Civil Practice and Procedure

This article summarizes the major developments in Virginia civil practice and procedure over the past two years, specifically covering significant decisions by the Supreme Court of Virginiaand changes to the Rules of the Supreme Court of Virginia dating from April 22, 2005, to April 20, 2007. The article also addresses legislative enactments by the General Assembly in its 2005 and 2006 sessions

Ascertainment of Minimal Clinically Important Differences in the Diabetes Distress Scale-17: a Secondary analysis of a Randomized Clinical Trial

IMPORTANCE: The Diabetes Distress Scale-17 (DDS-17) is a common measure of diabetes distress. Despite its popularity, there are no agreed-on minimal clinically important difference (MCID) values for the DDS-17. OBJECTIVE: to establish a distribution-based metric for MCID in the DDS-17 and its 4 subscale scores (interpersonal distress, physician distress, regimen distress, and emotional distress). DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized clinical trial used baseline and postintervention data from a hybrid (implementation-effectiveness) trial evaluating Empowering Patients in Chronic Care (EPICC) vs an enhanced form of usual care (EUC). Participants included adults with uncontrolled type 2 diabetes (glycated hemoglobin A1c [HbA1c] level \u3e8.0%) who received primary care during the prior year in participating Department of Veterans Affairs clinics across Illinois, Indiana, and Texas. Data collection was completed in November 2018, and data analysis was completed in June 2023. INTERVENTIONS: Participants in EPICC attended 6 group sessions led by health care professionals based on collaborative goal-setting theory. EUC included diabetes education. MAIN OUTCOMES AND MEASURES: The main outcome was distribution-based MCID values for the total DDS-17 and 4 DDS-17 subscales, calculated using the standard error of measurement. Baseline to postintervention changes in DDS-17 and its 4 subscale scores were grouped into 3 categories: improved, no change, and worsened. Multilevel logistic and linear regression models examined associations between treatment group and MCID change categories and whether improvement in HbA1c varied in association with MCID category. RESULTS: A total of 248 individuals with complete DDS-17 data were included (mean [SD] age, 67.4 [8.3] years; 235 [94.76%] men), with 123 participants in the EPICC group and 125 participants in the EUC group. The MCID value for DDS-17 was 0.25 and MCID values for the 4 distress subscales were 0.38 for emotional and interpersonal distress and 0.39 for physician and regimen distress. Compared with EUC, more EPICC participants were in the MCID improvement category on DDS-17 (63 participants [51.22%] vs 40 participants [32.00%]; P = .003) and fewer EPICC participants were in the worsened category (20 participants [16.26%] vs 39 participants [31.20%]; P = .008). There was no direct association of DDS-17 MCID improvement (β = -0.25; 95% CI, -0.59 to 0.10; P = .17) or worsening (β = 0.18; 95% CI, -0.22 to 0.59; P = .38) with HbA1c levels among all participants. CONCLUSIONS AND RELEVANCE: In this secondary analysis of data from a randomized clinical trial, an MCID improvement or worsening of more than 0.25 on the DDS-17 was quantitatively significant and patients in the EPICC group were more likely to experience improvement than those in the EUC group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01876485

Survey of variation in human transcription factors reveals prevalent DNA binding changes

Published in final edited form as: Science. 2016 Mar 25; 351(6280): 1450–1454. Published online 2016 Mar 24. doi: 10.1126/science.aad2257Sequencing of exomes and genomes has revealed abundant genetic variation affecting the coding sequences of human transcription factors (TFs), but the consequences of such variation remain largely unexplored. We developed a computational, structure-based approach to evaluate TF variants for their impact on DNA binding activity and used universal protein-binding microarrays to assay sequence-specific DNA binding activity across 41 reference and 117 variant alleles found in individuals of diverse ancestries and families with Mendelian diseases. We found 77 variants in 28 genes that affect DNA binding affinity or specificity and identified thousands of rare alleles likely to alter the DNA binding activity of human sequence-specific TFs. Our results suggest that most individuals have unique repertoires of TF DNA binding activities, which may contribute to phenotypic variation.National Institutes of Health; NHGRI R01 HG003985; P50 HG004233; A*STAR National Science Scholarship; National Science Foundatio

