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Linking variation in the structure and process of bedside glucose testing programs with patient outcomes.

OBJECTIVE: The objective of this study was to determine if variation in compliance to standards listed in Ancillary (Bedside) Blood Glucose Testing in Acute and Chronic Care Facilities (ABBGT) was linked to variation in patient outcomes. DESIGN AND SETTING: A retrospective analysis examined 450 hospitalized patients with a diagnosis of diabetes from three hospitals with high, medium, and low assessment scores for compliance with ABBGT guidelines. Patients with a diagnosis of diabetes without surgical interventions or intensive care unit stays were selected for the study. MAIN OUTCOMES MEASURED: percent bedside glucose tests that were out of normal range and length of stay. RESULTS: Compliance with ABBGT guidelines explained the variation for out of range bedside glucose tests---1.4% and length CONCLUSION: Within a narrow range and high level of compliance with ABBGT guidelines, the compliance scores had a small effect upon the selected outcomes. The hypothesis that following ABBGT guidelines improves patient outcomes was neither proven nor disproven with this study.

Aged↗

Perturbation of conjugation in internally solvated allylic lithium compounds: variation of ligand structure. NMR and X-ray crystallography.

Several allyic lithium compounds were prepared with different potential ligands tethered at C2. These are with CH3OCH2CH2NCH3CH2-, 5 and 1-TMS 6, with (CH3)2NCH2CH2NCH3CH2-, 1-TMS 7, and with ((CH3)2NCH2CH2)2NCH2-, 8 and 1-TMS 9. In all these compounds Li is fully coordinated to the pendant ligand and is sited off the axis perpendicular to the allyl plane at one of the allyl termini as indicated by a combination of X-ray crystallography and NMR spectra. Compounds 5 and 8 are Li-bridged dimers as shown by X-ray crystallography and also dimeric in benzene solution as determined from freezing point determinations. Compounds 6, 7, and 9 are monomeric in THF-d8 or diethyl ether-d10 solution and exhibit one bond 13C1, 6Li scalar coupling at low temperature. Taken together the crystallographic and NMR data indicate that all of these compounds incorporate partially delocalized allylic moieties. Compounds 5 and 8 undergo fast 1,3-Li-sigmatropic shifts that are proposed to take place within low concentrations of monomers in fast equilibrium with prevalent dimers. Averaging with increasing temperature of the one-bond 13C, 6Li coupling constant in 6, 7, and 13 provided the dynamics of bimolecular C-Li exchange with Delta H++ values of 6.7, 12, and 13 kcal x mol(-1), respectively. Averaging of the diastereotopic N(CH3)2 13C resonances of 7 is indicative of fast transfer of coordinated ligand between faces of the allyl plane Delta H++ = 5.3 kcal x mol(-1) combined with slower inversion at nitrogen. Compound 8 exhibits similar effects. It is concluded that variation of the ligand structure changes dynamic behavior of the compounds but has little influence of their degrees of delocalization.

Journal Article↗

Variations in the structure of thyroglobulins from normal and goitrous human thyroids.

Thyroglobulin samples were prepared individually be gel chromatography from the thyroids of five persons without thyroid disease and four with goiters. Gel electrophoresis at different pHs and gel concentrations showed a single major band corresponding to 19S thyroglobulin in rabbits, with occasional faint bands corresponding to 12S and 27S species. The thyroglobulins of the normals differed from each other in electrophoretic pattern on sodium dodecyl sulfate (SDS)-urea gels and in composition of iodine, monosaccharides, and amino acids. Nine amino acids showed significant variation among the five thyroglobulins at the P less than 0.01 level, and only two (lysine and alanine) did not vary. The content of both sialic acid and fucose varied widely, but their sum was similar among the five samples. Thyroglobulin samples from the goiters differed from the normals and from each other in composition and in pattern on SDS-urea gels. The variability itself was more impressive than were differences in any particular component. Relative to the normals, these thyroglobulins showed increases in content of sialic acid (P less than 0.01) and lysine (P less than 0.10), and increases in the faster bands on gel electrophoresis in SDS-urea. Two goiters were from patients with the multiple hamartoma syndrome, and the only metabolic abnormality found was a low content of iodothyronine in thyroglobulin. The other two goiters also showed inadequate coupling of iodotyrosyls. In addition, one contained a soluble iodoprotein of very high molecular weight, which was immunologically identical to 19S thyroglobulin but differed in chemical composition. We conclude from the compositional data that there is not a single structure for "normal" thyroglobulin, but that multiple molecular configurations occur naturally and are compatible with adequate hormone synthesis. Extensive variations in thyroglobulin structure are frequently found with goiter, and we suggest that these may be involved in its pathogenesis.

