"Greedy For Facts": Charles Darwin's Information Needs and Behaviors

Aptly describing himself as "greedy for facts" and exercising "industry in observing and collecting facts", Charles Darwin passionately sought and assiduously organized, managed, communicated, and used information throughout his life. From a 21st-century information age perspective, Darwin can be seen as a pre-Melvil Dewey, multidisciplinary, Victorian era proto-information manager, whose skillfully-employed information behaviors were fundamental to realizing his seminal Origin of Species (1859) and in influencing his life-long scientific development. A large body of research about Darwin exists but little has been written in the library and information science (LIS) field regarding Darwin and his pivotal relationship with information. Human information behavior (HIB) is an emerging LIS subfield, which has principally studied the information needs and information seeking behaviors of modern era human beings. Cambridge University is the foremost provider of print and electronic access to more than 14,000 transcribed and edited extant letters written by and to Darwin. Using historical case study methodology, this dissertation applies an HIB-oriented approach to investigate and inventory Darwin's information needs and behaviors through analysis of his surviving correspondence and other primary and secondary Darwin-related scholarly sources. A general framework is developed, designating five interrelated, broad context information behavior (BCIB) classification categories for conceptualizing Darwin's information behavior roles: as information seeker, organizer, manager, communicator, and user. In the vein of Ellis et al.'s (1993) study designating eight information seeking behaviors exhibited by contemporary British scientists, this dissertation utilizes grounded theory to derive and explain more than fifty descriptive information behaviors (DIBs) exhibited by Darwin. DIBs are conceptual constructs which are used to specify and describe, via words and examples from Darwin's correspondence and writings, the relevant characteristics and nuances of his diverse information behaviors. A case study examines and explicates the crucial ways in which Darwin's information behaviors proved instrumental in preserving priority for his evolutionary ideas during a crisis period involving rival evolutionary theorist Alfred Russel Wallace in 1858. An information-related timeline of Darwin's life, graphic models, and digital photographs illustrating his information behaviors are presented. Limitations of the study and areas for further research are also discussed

Ethical Issues of Big Data 2.0 Collaborations: Roles and Preparation of Information Specialists

The emerging Age of Big Data 2.0 promises myriad opportunities to advance human knowledge for the benefit of society. Across the globe, Big Data collaborative ventures are launching “moonshot” projects and establishing new organizations, such as Oxford University’s imminent Big Data Institute, an interdisciplinary research center, which “will focus on the analysis of large, complex, heterogeneous data sets for research into the causes and consequences, prevention and treatment of disease.” Managing and leveraging such vast quantities of data will test the professional and technical capabilities of those responsible for the systems providing access to this wealth of information. So too will the legal, ethical, and policy issues implicated by Big Data enterprises, which will arguably present equivalent, if not greater, challenges. Information professionals are already working in the research data space, providing access to external data sets, advising on data management plans, and assisting with data literacy education. Some information specialists are already helping their communities create local data infrastructures as consultants on metadata and also contributing to policy development, but their potential role in Big Data megaprojects is still largely unexplored. Our research uses a case study strategy to provide a real-world perspective on this problem. We are exploring five questions: • What are the chief legal, ethical, and policy issues raised by Big Data 2.0 initiatives? • What best practices are emerging that could inform responses to these challenges? • What roles can information professionals play in considerations of such issues and in the development and implementation of good practices? • What competencies (knowledge, skills, and abilities) will information professionals require to fulfill such roles? • How can library and information science educators prepare new and established information professionals for these responsibilities? The focus of the study is on the ethical tensions generated by very large-scale collaborative interdisciplinary human subject research that cuts across the public and private, nonprofit and for-profit sectors, and spans multiple jurisdictions; with particular reference to the stewardship responsibilities of the library and information profession, and our own responsibilities as educators to expose and explore issues arising from such ventures. After reviewing the literature on the subject to set our work in context, we identify several high-profile examples of Big Data initiatives originating in the United States and other countries (including the Pittsburgh Health Data Alliance, UK Biobank, Big Data Europe, the Personal Genome Project, the Precision Medicine Initiative, and the Oncology Research Information Exchange Network), and describe their key characteristics. We discuss specific issues and questions related to particular cases, then consider their implications in more general terms, looking at topical concerns such as privacy, anonymity, monetization, commodification, and peaceful/public good/public interest uses of data versus military/national security uses versus terrorist applications. Finally, we consider the roles, responsibilities, requirements, and relationships of information specialists operating in the Big Data 2.0 arena, especially the knowledge, skills, and abilities needed for stewardship positions and interventions; and how we can design, develop, and deliver curricula to prepare both novice and seasoned practitioners to act as the conscience of the big data world

Legal, Ethical, and Policy Issues of “Big Data 2.0” Collaborative Ventures and Roles for Information Professionals in Research Libraries

The emerging Age of Big Data 2.0 promises myriad imagined and yet-to-be-imagined opportunities for the advancement of human knowledge. Around the globe, Big Data collaborative ventures are launching “moonshot” projects; among them: Oxford University’s soon-to-be-opened Big Data Institute, which will analyze, synthesize, and hypothesize medical treatments and cures from human genomic data collected from 500,000 volunteers by the UK Biobank project The Pittsburgh Health Data Alliance, a transactional medicine and commercial capitalization partnership of Carnegie Mellon University, the University of Pittsburgh, and the University of Pittsburgh Medical Center (UPMC) Managing and leveraging these vast terabyte troves of information will test the capabilities and ingenuity of those working with and responsible for the knowledge management systems providing access to this intellectual capital. Legal, ethical, and policy issues implicated by such Big Data enterprises will present equivalent, if not greater, challenges on issues like data protection and use. But it is not just Big Data that we need to worry about. Big Data initiatives are grabbing headlines, but similar legal and ethical issues are arising with data from the smaller-scale projects that research libraries are increasingly interacting with on a daily basis. Throughout history, information professionals have applied theory and practice in gathering, organizing, providing access, and preserving data, in diverse forms for diverse functions. They have been integral in shaping, as well as safeguarding, offering guidance on, and, when deemed necessary, speaking up about laws, ethics, and policies undergirding and crosscutting individuals, societies, organizations, and nations. Many research libraries have already stepped up their efforts in scholarly communication, digital publishing, and data management, creating specialist roles requiring knowledge, skills, and abilities extending significant beyond traditional professional competency frameworks. However, the future promises a world of growing complexity and challenge where a majority of questions presented falls into the truly difficult category, and rising numbers of questions relate to the legal and ethical issues surrounding scholarly communication and research data. Copyright and intellectual property more generally has already been recognized as an area where expertise is needed across all library functions and services. However ethical issues have generally received less consideration, but are arguably set to become the wicked problem for higher education institutions in the immediate future, particularly in relation to data, and there is an urgent need for libraries to build capacity in this area. Our research uses a case study strategy to provide real-world context to the legal and ethical issues facing libraries in the Big Data world and explore these critical questions: • What are the chief legal, ethical, and policy issues triggered by Big Data (and Little Data) initiatives? • What Best Practices can be identified to address these kinds of legal, ethical and policy issues? • What are the roles that information professionals and research libraries can and will assume in contributing to considerations of the legal, ethical, and policy issues raised by such projects? • What are the competency implications in terms of the knowledge, skills, and abilities libraries need to acquire or develop for the Big Data world

C-Reactive Protein, Erythrocyte Sedimentation Rate and Orthopedic Implant Infection