Improving efficiency of analysis jobs in CMS

Hundreds of physicists analyze data collected by the Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider using the CMS Remote Analysis Builder and the CMS global pool to exploit the resources of the Worldwide LHC Computing Grid. Efficient use of such an extensive and expensive resource is crucial. At the same time, the CMS collaboration is committed to minimizing time to insight for every scientist, by pushing for fewer possible access restrictions to the full data sample and supports the free choice of applications to run on the computing resources. Supporting such variety of workflows while preserving efficient resource usage poses special challenges. In this paper we report on three complementary approaches adopted in CMS to improve the scheduling efficiency of user analysis jobs: automatic job splitting, automated run time estimates and automated site selection for jobs

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Bordetella pertussis Infection or Vaccination Substantially Protects Mice against B. bronchiseptica Infection

Although B. bronchiseptica efficiently infects a wide range of mammalian hosts and efficiently spreads among them, it is rarely observed in humans. In contrast to the many other hosts of B. bronchiseptica, humans are host to the apparently specialized pathogen B. pertussis, the great majority having immunity due to vaccination, infection or both. Here we explore whether immunity to B. pertussis protects against B. bronchiseptica infection. In a murine model, either infection or vaccination with B. pertussis induced antibodies that recognized antigens of B. bronchiseptica and protected the lower respiratory tract of mice against three phylogenetically disparate strains of B. bronchiseptica that efficiently infect naïve animals. Furthermore, vaccination with purified B. pertussis-derived pertactin, filamentous hemagglutinin or the human acellular vaccine, Adacel, conferred similar protection against B. bronchiseptica challenge. These data indicate that individual immunity to B. pertussis affects B. bronchiseptica infection, and suggest that the high levels of herd immunity against B. pertussis in humans could explain the lack of observed B. bronchiseptica transmission. This could also explain the apparent association of B. bronchiseptica infections with an immunocompromised state

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype

Measurement of associated Z plus charm production in proton-proton collisions at root s=8TeV

A study of the associated production of a Z boson and a charm quark jet (Z + c), and a comparison to production with a b quark jet (Z + b), in pp collisions at a centre-of-mass energy of 8 TeV are presented. The analysis uses a data sample corresponding to an integrated luminosity of 19.7 fb(-1), collected with the CMS detector at the CERN LHC. The Z boson candidates are identified through their decays into pairs of electrons or muons. Jets originating from heavy flavour quarks are identified using semileptonic decays of c or b flavoured hadrons and hadronic decays of charm hadrons. The measurements are performed in the kinematic region with two leptons with pT(l) > 20 GeV, vertical bar eta(l)vertical bar 25 GeV and vertical bar eta(jet)vertical bar Z + c + X) B(Z -> l(+)l(-)) = 8.8 +/- 0.5 (stat)+/- 0.6 (syst) pb. The ratio of the Z+c and Z+b production cross sections is measured to be sigma(pp -> Z+c+X)/sigma (pp -> Z+b+X) = 2.0 +/- 0.2 (stat)+/- 0.2 (syst). The Z+c production cross section and the cross section ratio are also measured as a function of the transverse momentum of theZ boson and of the heavy flavour jet. The measurements are compared with theoretical predictions.Peer reviewe

Measurement of the underlying event activity in inclusive Z boson production in proton-proton collisions at root s=13 TeV

This paper presents a measurement of the underlying event activity in proton-proton collisions at a center-of-mass energy of 13TeV, performed using inclusive Z boson production events collected with the CMS experiment at the LHC. The analyzed data correspond to an integrated luminosity of 2.1 fb(-1). The underlying event activity is quantified in terms of the charged particle multiplicity, as well as of the scalar sum of the charged particles' transverse momenta in different topological regions defined with respect to the Z boson direction. The distributions are unfolded to the stable particle level and compared with predictions from various Monte Carlo event generators, as well as with similar CDF and CMS measurements at center-of-mass energies of 1.96 and 7TeV respectively.Peer reviewe