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Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12–23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.
To investigate the association between parity and the risk of incident dementia in women.
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
We sought to characterize patients’ preferences for the role of religious and spiritual (R&S) beliefs and practices during cancer treatment and describe the R&S resources desired by patients during the perioperative period.
A cross-sectional survey was administered to individuals who underwent cancer-directed surgery. Data on demographics and R&S beliefs/preferences were collected and analyzed.
Among 236 participants, average age was 58.8 (SD = 12.10) years; the majority were female (76.2%), white (94.1%), had a significant other or spouse (60.2%), and were breast cancer survivors (43.6%). Overall, more than one-half (55.9%) of individuals identified themselves as being religious, while others identified as only spiritual (27.9%) or neither (16.2%). Patients who identified as religious wanted R&S integrated into their care more often than patients who were only spiritual or neither (p < 0.001). Nearly half of participants (49.6%) wanted R&S resources when admitted to the hospital including the opportunity to speak with an R&S leader (e.g., rabbi; 72.1%), R&S texts (64.0%), and journaling materials (54.1%). Irrespective of R&S identification, 68.0% of patients did not want their physician to engage with them about R&S topics.
Significance of results
Access to R&S resources is important during cancer treatment, and incorporating R&S into cancer care may be especially important to patients that identify as religious. R&S needs should be addressed as part of the cancer care plan.
For African American emerging adult men, developmental challenges are evident in their escalating substance abuse and depressive symptoms; this is particularly true for men from low-resource communities. The present study tests a developmental model linking childhood adversity and contemporaneous contextual stressors to increases in emerging adults’ substance use and depressive symptoms, indirectly, via increases in defensive/hostile relational schemas and social developmental risk factors (e.g., risky peers and romantic partners, lack of involvement in school or work). We also advance exploratory hypotheses regarding DNA methylation in the oxytocin receptor gene (OXTR) as a moderator of the effects of stress on relational schemas. Hypotheses were tested with three waves of data from 505 rural African American men aged 19–25 years. Adverse childhood experiences predicted exposure to emerging adult contextual stressors. Contextual stressors forecast increases in defensive/hostile relational schemas, which increased social developmental risk factors. Social developmental risk factors proximally predicted increases in substance abuse and depressive symptoms. OXTR DNA methylation moderated the effects of contextual stressors on defensive/hostile relational schemas. Findings suggest that early exposures to stress carry forward to affect the development of social developmental risk factors in emerging adulthood, which place rural African American men at risk for increased substance abuse and depressive symptoms during the emerging adult years.
Infrastructures of multilevel democracy are cumulative historical products. Their origins can date back to early state formation. Their institutional foundations were often laid before the arrival of mass democracy, national constitutional orders, state bureaucracies, or urban industrial society. Their formation and evolution has often followed distinct trajectories from national democratization, industrialization, and even the formation of national territorial states. For most of what are now developed democracies, the pivotal events took place over the long nineteenth century from the American Revolution to World War I. Over that period, throughout Europe, North America, and Japan, new national systems of local self-government and territorial administration at the scale of cities and communities established a local state. Introduced at the higher levels of states rather than localities themselves, enactments embedded into wider constitutional and administrative orders formalized a set of local institutions that had previously been informal or at best a patchwork, or had not existed before. In some instances this local state was the result of pressures from civil society. Other times it was the consequence of reform from above. Whatever its origins, this local state would shape the subsequent development of civic and political movements, and the emergence of the policy state.
In July of 1831, one year after the July Revolution established a constitutional monarchy in France, Alexis de Tocqueville and Gustave de Beaumont arrived in New York City on an official mission to investigate the US prison system. Over the next eight months their travels took them thousands of miles throughout the forty-year-old United States, from Canada to New Orleans. They spent only two weeks in the newly established national capital of Washington, DC. In the following decade, in a pivotal work that would become a touchstone of modern political science, Tocqueville expressed his admiration for a society where politics sprang from the many communities he visited rather than from the powerful hierarchies that still dominated Europe.
In the contemporary world of nation states and globalizing forces, institutions and governance arrangements at the scale of cities and communities remain a persistent fact of political life. Systems of local government addressed to this scale are a near-universal feature of contemporary democracies. In older democracies they grow out of long-established traditions, and take the form of highly institutionalized instances for decision-making, policy implementation, and political participation (Page and Goldsmith, 1987, Hesse and Sharpe, 1991, Pierre, 1999, Vetter, 2007, Lidström, 2003). The reasons governance at the local scale has persisted go well beyond the case that Tocqueville made for local institutions. Since long before he wrote, the scale of communities and cities was regarded in Western political theory as the most critical site of linkages between society and the state. Contemporary democracies, along with other states, still rely systematically on local institutions. Democracy at the local and the national scale, and the continued efforts of nation states to shape society through policy, have compounded this reliance.
