Subgroup Definition Research Articles

A novel M142T mutation in the B glycosyltransferase gene associated with B3 variant in Chinese

To investigate the molecular genetic basis of the B3 variant of ABO blood group system with mixed-field hemagglutination in Chinese. Serological techniques were performed to characterize the erythrocyte phenotype of two discrepant samples. A sequential agglutination method and 13 short tandem repeat (STR) loci were tested to exclude the possibility of exogenous or endogenous DNA chimera. Mutations in exons 6 and 7, including partial intron of the ABO gene, were screened by polymerase chain reaction and DNA sequencing. Haplotypes of the two individuals were also analyzed by sequencing. A mixed-field hemagglutination of RBCs with anti-B and anti-AB antibodies was detected in the two unrelated individuals. Exogenous ABO-incompatible RBC transfusion and endogenous genetic chimera were excluded by sequential agglutination method and STR. The ABO phenotypes of the two individuals were classified as A1B3 according to the ABO subgroup definition. The sequence region from intron 5 to 3'-UTR of the B allele was identical to that of ABO*B101 allele, except for a T to C substitution at nucleotide position 425 in exon 7. This substitution resulted in an amino acid change of M142T in the B glycosyltransferase. A novel B allele with 425T>C substitution resulting in B3 subgroup was identified in two Chinese individuals.

Prediction of functional specificity determinants from protein sequences using log-likelihood ratios

A number of methods have been developed to predict functional specificity determinants in protein families based on sequence information. Most of these methods rely on pre-defined functional subgroups. Manual subgroup definition is difficult because of the limited number of experimentally characterized subfamilies with differing specificity, while automatic subgroup partitioning using computational tools is a non-trivial task and does not always yield ideal results. We propose a new approach SPEL (specificity positions by evolutionary likelihood) to detect positions that are likely to be functional specificity determinants. SPEL, which does not require subgroup definition, takes a multiple sequence alignment of a protein family as the only input, and assigns a P-value to every position in the alignment. Positions with low P-values are likely to be important for functional specificity. An evolutionary tree is reconstructed during the calculation, and P-value estimation is based on a random model that involves evolutionary simulations. Evolutionary log-likelihood is chosen as a measure of amino acid distribution at a position. To illustrate the performance of the method, we carried out a detailed analysis of two protein families (LacI/PurR and G protein alpha subunit), and compared our method with two existing methods (evolutionary trace and mutual information based). All three methods were also compared on a set of protein families with known ligand-bound structures. SPEL is freely available for non-commercial use. Its pre-compiled versions for several platforms and alignments used in this work are available at ftp://iole.swmed.edu/pub/SPEL/

Influence of underlying disease on the outcome of critically ill patients with acute renal failure

Background and objective: The development of acute renal failure (ARF) in critically ill patients is associated with an increase in hospital mortality. Recently, it was shown that starting renal replacement therapy early and using high-filtrate flow rates can improve the outcome, but this could not be confirmed in later investigations. Studying selected patient subgroups could provide a useful basis for patient selection in future trials evaluating the outcome of renal replacement therapies. We, therefore, investigated the impact of the underlying disease on the outcome of patients with ARF. Methods: We retrospectively analysed 306 patients with ARF who were treated with renal replacement therapy. Patients were classified according to six initial diagnosis groups: haemorrhagic shock, post-cardiac surgery, post-liver transplantation, trauma, severe sepsis and miscellaneous. Univariate and multivariate multiple logistic regression analysis was used to determine which factors influenced the outcome. Results: Underlying disease proved to be the only independent risk factor for mortality that was present at intensive care unit (ICU) admission (P = 0.047). Patients with severe sepsis had a significantly higher mortality rate (68%) than ARF patients as a whole (51%) (P = 0.02). Length of stay in the ICU, the use of catecholamines, the delay before ARF onset, and the correlation between APACHE II score and ICU length of stay proved to be additional independent predictors of outcome. Conclusions: Patient selection and subgroup definition according to the underlying disease could augment the usefulness of future trials evaluating the outcome of ARF.

