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PubMed2003

Application of the maximum entropy method to absorption kinetic rate processes.

The maximum entropy method, originally developed for astronomical image restoration, has already been successfully applied to a variety of biophysical problems. Through numerical inverse Laplace transformation, the method determines the lifetime distribution function with the largest informational entropy. Starting from a flat distribution, it results in the consistent selection of a single distribution from the numerous possible ones that correctly fit the data. In this paper, we discuss the application of the method to kinetic processes that have both rise and decay components, and test the algorithm with different signal to noise ratio generated data. It is proved that the mass conservation constraint can be taken into account by reducing the search to a lower dimensional subspace. The effect of noise on the width of lifetime distribution is studied and it is shown that an inherent entropy connected to the underlying kinetics can be separated from the noise generated entropy. The possibility of the application of the method to the photocycle kinetics of bacteriorhodopsin is also shown.

Absorption↗
PubMed2000

Voronoi tessellation to study the numerical density and the spatial distribution of neurones.

The conditions of regularity and isotropy, required by standard morphometric procedures, are generally not fulfilled in the central nervous system (CNS) where cells are distributed in a highly complex manner. The evaluation of the mean numerical density of neuronal or glial cells does not take into account the topographical heterogeneity and thereby misses the information that it contains. A local measurement of the density can be obtained by evaluating the 'numerical density of one cell', i.e. the ratio 1/(the volume that the cell occupies). This volume is the region of space that is closer to that cell than to any other. It has the shape of a polyhedron, called Voronoi (or Dirichlet) polyhedron. In 2-D, the Voronoi polyhedron is a polygon, the sides of which are located at mid-distance from the neighbouring cells. The Voronoi polygons are contiguous and their set fills the space without interstice or overlap, i.e. they perform a 'tessellation' that may yield a density map when the same colours are used to fill polygons of similar sizes. The use of Voronoi polygons allows computing the confidence interval of a mean numerical density that makes statistical comparisons possible. The tessellation also provides information concerning spatial distribution; the areas of the Voronoi polygons do not vary much when the cells are regularly distributed. On the contrary, small and large polygons are found when cellular clusters are present. The coefficient of variation of the polygon areas is an objective measurement of their variability and helps to define 'regular', 'clustered' and 'random' distributions. When cells are clustered, small polygons are contiguous and may be objectively identified by simple algorithms. Voronoi tessellations are easily performed in 2-D. On an average the area of a polygon times the thickness of the section equals the volume of the corresponding polyhedron. 3-D tessellations that are theoretically possible and for which algorithms have been published remain to be adapted to histological works.

Algorithms↗
PubMed2003

Connectivity distribution of spatial networks.

We study spatial networks constructed by randomly placing nodes on a manifold and joining two nodes with an edge whenever their distance is less than a certain cutoff. We derive the general expression for the connectivity distribution of such networks as a functional of the distribution of the nodes. We show that for regular spatial densities, the corresponding spatial network has a connectivity distribution decreasing faster than an exponential. In contrast, we also show that scale-free networks with a power law decreasing connectivity distribution are obtained when a certain information measure of the node distribution (integral of higher powers of the distribution) diverges. We illustrate our results on a simple example for which we present simulation results. Finally, we speculate on the role played by the limiting case P(k) proportional, variant k(-1) which appears empirically to be relevant to spatial networks of biological origin such as the ones constructed from gene expression data.

Journal Article↗
PubMed2004

Variation of gene-based SNPs and linkage disequilibrium patterns in the human genome.

A principal goal in human genetics is to provide the tools necessary to enable genome-wide association studies. Extensive information on the distribution of gene-based single-nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) patterns across the genome is required in order to choose markers for efficient implementation of this approach. To obtain such information, we have genotyped a large Japanese cohort for SNPs identified by systematic resequencing of more than 14 000 autosomal genes. Analysis of these data led to the conclusion that the Japanese population contains approximately 130 000 common autosomal gene haplotypes (frequency >0.05), of which more than 35% are identified in the present study. We also examined allele frequencies and LD patterns according to the position of variants within genes, and their distribution across the genome. We found lower allele variability at exonic SNP sites (both non-synonymous and synonymous) compared with non-exonic SNP sites, and greater average LD between SNPs within exons of the same gene compared with other SNP combinations, both of which could be signals of selection. LD was correlated with the recombination rate per physical distance as estimated from the meiotic map, but the strength of the relationship varied considerably in different regions of the genome. Unique LD patterns, characterized by frequent instances of high LD between non-adjacent SNPs punctuated by blocks of low LD, were found in a 7 Mb region on chromosome 6p that includes the MHC (major histocompatibility complex) locus and many non-MHC genes. These results demonstrate the complexity that must be taken into account when considering SNP variability and LD patterns, while also providing tools necessary for implementation of efficient genome-wide association studies.

