indices studied were found to be almost identical statistically. The LTV indices of de Haan et al were the same in essence, while other LTV indices reflected only the fluctuation around the mean fetal heart rate. Analysis using a signal generator indicates that the value of the standard deviation of beat-to-beat difference (one STV index) of less than 7 msec, through the cardiotocomonitor is unreliable; if the standard deviation of beat-to-beat difference is to be measured with an accuracy of 1 msec, an accuracy of measurement of 0.11 msec is necessary even if the fetal heart beat data are sampled with a sampling interval of 1 msec.

Female↗

PubMed2005

Automated DNA fragments recognition and sizing through AFM image processing.

This paper presents an automated algorithm to determine DNA fragment size from atomic force microscope images and to extract the molecular profiles. The sizing of DNA fragments is a widely used procedure for investigating the physical properties of individual or protein-bound DNA molecules. Several atomic force microscope (AFM) real and computer-generated images were tested for different pixel and fragment sizes and for different background noises. The automated approach minimizes processing time with respect to manual and semi-automated DNA sizing. Moreover, the DNA molecule profile recognition can be used to perform further structural analysis. For computer-generated images, the root mean square error incurred by the automated algorithm in the length estimation is 0.6% for a 7.8 nm image pixel size and 0.34% for a 3.9 nm image pixel size. For AFM real images we obtain a distribution of lengths with a standard deviation of 2.3% of mean and a measured average length very close to the real one, with an error around 0.33%.

Algorithms↗

PubMed2005

Factors affecting the test-retest variability of Heidelberg retina tomograph and Heidelberg retina tomograph II measurements.

AIMS: To evaluate the test-retest variability of stereometric parameter measurements made with the Heidelberg retina tomograph (HRT) and Heidelberg retina tomograph-II (HRT-II), and to establish which parameter(s) provided the most repeatable and reliable measurements with both devices. An investigation into the factors affecting the repeatability of the measurements of this parameter(s) was conducted. METHODS: 43 ocular hypertensive and 31 glaucoma subjects were recruited to a test-retest study. One eye from each subject underwent HRT and HRT-II imaging by two observers on each of two occasions within 6 weeks of each other. Lens grading was carried out by LOCS III grading and Scheimpflug camera generated densitogram analysis. RESULTS: Rim area (RA) and mean cup depth measurements were found to be least variable. Both inter-test reference height difference and image quality had a strong relation (R(2)>0.5, p<0.0001) with inter-test RA difference and, together, are responsible for 70% of RA measurement variability. Image quality was influenced by lens opacity, cylindrical error, and age. Inter-test RA measurement differences were unrelated to the observer or visit interval. CONCLUSIONS: RA represents an appropriate measure for monitoring glaucomatous progression. Reference height difference and image quality were the factors that most influenced RA measurement variability. Image analysis strategies that address these factors may reduce test-retest variability.

Adult↗

PubMedDate not supplied

Incentives and barriers that influence clinical computerization in Hong Kong: a population-based physician survey.

OBJECTIVE: Given the slow adoption of medical informatics in Hong Kong and Asia, we sought to understand the contributory barriers and potential incentives associated with information technology implementation. DESIGN AND MEASUREMENTS: A representative sample of 949 doctors (response rate = 77.0%) was asked through a postal survey to rank a list of nine barriers associated with clinical computerization according to self-perceived importance. They ranked seven incentives or catalysts that may influence computerization. We generated mean rank scores and used multidimensional preference analysis to explore key explanatory dimensions of these variables. A hierarchical cluster analysis was performed to identify homogenous subgroups of respondents. We further determined the relationships between the sets of barriers and incentives/catalysts collectively using canonical correlation. RESULTS: Time costs, lack of technical support and large capital investments were the biggest barriers to computerization, whereas improved office efficiency and better-quality care were ranked highest as potential incentives to computerize. Cost vs. noncost, physician-related vs. patient-related, and monetary vs. nonmonetary factors were the key dimensions explaining the barrier variables. Similarly, within-practice vs external and "push" vs "pull" factors accounted for the incentive variables. Four clusters were identified for barriers and three for incentives/catalysts. Canonical correlation revealed that respondents who were concerned with the costs of computerization also perceived financial incentives and government regulation to be important incentives/catalysts toward computerization. Those who found the potential interference with communication important also believed that the promise of improved care from computerization to be a significant incentive. CONCLUSION: This study provided evidence regarding common barriers associated with clinical computerization. Our findings also identified possible incentive strategies that may be employed to accelerate uptake of computer systems.

