To save 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 saving content to .
To save content items to your Kindle, first ensure email@example.com
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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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.
ABSTRACT IMPACT: Congregations’ support for social, emotional, mental and spiritual wellness is foundational to human health and their community knowledge and presence can improve resilience and health in socially vulnerable neighborhoods. OBJECTIVES/GOALS: The Indiana CTSI Monon Collaborative is listening and understanding the most pressing health issues in the community and are working together to design and deliver community health solutions. We worked with our community ambassador to launch a health and wellness learning community for ten congregations seeking to build a health-connector network. METHODS/STUDY POPULATION: Study team used qualitative (interviews, focus groups, listening sessions, learning management system, participatory-design research) and quantitative (surveys) data collection methods in the development and ongoing implementation of the learning community. Study Population: Based on initial assessment of health and social vulnerability data within the Marion County neighborhoods in Indianapolis, community ambassador engaged congregations in more vulnerable neighborhoods to seek participation in learning community. Ten congregations signed a covenant of participation; learning community includes 10 clergy and 8 health advocates. RESULTS/ANTICIPATED RESULTS: Since the inception of the Learning Community in May 2020, we have developed a better understanding of the assets and barriers of LC participants around health and well-being. Through ongoing virtual gatherings (facilitated by community ambassador Good to the Soul), sharing of resources through our online modules on Canvas (LMS), and synthesis of data captured throughout our time together, LC participants have developed SMART goals which will inform priority setting for congregations to assist them in identifying the resources and connections necessary to drive forward solutions together as they seek out funding opportunities to support health improvement. DISCUSSION/SIGNIFICANCE OF FINDINGS: The learning community has provided a space and structure for congregations to align around a shared goal focused on health and wellness. Through regular gatherings we were able to connect people, organizations, and systems who were all eager to learn and work across boundaries leading to greater resilience in vulnerable communities.
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.
This article examines the conflict between traditional Marxist attitudes toward war and the problem of the nuclear revolution. It shows how the advent of the nuclear revolution in the 1950s undermined traditional Marxist-Leninist concepts of war, and then goes on to argue that this development must be placed at the centre of contemporary Marxian IR if it is to have explanatory power in the twenty-first century. To make this case directly, it engages with Justin Rosenberg’s revival of Trotsky’s idea of uneven and combined development and its subsidiary law of ‘the whip of external necessity’, and argues that the whip can remain salient today only if one accepts the political utility of nuclear war. The impasse created by the nuclear revolution, it concludes, points Marxist IR in the direction of classic Marxist visions of supranationalism and human unity.
Energy intake (EI) and energy expenditure (EE) should not be considered independent entities, but more an inter-connected system. With increased physical activity and reduced snacking initiatives as prevalent Public Health measures, any changes to subsequent EI from these recommendations should be monitored. The aim of this study was to investigate changes in acute EI and appetite over four conditions: (1) a control condition with no snack and no exercise (CON); (2) a snack condition (+1 MJ; SK); (3) a moderate-intensity cycling exercise condition (−1 MJ; EX); and finally (4) both snack and exercise condition (+1 MJ, −1 MJ; EXSK). Acute changes in appetite (visual analogue scale) and lunchtime EI (ad libitum pizza meal) were recorded in twenty boys and eighteen girls (12–13 years). Lunch EI was not significantly different between conditions or sexes (P>0·05). Relative EI was calculated, where the energy manipulation (+1 MJ from the snack or −1 MJ from the exercise) was added to lunchtime EI. Relative EI indicated no significant differences between the sexes (P>0·05); however, in the EX condition, relative EI was significantly lower (P<0·001) compared with all other conditions. Appetite increased significantly over time (P<0·001) and was significantly higher in the CON and EX conditions compared with the SK and EXSK conditions. No significant sex differences were found between conditions. When aiming to evoke an acute energy deficit, increasing EE created a significantly larger relative energy deficit than the removal of the mid-morning snack. Sex was not a confounder to influence EI or appetite between any of the conditions.
Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of lysosomal metabolism. The clinical phenotypic spectrum encompasses overlapping features of variable severity and is suggestive of individual single sulfatase deficiencies (i.e., metachromatic leukodystrophy, mucopolysaccharidosis, and X-linked ichthyosis).
We describe a 3-year-old male with severe hypotonia, developmental regression and progressive neurodegeneration, coarse facial features, nystagmus (from ocular albinism), and dysmyelinating motor sensory neuropathy. Ethics approval was obtained from the Western University Ontario.
