Variation in use of surveillance colonoscopy among colorectal cancer survivors in the United States.

BACKGROUND: Clinical practice guidelines recommend colonoscopies at regular intervals for colorectal cancer (CRC) survivors. Using data from a large, multi-regional, population-based cohort, we describe the rate of surveillance colonoscopy and its association with geographic, sociodemographic, clinical, and health services characteristics. METHODS: We studied CRC survivors enrolled in the Cancer Care Outcomes Research and Surveillance (CanCORS) study. Eligible survivors were diagnosed between 2003 and 2005, had curative surgery for CRC, and were alive without recurrences 14 months after surgery with curative intent. Data came from patient interviews and medical record abstraction. We used a multivariate logit model to identify predictors of colonoscopy use. RESULTS: Despite guidelines recommending surveillance, only 49% of the 1423 eligible survivors received a colonoscopy within 14 months after surgery. We observed large regional differences (38% to 57%) across regions. Survivors who received screening colonoscopy were more likely to: have colon cancer than rectal cancer (OR = 1.41, 95% CI: 1.05-1.90); have visited a primary care physician (OR = 1.44, 95% CI: 1.14-1.82); and received adjuvant chemotherapy (OR = 1.75, 95% CI: 1.27-2.41). Compared to survivors with no comorbidities, survivors with moderate or severe comorbidities were less likely to receive surveillance colonoscopy (OR = 0.69, 95% CI: 0.49-0.98 and OR = 0.44, 95% CI: 0.29-0.66, respectively). CONCLUSIONS: Despite guidelines, more than half of CRC survivors did not receive surveillance colonoscopy within 14 months of surgery, with substantial variation by site of care. The association of primary care visits and adjuvant chemotherapy use suggests that access to care following surgery affects cancer surveillance.

Common genetic variation and the control of HIV-1 in humans.

To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians.

Genome-wide scan of copy number variation in late-onset Alzheimer's disease.

Alzheimer's disease is a complex and progressive neurodegenerative disease leading to loss of memory, cognitive impairment, and ultimately death. To date, six large-scale genome-wide association studies have been conducted to identify SNPs that influence disease predisposition. These studies have confirmed the well-known APOE epsilon4 risk allele, identified a novel variant that influences disease risk within the APOE epsilon4 population, found a SNP that modifies the age of disease onset, as well as reported the first sex-linked susceptibility variant. Here we report a genome-wide scan of Alzheimer's disease in a set of 331 cases and 368 controls, extending analyses for the first time to include assessments of copy number variation. In this analysis, no new SNPs show genome-wide significance. We also screened for effects of copy number variation, and while nothing was significant, a duplication in CHRNA7 appears interesting enough to warrant further investigation.

Distribution, ecology, life history, genetic variation, and risk of extinction of nonhuman primates from Costa Rica

We examined the association between geographic distribution, ecological traits, life history, genetic diversity, and risk of extinction in nonhuman primate species from Costa Rica. All of the current nonhuman primate species from Costa Rica are included in the study; spider monkeys (Ateles geoffroyi), howling monkeys (Alouatta palliata), capuchins (Cebus capucinus), and squirrel monkeys (Saimiri oerstedii). Geographic distribution was characterized accessing existing databases. Data on ecology and life history traits were obtained through a literature review. Genetic diversity was characterized using isozyme electrophoresis. Risk of extinction was assessed from the literature. We found that species differed in all these traits. Using these data, we conducted a Pearson correlation between risk of extinction and ecological and life history traits, and genetic variation, for widely distributed species. We found a negative association between risk of extinction and population birth and growth rates; indicating that slower reproducing species had a greater risk of extinction. We found a positive association between genetic variation and risk of extinction; i.e., species showing higher genetic variation had a greater risk of extinction. The relevance of these traits for conservation efforts is discussed.

Mergers, Acquisitions, and Alliances

© 2012 by Oxford University Press. All rights reserved.This article considers the determinants and effects of M&As in the pharmaceutical industry, with a particular focus on innovation and R&D productivity. As is the case in other industries, mergers in the pharmaceutical field are driven by a variety of company motives and conditions. These include defensive responses to industry shocks as well as more proactive rationales, such as economies of scale and scope, access to new technologies, and expansion to new markets. It is important to take account of firms' characteristics and motivations in evaluating merger performance, rather than using a broad aggregate brushstroke. Research to date on pharmaceuticals suggests considerable variation in both motivation and outcomes. From an antitrust policy standpoint, the larger horizontal mergers in pharmaceuticals have run into few challenges from regulatory authorities in the United States and the European Union, given the option to spin off competing therapeutic products to other drug firms.

The effect of differences in methodology among some recent applications of shearing quotients.

