SEARCH · Search PubMed

Results for “Heterogeneity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed2004

Adrenal lesions with heterogeneous suppression on chemical shift imaging: clinical implications.

PURPOSE: To investigate the frequency and significance of adrenal lesions that demonstrate heterogeneous suppression on chemical shift magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective search of adrenal lesions identified on MR from November 1997-July 2001 was performed. The adrenal lesions were classified as having suppression typical for an adenoma, nonsuppression, or atypical heterogeneous suppression. Lesions with heterogeneous suppression were further reviewed. Follow-up for the heterogeneous lesions consisted of imaging studies or pathology from surgical excision. RESULTS: Adrenal lesions were identified in 242 patients. Heterogeneously suppressing lesions were seen in 34 (14%) patients. Several different patterns of heterogeneous suppression were identified. Imaging or pathologic follow-up was available for 18 of the heterogeneously suppressing lesions (one patient had both). Fifteen patients with follow-up imaging showed stability of the lesion over a significant interval, suggesting a benign lesion. Pathology was available for four patients revealing two patients with adenomas and two patients with nodular hyperplasia. Thus, all 18 patients with heterogeneous suppression had a benign lesion. CONCLUSION: Adrenal lesions that have a heterogeneous pattern of suppression on out-of-phase chemical shift MR images are a common finding. Our small series suggest that these lesions are probably benign.

Adenoma↗

PubMed2002

A graphical method for exploring heterogeneity in meta-analyses: application to a meta-analysis of 65 trials.

Heterogeneity can be a major component of meta-analyses and by virtue of that fact warrants investigation. Classic analysis methods, such as meta-regression, are used to explore the sources of heterogeneity. However, it may be difficult to apply such a method in complex cases or in the absence of an a priori hypothesis. This paper presents a graphical method to identify trials, groups of trials or groups of patients that are sources of heterogeneity. The contribution of these trials to the overall result can also be evaluated with this method. Each trial is represented by a dot on a 2D graph. The X-axis represents the contribution of the trial to the overall Cochran Q-test for heterogeneity. The Y-axis represents the influence of the trial, defined as the standardized squared difference between the treatment effects estimated with and without the trial. This approach has been applied to data from the Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) comprising 10,850 patients in 65 randomized trials. The graphical method allowed us to identify trials that contributed considerably to the overall heterogeneity and had a strong influence on the overall result. It also provided useful information for the interpretation of heterogeneity in this meta-analysis. The proposed graphical method identifies trials that account for most of the heterogeneity without having to explore all possible sources of heterogeneity by subgroup analyses. This method can also be applied to identify types of patients that explain heterogeneity in the treatment effect.

Clinical Trials as Topic↗

PubMed2004

Blood transit time heterogeneity is associated to oxygen extraction in exercising human skeletal muscle.

Capillary transit time and its heterogeneity have a marked impact on oxygen extraction in different tissues. Animal studies have shown that exercise shortens capillary transit time but the effects on capillary transit time heterogeneity have been controversial. We investigated whether exercise changes muscle blood transit time heterogeneity in humans in vivo and whether this heterogeneity correlates to muscle oxygen extraction. Muscle blood flow, blood volume, and oxygen uptake were measured during rest and low-intensity exercise in 12 healthy men using positron emission tomography (PET). Blood transit time was calculated from parametric PET images voxel by voxel by dividing blood volume with blood flow. Oxygen extraction was calculated by nonlinear fitting from dynamic 15O-O2 data. Relative dispersion (=SD/mean) was calculated as an index of heterogeneity of blood volume and blood transit time. As expected, exercise significantly shortened blood transit time and increased oxygen extraction. Furthermore, exercise decreased transit time heterogeneity (from 47 +/- 9% to 39 +/- 10%, P=0.07). Transit time heterogeneity correlated inversely to oxygen extraction in the exercising (r=-0.76, P=0.004) but not in the resting muscle (r=0.04, P=0.89). These results show that even low-intensity exercise shortens blood transit time markedly and decreases its heterogeneity in human skeletal muscle in vivo. Findings in correlation analyses suggest that less heterogeneous blood transit time associates to better muscle oxygen extraction during exercise. This may have effects on muscle oxygenation during exercise.

Adult↗

PubMed1994

Automatic detection of spatial and dynamic heterogeneity of repolarization.

Heterogeneity of ventricular repolarization is associated with the development of life-threatening ventricular arrhythmias. Temporal heterogeneity of repolarization may be manifest in an individual beat (spatial heterogeneity) or in a sequence of beats (dynamic heterogeneity). Spatial inhomogeneity of repolarization throughout the myocardium may be expressed electrocardiographically as dispersion of repolarization durations computed in simultaneously recorded leads. The beat-to-beat changes in the repolarization pattern (duration and/or amplitude) may account for a dynamic (time-dependent) dimension of heterogeneity, occasionally seen as T-wave alternans. A visual detection of heterogeneous repolarization is a time-consuming, observer-dependent, and frequently inaccurate process. Therefore, we developed computer algorithms designed to detect automatically (1) dispersion of repolarization and (2) nonvisible T-wave alternans from digitally recorded (1,000 Hz) X, Y, and Z electrocardiogram leads. This automatic approach was subsequently tested in 10 patients with idiopathic long QT syndrome and in 10 age-matched normal subjects. Long QT syndrome patients presented with significantly higher indices of heterogeneity in comparison with the control subjects; the dispersion of repolarization was 44 +/- 11 and 13 +/- 6 ms, respectively (P < .01), and T-wave alternans index was 0.40 +/- 0.37 and 0.03 +/- 0.06, respectively (P < .01). Simultaneous evaluation of spatial (dispersion of repolarization) and dynamic (T-wave alternans) aspects of repolarization provides new insight into heterogeneity of electrical recovery after myocardial depolarization. The automatic detection of repolarization dispersion and T-wave alternans in digital electrocardiogram recordings provides a practical method to evaluate heterogeneity of repolarization and may be useful for stratifying patients at risk of ventricular arrhythmias.

Arrhythmias, Cardiac↗

PubMed2001

Atmospheric secondary aerosol formation by heterogeneous reactions of aldehydes in the presence of a sulfuric acid aerosol catalyst.

Particle growth by the heterogeneous reaction of aldehydes was evaluated in 0.5 m3 Teflon film bags under darkness in the presence of background seed aerosols. The aldehydes used were as follows: glyoxal, butanal, hexanal, octanal, and decanal. To study acid catalyst effects on aldehyde heterogeneous reactions, one of the Teflon bags was initially filled with seed aerosols composed of ammonium sulfate-aerosol acidified with sulfuric acid. These results were compared to particle growth reactions that contained only ammonium sulfate as a background seed aerosol. The gas-phase aldehydes were then added to the Teflon bags. In selected experiments, 1-decanol was also added to the Teflon bags with aldehydes to clarify particle growth via a heterogeneous hemiacetal/acetal formation in the presence/absence of an acid catalyst. The particle size distribution and growth were measured using a scanning mobility particle sizer (TSI-SMPS), and the results were applied to predicting aerosol growth and size distribution changes by condensation and heterogeneous reactions. Aerosols created from the heterogeneous reactions of aldehydes were collected directly on an ungreased zinc selenide (ZnSe) FTIR disk (25 mm in diameter) by impaction. The ZnSe disks were directly analyzed for product functional groups inthe aerosol phase using a Fourier transform infrared (FTIR) spectrometer with a deuterated triglycine sulfate (DTGS) detector. Aerosol growth by heterogeneous aldehyde reactions proceeds via a hydration, polymerization process, and hemiacetal/acetal formation from the reaction of aldehydes with alcohols. These aldehyde heterogeneous reactions were accelerated in the presence of an acid catalyst, H2SO4, and led to higher aerosol yields than when H2SO4 was not present in the seed aerosol. The FTIR spectra obtained from the growing aerosol, also illustrated aldehyde group transformation in the particle phase as a function of the heterogeneous reaction. It was concluded that aldehydes, which can be produced by atmospheric photochemical reactions, can significantly contribute on secondary aerosol formation through heterogeneous reactions in the presence of an acid catalyst.