Attitude of Health Personnel↗

PubMed1997

Nearest-neighbor classification for identification of aggressive versus nonaggressive low-grade astrocytic tumors by means of image cytometry-generated variables.

The authors investigated whether cytometry-related variables generated by means of computer-assisted microscopic analysis of Feulgen-stained nuclei can contribute significant information toward the characterization of low-grade astrocytic tumor aggressiveness. This investigation was conducted using the nearest-neighbor rule (a traditional classification method used in pattern recognition) to analyze a series of 250 supratentorial astrocytic tumors from adult patients. This series included 39 low-grade astrocytomas and 211 high-grade astrocytic tumors (including 47 anaplastic astrocytomas and 164 glioblastomas multiforme [GBMs]). The results show that the 3-nearest-neighbors rule enabled a subgroup of "atypical" astrocytomas to be distinguished from the "typical" tumors. The atypical astrocytoma species exhibited a DNA content (DNA ploidy level) and morphonuclear characteristics that were statistically more similar to the characteristics of GBMs than to those exhibited by the typical astrocytomas. An analysis of survival data revealed that patients with atypical astrocytomas survived for a significantly shorter period (p < 0.001) than patients with typical lesions of this kind. In fact, patients with atypical astrocytomas had a survival period similar to that of patients with anaplastic astrocytomas, whereas patients with typical astrocytomas had a survival period significantly longer (p < 0.0001) than those associated with anaplastic astrocytomas and GBMs.

Adolescent↗

PubMed1999

Comparison of genetic algorithms and other classification methods in the diagnosis of female urinary incontinence.

Galactica, a newly developed machine-learning system that utilizes a genetic algorithm for learning, was compared with discriminant analysis, logistic regression, k-means cluster analysis, a C4.5 decision-tree generator and a random bit climber hill-climbing algorithm. The methods were evaluated in the diagnosis of female urinary incontinence in terms of prediction accuracy of classifiers, on the basis of patient data. The best methods were discriminant analysis, logistic regression, C4.5 and Galactica. Practically no statistically significant differences existed between the prediction accuracy of these classification methods. We consider that machine-learning systems C4.5 and Galactica are preferable for automatic construction of medical decision aids, because they can cope with missing data values directly and can present a classifier in a comprehensible form. Galactica performed nearly as well as C4.5. The results are in agreement with the results of earlier research, indicating that genetic algorithms are a competitive method for constructing classifiers from medical data.

Algorithms↗

PubMed2006

Limitations to practising holistically in the public sector in a rural sub-district in South Africa.

INTRODUCTION: The healthcare system in South Africa is based on the district health system through a primary healthcare approach. Although many vision and mission statements in the public healthcare sector in South Africa state that the service aspires to be holistic, it is at times unclear what exactly is meant by such an aspiration. The term 'holism' was coined in the 1920s and describes the phenomenon of the whole being greater than the sum of the parts. Over the past two decades the term has entered into many academic disciplines as well as popular culture. Also within public healthcare services, despite predominantly biomedical approaches, there is the aspiration to offer a more holistic service. As part of a larger research study, the limitations to working holistically in the public sector in a rural sub-district in South Africa were explored. METHODOLOGY: The study used a participatory action research design that allowed participants a large degree of influence over the direction of the study. The research group consisted of four primary healthcare nurses and one medical doctor, all working in the public sector in a rural sub-district. The research group took part in the process of design and data gathering phases, as well as analysing and making meaning of the data generated. After a thematic analysis of the transcribed meetings, interviews and field notes, the themes were shared with the participants, who arranged them into a graphic representation showing the interrelationships of the themes. RESULTS: From analysis of the data it was clear that there were significant limitations to practicing holistically in the public sector of the rural sub-district in which the study took place. The limitations were grouped into those arising from within the public healthcare system and those outside the healthcare system. Within the healthcare system, the main factors limiting holistic care were: limited resources; poor training in and knowledge of holistic care; poor supervision; distance from the community; the referral system, intersectoral work and bureaucracy. Outside the healthcare sector the following factors challenged the provision of holistic care: poverty; poor nutrition; HIV/AIDS; and the cultural context. All the limitations were found to contribute to the danger of burnout among healthcare workers who wanted to work holistically. The limitations were also found to have a negative impact on the healthcare worker-patient relationship, thereby further challenging holistic care. CONCLUSION: A number of aspects of the healthcare provision system that contributed to limiting the provision of holistic care could be changed quite readily, if there was a will to do so. Many of the issues seemed to plague the healthcare system generally, not only in relation to the provision of holistic care (such as supervision or a response to poverty). The close relationship between difficulty in providing a holistic healthcare service and burnout was an important finding that deserves further exploration.