A shearing quotient (SQ) is a way of quantitatively representing the Phase I shearing edges on a molar tooth. Ordinary or phylogenetic least squares regression is fit to data on log molar length (independent variable) and log sum of measured shearing crests (dependent variable). The derived linear equation is used to generate an 'expected' shearing crest length from molar length of included individuals or taxa. Following conversion of all variables to real space, the expected value is subtracted from the observed value for each individual or taxon. The result is then divided by the expected value and multiplied by 100. SQs have long been the metric of choice for assessing dietary adaptations in fossil primates. Not all studies using SQ have used the same tooth position or crests, nor have all computed regression equations using the same approach. Here we focus on re-analyzing the data of one recent study to investigate the magnitude of effects of variation in 1) shearing crest inclusion, and 2) details of the regression setup. We assess the significance of these effects by the degree to which they improve or degrade the association between computed SQs and diet categories. Though altering regression parameters for SQ calculation has a visible effect on plots, numerous iterations of statistical analyses vary surprisingly little in the success of the resulting variables for assigning taxa to dietary preference. This is promising for the comparability of patterns (if not casewise values) in SQ between studies. We suggest that differences in apparent dietary fidelity of recent studies are attributable principally to tooth position examined.

Variation in Inpatient Rehabilitation Utilization After Hospitalization for Burn Injury in the United States.

Approximately 45,000 individuals are hospitalized annually for burn treatment. Rehabilitation after hospitalization can offer a significant improvement in functional outcomes. Very little is known nationally about rehabilitation for burns, and practices may vary substantially depending on the region based on observed Medicare post-hospitalization spending amounts. This study was designed to measure variation in rehabilitation utilization by state of hospitalization for patients hospitalized with burn injury. This retrospective cohort study used nationally collected data over a 10-year period (2001 to 2010), from the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SIDs). Patients hospitalized for burn injury (n = 57,968) were identified by ICD-9-CM codes and were examined to see specifically if they were discharged immediately to inpatient rehabilitation after hospitalization (primary endpoint). Both unadjusted and adjusted likelihoods were calculated for each state taking into account the effects of age, insurance status, hospitalization at a burn center, and extent of burn injury by TBSA. The relative risk of discharge to inpatient rehabilitation varied by as much as 6-fold among different states. Higher TBSA, having health insurance, higher age, and burn center hospitalization all increased the likelihood of discharge to inpatient rehabilitation following acute care hospitalization. There was significant variation between states in inpatient rehabilitation utilization after adjusting for variables known to affect each outcome. Future efforts should be focused on identifying the cause of this state-to-state variation, its relationship to patient outcome, and standardizing treatment across the United States.

Variation in pediatric traumatic brain injury outcomes in the United States.

OBJECTIVE: To ascertain the degree of variation, by state of hospitalization, in outcomes associated with traumatic brain injury (TBI) in a pediatric population. DESIGN: A retrospective cohort study of pediatric patients admitted to a hospital with a TBI. SETTING: Hospitals from states in the United States that voluntarily participate in the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. PARTICIPANTS: Pediatric (age ≤ 19 y) patients hospitalized for TBI (N=71,476) in the United States during 2001, 2004, 2007, and 2010. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Primary outcome was proportion of patients discharged to rehabilitation after an acute care hospitalization among alive discharges. The secondary outcome was inpatient mortality. RESULTS: The relative risk of discharge to inpatient rehabilitation varied by as much as 3-fold among the states, and the relative risk of inpatient mortality varied by as much as nearly 2-fold. In the United States, approximately 1981 patients could be discharged to inpatient rehabilitation care if the observed variation in outcomes was eliminated. CONCLUSIONS: There was significant variation between states in both rehabilitation discharge and inpatient mortality after adjusting for variables known to affect each outcome. Future efforts should be focused on identifying the cause of this state-to-state variation, its relationship to patient outcome, and standardizing treatment across the United States.

USE OF VARIATION AND FUGUE IN PIANO MUSIC FOLLOWING THE CLASSICAL PERIOD

The variation and fugue originated from the 15th and 16th centuries and blossomed during the Baroque and Classical Periods. In a variation, a theme with a particular structure precedes a series of pieces that usually have the same or very similar structure. A fugue is a work written in imitative counterpoint in which the theme is stated successively in all voices of polyphonic texture. Beethoven’s use of variation and fugue in large scale works greatly influenced his contemporaries. After the Classical Period, variations continued to be popular, and numerous composers employed the technique in various musical genres. Fugues had pedagogical associations, and by the middle of 19th century became a requirement in conservatory instruction, modeled after Bach’s Well-Tempered Clavier. In the 20th century, the fugue was revived in the spirit of neoclassicism; it was incorporated in sonatas, and sets of preludes and fugues were composed. Schubert's Wanderer Fantasy presents his song Der Wanderer through thematic transformations, including a fugue and a set of variations. Liszt was highly influenced by this, as shown in his thematic transformations and the fugue as one of the transformations in his Sonata in b. In Schumann’s Symphonic Études, Rachmaninoff's Rhapsody on a Theme of Paganini and Copland’s Piano Variations, the variation serves as the basis for the entire work. Prokofiev and Schubert take a different approach in Piano Concerto No. 3 and Wanderer Fantasy, employing the variation in a single movement. Unlike Schubert and Liszt's use of the fugue as a part of the piece or movement, Franck’s Prelude Chorale et Fugue and Shchedrin’s Polyphonic Notebook use it in its independent form. Since the Classical Period, the variation and fugue have evolved from stylistic and technical influences of earlier composers. It is interesting and remarkable to observe the unique effects each had on a particular work. As true and dependable classic forms, they remain popular by offering the composer an organizational framework for musical imagination.

Mainland size variation informs predictive models of exceptional insular body size change in rodents.

The tendency for island populations of mammalian taxa to diverge in body size from their mainland counterparts consistently in particular directions is both impressive for its regularity and, especially among rodents, troublesome for its exceptions. However, previous studies have largely ignored mainland body size variation, treating size differences of any magnitude as equally noteworthy. Here, we use distributions of mainland population body sizes to identify island populations as 'extremely' big or small, and we compare traits of extreme populations and their islands with those of island populations more typical in body size. We find that although insular rodents vary in the directions of body size change, 'extreme' populations tend towards gigantism. With classification tree methods, we develop a predictive model, which points to resource limitations as major drivers in the few cases of insular dwarfism. Highly successful in classifying our dataset, our model also successfully predicts change in untested cases.

Thermodynamic and dynamic contributions to future changes in regional precipitation variance: focus on the Southeastern United States

© 2014, Springer-Verlag Berlin Heidelberg.The frequency and severity of extreme events are tightly associated with the variance of precipitation. As climate warms, the acceleration in hydrological cycle is likely to enhance the variance of precipitation across the globe. However, due to the lack of an effective analysis method, the mechanisms responsible for the changes of precipitation variance are poorly understood, especially on regional scales. Our study fills this gap by formulating a variance partition algorithm, which explicitly quantifies the contributions of atmospheric thermodynamics (specific humidity) and dynamics (wind) to the changes in regional-scale precipitation variance. Taking Southeastern (SE) United States (US) summer precipitation as an example, the algorithm is applied to the simulations of current and future climate by phase 5 of Coupled Model Intercomparison Project (CMIP5) models. The analysis suggests that compared to observations, most CMIP5 models (~60 %) tend to underestimate the summer precipitation variance over the SE US during the 1950–1999, primarily due to the errors in the modeled dynamic processes (i.e. large-scale circulation). Among the 18 CMIP5 models analyzed in this study, six of them reasonably simulate SE US summer precipitation variance in the twentieth century and the underlying physical processes; these models are thus applied for mechanistic study of future changes in SE US summer precipitation variance. In the future, the six models collectively project an intensification of SE US summer precipitation variance, resulting from the combined effects of atmospheric thermodynamics and dynamics. Between them, the latter plays a more important role. Specifically, thermodynamics results in more frequent and intensified wet summers, but does not contribute to the projected increase in the frequency and intensity of dry summers. In contrast, atmospheric dynamics explains the projected enhancement in both wet and dry summers, indicating its importance in understanding future climate change over the SE US. The results suggest that the intensified SE US summer precipitation variance is not a purely thermodynamic response to greenhouse gases forcing, and cannot be explained without the contribution of atmospheric dynamics. Our analysis provides important insights to understand the mechanisms of SE US summer precipitation variance change. The algorithm formulated in this study can be easily applied to other regions and seasons to systematically explore the mechanisms responsible for the changes in precipitation extremes in a warming climate.

Synchrony between sensory and cognitive networks is associated with subclinical variation in autistic traits

© 2015 Young, Smith, Coutlee and Huettel.Individuals with autistic spectrum disorders exhibit distinct personality traits linked to attentional, social, and affective functions, and those traits are expressed with varying levels of severity in the neurotypical and subclinical population. Variation in autistic traits has been linked to reduced functional and structural connectivity (i.e., underconnectivity, or reduced synchrony) with neural networks modulated by attentional, social, and affective functions. Yet, it remains unclear whether reduced synchrony between these neural networks contributes to autistic traits. To investigate this issue, we used functional magnetic resonance imaging to record brain activation while neurotypical participants who varied in their subclinical scores on the Autism-Spectrum Quotient (AQ) viewed alternating blocks of social and nonsocial stimuli (i.e., images of faces and of landscape scenes). We used independent component analysis (ICA) combined with a spatiotemporal regression to quantify synchrony between neural networks. Our results indicated that decreased synchrony between the executive control network (ECN) and a face-scene network (FSN) predicted higher scores on the AQ. This relationship was not explained by individual differences in head motion, preferences for faces, or personality variables related to social cognition. Our findings build on clinical reports by demonstrating that reduced synchrony between distinct neural networks contributes to a range of subclinical autistic traits.

