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In this article, we analyse the implications of the end of the Cold War for US non-proliferation policy and the non-proliferation regime. Contrary to widely held expectations, we show that the end of bipolarity did not undercut the pursuit of non-proliferation but supercharge it. While bipolarity had afforded non-proliferation hold-outs opportunities to evade superpower pressure, the structural condition of unipolarity both incentivised and enabled the United States to pursue a more robust non-proliferation policy than before. Against the view that contemporary unipolar power is severely circumscribed by the need to make compromises and adhere to social norms, unipolarity allowed the United States to entrench a regime that was widely considered unjust. We support this argument with an analysis of non-proliferation dynamics in the early 1990s, focusing in particular on the process that culminated with the indefinite extension of the Non-proliferation Treaty (NPT) in 1995.
Chemical, biological, radiological, and nuclear (CBRN) incidents require meticulous preparedness, particularly in the Middle East and North Africa (MENA) region. This study evaluated CBRN response operational flowcharts, tabletop training scenarios methods, and a health sector preparedness assessment tool specific to the MENA region.
Methods
An online Delphi survey engaging international disaster medicine experts was conducted. Content validity indices (CVIs) were used to validate the items. Consensus metrics, including interquartile ranges (IQRs) and Kendall’s W coefficient, were utilized to assess the panelists’ agreement levels. Advanced artificial intelligence computing methods, including sentiment analysis and machine-learning methods (t-distributed stochastic neighbor embedding [t-SNE] and k-means), were used to cluster the consensus data.
Results
Forty experts participated in this study. The item-level CVIs for the CBRN response flowcharts, preparedness assessment tool, and tabletop scenarios were 0.96, 0.85, and 0.84, respectively, indicating strong content validity. Consensus analysis demonstrated an IQR of 0 for most items and a strong Kendall’s W coefficient, indicating a high level of agreement among the panelists. The t-SNE and k-means identified four clusters with greater European response engagement.
Conclusions
This study validated essential CBRN preparedness and response tools using broad expert consensus, demonstrating their applicability across different geographic areas.
Soft wheat (Triticum aestivum L.) improvement could be enhanced by the identification of germplasm with superior end-use quality traits. Due to the geographic and historical separation of eastern and western US soft wheat germplasm ‘pools’, genetic differences in end-use quality may exist among cultivars arising from these two pools. To identify such differences, 30 US soft wheat cultivars were evaluated in ‘head-to-head’ trials over 3 years in Washington state. Cultivars were classified as: eastern soft red winter (SRW), eastern soft white winter (ESWW), western soft white (WSWW) and western Club. These four soft wheat cultivar classifications clearly differed systematically for some of the quality traits examined. The Club wheat cultivar group had the highest flour yield and flour ash. The Club group also had the lowest mixograph dough water absorption. Milling score (which incorporates break flour yield) was highest for Club and ESWW. Eastern soft red and white wheat cultivar groups had lower flour ash and alkaline water retention capacity (AWRC) compared to the western Club and soft white wheats; ESWW had the lowest AWRC of any classification. Cookie diameter was greatest for the ESWW group, followed by the SRW and Club groups (which were not significantly different), and then by the WSWW group. Individual cultivars with exceptional quality traits were also identified. These results indicate that the four US soft wheat germplasm pools differ, and they may be valuable genetic resources for ‘inter-pool’ wheat improvement.
Biophysical conditions played a fundamental role in early human colonization of insular territories, particularly in food-producing societies dealing with limited resources and the challenges of maintaining a sustainable carrying capacity. Studies on past human colonization of small oceanic islands thus offer insights into economic plasticity, ecological impacts, and adaptation of early food-producing groups. On the coast of southern Chile, early evidence is dated to 950 cal BP of island colonization by coastal populations with mainland subsistence systems based on the exploitation of marine resources, along with gathering, managing, and cultivating plants and hunting terrestrial animals. Strikingly, the extent to which these mixed economies contributed to insular colonization efforts is largely unknown. Here we used organic residue analysis of ceramic artifacts to shed light on the subsistence of populations on Mocha Island in southern Chile. We extracted and analyzed lipids from 51 pottery sherds associated with the El Vergel cultural complex that flourished in southern Chile between 950 and 400 cal BP. Chemical and stable isotope analysis of the extracts identified a range of food products, including C3 and C4 plants and marine organisms. The results reveal the central role of mixed subsistence systems in fueling the colonization of Mocha Island.
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.
Objectives:
To develop a standardized post-referral evaluation pathway for babies with a positive SMA NBS screen result.
Methods:
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.