Burnout, Professional↗

PubMed1994

The automated white blood cell differential. A current perspective.

The white blood cell differential count represents a major portion of the workload in the hematology laboratory. The traditional procedure whereby a technologist examines a Romanowsky-stained blood film and classifies 100 cells is both labor intensive and imprecise. To significantly improve the precision, the technologist would have to count and classify at least 1000 cells, which is obviously impractical in terms of time and efficiency. Until the availability of the automated hematology instruments, it was not possible to obtain a differential count that could be regarded as statistically significant. Automation is therefore necessary and desirable for both economic and clinical reasons. Automation can also provide a number of instrument-derived parameters tha have attained diagnostic significance in their own right. Analytic and technologic advances have occurred with every generation of hematology instruments. As the means of analysis becomes more sophisticated, additional categories of cells may be expected to be classified, and current categories may be more accurately and precisely defined. It is hoped this will lead to even greater clinical utility, as well as provide quality assurance and assessment methods that need to be developed similar to other procedures in the clinical laboratory.

Autoanalysis↗

PubMed2001

Recovery time of independent poststroke life habits: Part II.

The purposes of this study were to determine the time of the recovery of poststroke life habits and to identify prognostic indicators associated with recovery time among stroke patients in a rehabilitation program. A sample of 421 stroke patients who were admitted to a rehabilitation center was recruited from medical records available from January 1987 to December 1992. The relation between the achievement of independent life habits including bed mobility, transfers and ambulation, bathing activities, dressing activities, eating activities, home activities, sphincter control, and sleep with the potential covariates associated with recovery time was assessed through the analysis of survival data using the Cox maximum-likelihood proportional hazard models. The poststroke life habits obtained generated mean recovery times ranging from 5.51 to 57.60 days from admission to rehabilitation. The survival analysis revealed that the recovery time of the selected poststroke abilities was significantly influenced (p <.05) by one or several indicators; these included physical ability and neuropsychological and life habit characteristics. With this precious information, stroke rehabilitation specialists may be able to reduce the length of time required to recover independent poststroke life habits by treating the specific neuropsychological, physical, and life habit characteristics identified in this study. A faster poststroke recovery would reduce the socioeconomic impact generated by stroke disability and would also ensure a better quality of life to the stroke survivor.

Journal Article↗

PubMed1998

Periodontitis detection efficacy of film and digital images.

OBJECTIVE: The objective of this study was to evaluate the accuracy of alveolar crestal bone detection in a comparison of unenhanced and enhanced Sidexis (Siemens Medical Systems, Inc., Bensheim, Germany) digital images with Ektaspeed Plus (Eastman Kodak, Rochester, N.Y.) films by means of receiver operating characteristic analysis. STUDY DESIGN: More than 100 proximal and furcal areas in the anterior and posterior areas of the mandible and maxilla of each of three tissue-equivalent human skull phantoms were imaged with film, direct digital images, and contrast- and brightness-enhanced digital images. Alveolar crest status was assessed by a consensus panel of three experts who used the Delphi method and evaluated information from all of the imaging modalities concurrently. Five observers assessed all images for the presence or absence of crestal bone loss using a five-point confidence scale. Receiver operating characteristic curves were generated, and calculated areas (Az) were analyzed by means of analysis of variance. RESULTS: The expert panel determined that of 106 crestal areas, 48 were disease free and 58 exhibited bone loss greater than 2 mm apical to the cemento-enamel junction. Analysis of variance of observer Az scores showed significant differences among readers (p < 0.001) and among readings (p = 0.027), but not among modalities (p = 0.435). Mean Az values for the different modalities were as follows: Sidexis, 0.70; enhanced Sidexis, 0.71; Ektaspeed Plus films, 0.735. CONCLUSION: The Sidexis digital imaging system was not significantly different from Ektaspeed Plus film for crestal bone evaluation in this in vitro study.

