Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer

BACKGROUND: New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain.METHODS: A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests.RESULTS: Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention-to-screen basis, including acceptability, is essential. Cancer-specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac-based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4-phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention-to-screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true-positive and false-positive rates, and the number needed to colonoscope to detect a target lesion.CONCLUSIONS: New screening tests can be evaluated efficiently by this stepwise comparative approach. Cancer 2016;122:826-39. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.</p

Convergent Evolution in Aquatic Tetrapods: Insights from an Exceptional Fossil Mosasaur

Mosasaurs (family Mosasauridae) are a diverse group of secondarily aquatic lizards that radiated into marine environments during the Late Cretaceous (98–65 million years ago). For the most part, they have been considered to be simple anguilliform swimmers – i.e., their propulsive force was generated by means of lateral undulations incorporating the greater part of the body – with unremarkable, dorsoventrally narrow tails and long, lizard-like bodies. Convergence with the specialized fusiform body shape and inferred carangiform locomotory style (in which only a portion of the posterior body participates in the thrust-producing flexure) of ichthyosaurs and metriorhynchid crocodyliform reptiles, along with cetaceans, has so far only been recognized in Plotosaurus, the most highly derived member of the Mosasauridae. Here we report on an exceptionally complete specimen (LACM 128319) of the moderately derived genus Platecarpus that preserves soft tissues and anatomical details (e.g., large portions of integument, a partial body outline, putative skin color markings, a downturned tail, branching bronchial tubes, and probable visceral traces) to an extent that has never been seen previously in any mosasaur. Our study demonstrates that a streamlined body plan and crescent-shaped caudal fin were already well established in Platecarpus, a taxon that preceded Plotosaurus by 20 million years. These new data expand our understanding of convergent evolution among marine reptiles, and provide insights into their evolution's tempo and mode

Measurement of the Branching Fraction for B- --> D0 K*-

We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid Communications

A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 ${\rm fb}^{-1}$ recorded at the $\Upsilon(4S)$ resonance and 3.9 ${\rm fb}^{-1}$ off-resonance. One of the neutral B mesons, which are produced in pairs at the $\Upsilon(4S)$, is fully reconstructed in the CP decay modes $J/\psi K^0_S$, $\psi(2S) K^0_S$, $\chi_{c1} K^0_S$, $J/\psi K^{*0}$ ($K^{*0}\to K^0_S\pi^0$) and $J/\psi K^0_L$, or in flavor-eigenstate modes involving $D^{(*)}\pi/\rho/a_1$ and $J/\psi K^{*0}$ ($K^{*0}\to K^+\pi^-$). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds $\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}$. The value of the asymmetry amplitude $\sin2\beta$ is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged $B^0$ decays in the CP-eigenstate modes. We find $\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}$, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review

Measurement of Branching Fraction and Dalitz Distribution for B0->D(*)+/- K0 pi-/+ Decays

We present measurements of the branching fractions for the three-body decays B0 -> D(*)-/+ K0 pi^+/-$and their resonant submodes$B0 -> D(*)-/+ K*+/- using a sample of approximately 88 million BBbar pairs collected by the BABAR detector at the PEP-II asymmetric energy storage ring. We measure: B(B0->D-/+ K0 pi+/-)=(4.9 +/- 0.7(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K0 pi+/-)=(3.0 +/- 0.7(stat) +/- 0.3 (syst)) 10^{-4} B(B0->D-/+ K*+/-)=(4.6 +/- 0.6(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K*+/-)=(3.2 +/- 0.6(stat) +/- 0.3 (syst)) 10^{-4} From these measurements we determine the fractions of resonant events to be : f(B0-> D-/+ K*+/-) = 0.63 +/- 0.08(stat) +/- 0.04(syst) f(B0-> D*-/+ K*+/-) = 0.72 +/- 0.14(stat) +/- 0.05(syst)Comment: 7 pages, 3 figures submitted to Phys. Rev. Let