Extensive investigative work-up identified deficiencies of multiple sulfatases: heparan sulfate sulfamidase: 6.5 nmoles/mg/protein/17 hour (reference 25.0-75.0), iduronate-2-sulfate sulfatase: 9 nmol/mg/protein/4 hour (reference 31-110), and arylsulfatase A: 3.8 nmoles/hr/mg protein (reference 22-50). The identification of compound heterozygous pathogenic mutations in the SUMF1 gene c.836 C>T (p.A279V) and c.1045C>T (p.R349W) confirmed the diagnosis of MSD.
The complex clinical manifestations of MSD and the unrelated coexistence of ocular albinism as in our case can delay diagnosis. Genetic counselling should be provided to all affected families.
For more than four decades the twin goals of nuclear nonproliferation and disarmament have been an almost unchallenged objective of the “international community.” Like drought prevention, or bans on the use of child soldiers, nonproliferation remains a mostly uncontroversial, largely universalistic initiative to which few object. The proponents of nonproliferation are fond of stressing that the Treaty on the Nonproliferation of Nuclear Weapons (NPT) has more signatories than any other arms control treaty. Who would not want to prevent more states from obtaining nuclear weapons? And who, for that matter, would oppose the ideal of a world free of such weapons?
Patient registries represent an important method of organizing “real world” patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry.
We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).
The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 “index disease” patients. Another 618 “non-index” patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. “Index disease” patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS.
The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.
While the summit of the Antarctic Plateau has long been expected to harbor the best ground-based sites for terahertz (THz) frequency astronomical investigations, it is only recently that direct observations of exceptional THz atmospheric transmission and stability have been obtained. These observations, in combination with recent technological advancements in astronomical instrumentation and autonomous field platforms, make the recognition and realization of terahertz observatories on the high plateau feasible and timely. Here, we will explore the context of terahertz astronomy in the era of Herschel, and the crucial role that observatories on the Antarctic Plateau can play. We explore the important scientific questions to which observations from this unique environment may be most productively applied. We examine the importance and complementarity of Antarctic THz astronomy in the light of contemporary facilities such as ALMA, CCAT, SOFIA and (U)LDB ballooning. Finally, building from the roots of THz facilities in Antarctica to present efforts, we broadly highlight future facilities that will exploit the unique advantages of the Polar Plateau and provide a meaningful, lasting astrophysical legacy.
We carried out a population-based study of dystrophin mutations in patients followed by members of the Canadian Paediatric Neuromuscular Group (CPNG) over a ten-year period.
We aimed to describe the changes in diagnostic testing for dystrophinopathy and to determine the frequency of dystrophin mutations from 2000 to 2009.
De-identified data containing the clinical phenotypes, diagnostic methods, and mutational reports from dystrophinopathy patients followed by CPNG centres from January 2000 to December 2009 were analyzed using descriptive statistics.
773 patients had a confirmed diagnosis of dystrophinopathy based on genetic testing (97%), muscle biopsy (2%), or family history (1%). 573 (74%) had complete deletion/duplication analysis of all 79 exons or whole gene sequencing, resulting in 366 (64%) deletions, 64 (11%) duplications, and 143 (25%) point mutations. The percentage of patients who were diagnosed using currently accepted genetic testing methods varied across Canada, with a mean of 63% (SD 23). 246 (43%) mutations involved exons 45 to 53. The top ten deletions (n=147, 26%) were exons 45-47, 45-48, 45, 45-50, 45-55, 51, 45-49, 45-52, 49-50, and 46-47. 169 (29%) mutations involved exons 2 to 20. The most common duplications (n=29, 5.1%) were exons 2, 2-7, 2-17, 3-7, 8-11, 10, 10-11, and 12.
This is the most comprehensive report of dystrophin mutations in Canada. Consensus guidelines regarding the diagnostic approach to dystrophinopathy will hopefully reduce the geographical variation in mutation detection rates in the coming decade.
The Abecedarian study was designed to learn the extent to which an early childhood intervention program might prevent progressive developmental retardation among children born into poverty. Forty years ago, cross-sectional examinations of the cognitive development of children from poor families indicated that their cognitive test scores tended to be within the average range in infancy, but that disproportionate declines occurred after that period (Ramey, 1971). A particularly striking cross-sectional graph charted this kind of progressive decline in intellectual test performance among children born to mothers who themselves had low IQs (Heber, Dever, & Conry, 1968). Because at that time no biologically based etiology for most cases of mild retardation had been identified, many scientists believed that early “social deprivation or environmental deprivation” was implicated in the development of this condition. It followed that intervening to improve the intellectual stimulus value of the environment might prevent or ameliorate the disorder.
Largely based on animal research, evidence mounted that early experience supported development in ways that were critical for later functioning (e.g., Hunt, 1961). More to the point, this line of reasoning was supported by human-subject research conducted by Skeels and his colleagues (1938) in which one group of infants reared within institutions showed dramatic gains in developmental abilities when they were given the kinds of affectionate attention and handling not experienced by others from the same orphanage.