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PubMed1981

The "iron screen": modification of standard laboratory practice with data analysis.

Multivariate analysis was applied to iron deficiency anemia to generate an efficient sequence of diagnostic laboratory tests. A three step diagnostic system--serum ferritin level and mean corpuscular volume as a screen in all patients, followed by serum iron level and total iron binding capacity in some patients, and by erythrocyte sedimentation rate in a few patients--was constructed using a previously validated data reduction system. When compared to bone marrow iron stores, this system was found to have 96 per cent accuracy. In one year of clinical trial the "iron screen" classified 396 of 416 patients in a hospital setting. This sequential strategy shows how clinical laboratory data can be utilized to render diagnoses of defined probability.

Anemia, Hypochromic↗

PubMed2004

A model to facilitate reflective thinking in clinical nursing education.

A qualitative, contextual, exploratory and descriptive design for theory generation was used to develop a model to facilitate reflective thinking in clinical nursing education (Mouton & Marais, 1990:43; Mouton, 1996: 103-109; Chinn & Kramer 1991:79-120). A model was developed within the existing frameworks of theory generation. Wilson (1963:23-39) and Gift (1997:75,76) provided a theoretical framework for a concept analysis of reflective thinking in phase one of the study. Further conceptual meaning was attained through a perceptual survey where twelve nurse educators participated in a focus group interview with regard to how reflective thinking can be facilitated in clinical nursing education. Classification of the main concepts and sub-concepts was made through a conceptualisation process within Dickoff, James and Wiedenbach's (1968:415-435) theoretical framework using the six elements of practice theory. Concluding relation statements were inferred through deductive analysis and synthesis after conceptualisation of each main concept. The relation statements provided the basis for model description (Chinn & Kramer, 1991:107-125). Definitions of the main concepts and sub-concepts were described using the basic rules by (Rossouw, 2001:10-11; Cohen & Copi, 1994:192-195). The adapted educational process from five learning theories provided a framework through which the procedure to facilitate reflective thinking in clinical nursing education was described. Lastly, the model was evaluated using the pre-determined criteria by Chinn and Kramer (1991:128-137) and refined by experts in qualitative research and theory generation. Guidelines were developed which do not form part of this article. Theoretical validity was ensured. Recommendations, limitations, challenging hypothesis and a conclusion were made.

Decision Making↗

PubMed1998

Unenhanced helical CT criteria to differentiate distal ureteral calculi from pelvic phleboliths.

PURPOSE: To identify imaging features at unenhanced helical computed tomography (CT) that help differentiate distal ureteral calculi from pelvic phleboliths. MATERIALS AND METHODS: Retrospective analysis was performed of 184 pelvic calcifications identified at unenhanced helical CT in 113 patients. The size, shape, and attenuation of each calcification were recorded in addition to the presence of a central lucency and the appearance of the adjacent soft tissues. With profile analysis, a graphic representation was generated of attenuation in each pixel along a line drawn through each calcification. RESULTS: Geometric configuration was seen in eight (21%) calculi but not in any phleboliths. Differences were significant (P < .0001) between the mean attenuation of calculi and that of phleboliths. Among phleboliths, none had a mean attenuation greater than 278 HU, 13 (9%) had a visible central lucency, 31 (21%) had a bifid peak at profile analysis, 30 (21%) had the "comet sign" (adjacent eccentric, tapering soft-tissue mass corresponding to the noncalcified portion of a pelvic vein), and three (2%) had the soft-tissue rim sign (edema of the ureteral wall). Among calculi, none had a central lucency, bifid peak, or comet sign, but 29 (76%) had the soft-tissue rim sign. CONCLUSION: Analysis of pelvic calcifications at unenhanced helical CT can help differentiate calculi from phleboliths.

Calculi↗

PubMed2005

Modeling the energy content of combustible ship-scrapping waste at Alang-Sosiya, India, using multiple regression analysis.

