Dihydropyrimidinase and β-ureidopropionase gene variation and severe fluoropyrimidine-related toxicity

AIMS To assess the association of DPYS and UPB1 genetic variation, encoding the catabolic enzymes downstream of dihydropyrimidine dehydrogenase, with early-onset toxicity from fluoropyrimidine-based chemotherapy. PATIENTS & METHODS The coding and exon-flanking regions of both genes were sequenced in a discovery subset (164 patients). Candidate variants were genotyped in the full cohort of 514 patients. RESULTS & CONCLUSIONS Novel rare deleterious variants in DPYS (c.253C > T and c.1217G > A) were detected once each in toxicity cases and may explain the occurrence of severe toxicity in individual patients, and associations of common variants in DPYS (c.1-1T > C: padjusted = 0.003; OR = 2.53; 95% CI: 1.39-4.62, and c.265-58T > C: padjusted = 0.039; OR = 0.61; 95% CI: 0.38-0.97) with 5-fluorouracil toxicity were replicated.

Intra-articular corticosteroid for knee osteoarthritis.

BACKGROUND Knee osteoarthritis is a leading cause of chronic pain, disability, and decreased quality of life. Despite the long-standing use of intra-articular corticosteroids, there is an ongoing debate about their benefits and safety. This is an update of a Cochrane review first published in 2005. OBJECTIVES To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain, physical function, quality of life, and safety. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE (from inception to 3 February 2015), checked trial registers, conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA We included randomised or quasi-randomised controlled trials that compared intra-articular corticosteroids with sham injection or no treatment in people with knee osteoarthritis. We applied no language restrictions. DATA COLLECTION AND ANALYSIS We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain, function, quality of life, joint space narrowing, and risk ratios (RRs) for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis. MAIN RESULTS We identified 27 trials (13 new studies) with 1767 participants in this update. We graded the quality of the evidence as 'low' for all outcomes because treatment effect estimates were inconsistent with great variation across trials, pooled estimates were imprecise and did not rule out relevant or irrelevant clinical effects, and because most trials had a high or unclear risk of bias. Intra-articular corticosteroids appeared to be more beneficial in pain reduction than control interventions (SMD -0.40, 95% CI -0.58 to -0.22), which corresponds to a difference in pain scores of 1.0 cm on a 10-cm visual analogue scale between corticosteroids and sham injection and translates into a number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 6 to 13). An I(2) statistic of 68% indicated considerable between-trial heterogeneity. A visual inspection of the funnel plot suggested some asymmetry (asymmetry coefficient -1.21, 95%CI -3.58 to 1.17). When stratifying results according to length of follow-up, benefits were moderate at 1 to 2 weeks after end of treatment (SMD -0.48, 95% CI -0.70 to -0.27), small to moderate at 4 to 6 weeks (SMD -0.41, 95% CI -0.61 to -0.21), small at 13 weeks (SMD -0.22, 95% CI -0.44 to 0.00), and no evidence of an effect at 26 weeks (SMD -0.07, 95% CI -0.25 to 0.11). An I(2) statistic of ≥ 63% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.001), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.43). There was evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.05) or at least 100 participants per group (P=0.013), in trials that used concomittant viscosupplementation (P=0.08), and in trials that used concomitant joint lavage (P≤0.001).Corticosteroids appeared to be more effective in function improvement than control interventions (SMD -0.33, 95% CI -0.56 to -0.09), which corresponds to a difference in functions scores of -0.7 units on standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10 and translates into a NNTB of 10 (95% CI 7 to 33). An I(2) statistic of 69% indicated a moderate to large degree of between-trial heterogeneity. A visual inspection of the funnel plot suggested asymmetry (asymmetry coefficient -4.07, 95% CI -8.08 to -0.05). When stratifying results according to length of follow-up, benefits were small to moderate at 1 to 2 weeks after end of treatment (SMD -0.43, 95% CI -0.72 to -0.14), small to moderate at 4 to 6 weeks (SMD -0.36, 95% CI -0.63 to -0.09), and no evidence of an effect at 13 weeks (SMD -0.13, 95% CI -0.37 to 0.10) or at 26 weeks (SMD 0.06, 95% CI -0.16 to 0.28). An I(2) statistic of ≥ 62% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.004), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.52). We found evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.023), in unpublished trials (P=0.023), in trials that used non-intervention controls (P=0.031), and in trials that used concomitant viscosupplementation (P=0.06).Participants on corticosteroids were 11% less likely to experience adverse events, but confidence intervals included the null effect (RR 0.89, 95% CI 0.64 to 1.23, I(2)=0%). Participants on corticosteroids were 67% less likely to withdraw because of adverse events, but confidence intervals were wide and included the null effect (RR 0.33, 95% CI 0.05 to 2.07, I(2)=0%). Participants on corticosteroids were 27% less likely to experience any serious adverse event, but confidence intervals were wide and included the null effect (RR 0.63, 95% CI 0.15 to 2.67, I(2)=0%).We found no evidence of an effect of corticosteroids on quality of life compared to control (SMD -0.01, 95% CI -0.30 to 0.28, I(2)=0%). There was also no evidence of an effect of corticosteroids on joint space narrowing compared to control interventions (SMD -0.02, 95% CI -0.49 to 0.46). AUTHORS' CONCLUSIONS Whether there are clinically important benefits of intra-articular corticosteroids after one to six weeks remains unclear in view of the overall quality of the evidence, considerable heterogeneity between trials, and evidence of small-study effects. A single trial included in this review described adequate measures to minimise biases and did not find any benefit of intra-articular corticosteroids.In this update of the systematic review and meta-analysis, we found most of the identified trials that compared intra-articular corticosteroids with sham or non-intervention control small and hampered by low methodological quality. An analysis of multiple time points suggested that effects decrease over time, and our analysis provided no evidence that an effect remains six months after a corticosteroid injection.