The growth and consolidation of a state built around policy marked the maturation of the three distinct varieties of multilevel democracy. Over the late twentieth and early twenty-first centuries, despite pressures toward convergence, distinctions between the three types have persisted. The multilevel lens through which we have examined these national systems of local institutions and their origins casts new light on a whole range of literatures that have compared national democratic processes and policy performance among advanced industrial democracies. Comparisons of national democratic institutions, welfare states, and varieties of capitalism point to a variety of clear correspondences between national institutions, policy performance, and the overall quality of democracy. A multilevel conception of state–society relations opens a new window onto the operational realities that determine how these relationships work. Local and multilevel institutions further illuminate familiar differences among national democratic systems, and elucidate other variations in the quality of democracy that analyses of national institutions have struggled to explain. In demonstrating that local institutions were much more than an outgrowth of the main variations in national democratic traditions, we have shown how they repeatedly shaped the construction of democratic institutions at the national scale. Their consequences remain apparent in the contemporary operational realities of democracies at the local scale, and continue to influence the quality of democratic institutions today.
We began this volume with an examination of several alternative ways that democratic nation states incorporate civil society and local institutions. Historical analysis traced the origins of contemporary differences in multilevel democracy. Comparison showed them to have affected both the performance of policy and the overall quality of democracy over the long run. Even among the relatively successful multilevel democracies examined in this study, however, the problem of enhancing and sustaining multilevel democracy poses persistent challenges. Across the developing world, even greater challenges confront efforts to construct new, more inclusive and effective institutions at the local scale. Following a brief summary of the overall argument, this chapter briefly sketches these questions for the future.
In the perspective of multilevel democratic theory, local democracy is fundamental to national democracy. In ways that previous typologies of national democratic institutions have neglected, local institutions and their linkages to governance at higher levels matter for how, as well as how well, democracy works. Alternative models of multilevel democracy depend on distinctive infrastructures of local government and administration, on particular forms of organization in civil society, and on divergent patterns of relations between the state and society at the local as well as the supralocal scale. Logics of infrastructural power, democratic accountability, and contestation foster overarching complementarities among institutions that are usually analyzed separately, from local government and national administration to political parties and organized interests. In countries with a state-dependent local government, hierarchical administration, and restricted incorporation of a local elitist model, civic participation and organization should remain limited. In countries with the independent local government and broad local societal incorporation of the civic localist model, civic organization should be broad based but have limited organizational hierarchies. Where a nationalized infrastructure assigns responsibility for national policy to institutions at the local scale, broad civic and political participation should be incorporated into hierarchical organizations at both the national and the local level.
The final stage in the elaboration of contemporary infrastructures for multilevel local governance was a wider transformation in the tasks and operation of the state. In a vast range of domains, new institutions established the development and pursuit of specific collective aims, or public policies, as a defining feature of public life. On top of constitutional hierarchies among governments, and the general features of administrative capacity linked to national bureaucracies, new layers of policymaking institutions introduced rules and procedures that reordered relationships among governments as well as between the state and society. The growth of the welfare state has been perhaps the most studied of these developments. The emergence of social policy created new domains of state activity from education to health to social insurance. These were only a part of an even wider expansion of public policy throughout society, to consumer protection, economic development, economic regulation, and environmental quality. Even policies that were already a feature of early states, such as policing and emergency services, became regularized and professionalized.
Throughout Europe, North America, and Japan, the era that has come to be known as the long nineteenth century was a period of growth in civic, political, and economic associations (Hoffmann, 2003). Even in industrialized societies that only later became established democracies, many of the leading political parties, organized economic interests, and civic organizations of today trace their founding to this era. Middle- and working-class movements mobilized, organized electoral competition diffused increasingly across borders, and political interests organized around the economic and social structures of industrial capitalism (e.g., Bartolini, 2000, Tarrow, 1994, Katznelson and Zolberg, 1986). The wider societal shifts that contributed to civic formation, from urbanization to the spread of literacy and the rise of professionalized middle classes (Bermeo and Nord, 2000, Morton et al., 2006), also played out at the local scale. The emergent multilevel state largely preceded and helped give shape to these transformations, even as its own architecture increasingly reflected their influence. An increasingly vast literature has examined these developments through a variety of lenses, from general historical overviews of civic associational development to more focused accounts of the emergence of consociational democracy, political party systems, and organized business associations and working-class movements.