Reapportionment, Regional Politics and Partisan Gains

Geographers and demographers have been analyzing U.S. regional population change for decades. From the perspective of politics and governance, understanding these population changes over time is very important because seats in the House of Representatives are reapportioned every decade in accordance with the U.S. Constitution. Representation in the House, in turn, affects the distribution of votes in the Electoral College and thus the impact of regional population change affects the presidency as well as the Congress. As political geographers we have studied the possible impacts of this population change on elections, issues in Congress and the nation, and if a particular political party has gained or lost in the process. This article is adapted from our recently published co-edited book, Atlas of the 2012 Elections, which examines both short-term and long-term state and regional gains and losses in the House of Representatives and Electoral College to see how the Democrats and Republicans have fared

Single-arm Trials with External Comparators and Confounder Misclassification: How Adjustment Can Fail

Background:"Single-arm trials" with external comparators that contrast outcomes in those on experimental therapy to real-world patients have been used to evaluate efficacy and safety of experimental drugs in rare and severe diseases. Regulatory agencies are considering expanding the role these studies can play; guidance thus far has explicitly considered outcome misclassification with little discussion of misclassification of confounding variables.Objectives:This work uses causal diagrams to illustrate how adjustment for a misclassified confounder can result in estimates farther from the truth than ignoring it completely. This theory is augmented with quantitative examples using plausible values for misclassification of smoking in real-world pharmaceutical claims data. A tool is also provided for calculating bias of adjusted estimates with specific input parameters.Results:When confounder misclassification is similar in both data sources, adjustment generally brings estimates closer to the truth. When it is not, adjustment can generate estimates that are considerably farther from the truth than the crude. While all nonrandomized studies are subject to this potential bias, single-arm studies are particularly vulnerable due to perfect alignment of confounder measurement and treatment group. This is most problematic when the prevalence of the confounder does not differ between data sources and misclassification does, but can occur even with strong confounder-data source associations.Discussion:Researchers should consider differential confounder misclassification when designing protocols for these types of studies. Subsample validation of confounders, followed by imputation or other bias correction methods, may be a key tool for combining trial and real-world data going forward

Initiator Types and the Causal Question of the Prevalent New-User Design: A Simulation Study

New-user designs restricting to treatment initiators have become the preferred design for studying drug comparative safety and effectiveness using nonexperimental data. This design reduces confounding by indication and healthy-adherer bias at the cost of smaller study sizes and reduced external validity, particularly when assessing a newly approved treatment compared with standard treatment. The prevalent new-user design includes adopters of a new treatment who switched from or previously used standard treatment (i.e., the comparator), expanding study sample size and potentially broadening the study population for inference. Previous work has suggested the use of time-conditional propensity-score matching to mitigate prevalent user bias. In this study, we describe 3 "types"of initiators of a treatment: new users, direct switchers, and delayed switchers. Using these initiator types, we articulate the causal questions answered by the prevalent new-user design and compare them with those answered by the new-user design. We then show, using simulation, how conditioning on time since initiating the comparator (rather than full treatment history) can still result in a biased estimate of the treatment effect. When implemented properly, the prevalent new-user design estimates new and important causal effects distinct from the new-user design

How subgroup analyses can miss the trees for the forest plots: A simulation study

Objectives: Subgroup analyses of clinical trial data can be an important tool for understanding when treatment effects differ across populations. That said, even effect estimates from prespecified subgroups in well-conducted trials may not apply to corresponding subgroups in the source population. While this divergence may simply reflect statistical imprecision, there has been less discussion of systematic or structural sources of misleading subgroup estimates. Study Design and Setting: We use directed acyclic graphs to show how selection bias caused by associations between effect measure modifiers and trial selection, whether explicit (e.g., eligibility criteria) or implicit (e.g., self-selection based on race), can result in subgroup estimates that do not correspond to subgroup effects in the source population. To demonstrate this point, we provide a hypothetical example illustrating the sorts of erroneous conclusions that can result, as well as their potential consequences. We also provide a tool for readers to explore additional cases. Conclusion: Treating subgroups within a trial essentially as random samples of the corresponding subgroups in the wider population can be misleading, even when analyses are conducted rigorously and all findings are internally valid. Researchers should carefully examine associations between (and consider adjusting for) variables when attempting to identify heterogeneous treatment effects

Nondifferential Treatment Misclassification Biases Toward the Null? Not a Safe Bet for Active Comparator Studies

Active comparator studies are increasingly common, particularly in pharmacoepidemiology. In such studies, the parameter of interest is a contrast (difference or ratio) in the outcome risks between the treatment of interest and the selected active comparator. While it may appear treatment is dichotomous, treatment is actually polytomous as there are at least 3 levels: no treatment, the treatment of interest, and the active comparator. Because misclassification may occur between any of these groups, independent nondifferential treatment misclassification may not be toward the null (as expected with a dichotomous treatment). In this work, we describe bias from independent nondifferential treatment misclassification in active comparator studies with a focus on misclassification that occurs between each active treatment and no treatment. We derive equations for bias in the estimated outcome risks, risk difference, and risk ratio, and we provide bias correction equations that produce unbiased estimates, in expectation. Using data obtained from US insurance claims data, we present a hypothetical comparative safety study of antibiotic treatment to illustrate factors that influence bias and provide an example probabilistic bias analysis using our derived bias correction equations