Alveolar Bone Loss↗

PubMed2006

Functional significance of the sperm head morphometric size and shape for determining freezability in iberian red deer (Cervus elaphus hispanicus) epididymal sperm samples.

In the present study, computer-automated sperm head morphometry of epididymal samples was used to determine if sperm head area and shape are useful measurements for separating "good" and "bad" Iberian red deer freezers. A microscope slide was prepared from single diluted sperm fresh samples collected from 38 mature stags. Slides were air-dried and stained with Hemacolor. The sperm head area and shape (length/width) for a minimum of 145 sperm heads were determined for each male by means of the Sperm-Class Analyser. The remainder of each sample was frozen. After thawing, sperm cryosurvival was judged in vitro by microscopic assessments of individual sperm motility and of plasma membrane and acrosome integrities. All sperm parameters evaluated at thawing were placed in a statistical database and a multivariate cluster analysis performed. Mean sperm parameters of the 2 clusters generated ("bad" and "good" freezers) were compared by ANOVA. Our results show that sperm quality at thawing for all sperm parameters evaluated was significantly higher (P < .01) for "good" freezers than for the "bad" ones (sperm motility index: 67.4 +/- 2.0 vs 57.1 +/- 2.8; NAR: 67.1 +/- 2.5 vs 54.5 +/- 3.5; viability: 68.8 +/- 2.0 vs 60.1 +/- 2.8; HOST: 71.3 +/- 2.2 vs 63.1 +/- 3.1). Additionally, differences (P < .01) in epididymal sperm head area and shape were found between "good" and "bad" freezers before freezing, with the smallest overall sperm head dimensions found in the "good" freezers group (area: 32.04 microm2 vs 34.42 microm2). Thus, the lower the sperm head area in the fresh samples, the greater the sperm cryoresistance. Our results show that the 2 groups of males also differ in sperm head shape in fresh samples (good: 1.96 vs poor: 1.72; P < .01). It is possible that sperm head area and shape influence total sperm volume, thus causing differences in heat exchange as well as in movements of water, ions, and cryoprotectants and, in turn, on sperm freezability.

Animals↗

PubMed1993

A maximum-likelihood model-fitting approach to conducting a Hayman analysis of diallel tables with complete or missing data.

A method is presented for conducting a Hayman analysis of non-replicated diallel tables using a maximum-likelihood (ML) model-fitting approach, rather than a traditional analysis of variance (ANOVA) approach. Hayman's linear model for a diallel analysis is used to generate a table of expected cell means. This table of expected cell means is fit to a table of observed cell means, and the fit is assessed using a chi-square value. Often data collected from diallel crosses fail to meet the underlying assumptions of ANOVA. The ML method makes no assumptions about equal cell sizes or homogeneity of variance. Thus, the ML method for diallel analysis provides some statistical advantages over ANOVA methods. The ML method also offers the advantage of having the ability to analyze diallels with missing cells. Using the ML method, incomplete diallel tables can be analyzed, and the partitioning of all the sources of variation in a diallel table is still accomplished from the remaining crosses. These advantages make the ML method an attractive approach for extracting the maximum amount of information from a diallel table.

Alleles↗

PubMed2005

Risk aversion and uncertainty in cost-effectiveness analysis: the expected-utility, moment-generating function approach.

The availability of patient-level data from clinical trials has spurred a lot of interest in developing methods for quantifying and presenting uncertainty in cost-effectiveness analysis (CEA). Although the majority has focused on developing methods for using sample data to estimate a confidence interval for an incremental cost-effectiveness ratio (ICER), a small strand of the literature has emphasized the importance of incorporating risk preferences and the trade-off between the mean and the variance of returns to investment in health and medicine (mean-variance analysis). This paper shows how the exponential utility-moment-generating function approach is a natural extension to this branch of the literature for modelling choices from healthcare interventions with uncertain costs and effects. The paper assumes an exponential utility function, which implies constant absolute risk aversion, and is based on the fact that the expected value of this function results in a convenient expression that depends only on the moment-generating function of the random variables. The mean-variance approach is shown to be a special case of this more general framework. The paper characterizes the solution to the resource allocation problem using standard optimization techniques and derives the summary measure researchers need to estimate for each programme, when the assumption of risk neutrality does not hold, and compares it to the standard incremental cost-effectiveness ratio. The importance of choosing the correct distribution of costs and effects and the issues related to estimation of the parameters of the distribution are also discussed. An empirical example to illustrate the methods and concepts is provided.