Chromosomes, Human, Pair 6↗
PubMed2004

Distribution of laminins in the basement membranes of the upper gastrointestinal tract and Barrett's oesophagus.

Barrett's oesophagus predisposes to oesophageal adenocarcinoma. In vitro, laminin, a component of the epithelial basement membrane (BM), is important in regulation of cell differentiation. There is limited information on the distribution of laminin chains in the upper gastrointestinal tract (GIT) and none in Barrett's oesophagus. This study aimed to investigate qualitatively the distribution of laminins in the normal upper GIT mucosa and Barrett's oesophagus in order to understand the role of laminins in metaplasia. Immunoperoxidase staining for laminin chains alpha1, alpha2, alpha3, alpha5, beta1, beta2, beta3, gamma1, and gamma2 was performed on frozen endoscopic squamous and Barrett's oesophageal biopsies and surgical resection specimens from squamous oesophagus (in resection specimens for oesophageal cancer), and in oesophageal and gastric biopsies from control subjects. alpha1 laminin was expressed in the BM of submucosal glands and ducts in squamous oesophagus and Brunner's glands in the duodenum, but not in Barrett's oesophagus or elsewhere in the upper GIT. alpha2 laminin chain was expressed in a granular distribution in the BM of squamous epithelium. In columnar epithelium, including Barrett's oesophagus, alpha2 laminin chain was expressed continuously in the BM of glands and deeper pits, but expression was reduced and granular in the surface epithelial BM. beta2 laminin was continuous in squamous epithelial BM, but in Barrett's and cardia, gastric body, and duodenum, it was expressed faintly in the surface but continuously in the BM of glands and deeper pits. The constituents of laminin-5 were continuously expressed in the BM of squamous epithelium, but in the cardia, gastric body, duodenum, and Barrett's, they were expressed only in the BM of surface epithelium, with a sharp decline in the glandular and deeper pit BM. Site-specific distribution of the alpha2 and beta2 laminin chains may therefore have an important role in Barrett's metaplasia. However, the absence of alpha1 laminin in Barrett's mucosa suggests that this is unlikely to play an important role in columnar metaplasia.

Barrett Esophagus↗
PubMed2007

BARCSoySNP23: a panel of 23 selected SNPs for soybean cultivar identification.

This report describes a set of 23 informative SNPs (BARCSoySNP23) distributed on 19 of the 20 soybean linkage groups that can be used for soybean cultivar identification. Selection of the SNPs to include in this set was made based upon the information provided by each SNP for distinguishing a diverse set of soybean genotypes as well as the linkage map position of each SNP. The genotypes included the ancestors of North American cultivars, modern North American cultivars and a group of Korean cultivars. The procedure used to identify this subset of highly informative SNP markers resulted in a significant increase in the power of identification versus any other randomly selected set of equal number. This conclusion was supported by a simulation which indicated that the 23-SNP panel can uniquely distinguish 2,200 soybean cultivars, whereas sets of randomly selected 23-SNP panels allowed the unique identification of only about 50 cultivars. The 23-SNP panel can efficiently distinguish each of the genotypes within four maturity group sets of additional cultivars/lines that have identical classical pigmentation and morphological traits. Comparatively, the 13 trinucleotide SSR set published earlier (BARCSoySSR13) has more power on a per locus basis because of the multi-allelic nature of SSRs. However, the assay of bi-allelic SNP loci can be multi-plexed using non-gel based techniques allowing for rapid determination of the SNP alleles present in soybean genotypes, thereby compensating for their relatively low information content. Both BARCSoySNP23 and BARCSoySSR13 were highly congruent relative to identifying genotypes and for estimating population genetic differences.

Alleles↗
PubMed2006

Joint distribution approaches to simultaneously quantifying benefit and risk.

BACKGROUND: The benefit-risk ratio has been proposed to measure the tradeoff between benefits and risks of two therapies for a single binary measure of efficacy and a single adverse event. The ratio is calculated from the difference in risk and difference in benefit between therapies. Small sample sizes or expected differences in benefit or risk can lead to no solution or problematic solutions for confidence intervals. METHODS: Alternatively, using the joint distribution of benefit and risk, confidence regions for the differences in risk and benefit can be constructed in the benefit-risk plane. The information in the joint distribution can be summarized by choosing regions of interest in this plane. Using Bayesian methodology provides a very flexible framework for summarizing information in the joint distribution. RESULTS: Data from a National Institute of Child Health & Human Development trial of hydrocortisone illustrate the construction of confidence regions and regions of interest in the benefit-risk plane, where benefit is survival without supplemental oxygen at 36 weeks postmenstrual age, and risk is gastrointestinal perforation. For the subgroup of infants exposed to chorioamnionitis the confidence interval based on the benefit-risk ratio is wide (Benefit-risk ratio: 1.52; 90% confidence interval: 0.23 to 5.25). Choosing regions of appreciable risk and acceptable risk in the benefit-risk plane confirms the uncertainty seen in the wide confidence interval for the benefit-risk ratio--there is a greater than 50% chance of falling into the region of acceptable risk--while visually allowing the uncertainty in risk and benefit to be shown separately. Applying Bayesian methodology, an incremental net health benefit analysis shows there is a 72% chance of having a positive incremental net benefit if hydrocortisone is used in place of placebo if one is willing to incur at most one gastrointestinal perforation for each additional infant that survives without supplemental oxygen. CONCLUSION: If the benefit-risk ratio is presented, the joint distribution of benefit and risk also should be shown. These regions avoid the ambiguity associated with collapsing benefit and risk to a single dimension. Bayesian methods allow even greater flexibility in simultaneously quantifying benefit and risk.

Anti-Inflammatory Agents↗
PubMed1985

Arithmetic model for the distributed encoding in the neuron-module.

A class of arithmetic code defined in residue number system (RNS) is proposed as a mathematical model of neural encoding. The formalism of RNS provides for a vectorial representation in which the digits in the code-words (the "coordinates") contain the information in a distributed manner. These digits and the code-words are assumed to represent the states of the neurons and neuron-modules, respectively. The involved mechanism appears physiologically possible. After the number-theoretical background is summarized in a brief though self-contained way, mathematical assertions are drawn on the error detecting and correction capacities of the formalized modules. It is concluded that RNS provides an appropriate model of neural encoding though drawing inference by the neurons (the evaluation of the encoded information) requires another formalism.

Brain↗
PubMed1994

Homogeneity in the distribution of matrix components in the hamster zona pellucida as revealed by backscattered electron imaging fracture-label.

BACKGROUND: Backscattered electron imaging fracture-label (BEI-FL), an adaptation of the fracture-label method for scanning electron microscopy, offers the advantage of providing information about the distribution of antigenic and receptor sites with respect to the three-dimensional organization of tissues and cells over relatively large surfaces. Recently, using post-embedding cytochemistry on thin-sections of Lowicryl-embedded oocytes, a homogenous distribution of glycoproteins in the zona pellucida (ZP) was demonstrated (Kan et al., 1989. Biol. Reprod., 40:585-598, Anat. Rec., 226:37-47; Roux and Kan, 1991. Anat. Rec., 230:347-360). However, it can be argued that the chemical nature of resins and the physical conditions of tissue processing required for post-embedding cytochemistry may introduce changes in the tissue components and result in altered distribution of components. On the other hand, freeze-fracture exposes constituents in a minimally denaturing manner and, since no embedding media are used, binding sites are sterically available to the probe. We have, therefore, applied BEI-FL to examine the distribution of matrix glycoproteins in the ZP of hamster oocytes. METHODS: Ovaries and cumulus masses obtained from superovulated female golden hamsters were fixed by immersion in 2.5% glutaraldehyde and processed for fracture-label. Tissues were labeled, respectively, with Wheat germ agglutinin (WGA) followed by ovomucoid-colloidal gold, Ricinus communis agglutinin I (RCA I)-colloidal gold or a monoclonal antibody against Hamster Oviductin-1 followed by protein A-gold, and then examined in the scanning electron microscope. RESULTS: Backscattered electron imaging revealed a homogenous distribution of WGA and RCA I binding sites throughout the cross-fractured matrix of the ZP of ovarian and postovulatory oocytes. Hamster Oviductin-1, an oviductal glycoprotein which is transferred to the ZP of oocytes during oviductal transit, was also found to be uniformly distributed throughout the ZP of postovulatory oocytes. CONCLUSIONS: Our results indicate that BEI-FL can be advantageously used to examine extracellular matrices and are consistent with the concept that glycoproteins are uniformly distributed throughout the ZP of the hamster oocyte.

Animals↗
PubMed2002

[Recent data for frequency of autopsy in Germany].

BACKGROUND AND OBJECTIVE: : Today clinico-pathological autopsies serve as a measure of quality assurance in clinical medicine. Furthermore reliable information on the distribution of different causes of death can only be gained by a significant autopsy rate. Medicolegal autopsies are essential for the discovery of non-natural or violent deaths. This study provides information on changes in clinico-pathological and medicolegal autopsy rates between 1994 and 1999. METHODS: : A survey of autopsy rates in 1994 and 1999 was undertaken covering all German pathological and medicolegal institutes. The autopsy figures of the different states were analysed separately. Most autopsies performed in pathological institutes were clinico-pathological autopsies and almost all autopsies performed in Institutes of Legal Medicine were medicolegal autopsies. RESULTS: Between 1994 and 1999 the frequency of clinico-pathological autopsies decreased from about 4 % to 3 % of all deaths. The medicolegal autopsy rate remained stable on a low level at about 2 %. The differences between various states are up to 4-fold for clinico-pathological autopsies and up to 5-fold for medicolegal autopsies. CONCLUSIONS: : The autopsy rates in Germany are frighteningly low compared to other European countries. Considering the dramatic decline of clinico-pathological autopsy rates the role of the post-mortem examination as a control of clinical medicine and death statistics cannot be fulfilled properly. The low medicolegal autopsy rate is responsible for the high number of undetected non-natural or violent deaths.

Autopsy↗
PubMed1997

Radiation absorbed dose to the embryo/fetus from radiopharmaceuticals.

Radiation protection practice requires the knowledge of estimated absorbed radiation doses to aid in the understanding of the potential detriment of various exposures. In nuclear medicine, the radiation doses to the internal organs of the subject are commonly calculated using the MIRD methods and equations. The absorbed dose to the embryo or fetus has long been an area of concern. The recent release of the pregnant female phantom series, and its incorporation into the MIRDOSE 3 computer software, has made possible the estimation of absorbed doses from radionuclides in the body to the fetus in early pregnancy and at 3, 6, and 9 mo gestation. A survey of several major medical institutions was made to determine the radiopharmaceuticals which might be given, whether intentionally or not, to women of childbearing years. Biokinetic data for these radiopharmaceuticals were gathered from various documents and other resources, and the absorbed doses to the embryo and fetus at these different stages of gestation from radiations originating within the mother's organs were estimated. In addition, information about activity distributed within the placenta and fetus was included where quantitative data were available. These absorbed dose estimates can be used to evaluate the risk associated with the use of different radiopharmaceuticals so that a more informed evaluation of the risks and benefits of the different procedures may be made. Further research is needed into the mechanisms and quantitative aspects of the placental transfer of many radiopharmaceuticals.

Embryo, Mammalian↗
PubMed2002

Global and regional estimates of cancer mortality and incidence by site: I. Application of regional cancer survival model to estimate cancer mortality distribution by site.

BACKGROUND: The Global Burden of Disease 2000 (GBD 2000) study starts from an analysis of the overall mortality envelope in order to ensure that the cause-specific estimates add to the total all cause mortality by age and sex. For regions where information on the distribution of cancer deaths is not available, a site-specific survival model was developed to estimate the distribution of cancer deaths by site. METHODS: An age-period-cohort model of cancer survival was developed based on data from the Surveillance, Epidemiology, and End Results (SEER). The model was further adjusted for the level of economic development in each region. Combined with the available incidence data, cancer death distributions were estimated and the model estimates were validated against vital registration data from regions other than the United States. RESULTS: Comparison with cancer mortality distribution from vital registration confirmed the validity of this approach. The model also yielded the cancer mortality distribution which is consistent with the estimates based on regional cancer registries. There was a significant variation in relative interval survival across regions, in particular for cancers of bladder, breast, melanoma of the skin, prostate and haematological malignancies. Moderate variations were observed among cancers of colon, rectum, and uterus. Cancers with very poor prognosis such as liver, lung, and pancreas cancers showed very small variations across the regions. CONCLUSIONS: The survival model presented here offers a new approach to the calculation of the distribution of deaths for areas where mortality data are either scarce or unavailable.

Age Distribution↗
PubMed1989

Free condoms in the schools of Copenhagen, Denmark.

Attitudes of ninth grade students and their classroom teachers toward using condoms as a preventive measure against contracting AIDS were studied. Students (N = 438) and their teachers (N = 28) in the council schools of the Municipality of Copenhagen were surveyed using a structured questionnaire. Overall, results demonstrated that the message regarding "safe sex" had been well understood. However, 42% of pupils reported not using a condom during their last sexual intercourse. Many pupils indicated difficulty in using condoms. A continuing need exists for advice to the young. An information campaign, with distribution of free condoms, was well accepted by pupils and teachers. Almost all (94%) pupils indicated they will use condoms more frequently in the future. This campaign differed from other efforts that focused more on general information. The importance of other strategies designed to alter behavior to reduce the risk of contracting AIDS is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Dealing with an information overload of health science data: structured utilisation of libraries, distributed knowledge in databases and Web content.

