The development of norms of pediatric interpupillary distance

Interpupillary distances (PDs) were measured on 220 Caucasian children, newborn to six years of age, at fixation distances of 3 m and 40 em. A photographic method was used to determine the distance between the corneal light reflexes provided by the camera flash. The subjects were divided into six groups based on age. The average PDs (mm) for each age group were: Group 1 (newborn-11 months): NA/40.5; Group 2 (12-23 months): 46.5/43.0; Group 3 (24-35 months): 47.5/43.5; Group 4 (36-47 months): 49.5/46.0; Group 5 (48-59 months): 51.0/46.5; Group 6 (60-71 months): 51.0/46.5; far/near respectively

3Rs‐friendly approach to exogenous metabolic activation that supports high‐throughput genetic toxicology testing

MultiFlow® DNA Damage—p53, γH2AX, Phospho‐Histone H3 is a miniaturized, flow cytometry‐based assay that provides genotoxic mode of action information by distinguishing clastogens, aneugens, and nongenotoxicants. Work to date has focused on the p53‐competent human cell line TK6. While mammalian cell genotoxicity assays typically supply exogenous metabolic activation in the form of concentrated rat liver S9, this is a less‐than‐ideal approach for several reasons, including 3Rs considerations. Here, we describe our experiences with low concentration S9 and saturating co‐factors which were allowed to remain in contact with cells and test chemicals for 24 continuous hours. We exposed TK6 cells in 96‐well plates to each of 15 reference chemicals over a range of concentrations, both in the presence and absence of 0.25% v/v phenobarbital/β‐naphthoflavone‐induced rat liver S9. After 4 and 24 hr of treatment cell aliquots were added to wells of a microtiter plate containing the working detergent/stain/antibody cocktail. After a brief incubation robotic sampling was employed for walk‐away flow cytometric data acquisition. PROAST benchmark dose (BMD) modeling was used to characterize the resulting dose–response curves. For each of the 8 reference pro‐genotoxicants studied, relative nuclei count, γH2AX, and/or p53 biomarker BMD values were order(s) of magnitude lower for 0.25% S9 conditions compared to 0% S9. Conversely, several of the direct‐acting reference chemicals exhibited appreciably lower cytotoxicity and/or genotoxicity BMD values in the presence of S9 (eg, resorcinol). These results prove the efficacy of the low concentration S9 system, and indicate that an efficient and highly scalable multiplexed assay can effectively identify chemicals that require bioactivation to exert their genotoxic effects.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154945/1/em22361_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154945/2/em22361.pd

Assessing health risks from multiple environmental stressors: Moving from G×E to I×E.

Research on disease causation often attempts to isolate the effects of individual factors, including individual genes or environmental factors. This reductionist approach has generated many discoveries, but misses important interactive and cumulative effects that may help explain the broad range of variability in disease occurrence observed across studies and individuals. A disease rarely results from a single factor, and instead results from a broader combination of factors, characterized here as intrinsic (I) and extrinsic (E) factors. Intrinsic vulnerability or resilience emanates from a variety of both fixed and shifting biological factors including genetic traits, while extrinsic factors comprise all biologically-relevant external stressors encountered across the lifespan. The I×E concept incorporates the multi-factorial and dynamic nature of health and disease and provides a unified, conceptual basis for integrating results from multiple areas of research, including genomics, G×E, developmental origins of health and disease, and the exposome. We describe the utility of the I×E concept to better understand and characterize the cumulative impact of multiple extrinsic and intrinsic factors on individual and population health. New research methods increasingly facilitate the measurement of multifactorial and interactive effects in epidemiological and toxicological studies. Tiered or indicator-based approaches can guide the selection of potentially relevant I and E factors for study and quantification, and exposomics methods may eventually produce results that can be used to generate a response function over the life course. Quantitative data on I×E interactive effects should generate a better understanding of the variability in human response to environmental factors. The proposed I×E concept highlights the role for broader study design in order to identify extrinsic and intrinsic factors amenable to interventions at the individual and population levels in order to enhance resilience, reduce vulnerability and improve health

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Measurements of branching fraction ratios and CP-asymmetries in suppressed B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^- decays

We report the first reconstruction in hadron collisions of the suppressed decays B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^-, sensitive to the CKM phase gamma, using data from 7 fb^-1 of integrated luminosity collected by the CDF II detector at the Tevatron collider. We reconstruct a signal for the B^- -> D(-> K^+ pi^-)K^- suppressed mode with a significance of 3.2 standard deviations, and measure the ratios of the suppressed to favored branching fractions R(K) = [22.0 \pm 8.6(stat)\pm 2.6(syst)]\times 10^-3, R^+(K) = [42.6\pm 13.7(stat)\pm 2.8(syst)]\times 10^-3, R^-(K)= [3.8\pm 10.3(stat)\pm 2.7(syst]\times 10^-3, as well as the direct CP-violating asymmetry A(K) = -0.82\pm 0.44(stat)\pm 0.09(syst) of this mode. Corresponding quantities for B^- -> D(-> K^+ pi^-)pi^- decay are also reported.Comment: 8 pages, 1 figure, accepted by Phys.Rev.D Rapid Communications for Publicatio

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic