From Condemnation to Conformity: Carter and Reagan\u27s Foreign Policy towards the Argentine Junta, 1977-1982.

This study examines how the administrations of Jimmy Carter and Ronald Reagan responded to the widespread human rights abuses committed by the Argentine military during the country\u27s Dirty War between 1977 and 1982. The objective is to gain a broader understanding of the policies pursued by both administrations. Under Carter, who brought human rights to the forefront of American foreign policy, Argentina was heavily targeted and sanctioned with the anticipation that such measures would enhance the human rights status in Argentina. Ultimately, such policies resulted in open hostility in bilateral relations, culminating in Argentina\u27s refusal to support Carter\u27s proposed grain embargo on the Soviet Union in 1980. Reagan moved to restore relations until Argentina\u27s invasion of the Falklands in April, 1982. The works of many authors were consulted in conjunction with newspapers, journal articles, government proceedings and declassified documents obtained from the National Security Archives

Public wealth, public health, and private stealth: Australia's black market in cigarettes

Taxes on tobacco provide a significant income for the Australian government – $5.1 billion in 2001. At the same time, health officials are making strenuous efforts to reduce smoking, particularly among teenagers. Some economists suggest that raising taxes on tobacco will produce more revenue while at the same time lowering smoking rates, particularly among youths who have less discretionary spending power than adults. But a by-product of excise tax in Australia has been the emerging market in ‘chop-chop,’ tobacco diverted from legal channels by growers who receive considerably higher prices for a part of their yield than they can obtain from legal manufacturers. The article details this situation and suggests that only bold solutions may be able to reduce tensions in tax policies, smoking rates and the ‘chop-chop’ black market

Joint Multiple Testing Procedures for Graphical Model Selection with Applications to Biological Networks

Gaussian graphical models have become popular tools for identifying relationships between genes when analyzing microarray expression data. In the classical undirected Gaussian graphical model setting, conditional independence relationships can be inferred from partial correlations obtained from the concentration matrix (= inverse covariance matrix) when the sample size n exceeds the number of parameters p which need to estimated. In situations where n \u3c p, another approach to graphical model estimation may rely on calculating unconditional (zero-order) and first-order partial correlations. In these settings, the goal is to identify a lower-order conditional independence graph, sometimes referred to as a ‘0-1 graphs’. For either choice of graph, model selection may involve a multiple testing problem, in which edges in a graph are drawn only after rejecting hypotheses involving (saturated or lower-order) partial correlation parameters. Most multiple testing procedures applied in previously proposed graphical model selection algorithms rely on standard, marginal testing methods which do not take into account the joint distribution of the test statistics derived from (partial) correlations. We propose and implement a multiple testing framework useful when testing for edge inclusion during graphical model selection. Two features of our methodology include (i) a computationally efficient and asymptotically valid test statistics joint null distribution derived from influence curves for correlation-based parameters, and (ii) the application of empirical Bayes joint multiple testing procedures which can effectively control a variety of popular Type I error rates by incorpo- rating joint null distributions such as those described here (Dudoit and van der Laan, 2008). Using a dataset from Arabidopsis thaliana, we observe that the use of more sophisticated, modular approaches to multiple testing allows one to identify greater numbers of edges when approximating an undirected graphical model using a 0-1 graph. Our framework may also be extended to edge testing algorithms for other types of graphical models (e.g., for classical undirected, bidirected, and directed acyclic graphs)

Resampling-Based Empirical Bayes Multiple Testing Procedures for Controlling Generalized Tail Probability and Expected Value Error Rates:

This article proposes resampling-based empirical Bayes multiple testing procedures for controlling a broad class of Type I error rates, defined as generalized tail probability (gTP) error rates, gTP(q,g) = Pr(g(Vn,Sn) \u3e q), and generalized expected value (gEV) error rates, gEV(g) = [g(Vn,Sn)], for arbitrary functions g(Vn,Sn) of the numbers of false positives Vn and true positives Sn. Of particular interest are error rates based on the proportion g(Vn,Sn) = Vn/(Vn + Sn) of Type I errors among the rejected hypotheses, such as the false discovery rate (FDR), FDR = [Vn/(Vn + Sn)]. The proposed procedures offer several advantages over existing methods. They provide Type I error control for general data generating distributions, with arbitrary dependence structures among variables. Gains in power are achieved by deriving rejection regions based on guessed sets of true null hypotheses and null test statistics randomly sampled from joint distributions that account for the dependence structure of the data. The Type I error and power properties of an FDR-controlling version of the resampling-based empirical Bayes approach are investigated and compared to those of widely-used FDR-controlling linear step-up procedures in a simulation study. The Type I error and power trade-off achieved by the empirical Bayes procedures under a variety of testing scenarios allows this approach to be competitive with or outperform the Storey and Tibshirani [2003] linear step-up procedure, as an alternative to the classical Benjamini and Hochberg [1995] procedure