Study of e+e- --> pi+ pi- pi0 process using initial state radiation with BABAR

The process e+e- --> pi+ pi- pi0 gamma has been studied at a center-of-mass energy near the Y(4S) resonance using a 89.3 fb-1 data sample collected with the BaBar detector at the PEP-II collider. From the measured 3pi mass spectrum we have obtained the products of branching fractions for the omega and phi mesons, B(omega --> e+e-)B(omega --> 3pi)=(6.70 +/- 0.06 +/- 0.27)10-5 and B(phi --> e+e-)B(phi --> 3pi)=(4.30 +/- 0.08 +/- 0.21)10-5, and evaluated the e+e- --> pi+ pi- pi0 cross section for the e+e- center-of-mass energy range 1.05 to 3.00 GeV. About 900 e+e- --> J/psi gamma --> pi+ pi- pi0 gamma events have been selected and the branching fraction B(J/psi --> pi+ pi- pi0)=(2.18 +/- 0.19)% has been measured.Comment: 21 pages, 37 postscript figues, submitted to Phys. Rev.

Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions

The weak nucleon axial-vector form factor for quasi-elastic interactions is determined using neutrino interaction data from the K2K Scintillating Fiber detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of which half are charged-current quasi-elastic interactions nu-mu n to mu- p occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for oxygen and assume the form factor is approximately a dipole with one parameter, the axial vector mass M_A, and fit to the shape of the distribution of the square of the momentum transfer from the nucleon to the nucleus. Our best fit result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated vector form factors from recent electron scattering experiments and a discussion of the effects of the nucleon momentum on the shape of the fitted distributions.Comment: 14 pages, 10 figures, 6 table

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Evidence for the Rare Decay B -> K*ll and Measurement of the B -> Kll Branching Fraction

We present evidence for the flavor-changing neutral current decay $B\to K^*\ell^+\ell^-$ and a measurement of the branching fraction for the related process $B\to K\ell^+\ell^-$, where $\ell^+\ell^-$ is either an $e^+e^-$ or $\mu^+\mu^-$ pair. These decays are highly suppressed in the Standard Model, and they are sensitive to contributions from new particles in the intermediate state. The data sample comprises $123\times 10^6$ $\Upsilon(4S)\to B\bar{B}$ decays collected with the Babar detector at the PEP-II $e^+e^-$ storage ring. Averaging over $K^{(*)}$ isospin and lepton flavor, we obtain the branching fractions ${\mathcal B}(B\to K\ell^+\ell^-)=(0.65^{+0.14}_{-0.13}\pm 0.04)\times 10^{-6}$ and ${\mathcal B}(B\to K^*\ell^+\ell^-)=(0.88^{+0.33}_{-0.29}\pm 0.10)\times 10^{-6}$, where the uncertainties are statistical and systematic, respectively. The significance of the $B\to K\ell^+\ell^-$ signal is over $8\sigma$, while for $B\to K^*\ell^+\ell^-$ it is $3.3\sigma$.Comment: 7 pages, 2 postscript figues, submitted to Phys. Rev. Let

Search for the W-exchange decays B0 --> Ds(*)- Ds(*)+

We report a search for the decays $B^{0} \to D_{s}^{-} D_{s}^{+}$, $B^{0} \to D_{s}^{*-} D_{s}^{+}$, $B^{0} \to D_{s}^{*-} D_{s}^{*+}$ in a sample of 232 million $\Upsilon(4S)$ decays to \BBb ~pairs collected with the \babar detector at the PEP-II asymmetric-energy $e^+ e^-$ storage ring. We find no significant signal and set upper bounds for the branching fractions: ${\cal B}(B^{0} \to D_{s}^{-} D_{s}^{+}) < 1.0 \times 10^{-4}, {\cal B}(B^{0} \to D_{s}^{*-} D_{s}^{+}) < 1.3 \times 10^{-4}$ and ${\cal B}(B^{0} \to D_{s}^{*-} D_{s}^{*+}) < 2.4 \times 10^{-4}$ at 90% confidence level.Comment: 8 pages, 2 figures, submitted to PRD-R