Alang-Sosiya is the largest ship-scrapping yard in the world, established in 1982. Every year an average of 171 ships having a mean weight of 2.10 x 10(6)(+/-7.82 x 10(5)) of light dead weight tonnage (LDT) being scrapped. Apart from scrapped metals, this yard generates a massive amount of combustible solid waste in the form of waste wood, plastic, insulation material, paper, glass wool, thermocol pieces (polyurethane foam material), sponge, oiled rope, cotton waste, rubber, etc. In this study multiple regression analysis was used to develop predictive models for energy content of combustible ship-scrapping solid wastes. The scope of work comprised qualitative and quantitative estimation of solid waste samples and performing a sequential selection procedure for isolating variables. Three regression models were developed to correlate the energy content (net calorific values (LHV)) with variables derived from material composition, proximate and ultimate analyses. The performance of these models for this particular waste complies well with the equations developed by other researchers (Dulong, Steuer, Scheurer-Kestner and Bento's) for estimating energy content of municipal solid waste.

Conservation of Energy Resources↗

PubMed1996

Clinical use of prediction regions for motion analysis.

This study assesses the diagnostic capability of statistically defined prediction regions, developed by a 'bootstrap' method, for assessing the curves of angular rotation of joints in children as they walk. The prediction regions had been previously developed in the authors' laboratory from a study of 309 normal children. The goal of the present study was to determine whether these computer-generated prediction regions could be used as a screen in clinical gait analysis, to determine whether a movement falls outside the normal range of variability. Kinematic analysis of 38 consecutive children referred to the motion analysis laboratory for clinical gait assessment provided 912 curves of lower-extremity joint angle dynamics. An experienced observer first inspected the patients' curves with mean normal curves superimposed and designated the curves as normal or abnormal. The performance of the computer-generated prediction regions was judged by comparison with the experienced observer's designations. The prediction regions were found to have a high sensitivity (81%), indicating that they can be used as an initial screen to identify deficits in lower limb function.

Child↗

PubMed2004

Non-stationary time series and the robustness of circadian rhythms.

Circadian rhythms are regular oscillations in the value of behavioral and physiological variables of organisms that recur on a daily basis. The purpose of this study was to evaluate the extent of non-stationarity of circadian rhythms over several days, to determine how damaging is the violation of the assumption of stationarity in the analysis of circadian rhythms, and to formalize the concept of "rhythm robustness" as an index of oscillatory ("weak") stationarity. Simulated (computer-generated) and experimental data sets (rhythms of body temperature and running-wheel activity in several rodent species) were analysed. Tests of stationarity based on the variance of the daily means and the variance of the daily variances revealed that most experimental data sets are not stationary. Analysis of linear trends indicated that significant trends are rare in experimental data sets. Although the non-stationarity of the experimental data sets reduced the spectral energy of the Enright periodogram used to assess rhythmicity, detection of circadian rhythmicity was not prevented in any of the rhythmic data sets. The results of the various analyses allow the inference that, after high-frequency noise is filtered out, the value of the periodogram's Q(P) statistic reflects the extent of stationarity of the time series. Thus, the "robustness" of a circadian rhythm (i.e. the magnitude of the empirical Q(P) value as compared to the Q(P) value associated with a perfectly rhythmic time series) can serve as an index of the stationarity of the rhythm.

Analysis of Variance↗

PubMed2000

Precise spatiotemporal repeating patterns in monkey primary and supplementary motor areas occur at chance levels.

Precise spatiotemporal patterns in neural discharge are a possible mechanism for information encoding in the brain. Previous studies have found that such patterns repeat and appear to relate to key behavioral events. Whether these patterns occur above chance levels remains controversial. To address this question, we have made simultaneous recordings from between two and nine neurons in the primary motor cortex and supplementary motor area of three monkeys while they performed a precision grip task. Out of a total of 67 neurons, 46 were antidromically identified as pyramidal tract neurons. Sections of recordings 60 s long were searched for patterns involving three or more spikes that repeated at least twice. The allowed jitter for pattern repetition was 3 ms, and the pattern length was limited to 192 ms. In all 11 recordings analyzed, large numbers of repeating patterns were found. To assess the expected chance level of patterns, "surrogate" datasets were generated. These had the same moment-by-moment modulation in firing rate as the experimental spike trains, and matched their interspike interval distribution, but did not preserve the precise timing of individual spikes. The number of repeating patterns in 10 randomly generated surrogates was used to form 99% confidence limits on the repeating pattern count expected by chance. There was close agreement between these confidence limits and the number of patterns seen in the experimental data. Analysis of high complexity patterns was carried out in four long recordings (mean duration 23.2 min, mean number of neurons simultaneously recorded 7.5). This analysis logged only patterns composed of a larger number (7-11) of spikes. The number of patterns seen in the surrogate datasets showed a small but significant excess over those seen in the original experimental data; this is discussed in the context of surrogate generation. The occurrence of repeating patterns in the experimental data were strongly associated with particular phases of the precision grip task; however, a similar task dependence was seen for the surrogate data. When a repeating pattern was used as a template to find inexact matches, in which up to half of the component spikes could be missing, similar numbers of matches were found in experimental and surrogate data, and the time of occurrence of such matches showed the same task dependence. We conclude that the existence of precise repeating patterns in our data are not due to cortical mechanisms that favor this form of coding, since as many, if not more, patterns are produced by spike trains constructed only to modulate their firing rate in the same way as the experimental data, and to match the interspike interval histograms. The task dependence of pattern occurrence is explicable as an artifact of the modulation of neural firing rate. The consequences for theories of temporal coding in the cortex are discussed.

