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At least 739 records · Page 41Linked to original sources
PubMed1992

Doppler sonographic pulse curve analysis for estimation of the haemodynamic function.

Experience with Doppler sonographic pulse curve analysis is given from 40 glaucoma patients (examination of the temporal posterior ciliary artery), and from premature babies (blood flow in the anterior cerebral artery). In the latter group the reaction to pain and stress connected with blood sampling was studied. In the glaucoma patients focus was on the influence of IOP level on vascular autoregulation, and the possible response to therapy with beta-blockers. Describing an averaging technique, methodological problems are discussed as relevant for the detection of changes in flow and velocity in small blood vessels.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[The telephone interview: the methodological strategy for collecting population data].

The interview by telephone is not an ordinary procedure to obtain investigation data. By knowing that is rarely used in Brazil, the study was planned aiming to: identify the individuals' characteristics who answer the sampled telephones; raise the interviews' statements about the operational technique and evaluate the telephone used as data collection procedure. The data indicate that most of the people who were interviewed, were females, between 30 and 40 years old and housewives. The interviewers considered between 30 and 40 years old and housewives. The interviewers considered the experience interesting, in despite of the difficulty to maintain people talking on the phone. The authors state that the interview by telephone is an efficient and fast way of bringing up data for investigation which aims to raise opinions about certain matters.

Adolescent↗
PubMed1995

Analysis of mycotoxins in food and feed: certification of DON in wheat and maize.

Worldwide there are either statutory limits or in some instances advisory guidelines for the maximum levels of mycotoxins in foods and feeds. These limits which have been agreed for the protection of human health and as standards for trade are often set at surprisingly low levels in view of both the problems of sampling and the abundant evidence of the difficulties of mycotoxin analysis, particularly so when approaching the limits of detection. Improved methodology for mycotoxins and improvements in performance even of expert laboratories have, however, been achieved through intercomparison exercises organised by the EC Measurement and Testing programme (formerly BCR). On a wider scale, participation in proficiency testing through schemes such as the UK Food Analysis Performance Assessment Scheme (FAPAS) have indicated that between 10 and 40% of laboratories experience difficulties in obtaining satisfactory results in monitoring mycotoxins. Reference materials provide an important means of checking method performance. BCR has made a unique contribution in the production and certification of maize and wheat reference materials naturally contaminated with the Fusarium mycotoxin 4-deoxynivalenol (DON), which has now been available for purchase for some 2 years.

Calibration↗
PubMed2000

Application of nano-probe NMR for structure determination of low nanomole amounts of arabinoxylan oligosaccharides fractionated by analytical HPAEC-PAD.

A methodology for NMR analysis of low nanomole amounts of oligosaccharides fractionated by analytical HPAEC is presented. Arabinoxylan derived oligosaccharides purified by HPAEC-PAD on an analytical column, by single injections, were analyzed with nano-probe NMR and MALDI-TOF MS to provide full structural assignment. The NMR data were obtained with a 500 MHz NMR spectrometer equipped with a 1H-observe nano-probe. Both one- and two-dimensional experiments on arabinoxylan samples in the low nanomole range were performed, including 1H-1H DQF-COSY, 1H-1H TOCSY and 1H-1H ROESY. These experiments allowed, in combination with MALDI-TOF MS and literature NMR data, a complete structural determination of several tetra-, penta-, hexa- and heptasaccharides. Two new structures: alpha-L-Araf-(1 --> 2)-beta-D-Xylp-(1 --> 4)-beta-D-Xylp-(1 --> 4)-beta-D-Xylp-(1 --> 4)-D-Xylp and alpha-L-Araf-(1 --> 2)[alpha-L-Araf-(1 --> 3)]-beta-D-Xylp-(1 --> 4)-beta-D-Xylp-(1 --> 4)-beta-D-Xylp-(1 --> 4)-D-Xylp) were characterized, as well as some previously published structures.

Carbohydrate Conformation↗
PubMed1999

Imaging living cells and tissues by two-photon excitation microscopy.