Influence of CYP3A5 genetic variation on everolimus maintenance dosing after cardiac transplantation

BACKGROUND Everolimus (ERL) has become an alternative to calcineurin inhibitors (CNIs) due to its renal-sparing properties, especially in heart transplant (HTx) recipients with kidney dysfunction. However, ERL dosing is challenging due to its narrow therapeutic window combined with high inter-individual pharmacokinetic variability. Our aim was to evaluate the effect of clinical and genetic factors on ERL dosing in a pilot cohort of 37 HTx recipients. METHODS Variants in CYP3A5, CYP3A4, CYP2C8, POR, NR1I2, and ABCB1 were genotyped and clinical data were retrieved from patient charts. RESULTS While ERL trough concentration (C0 ) was within the targeted range for most patients, over 30-fold variability in the dose-adjusted ERL C0 was observed. Regression analysis revealed a significant effect of the non-functional CYP3A5*3 variant on the dose-adjusted ERL C0 (P = 0.031). ERL dose requirement was 0.02 mg/kg/day higher in patients with CYP3A5*1/*3 genotype compared to patients with CYP3A5*3/*3 to reach the targeted C0 (P = 0.041). ERL therapy substantially improved estimated glomerular filtration rate (28.6 ± 6.6 ml/min/1.73m(2) ) in patients with baseline kidney dysfunction. CONCLUSION ERL pharmacokinetics in HTx recipients is highly variable. Our preliminary data on patients on a CNI-free therapy regimen suggest that CYP3A5 genetic variation may contribute to this variability. This article is protected by copyright. All rights reserved.