Action Potentials↗

PubMed2004

Comparative analysis of isolated cellular organelles by means of soft X-ray contact microscopy with laser-plasma source and transmission electron microscopy.

Soft X-ray contact microscopy (SXCM) is, at present, a useful tool for the examination at submicrometre resolution of biological systems maintained in their natural hydrated conditions. Among current X-ray-generating devices, laser-plasma sources are now easily available and, owing to their pulse nature, offer the opportunity to observe living biological samples before radiation damage occurs, even if the resolution achievable is not as high as with synchrotron-produced X-rays. To assess the potential of laser-plasma source SXCM in the study of cellular organelles, we applied it for the analysis of chloroplasts extracted from spinach leaves and mitochondria isolated from bovine heart and liver. X-ray radiation was generated by a nanosecond laser-plasma source, produced by a single shot excimer XeCl laser focused onto an yttrium target. The images obtained with SXCM were then compared with those produced by transmission electron microscopy observation of the same samples prepared with negative staining, a technique requiring no chemical fixation, in order to facilitate their interpretation and test the applicability of SXCM imaging.

Animals↗

PubMed2004

Application of linear discriminant analysis to the biochemical and haematological differentiation of opiate addicts from healthy subjects: a case-control study.

OBJECTIVE: Biochemical and haematological parameters of nutritional interest were determined in the serum of opiate addicts in order to compare them with those obtained in healthy subjects. Linear discriminant analysis was applied for the differentiation of the opiate addicts. SUBJECTS: Sera of 106 opiate addicts in detoxification treatment (n=19) or in Methadone Maintenance Treatment Program (MMTP) (n=87) were studied. DESIGN: : The determination of classical biochemical and haematological parameters in blood samples was carried out using standardized methods. Determination of retinol and alpha-tocopherol was carried out by high-performance liquid chromatography with diode-array detector. Folic acid and vitamin B(12) were determined using competitive binding techniques. Minerals were determined by flame emission spectrometry (Na and K) and atomic absorption spectrometry with air-acetylene flame (Ca, Mg, Fe, Cu and Zn) or with hydride generation (Se). Phosphorous was determined using a colorimetric method with ammonium molibdate. All statistical analyses were performed by means of the SPSS version 10.0 software for Windows. RESULTS: Stepwise linear discriminant analysis simplified the system to the following variables: Na, K, Mg, number of leucocytes, triglycerides, GPT, glucose, albumin, retinol and folic acid; and 90.1% (86.4% after crossvalidation) of correct classification was obtained. Representing the first and second discriminant functions, the control groups were well separated from opiate addicts. CONCLUSIONS: Applying linear discriminant analysis on several biochemical and haematological parameters, the opiate addicts could clearly be differentiated from the control individuals, and a tendency to differentiate the opiate addicts in MMTP and in detoxification treatment was observed.

Adult↗

PubMed2000

The quest to deduce protein function from sequence: the role of pattern databases.