Two-photon excitation microscopy provides attractive advantages over confocal microscopy for three-dimensionally resolved fluorescence imaging. Since two-photon excitation occurs only at the focal point of the microscope, it inherently provides three-dimensional resolution. This localization of excitation also minimizes photobleaching and photodamage, which are the ultimate limiting factors in imaging living cells. Furthermore, no pinhole is required to attain three-dimensional discrimination, so the efficiency of fluorescence collection is increased. These advantages allow experiments on thick living samples that would not be possible with other imaging techniques. The cost and complexity of the lasers required for two-photon excitation microscopy have limited its use, but appropriate turn-key lasers have now been introduced, and their cost should decrease. Finally, the recent introduction of commercial two-photon excitation laser-scanning microscope systems allows a much larger group of researchers access to this state-of-the-art methodology.

Animals↗
PubMed1993

Kinetics and mechanism of DNA repair: an automated programmable apparatus for fast time-resolved studies of the repair of mammalian DNA after u.v. irradiation.

An automated apparatus, designed and constructed for use in fast time-resolved studies of mammalian DNA repair after u.v. irradiation, is described. The methodology makes use of caged DNA-break-trapping reagents, e.g. [alpha-32P]dideoxyadenosine triphosphate [see Meldrum, Shall, Trentham and Wharton (1990) Biochem J. 266, 885-890] and the apparatus incorporates excimer lasers both for the delivery of u.v. damage and for the photoactivation of the caged reagents. The design is based on a sample-changing turntable which permits the sequential irradiation and quenching of samples. A maximum of eight samples can be processed in a single experiment, the sequence of events being programmed on a microcomputer, which permits a very generalized experimental sequence. Pipettes for addition of cells, nucleotides and quenching agent are driven pneumatically. A pair of pneumatically operated platinum electrodes allows electroporation of cells for loading of negatively charged reagents prior to irradiation. The time resolution of the apparatus is dependent upon the experimental scheme used and can be very short (e.g. 1 ms) when caged reagents are used; a more usual period is 1 s for the shortest incubation.

Animals↗
PubMed1996

Healing of adult male survivors of childhood sexual abuse.

OBJECTIVE: To generate a framework of healing by male survivors of childhood sexual abuse. DESIGN: Qualitative using grounded theory methodology. POPULATION, SAMPLE, SETTING, YEARS: Population was American men living in the community who have experienced some healing from childhood sexual abuse. Sample was 19 men who were recommended by area therapists or who had publicly identified themselves as survivors. Participants were interviewed in 1993 and 1994. METHOD: Formal, unstructured interviews using open-ended questions. FINDINGS: The core variable that emerged was "Escaping the dungeon: The journey to freedom." The metaphor of "dungeon" reflects the men's experiences of powerlessness, isolation, silence and darkness, shame, and pain from their abuse. Healing was described as breaking free, living free, and freeing those left behind. CONCLUSIONS: Healing involves a struggle against an internal force, emotional pain, and against an external force, the sociocultural prescription that men should not be victims. CLINICAL IMPLICATIONS: Clinicians working with adult male survivors should consider the pervasive effects of some childhood sexual abuse experiences. Therapists can address the intrapsychic wounds of male survivors while acknowledging the context of their healing, a society where the victimization of men is often invalidated.

Adult↗
PubMed1997

Assessment of methodological practices in the evaluation of alcohol and other drug (AOD) abuse prevention.

No authoritative consensus has been achieved on which substance abuse prevention activities are effective for given populations. One response to concern about "what works" took the form of a National Structured Evaluation (NSE), mandated by the Anti-Drug Abuse Act of 1988. The present paper describes the NSE's pivotal task of determining whether evaluation methodologies applied to substance abuse prevention were adequate to produce credible findings. The lessons learned from this evaluation experience, in turn, offer guidance on changes that must be made in the application of evaluation methodology prior to a conclusive demonstration of the value of prevention efforts.

Alcoholism↗
PubMedDate not supplied

Free oxygen radical-induced acute pancreatitis. A light and electron microscopic study.