Influence of underlying disease on the outcome of critically ill patients with acute renal failure

The development of acute renal failure (ARF) in critically ill patients is associated with an increase in hospital mortality. Recently, it was shown that starting renal replacement therapy early and using high-filtrate flow rates can improve the outcome, but this could not be confirmed in later investigations. Studying selected patient subgroups could provide a useful basis for patient selection in future trials evaluating the outcome of renal replacement therapies. We, therefore, investigated the impact of the underlying disease on the outcome of patients with ARF. We retrospectively analysed 306 patients with ARF who were treated with renal replacement therapy. Patients were classified according to six initial diagnosis groups: haemorrhagic shock, post-cardiac surgery, post-liver transplantation, trauma, severe sepsis and miscellaneous. Univariate and multivariate multiple logistic regression analysis was used to determine which factors influenced the outcome. Underlying disease proved to be the only independent risk factor for mortality that was present at intensive care unit (ICU) admission (P = 0.047). Patients with severe sepsis had a significantly higher mortality rate (68%) than ARF patients as a whole (51%) (P = 0.02). Length of stay in the ICU, the use of catecholamines, the delay before ARF onset, and the correlation between APACHE II score and ICU length of stay proved to be additional independent predictors of outcome. Patient selection and subgroup definition according to the underlying disease could augment the usefulness of future trials evaluating the outcome of ARF.

THE USE OF DISEASE SUB-GROUP CLASSIFICATION WITHIN THE BROAD SPECTRUM OF CHILDHOOD ASTHMA AND ATOPY WHEN EXAMINING ENVIRONMENTAL DETERMINANTS.

The clinical syndrome of asthma encompasses several subgroups that reflect airway obstruction of differing aetiologies. We discuss epidemiologic approaches that may be used to reduce disease misclassification with regard to allergen-induced airway obstruction and demonstrate these approaches using two recent analyses. First, we examine infant synthetic bedding and subsequent child wheeze. While house dust mite (HDM) sensitisation is only weakly associated with asthma (RR = 1.7), it is strongly associated with frequent wheeze (more than 12 episodes compared to no wheeze over the past year) (RR = 19.6). Thus, a focus on severe symptoms such as frequent wheeze should reduce disease misclassification in studies examining HDM-related airway disease. We examined a 1988 birth cohort in Tasmania (n = 863, 78% traced) with data available on infant bedding at one month of age and respiratory symptoms at age seven. The associations between synthetic bedding and asthma were not strong. However, strong associations emerged when the frequent wheeze was examined. We found synthetic pillow use at one month of age was associated with frequent wheeze at age seven (ARR 2.5 (1.2–5.5)), independent of childhood exposure. Current synthetic pillow and quilt use was strongly associated with frequent wheeze. Among children with asthma, the age of onset of asthma occurred earlier (p = 0.03) if infant synthetic bedding was used. This shift was particularly evident among children with frequent wheeze. Thus in this cohort, synthetic bedding was strongly and consistently associated with frequent wheeze. These associations would not have been evident if only the global outcome of asthma was considered. Second, we examine the use of mutually exclusive allergen-specific classifications within the broad category of atopy. Our aim was to examine the relative importance of family size on sensitisation to two different allergens:- ryegrass and HDM. An eight-year follow-up birth cohort study of children born 1988–1989 was conducted. The follow-up sample consisted of 498 children residing in Northern Tasmania in 1997 (84% of eligible). Outcome measures included skin prick test reaction to nine aeroallergens. Family size was defined as sibling number in 1997. Children with a positive skin prick test to (SPT) either Der p or Der f HDM but not ryegrass were classified as HDM-exclusive (n = 84). Children with a positive SPT to ryegrass but not HDM were classified as ryegrass-exclusive (n = 43). Family size was associated with reduced ryegrass-exclusive sensitisation (AOR 0.57 (0.39, 0.84) per increase in sibling number) but not HDM-exclusive sensitisation (AOR 0.97 (0.77, 1.23)). The difference in the effect of family size on these sensitisation outcomes was significant (p = 0.02). Thus, large family size was strongly associated with reduced sensitisation for ryegrass allergens but not HDM allergens. Further work is required to assess whether these findings reflect differences between these allergens with regard to the level or timing of early life exposure. These two cohort analyses demonstrate that careful sub-group definition within the broad spectrum of asthma or atopy may lead to new insights on the environmental determinants of atopic disease in childhood.

Matrix decomposition model for investigating prehistoric intracemetery biological variation.

A matrix decomposition model for analyzing prehistoric intracemetery biological variability is presented. The model, based on the correlation between interindividual biological and burial distance matrices, provides an estimate of the number of distinct burial populations interred within a single cemetery, which effectively ameliorates identifiability problems typical of general variability analyses (Raemsch [1995] Ph.D. dissertation, SUNY at Albany). Unlike other methods for analyzing intrasite variability analysis (e.g., kinship analysis and microchronology), this method is not reliant on a priori subgroup definition. Assuming a kin-structured burial pattern, a residual matrix is defined based on the raw data matrices; the proportion of negative or zero residuals to the total number of residuals provides an estimate of the number of hidden subgroupings (lineages) within the cemetery. The comparative utility of the model is demonstrated on a series of protohistoric and historic period skeletal samples from the Georgia coast, where it demonstrated that the increase in phenotypic variability during the early mission period is the result of population aggregation at the missions and not necessarily genetic admixture between local and nonlocal groups.