Aerosols↗

PubMed2003

Quantitative reconstruction of cardiac electromechanics in human myocardium: regional heterogeneity.

INTRODUCTION: Regional heterogeneity of electrophysiologic properties within the human ventricles is based on changes in ion channel kinetics and density inside the wall. The heterogeneity not only influences the electrophysiologic properties but also cellular force development. In this study, the influence of heterogeneity was investigated using mathematical models. METHODS AND RESULTS: An overview of measurements of the heterogeneity of electrophysiology and force development is presented. This knowledge is transferred to an electromechanical heart model composed of a human ionic cell model describing electrophysiologic properties and a model for the development of forces. Heterogeneity is included in the ionic model by changing ion channel kinetics and density. The characteristics and dependencies of the electromechanical model are demonstrated in a single-cell environment and a multicell environment. In the single-cell environment, the effects of heterogeneity on electrical activity are demonstrated. The notch in the action potential decreases from epicardium to endocardium, and action potential duration is longest in the mid-myocardium. The developed forces are largest in the subendocardial cells and decrease continuously toward the epicardium. The multicell environment describes a transmural line of cells in the left ventricular free wall using a bidomain approach. The transmural ECG shows typical characteristics with a positive monophasic T wave. CONCLUSIONS: This work demonstrates the need to incorporate regional heterogeneity in order to model human cardiac electromechanics. The results of electrophysiologic simulations correspond to measured data. The dependencies of regional heterogeneity on force development need to be validated in experiments, because little is known about the influence of heterogeneity on electromechanical coupling.

Action Potentials↗

PubMed1974

Ontogeny of B-lymphocyte function. I. Restricted heterogeneity of the antibody response of B lymphocytes from neonatal and fetal mice.

The ontogeny of the ability of B lymphocytes to produce an antihapten response which is heterogeneous with respect to affinity for the antigenic determinant was studied in a cell transfer system. The heterogeneity of affinity of the immune response of lethally irradiated mice reconstituted with syngeneic, adult thymus cells and fetal or neonatal tissues as a source of B lymphocytes was studied. It was found that B cells from 17 day fetal liver or neonatal liver are highly restricted with respect to heterogeneity of affinity as compared with adult spleen or bone marrow. The B-cell population achieves an adult character with respect to heterogeneity of affinity by 2 wk of age. The peripheral lymphoid tissues (spleen) appear to mature in this respect more rapidly than do central lymphoid tissues (bone marrow). Spleens from 10-day old donors behave in an adult, heterogeneous manner while bone marrow from the same donors exhibit a marked restriction in heterogeneity of affinity. Germfree mice produce an immune response which is indistinguishable from conventionally reared adult animals with respect to heterogeneity of affinity. The earlier appearance of the ability to transfer a heterogeneous immune response in spleen as compared with bone marrow suggests that the increasing heterogeneity of the B-lymphocyte population which occurs between birth and 2 wk of age is the result of a differentiation event and not of a somatic mutation or recombination event.

Animals↗

PubMed1993

The application of correlated sampling to the computation of electron beam dose distributions in heterogeneous phantoms using the Monte Carlo method.

Although the Monte Carlo method is capable of computing the dose distribution in heterogeneous phantoms directly, there are some advantages to computing a heterogeneity correction factor. If this approach is adopted there are savings in time using correlated sampling. This technique forces histories to have the same energy, position, direction and random number seed as incident on both the heterogeneous and homogeneous water phantom. This ensures that a history that has, by chance, travelled through only water in the heterogeneous phantom will have the same path as it would have through the homogeneous phantom, resulting in a reduced variance when a ratio of heterogeneous dose to homogeneous dose is formed. Metrics to describe the distributions of uncertainty, efficiency, and degree of correlation are defined. EGS4 Monte Carlo calculation of the dose distribution from a 20 MeV electron beam on water phantoms containing aluminum or air slab heterogeneities illustrate that this technique is the most efficient when the heterogeneity is deep within the phantom, but that improved efficiency can be realized even when the heterogeneity is at or near the surface. This is because some correlation between the two histories is retained despite passage through the heterogeneity.

Electrons↗

PubMed1988

Heterogeneity of phenotypic expression in normal and neoplastic B-cell proliferations detected by monoclonal antibodies LN-1 and DLC-48.

Recently developed monoclonal antibodies DLC-48 and LN-1 have been shown to be effective reagents for complement-mediated cell lysis of human B-cells. The authors have initially found that these reagents are useful in elimination of malignant lymphomas cells from human bone marrow for autologous bone marrow transplantation. In the current study, the authors have further characterized the reactivity of these antibodies in B-cell neoplasia and have analyzed the heterogeneity of antigenic expression among benign and neoplastic lymphoid cells for B-cell monoclonal antibodies. With the use of quantitative flow cytometric techniques to assess heterogeneity of antigen expression, the findings indicate that phenotypic heterogeneity within neoplasms from individual patients exists for a number of B-cell-related monoclonal antibodies, including B1, common acute lymphocyte leukemia antigen (CALLA), Ia, Ba-1, DLC-48, and LN-1. Within a given histologic class of lymphoid neoplasia, phenotypic heterogeneity was found to be a property of some individual cases and not others for all B-cell monoclonal antibodies examined. This heterogeneity was not consistently expressed in patients with similar tumors, nor was it a consistent property of a given antigen. Using cell lines derived from large cell lymphomas, the authors were able to find phenotypic heterogeneity within neoplastic cell lines that can be used to develop models for dealing with phenotypic heterogeneity in the context of complement-mediated cell lysis. They also established that for DLC-48 and LN-1, the heterogeneity was not related to the phase of the cell cycle of the proliferating cells. The results suggest that single monoclonal antibody treatment for bone marrow depletion of neoplastic cell may be insufficient to overcome phenotypic heterogeneity of B-cell neoplasms.

Antibodies, Monoclonal↗

PubMed2006

Small-scale heterogeneity in soil quality influences photosynthetic efficiency and habitat selection in a clonal plant.

BACKGROUND AND AIMS: In clonal plants, internode connections allow translocation of photosynthates, water, nutrients and other substances among ramets. Clonal plants form large systems that are likely to experience small-scale spatial heterogeneity. Physiological and morphological responses of Fragaria vesca to small-scale heterogeneity in soil quality were investigated, together with how such heterogeneity influences the placement of ramets. As a result of their own activities plants may modify the suitability of their habitats over time. However, most experiments on habitat selection by clonal plants have not generally considered time as an important variable. In the present study, how the foraging behaviour of clonal plants may change over time was also investigated. METHODS: In a complex of environments with different heterogeneity, plant performance was determined in terms of biomass, ramet production and photosynthetic activity. To identify habitat selection, the number of ramets produced and patch where they rooted were monitored. KEY RESULTS: Parent ramets in heterogeneous environments showed significantly higher maximum and effective quantum yields of photosystem II than parents in homogeneous environments. Parents in heterogeneous environments also showed significantly higher investment in photosynthetic biomass and stolon/total biomass, produced longer stolons, and had higher mean leaf size than parents in homogeneous environments. Total biomass and number of offspring ramets were similar in both environments. However, plants in homogeneous environments showed random allocation of offspring ramets to surrounding patches, whereas plants in heterogeneous environments showed preferential allocation of offspring to higher-quality patches. CONCLUSIONS: The results suggest that F. vesca employs physiological and morphological strategies to enable efficient resource foraging in heterogeneous environments and demonstrate the benefits of physiological integration in terms of photosynthetic efficiency. The findings indicate that short-term responses cannot be directly extrapolated to the longer term principally because preferential colonization of high-quality patches means that these patches eventually show reduced quality. This highlights the importance of considering the time factor in experiments examining responses of clonal plants to heterogeneity.