In the wake of the numerous now-fruitful genome projects, we have witnessed a 'tsunami' of sequence data and with it the birth of the field of bioinformatics. Bioinformatics involves the application of information technology to the management and analysis of biological data. For many of us, this means that databases and their search tools have become an essential part of the research environment. However, the rate of sequence generation and the haphazard proliferation of databases have made it difficult to keep pace with developments, even for the cognoscenti. Moreover, increasing amounts of sequence information do not necessarily equate with an increase in knowledge, and in the panic to automate the route from raw data to biological insight, we may be generating and propagating innumerable errors in our precious databases. In the genome era upon us, researchers want rapid, easy-to-use, reliable tools for functional characterisation of newly determined sequences. For the pharmaceutical industry in particular, the Pandora's box of bioinformatics harbours an information-rich nugget, ripe with potential drug targets and possible new avenues for the development of therapeutic agents. This review outlines the current status of the major pattern databases now used routinely in the analysis of protein sequences. The review is divided into three main sections. In the first, commonly used terms are defined and the methods behind the databases are briefly described; in the second, the structure and content of the principal pattern databases are discussed; and in the final part, several alignment databases, which are frequently confused with pattern databases, are mentioned. For the new-comer, the array of resources, the range of methods behind them and the different tools required to search them can be confusing. The review therefore also briefly mentions a current international endeavour to integrate the diverse databases, which effort should facilitate sequence analysis in the future. This is particularly important for target-discovery programmes, where the challenge is to rationalise the enormous numbers of potential targets generated by sequence database searches. This problem may be addressed, at least in part, by reducing search outputs to the more focused and manageable subsets suggested by searches of integrated groups of family-specific pattern databases.

Amino Acid Motifs↗

PubMed1994

Power of segregation analysis for detection of major gene effects on quantitative traits.

The power to detect major gene effects by rejection of the "no major gene" null hypothesis against a mixed model alternative was determined in random samples of nuclear families over a variety of conditions. Benchmarks have been developed using a varying number of families whose structure includes both parents and three children. Phenotypes were simulated assuming a Mendelian major gene under either recessive or dominant inheritance, with 0-30% residual polygenic heritability. Three trait prevalences--5, 10, and 20%--were considered in combination with increasing displacement between homozygous means, spanning a range of 14 to 36% of the phenotypic variance attributable to the major gene effect. All other assumptions of the traditional mixed model were adopted in the generating models. Segregation analysis was carried out on the simulated data sets and the proportion of samples out of 200 replications in which the null hypothesis q = 0 was rejected is reported as the power. Thus, failure to detect a major gene effect in this context is solely due to sampling variation, since no other perturbations were introduced. In general, there appears to be greater power to detect dominant major gene effects as opposed to recessive ones using otherwise comparable parameter values, and the effect of varying sibship size under dominant models appears to be greater as well. The use of joint vs. conditional likelihood calculations also was evaluated: substantial drops in power were observed when using conditional likelihoods under recessive inheritance, while the differences in power appeared to be nominal under dominant inheritance. The results of this investigation are offered as a guide to assist in the design of family studies whose aim is to detect major gene effects.

Bias↗

PubMed2002

Postsynaptic effects of GABAergic synaptic diversity: regulation of neuronal excitability by changes in IPSC variance.

GABAergic synaptic inputs to principal cells are heterogeneous in terms of their anatomical, molecular and physiological properties. Whether diversity in GABAergic synaptic inputs affects the efficacy of GABAergic inhibition is not understood. Here we show that alterations in the heterogeneity of IPSC populations arriving at single cells can significantly modify the effects of GABAergic inputs on neuronal excitability. The effects of IPSC diversity were examined in a computational model that incorporated experimentally measured values for spontaneous IPSCs and CA1 pyramidal cell electrophysiological properties. The simulations showed that increased variance in the conductance or decay of IPSCs could potently modulate the firing rate of the postsynaptic cells. The actual direction of the IPSC variance-induced modulation in postsynaptic cell discharges depended on the mean IPSC conductance and mean decay time constant around which the variance was introduced, as well as on the degree of depolarization and firing of the postsynaptic cell. Further analysis of the underlying mechanisms determined that these effects of IPSC variance on neuronal excitability were entirely predicted from the non-linear actions of IPSCs on action potential generation. The variance effects on neuronal excitability could be strong enough to overcome even large changes in mean IPSC conductance, demonstrating that increased mean synaptic conductance (or increased mean IPSC or IPSP) alone does not necessarily imply a more effective inhibition, a finding which has important implications for epilepsy research. These data show that the degree of heterogeneity of the GABAergic synaptic inputs to principal cells can powerfully modulate the efficacy of GABAergic inhibition. The results indicate the functional importance of the diversity of interneurons in cortical and hippocampal circuits, and suggest that plastic changes in GABAergic synaptic diversity may modulate neuronal excitability under both normal and pathological conditions.