Estimating Intra-Party Preferences: Comparing Speeches to Votes

Well-established methods exist for measuring party positions, but reliable means for estimating intra-party preferences remain underdeveloped. While most efforts focus on estimating the ideal points of individual legislators based on inductive scaling of roll call votes, this data suffers from two problems: selection bias due to unrecorded votes and strong party discipline, which tends to make voting a strategic rather than a sincere indication of preferences. By contrast, legislative speeches are relatively unconstrained, as party leaders are less likely to punish MPs for speaking freely as long as they vote with the party line. Yet, the differences between roll call estimations and text scalings remain essentially unexplored, despite the growing application of statistical analysis of textual data to measure policy preferences. Our paper addresses this lacuna by exploiting a rich feature of the Swiss legislature: on most bills, legislators both vote and speak many times. Using this data, we compare text-based scaling of ideal points to vote-based scaling from a crucial piece of energy legislation. Our findings confirm that text scalings reveal larger intra-party differences than roll calls. Using regression models, we further explain the differences between roll call and text scalings by attributing differences to constituency-level preferences for energy policy.

Expansion load: recessive mutations and the role of standing genetic variation

Expanding populations incur a mutation burden – the so-called expansion load. Previous studies of expansion load have focused on codominant mutations. An important consequence of this assumption is that expansion load stems exclusively from the accumulation of new mutations occurring in individuals living at the wave front. Using individual-based simulations, we study here the dynamics of standing genetic variation at the front of expansions, and its consequences on mean fitness if mutations are recessive. We find that deleterious genetic diversity is quickly lost at the front of the expansion, but the loss of deleterious mutations at some loci is compensated by an increase of their frequencies at other loci. The frequency of deleterious homozygotes therefore increases along the expansion axis, whereas the average number of deleterious mutations per individual remains nearly constant across the species range. This reveals two important differences to codominant models: (i) mean fitness at the front of the expansion drops much faster if mutations are recessive, and (ii) mutation load can increase during the expansion even if the total number of deleterious mutations per individual remains constant. We use our model to make predictions about the shape of the site frequency spectrum at the front of range expansion, and about correlations between heterozygosity and fitness in different parts of the species range. Importantly, these predictions provide opportunities to empirically validate our theoretical results. We discuss our findings in the light of recent results on the distribution of deleterious genetic variation across human populations and link them to empirical results on the correlation of heterozygosity and fitness found in many natural range expansions.

The Effects of Density, Spatial Pattern, and Competitive Symmetry on Size Variation in Simulated Plant Populations

Patterns of size inequality in crowded plant populations are often taken to be indicative of the degree of size asymmetry of competition, but recent research suggests that some of the patterns attributed to size‐asymmetric competition could be due to spatial structure. To investigate the theoretical relationships between plant density, spatial pattern, and competitive size asymmetry in determining size variation in crowded plant populations, we developed a spatially explicit, individual‐based plant competition model based on overlapping zones of influence. The zone of influence of each plant is modeled as a circle, growing in two dimensions, and is allometrically related to plant biomass. The area of the circle represents resources potentially available to the plant, and plants compete for resources in areas in which they overlap. The size asymmetry of competition is reflected in the rules for dividing up the overlapping areas. Theoretical plant populations were grown in random and in perfectly uniform spatial patterns at four densities under size‐asymmetric and size‐symmetric competition. Both spatial pattern and size asymmetry contributed to size variation, but their relative importance varied greatly over density and over time. Early in stand development, spatial pattern was more important than the symmetry of competition in determining the degree of size variation within the population, but after plants grew and competition intensified, the size asymmetry of competition became a much more important source of size variation. Size variability was slightly higher at higher densities when competition was symmetric and plants were distributed nonuniformly in space. In a uniform spatial pattern, size variation increased with density only when competition was size asymmetric. Our results suggest that when competition is size asymmetric and intense, it will be more important in generating size variation than is local variation in density. Our results and the available data are consistent with the hypothesis that high levels of size inequality commonly observed within crowded plant populations are largely due to size‐asymmetric competition, not to variation in local density.

