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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Single institutional review board (IRB) review of multisite research increased in frequency over a decade ago with a proliferation of master IRB reliance agreements supporting statewide and regional consortia and disease- and population-specific networks. Although successful, the increasing number of agreements presented significant challenges and illuminated potential benefits of a single, nationwide agreement. Anticipated changes in federal regulations highlighted the need to systematize and simplify IRB reliance. To address these challenges, the NIH National Center for Advancing Translational Sciences funded a project to establish a national IRB reliance network that would support national adoption of single IRB (sIRB) review. The Streamlined, Multisite, Accelerated Resources for Trials (SMART) IRB Platform launched in July 2016 to facilitate dissemination, adoption, and implementation of a collaboratively developed master IRB reliance agreement and supportive tools and resources. More than 580 institutions have joined SMART IRB’s Master Common Reciprocal Institutional Review Board Authorization Agreement and begun using the SMART IRB platform to support sIRB arrangements. Here, we describe the tenets of the agreement and operational benefits and challenges of its use. SMART IRB’s early success affirms the utility of collaborative, flexible, and centralized approaches to supporting sIRB review while highlighting the need for further national harmonization.
For decades, fructose intake has been recognized as an environmental risk for metabolic syndromes and diseases. Here, we comprehensively examined effects of fructose intake on mice liver transcriptomes. Fructose supplemented water (34%; wt/vol) was fed to both male and female C57BL/6N mice at their free will for six weeks, followed by hepatic transcriptomics analysis. Based on our criteria, differentially expressed genes (DEGs) were selected and subjected to further computational analyses to predict key pathways and upstream regulator(s). Subsequently, predicted genes and pathways from the transcriptomics dataset were validated via quantitative RT-PCR analyses. As results, we identified 89 down-regulated and 88 up-regulated mRNAs in fructose-fed mice livers. These DEGs were subjected to bioinformatic analysis tools in which DEGs were mainly enriched in xenobiotic metabolic processes; further, in the Ingenuity Pathway Analysis software, it was suggested that the aryl hydrocarbon receptor (AhR) is an upstream regulator governing overall changes, while fructose suppresses the AhR signaling pathway. In our quantitative RT-PCR validation, we confirmed that fructose suppressed AhR signaling through modulating expressions of transcription factor (Arnt) and upstream regulators (Ncor2, and Rb1). Altogether, we demonstrated that ad libitum fructose intake suppresses the canonical AhR signaling pathway in C57BL/6N mice liver. Based on our current observations, further studies are warranted, especially with regard to the effects of co-exposure to fructose on 1) other types of carcinogens and 2) inflammation inducing agents (or even diets such as a high-fat diet), to find implications of fructose induced-AhR suppression.
Antipseudomonal carbapenems are an important target for antimicrobial stewardship programs. We evaluated the impact of formulary restriction and preauthorization on relative carbapenem use for medical and surgical intensive care units at a large, urban academic medical center using interrupted time-series analysis.
How politically powerful is business in American politics? Does the political power of business distort the quality of democratic representation? This chapter reviews the literature on these vital questions, discussing selected studies in political science, sociology, history, and other fields. It finds that assessments of business influence in American politics have varied considerably over time, but it also observes there has been a broad turn in recent scholarship toward the notion that business is “more equal” than other groups in the American political system. A small but growing number of studies—especially studies focusing on politics in our time—has begun to provide credible evidence of business influence. We have also seen the introduction of some exciting new ideas about the ways that business influence, economic inequality, and political representation may be theoretically connected. But definitive conclusions remain elusive. We do not really know whether business is disproportionately powerful and how business influence affects the performance of American democracy. The chapter concludes with some suggestions about the kind of studies that are needed going forward.
We provide an overview of the concept of the “policyscape,” a dense network of policies that structure the current political order, and then assess its relationship with four aspects of American institutional behavior: the creation of new policies; the maintenance of existing policies and programs; policy “thickening” that may lead to additional gridlock and dysfunction during what is an already laborious lawmaking process; and the monitoring of the current policyscape through executive oversight in Congress. We address, among other questions, why new and broad-reaching policy reforms have been scarce in recent years; why Congress has failed to update extant policies in accordance with social, economic, political, and technological developments; and how partisan polarization has affected Congress’ ability to oversee policy implementation and hold the executive branch accountable for administrative failures.
This volume analyzes how rising party polarization and economic inequalities affect the performance of American governing institutions. It is organized around two themes: (1) the changing nature of representation in the United States and (2) how changes in the political environment have affected the internal processes of institutions, as well as overall government performance and policy outcomes.
Calls for a return to a traditional method of lawmaking known as “regular order” have proliferated as unorthodox lawmaking has grown more dominant in Congress. Proponents claim regular order enhances deliberation on legislation. This chapter examines deliberation under one form of regular order: open rules permitting unlimited amending in the House of Representatives. We find evidence of substantial minority influence on the inputs and outputs of the appropriations process. Regular order gives the minority party members the opportunity to present and win adoption of their policy proposals. Our evidence also shows that ideological extremists play an outsized role in debate. They offer more amendments than other members, and their amendments tend to win less support and face defeat more often than moderates. The paradox of regular order is that it simultaneously offers the opportunity for bipartisan deliberation over legislation while exposing the majority party to problems that may make its management of the floor more difficult.
This volume grows out of the well-documented psychological impulse to bring information to bear on sources of anxiety. In politics, as in other realms of life, anxiety triggers a quest for information. Perceived threats focus the attention (Marcus, Neuman, and MacKuen, 2000). Anxious citizens take more interest in politics, have more motivation to learn, and weigh the information they collect more judiciously (Marcus and MacKuen, 1993, MacKuen et al, 2010, Albertson and Gadarian, 2015). In these respects, worried citizens are better citizens (Brader, 2005, Valentino et al, 2008).
Scholars and observers worry that Congress has lost its capacity to perform its functions in the American political system. Drawing on an array of data on Congress’s activities and processes along with in-depth interviews with long-serving lawmakers and high-level staffers, we take stock of how changes to internal processes have affected Congress’s institutional capacities. In doing so, we make two interrelated arguments. First, we argue that Congress can take transformative action whether the legislative process is centralized and leadership-led or whether it is decentralized and committee-led. Second, we argue that Congress is better able than in previous eras to engage in conflict-clarifying representation in order to express and educate the public on the positions of the parties. We conclude that changes to congressional processes in recent years should be viewed as adaptations to the challenges of contemporary lawmaking. These adaptations help preserve Congress’s institutional capacity, but they have undoubtedly had negative consequences for open deliberation and individual member input into legislation.
Paediatric heart transplantation in Australia is centralised at The Royal Children’s Hospital, Melbourne. Survival to adulthood is improving but the ongoing need for complex medical therapy, surveillance, and potential for late complications continues to impact on quality of life. Quality of life in adults who underwent heart transplantation in childhood in Australia has not been assessed.
Cross-sectional quality of life data were collected from paediatric heart transplant survivors >18 years of age using Rand 36-Item Health Survey. Self-reported raw scores were transformed to a 0–100 scale with higher scores indicating better quality of life. Mean scores were compared to National Health Survey Short Form-36 Population Norms data using the independent sample t-test.
A total of 64 patients (64/151) who underwent transplantation at The Royal Children’s Hospital between 1988 and 2016 survived to adulthood. In total 51 patients (51/64, 80%) were alive at the time of the study and 27 (53%) responded with a mean age of 25 ± 6 years, being a median of 11 years (interquartile range 7–19) post-transplantation. Most self-reported quality of life subscale scores were not significantly different from the Australian normative population data. However, self-reported ‘General Health’ was significantly worse than normative data (p = 0.02). Overall, 93% (25/27) reported their general health as being the same or better compared to 1-year ago.
Adult survivors after paediatric heart transplantation in Australia report good quality of life in multiple domains and demonstrate independence in activities of daily living and employment. However, lifelong medical treatment may affect perceptions of general health.
Can America Govern Itself? brings together a diverse group of distinguished scholars to analyze how rising party polarization and economic inequality have affected the performance of American governing institutions. It is organized around two themes: the changing nature of representation in the United States; and how changes in the political environment have affected the internal processes of institutions, overall government performance, and policy outcomes. The chapters in this volume analyze concerns about power, influence and representation in American politics, the quality of deliberation and political communications, the management and implementation of public policy, and the performance of an eighteenth century constitution in today's polarized political environment. These renowned scholars provide a deeper and more systematic grasp of what is new, and what is perennial in challenges to democracy at a fraught moment.