Resampling-Based Multiple Hypothesis Testing with Applications to Genomics: New Developments in the R/Bioconductor Package multtest

The multtest package is a standard Bioconductor package containing a suite of functions useful for executing, summarizing, and displaying the results from a wide variety of multiple testing procedures (MTPs). In addition to many popular MTPs, the central methodological focus of the multtest package is the implementation of powerful joint multiple testing procedures. Joint MTPs are able to account for the dependencies between test statistics by effectively making use of (estimates of) the test statistics joint null distribution. To this end, two additional bootstrap-based estimates of the test statistics joint null distribution have been developed for use in the package. For asymptotically linear estimators involving single-parameter hypotheses (such as tests of means, regression parameters, and correlation parameters using t-statistics), a computationally efficient joint null distribution estimate based on influence curves is now also available. New MTPs implemented in multtest include marginal adaptive procedures for control of the false discovery rate (FDR) as well as empirical Bayes joint MTPs which can control any Type I error rate defined as a function of the numbers of false positives and true positives. Examples of such error rates include, among others, the family-wise error rate and the FDR. S4 methods are available for objects of the new class EBMTP, and particular attention has been given to reducing the need for repeated resampling between function calls

Networks Fighting Nicotine: Will Visitors to a Tobacco Cessation Website Engage in an Online Support Community?

Background: Online tobacco cessation social networks may influence effectiveness of Web-Assisted Tobacco Interventions (WATIs). Purpose: To understand characteristics and quit rates of WATI participants navigating to BecomeAnEx.org, an online cessation network. Methods: We recruited 759 smokers to a WATI (decide2quit.org), through in-person primary care and dental office referrals and Google ads. We used online surveys to gather data on sociodemographics, tobacco use, and readiness to quit. Smokers were able to navigate online from the WATI to an online social network supporting cessation (BecomeAnEx.org). We identified visitors to and registrants with BecomeAnEx.org, examining associations between BecomeAnEx.org use and sociodemographic characteristics, patterns of WATI use and likelihood of tobacco cessation. Results: One-quarter (26.0%) of WATI users visited BecomeAnEx.org ; 7.5% registered. BecomeAnEx.org visitors were more likely than nonvisitors to be female (73.0% vs. 62.6% p\u3c0.01) and more likely to have visited a smoking cessation website before (43.9% vs 17.4%, p\u3c.01). Registrants were more likely to engage in other WATI tools including e-mails to trained tobacco specialists (68.4% vs 28.8). No significant association was found between BecomeAnEx.org use (visiting or registration) and tobacco cessation. Conclusions: BecomeAnEx.org navigation from our WATI was limited, attracting those already inclined toward online cessation tools. Future studies must explore whether online cessation social networks may have additional benefits if designed to attract larger audiences

MBASED: allele-specific expression detection in cancer tissues and cell lines

Allele-specific gene expression, ASE, is an important aspect of gene regulation. We developed a novel method MBASED, meta-analysis based allele-specific expression detection for ASE detection using RNA-seq data that aggregates information across multiple single nucleotide variation loci to obtain a gene-level measure of ASE, even when prior phasing information is unavailable. MBASED is capable of one-sample and two-sample analyses and performs well in simulations. We applied MBASED to a panel of cancer cell lines and paired tumor-normal tissue samples, and observed extensive ASE in cancer, but not normal, samples, mainly driven by genomic copy number alterations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0405-3) contains supplementary material, which is available to authorized users

Cluster-randomized trial of a web-assisted tobacco quality improvement intervention of subsequent patient tobacco product use: A national dental PBRN study

ABSTRACT: BACKGROUND: Brief clinician delivered advice helps in tobacco cessation efforts. This study assessed the impact of our intervention on instances of advice given to dental patients during visits on tobacco use quit rates 6 months after the intervention. METHODS: The intervention was cluster randomized trial at the dental practice level. Intervention dental practices were provided a longitudinal technology-assisted intervention, oralcancerprevention.org that included a series of interactive educational cases and motivational email cues to remind dental provides to complete guideline-concordant brief behavioral counseling at the point of care. In all dental practices, exit cards were given to the first 100 consecutive patients, in which tobacco users provided contact information for a six month follow-up telephone survey. RESULTS: A total of 564 tobacco using dental patients completed a six month follow-up survey. Among intervention patients, 55% reported receiving advice to quit tobacco, and 39% of control practice patients reported receiving advice to quit tobacco (p \u3c 0.01). Six-month tobacco use quit rates were not significantly between the Intervention (9%) and Control (13%) groups, (p = 0.088). CONCLUSION: Although we increased rates of cessation advice delivered in dental practices, this study shows no evidence that brief advice by dentist\u27s increases long-term abstinence in smokers.Trial registration: ClinicalTrials.gov NCT00627185