BACKGROUND: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have been shown to be useful for diagnosis of prosthetic hip and knee infection. Little information is available on CRP and ESR in patients undergoing revision or resection of shoulder arthroplasties or spine implants. METHODS/RESULTS: We analyzed preoperative CRP and ESR in 636 subjects who underwent knee (n=297), hip (n=221) or shoulder (n=64) arthroplasty, or spine implant (n=54) removal. A standardized definition of orthopedic implant-associated infection was applied. Receiver operating curve analysis was used to determine ideal cutoff values for differentiating infected from non-infected cases. ESR was significantly different in subjects with aseptic failure infection of knee (median 11 and 53.5 mm/h, respectively, p=<0.0001) and hip (median 11 and 30 mm/h, respectively, p=<0.0001) arthroplasties and spine implants (median 10 and 48.5 mm/h, respectively, p=0.0033), but not shoulder arthroplasties (median 10 and 9 mm/h, respectively, p=0.9883). Optimized ESR cutoffs for knee, hip and shoulder arthroplasties and spine implants were 19, 13, 26, and 45 mm/h, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 89 and 74% for knee, 82 and 60% for hip, and 32 and 93% for shoulder arthroplasties, and 57 and 90% for spine implants. CRP was significantly different in subjects with aseptic failure and infection of knee (median 4 and 51 mg/l, respectively, p<0.0001), hip (median 3 and 18 mg/l, respectively, p<0.0001), and shoulder (median 3 and 10 mg/l, respectively, p=0.01) arthroplasties, and spine implants (median 3 and 20 mg/l, respectively, p=0.0011). Optimized CRP cutoffs for knee, hip, and shoulder arthroplasties, and spine implants were 14.5, 10.3, 7, and 4.6 mg/l, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 79 and 88% for knee, 74 and 79% for hip, and 63 and 73% for shoulder arthroplasties, and 79 and 68% for spine implants. CONCLUSION: CRP and ESR have poor sensitivity for the diagnosis of shoulder implant infection. A CRP of 4.6 mg/l had a sensitivity of 79 and a specificity of 68% to detect infection of spine implants

Circum-Arctic distribution of chemical anti-herbivore compounds suggests biome-wide trade-off in defence strategies in Arctic shrubs

Spatial variation in plant chemical defence towards herbivores can help us understand variation in herbivore top-down control of shrubs in the Arctic and possibly also shrub responses to global warming. Less defended, non-resinous shrubs could be more influenced by herbivores than more defended, resinous shrubs. However, sparse field measurements limit our current understanding of how much of the circum-Arctic variation in defence compounds is explained by taxa or defence functional groups (resinous/non-resinous). We measured circum-Arctic chemical defence and leaf digestibility in resinous (Betula glandulosa, B. nana ssp. exilis) and non-resinous (B. nana ssp. nana, B. pumila) shrub birches to see how they vary among and within taxa and functional groups. Using liquid chromatography-mass spectrometry (LC-MS) metabolomic analyses and in vitro leaf digestibility via incubation in cattle rumen fluid, we analysed defence composition and leaf digestibility in 128 samples from 44 tundra locations. We found biogeographical patterns in anti-herbivore defence where mean leaf triterpene concentrations and twig resin gland density were greater in resinous taxa and mean concentrations of condensing tannins were greater in non-resinous taxa. This indicates a biome-wide trade-off between triterpene- or tannin-dominated defences. However, we also found variations in chemical defence composition and resin gland density both within and among functional groups (resinous/non-resinous) and taxa, suggesting these categorisations only partly predict chemical herbivore defence. Complex tannins were the only defence compounds negatively related to in vitro digestibility, identifying this previously neglected tannin group as having a potential key role in birch anti-herbivore defence. We conclude that circum-Arctic variation in birch anti-herbivore defence can be partly derived from biogeographical distributions of birch taxa, although our detailed mapping of plant defence provides more information on this variation and can be used for better predictions of herbivore effects on Arctic vegetation

Association of low-level inorganic arsenic exposure from rice with age-standardized mortality risk of cardiovascular disease (CVD) in England and Wales

