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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.
This paper describes the results of two seasons of excavation and associated palaeoenvironmental analyses of a wetland site on Beccles Marshes, Beccles, Suffolk. The site has been identified as a triple post alignment of oak timbers (0.6–2.0 m long), over 100 m in length, and 3–4 m wide, running north-west to south-east towards the River Waveney. It was constructed in a single phase which has been dated dendrochronologically to 75 BC, although discrete brushwood features identified as possible short trackways have been dated by radiocarbon to both before and after the alignment was built. It is unclear if the posts ever supported a superstructure but notches (‘halving lap joints’) in some of the posts appear to have held timbers to support the posts and/or aid in their insertion. In addition, fragments of both Iron Age and Romano-British pottery were recovered. A substantial assemblage of worked wooden remains appears to reflect the construction of the post row itself and perhaps the on-site clearance of floodplain vegetation. This assemblage also contains waste material derived from the reduction splitting of timbers larger than the posts of the alignment, but which have not been recovered from the site. Environmental analyses indicate that the current landscape context of the site with respect to the River Waveney is probably similar to that which pertained in prehistory. The coleoptera (beetle) record illustrates a series of changes in the on-site vegetation in the period before, during and after the main phase of human activity which may be related to a range of factors including floodplain hydrology and anthropogenic utilisation of Beccles Marshes. The possible form and function of the site is discussed in relation to the later prehistoric period in Suffolk.
During the 1960s and 1970s, aerial reconnaissance on the northern side of the confluence of the Rivers Trent, Tame, and Mease in Staffordshire revealed a cluster of features indicative of prehistoric ceremonial activity. Some of the features within the cluster are morphologically unique, but a lack of previous investigation meant that their dating, phasing, and function were unknown. This paper details the results of a multi-disciplinary approach to addressing these questions about the complex and to place it into its contemporary landscape context. The results indicate that the complex represents numerous phases of symbolic and ceremonial activity extending from the late Neolithic and into the early Bronze Age. Furthermore, it has shown how these structures fit within a wider landscape of ceremonial activity extending back to the earlier Neolithic and continuing into the Bronze Age.
Epontic and benthic amphipods (Onisimus litoralis, Onisimus juveniles, Gammarus setosus, Anonyx nugax, and A. makarovi) and a pelagic mysid (Mysis oculatus) were collected under ice at Little Cornwallis Island, Northwest Territories, Canada. They were exposed, on site, to dissolved zinc and lead to determine lethal concentrations (LC50s). Incidental information was obtained on salinity and temperature tolerance. Subsequent testing of a temperate amphipod and oyster larvae exposed to the two metals provided comparative data to augment a literature review. The Arctic invertebrates were surprisingly insensitive under all test conditions. The implications for Arctic developments, particularly those involving near-shore, point-source discharges, are discussed and recommendations are made for effectively expanding a presently depauperate Arctic marine toxicity database.
A low activity mutant of glucose-6-phosphate dehydrogenase, G6pda-m1Neu has been used to position G6pd in the mouse X chromosome. Linkage tests with tabby, Ta and harlequin, Hq, indicate a likely gene order of Hq–G6pd–Ta. Muscular dystrophy, mdx, has been located by two-and three-point crosses using Hprt, Pgk-1 and Moblo and suggest a gene order of Hprt–mdx–Pgk-1–Moblo. Together with existing linkage data a tentative order for the seven loci is Hq–Hprt–G6pd–mdx–Ta–Pgk-1–Moblo. The relative positions of G6pd and mdx have not been directly tested and G6pd is assigned provisionally proximal to mdx. In the three point test using Hq, G6pd and Ta the recombination frequency found between Hq and Ta was 9·9 ± 2·6%, substantially less than the value of 20·5 ± 2·1% reported by Isaacson et al. (1974).
People wounded during bombings or other events resulting in mass casualties or in conjunction with the resulting emergency response may be exposed to blood, body fluids, or tissue from other injured people and thus be at risk for bloodborne infections such as hepatitis B virus, hepatitis C virus, human immunodeficiency virus, or tetanus. This report adapts existing general recommendations on the use of immunization and postexposure prophylaxis for tetanus and for occupational and nonoccupational exposures to bloodborne pathogens to the specific situation of a mass casualty event. Decisions regarding the implementation of prophylaxis are complex, and drawing parallels from existing guidelines is difficult. For any prophylactic intervention to be implemented effectively, guidance must be simple, straightforward, and logistically undemanding. Critical review during development of this guidance was provided by representatives of the National Association of County and City Health Officials, the Council of State and Territorial Epidemiologists, and representatives of the acute injury care, trauma, and emergency response medical communities participating in the Centers for Disease Control and Prevention’s Terrorism Injuries: Information, Dissemination and Exchange project. The recommendations contained in this report represent the consensus of US federal public health officials and reflect the experience and input of public health officials at all levels of government and the acute injury response community. (Disaster Med Public Health Preparedness. 2008;2:150–165)
There is a pressing need for region-specific information on the response of polar species to contaminants. The Protocol on Environmental Protection to the Antarctic Treaty states “…regular and effective monitoring shall take place to allow assessment of the impacts of ongoing activities, including the verification of predicted impact…”. Although the Treaty only applies to the Antarctic, similar requirements exist for the Arctic; thus, our comments below apply to both polar regions. Without ecotoxicological information all the effort that is directed towards contaminants monitoring is largely meaningless as it does not tell us whether the levels detected pose an environmental risk.
An outbreak of vancomycin-resistant Enterococcus faecium involving 28 infants in a neonatal intensive care unit was observed. Successful control of the outbreak was achieved following use of patient and staff cohorting, contact isolation precautions, patient and environmental surveillance cultures, environmental decontamination, molecular typing, introduction of an alcohol-based hand disinfectant, and decreased use of vancomycin.
Relatively poor memory for dreams is important evidence for Hobson et al.'s model of conscious states. We describe the time-gap experience as evidence that everyday memory for waking states may not be as good as they assume. As well as being surprisingly sparse, everyday memories may themselves be systematically distorted in the same manner that Revonsuo attributes uniquely to dreams.
Objectives: Although cost-utility analysis (CUA) has been
recommended by some experts as the preferred technique for economic
evaluation, there is controversy regarding what costs should be included and
how they should be measured. The purpose of this study was to: a) identify the
cost components that have been included in published CUAs; b) catalogue the
sources of valuation used; c) examine the methods employed for estimating
costs; and d) explore whether methods have changed over time.
Methods: We conducted a comprehensive search of the published
literature and systematically collected data on the cost estimation of CUAs.
We audited the cost estimates in 228 CUAs.
Results: In most studies (99%), analysts included some direct
healthcare costs. However, the inclusion of direct non-healthcare and time
costs (17%) was generally lacking, as was productivity costs (8%). Only 6% of
studies considered future costs in added life-years. In general, we found
little evidence of change in methods over time. The most frequently used
source for valuation of healthcare services was published estimates (73%). Few
studies obtained utilization data from RCTs (10%) or relied on other primary
data (23%). About two-thirds of studies conducted sensitivity analyses on cost
Conclusions: We found wide variations in the estimation of costs
in published CUAs. The study underscores the need for more uniformity and
transparency in the field, and continued vigilance over cost estimates in CUAs
on the part of analysts, reviewers, and journal editors.
This paper reports further data from the Stoke study of postnatal depression and examines whether psychosocial characteristics and symptom profiles differ between postnatal and control depression.
Two hundred and thirty-two postnatal and non-postnatal control women were screened with the Edinburgh Postnatal Depression Scale; all high scorers and a sample of low scorers were interviewed with the Standardised Psychiatric Interview and modified Social Maladjustment Schedule. Depression was diagnosed using the Research Diagnostic Criteria.
Postnatal but not control depression was associated with a poor relationship with the woman's own mother and greater occupational instability. Depression in control women was associated with low income, having three or more children, performing manual work and occupational dissatisfaction, but postnatal depression was not. There were no differences in the symptom profiles of the postnatal and control women nor between early and late onset postnatal depression.
Depression is a common and socially disabling disorder affecting mothers of young children. Postnatal depression is more contingent on acute biopsychosocial stresses caused by the arrival of a new family member. Depression in women with older children is more closely related to longer term social adversity.