Predicting the frequency dispersion of electronic hyperpolarizabilities on the basis of absorption data and thomas-kuhn sum rules

Successfully predicting the frequency dispersion of electronic hyperpolarizabilities is an unresolved challenge in materials science and electronic structure theory. We show that the generalized Thomas-Kuhn sum rules, combined with linear absorption data and measured hyperpolarizability at one or two frequencies, may be used to predict the entire frequency-dependent electronic hyperpolarizability spectrum. This treatment includes two- and three-level contributions that arise from the lowest two or three excited electronic state manifolds, enabling us to describe the unusual observed frequency dispersion of the dynamic hyperpolarizability in high oscillator strength M-PZn chromophores, where (porphinato)zinc(II) (PZn) and metal(II)polypyridyl (M) units are connected via an ethyne unit that aligns the high oscillator strength transition dipoles of these components in a head-to-tail arrangement. We show that some of these structures can possess very similar linear absorption spectra yet manifest dramatically different frequency dependent hyperpolarizabilities, because of three-level contributions that result from excited state-to excited state transition dipoles among charge polarized states. Importantly, this approach provides a quantitative scheme to use linear optical absorption spectra and very limited individual hyperpolarizability measurements to predict the entire frequency-dependent nonlinear optical response. Copyright © 2010 American Chemical Society.

Quantifying data quality for clinical trials using electronic data capture.

BACKGROUND: Historically, only partial assessments of data quality have been performed in clinical trials, for which the most common method of measuring database error rates has been to compare the case report form (CRF) to database entries and count discrepancies. Importantly, errors arising from medical record abstraction and transcription are rarely evaluated as part of such quality assessments. Electronic Data Capture (EDC) technology has had a further impact, as paper CRFs typically leveraged for quality measurement are not used in EDC processes. METHODS AND PRINCIPAL FINDINGS: The National Institute on Drug Abuse Treatment Clinical Trials Network has developed, implemented, and evaluated methodology for holistically assessing data quality on EDC trials. We characterize the average source-to-database error rate (14.3 errors per 10,000 fields) for the first year of use of the new evaluation method. This error rate was significantly lower than the average of published error rates for source-to-database audits, and was similar to CRF-to-database error rates reported in the published literature. We attribute this largely to an absence of medical record abstraction on the trials we examined, and to an outpatient setting characterized by less acute patient conditions. CONCLUSIONS: Historically, medical record abstraction is the most significant source of error by an order of magnitude, and should be measured and managed during the course of clinical trials. Source-to-database error rates are highly dependent on the amount of structured data collection in the clinical setting and on the complexity of the medical record, dependencies that should be considered when developing data quality benchmarks.

Electron tomography of cryofixed, isometrically contracting insect flight muscle reveals novel actin-myosin interactions.

BACKGROUND: Isometric muscle contraction, where force is generated without muscle shortening, is a molecular traffic jam in which the number of actin-attached motors is maximized and all states of motor action are trapped with consequently high heterogeneity. This heterogeneity is a major limitation to deciphering myosin conformational changes in situ. METHODOLOGY: We used multivariate data analysis to group repeat segments in electron tomograms of isometrically contracting insect flight muscle, mechanically monitored, rapidly frozen, freeze substituted, and thin sectioned. Improved resolution reveals the helical arrangement of F-actin subunits in the thin filament enabling an atomic model to be built into the thin filament density independent of the myosin. Actin-myosin attachments can now be assigned as weak or strong by their motor domain orientation relative to actin. Myosin attachments were quantified everywhere along the thin filament including troponin. Strong binding myosin attachments are found on only four F-actin subunits, the "target zone", situated exactly midway between successive troponin complexes. They show an axial lever arm range of 77°/12.9 nm. The lever arm azimuthal range of strong binding attachments has a highly skewed, 127° range compared with X-ray crystallographic structures. Two types of weak actin attachments are described. One type, found exclusively in the target zone, appears to represent pre-working-stroke intermediates. The other, which contacts tropomyosin rather than actin, is positioned M-ward of the target zone, i.e. the position toward which thin filaments slide during shortening. CONCLUSION: We present a model for the weak to strong transition in the myosin ATPase cycle that incorporates azimuthal movements of the motor domain on actin. Stress/strain in the S2 domain may explain azimuthal lever arm changes in the strong binding attachments. The results support previous conclusions that the weak attachments preceding force generation are very different from strong binding attachments.

