How many more? Sample size determination in studies of morphological integration and evolvability

1. The variational properties of living organisms are an important component of current evolutionary theory. As a consequence, researchers working on the field of multivariate evolution have increasingly used integration and evolvability statistics as a way of capturing the potentially complex patterns of trait association and their effects over evolutionary trajectories. Little attention has been paid, however, to the cascading effects that inaccurate estimates of trait covariance have on these widely used evolutionary statistics. 2. Here, we analyse the relationship between sampling effort and inaccuracy in evolvability and integration statistics calculated from 10‐trait matrices with varying patterns of covariation and magnitudes of integration. We then extrapolate our initial approach to different numbers of traits and different magnitudes of integration and estimate general equations relating the inaccuracy of the statistics of interest to sampling effort. We validate our equations using a data set of cranial traits and use them to make sample size recommendations. 3. Our results suggest that highly inaccurate estimates of evolvability and integration statistics resulting from small sample sizes are likely common in the literature, given the sampling effort necessary to properly estimate them. We also show that patterns of covariation have no effect on the sampling properties of these statistics, but overall magnitudes of integration interact with sample size and lead to varying degrees of bias, imprecision and inaccuracy. 4. Finally, we provide r functions that can be used to calculate recommended sample sizes or to simply estimate the level of inaccuracy that should be expected in these statistics, given a sampling design

Correlated evolution of multivariate traits: detecting co-divergence across multiple dimensions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75039/1/j.1420-9101.2007.01415.x.pd

Rapid clearance profile of plasma circulating tumor HPV type 16 DNA during chemoradiotherapy correlates with disease control in HPV-associated oropharyngeal cancer

Purpose: To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Experimental Design: A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16- positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (types 16/18/31/33/35) in plasma. A control cohort of 55 healthy volunteers and 60 patients with non-HPV-associated malignancy was also analyzed. Results: Baseline plasma ctHPVDNA had high specificity (97%) and high sensitivity (89%) for detecting newly diagnosed HPV-associated OPSCC. Pretreatment ctHPV16DNA copy number correlated with disease burden, tumor HPV copy number, and HPV integration status. We define a ctHPV16DNA favorable clearance profile as having high baseline copy number (>200 copies/mL) and >95% clearance of ctHPV16DNA by day 28 of CRT. Nineteen of 67 evaluable patients had a ctHPV16DNA favorable clearance profile, and none had persistent or recurrent regional disease after CRT. In contrast, patients with adverse clinical risk factors (T4 or >10 pack years) and an unfavorable ctHPV16DNA clearance profile had a 35% actuarial rate of persistent or recurrent regional disease after CRT (P = 0.0049). Conclusions: A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPVassociated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters

High Precision Measurement of the Proton Elastic Form Factor Ratio μpGE/GM\mu_pG_E/G_M at low Q2Q^2

We report a new, high-precision measurement of the proton elastic form factor ratio \mu_p G_E/G_M for the four-momentum transfer squared Q^2 = 0.3-0.7 (GeV/c)^2. The measurement was performed at Jefferson Lab (JLab) in Hall A using recoil polarimetry. With a total uncertainty of approximately 1%, the new data clearly show that the deviation of the ratio \mu_p G_E/G_M from unity observed in previous polarization measurements at high Q^2 continues down to the lowest Q^2 value of this measurement. The updated global fit that includes the new results yields an electric (magnetic) form factor roughly 2% smaller (1% larger) than the previous global fit in this Q^2 range. We obtain new extractions of the proton electric and magnetic radii, which are ^(1/2)=0.875+/-0.010 fm and ^(1/2)=0.867+/-0.020 fm. The charge radius is consistent with other recent extractions based on the electron-proton interaction, including the atomic hydrogen Lamb shift measurements, which suggests a missing correction in the comparison of measurements of the proton charge radius using electron probes and the recent extraction from the muonic hydrogen Lamb shift.Comment: 12 pages, 3 figure