An empirical comparison of methods for meta-analysis of diagnostic accuracy showed hierarchical models are necessary

OBJECTIVE: Meta-analysis of studies of the accuracy of diagnostic tests currently uses a variety of methods. Statistically rigorous hierarchical models require expertise and sophisticated software. We assessed whether any of the simpler methods can in practice give adequately accurate and reliable results. STUDY DESIGN AND SETTING: We reviewed six methods for meta-analysis of diagnostic accuracy: four simple commonly used methods (simple pooling, separate random-effects meta-analyses of sensitivity and specificity, separate meta-analyses of positive and negative likelihood ratios, and the Littenberg-Moses summary receiver operating characteristic [ROC] curve) and two more statistically rigorous approaches using hierarchical models (bivariate random-effects meta-analysis and hierarchical summary ROC curve analysis). We applied the methods to data from a sample of eight systematic reviews chosen to illustrate a variety of patterns of results. RESULTS: In each meta-analysis, there was substantial heterogeneity between the results of different studies. Simple pooling of results gave misleading summary estimates of sensitivity and specificity in some meta-analyses, and the Littenberg-Moses method produced summary ROC curves that diverged from those produced by more rigorous methods in some situations. CONCLUSION: The closely related hierarchical summary ROC curve or bivariate models should be used as the standard method for meta-analysis of diagnostic accuracy.

Survival of bonded lingual retainers with chemical or photo polymerization over a 2-year period: a single-center, randomized controlled clinical trial

INTRODUCTION The objective of this trial was to compare the survival rates of mandibular lingual retainers bonded with either chemically cured or light-cured adhesive after orthodontic treatment. METHODS Patients having undergone orthodontic treatment at a private orthodontic office were randomly allocated to fixed retainers placed with chemically cured composite or light-cured composite. Eligibility criteria included no active caries, restorations, or fractures on the mandibular anterior teeth, and adequate oral hygiene. The main outcome was any type of first-time lingual retainer breakage; pattern of failure (adapted adhesive remnant index scores) was a secondary outcome. Randomization was accomplished with random permuted blocks of 20 patients with allocation concealed in sequentially numbered, opaque, sealed envelopes. Blinding was applicable for outcome assessment only. Patients were reviewed at 1, 3, and 6 months and then every 6 months after placement of the retainer until completion of the study. Data were analyzed using survival analysis including Cox regression; sensitivity analysis was carried out after data imputation for subjects lost to follow-up. RESULTS Two hundred twenty patients (median age, 16 years; interquartile range, 2; range, 12-47 years) were randomized in a 1:1 ratio to either chemical or light curing. Baseline characteristics were similar between groups, the median follow-up period was 2.19 years (range, 0.003-3.64 years), and 16 patients were lost to follow-up. At a minimum follow-up of 2 years, 47 of 110 (42.7%) and 55 of 110 (50.0%) retainers had some type of failure with chemically cured and light-cured adhesive, respectively (log-rank test, P = 0.35). Data were analyzed on an intention-to-treat basis, and the hazard ratio (HR) was 1.15 (95% confidence interval [CI], 0.88-1.70; P = 0.47). There was weak evidence that age is a significant predictor for lingual retainer failures (HR, 0.96; 95% CI, 0.93-1.00; P = 0.08). Adhesive remnant index scoring was possible for only 66 of the 102 (64.7%) failures and did not differ between composites (Fisher exact test, P = 0.16). No serious harm was observed other than gingivitis associated with plaque accumulation. CONCLUSIONS The results of this study indicated no evidence that survival of mandibular lingual retainers differs between chemically and light-cured adhesives. The overall failure rate was 46.4%; however, this included any type of failure, which may have exaggerated the overall failure rate.