Fragaria↗

PubMed1986

Expression of methicillin resistance in heterogeneous strains of Staphylococcus aureus.

The phenotypic expression of methicillin resistance was studied in a number of clinical isolates and laboratory strains of Staphylococcus aureus. The methicillin-resistant S. aureus strains could be divided into three classes, homogeneous, heterogeneous, and thermosensitive heterogeneous methicillin-resistant S. aureus, on the basis of their plating efficiencies at 30 or 37 degrees C on methicillin-containing agar plates. Heterogeneous strains of methicillin-resistant S. aureus were composed of two subpopulations: a small minority of cells (10(-5) to 10(-3); MIC, 600 to 1,000 micrograms/ml) that expressed resistance to high concentrations of methicillin at 37 degrees C, and a majority of cells (MIC, 5 micrograms/ml) that remained susceptible to the drug at 37 degrees C. Cultures of a thermosensitive heterogeneous strain were able to grow in the presence of high concentrations of methicillin, provided that the growth temperature was 30 degrees C. Such cultures lost their phenotypic resistance within 30 min (i.e., in less than one doubling time) after the growth temperature was shifted to the nonpermissive 37 degrees C. Shift of the temperature of the culture in the reverse direction (37 to 30 degrees C) resulted in an equally rapid expression of phenotypic resistance. The majority of the cells in such heterogeneous strains may be considered heat (or salt) conditional in their phenotypic expression of methicillin resistance. Both heterogeneous and thermosensitive heterogeneous strains, irrespective of their temperature of cultivation and degree of phenotypic resistance, contained detectable quantities of the 78-kilodalton penicillin-binding protein 2a (PBP 2a) that previous studies have suggested is a biochemical correlate of methicillin resistance in homogeneous strains of methicillin-resistant S. aureus. However, in contrast to the homogeneous stains, in heterogeneous and thermosensitive heterogeneous isolates the ability to synthesize PBP 2a is apparently not sufficient to provide a resistant phenotype. In these strains some additional, as yet undefined factor(s) is also needed for the expression of methicillin resistance.

Bacterial Proteins↗

PubMed2003

Intracellular calcium handling heterogeneities in intact guinea pig hearts.

Regional heterogeneities of ventricular repolarizing currents and their role in arrhythmogenesis have received much attention; however, relatively little is known regarding heterogeneities of intracellular calcium handling. Because repolarization properties and contractile function are heterogeneous from base to apex of the intact heart, we hypothesize that calcium handling is also heterogeneous from base to apex. To test this hypothesis, we developed a novel ratiometric optical mapping system capable of measuring calcium fluorescence of indo-1 at two separate wavelengths from 256 sites simultaneously. With the use of intact Langendorff-perfused guinea pig hearts, ratiometric calcium transients were recorded under normal conditions and during administration of known inotropic agents. Ratiometric calcium transients were insensitive to changes in excitation light intensity and fluorescence over time. Under control conditions, calcium transient amplitude near the apex was significantly larger (60%, P < 0.01) compared with the base. In contrast, calcium transient duration was significantly longer (7.5%, P < 0.03) near the base compared with the apex. During isoproterenol (0.05 microM) and verapamil (2.5 microM) administration, ratiometric calcium transients accurately reflected changes in contractile function, and, the direction of base-to-apex heterogeneities remained unchanged compared with control. Ratiometric optical mapping techniques can be used to accurately quantify heterogeneities of calcium handling in the intact heart. Significant heterogeneities of calcium release and sequestration exist from base to apex of the intact heart. These heterogeneities are consistent with base-to-apex heterogeneities of contraction observed in the intact heart and may play a role in arrhythmogenesis under abnormal conditions.