Cerebral Cortex↗

PubMed2004

Behavioural structuring of relatedness in the spotted hyena (Crocuta crocuta) suggests direct fitness benefits of clan-level cooperation.

Spotted hyenas (Crocuta crocuta) are gregarious carnivores that live in multigenerational social groups, called clans, containing one to several matrilines. Members of multiple matrilines within a clan cooperate during dangerous interactions with inter- and intraspecific competitors. The evolution of cooperation may be influenced by relatedness between individuals, which in turn is influenced by reproductive skew and mate choice, dispersal and territorial behaviours. Behavioural data exist for spotted hyenas, but corresponding data on patterns of relatedness are unavailable; this lack of data makes it difficult to assess the relative importance of selection pressures favouring cooperative behaviour within and among groups. Therefore we conducted a longitudinal analysis of relatedness within a single large clan of spotted hyenas, as well as a cross-sectional analysis of relatedness among hyenas from multiple clans. Within a clan, patterns of relatedness reflected known pedigree relationships, and relatedness was higher within than among matrilines, even across generations. Although mean within-matriline relatedness varied among matrilines, it did not decline with matriline rank. On average, clan members were not related closely, due to high levels of male-mediated gene flow among clans, and relatedness declined very slightly across clan borders. Low mean relatedness within clans suggests that spotted hyenas cooperate with unrelated clan-mates against close paternal kin in other clans. Our data also suggest that spotted hyenas must derive large net direct fitness benefits from group living and cooperation.

Animals↗

PubMed1993

Prenatal development of glucocorticoid receptor gene expression and immunoreactivity in the rat brain and pituitary gland: a combined in situ hybridization and immunocytochemical analysis.

By means of in situ hybridization and immunocytochemical techniques it has been possible to follow the prenatal development of glucocorticoid receptor (GR) messenger RNA (mRNA) expression and GR immunoreactivity (IR) in the rat brain from embryonic day (E) 15 to 22. A 700-base-pair GR cDNA fragment was used for RNA probe generation. In the immunocytochemical analysis a mouse monoclonal antibody (IgG2a) against the rat liver GR was used in combination with the indirect fluorescence technique or the avidin-biotin immunoperoxidase method. At E15 till E22 a moderate to strong GR mRNA signal was observed within the neuro-epithelium from the medulla oblongata to the telencephalon. A moderate to strong labelling was also present within the paraventricular hypothalamic nucleus, the arcuate nucleus, the nucleus raphe magnus, the nucleus raphe obscurus and the locus coeruleus. In these areas a weak to moderate nuclear GR IR developed in nerve cells 1 or 2 days after the appearance of the GR mRNA signal. From E15 the adenohypophysis showed the strongest expression of GR mRNA. At E17 a strong GR IR was especially demonstrated in the nuclei of many pituitary cells, some exhibiting adrenocorticotropin IR. The results open up the possibility that there exist active GR in embryonic life capable of regulating proliferation events within the adenohypophysis and the neuro-epithelia of the brain. This embryonic GR may modulate the development of inter alia neuro-endocrine areas such as the paraventricular and arcuate nuclei and arousal-related areas such as the central 5-hydroxytryptamine and noradrenaline neuronal systems. Provided that this embryonic GR is capable of becoming activated by glucocorticoids in fetal life, it may mediate several neurochemical and behavioural impairments caused by prenatal stress.

Animals↗

PubMed2006

Network analysis of human in-stent restenosis.

