556 research outputs found
An all-Ireland epidemiological study of MND, 2004-2005
Background and methods: We conducted an all-Ireland population-based prospective epidemiological survey of motor neurone disease (MND) using the Northern Ireland and Republic of Ireland MND registers to examine the incidence and prevalence of the disease over the period 2004–2005.Results and conclusions: Incidence of MND was 1.9 per 100 000 person-years and rates were comparable in both the north and south of Ireland. Prevalence of MND was 5.0 per 100 000 population. When compared with previous published surveys of MND performed in the Republic of Ireland over the last 10 years, rates of disease have remained relatively constant. When standardized to the 1990 US population, the incidence of MND in Ireland was found to be consistent with other European prospective surveys of MND
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The Met Office HadGEM3-ES chemistry–climate model: evaluation of stratospheric dynamics and its impact on ozone
Free-running and nudged versions of a Met Office chemistry–climate model are evaluated and used to investigate the impact of dynamics versus transport and chemistry within the model on the simulated evolution of stratospheric ozone. Metrics of the dynamical processes relevant for simulating stratospheric ozone are calculated, and the free-running model is found to outperform the previous model version in 10 of the 14 metrics. In particular, large biases in stratospheric transport and tropical tropopause temperature, which existed in the previous model version, are substantially reduced, making the current model more suitable for the simulation of stratospheric ozone. The spatial structure of the ozone hole, the area of polar stratospheric clouds, and the increased ozone concentrations in the Northern Hemisphere winter stratosphere following sudden stratospheric warmings, were all found to be sensitive to the accuracy of the dynamics and were better simulated in the nudged model than in the free-running model. Whilst nudging can, in general, provide a useful tool for removing the influence of dynamical biases from the evolution of chemical fields, this study shows that issues can remain in the climatology of nudged models. Significant biases in stratospheric vertical velocities, age of air, water vapour, and total column ozone still exist in the Met Office nudged model. Further, these can lead to biases in the downward flux of ozone into the troposphere
Insular Celtic population structure and genomic footprints of migration
Previous studies of the genetic landscape of Ireland have suggested homogeneity, with population substructure undetectable using single-marker methods. Here we have harnessed the haplotype-based method fineSTRUCTURE in an Irish genome-wide SNP dataset, identifying 23 discrete genetic clusters which segregate with geographical provenance. Cluster diversity is pronounced in the west of Ireland but reduced in the east where older structure has been eroded by historical migrations. Accordingly, when populations from the neighbouring island of Britain are included, a west-east cline of Celtic-British ancestry is revealed along with a particularly striking correlation between haplotypes and geography across both islands. A strong relationship is revealed between subsets of Northern Irish and Scottish populations, where discordant genetic and geographic affinities reflect major migrations in recent centuries. Additionally, Irish genetic proximity of all Scottish samples likely reflects older strata of communication across the narrowest inter-island crossing. Using GLOBETROTTER we detected Irish admixture signals from Britain and Europe and estimated dates for events consistent with the historical migrations of the Norse-Vikings, the Anglo-Normans and the British Plantations. The influence of the former is greater than previously estimated from Y chromosome haplotypes. In all, we paint a new picture of the genetic landscape of Ireland, revealing structure which should be considered in the design of studies examining rare genetic variation and its association with traits