Adverse health outcomes, including death from cardiovascular disease (CVD), arising from chronic exposure to inorganic arsenic (iAs) are well documented. Consumption of rice is a major iAs exposure route for over 3 billion people, however, there is still a lack of epidemiological evidence demonstrating the association between iAs exposure from rice intake and CVD risks. We explored this potential association through an ecological study using data at local authority level across England and Wales. Local authority level daily per capita iAs exposure from rice (E-iAsing,rice) was estimated using ethnicity as a proxy for class of rice consumption. A series of linear and non-linear models were applied to estimate the association between E-iAsing,rice and CVD age-standardized mortality rate (ASMR), using Akaike's Information Criterion as the principle model selection criterion. When adjusted for significant confounders, notably smoking prevalence, education level, employment rate, overweight percentage, PM2.5, female percentage and medical and care establishments, the preferred non-linear model indicated that CVD risks increased with iAs exposure from rice at exposures above 0.3 μg/person/day. Also, the best-fitted linear model indicated that CVD ASMR in the highest quartile of iAs exposure (0.375–2.71 μg/person/day) was 1.06 (1.02, 1.11; p-trend <0.001) times higher than that in the lowest quartile (<0.265 μg/person/day). Notwithstanding the well-known limitations of ecological studies, this study further suggests exposure to iAs, including from rice intake, as a potentially important confounder for studies of the factors controlling CVD risks

Benefits and risks of antiretroviral therapy for perinatal HIV prevention.

CAPRISA, 2016.Abstract available in pdf

Methotrexate Decreases Tenofovir Exposure in Antiretroviral-Suppressed Individuals Living With HIV.

BackgroundTo mitigate increased risk of premature cardiovascular disease in antiretroviral therapy (ART) suppressed adults living with HIV (PWH), low-dose methotrexate (LDMTX) was evaluated in a multicenter randomized placebo controlled clinical trial of 176 PWH taking various ART regimens (ACTG A5314). Given shared methotrexate (MTX) and tenofovir (TFV) pharmacokinetic (PK) pathways, a substudy was conducted to investigate whether LDMTX alters TFV exposure.MethodsAdults virally suppressed on ART for &gt;24 weeks were randomized to LDMTX or placebo. The first 66 participants taking a tenofovir disoproxil fumarate-containing regimen underwent intensive PK sampling over 24 hours after the second dose of LDMTX 10 mg or placebo. TFV and MTX levels were quantified using validated mass spectrometry methods. TFV PK between LDMTX and placebo groups were compared and MTX PK was characterized.ResultsForty-eight participants completed this substudy (n = 20 on LDMTX and 28 on placebo). Baseline characteristics were balanced except for protease inhibitor (PI)-use (25% in LDMTX and 43% in placebo groups). For TFV, AUC6 (primary endpoint), and AUC24,imputed, Cmax, and Cmin (secondary endpoints) were on average 22%, and 24%, 27%, and 31% less in the LDMTX versus placebo groups, with reductions in secondary endpoints reaching statistical significance. Additional analyses suggested a greater reduction in the absence of PI although not significant.ConclusionLower TFV AUC24,imputed and Cmax indicates that LDMTX reduces TFV exposure in PWH. However, this change was modest, not warranting a change in TFV dosing at this time. Further studies of TFV PK with LDMTX, especially without PI co-administration, are warranted

Five-Year Safety Evaluation of Maraviroc in HIV-1–Infected Treatment-Experienced Patients

BACKGROUND: Maraviroc is unique among approved antiretroviral drugs in targeting the host-cell chemokine coreceptor type-5 receptor. With its novel mechanism of action, we sought to describe the 5-year safety profile of maraviroc. METHODS: Two large phase 3 studies of maraviroc enrolled HIV-infected treatment-experienced patients and followed them up for 5 or more years. Survival and selected clinical end points were identified and assessed. RESULTS: A total of 938 enrolled patients received maraviroc-containing regimens. Rates of death and selected clinical events (eg, hepatic failure, malignancy, and myocardial infarction) were low during follow-up. CONCLUSIONS: Maraviroc was generally safe in treatment-experienced participants for >5 years