The SmartTarget BIOPSY trial: A prospective, within-person randomised, blinded trial comparing the accuracy of visual-registration and MRI/ultrasound image-fusion targeted biopsies for prostate cancer risk stratification

Background: Multiparametric magnetic resonance imaging (mpMRI)-targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the overdetection of insignificant cancers. Whether visual-registration targeting is sufficient or if augmentation with image-fusion software is needed is unknown. Objective: To assess concordance between the two methods. Design, Setting, and Participants: We conducted a blinded, within-person randomised, paired validating clinical trial. From 2014 to 2016, 141 men who had undergone a prior (positive or negative) transrectal ultrasound biopsy and had a discrete lesion on mpMRI (score 3 to 5) requiring targeted transperineal biopsy were enrolled at a UK academic hospital; 129 underwent both biopsy strategies and completed the study. Intervention: The order of performing biopsies using visual-registration and a computer-assisted MRI/ultrasound image-fusion system (SmartTarget) on each patient was randomised. The equipment was reset between biopsy strategies to mitigate incorporation bias. Outcome Measurements and Statistical Analysis: The proportion of clinically significant prostate cancer (primary outcome: Gleason pattern ≥3+4=7, maximum cancer core length ≥4 mm; secondary outcome: Gleason pattern ≥4+3=7, maximum cancer core length ≥6 mm) detected by each method was compared using McNemar's test of paired proportions. Results and Limitations: The two strategies combined detected 93 clinically significant prostate cancers (72% of the cohort). Each strategy individually detected 80/93 (86%) of these cancers; each strategy detected 13 cases missed by the other. Three patients experienced adverse events related to biopsy (urinary retention, urinary tract infection, nausea and vomiting). No difference in urinary symptoms, erectile function, or quality of life between baseline and follow-up (median 10.5 weeks) was observed. The key limitation was lack of parallel-group randomisation and limit on number of targeted cores. Conclusions: Visual-registration and image-fusion targeting strategies combined had the highest detection rate for clinically significant cancers. Targeted prostate biopsy should be performed using both strategies together. Patient Summary: We compared two prostate cancer biopsy strategies: visual-registration and image-fusion. The combination of the two strategies found the most clinically important cancers and should be used together whenever targeted biopsy is being performed

Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials

Objective: Interobserver agreement in the context of oral epithelial dysplasia (OED) grading has been notoriously unreliable and can impose barriers for developing new molecular markers and diagnostic technologies. This paper aimed to report the details of a 3-stage histopathology review and adjudication process with the goal of achieving a consensus histopathologic diagnosis of each biopsy. Study Design: Two adjacent serial histologic sections of oral lesions from 846 patients were independently scored by 2 different pathologists from a pool of 4. In instances where the original 2 pathologists disagreed, a third, independent adjudicating pathologist conducted a review of both sections. If a majority agreement was not achieved, the third stage involved a face-to-face consensus review. Results: Individual pathologist pair κ values ranged from 0.251 to 0.706 (fair-good) before the 3-stage review process. During the initial review phase, the 2 pathologists agreed on a diagnosis for 69.9% of the cases. After the adjudication review by a third pathologist, an additional 22.8% of cases were given a consensus diagnosis (agreement of 2 out of 3 pathologists). After the face-to-face review, the remaining 7.3% of cases had a consensus diagnosis. Conclusions: The use of the defined protocol resulted in a substantial increase (30%) in diagnostic agreement and has the potential to improve the level of agreement for establishing gold standards for studies based on histopathologic diagnosis

Exciton Spin Dynamics in Semiconductor Quantum Wells

In this paper we will review Exciton Spin Dynamics in Semiconductor Quantum Wells. The spin properties of excitons in nanostructures are determined by their fine structure. We will mainly focus in this review on GaAs and InGaAs quantum wells which are model systems.Comment: 55 pages, 27 figure

The Milky Way Bulge: Observed properties and a comparison to external galaxies

The Milky Way bulge offers a unique opportunity to investigate in detail the role that different processes such as dynamical instabilities, hierarchical merging, and dissipational collapse may have played in the history of the Galaxy formation and evolution based on its resolved stellar population properties. Large observation programmes and surveys of the bulge are providing for the first time a look into the global view of the Milky Way bulge that can be compared with the bulges of other galaxies, and be used as a template for detailed comparison with models. The Milky Way has been shown to have a box/peanut (B/P) bulge and recent evidence seems to suggest the presence of an additional spheroidal component. In this review we summarise the global chemical abundances, kinematics and structural properties that allow us to disentangle these multiple components and provide constraints to understand their origin. The investigation of both detailed and global properties of the bulge now provide us with the opportunity to characterise the bulge as observed in models, and to place the mixed component bulge scenario in the general context of external galaxies. When writing this review, we considered the perspectives of researchers working with the Milky Way and researchers working with external galaxies. It is an attempt to approach both communities for a fruitful exchange of ideas.Comment: Review article to appear in "Galactic Bulges", Editors: Laurikainen E., Peletier R., Gadotti D., Springer Publishing. 36 pages, 10 figure

‘Cytology-on-a-chip’ based sensors for monitoring of potentially malignant oral lesions

Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. Objective To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. Materials and methods Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new ‘cytology-on-a-chip’ approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. Results Binary “low-risk”/“high-risk” models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity + specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. Conclusions This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum

Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya

Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization

Global Search for New Physics with 2.0/fb at CDF

Data collected in Run II of the Fermilab Tevatron are searched for indications of new electroweak-scale physics. Rather than focusing on particular new physics scenarios, CDF data are analyzed for discrepancies with the standard model prediction. A model-independent approach (Vista) considers gross features of the data, and is sensitive to new large cross-section physics. Further sensitivity to new physics is provided by two additional algorithms: a Bump Hunter searches invariant mass distributions for "bumps" that could indicate resonant production of new particles; and the Sleuth procedure scans for data excesses at large summed transverse momentum. This combined global search for new physics in 2.0/fb of ppbar collisions at sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D Rapid Communication

Observation of Orbitally Excited B_s Mesons

We report the first observation of two narrow resonances consistent with states of orbitally excited (L=1) B_s mesons using 1 fb^{-1} of ppbar collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the Fermilab Tevatron. We use two-body decays into K^- and B^+ mesons reconstructed as B^+ \to J/\psi K^+, J/\psi \to \mu^+ \mu^- or B^+ \to \bar{D}^0 \pi^+, \bar{D}^0 \to K^+ \pi^-. We deduce the masses of the two states to be m(B_{s1}) = 5829.4 +- 0.7 MeV/c^2 and m(B_{s2}^*) = 5839.7 +- 0.7 MeV/c^2.Comment: Version accepted and published by Phys. Rev. Let

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe