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We present a method for estimating partial atomic charges that uses all of the measured ionization energies (first, second, third, etc.) for every atom in the periodic table. We build on the charge equilibration (Qeq) method of Rappé and Goddard (which used only the first ionization energies) but reduce the number of ad hoc parameters from at least one for every type of atom to just two global parameters: a dielectric strength and a modified parameter for hydrogen atoms. Periodic electrostatic interactions are calculated via Ewald sums, and the partial charges are determined by simultaneously solving a system of linear equations; no iteration is required. We compare the predicted partial atomic charges of this extended charge equilibration (EQeq) scheme against plane-wave density-functional theory derived charges determined via the REPEAT method for 12 diverse metal-organic frameworks (MOFs). We also compare EQeq charges against ChelpG charges calculated using nonperiodic MOF fragments, as well as against Qeq charges as implemented in Accelrys Materials Studio. We demonstrate that for the purpose of ranking MOFs from best to worst for carbon capture applications, EQeq charges perform as well as charges derived from electrostatic potentials, but EQeq requires only a tiny fraction of the computational cost (seconds vs days for the MOFs studied). The source code for the EQeq algorithm is provided.

The strength of association between surrogate end points and survival in oncology is important to understand because surrogate end points are frequently used in oncology clinical trials, supporting US Food and Drug Administration approvals and National Comprehensive Cancer Network guideline recommendations. OBJECTIVE To identify and evaluate trial-level meta-analyses of randomized clinical trials quantifying the association between a surrogate end point and overall survival in medical oncology. Trial-level correlations test whether treatments that improve the surrogate end point also improve the final end point and are widely considered the strongest evidence to validate a surrogate end point. EVIDENCE REVIEW Our literature search was built on earlier reported data sets and updated with Google Scholar and MEDLINE searches conducted on December 26, 2014. For MEDLINE, search terms included ("regression" or "correlation") and "surrogate" and "end point [or endpoint]" and ("oncology" or "cancer"). For Google scholar, search terms included ("regression" or "correlation") and "surrogate end point [or endpoint]" and "overall survival" and "trial level." A total of 108 abstracts were retrieved, and 62 articles were read in full in addition to articles identified through prior reviews. FINDINGS We found 36 articles in which 65 specific correlations between a surrogate end point and survival were identified. Surrogate end points were studied in the neoadjuvant, adjuvant, locally advanced, and metastatic settings. The most common sources for trials included in the 36 articles were systematic reviews of the published literature (10 of 36; 28%), and published literature and meeting abstracts (14 of 36; 39%). Four meta-analyses (11%) used a convenience sample, and only 5 studies (14%) attempted to include unpublished trials by surveying clinical trial registries. Among these 5 studies, only 352 of 684 eligible trials (51.1%) were included in the analyses. More than half of reported correlations (34 of 65; 52%) were of low strength (r Յ 0.7). Approximately a quarter (16 of 65; 25%) were of medium strength (r > 0.7 to r < 0.85), and 15 of 65 (23%) were highly correlated (r Ն 0.85) with survival. CONCLUSIONS AND RELEVANCE Most trial-level validation studies of surrogate end points in oncology find low correlations with survival. All validation studies use only a subset of available trials. The evidence supporting the use of surrogate end points in oncology is limited.

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