Adult↗

Temporal variation in genetic structure of a colonising species: Aedes albopictus in the United States.

The medically important mosquito, Aedes albopictus, has recently become established in several locations within the United States. A three-year survey of temporal variation in allele frequencies at ten enzymatic loci in 17 populations was undertaken to determine the extent and direction of change since the colonization event. Significant, but non-directional, changes were detected in allele frequencies at most of the loci in all populations. Some alleles detected at low frequencies in earlier samples were not found in subsequent samples. Variance of allele frequencies remained unchanged. In at least two locations, there was an increase in mean heterozygosity, perhaps because of gene flow. There was no significant change in the levels of genetic variation within and among populations. The results from this study indicate that the breeding structure of Ae. albopictus in the U.S. did not differ substantially from that in a native habitat, either soon after colonisation or after several generations in the new habitat. We suggest that a large founder population, gene flow and a rapid population expansion could explain the present breeding structure of Ae. albopictus.

Aedes↗

Generating three-dimensional genome structures with a variational quantum algorithm.

Chromosome conformation capture experiments have revealed the underlying spatial interactions that govern three-dimensional (3D) genome organization and topology. Detecting 3D contacts between genomic loci considerably enhances our understanding of fundamental regulatory processes. Modeling 3D structures from experimental contact matrices can further contextualize the relationship between 3D genome organization and regulation. While classical algorithms have been successful in reconstructing genomic conformations, we investigate the prospect of quantum computation to aid in modeling the conformational space. In this context, we propose a novel variational quantum algorithm (VQA) to model the distribution of 3D genomic structures from experimental contact data. Through rigorous evaluations, we demonstrate the capability of our algorithm to sample ensembles of viable 3D conformations that agree well with experimental and simulated contact data. Furthermore, we extend our methodology to model the conformational space of a single cell or a population of cells. In the advent of sufficient quantum utility, the insights gained from this study can serve as a foundation for investigating high-resolution, large-scale ensembles of genomic conformations through generative VQAs.

Algorithms↗

Variation of the structure and course of the interlobular arteries in human kidney.

In microangiograms and clearing preparations obtained from 25 adult human kidneys, the variations of number, origin, length and ramification pattern of the interlobular arteries were investigated. In the examined material, the interlobular arteries arose from the arcuate arteries at various angles, most frequently as a common trunk dividing in its course into 2 to 5 proper interlobular arteries. Their length was varied in the particular portions of the renal cortex and correlated with its thickness.

Adult↗

Structural defects and variations in the HIV-1 nef gene from rapid, slow and non-progressor children.

OBJECTIVES: Evaluation of sequence evolution as well as structural defects and mutations of the human immunodeficiency virus-type 1 (HIV-1) nef gene in relation to disease progression in infected children. DESIGN: We examined a large number of nef alleles sequentially derived from perinatally HIV-1-infected children with different rates of disease progression: six non-progressors (NPs), four rapid progressors (RPs), and three slow progressors (SPs). METHODS: Nef alleles (182 total) were isolated from patients' peripheral blood mononuclear cells (PBMCs), sequenced and analysed for their evolutionary pattern, frequency of mutations and occurrence of amino acid variations associated with different stages of disease. RESULTS: The evolution rate of the nef gene apparently correlated with CD4+ decline in all progression groups. Evidence for rapid viral turnover and positive selection for changes were found only in two SPs and two RPs respectively. In NPs, a higher proportion of disrupted sequences and mutations at various functional motifs were observed. Furthermore, NP-derived Nef proteins were often changed at residues localized in the folded core domain at cytotoxic T lymphocytes (CTL) epitopes (E(105), K(106), E(110), Y(132), K(164), and R(200)), while other residues outside the core domain are more often changed in RPs (A(43)) and SPs (N(173) and Y(214)). CONCLUSIONS: Our results suggest a link between nef gene functions and the progression rate in HIV-1-infected children. Moreover, non-progressor-associated variations in the core domain of Nef, together with the genetic analysis, suggest that nef gene evolution is shaped by an effective immune system in these patients.