BACKGROUND/AIMS: To date direct toxic effects of free oxygen radicals in vivo on pancreatic parenchyma have not been studied thoroughly. We aimed to study: 1) the detailed histopathological changes induced by free oxygen radicals in pancreas; and 2) the preventive effect of intraductal catalase in H2O2-induced acute pancreatitis. METHODOLOGY: Wistar Albine rats were randomized into six groups. 1) First experiment: Bile-pancreatic duct was cannulated close to the liver and perfused through the duodenum with (i) normal saline solution, (ii) iron sulfate (FeSO4), (iii) hydrogen peroxide (H2O2), (iv) hydrogen peroxide and iron sulfate simultaneously. 2) Second experiment: Bile pancreatic duct was perfused either with H2O2 or H2O2 + catalase. Serum amylase and pancreas malondialdehyde levels were measured in both experiments after 3 hours of perfusion period. Tissue samples were obtained for histopathological examinations. RESULTS: 1) First experiment: Intraductal perfusion of FeSO4 or H2O2 or H2O2 + FeSO4 induced acute edematous pancreatitis with focal parenchymal necrosis. At the ultrastructural level, intracytoplasmic formation of vacuoles. fusion of the vacuoles and zymogen granules, and autophagosomes containing cellular organelles were found. Serum amylase and pancreas malondialdehyde levels, and morphological score were significantly higher in these groups than control group (p < 0.001). 2) Second experiment: Catalase perfusion simultaneously with H2O2 decreased the serum amylase and pancreas malondialdehyde levels, and morphological score significantly (p < 0.001) and prevented the desquamation of the columnar epithelium and development of gross edema but not parenchymal necrosis. CONCLUSIONS: Intraductal perfusion of FeSO4 or H2O2 or H2O2 + FeSO4-induced acute pancreatitis with marked light and electronmicroscopic changes. Intraductal perfusion of catalase and H2O2 simultaneously did not prevent or lessen the parenchymal necrosis. These findings have suggested that another mechanism of injury may also play a role in parenchymal injury in oxygen radical-induced acute pancreatitis.

Acute Disease↗
PubMed1996

Counting of apoptotic cells: a methodological study in invasive breast cancer.

Aims-To arrive at a reproducible sampling technique for counting apoptotic cells in tissue sections of invasive breast cancer that can serve as a protocol for further clinical studies.Methods-In 4 mum thick haematoxylin and eosin stained tissue sections of 12 breast cancers, apoptotic cells, recognised by strict morphological criteria, were counted in consecutive fields of vision at x1000 magnification in a marked area in the most poorly differentiated region of tumour. These counts were regarded as the gold standard. Subsequently, in a systematic sampling experiment, the number of fields that had to be counted to derive an acceptable coefficient of variation (CV) was determined. To compare counts at different magnifications, all fields of vision were also counted at x630 and x400. The intra- and inter-observer reproducibility was tested by repeated measurements at these magnifications in 10 systematically selected fields of vision.Results-Apoptosis seemed to be a rare event, affecting, on average, about 1% of tumour cells. Noticeable clustering of apoptotic cells was observed. The systematic sampling experiment showed that at x1000 magnification, the CV was improved by counting up to 20 fields. When comparing x400 and x630 magnifications with the x1000 magnification, the correlation coefficients were 0.88 and 0.87, respectively. However, the lower magnifications yielded lower counts. With regard to reproducibility, the intra-observer correlation coefficient was 0.91 at x630 and 0.76 at x400. The inter-observer correlation coefficient was 0.77 at x630 and 0.68 at x400.Conclusions-Apoptotic cells can be counted readily in haematoxylin and eosin stained tissue sections. However, a systematic sampling protocol must be followed and cells should be counted at a relatively high magnification to obtain acceptable reproducibility. The suggested protocol will permit further correlative and prognostic studies and the monitoring of the effects of treatment.

Journal Article↗
PubMed2023

Evaluating the impact of modeling choices on the performance of integrated genetic and clinical models.