Animals↗

PubMed2006

Gene expression profiling in cervical cancer: an exploration of intratumor heterogeneity.

PURPOSE: To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer. EXPERIMENTAL DESIGN: A total of 33 biopsies were obtained from 11 patients, sampling between two and five different areas for each tumor. The extracted RNA was hybridized onto the Affymetrix U133 Plus 2.0 oligonucleotide chip. The variance of expression within a patient (W), between patients (B) and the total variance (T = W + B) were calculated for each ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity. Gene Ontology functional analysis was done to assess the function of genes that had high W/T (top 10%) and low W/T (bottom 10%) values. RESULTS: In total, 448 ProbeSets (2.2% of the total) had W/T < 0.10, indicating low intratumor heterogeneity, and 537 ProbeSets (2.7% of the total) had W/T > 0.90, indicating high intratumor heterogeneity. In total 14,473 ProbeSets (72.4%) had higher intertumor than intratumor heterogeneity (W/T < 0.5). Genes with low intratumor heterogeneity were characterized by a statistically significant enrichment of immune-related functions (P < 0.0001). Genes with high intratumor heterogeneity were characterized by a significant tendency towards nuclear localization and nucleic acid binding (both P < 0.0001). For genes with W/T > 0.5, more than six biopsies would be required to minimize the intratumoral heterogeneity to <0.15; if W/T is 0.3 to 0.4, four biopsies are required; and for low W/T of 0.16 to 0.3, only two to three biopsies would be needed. CONCLUSION: Although the intratumor heterogeneity was low for the majority of the tested ProbeSets, for many genes, multiple biopsies are required to obtain a reliable estimate of gene expression.

Adenocarcinoma↗

PubMed2005

Investigation of Staphylococcus strains with heterogeneous resistance to glycopeptides in a Turkish university hospital.

BACKGROUND: The hetero-glycopeptide intermediate staphylococci is considered to be the precursor of glycopeptide intermediate staphylococci especially vancomycin intermediate Staphylococcus aureus (VISA). For this purpose, we aimed to investigate the heterogeneous resistance to glycopeptide and their frequencies in 135 Staphylococcus strains. METHODS: Heterogeneous resistance of Staphylococcus strains was detected by inoculating the strains onto Brain Heart Infusion agar supplemented with 4 mg/L of vancomycin (BHA-V4). Agar dilution method was used for determining MICs of glycopeptides and population analysis profile was performed for detecting frequency of heterogeneous resistance for the parents of selected strains on BHA-4. RESULTS: Eight (6%) out of 135 Staphylococcus strains were exhibited heterogeneous resistance to at least one glycopeptide. One (1.2%) out of 81 S. aureus was found intermediate resistance to teicoplanin (MIC 16 mg/L). Other seven strains were Staphylococcus haemolyticus (13%) out of 54 coagulase negative staphylococci (CoNS). Six of the seven strains were detected heterogeneously reducing susceptibility to vancomycin (MICs ranged between 5-8 mg/L) and teicoplanin (MICs ranged between 32-64 mg/L), and one S. haemolyticus was found heterogeneous resistance to teicoplanin (MIC 32 mg/L). Frequencies of heterogeneous resistance were measured being one in 10(6) - 10(7) cfu/ml. MICs of vancomycin and teicoplanin for hetero-staphylococci were determined as 2-6 folds and 3-16 folds higher than their parents, respectively. These strains were isolated from six patients (7%) and two (4%) of health care workers hands. Hetero-VISA strain was not detected. CONCLUSION: Heterogeneous resistance to glycopeptide in CoNS strains was observed to be significantly more emergent than those of S. aureus strains (vancomycin P 0.001, teicoplanin, P 0.007). The increase MICs of glycopeptide resistance for subpopulations of staphylococci comparing with their parents could be an important clue for recognizing the early steps in the appearance of VISA strains. We suggested to screen clinical S. aureus and CoNS strains, systematically, for the presence of heterogeneously resistance to glycopeptide.