Prognosis of Children with HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa: A Collaborative Analysis of Treatment Programs

BACKGROUND: Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. METHODS: We analyzed data from children ≤10 years old who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004-2010. Children lost to follow-up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct two prognostic models: one with CD4%, age, WHO clinical stage, weight-for-age z-score (WAZ) and anemia and one without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. RESULTS: Among 12655 children, 877 (6.9%) died in the first year of ART. 1780 children were lost to follow-up/transferred and excluded from main analyses; 10875 children were included. With the CD4% model probability of death at 1 year ranged from 1.8% (95% CI: 1.5-2.3) in children 5-10 years with CD4% ≥10%, WHO stage I/II, WAZ ≥-2 and without severe anemia to 46.3% (95% CI: 38.2-55.2) in children <1 year with CD4% <5%, stage III/IV, WAZ< -3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8-2.7) to 33.4% (95% CI: 28.2-39.3). Agreement between predicted and observed mortality was good (C-statistics=0.753 and 0.745 for models with and without CD4% respectively). CONCLUSION: These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.

Heterotic T-folds with a small number of neutral moduli

We discuss non-geometric supersymmetric heterotic string models in D=4, in the framework of the free fermionic construction. We perform a systematic scan of models with four a priori left-right asymmetric Z2 projections and shifts. We analyze some 220 models, identifying 18 inequivalent classes and addressing variants generated by discrete torsions. They do not contain geometrical or trivial neutral moduli, apart from the dilaton. However, we show the existence of flat directions in the form of exactly marginal deformations and identify patterns of symmetry breaking where product gauge groups, realized at level one, are broken to their diagonal at higher level. We also describe an “inverse Gepner map” from Heterotic to Type II models that could be used, in certain non geometric settings, to define “effective” topological invariants.

Recurrent stroke predictors differ in medically treated patients with pathogenic vs other PFOs

OBJECTIVE: To examine predictors of stroke recurrence in patients with a high vs a low likelihood of having an incidental patent foramen ovale (PFO) as defined by the Risk of Paradoxical Embolism (RoPE) score.METHODS: Patients in the RoPE database with cryptogenic stroke (CS) and PFO were classified as having a probable PFO-related stroke (RoPE score of >6, n = 647) and others (RoPE score of with stroke recurrence using Cox survival models with component database as a stratification factor. An interaction with RoPE score was checked for the variables that were significant.RESULTS: Follow-up was available for 92%, 79%, and 57% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA. For all other predictors, effects were significantly different in the 2 RoPE score categories. For the low RoPE score group, but not the high RoPE score group, older age and antiplatelet (vs warfarin) treatment predicted recurrence. Conversely, echocardiographic features (septal hypermobility and a small shunt) and a prior (clinical) stroke/TIA were significant predictors in the high but not low RoPE score group.CONCLUSION: Predictors of recurrence differ when PFO relatedness is classified by the RoPE score, suggesting that patients with CS and PFO form a heterogeneous group with different stroke mechanisms. Echocardiographic features were only associated with recurrence in the high RoPE score group.

Multi-channel search for squarks and gluinos in sqrts=7 TeV pp collisions with the ATLAS detector

A search for supersymmetric particles in final states with zero, one, and two leptons, with and without jets identified as originating from b-quarks, in 4.7 fb(-1) of root s = 7 TeV pp collisions produced by the Large Hadron Collider and recorded by the ATLAS detector is presented. The search uses a set of variables carrying information on the event kinematics transverse and parallel to the beam line that are sensitive to several topologies expected in supersymmetry. Mutually exclusive final states are defined, allowing a combination of all channels to increase the search sensitivity. No deviation from the Standard Model expectation is observed. Upper limits at 95 % confidence level on visible cross-sections for the production of new particles are extracted. Results are interpreted in the context of the constrained minimal supersymmetric extension to the Standard Model and in supersymmetry-inspired models with diverse, high-multiplicity final states.

