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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
In today's age of restrictionism, a growing number of countries are closing their gates of admission to most categories of would-be immigrants with one important exception. Governments increasingly seek to lure and attract “high value” migrants, especially those with access to large sums of capital. These individuals are offered golden visa programs that lead to fast-tracked naturalization in exchange for a hefty investment, in some cases without inhabiting or even setting foot in the passport-issuing country to which they now officially belong. In the U.S. context, the contrast between the “Dreamers” and “Parachuters” helps to draw out this distinction between civic ties and credit lines as competing bases for membership acquisition. Drawing attention to these seldom-discussed citizenship-for-sale practices, this essay highlights their global surge and critically evaluates the legal, normative, and distributional quandaries they raise. I further argue that purchased membership goods cannot replicate or substitute the meaningful links to a political community that make citizenship valuable and worth upholding in the first place.
Debates on “rising powers” and a possible end to the liberal international order mostly focus on two kinds of actors: the hegemon (the United States), privileged by the power distribution of yesteryear, and rising powers (notably China). Europe's curious position brings to light some intriguing dynamics of the emerging world order—nuances needed to capture a more differentiated future. This essay traces the threats and opportunities to Europe presented by the emerging order in four domains. In terms of overall power (polarity) and economics, far-reaching change registers but is rarely designated as threatening. In contrast, change regarding values (human rights and democracy especially) triggers more alarm. Finally, in the domain of institutions, change elicited a relative lack of concern prior to 2016, but worries have grown since then. For Europe, peaceful change primarily demands that rising powers rearticulate rather than confront classical Western values because, in contrast to the United States, there is little sense of loss in Europe in relation to the global structures of power and economics.
In the early years of the twenty-first century the narrative of “emerging powers” and “rising powers” seemed to provide a clear and powerful picture of how international relations and global politics were changing. Yet dramatic changes in the global system have led many to conclude that the focus on the BRICS and the obsession with the idea of rising powers reflected a particular moment in time that has now passed. The story line is now about backlash at the core; and, with the exception of China, rising powers have returned to their role as secondary or supporting actors in the drama of global politics. Such a conclusion is profoundly mistaken for three sets of reasons: the continued reality of the post-Western global order; the need to understand nationalist backlash as a global phenomenon; and the imperative of locating and strengthening a new pluralist conception of global order.
While Russian leaders are clearly dissatisfied with the United States and the European Union, they are not inherently opposed to a liberal world order. The question of Russia's desire to change a liberal international order hangs on the type of liberalism embedded in that order. Despite some calls from within for it to create a new, post-liberal order premised on conservative nationalism and geopolitics, Russia is unlikely to fare well in such a world.
The crisis of the American-led international order would seem to open up new opportunities for rising states—led by China, India, and other non-Western developing countries—to reshape the global order. As their capacities and influence grow, will these states rise up and integrate into the existing order or will they seek to overturn and reorganize it? The realist hegemonic perspective expects today's power transition to lead to growing struggles between the West and the “rest” over global rules and institutions. In contrast, this essay argues that although America's hegemonic position may be declining, the liberal international characteristics of order—openness, rules, and multilateralism—are deeply rooted and likely to persist. And even as China seeks in various ways to build rival regional institutions, there are stubborn limits on what it can do.
India is gradually changing its course from decades of inward-looking economics and strong anti-Western foreign policies. It has become more pragmatic, seeing important economic benefits from globalization, and some political benefits of working with the United States to achieve New Delhi's great-power aspirations. Despite these changes, I argue that India's deep-seated anti-colonial nationalism and commitment to strategic autonomy continues to form the core of Indian identity. This makes India's commitment to Western-dominated multilateral institutions and Western norms, such as humanitarian intervention, partial and instrumental. Thus, while Indian foreign-policy discourse shows little sign of seeking to fully challenge the U.S.-led international order beyond largely reformist measures of building parallel institutions such as the New Development Bank, India will continue to strongly resist Western actions that weaken sovereignty norms.
In this essay I survey the key themes within China's discourse on international order, especially how China views its position and role in shaping the existing and future order. I go on to explore the possible implications of China's thinking and actions toward the existing international order. I conclude that overall, China sees no need for and hence does not seek fundamental transformation, but rather piecemeal modification of the existing order. In fact, China has been quite content with the existing order that supports globalization, despite occasional rhetoric indicating otherwise. In the near future, China will likely invest heavily in two key issue areas: (1) regionalism in East Asia and Central Asia; and (2) interregional cooperation and coordination. Perhaps unsurprisingly, China's ambitious “One Belt and One Road” initiative seeks to integrate these two issue areas.
Four recent books, taken together, offer a wealth of important insights on how we might effectively tackle corruption. All of the books’ authors agree that there is something akin to a universal understanding of what corruption is, and all dispute the idea that corruption may simply be in the eye of the beholder. However, there are also sharp disagreements—for example over whether corruption is best eliminated from the top down, or whether bottom-up approaches are more effective. If the books share one weakness, it is that they do not sufficiently emphasize the importance of getting people to believe and feel that they have fair opportunities for good lives, even after institutional and legal reforms are made. Tackling corruption involves taking seriously the substantive link between actual fair treatment and the belief that fair treatment prevails. This will require further research examining how to shift and update people’s deeply held sentiments.