Adolescent↗

Population structure and skeletal variation in the Late Woodland of west-central Illinois.

This paper analyzes nonmetric trait variation in 11 late Late Woodland (ca. AD 700-1000) and one Mississippian (AD 1000-1300) skeletal samples from west-central Illinois from a population-structure perspective. Most of the sites are of the Bluff phase of Late Woodland in the lower Illinois River valley; others are from a nearby, contemporary archaeological phase. Late Woodland as a whole era (ca. AD 250-1000) was a period of marked population growth and expansion into new regional environments, trends that accompanied horticultural intensification in the area. Overall variation between sites was low, but males, females, and the total sample exhibited a significant geographic component to variation due to interregional morphological differences. The Bluff sites tended to group together relative to the non-Bluff sites. However, there was no significant geographic component to variation among the Bluff sites. The results are only partially consistent with archaeological data suggesting population growth and expansion through fissioning. Previous studies have demonstrated significant heterogeneity for nonmetric trait frequencies among Middle Woodland (ca. 100 BC to AD 250) sites, suggesting a Middle to Late Woodland change in population structure that lowered levels of morphological variation. This supports a model of increased intra- and interregional interaction from Middle to Late Woodland times developed from ceramic data by Braun and by Braun and Plog.

Bone and Bones↗

Genetic variation and population structure of the mosquito Anopheles jeyporiensis in southern China.

Genetic differentiation among populations of Anopheles jeyporiensis was examined using 76 mtDNA COII sequences from 16 sites throughout southern China and northern Vietnam. The COII sequences are AT-rich (74.58%) and reveal high levels of diversity with 39 of 685 sites polymorphic and 50 different haplotypes present. Genetic variation is high within populations and significant geographical structure was detected at both population and regional levels. In the larger samples, the distributions of haplotypes suggest recent population expansion.

Analysis of Variance↗

Structural and functional variations in capillary systems within the brain.

The major hypothesis of this study is that there are differences among brain areas in capillary bed structure and function. Three general differences between circumventricular organ and non-CVO capillary beds were found. First, the PS products for AIB were about 300 times greater in CVO capillaries than in non-CVO (blood-brain barrier) capillaries. Second, the frequency of endothelial cell fenestrations was much greater in CVO capillaries than in non-CVO capillaries and the fenestrae may be structural modifications of endothelial cells that permit ready passage of solutes such as AIB. Third, the frequency of mitochondria was greater in BBB capillaries than in CVO capillaries; this high metabolic potential of BBB capillaries may be associated, in part, with "carrier-mediated" transport of various solutes between plasma and cerebral interstitial fluid. Capillary bed differences among all (i.e., both CVO and non-CVO) brain structures were also observed. Among these differences are: rate of blood flow, mean transit time of albumin, capillary volume and surface area, perfused microvessel blood volume, apparent percentage of perfused capillaries, PS products for AIB, and frequency within the endothelium of vesicular profiles.

Aminoisobutyric Acids↗

Variation in the structure of Toxoplasma gondii and the roles of selfing, drift, and epistatic selection in maintaining linkage disequilibria.

Previous studies of Toxoplasma gondii, based on samples dominated by clinical isolates, have concluded that its population structure is clonal, despite the sexual reproduction that occurs in cats. To determine whether this applies to non-clinical isolates, we compared patterns of linkage disequilibrium (LD) among seven loci in samples of T. gondii from Brazil and the US. LD was detected in both locations, but it was substantially lower in Brazil. The lower LD in Brazil can be explained by a higher rate of sexual reproduction between different genotypes (outcrossing) because of a higher rate of transmission. The extent of LD between pairs of physically unlinked loci varied significantly in each location. Moreover, the magnitude of LD between corresponding locus pairs in Brazil and the US was correlated, despite minimal gene exchange between the continents (mean FST = 0.19). The heterogeneity among locus pairs and the correlation in LD between physically unlinked locus pairs from different continents suggests that locus-specific factors, such as epistatic selection are involved in maintaining LD in T. gondii. Possibly, the unique life cycle of T. gondii with its unpredictable transmission among diverse host species and distinct ecological habitats requires specific combinations of alleles from multiple loci. The usefulness of typing isolates based on physically unlinked loci is questioned not only by the geographic variation in the reproductive population structure, but mainly by the low overall predictability of the genotype of one locus based on the genotype in another (unlinked) locus. This predictability ranged between 23 and 45%, but was close to nil for a considerable fraction of locus pairs.

Alleles↗

Permanent dipole moment of tRNA's and variation of their structure in solution.

The structure of six different tRNA molecules has been analyzed in solution by electrooptical measurements and by bead model simulations. The electric dichroism measured as a function of the field strength shows that tRNA's are associated with substantial permanent dipole moments, which are in the range of 1 x 10(-27) cm(identical to 300 D; before correction for the internal directing field). Rotational diffusion time constants of tRNA molecules in their native state at 2 degrees C show a considerable variation. A particularly large value found for tRNA(Tyr) (50 ns) can be explained by its nine additional nucleotide residues. However, remarkable variations remain for tRNA molecules with the standard number of 76 nucleotide residues (tRNA(Phe) [yeast] 41.6 ns, tRNA(Val) [Escherichia coli] 44.9 ns, tRNA(Glu) [E. coli] 46.8 ns; tRNA(Phe) [E. coli] 48.3 ns). These variations indicate modulations of the tertiary structure, which may be due to a change of the L-hinge angle. Bead models are used to simulate both electric and hydrodynamic parameters of tRNA molecules according to the crystal structure of tRNA(Phe) (yeast). The asymmetric distribution of phosphate charges with respect to the center of diffusion leads, under the assumption of a constant charge reduction to 15% by ion condensation, to a theoretical dipole moment of 7.2 x 10(-28) cm, which is in reasonable agreement with the measurements. The dichroism decay curve calculated for tRNA(Phe) (yeast) is also consistent with the measurements and thus the structure in solution and in the crystal must be very similar in this case. However, our measurements also indicate that the structure of some other tRNA's in solution is different, even in cases with the same number of nucleotide residues.

Magnesium↗

Genetic structure and AFLP variation of remnant populations in the rare plant Pedicularis palustris (Scrophulariaceae) and its relation to population size and reproductive components.

We investigated plant reproduction in relation to genetic structure, population size, and habitat quality in 13 populations of the rare biennial plant Pedicularis palustris with 3-28500 flowering individuals. We used AFLP (amplified fragment length polymorphism) profiles to analyze genetic similarities among 129 individuals (3-15 per population). In a cluster analysis of genetic similarities most individuals (67%) were arranged in population-specific clusters. Analysis of molecular variance indicated significant genetic differentiation among populations and among and within subpopulations (P < 0.001). Gene flow (N(e) m) was low (0.298). On average, plants produced 55 capsules, 17 seeds per fruit, and 42 seedlings in the following growing season. The number of seeds per capsule was independent of population size and of genetic variability. In contrast, the number of capsules per plant (P < 0.05) and the number of seedlings per plant (P < 0.05) were positively correlated with population size. The relation between population size and the number of seeds per plant was not significant (P = 0.075). The number of capsules and of seeds and seedlings per plant (P < 0.01) were positively correlated with genetic variability. Genetic variability was independent of actual population size, suggesting that historical population processes have to be taken into account, too. Stepwise multiple regressions revealed additional significant relationships of habitat parameters (soil pH, C:N ratio), vegetation composition, and standing crop on reproductive components. We conclude that populations of P. palustris are genetically isolated and that reproductive success most likely is influenced by population size, genetic variability, and habitat quality. Management strategies such as moderate grazing, mowing, and artificial gene flow should endeavor to increase population size as well as genetic variation.