Search for supersymmetry in events with photons, bottom quarks, and missing transverse momentum in proton-proton collisions at a centre-of-mass energy of 7 TeV with the ATLAS detector

A search has been performed for the experimental signature of an isolated photon with high transverse momentum, at least one jet identified as originating from a bottom quark, and high missing transverse momentum. Such a final state may originate from supersymmetric models with gauge-mediated supersymmetry breaking in events in which one of a pair of higgsino-like neutralinos decays into a photon and a gravitino while the other decays into a Higgs boson and a gravitino. The search is performed using the full dataset of 7 TeV proton-proton collisions recorded with the ATLAS detector at the LHC in 2011, corresponding to an integrated luminosity of 4.7 fb(-1). A total of 7 candidate events are observed while 7.5 +/- 2.2 events are expected from the Standard Model background. The results of the search are interpreted in the context of general gauge mediation to exclude certain regions of a benchmark plane for higgsino-like neutralino production.

Search for dark matter candidates and large extra dimensions in events with a photon and missing transverse momentum in pp collision data at sqrts=7 TeV w the ATLAS detector

Results of a search for new phenomena in events with an energetic photon and large missing transverse momentum in proton-proton collisions at root s = 7 TeV are reported. Data collected by the ATLAS experiment at the LHC corresponding to an integrated luminosity of 4.6 fb(-1) are used. Good agreement is observed between the data and the standard model predictions. The results are translated into exclusion limits on models with large extra spatial dimensions and on pair production of weakly interacting dark matter candidates.

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using 4.7 fb⁻¹ of sqrts=7 TeV proton-pro collision data

A search for squarks and gluinos in final states containing jets, missing transverse momentum and no high-p(T) electrons or muons is presented. The data represent the complete sample recorded in 2011 by the ATLAS experiment in 7 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 4.7 fb(-1). No excess above the Standard Model background expectation is observed. Gluino masses below 860 GeV and squark masses below 1320 GeV are excluded at the 95% confidence level in simplified models containing only squarks of the first two generations, a gluino octet and a massless neutralino, for squark or gluino masses below 2 TeV, respectively. Squarks and gluinos with equal masses below 1410 GeV are excluded. In minimal supergravity/constrained minimal supersymmetric Standard Model models with tan beta = 10, A(0) = 0 and mu > 0, squarks and gluinos of equal mass are excluded for masses below 1360 GeV. Constraints are also placed on the parameter space of supersymmetric models with compressed spectra. These limits considerably extend the region of supersymmetric parameter space excluded by previous measurements with the ATLAS detector.

Search for charginos nearly mass-degenerate with the lightest neutralino based on a disappearing-track signature in pp collisions at sqrts = 8 TeV with the ATLAS detector

A search is presented for direct chargino production based on a disappearing-track signature using 20.3  fb−1 of proton-proton collisions at s√=8  TeV collected with the ATLAS experiment at the LHC. In anomaly-mediated supersymmetry breaking (AMSB) models, the lightest chargino is nearly mass degenerate with the lightest neutralino and its lifetime is long enough to be detected in the tracking detectors by identifying decays that result in tracks with no associated hits in the outer region of the tracking system. Some models with supersymmetry also predict charginos with a significant lifetime. This analysis attains sensitivity for charginos with a lifetime between 0.1 and 10 ns, and significantly surpasses the reach of the LEP experiments. No significant excess above the background expectation is observed for candidate tracks with large transverse momentum, and constraints on chargino properties are obtained. In the AMSB scenarios, a chargino mass below 270 GeV is excluded at 95% confidence level.

First order thermal phase transition with 126 GeV Higgs mass

We study the strength of the electroweak phase transition in models with two light Higgs doublets and a light SU(3)c triplet by means of lattice simulations in a dimensionally reduced effective theory. In the parameter region considered the transition on the lattice is significantly stronger than indicated by a 2-loop perturbative analysis. Within some ultraviolet uncertainties, the finding applies to MSSM with a Higgs mass mh ≈ 126 GeV and shows that the parameter region useful for electroweak baryogenesis is enlarged. In particular (even though only dedicated analyses can quantify the issue), the tension between LHC constraints after the 7 TeV and 8 TeV runs and frameworks where the electroweak phase transition is driven by light stops, seems to be relaxed.