The value of genetic information for improving the performance of clinical risk prediction models has yielded variable conclusions. Many methodological decisions have the potential to contribute to differential results across studies. Here, we performed multiple modeling experiments integrating clinical and demographic data from electronic health records (EHR) and genetic data to understand which decision points may affect performance. Clinical data in the form of structured diagnostic codes, medications, procedural codes, and demographics were extracted from two large independent health systems and polygenic risk scores (PRS) were generated across all patients with genetic data in the corresponding biobanks. Crohn's disease was used as the model phenotype based on its substantial genetic component, established EHR-based definition, and sufficient prevalence for model training and testing. We investigated the impact of PRS integration method, as well as choices regarding training sample, model complexity, and performance metrics. Overall, our results show that including PRS resulted in higher performance by some metrics but the gain in performance was only robust when combined with demographic data alone. Improvements were inconsistent or negligible after including additional clinical information. The impact of genetic information on performance also varied by PRS integration method, with a small improvement in some cases from combining PRS with the output of a clinical model (late-fusion) compared to its inclusion an additional feature (early-fusion). The effects of other modeling decisions varied between institutions though performance increased with more compute-intensive models such as random forest. This work highlights the importance of considering methodological decision points in interpreting the impact on prediction performance when including PRS information in clinical models.

Preprint↗
PubMed2006

Water, solute, and segmental dynamics in polysaccharide hydrogels.

Polysaccharide hydrogels have found several applications in the food industry, in biomedicine, and cosmetics. The study of polysaccharide hydrogels offers a challenging scenario of intrinsic heterogeneities in the crosslinking density and large time and space ranges that characterize a number of dynamic processes entailing segmental motions, water diffusion, and small-molecule diffusion. The understanding of such complex features is essential because of the extensive use of polysaccharidic moieties in the food industry, biomedical devices, and cosmetics. The study of phenomena occurring at the nanoscale to the mesoscale requires the combination of investigative tools to probe different time and distance scales and the structural characterization of the networks by established methodologies such as swelling and elastic modulus measurements. Elastic and quasielastic neutron scattering, and fluorescence recovery after photobleaching are emerging methodologies in this field. In this feature article we focus, somewhat arbitrarily, on these new approaches because other techniques, such as low-resolution proton NMR relaxometry and rheology, have been already described thoroughly in the literature. Case examples of polysaccharide hydrogels studied by neutron scattering and fluorescence recovery are presented here as contributions to the comprehension of the dynamic behavior of physical and chemical hydrogels based on polysaccharides. Quasielastic incoherent neutron scattering experiment on a Sephadex hydrogel sample at different temperatures.

Elasticity↗
PubMedDate not supplied

Estimating effects of a single gene and polygenes on quantitative traits from a diallel design.

A genetic model is developed with additive and dominance effects of a single gene and polygenes as well as general and specific reciprocal effects for the progeny from a diallel mating design. The methods of ANOVA, minimum norm quadratic unbiased estimation (MINQUE), restricted maximum likelihood estimation (REML), and maximum likelihood estimation (ML) are suggested for estimating variance components, and the methods of generalized least squares (GLS) and ordinary least squares (OLS) for fixed effects, while best linear unbiased prediction, linear unbiased prediction (LUP), and adjusted unbiased prediction are suggested for analyzing random effects. Monte Carlo simulations were conducted to evaluate the unbiasedness and efficiency of statistical methods involving two diallel designs with commonly used sample sizes, 6 and 8 parents, with no and missing crosses, respectively. Simulation results show that GLS and OLS are almost equally efficient for estimation of fixed effects, while MINQUE (1) and REML are better estimators of the variance components and LUP is most practical method for prediction of random effects. Data from a Drosophila melanogaster experiment (Gilbert 1985a, Theor appl Genet 69:625-629) were used as a working example to demonstrate the statistical analysis. The new methodology is also applicable to screening candidate gene(s) and to other mating designs with multiple parents, such as nested (NC Design I) and factorial (NC Design II) designs. Moreover, this methodology can serve as a guide to develop new methods for detecting indiscernible major genes and mapping quantitative trait loci based on mixture distribution theory. The computer program for the methods suggested in this article is freely available from the authors.