Cost-Benefit Analysis↗

PubMed1988

Early diagnosis and treatment of pancreas allograft rejection.

A major problem in vascularized pancreas transplantation is the lack of reliable methods for the early diagnosis and effective treatment of allograft rejection. Over a 2-year period, 54 rejection episodes occurred in 31 patients (13 isolated pancreas, 18 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 253 radionuclide pancreas examinations were performed (mean 8.4 per patient) utilizing 99mtechnetium-DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft caused the technetium index (TI). Rejection episodes were characterized as isolated pancreas (22), combined pancreas-kidney (16), or isolated renal (16) allograft rejection in combined engraftments. The majority of rejection episodes occurred early (within 3 months of transplant, N = 47) and were more responsive than late rejection to anti-rejection therapy (89.4% vs 42.9%, P = 0.01). Mean urinary amylase (UA) levels and TI during normal allograft function were 29,398 U/l and 0.55%, while levels heralding rejection were 6,528 U/l and 0.40%, respectively (P less than 0.05). The treatment of rejection based upon renal dysfunction or combined renal and pancreas dysfunction resulted in significantly higher graft salvage with a lower incidence of hyperglycemia when compared to isolated pancreas allograft rejection. Of the 11 patients who developed hyperglycemia, 8 (72.7%) ultimately lost their pancreas grafts (P less than 0.001). Following therapy, a TI above 0.3% was associated with 97.4% graft survival, while levels below 0.3% resulted in a 70% rate of graft loss (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

PubMed1985

Analysis of immunoglobulin G kinetics in the non-steady state.

The effect of specific intravascular IgG depletion on IgG catabolism, generation, and intrabody transfer has been studied in rabbits. In contrast to previous studies, the radiolabeled IgG kinetics were analyzed in the non-steady state. A two-pool model was used to determine IgG distribution, catabolism, generation, and intrabody mass transfer after intravenous injection of 125I-IgG. Circulating IgG was then specifically removed by plasma perfusion through a Protein-A Sepharose column in an extracorporeal circuit. Based on the two-pool analysis, IgG catabolic clearance fell after IgG removal (1.0 ml/hr vs. 0.7 ml/hr), and mean generation rate was unchanged. Plasma levels rose 20 hours after IgG removal as a result equally of contributions from intrabody transfer and of generation. Model parameters from plasma 125I decay analysis overestimated plasma 125I levels in the first 24 hours after removal, although predicted endogenous levels corresponded well with experimental results over a 7-day period. Rapid intravenous infusion of a 7% body weight volume of saline solution during IgG removal resulted in 50% greater plasma levels of 125I-IgG 24 hours after removal. This indicated that an increased lymphatic flow had occurred, resulting in increased IgG transfer from the extravascular to the intravascular space. The two-pool model adequately describes circulating IgG levels after specific IgG removal. Catabolic clearance was found to be a function of IgG level, whereas generation does not appear to be similarly dependent. Both the two-pool model and saline infusion procedure may be applied directly to the planning and optimization of plasma exchange therapy regimens in human autoimmune disease.

Animals↗

PubMed2004

Here is the evidence, now what is the hypothesis? The complementary roles of inductive and hypothesis-driven science in the post-genomic era.

It is considered in some quarters that hypothesis-driven methods are the only valuable, reliable or significant means of scientific advance. Data-driven or 'inductive' advances in scientific knowledge are then seen as marginal, irrelevant, insecure or wrong-headed, while the development of technology--which is not of itself 'hypothesis-led' (beyond the recognition that such tools might be of value)--must be seen as equally irrelevant to the hypothetico-deductive scientific agenda. We argue here that data- and technology-driven programmes are not alternatives to hypothesis-led studies in scientific knowledge discovery but are complementary and iterative partners with them. Many fields are data-rich but hypothesis-poor. Here, computational methods of data analysis, which may be automated, provide the means of generating novel hypotheses, especially in the post-genomic era.

Animals↗