Contracting Freedom: Governance and East Indian Indenture in the British Atlantic, 1838-1917

This is a dissertation about identity and governance, and how they are mutually constituted. Between 1838 and 1917, the British brought approximately half a million East Indian laborers to the Atlantic to work on sugar plantations. The dissertation argues that contrary to previous historiographical assumptions, indentured East Indians were an amorphous mass of people drawn from various regions of British India. They were brought together not by their innate "Indian-ness" upon their arrival in the Caribbean, but by the common experience of indenture recruitment, transportation and plantation life. Ideas of innate "Indian-ness" were products of an imperial discourse that emerged from and shaped official approaches to governing East Indians in the Atlantic. Government officials and planters promoted visions of East Indians as "primitive" subjects who engaged in child marriage and wife murder. Officials mobilized ideas about gender to sustain racialized stereotypes of East Indian subjects. East Indian women were thought to be promiscuous, and East Indian men were violent and depraved (especially in response to East Indian women's promiscuity). By pointing to these stereotypes about East Indians, government officials and planters could highlight the promise of indenture as a civilizing mechanism. This dissertation links the study of governance and subject formation to complicate ideas of colonial rule as static. It uncovers how colonial processes evolved to handle the challenges posed by migrant populations.

The primary architects of indenture, Caribbean governments, the British Colonial Office, and planters hoped that East Indian indentured laborers would form a stable and easily-governed labor force. They anticipated that the presence of these laborers would undermine the demands of Afro-Creole workers for higher wages and shorter working hours. Indenture, however, was controversial among British liberals who saw it as potentially hindering the creation of a free labor market, and abolitionists who also feared that indenture was a new form of slavery. Using court records, newspapers, legislative documents, bureaucratic correspondence, memoirs, novels, and travel accounts from archives and libraries in Britain, Guyana, and Trinidad and Tobago, this dissertation explores how indenture was envisioned and constantly re-envisioned in response to its critics. It chronicles how the struggles between the planter class and the colonial state for authority over indentured laborers affected the way that indenture functioned in the British Atlantic. In addition to focusing on indenture's official origins, this dissertation examines the actions of East Indian indentured subjects as they are recorded in the imperial archive to explore how these people experienced indenture.

Indenture contracts were central to the justification of indenture and to the creation of a pliable labor force in the Atlantic. According to English common law, only free parties could enter into contracts. Indenture contracts limited the period of indenture and affirmed that laborers would be remunerated for their labor. While the architects of indenture pointed to contracts as evidence that indenture was not slavery, contracts in reality prevented laborers from participating in the free labor market and kept the wages of indentured laborers low. Further, in late nineteenth-century Britain, contracts were civil matters. In the British Atlantic, indentured laborers who violated the terms of their contracts faced criminal trials and their associated punishments such as imprisonment and hard labor. Officials used indenture contracts to exploit the labor and limit the mobility of indentured laborers in a manner that was reminiscent of slavery but that instead established indentured laborers as subjects with limited rights. The dissertation chronicles how indenture contracts spawned a complex inter-imperial bureaucracy in British India, Britain, and the Caribbean that was responsible for the transportation and governance of East Indian indentured laborers overseas.

Electronic Techtonics: Thinking at the Interface

This volume originated in HASTAC’s first international conference, “Electronic Techtonics: Thinking at the Interface,” held at Duke University during April 19-21, 2007. “Electronic Techtonics” was the site of truly unforgettable conversations and encounters that traversed domains, disciplines, and media – conversations that explored the fluidity of technology both as interface as well as at the interface. This hardcopy version of the conference proceedings is published in conjunction with its electronic counterpart (found at www.hastac.org). Both versions exist as records of the range and depth of conversations that took place at the conference. Some of the papers in this volume are almost exact records of talks given at the conference, while others are versions that were revised and reworked some time after the conference. These papers are drawn from a variety of fields and we have not made an effort to homogenize them in any way, but have instead retained the individual format and style of each author.

Using electronic health record data for substance use Screening, Brief Intervention, and Referral to Treatment among adults with type 2 diabetes: Design of a National Drug Abuse Treatment Clinical Trials Network study.

BACKGROUND: The Affordable Care Act encourages healthcare systems to integrate behavioral and medical healthcare, as well as to employ electronic health records (EHRs) for health information exchange and quality improvement. Pragmatic research paradigms that employ EHRs in research are needed to produce clinical evidence in real-world medical settings for informing learning healthcare systems. Adults with comorbid diabetes and substance use disorders (SUDs) tend to use costly inpatient treatments; however, there is a lack of empirical data on implementing behavioral healthcare to reduce health risk in adults with high-risk diabetes. Given the complexity of high-risk patients' medical problems and the cost of conducting randomized trials, a feasibility project is warranted to guide practical study designs. METHODS: We describe the study design, which explores the feasibility of implementing substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT) among adults with high-risk type 2 diabetes mellitus (T2DM) within a home-based primary care setting. Our study includes the development of an integrated EHR datamart to identify eligible patients and collect diabetes healthcare data, and the use of a geographic health information system to understand the social context in patients' communities. Analysis will examine recruitment, proportion of patients receiving brief intervention and/or referrals, substance use, SUD treatment use, diabetes outcomes, and retention. DISCUSSION: By capitalizing on an existing T2DM project that uses home-based primary care, our study results will provide timely clinical information to inform the designs and implementation of future SBIRT studies among adults with multiple medical conditions.