Anti-Bacterial Agents↗

PubMed2006

Mathematical modeling of tumor therapy with oncolytic viruses: effects of parametric heterogeneity on cell dynamics.

BACKGROUND: One of the mechanisms that ensure cancer robustness is tumor heterogeneity, and its effects on tumor cells dynamics have to be taken into account when studying cancer progression. There is no unifying theoretical framework in mathematical modeling of carcinogenesis that would account for parametric heterogeneity. RESULTS: Here we formulate a modeling approach that naturally takes stock of inherent cancer cell heterogeneity and illustrate it with a model of interaction between a tumor and an oncolytic virus. We show that several phenomena that are absent in homogeneous models, such as cancer recurrence, tumor dormancy, and others, appear in heterogeneous setting. We also demonstrate that, within the applied modeling framework, to overcome the adverse effect of tumor cell heterogeneity on the outcome of cancer treatment, a heterogeneous population of an oncolytic virus must be used. Heterogeneity in parameters of the model, such as tumor cell susceptibility to virus infection and the ability of an oncolytic virus to infect tumor cells, can lead to complex, irregular evolution of the tumor. Thus, quasi-chaotic behavior of the tumor-virus system can be caused not only by random perturbations but also by the heterogeneity of the tumor and the virus. CONCLUSION: The modeling approach described here reveals the importance of tumor cell and virus heterogeneity for the outcome of cancer therapy. It should be straightforward to apply these techniques to mathematical modeling of other types of anticancer therapy. REVIEWERS: Leonid Hanin (nominated by Arcady Mushegian), Natalia Komarova (nominated by Orly Alter), and David Krakauer.

Journal Article↗

PubMed2006

Heterogeneity in fecundability studies: issues and modelling.

Modelization of fecundability stepped recently from demography and population-based contexts to reproductive biology and treatment of infertility. This created a strong call for flexibility and robustness. Indeed, explained and unexplained heterogeneities are non-negligible sources of bias that result in false conclusions as to the determinants of fertility or to the success rates of reproductive techniques, among other examples. There are two main sources of heterogeneity: biological heterogeneity and heterogeneity of sexual behaviour. A uniform presentation of time-to-pregnancy and Barrett-Marshall models is proposed to enlighten their similarities and differences in modelling heterogeneity of fecundability. Mixed models for fecundability studies are presented as tools to allow for unexplained heterogeneity and to quantify heterogeneity of the effect of observed factors and variability of size of this unexplained heterogeneity between subpopulations. Some criteria for the modelling strategy in fecundability studies are suggested with emphasis on the unit-treatment additivity criterion. The strong and complex selection process resulting from heterogeneity is described as well as the selection and cross-selection processes of observed and unobserved fecundability factors. Consequences regarding data collection and statistical inference are discussed. In the current context, a consensus setting general rules for data collection and statistical analysis would be useful to compare the results and increase the reliability of these results in medical practice.

Female↗

PubMed2004

[Response of fine roots to soil nutrient spatial heterogeneity].