The organizational structures of web contents and electronic information resources must adapt to the demands of a growing volume of information and user requirements. Otherwise the information society will be threatened by disinformation. The biomedical sciences are especially vulnerable in this regard, since they are strongly oriented toward text-based knowledge sources. Here sustainable improvement can only be achieved by using a comprehensive, integrated approach that not only includes data management but also specifically incorporates the editorial processes, including structuring information sources and publication. The technical resources needed to effectively master these tasks are already available in the form of the data standards and tools of the Semantic Web. They include Rich Site Summaries (RSS), which have become an established means of distributing and syndicating conventional news messages and blogs. They can also provide access to the contents of the previously mentioned information sources, which are conventionally classified as 'deep web' content.

Computer Communication Networks↗
PubMed2002

Characterisation of an antibody coated microcantilever as a potential immuno-based biosensor.

In this study, we investigated the activity, stability, lifetime and re-usability of monoclonal antibodies to myoglobin covalently immobilised onto microfabricated cantilever surfaces. These sensing surfaces are of interest to us in the development of novel cantilever-based immunosensors. For such sensors the antibody layer represents the sensing element while the microcantilever acts as a mechanical transducer. A procedure for producing re-usable biological coatings has been tested with different independent techniques. An Enzyme Linked Immunosorbent Assay (ELISA) was used to determine the presence of an active antibody coating, and to monitor the lifetime and stability of the immobilised antibody. Through this analysis, the activity of the immobilised antibody layer was found to be more stable with the introduction of sucrose, as a stabilising agent. Sucrose was applied to the immobilised antibody layer after each regeneration step. The immobilised antibody was found to have a stable active lifetime for up to 7 weeks. Fluorescence microscopy was used to give information on the distribution of the coating on the gold and silicon nitride sides of the cantilever. Atomic Force Microscopy was used to determine the presence of the biological coating on the cantilever and to obtain information on the surface morphology of the biological element of the sensor. The combined results provide valuable information on the development of an optimised sensing element and demonstrate a set of methods to use for future sensor-to-sensor characterisation. Preliminary experimental results showing the antibody activity against myoglobin, detected with a microcantilever based sensor prototype confirmed the motivations and potentialities of the proposed immunosensing technique.

Biosensing Techniques↗
PubMed2002

Patient's opinion about written information before laparoscopy: a consecutive series of 100 cases.

PURPOSE: The aim of this study was to assess the opinion of the surgical patient concerning written information before laparoscopic operations. MATERIAL AND METHODS: A prospective and consecutive series of 100 patients was studied. Information sheets concerning the planned laparoscopic operation were distributed at preoperative consultation. A short and clear questionnaire regarding this information was answered upon hospitalization. RESULTS: The majority of the 87 patients, who had read the information, were very pleased to be informed about the techniques (91%) and the risks (97%), although a significant group was worried by the explanations of the risks (41%). None of the patients cancelled the planned operation. None of the patients had become less confident in the surgeon. Most of the patients (95%) found this system of informed consent necessary. CONCLUSIONS: Surgeons should no longer be reluctant to distribute standardized information sheets, as a majority of patients find this system of information necessary.

Female↗
PubMed2002

AIDS Drug Assistance Programs: highlighting inequities in human immunodeficiency virus-infection health care in the United States.

The AIDS Drug Assistance Programs (ADAPs) were founded in 1987 to pay for human immunodeficiency virus (HIV)-related medications in the United States and to help provide prescriptions for HIV-infected patients ineligible for Medicaid who have no private health insurance. As HIV care has shifted from the inpatient to the outpatient arena and as patients live longer because of more-effective antiretroviral therapy, medication costs have increased, and ADAPs have increasingly been operating under emergency measures, with coverage limitations and eligibility restrictions. Because these programs operate at the state level, inequalities in resource distribution to those in need are manifest and appear to contribute to differences in disease outcomes that are based solely on patients' place of residence. Cost-effectiveness analysis would offer a more informed basis for distribution of ADAP resources in an efficient and equitable manner, leading to a standardized national structure.

Acquired Immunodeficiency Syndrome↗
PubMed1995

A segmentation analysis of consumer uses of health information.

Public and private health data organizations are receiving increased pressure to produce consumer-level health information. In addition, the proposed health care reforms imply that health care networks will have to market their health plans. However, little attention has been given to what format the information should have and what the consumers' information needs are. This article discusses the health services marketing literature published to date on the subject, compares it to general marketing literature, and suggests some general guidelines for the effective publication and distribution of health information.

Aged↗