Alleles↗
PubMed1985

The classification of children's knowledge: development on the balance-scale and inclined-plane tasks.

R.S. Siegler (1981, Monographs of the Society for Research in Child Development, 46 C2, Serial No. 189) has shown that performance on several Piagetian tasks is governed by similar rule structures. The purpose of the first study was to extend his analysis to the inclined-plane task, replicate his original observations about development on the balance-scale task, and determine the consistency in children's rule usage across tasks. We found that Siegler's (1981) binary decision representations adequately characterized development on these tasks, and there was fair correspondence of rule classifications across tasks. An alternative classification procedure, used to diagnose the rules of children who failed our original classification criteria, showed that most of these children's performance patterns were very similar to Siegler's rule patterns. In the second experiment, we improved the diagnosticity of our rule-assessment protocol in light of F. Wilkening and N. H. Anderson's (1982, Psychological Bulletin, 92, 215-237) criticisms, and observed that many Rule III children's predictions were associated with those of integration rules on both tasks. Despite these methodological improvements, many children, especially 5- to 7-year-olds, evidenced use of centration and lexicographic strategies, suggesting that these classifications are not simply an artifact of problem sampling. Some of the problems associated with the classification of children's knowledge are discussed.

Child↗
PubMed2005

New magnetic nano-absorbent for the determination of n-octanol/water partition coefficients.

A novel and generic miniaturization methodology for the determination of partition coefficient values of organic compounds in n-octanol/water by using magnetic nanoparticles is, for the first time, described. We have successfully designed, synthesised and characterised new colloidal stable porous silica-encapsulated magnetic nanoparticles of controlled dimensions. These nanoparticles absorbing a tiny amount of n-octanol in their porous silica over-layer are homogeneously dispersed into a bulk aqueous phase (pH 7.40) containing an organic compound prior to magnetic separation. The small size of the particles and the efficient mixing allow a rapid establishment of the partition equilibrium of the organic compound between the solid supported n-octanol nano-droplets and the bulk aqueous phase. UV-vis spectrophotometry is then applied as a quantitative method to determine the concentration of the organic compound in the aqueous phase both before and after partitioning (after magnetic separation). logD values of organic compounds of pharmaceutical interest (0.65-3.50), determined by this novel methodology, were found to be in excellent agreement with the values measured by the shake-flask method in two independent laboratories, which are also consistent with the literature data. It was also found that this new technique gives a number of advantages such as providing an accurate measurement of logD value, a much shorter experimental time and a smaller sample size required. With this approach, the formation of a problematic emulsion, commonly encountered in shake-flask experiments, is eliminated. It is envisaged that this method could be applicable to the high throughput logD screening of drug candidates.

Ferric Compounds↗
PubMed2003

Meta-analysis of the effects of endothelin receptor blockade on survival in experimental heart failure.

BACKGROUND: Although an initial study of endothelin receptor blockade reported positive findings, subsequent experiments and clinical trials in humans found little or no benefit. METHODS: We applied meta-analytic methods to assess the methodologic rigor of preclinical studies of endothelin blockade and to quantitatively evaluate the totality of evidence regarding the effect of endothelin receptor blockers in experimental heart failure. A total of 396 animals were assigned to control and 594 were assigned to experimental therapy in the pooled analysis. Of the 9 studies identified, no study reported a priori sample size justification. Although there was a tendency to increased mortality with early administration (relative risk 1.39, P=.15) and decreased mortality with late administration (relative risk 0.85, P=.6), in the overall analysis, there was no significant evidence of benefit or harm (relative risk 1.03, P=.9). Studies with a small sample size had estimated effects that tended to deviate further from the pooled estimate of all studies. CONCLUSIONS: Consideration of mortality effects in the totality of studies revealed no significant effect of endothelin antagonists in animal models of experimental heart failure. Given the potential for between-study variability, reliance on studies with small sample size may lead to unrealistic expectations when extrapolating preclinical experimental results to future research.

Animals↗