Journal Article↗

DNA sequence variation and haplotype structure of the ICAM1 and TNF genes in 12 ethnic groups of India reveal patterns of importance in designing association studies.

We have examined the patterns of DNA sequence variation in and around the genes coding for ICAM1 and TNF, which play functional and correlated roles in inflammatory processes and immune cell responses, in 12 diverse ethnic groups of India. We aimed to (a) quantify the nature and extent of the variation, and (b) analyse the observed patterns of variation in relation to population history and ethnic background. At the ICAM1 and TNF loci, respectively, the total numbers of SNPs that were detected were 28 and 12. Many of these SNPs are not shared across ethnic groups and are unreported in the dbSNP or TSC databases, including two fairly common non-synonymous SNPs at positions 13487 and 13542 in the ICAM1 gene. Conversely, the TNF-376A SNP that is reported to be associated with susceptibility to malaria was not found in our study populations, even though some of the populations inhabit malaria endemic areas. Wide between-population variation in the frequencies of shared SNPs and coefficients of linkage disequilibrium have been observed. These findings have profound implications in case-control association studies.

Chromosome Mapping↗

Allozyme variation and population genetic structure of Betula alnoides from Guangxi, China.

Allozyme variation and population genetic structure of Betula alnoides Buch Ham. ex D. Don in 11 natural populations from Guangxi Zhuang Autonomous Region, China, were investigated by starch gel electrophoresis. Variation at 15 loci from 10 enzyme systems was analyzed. Allozyme analysis revealed a high level of genetic variation in this species, with percentage of polymorphic loci (P(p)), the average number of alleles per locus (A(p)), and the expected heterozygosity (H(ep)) being 55.2%, 2.0, and 0.204, respectively, which exceeds the average level among out-crossing wind-pollinated woody species at the population level. At the species level, P(s), A(s), and H(es) were 60.0%, 2.67, and 0.206, respectively. The observed heterozygosity (H(op)) was higher than H(ep), indicating the existence of natural selection against homozygotes. The negative fixation index (F = -0.216) implied a significant excess of heterozygosity at the population level Among-population differentiation (F(ST)) accounted for 4.0% of the total variation. No significant correlation was detected between the genetic distance and geographic distance among populations. Extensive gene flow was inferred, based on the allozyme data (N(m) = 6.000 from F(ST), N(m) = 5.605 from the "private allele" method). The results demonstrated that the fragmentation status of B. alnoides had no remarkable effects on the population genetic structure of this species. Some populations are recommended for both in situ genetic conservation and germplasm collection for breeding programs.

Betula↗

RNA aptamers to the adenosine moiety of S-adenosyl methionine: structural inferences from variations on a theme and the reproducibility of SELEX.

We used in vitro selection (SELEX) to isolate RNA 'aptamers' to S-adenosyl methionine (SAM). Individual aptamer sequences conform to the structural element noted previously for adenosine binding in selections for aptamers to ATP and NAD+. When we compare the patterns of sequence conservation among 65 adenosine-binding sequences to the published structure of the adenosine aptamer, we find that the most highly conserved nucleotides contact the bound adenosine directly, and that one conserved nucleotide outside the binding pocket is in position to stabilize nucleotides within the binding pocket. The aptamer's ability to bind diverse adenosine-containing cofactors is easily understood in terms of its mode of binding, which leaves the 5'position exposed to solvent. We propose that aptamers that bind their targets away from the reactive moiety may be particularly well suited for catalysis. Finally, we estimate that one sequence in 10(11) may be able to form this structural motif, and that there may be many other adenosine-binding motifs that have escaped detection because of their lower representation in the starting random pools.

Adenosine↗