VARIATION FORMS: A SURVEY THROUGH FOUR CENTURIES OF VIOLIN REPERTOIRE

Variation, or the re-working of existing musical material, has consistently attracted the attention of composers and performers throughout the history of Western music. In three recorded recitals at the University of Maryland School of Music, this dissertation project explores a diverse range of expressive possibilities for violin in seven types of variation form in Austro-German works for violin from the 17th through the 20th centuries. The first program, consisting of Baroque Period works, performed on period instrument, includes the divisions on “John come kiss me now” from The Division Violin by Thomas Baltzar (1631 – 1663), constant bass variations in Sonate Unarum Fidium by Johann Heinrich von Schmelzer (1623 – 1680), arbitrary variation in Sonata for Violin and Continuo in E Major, Op. 1, No. 12 “Roger” by George Friedrich Händel (1685 – 1759), and French Double style, melodic-outline variation in Partita for Unaccompanied Violin in B Minor by Johan Sebastian Bach (1685 – 1750). Theme and Variations, a popular Classical Period format, is represented by the Sonata for Piano and Violin in G Major K. 379 by Wolfgang Amadeus Mozart (1756 – 1791) and Sonata for Violin and Piano in A Major, Op. 47 No. 9 the “Kreutzer” by Ludwig van Beethoven (1770 – 1827). Fantasy for Piano and Violin in C Major D. 934 by Franz Schubert (1797 – 1828) represents the 19th century fantasia variation. In these pieces, the piano and violin parts are densely interwoven, having equal importance. Many 20th century composers incorporated diverse types of variations in their works and are represented in the third recital program comprising: serial variation in the Phantasy for Violin and Piano Op.47 of Arnold Schoenberg (1874 – 1951); a strict form of melodic-outline variation in Sonate für Violine allein, Op. 31, No. 2 of Paul Hindemith (1895 – 1963); ostinato variation in Johan Halvorsen’s (1864 – 1935) Passacaglia for Violin and Viola, after G. F. Handel’s Passacaglia from the Harpsichord Suite No. 7 in G Minor. Pianist Audrey Andrist, harpsichordist Sooyoung Jung, and violist Dong-Wook Kim assisted in these performances.

Genomic and Functional Variation at a Normal Human Centromere

Centromeres are chromosomal loci essential for genome stability. Their malfunction can cause chromosome instability associated with cancer, infertility, and birth defects. This study focused on an intriguing centromere on human chromosome 17, which displays normal functional variation. Centromere identity can be found on either of two large arrays of repetitive DNA. We investigated inter-individual sequence variation on these two arrays and found association between array size, array variation, and centromere function. Our data suggest a functional influence of DNA sequence at this critical epigenetic locus.

A Quantitative Analysis of Growth and Size Regulation in Manduca sexta: The Physiological Basis of Variation in Size and Age at Metamorphosis.

Body size and development time are important life history traits because they are often highly correlated with fitness. Although the developmental mechanisms that control growth have been well studied, the mechanisms that control how a species-characteristic body size is achieved remain poorly understood. In insects adult body size is determined by the number of larval molts, the size increment at each molt, and the mechanism that determines during which instar larval growth will stop. Adult insects do not grow, so the size at which a larva stops growing determines adult body size. Here we develop a quantitative understanding of the kinetics of growth throughout larval life of Manduca sexta, under different conditions of nutrition and temperature, and for genetic strains with different adult body sizes. We show that the generally accepted view that the size increment at each molt is constant (Dyar's Rule) is systematically violated: there is actually a progressive increase in the size increment from instar to instar that is independent of temperature. In addition, the mass-specific growth rate declines throughout the growth phase in a temperature-dependent manner. We show that growth within an instar follows a truncated Gompertz trajectory. The critical weight, which determines when in an instar a molt will occur, and the threshold size, which determines which instar is the last, are different in genetic strains with different adult body sizes. Under nutrient and temperature stress Manduca has a variable number of larval instars and we show that this is due to the fact that more molts at smaller increments are taken before threshold size is reached. We test whether the new insight into the kinetics of growth and size determination are sufficient to explain body size and development time through a mathematical model that incorporates our quantitative findings.