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Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Non-typhoidal Salmonella (NTS) serovars, sequences types and antimicrobial susceptibility profiles have specific associations with animal and human infections in Vietnam. Antimicrobial resistance may have an effect on the manifestation of human NTS infections, with isolates from asymptomatic individuals being more susceptible to antimicrobials than those associated with animals and human diarrhoea.
Allotment food gardens represent important sources of food security for urban residents. Since urban gardeners rarely receive formal agricultural education and have extremely limited space, they may be relying on readily available gardening advice (e.g., seed packet instructions), inventing cultural strategies that consider inter-specific competitive dynamics, or making poor planting decisions. Knowledge of garden crop diversity and planting arrangements can aid in designing strategies for productive urban gardens and food systems. We surveyed 96 individual plots in 10 allotment gardens in the Toronto region, assessed crop diversity within gardens and recorded planting practices used by urban gardeners by measuring the proximity of individual plants relative to similar or different crop species. We also compared planting densities used by urban gardeners with those recommended by major seed distributers. Collectively, Toronto urban agriculture contributes substantially to urban plant diversity (108 crops), but each plot tends to be relatively depauperate. Carrots and lettuce were three to five times more likely to be planted in clusters than intermingled with other crops (P < 0.05); whereas gardeners did not appear to use consistent planting arrangements for tomatoes or zucchini. Gardeners tended to plant tomatoes and zucchini 56–62.5% more densely than recommended by seed distributers (P < 0.001), whereas they planted 147 times fewer carrots in a given area than recommended (P < 0.05). Furthermore, neither crop planting density nor crop diversity changed with plot size. The planting arrangements we have documented suggest gardeners using allotment plots attempt plant densely in extremely limited space, and are employing cultural strategies that intensify competitive dynamics within gardens. Future research should assess the absolute and relative effect of altered cultural practices on yield, such that any modifications can be prioritized by their impact on yield.
Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.
Increased dietary Na intake and decreased dietary K intake are associated with higher blood pressure. It is not known whether the dietary Na:K ratio is associated with all-cause mortality or stroke incidence and whether this relationship varies according to race. Between 2003 and 2007, the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort enrolled 30 239 black and white Americans aged 45 years or older. Diet was assessed using the Block 98 FFQ and was available on 21 374 participants. The Na:K ratio was modelled in race- and sex-specific quintiles for all analyses, with the lowest quintile (Q1) as the reference group. Data on other covariates were collected using both an in-home assessment and telephone interviews. We identified 1779 deaths and 363 strokes over a mean of 4·9 years. We used Cox proportional hazards models to obtain multivariable-adjusted hazard ratios (HR). In the highest quintile (Q5), a high Na:K ratio was associated with all-cause mortality (Q5 v. Q1 for whites: HR 1·22; 95 % CI 1·00, 1·47, P for trend = 0·084; for blacks: HR 1·36; 95 % CI 1·04, 1·77, P for trend = 0·028). A high Na:K ratio was not significantly associated with stroke in whites (HR 1·29; 95 % CI 0·88, 1·90) or blacks (HR 1·39; 95 % CI 0·78, 2·48), partly because of the low number of stroke events. In the REGARDS study, a high Na:K ratio was associated with all-cause mortality and there was a suggestive association between the Na:K ratio and stroke. These data support the policies targeted at reduction of Na from the food supply and recommendations to increase K intake.
The October 2012 issue of PS published a symposium of presidential and congressional forecasts made in the months leading up to the election. In the following articles, the forecasters assess the accuracy of their models.
On September 10, 2012, immediately following the close of the Democratic Party's national nominating convention and 57 days before Election Day on November 6, my Convention Bump and Economy Model predicted that Barack Obama was likely to receive 51.3% of the national two-party popular vote. The Convention Bump and Economy Model consists of Gallup's preconvention preference poll, the net convention bump in the polls, and an adjusted second quarter GDP growth rate. The forecast pegged the certainty of an Obama plurality at 67%. No sure thing, but more likely than not. The traditional Trial-Heat and Economy Model predicted Obama's vote at 52.0%. The Convention Bump and Economy Model's prediction was the preferred forecast in 2012 because of the lateness of the parties' nominating conventions. Democrats did not even begin their convention until after Labor Day.
This symposium presents 13 articles forecasting the 2012 US national elections. Included in this collection are the eight national and one state presidential vote forecasting models published in PS: Political Science & Politics during the 2008 elections along with three additional forecasts and one article offering a composite of the forecasts. Although the focus remains on the presidential contest, as in past years, several articles extend their scope to cover the congressional elections as well.
This article presents forecasts of the 2012 presidential and US House of Representatives elections. The presidential forecasts are of the national two-party presidential vote percentage for the in-party candidate and are based on the trial-heat and economy forecasting equation and its companion convention-bump equation. The House election forecast is of the net seat change for the Democratic Party from 2010 to 2012. This forecast is produced from two versions of a seats-in-trouble forecasting equation.