Effects of variation in nest curtain design on pre-laying behaviour of domestic hens

Laying hens in loose-housing systems select a nest daily in which to lay their eggs among many identical looking nests, they often prefer corner nests. We investigated whether heterogeneity in nest curtain appearance – via colours and symbols – would influence nest selection and result in an even distribution of eggs among nests. We studied pre-laying behaviour in groups of 30 LSL hens across two consecutive trials with eight groups per trial. Half of the groups had access to six identical rollaway group-nests, while the others had access to six nests of the same type differing in outer appearance. Three colours (red, green, yellow) and three black symbols (cross, circle, rectangle) were used to create three different nest curtain designs per pen. Nest position and the side of entrance to the pens were changed at 28 and 30 weeks of age, respectively, whereby the order of changes was counterbalanced across trials. Nest positions were numbered 1–6, with nest position 1 representing the nest closest to the pen entrance. Eggs were counted per nest daily from week of age 18 to 33. Nest visits were recorded individually with an RFID system for the first 5 h of light throughout weeks 24–33. Hens with access to nests differing in curtain appearance entered fewer nests daily than hens with identical nests throughout the study but both groups entered more nests with increasing age. We found no other evidence that curtain appearance affected nest choice and hens were inconsistent in their daily nest selection. A high proportion of eggs were laid in corner nests especially during the first three weeks of lay. The number of visits per egg depended upon nest position and age: it increased with age and was higher after the nest position change than before in nest position 1, whereas it stayed stable over time in nest position 6. At 24 weeks of age, gregarious nest visits (hens visiting an occupied nest when there was at least one unoccupied nest) and solitary nest visits (hens visiting an unoccupied nest when there was at least one occupied nest) accounted for a similar amount of nest visits, however, after the door switch, gregarious nest visits made up more than half of all nest visits, while the number of solitary nest visits had decreased. The visual cues were too subtle or inadequate for hens to develop individual preferences while nest position, entrance side, age and nest occupancy affected the quantity and type of nest visits.

Measurement and correlates of physical activity behavior among older minority women

Research has shown that physical activity serves a preventive function against the development of several major chronic diseases. However, studying physical activity and its health benefits is difficult due to the complexity of measuring physical activity. The overall aim of this research is to contribute to the knowledge of both correlates and measurement of physical activity. Data from the Women On The Move study were used for this study (n = 260), and the results are presented in three papers. The first paper focuses on the measurement of physical activity and compares an alternate coding method with the standard coding method for calculating energy expenditure from a 7-day activity diary. Results indicate that the alternative coding scheme could produce similar results to the standard coding in terms of total activity expenditure. Even though agreement could not be achieved by dimension, the study lays the groundwork for a coding system that saves considerable amount of time in coding activity and has the ability to estimate expenditure more accurately for activities that can be performed at varying intensity levels. The second paper investigates intra-day variability in physical activity by estimating the variation in energy expenditure for workers and non-workers and identifying the number of days of diary self-report necessary to reliably estimate activity. The results indicate that 8 days of activity are needed to reliably estimate total activity for individuals who don't work and 12 days of activity are needed to reliably estimate total activity for those who work. Days of diary self-report required by dimension for those who don't work range from 6 to 16 and for those who work from 6 to 113. The final paper presents findings on the relationship between daily living activity and Type A behavior pattern. Significant findings are observed for total activity and leisure activity with the Temperament Scale summary score. Significant findings are also observed for total activity, household chores, work, leisure activity, exercise, and inactivity with one or more of the individual items on the Temperament Scale. However, even though some significant findings were observed, the overall models did not reveal meaningful associations. ^

Identifying Individual and Group Effects in the Presence of Sorting: A Neighborhood Effects Application