BACKGROUND: Recent successes in the treatment of in-stent restenosis (ISR) by drug-eluting stents belie the challenges still faced in certain lesions and patient groups. We analyzed human coronary atheroma in de novo and restenotic disease to identify targets of therapy that might avoid these limitations. METHODS AND RESULTS: We recruited 89 patients who underwent coronary atherectomy for de novo atherosclerosis (n=55) or in-stent restenosis (ISR) of a bare metal stent (n=34). Samples were fixed for histology, and gene expression was assessed with a dual-dye 22,000 oligonucleotide microarray. Histological analysis revealed significantly greater cellularity and significantly fewer inflammatory infiltrates and lipid pools in the ISR group. Gene ontology analysis demonstrated the prominence of cell proliferation programs in ISR and inflammation/immune programs in de novo restenosis. Network analysis, which combines semantic mining of the published literature with the expression signature of ISR, revealed gene expression modules suggested as candidates for selective inhibition of restenotic disease. Two modules are presented in more detail, the procollagen type 1 alpha2 gene and the ADAM17/tumor necrosis factor-alpha converting enzyme gene. We tested our contention that this method is capable of identifying successful targets of therapy by comparing mean significance scores for networks generated from subsets of the published literature containing the terms "sirolimus" or "paclitaxel." In addition, we generated 2 large networks with sirolimus and paclitaxel at their centers. Both analyses revealed higher mean values for sirolimus, suggesting that this agent has a broader suppressive action against ISR than paclitaxel. CONCLUSIONS: Comprehensive histological and gene network analysis of human ISR reveals potential targets for directed abrogation of restenotic disease and recapitulates the results of clinical trials of existing agents.

ADAM Proteins↗

PubMed2005

Tumor growth instability and the onset of invasion.

Motivated by experimental observations, we develop a mathematical model of chemotactically directed tumor growth. We present an analytical study of the model as well as a numerical one. The mathematical analysis shows that: (i) tumor cell proliferation by itself cannot generate the invasive branching behavior observed experimentally, (ii) heterotype chemotaxis provides an instability mechanism that leads to the onset of tumor invasion, and (iii) homotype chemotaxis does not provide such an instability mechanism but enhances the mean speed of the tumor surface. The numerical results not only support the assumptions needed to perform the mathematical analysis but they also provide evidence of (i), (ii), and (iii). Finally, both the analytical study and the numerical work agree with the experimental phenomena.

Animals↗

PubMed2005

The aerodynamics of hovering flight in Drosophila.

Using 3D infrared high-speed video, we captured the continuous wing and body kinematics of free-flying fruit flies, Drosophila melanogaster, during hovering and slow forward flight. We then 'replayed' the wing kinematics on a dynamically scaled robotic model to measure the aerodynamic forces produced by the wings. Hovering animals generate a U-shaped wing trajectory, in which large drag forces during a downward plunge at the start of each stroke create peak vertical forces. Quasi-steady mechanisms could account for nearly all of the mean measured force required to hover, although temporal discrepancies between instantaneous measured forces and model predictions indicate that unsteady mechanisms also play a significant role. We analyzed the requirements for hovering from an analysis of the time history of forces and moments in all six degrees of freedom. The wing kinematics necessary to generate sufficient lift are highly constrained by the requirement to balance thrust and pitch torque over the stroke cycle. We also compare the wing motion and aerodynamic forces of free and tethered flies. Tethering causes a strong distortion of the stroke pattern that results in a reduction of translational forces and a prominent nose-down pitch moment. The stereotyped distortion under tethered conditions is most likely due to a disruption of sensory feedback. Finally, we calculated flight power based directly on the measurements of wing motion and aerodynamic forces, which yielded a higher estimate of muscle power during free hovering flight than prior estimates based on time-averaged parameters. This discrepancy is mostly due to a two- to threefold underestimate of the mean profile drag coefficient in prior studies. We also compared our values with the predictions of the same time-averaged models using more accurate kinematic and aerodynamic input parameters based on our high-speed videography measurements. In this case, the time-averaged models tended to overestimate flight costs.

Animals↗

PubMed1984

Locating peptides generated by limited proteolysis in known protein sequences by means of computer search.

A computational method is presented for locating peptides on known protein sequences using their molecular weights (estimated by SDS polyacrylamide gel electrophoresis) and their composition (obtained by amino acid analysis from eluted gel bands). The technique is easy and rapid, and appears particularly valuable if recoveries of peptides are low, or if they are heterogeneous due to secondary proteolytic degradation. An analysis of limited proteolysis of maltoporin (Schenkman, S. et al. [1984] J. Biol. Chem. 259, 7570-7576) is used to illustrate applicability and reliability of the method, which can also be applied to confirm gene-derived sequences.

Amino Acid Sequence↗