Determinants of antithrombotic choice for patent foramen ovale in cryptogenic stroke

Objective: We examined the influence of clinical, radiologic, and echocardiographic characteristics on antithrombotic choice in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), hypothesizing that features suggestive of paradoxical embolism might lead to greater use of anticoagulation. Methods: The Risk of Paradoxical Embolism Study combined 12 databases to create the largest dataset of patients with CS and known PFO status. We used generalized linear mixed models with a random effect of component study to explore whether anticoagulation was preferentially selected based on the following: (1) younger age and absence of vascular risk factors, (2) “high-risk” echocardiographic features, and (3) neuroradiologic findings. Results: A total of 1,132 patients with CS and PFO treated with anticoagulation or antiplatelets were included. Overall, 438 participants (39%) were treated with anticoagulation with a range (by database) of 22% to 54%. Treatment choice was not influenced by age or vascular risk factors. However, neuroradiologic findings (superficial or multiple infarcts) and high-risk echocardiographic features (large shunts, shunt at rest, and septal hypermobility) were predictors of anticoagulation use. Conclusion: Both antithrombotic regimens are widely used for secondary stroke prevention in patients with CS and PFO. Radiologic and echocardiographic features were strongly associated with treatment choice, whereas conventional vascular risk factors were not. Prior observational studies are likely to be biased by confounding by indication.

Gauged R-symmetry and its anomalies in 4D N=1 supergravity and phenomenological implications

We consider a class of models with gauged U(1) R symmetry in 4D N=1 super-gravity that have, at the classical level, a metastable ground state, an infinitesimally small (tunable) positive cosmological constant and a TeV gravitino mass. We analyse if these properties are maintained under the addition of visible sector (MSSM-like) and hidden sector state(s), where the latter may be needed for quantum consistency. We then discuss the anomaly cancellation conditions in supergravity as derived by Freedman, Elvang and Körs and apply their results to the special case of a U(1) R symmetry, in the presence of the Fayet-Iliopoulos term (ξ) and Green-Schwarz mechanism(s). We investigate the relation of these anomaly cancellation conditions to the “naive” field theory approach in global SUSY, in which case U(1) R cannot even be gauged. We show the two approaches give similar conditions. Their induced constraints at the phenomenological level, on the above models, remain strong even if one lifted the GUT-like conditions for the MSSM gauge couplings. In an anomaly-free model, a tunable, TeV-scale gravitino mass may remain possible provided that the U(1) R charges of additional hidden sector fermions (constrained by the cubic anomaly alone) do not conflict with the related values of U(1) R charges of their scalar superpartners, constrained by existence of a stable ground state. This issue may be bypassed by tuning instead the coefficients of the Kahler connection anomalies (b K , b CK ).

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton--proton collision data

A search for squarks and gluinos in final states containing high-pT jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in √s = 8TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850GeV (440GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A0 = −2m0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector.

Search for supersymmetry in events with four or more leptons in √s = 8 TeV pp collisions with the ATLAS detector

Results from a search for supersymmetry in events with four or more leptons including electrons, muons and taus are presented. The analysis uses a data sample corresponding to 20.3  fb −1 of proton-proton collisions delivered by the Large Hadron Collider at s √ =8  TeV and recorded by the ATLAS detector. Signal regions are designed to target supersymmetric scenarios that can be either enriched in or depleted of events involving the production of a Z boson. No significant deviations are observed in data from standard model predictions and results are used to set upper limits on the event yields from processes beyond the standard model. Exclusion limits at the 95% confidence level on the masses of relevant supersymmetric particles are obtained. In R -parity-violating simplified models with decays of the lightest supersymmetric particle to electrons and muons, limits of 1350 and 750 GeV are placed on gluino and chargino masses, respectively. In R -parity-conserving simplified models with heavy neutralinos decaying to a massless lightest supersymmetric particle, heavy neutralino masses up to 620 GeV are excluded. Limits are also placed on other supersymmetric scenarios.