Conclusions:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Head injury is an important cause of morbidity and mortality in pediatrics. Comprehensive studies on outcome are scarce despite significant clinical concern that multiple areas of functioning may be impaired following moderate to severe head injury. The literature suggests that sequelae include not only medical problems but also impairments in cognitive functioning.
Methods:
Aretrospective medical and psychology chart review of patients, age 1-18 years, admitted to the Children's Hospital of Eastern Ontario with moderate (Glasgow Coma Scale [GCS] 9-12) or severe head injury (GCS ≤ 8) from November 1, 1993 until December 31, 1998 was conducted. Correlations were performed between medical variables (i.e., GCS, Pediatric Risk of Mortality [PRISM] III score, duration of ICU and hospital stay) and measures of intelligence and memory functioning.
Results:
Eighty-three children age 1 to 18 were included. Seventy percent of the children were classified as having a severe head injury. There was a mortality rate of thirteen percent. Younger age at injury, lower GCS, and higher PRISM III scores predicted higher mortality. Medical complications were documented systematically. Forty-four patients underwent at least one cognitive assessment and 17 of these children had intelligence testing at three points in time: baseline (< four months), early recovery (five to 15 months) and follow-up (16 to 38 months). The mean intelligence and memory scores fell within the average range at the latest point in follow-up. For those children who underwent three serial assessments, the mean verbal and performance IQ fell within the low average range at baseline improving significantly to fall within the average range by early recovery. Continued improvements were apparent in verbal memory beyond early recovery, with the mean obtained at follow-up falling within 1 SD of the normative mean. Despite the return to normal ranges for the group means the proportion of scores falling below 1.5 standard deviations from the mean was greater than population norms for verbal IQ, performance IQ and verbal memory. Lower GCS scores and longer duration of stay in ICU or hospital were predictive of lower nonverbal intelligence. Lower GCS was also predictive of lower visual memory scores.
Conclusions:
This study describes a population of Canadian children who suffered moderate or severe traumatic brain injury. Initial GCS was the best predictor of mortality and cognitive outcome. These children demonstrated a temporal improvement in intelligence and memory functioning, with their mean performance on these cognitive measures falling within the average range at 16 to 38 months postinjury, although there was considerable variability in the outcomes between individuals.
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.
Polyarteritis nodosa (PAN) is a rare, systemic necrotizing vasculitis of medium-sized arteries. The American College of Rheumatology criteria for the diagnosis of PAN includes at least three of: 1. weight loss < 4 kg, 2. livedo reticularis, 3. testicular pain or tenderness, 4. myalgias, weakness or leg tenderness, 5. mono-or polyneuropathy, 6. diastolic hypertension, 7. elevated blood creatinine or urea, 8. hepatitis B antigen or antibody in the serum, 9. aneurysms or occlusions of visceral arteries or 10. granulocytes on small or medium sized artery biopsy. Common sites of involvement include skin, joints, kidneys, gastrointestinal tract and peripheral nerves. Central nervous system involvement has been reported in up to 40% of cases; the usual manifestations are encephalopathy, focal deficits and seizures. Descriptions of PAN in the pediatric literature has been reported in fewer than 250 children.
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.
Objectives:
We aimed to describe the changes in diagnostic testing for dystrophinopathy and to determine the frequency of dystrophin mutations from 2000 to 2009.
Methods:
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.
Results:
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.
Conclusion:
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.
Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood.
Method:
To assess the current care of paediatric DMD patients in Canada, a questionnaire was mailed to 17 physicians who were members of the Canadian paediatric neuromuscular group. Areas of enquiry included; 1) multidisciplinary team composition; 2) means of DMD diagnosis; 3) corticosteroid use; surveillance and management for: 4) orthopaedic, 5) respiratory and 6) cardiac complications and 7) health maintenance (nutrition & immunizations).
Results:
Completed surveys were returned by 14/17 (82%) of physicians. Twelve respondents followed DMD patients. All centres had multidisciplinary teams, including respirology (11/12), child neurology or physiatry (11), physiotherapy (9), occupational therapy (9) and orthopaedic surgery (7). Deflazacort 0.9mg/kg/d was used at all centres, which was continued after loss of independent ambulation (11), along with routine calcium and vitamin D supplementation (10). Night splints were prescribed at all centres. Routine surveillance studies included pulmonary function testing (11), sleep studies (10), EKG/echocardiogram (10), bone density (DEXA) scans (10), spine radiography (9), and dietician referral (4).
Conclusion:
Paediatric DMD patients are receiving relatively consistent care in multidisciplinary clinics across Canada, in accordance with recommended guidelines for DMD.
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).
Case Report
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.
Results
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.
Conclusion
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.
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.
Methods:
We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).
Results:
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.
Conclusions:
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.