Environmental management decision-making in certified hotels

This paper analyses environmental decision-making against two axes, motivations and decision-making processes, to understand the reasons for pro-environmental behaviour by the managements of Spanish Eco-management and Audit Scheme (EMAS)-certified hotels. Mixed methods were used to study perceptions of EMAS and reasons for being certified, with current and lapsed EMAS-certified firms triangulated against expert interviews and documentary evidence. Four groups of hotels were differentiated: Strategic hotels (22%) (with high levels of integrated environmental management), Followers (48%), Greenwashers (11%) and Laggers (19%) (with low levels of integrated environmental management). Most hotels were found to be internally driven in their purpose and ad hoc in their decision-making, with limited understanding of externally driven benefits and motivation for more systematic management systems. This questions the success of EMAS as both a continuous improvement management and as a market-based regulation tool for hotels. Few hotels overall related high environmental standards to the possibilities of gaining market advantage: most wished to avoid legal challenges. The paper also illustrates the ways in which hotels opportunistically switch certification systems to get what they see as a better deal. © 2011 Taylor & Francis

On the optical counterpart of NGC300 X-1 and the global Wolf-Rayet content of NGC300

(Conext:) Surveys of Wolf-Rayet (WR) populations in nearby galaxies provide tests of evolutionary models plus Type Ib/c supernova progenitors. This spectroscopic study complements the recent imaging survey of the spiral galaxy NGC 300 by Schild et al. (Aims): Revisions to the known WR content of NGC 300 are presented. We investigate the WR nature of candidate #41 from Schild et al. which is spatially coincident with the bright X-ray point source NGC 300 X-1; (Methods:) VLT/FORS2 multi-object spectroscopy of WR candidates in NGC 300 is obtained; (Results:) We establish an early-type WN nature of #41, i.e. similar to the optical counterpart of IC 10 X-1, which closely resembles NGC 300 X-1. We confirm 9 new WR stars, bringing the current WR census of the inner disk to 31, with N(WC)/N(WN)~0.9. (Conclusions:) If #41 is the optical counterpart for NGC 300 X-1, we estimate a WR mass of 38 Msun based upon ground-based photometry, from which a black hole mass of > 10 Msun results from the 32.8 hr period of the system and WR wind velocity of 1250 km/s. We estimate an 95% completeness among WC stars and 70% among WN stars, such that the total WR content is ~40, with N(WC)/N(WN)~0.7. From the Halpha-derived star formation rate of the inner galaxy, we infer N(WR)/N(O)~0.04Comment: 5 pages, 5 figures, accepted for A&A Letter

Gender Equity in Transplantation: A Report From the Women in Transplantation Workshop of The Transplantation Society of Australia and New Zealand

The exponential growth of young talented women choosing science and medicine as their professional career over the past decade is substantial. Currently, more than half of the Australian medical doctoral graduates and early career researchers are comprised of women, but less than 20% of all academic professorial staff are women. The loss of female talent in the hierarchical ladder of Australian academia is a considerable waste of government investment, productivity, and scientific innovation. Gender disparity in the professional workforce composition is even more striking within the field of transplantation. Women are grossly underrepresented in leadership roles, with currently no female heads of unit in any of the Australian and New Zealand transplanting centers. At the same time, there is also gender segregation with a greater concentration of women in lower-status academic position compared with their male counterparts. Given the extent and magnitude of the disparity, the Women in Transplantation Committee, a subcommittee of The Transplantation Society of Australia and New Zealand established a workshop comprising 8 female clinicians/scientists in transplantation. The key objectives were to (i) identify potential gender equity issues within the transplantation workforce; (ii) devise and implement potential strategies and interventions to address some of these challenges at a societal level; (iii) set realistic and achievable goals to enhance and facility gender equality, equity, and diversity in transplantation

A Single-Photon Server with Just One Atom

Neutral atoms are ideal objects for the deterministic processing of quantum information. Entanglement operations have been performed by photon exchange or controlled collisions. Atom-photon interfaces were realized with single atoms in free space or strongly coupled to an optical cavity. A long standing challenge with neutral atoms, however, is to overcome the limited observation time. Without exception, quantum effects appeared only after ensemble averaging. Here we report on a single-photon source with one-and-only-one atom quasi permanently coupled to a high-finesse cavity. Quasi permanent refers to our ability to keep the atom long enough to, first, quantify the photon-emission statistics and, second, guarantee the subsequent performance as a single-photon server delivering up to 300,000 photons for up to 30 seconds. This is achieved by a unique combination of single-photon generation and atom cooling. Our scheme brings truly deterministic protocols of quantum information science with light and matter within reach.Comment: 4 pages, 3 figure

Introducing longitudinal cumulative dose to describe chemotherapy patterns over time: Case study of a colon cancer trial

Adjuvant chemotherapy regimens take months to complete. Despite this, studies evaluate chemotherapy adherence via measures assessed at the end of treatment (eg, number of patients missing any dose, relative dose intensity [RDI]). This approach ignores information like the timing of treatment delays. We propose longitudinal cumulative dose (LCD) to integrate impacts of dose reductions, missed doses and dose delays over time. We obtained data from the 2246 participants in the MOSAIC trial randomized to FOLFOX (all three agents) or 5-FU/LV (only 5-fluorouracil and leucovorin). We evaluated proportions of patients stopping treatment early and reducing, missing or delaying a dose in each arm for each chemotherapy agent at each cycle. We calculated LCD, the fraction of the final standard dose a participant reached by a given day, for each participant and each agent and compared it over time and at 24 weeks between treatment arms. Participants randomized to FOLFOX were more likely to stop treatment, reduce doses, miss doses or delay cycles; these differences increased over time. Median LCD for oxaliplatin in the FOLFOX arm at 24 weeks was 77%. The LCD for 5-fluorouracil differed between arms (FOLFOX arm median: 81%; 5-FU/LV arm median: 96%). Visualizing LCD highlighted the timing of deviations from standard administration in a way RDI could not, with major differences in 5-fluorouracil LCD across treatment arms beginning after the sixth dose. Further evaluation of LCD and its impacts on clinical outcomes may clarify mechanisms for heterogeneous patient outcomes