Pathophysiology and Treatment of Non-motor Dysfunction in Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease typically presenting with bulbar or limb weakness. There is increasing evidence that amyotrophic lateral sclerosis is a multisystem disease with early and frequent impacts on cognition, behaviour, sleep, pain and fatigue. Dysfunction of normal physiological and metabolic processes also appears common. Evidence from pre-symptomatic studies and large epidemiological cohorts examining risk factors for the future development of amyotrophic lateral sclerosis have reported a high prevalence of changes in behaviour and mental health before the emergence of motor weakness. This suggests that changes beyond the motor system are underway at an early stage with dysfunction across brain networks regulating a variety of cognitive, behavioural and other homeostatic processes. The full impact of non-motor dysfunction continues to be established but there is now sufficient evidence that the presence of non-motor symptoms impacts overall survival in amyotrophic lateral sclerosis, and with up to 80% reporting non-motor symptoms, there is an urgent need to develop more robust therapeutic approaches. This review provides a contemporary overview of the pathobiology of non-motor dysfunction, offering readers a practical approach with regard to assessment and management. We review the current evidence for pharmacological and non-pharmacological treatment of non-motor dysfunction in amyotrophic lateral sclerosis and highlight the need to further integrate non-motor dysfunction as an important outcome measure for future clinical trial design
Root canal instrumentation efficacy of non-fused and fused primary molar roots:a micro-computed tomography study
Purpose Pulpectomy may be indicated in restorable primary teeth exhibiting irreversible pulpitis or pulpal necrosis. The purpose of this study was to compare the cleaning and shaping efficacy of NiTi systems (Reciproc(R) Blue and MTwo(R)) with manual stainless-steel instrumentation in primary molars using micro-CT analysis. Methods Fifty-seven maxillary second primary molars were scanned using micro-CT. Teeth with three divergent roots were divided randomly (n = 15) according to instrument type (K file, MTwo (R), and Reciproc (R) Blue). Teeth with root fusion were instrumented manually as a separate group (n = 12). Pre- and post-instrumentation micro-CT images were superimposed, and the instrumentation area (IA) and procedural complications were recorded. Results No statistically significant differences in IA between file systems was observed in the non-fused teeth. The mean IA of fused roots was significantly lower than in the non-fused distobuccal (p = 0.003) and palatal (p 60%) occurred in both non-fused and fused primary teeth with fewer procedural complications observed after manual instrumentation
Concurrent sodium channelopathies and amyotrophic lateral sclerosis supports shared pathogenesis
Amyotrophic lateral sclerosis (ALS) is an invariably fatal adult-onset neurodegenerative disorder; approximately 10% of ALS is monogenic but all ALS exhibits significant heritability. The skeletal muscle sodium channelopathies are a group of inherited, non-dystrophic ion channel disorders caused by heterozygous point mutations in the SCN4A gene, leading to clinical manifestations of congenital myotonia, paramyotonia, and periodic paralysis syndromes. We provide clinical and genetic evidence of concurrence of these two rare disorders which implies a possible shared underlying pathophysiology in two patients. We then identify an enrichment of ALS-associated mutations in another sodium channel, SCN7A, from whole genome sequencing data of 4495 ALS patients and 1925 controls passing multiple testing correction (67 variants, p = 0.0002, Firth logistic regression). These findings suggest dysfunctional sodium channels may play a role upstream in the pathogenesis of ALS in a subset of patients, potentially opening the door to novel personalized medicine approaches
Benefits, pitfalls, and future design of population-based registers in neurodegenerative disease
Population-based disease registers identify and characterize all cases of disease, including those that might otherwise be neglected. Prospective population-based registers in neurodegeneration are necessary to provide comprehensive data on the whole phenotypic spectrum and can guide planning of health services. With the exception of the rare disease amyotrophic lateral sclerosis, few complete population-based registers exist for neurodegenerative conditions. Incomplete ascertainment, limitations and uncertainty in diagnostic categorization, and failure to recognize sources of bias reduce the accuracy and usefulness of many registers. Common biases include population stratification, the use of prevalent rather than incident cases in earlier years, changes in disease understanding and diagnostic criteria, and changing demographics over time. Future registers are at risk of funding shortfalls and changes to privacy legislation. Notwithstanding, as heterogeneities of clinical phenotype and disease pathogenesis are increasingly recognized in the neurodegenerations, well-designed longitudinal population-based disease registers will be an essential requirement to complete clinical understanding of neurodegenerative diseases.Health Research Board (Ireland
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