Researchers have long recognized that the non-random sorting of individuals into groups generates correlation between individual and group attributes that is likely to bias naive estimates of both individual and group effects. This paper proposes a non-parametric strategy for identifying these effects in a model that allows for both individual and group unobservables, applying this strategy to the estimation of neighborhood effects on labor market outcomes. The first part of this strategy is guided by a robust feature of the equilibrium in the canonical vertical sorting model of Epple and Platt (1998), that there is a monotonic relationship between neighborhood housing prices and neighborhood quality. This implies that under certain conditions a non- parametric function of neighborhood housing prices serves as a suitable control function for the neighborhood unobservable in the labor market outcome regression. The second part of the proposed strategy uses aggregation to develop suitable instruments for both exogenous and endogenous group attributes. Instrumenting for each individual's observed neighborhood attributes with the average neighborhood attributes of a set of observationally identical individuals eliminates the portion of the variation in neighborhood attributes due to sorting on unobserved individual attributes. The neighborhood effects application is based on confidential microdata from the 1990 Decennial Census for the Boston MSA. The results imply that the direct effects of geographic proximity to jobs, neighborhood poverty rates, and average neighborhood education are substantially larger than the conditional correlations identified using OLS, although the net effect of neighborhood quality on labor market outcomes remains small. These findings are robust across a wide variety of specifications and robustness checks.

The Effect of Classmate Characteristics on Individual Outcomes: Evidence from the Add Health

We use data from the National Longitudinal Study of Adolescent Health (Add Health) to examine the effects of classmate characteristics on economic and social outcomes of students. The unique structure of the Add Health allows us to estimate these effects using comparisons across cohorts within schools, and to examine a wider range of outcomes than other studies that have used this identification strategy. This strategy yields variation in cohort composition that is uncorrelated with student observables suggesting that our estimates are not biased by the selection of students into schools or grades based on classmate characteristics. We find that increases in the percent of classmates whose mother is college educated has significant, desirable effects on educational attainment and substance use. We do not find much evidence that the percent of classmates who are black or Hispanic has significant effects on individual outcomes, on average. Additional analyses suggest, however, that an increase in the percent black or Hispanic may increase dropout rates among black students and post-high school idleness among males.

Clinical relevance of polymorphic DNA copy number variation (CNV) in African American women with stage I-II breast cancer

Objectives. The chief goal of this study was to analyze copy number variation (CNV) in breast cancer tumors from 25 African American women with early stage breast cancer (BC) using molecular inversion probes (MIP) in order to: (1) compare the degree of CNV in tumors compared to normal lymph nodes, and (2) determine whether gains and/or losses of genes in specific chromosomes differ between pathologic subtypes of breast cancer defined by known prognostic markers, (3) determine whether gains/losses in CN are associated with known oncogenes or tumor suppressor genes, and (4) determine whether increased gains/losses in CN for specific chromosomes were associated with differences in breast cancer recurrence. ^ Methods. Twenty to 37 nanograms of DNA extracted from 25 formalin-fixed paraffin embedded (FFPE) tumor samples and matched normal lymph nodes were added to individual tubes. Oligonucleotide probes with recognition sequences at each terminus were hybridized with a genomic target sequence to form a circular structure. Probes are released from genomic DNA obtained from FFPE samples, and those which have been correctly "circularized" in the proper allele/nucleotide reaction combination are amplified using polymerase chain reaction (PCR) primers. Amplicons were fluorescently labeled and the tag sequences released from the genome homology regions by treatment with uracil-N-glycosylase to cleave the probe at the site where uracils are present, and detected using a complementary tag array developed by Affymetrix. ^ Results. Analysis of CN gains and losses from tumors and normal tissues showed marked differences in tumors with numerous chromosomes affected. Similar changes were not observed in normal lymph nodes. When tumors were stratified into four groups based on expression or lack of expression of the estrogen receptor and HER2/neu, distinct patterns of CNV for different chromosomes were observed. Gains or losses in CN for specific chromosomes correlated with amplifications/deletions of particular oncogenes or tumor suppressor genes (i.e. such as found on chromosome 17) known to be associated with aggressive tumor phenotype and poor prognosis. There was a trend for increases in CN observed for chromosome 17 to correlate inversely with time to recurrence of BC (p=0.14 for trend). CNV was also observed for chromosomes 5, 8, 10, 11, and 16, which are known sites for several breast cancer susceptibility alleles. ^ Conclusions. This study is the first to validate the MIP technique, to correlate differences in gene expression with known prognostic tumor markers, and to correlate significant increases/decreases in CN with known tumor markers associated with prognosis. The results of this study may have far reaching public health implications towards identifying new high-risk groups based on genomic differences in CNP, both with respect to prognosis and response to therapy, and to eventually identify new therapeutic targets for prevention and treatment of this disease. ^