Profiling the Dead: Generating Microsatellite Data from Fossil Bones of Extinct Megafauna—Protocols, Problems, and Prospects

We present the first set of microsatellite markers developed exclusively for an extinct taxon. Microsatellite data have been analysed in thousands of genetic studies on extant species but the technology can be problematic when applied to low copy number (LCN) DNA. It is therefore rarely used on substrates more than a few decades old. Now, with the primers and protocols presented here, microsatellite markers are available to study the extinct New Zealand moa (Aves: Dinornithiformes) and, as with single nucleotide polymorphism (SNP) technology, the markers represent a means bywhich the field of ancient DNA can (preservation allowing) move on from its reliance on mitochondrial DNA. Candidate markers were identified using high throughput sequencing technology (GS-FLX) on DNA extracted from fossil moa bone and eggshell. From the ‘shotgun’ reads, .60 primer pairs were designed and tested on DNA from bones of the South Island giant moa (Dinornis robustus). Six polymorphic loci were characterised and used to assess measures of genetic diversity. Because of low template numbers, typical of ancient DNA, allelic dropout was observed in 36–70% of the PCR reactions at each microsatellite marker. However, a comprehensive survey of allelic dropout, combined with supporting quantitative PCR data, allowed us to establish a set of criteria that maximised data fidelity. Finally, we demonstrated the viability of the primers and the protocols, by compiling a full Dinornis microsatellite dataset representing fossils of c. 600–5000 years of age. A multi-locus genotype was obtained from 74 individuals (84% success rate), and the data showed no signs of being compromised by allelic dropout. The methodology presented here provides a framework by which to generate and evaluate microsatellite data from samples of much greater antiquity than attempted before, and opens new opportunities for ancient DNA research

Secure Asynchronous Communication Between Smokers and Tobacco Treatment Specialists: Secondary Analysis of a Web-Assisted Tobacco Intervention in the QUIT-PRIMO and National Dental PBRN Networks

BACKGROUND: Within a web-assisted tobacco intervention, we provided a function for smokers to asynchronously communicate with a trained tobacco treatment specialist (TTS). Previous studies have not attempted to isolate the effect of asynchronous counseling on smoking cessation. OBJECTIVE: This study aimed to conduct a semiquantitative analysis of TTS-smoker communication and evaluate its association with smoking cessation. METHODS: We conducted a secondary analysis of data on secure asynchronous communication between trained TTSs and a cohort of smokers during a 6-month period. Smokers were able to select their preferred TTS and message them using a secure web-based form. To evaluate whether the TTS used evidence-based practices, we coded messages using the Motivational Interviewing Self-Evaluation Checklist and Smoking Cessation Counseling (SCC) Scale. We assessed the content of messages initiated by the smokers by creating topical content codes. At 6 months, we assessed the association between smoking cessation and the amount of TTS use and created a multivariable model adjusting for demographic characteristics and smoking characteristics at baseline. RESULTS: Of the 725 smokers offered asynchronous counseling support, 33.8% (245/725) messaged the TTS at least once. A total of 1082 messages (TTSs: 565; smokers 517) were exchanged between the smokers and TTSs. The majority of motivational interviewing codes were those that supported client strengths (280/517, 54.1%) and promoted engagement (280/517, 54.1%). SCC code analysis showed that the TTS provided assistance to smokers if they were willing to quit (247/517, 47.8%) and helped smokers prepare to quit (206/517, 39.8%) and anticipate barriers (197/517, 38.1%). The majority of smokers\u27 messages discussed motivations to quit (234/565, 41.4%) and current and past treatments (talking about their previous use of nicotine replacement therapy and medications; 201/565, 35.6%). The majority of TTS messages used behavioral strategies (233/517, 45.1%), offered advice on treatments (189/517, 36.5%), and highlighted motivations to quit (171/517, 33.1%). There was no association between the amount of TTS use and cessation. In the multivariable model, after adjusting for gender, age, race, education, readiness at baseline, number of cigarettes smoked per day at baseline, and the selected TTS, smokers messaging the TTS one or two times had a smoking cessation odds ratio (OR) of 0.8 (95% CI 0.4-1.4), and those that messaged the TTS more than two times had a smoking cessation OR of 1.0 (95% CI 0.4-2.3). CONCLUSIONS: Our study demonstrated the feasibility of using asynchronous counseling to deliver evidence-based counseling. Low participant engagement or a lack of power could be potential explanations for the nonassociation with smoking cessation. Future trials should explore approaches to increase participant engagement and test asynchronous counseling in combination with other approaches for improving the rates of smoking cessation. Phillips, Jessica H Williams, Sarah L Cutrona, Midge N Ray, Gregg H Gilbert, Thomas K Houston, QUITPRIMO, National Dental PBRN Collaborative Group. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.05.2020