To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Spinal muscular atrophy (SMA) is characterized by the progressive loss of motor neurons causing muscle atrophy and weakness. Nusinersen, the first effective SMA therapy was approved by Health Canada in June 2017 and has been added to the provincial formulary of all but one Canadian province. Access to this effective therapy has triggered the inclusion of SMA in an increasing number of Newborn Screening (NBS) programs. However, the range of disease-modifying SMN2 gene copy numbers encountered in survival motor neuron 1 (SMN1)-null individuals means that neither screen-positive definition nor resulting treatment decisions can be determined by SMN1 genotype alone. We outline an approach to this challenge, one that specifically addresses the case of SMA newborns with four copies of SMN2.
To develop a standardized post-referral evaluation pathway for babies with a positive SMA NBS screen result.
An SMA NBS pilot trial in Ontario using first-tier MassARRAY and second-tier multi-ligand probe amplification (MLPA) was launched in January 2020. Prior to this, Ontario pediatric neuromuscular disease and NBS experts met to review the evidence regarding the diagnosis and treatment of children with SMA as it pertained to NBS. A post-referral evaluation algorithm was developed, outlining timelines for patient retrieval and management.
Ontario’s pilot NBS program has created a standardized path to facilitate early diagnosis of SMA and initiation of treatment. The goal is to provide timely access to those SMA infants in need of therapy to optimize motor function and prolong survival.
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.
The beginning of Macbeth’s soliloquy in Act 2, scene 1 is one of the most recognisable passages in the canon. ‘Is this a dagger which I see before me, / The handle toward my hand? Come, let me clutch thee’ (Mac. 2.1.33–34). The words may be familiar but they still have some secrets.
The matter of attribution has to do with identifying the author (or even the most likely candidates) for a text whose authorship is doubtful, collaborative, or unknown. Such work has been practiced down the centuries, most often for the rectification of literary history but also in political and theological disputation where the authenticity of a document is at issue. Its apparent value in legal inquiry is limited by the fact that few criminals offer a substantial corpus of their writings. The notorious US Unabomber, who might well have written himself into gaol without benefit of other evidence, was a striking exception.
As chemical management options for weeds become increasingly limited due to selection for herbicide resistance, investigation of additional nonchemical tools becomes necessary. Harvest weed seed control (HWSC) is a methodology of weed management that targets and destroys weed seeds that are otherwise dispersed by harvesters following threshing. It is not known whether problem weeds in western Canada retain their seeds in sufficient quantities until harvest at a height suitable for collection. A study was conducted at three sites over 2 yr to determine whether retention and height criteria were met by wild oat, false cleavers, and volunteer canola. Wild oat consistently shed seeds early, but seed retention was variable, averaging 56% at the time of wheat swathing, with continued losses until direct harvest of wheat and fababean. The majority of retained seeds were >45 cm above ground level, suitable for collection. Cleavers seed retention was highly variable by site-year, but generally greater than wild oat. The majority of seed was retained >15 cm above ground level and would be considered collectable. Canola seed typically had >95% retention, with the majority of seed retained >15 cm above ground level. The suitability ranking of the species for management with HWSC was canola>cleavers>wild oat. Efficacy of HWSC systems in western Canada will depend on the target species and site- and year-specific environmental conditions.