Hospital and environmental variation in Texas nonprofit hospital organizational policies regarding charity care

The 2005 Annual Statement of Community Benefits Standard (ASCBS) and the annual report of the Community Benefits Plan, Summary of Current Hospital Charity Care Policy and Community Benefits, were used to identify various environmental and policy relationships with regard to eligibility for charity care requirements, a component for meeting the nonprofit requirements established by the Texas Legislature for nonprofit tax exemption (Texas Health and Safety Code, §311.04610). ^ Charity care policies are established by the individual hospital (or systems) and are generally defined as rules concerning care provided by the institution without the expectation of payment. This study has been undertaken to provide specific information about the charity care eligibility requirement policies of nonprofit hospitals. These hospitals are the part of the safety net for those persons who are indigent, low-income and uninsured. This study examines nonprofit hospitals by physical location, bed size, religious affiliation, trauma level, disproportionate share, and teaching designations. County information includes population, percentage of residents eligible for Medicaid benefits, ethnic makeup of county residents, poverty level, designation of a hospital district or operators of a public hospital, and the number of nonprofit and for-profit hospitals located in the county. Although this information has been collected by the Texas Department of State Health Services (DSHS), no other analysis has been conducted. ^

Genetic epidemiology of gallbladder disease in Mexican Americans and cholesterol 7$\alpha$-hydroxylase gene sequence variation

Among Mexican Americans, the second largest minority group in the United States, the prevalence of gallbladder disease is markedly elevated. Previous data from both genetic admixture and family studies indicate that there is a genetic component to the occurrence of gallbladder disease in Mexican Americans. However, prior to this thesis no formal genetic analysis of gallbladder disease had been carried out nor had any contributing genes been identified.^ The results of complex segregation analysis in a sample of 232 Mexican American pedigrees documented the existence of a major gene having two alleles with age- and gender-specific effects influencing the occurrence of gallbladder disease. The estimated frequency of the allele increasing susceptibility was 0.39. The lifetime probabilities that an individual will be affected by gallbladder disease were 1.0, 0.54, and 0.00 for females of genotypes "AA", "Aa", and "aa", respectively, and 0.68, 0.30, and 0.00 for males, respectively. This analysis provided the first conclusive evidence for the existence of a common single gene having a large effect on the occurrence of gallbladder disease.^ Human cholesterol 7$\alpha$-hydroxylase is the rate-limiting enzyme in bile acid synthesis. The results of an association study in both a random sample and a matched case/control sample showed that there is a significant association between cholesterol 7$\alpha$-hydroxylase gene variation and the occurrence of gallbladder disease in Mexican Americans males but not in females. These data have implicated a specific gene, 7$\alpha$-hydroxylase, in the etiology of gallbladder disease in this population.^ Finally, I asked whether the inferred major gene from complex segregation analysis is genetically linked to the cholesterol 7$\alpha$-hydroxylase gene. Three pedigrees predicted to be informative for linkage analysis by virtue of supporting the major gene hypothesis and having parents with informative genotypes and multiple offspring were selected for this linkage analysis. In each of these pedigrees, the recombination fractions maximized at 0 with a positive, albeit low, LOD score. The results of this linkage analysis provide preliminary and suggestive evidence that the cholesterol 7$\alpha$-hydroxylase gene and the inferred gallbladder disease susceptibility gene are genetically linked. ^