The spatial heterogeneity is the complexity and variation of systems or their attributes, and the heterogeneity of soil nutrients is ubiquitous in all natural ecosystems. The scale of spatial heterogeneity varies considerably among different ecosystems, from tens of centimeters to hundred meters. Some of the scales can be detected by individual plant. Because the growth of individual plants can be strongly influenced by soil heterogeneity, it follows that the inter-specific competition should also be affected. During the long process of evolution, plants developed various plastic responses with their root system, including morphological, physiological and mycorrhizal plasticity, to maximize the nutrient acquisition from heterogeneous soil resources. Morphological plasticity, an adjustment in root system spatial allocation and architecture in response to spatial heterogeneous distribution of available soil resources, has been most intensively studied, and root proliferation in nutrient rich patches has been certified for many species. The species that do respond may have an increased rate of nutrient uptake, leading to a competitive advantage. Scale and precision are two important features employed in describing the size and foraging behavior of root system. It was hypothesized that scale and precision is negatively related, i. e., the species with high scale of root system tend to be a less precise forager. The outcomes of different research work have been diverse, far from reaching a consensus. Species with high scale are not necessarily less precise in fine root allocation, and vice versa. The proliferation of fine root in enriched micro-sites is species dependent, and also affected by other factors, such as patch attributes (size and nutrients concentration), nutrients, and overall soil fertility. Beside root proliferation in nutrient enriched patches, plants can also adapt themselves to the heterogeneous soil environment by altering other root characteristics such as fine root diameter, branch angle, length, and spatial architecture of root system. Physiological and mycorrhizal plasticity can add some influence on the morphological plasticity to some extent, but they are less studied. Roots located in different patches can quickly regulate their nutrient uptake kinetics within different nutrient patches, and increase overall nutrient uptake. Physiological response may, to certain extent, reduce morphological response, and is meaningful for plant growth on soils with frequently changing spatial and temporal heterogeneity. Mycorrhizal plasticity has been least studied so far. Some researches revealed that mycorrhiza, rather than fine root, proliferated in enriched patches. But, it is not the case with other studies. The proliferation of mycorrhiza within enriched patches is more profitable in term of carbon invest. The effect of fine root proliferation on nutrient uptake is complex, depending on ion mobility and whether or not neighboring plant exists. The influence of root plasticity on the growth of plants is species specific. Some species (sensitive species) gain growth benefit, while others don't. The ability of an individual plant to response to heterogeneous resources has significant effect on its competitive ability and its fate within the community, and eventually shapes the composition and structure of the community.

Adaptation, Physiological↗

PubMed1998

Intratumoral cytogenetic heterogeneity detected by comparative genomic hybridization and laser scanning cytometry in human gliomas.

Although it is well-known that cancers show intratumoral phenotypic heterogeneity, genotypic studies have been scarce. Using comparative genomic hybridization and laser scanning cytometric analyses, we investigated intratumoral cytogenetic heterogeneity in 21 surgically removed gliomas including 11 glioblastomas (GBMs), 8 anaplastic astrocytomas (AAs) and 2 low-grade astrocytomas. Comparative genomic hybridization analysis revealed gain or amplification of 7p in 63%, gain of 7q in 73%, loss of 9p in 53%, loss of 10p in 47%, loss of 10q in 47%, loss of 13q in 53%, and loss of 22q in 37% of high-grade astrocytomas. Because these aberrations were region-independent within the same tumor, they did not contribute to intratumoral cytogenetic heterogeneity. Such heterogeneity was due to cytogenetic changes other than the above region-independent aberrations. Intratumoral cytogenetic heterogeneity was detected in 8 of 11 GBMs, 4 of 8 AAs, and none of the 2 low-grade astrocytomas. These observations suggest that cytogenetic changes at chromosomes 7, 9p, 10, 13, and 22 are primary events in high-grade astrocytomas and that subsequent cytogenetic changes involving increases in copy number provide intratumoral heterogeneity. DNA aneuploidy was detected by laser scanning cytometry in 5 of 11 GBMs and 1 of 8 AAs. All tumors with DNA aneuploidy exhibited intratumoral cytogenetic heterogeneity, and there was a significant correlation between DNA aneuploidy and intratumoral cytogenetic heterogeneity. These results support the notion that cytogenetic heterogeneity results from genetic instability within a tumor.

Adult↗