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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.
What is normal trade law? The completion of the Uruguay Round in 1994 and the establishment of the World Trade Organization (WTO) seemed to mark the achievement of normal trade law, both in the sense of normalizing regulation of international trade relations by legal norms and institutions and in the sense of a normal content of trade law involving significant international convergence rather than sovereign diversity. Both of these senses of normal trade law now seem to be under pressure. The stalemate at the WTO, the turn to preferential agreements and the more recent return of belligerent sovereign unilateralism all suggest the need to interrogate again the legal context in which global trade and investment is embedded. Going forward, trade law may need to emphasize less convergent substantive concepts such as exceptions, differential treatment, interface and variable geometry. But this may also be the moment to rethink whether normal trade law involves a return to a more open role for international politics (including negotiation, threats and conflict), as well as a normal role for law better understood through the frames of transnational law and legal pluralism.
The Concept of Normal Trade
Defining normal trade in international economic relations was clearly a contested and negotiated task during the era of the General Agreement on Tariffs and Trade (GATT), with relatively thin international-level trade regulation combined with plural varieties of domestic market regulation, including in socialist states. The contested nature of normal trade was strikingly exemplified by US– China trade relations before 2000, which were significantly framed around the annual political maneuvering to grant the presidential waiver that would allow for the formal status of normal trade relations with China under US trade law. Normal trade relations involved the continuation of the most-favored-nation (MFN) treatment already extended by the United States to most of its trading partners, including all of the WTO– GATT membership. A major change in the character of the trade relationship between two distinct national economies therefore was marked when Congress passed legislation to grant China permanent normal trade relations (PNTR) in anticipation of the accession of China to the WTO in 2001. Similarly, Russia gained PNTR in 2012.
This study presents the first complete glacier inventory of the Torngat Mountains, northern Labrador, Canada. In total, 195 glaciers and ice masses are identified, covering a total area of 24.5 ± 1.8 km2. Mapped ice masses range in size from 0.01 to 1.26 km2, with a median size of 0.08 km2. Ice masses have a median elevation of 776 m a.s.l. and span an altitudinal range of 290–1500 m a.s.l. Indications of ice flow suggest at least 105 active glaciers in the Torngat Mountains. Analysis of morphometric and topographic parameters suggests that the regional distribution of ice masses is linked to physiographic setting while the preservation of coastal ice masses at low elevation is related to local meteorological conditions. In the most coastal environments, ice masses are shown to exist below the regional glaciation level due to topographic shadowing, coastal proximity and widespread debris cover. This study provides a baseline for future change assessment.
Chloride ion concentration can be used as a biomarker for the level of pollen exposure in allergic asthma, chronic cough and airway acidification related to respiratory disease. AlGaN/GaN high electron mobility transistor (HEMT) with an InN thin film in the gate region was used for real time detection of chloride ion detection. The InN thin film provided surface sites for reversible anion coordination. The sensor exhibited significant changes in channel conductance upon exposure to various concentrations of NaCl solutions. The sensor was tested over the range of 100 nM to 100 μM NaCl solutions. The effect of cations on the chloride ion detection was also studied.
Reaction time (RT) variability is one of the strongest findings to emerge in cognitive-experimental research of attention deficit hyperactivity disorder (ADHD). We set out to confirm the association between ADHD and slow and variable RTs and investigate the degree to which RT performance improves under fast event rate and incentives. Using a group familial correlation approach, we tested the hypothesis that there are shared familial effects on RT performance and ADHD.
A total of 144 ADHD combined-type probands, 125 siblings of the ADHD probands and 60 control participants, ages 6–18, performed a four-choice RT task with baseline and fast-incentive conditions.
ADHD was associated with slow and variable RTs, and with greater improvement in speed and RT variability from baseline to fast-incentive condition. RT performance showed shared familial influences with ADHD. Under the assumption that the familial effects represent genetic influences, the proportion of the phenotypic correlation due to shared familial influences was estimated as 60–70%.
The data are inconsistent with models that consider RT variability as reflecting a stable cognitive deficit in ADHD, but instead emphasize the extent to which energetic or motivational factors can have a greater effect on RT performance in ADHD. The findings support the role of RT variability as an endophenotype mediating the link between genes and ADHD.
Several randomized controlled trials have suggested that mild induced hypothermia may improve neurologic outcome in comatose cardiac arrest survivors. This systematic review of randomized controlled trials was designed to determine if mild induced hypothermia improves neurologic outcome, decreases mortality, or is associated with an increased incidence of adverse events.
The following databases were reviewed: Cochrane Controlled Trials Register (Issue 4, 2005), MEDLINE (January 1966 to November 2005), EMBASE (1980 to November 2005), CINAHL (1982 to November 2005) and Web of Science (1989 to November 2005). For each included study, references were reviewed and the primary author contacted to identify any additional studies.
Studies that met inclusion criteria were randomized controlled trials of adult patients (>18 years of age) with primary cardiac arrest who remained comatose after return of spontaneous circulation. Patients had to be randomized to mild induced hypothermia (32°C-34°C) or normothermia within 24 hours of presentation. Only studies reporting pre-determined outcomes including discharge neurologic outcome, mortality or significant treatment-related adverse events were included. There were no language or publication restrictions.
Four studies involving 436 patients, with 232 cooled to a core temperature of 32°C-34°C met inclusion criteria. Pooled data demonstrated that mild hypothermia decreased inhospital mortality (relative ratio [RR] 0.75; 95% confidence interval [CI], 0.62-0.92) and reduced the incidence of poor neurologic outcome (RR 0.74; 95% CI, 0.62-0.84). Numbers needed to treat were 7 patients to save 1 life, and 5 patients to improve neurologic outcome. There was no evidence of treatment-limiting side effects.
Therapeutically induced mild hypothermia decreases in-hospital mortality and improves neurologic outcome in comatose cardiac arrest survivors. The possibility of treatment-limiting side effects cannot be excluded.
This article discusses four judgments of the Supreme Court of Canada that transformed private international law in Canada and represent a striking episode in the internationalization of law — a form of judicial activism in the name of the international. It is argued that these cases evidence a mode of internationalization by internationalist policy consciousness that is distinct from, although often complementary to, internationalization via the mechanism of international treaties or changes in customary international law. The key features of this approach suggest some resemblances to the vision found in the traditions of liberal internationalism, Canadian internationalism, and public international law. The article cautions against several general dangers in the use of this approach in law reform and adjudication and uses two specific doctrinal issues in private international law to demonstrate what a richer policy discourse concerning internationalism would be.
Studies have shown that management training and development (MTD) can be a strategic weapon in improving performance and in building and sustaining competitive advantage. However, recent studies suggest that MTD is under-valued and under-used as a strategic tool by New Zealand firms as, despite a managerial skill shortage, New Zealand firms have not invested heavily in MTD. The present paper discusses a study of employer-based MTD in New Zealand that investigated managerial attitudes towards, and propensity to engage in, MTD. The study found several indicators that predict four MTD related variables (the MTD index, the percent of payroll spent on MTD, the increase in training expenditure and expected future increases in the MTD budget). The results suggest organisations that engage in MTD improve organisational effectiveness and implement their business strategy better and that MTD was seen as an important tool in gaining a competitive advantage.
We describe a reversible technique for locally modifying the oxygen stoichiometry and electrical transport properties of superconducting thin films. A focused argon ion laser beam is scanned across the surface of a YBa2Cu3O7-x thinfilm, contained in a vacuum, at incident power levels well below those necessary for ablation. The change in oxygen stoichiometry is monitored in-situ by the room temperature electrical resistance. We have measured the superconducting properties of these locally modified films. The resulting R vs T curve for the composite structure (film/laserstripe/film) shows the expected double transition. The first transition, corresponding to the unmodified film, occurs at 87 K while the second transition, corresponding to the modified stripe, occurs at a lower temperature and is a function of the laser induced change in the room temperature electrical resistance. The critical current for the composite structure is depressed from the original film. The laser writing can be erasedor bleached out by room temperature exposure to an oxygen plasma.