Use of tree-based models to identify subgroups and increase power to detect linkage to cardiovascular disease traits.

BackgroundOur goal was to identify subgroups of sib pairs from the Framingham Heart Study data set that provided higher evidence of linkage to particular candidate regions for cardiovascular disease traits. The focus of this method is not to claim identification of significant linkage to a particular locus but to show that tree models can be used to identify subgroups for use in selected sib-pair sampling schemes.ResultsWe report results using a novel recursive partitioning procedure to identify subgroups of sib pairs with increased evidence of linkage to systolic blood pressure and other cardiovascular disease-related quantitative traits, using the Framingham Heart Study data set provided by the Genetic Analysis Workshop 13. This procedure uses a splitting rule based on Haseman-Elston regression that recursively partitions sib-pair data into homogeneous subgroups.ConclusionsUsing this procedure, we identified a subgroup definition for use as a selected sib-pair sampling scheme. Using the characteristics that define the subgroup with higher evidence for linkage, we have identified an area of focus for further study.

A program to implement a search method for identification of clinical subgroups

A procedure for identifying subgroups that are homogeneous with respect to an outcome variable is described. The method, search partition analysis (SPAN), is formulated in terms of a numeric outcome variable y and a set of predictors, explanatory variables or risk factors x = x1,x2,...,x p. The objective is to split observations into two groups by a binary partition, specified using Boolean expressions of the predictors, x, such that y is as homogeneous as possible in the resultant groups; uniformly ¿low' in one and uniformly ¿high' in the other. Subgroups within each of the two groups can be identified from the Boolean expressions. SPAN implements a search for the ¿best' partition from among a class of regular Boolean expressions. Features of the method are described, including how to measure partition homogeneity, complexity penalizing, search strategies and subgroup definition and representation. The approach is illustrated with analyses of predictors of low birth weight and predictors of impaired glucose tolerance for screening purposes.

Shrink‐Swell Potential of Montmorillonitic Soils in Udic Moisture Regimes

AbstractThirty‐two montmorillonitic soil pedons representative of Vertisols, Inceptisols, and aquic, typic, or vertic subgroups of Alfisols and Ultisols in the udic moisture regime of Alabama were evaluated for their shrink‐swell properties. Soil shrink‐swell potential was evaluated on control section samples from coefficients of linear extensibility (COLE) measured by thermo‐mechanical analysis (TMA), percent volume change (PVC) of remolded samples measured by a micrometer, interlamellar shrinkage (IS) determined by x‐ray diffraction analysis, and from field expression of soil cracking. No significant differences in COLE, PVC, IS, smectite or clay content were encountered between soils with and without vertic characteristics. Discrepancies were found between laboratory measured and field observed shrinking potential of aquic/typic/vertic Ultisols primarily due to lack of wide cracks. The poor field expression of cracking in montmorillonitic Hapludults was better explained by a combination of physical and morphological characteristics such as texture and thickness of the surface layer, size and type of structural units, solum thickness and depth to Cr, soil moisture deficit, drainage and vegetation than by variation in physical, chemical, or mineralogical properties. At present, classification of montmorillonitic Hapludults in vertic subgroups is proscribed by lack of evidence of wide or deep cracking. Modifications in the current vertic subgroup definition are suggested to account for agronomic and/or engineering limitations of these soils.

A DSS for management of patients with a chronic illness

There is uncertainty in the management of an individual with a chronic illness. The uncertainty results from lack of information about groups of similar patients. A feedback model for patient care is presented and its implementation discussed. The model requires characterization of patients at the time of entry into the health-care system, cataloging the methods of management used and assessing the response to treatments by following the patient over long periods of time.With a computer-based data management system, the doctor can select a subgroup of like patients and review their management and their responses. Using the experiences of other patients, the doctor and patient can map out the most appropriate treatment. By following the patient over time, his treatment response can be compared with those in the subgroup. If the responses are not equivalent, the subgroup definition can be modified and another treatment selected. An example of the use of this strategy in determining time of discharge for patients on a coronary care unit is presented.