Inappropriate imaging utilization in Texas: Geographic variation and predictive factors

Objective::Describe and understand regional differences and associated multilevel factors (patient, provider and regional) to inappropriate utilization of advance imaging tests in the privately insured population of Texas. Methods: We analyzed Blue Cross Blue Shield of Texas claims dataset to study the advance imaging utilization during 2008-2010 in the PPO/PPO+ plans. We used three of CMS "Hospital Outpatient Quality Reporting" imaging efficiency measures. These included ordering MRI for low back pain without prior conservative management (OP-8) and utilization of combined with and without contrast abdominal CT (OP-10) and thorax CT (OP-11). Means and variation by hospital referral regions (HRR) in Texas were measured and a multilevel logistic regression for being a provider with high values for any the three OP measures was used in the analysis. We also analyzed OP-8 at the individual level. A multilevel logistic regression was used to identify predictive factors for having an inappropriate MRI for low back pain. Results: Mean OP-8 for Texas providers was 37.89%, OP-10 was 29.94% and OP-11 was 9.24%. Variation was higher for CT measure. And certain HRRs were consistently above the mean. Hospital providers had higher odds of high OP-8 values (OP-8: OR, 1.34; CI, 1.12-1.60) but had smaller odds of having high OP-10 and OP-11 values (OP-10: OR, 0.15; CI, 0.12-0.18; OP-11: OR, 0.43; CI, 0.34-0.53). Providers with the highest volume of imaging studies performed, were less likely to have high OP-8 measures (OP-8: OR, 0.58; CI, 0.48-0.70) but more likely to perform combined thoracic CT scans (OP-11: OR, 1.62; CI, 1.34-1.95). Males had higher odds of inappropriate MRI (OR, 1.21; CI, 1.16-1.26). Pattern of care in the six months prior to the MRI event was significantly associated with having an inappropriate MRI. Conclusion::We identified a significant variation in advance imaging utilization across Texas. Type of facility was associated with measure performance, but the associations differ according to the type of study. Last, certain individual characteristics such as gender, age and pattern of care were found to be predictors of inappropriate MRIs.^

Shell size variation of Neogloboquadrina pachyderma sin. in the Norwegian-Greenland Sea during the last 1.3 Myr

We present measurements of the maximum diameter of the planktonic foraminifer Neogloboquadrina pachyderma sin. from six sediment cores (Ocean Drilling Program sites 643, 644, 907, 909, 985 and 987) from the Norwegian-Greenland Sea. Our data show a distinct net increase in mean shell size of N. pachyderma sin. at all sites during the last 1.3 Ma, with largest shell sizes reached after 0.4 Ma. External factors such as glacial-interglacial variability and carbonate dissolution alone cannot account for the observed variation in mean shell size of N. pachyderma sin. We consider the observed shell size increase to mirror an evolutionary trend towards better adaptation of N. pachyderma sin. to the cold water environment after 1.1-1.0 Ma. Probably, the Mid Pleistocene climate shift and the associated change of amplitude and frequency of glacial-interglacial fluctuations have triggered the evolution of this planktonic foraminifer. Oxygen and carbon stable isotope analyses of different shell size classes indicate that the observed shell size increase could not be explained by the functional concept that larger shells promote increasing sinking velocities during gametogenesis. For paleoceanographic reconstructions, the evolutionary adaptation of Neogloboquadrina pachyderma sin. to the cold water habitat has significant implications. Carbonate sedimentation in highest latitudes is highly dependent on the presence of this species. In the Norwegian-Greenland Sea, carbonate-poor intervals before 1.1 Ma are, therefore, not necessarily related to severe glacial conditions. They are probably attributed to the absence of this not yet polar-adapted species. Further, transfer function and modern analog techniques used for the reconstruction of surface water conditions in high latitudes could, therefore, contain a large range of errors if they were applied to samples older than 1.1-1.0 Myrs.