Urinary biomarkers for amyotrophic lateral sclerosis: candidates, opportunities and considerations.

Amyotrophic lateral sclerosis is a relentless neurodegenerative disease that is mostly fatal within 3-5 years and is diagnosed on evidence of progressive upper and lower motor neuron degeneration. Around 15% of those with amyotrophic lateral sclerosis also have frontotemporal degeneration, and gene mutations account for ∼10%. Amyotrophic lateral sclerosis is a variable heterogeneous disease, and it is becoming increasingly clear that numerous different disease processes culminate in the final degeneration of motor neurons.

Phase 2 randomized placebo controlled double blind study to assess the efficacy and safety of tecfidera in patients with amyotrophic lateral sclerosis (TEALS Study): Study protocol clinical trial (SPIRIT Compliant).

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder of the human motor system. Neuroinflammation appears to be an important modulator of disease progression in ALS. Specifically, reduction of regulatory T cell (Treg) levels, along with an increase in pro-inflammatory effector T cells, macrophage activation and upregulation of co-stimulatory pathways have all been associated with a rapid disease course in ALS.

DSP-01 Barriers to the diagnosis of motor neuron disease - a South Australian study.

MND is a progressive neurodegenerative disease characterised by death of upper and lower motor neurons, leading to progressive weakness of the bulbar, limb, thoracic and abdominal muscles. MND has a fairly stereotypical course, with death from respiratory failure occurring 2-4 years after symptom onset in most cases (1). Making the diagnosis of MND can be straightforward when key clinical criteria are met; however, at first presentation, rarely do patients meet these criteria, neurological changes may be subtle and disease progression slow.

Factors contributing to delays in the diagnosis of motor neuron disease - A South Australian study.

Objective(s): To characterize the clinical factors that influence time to diagnosis of motor neuron disease (MND) in a cohort of patients living in South Australia.

Design: A retrospective study.

Setting: Single centre study of patients managed at a tertiary referral hospital.

Parallel Methods for Finding k-Mismatch Shortest Unique Substrings Using GPU.

k-mismatch shortest unique substring (SUS) queries have been proposed and studied very recently due to its useful applications in the subfield of computational biology. The k-mismatch SUS query over one given position of a string asks for a shortest substring that covers the given position and does not have a duplicate (within a Hamming distance of k) elsewhere in the string. The challenge in SUS query is to collectively find the SUS for every position of a massively long string in a both time- and space-efficient manner.

The Influence of Electrostatic Controls on MDI Size Distribution Measurements.

Cascade impactor testing is widely used to characterize the aerodynamic particle-size distribution of metered dose inhaler aerosols. Charge is often imparted to MDI aerosols by triboelectrification as formulation rapidly travels through the valve stem and actuator during atomization. The presence of charge on MDI aerosols can impact the accuracy and reproducibility of APSD measurements made using cascade impactors.

Motor neurone disease: progress and challenges.

Major progress has been made over the past decade in the understanding of motor neurone disease (MND), changing the landscape of this complex disease. Through identifying positive prognostic factors, new evidence-based standards of care have been established that improve patient survival, reduce burden of disease for patients and their carers, and enhance quality of life. These factors include early management of respiratory dysfunction with non-invasive ventilation, maintenance of weight and nutritional status, as well as instigation of a multidisciplinary team including neurologists, general practitioners and allied health professionals.

EPITHET: Positive Result After Reanalysis Using Baseline Diffusion-Weighted Imaging/Perfusion-Weighted Imaging Co-Registration.

Background And Purpose: the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a prospective, randomized, double-blinded, placebo-controlled, phase II trial of alteplase between 3 and 6 hours after stroke onset. The primary outcome of infarct growth attenuation on MRI with alteplase in mismatch patients was negative when mismatch volumes were assessed volumetrically, without coregistration, which underestimates mismatch volumes. We hypothesized that assessing the extent of mismatch by coregistration of perfusion and diffusion MRI maps may more accurately allow the effects of alteplase vs placebo to be evaluated.

CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration.

Objective: To determine if CFH and LOC387715/ARMS2 genotypes influence treatment response to AREDS-type nutritional supplementation with antioxidants and zinc.

Design: Retrospective analysis of participants in a randomized, controlled clinical trial, the Age-Related Eye Disease Study (AREDS).

Participants And/or Controls: Eight hundred seventy-six AREDS study participants who were considered at high risk for developing advanced age-related macular degeneration (AMD).

Haplotypes in the complement factor H (CFH) gene: associations with drusen and advanced age-related macular degeneration.

Background: Age-related macular degeneration (AMD), the leading cause of blindness in the Western world, is a complex disease that affects people over 50 years old. The complement factor H (CFH) gene has been repeatedly shown to be a major factor in determining susceptibility to the advanced form of the condition. We aimed to better understand the functional role of this gene in the AMD disease process and assess whether it is associated with earlier forms of the disease.

Association of CFH Y402H and LOC387715 A69S with progression of age-related macular degeneration.

Context: Studies have reported that single-nucleotide polymorphisms in the genes CFH and LOC387715 are associated with age-related macular degeneration (AMD).

Objective: To assess whether these genetic variants have prognostic importance for progression to advanced AMD and related visual loss.

Design, Setting, And Participants: Prospective analysis of 1466 white participants in the Age-Related Eye Disease Study (AREDS), a US multicenter clinical trial conducted from 1990 to 2001 with a mean follow-up time of 6.

The LOC387715 gene, smoking, body mass index, environmental associations with advanced age-related macular degeneration.

Background And Aims: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western World. It is now evident that both genetic and environmental factors contribute to disease susceptibility. We tested the hypotheses that (a) a common coding SNP in the LOC387715 gene is associated with advanced AMD (geographic atrophy or choroidal neovascularization), and (b) that modifiable environmental exposures alter AMD susceptibility associated with this SNP.

Expanded genome scan in extended families with age-related macular degeneration.

Purpose: To investigate further the genetic contribution to age-related macular degeneration (AMD), increasing the power of a previous analysis and reproducing the original findings.

Methods: A large cohort of families with this condition was assembled, and an expanded genome scan was performed with 556 microsatellite markers. In 2003, the results were reported of a genome-wide linkage analysis of 70 of these pedigrees.

Genetic and phenotypic heterogeneity in pattern dystrophy.

Background: The pattern dystrophies (PD) represent a clinically heterogeneous family of inherited macular diseases frequently caused by mutations in the peripherin/RDS gene. Most previous studies have detailed the clinical findings in single families, making it difficult to derive data from which progression and visual outcome can be generalised.

Methods: Families were ascertained and clinically evaluated including angiography and electrophysiology where appropriate.

HEMICENTIN-1 (FIBULIN-6) and the 1q31 AMD locus in the context of complex disease: review and perspective.

Age-related macular degeneration (AMD) is the most common blinding disorder in the Western world. Similar to other common diseases in which age is a risk factor (e.g.

Meta-analysis of genome scans of age-related macular degeneration.

A genetic contribution to the development of age-related macular degeneration (AMD) is well established. Several genome-wide linkage studies have identified a number of putative susceptibility loci for AMD but only a few of these regions have been replicated in independent studies. Here, we perform a meta-analysis of six AMD genome screens using the genome-scan meta-analysis method, which allows linkage results from several studies to be combined, providing greater power to identify regions that show only weak evidence for linkage in individual studies.

A novel diagnostic test detects a low frequency of the hemicentin Gln5345Arg variant among Northern Irish age related macular degeneration patients.

Purpose: Age related macular degeneration (AMD) is a common cause of severe vision loss. Identification of genes involved in AMD will facilitate early detection and ultimately help to identify pathways for treatment for this disorder. The A16,263G mutation in the HEMICENTIN-1 gene produces a non-conservative substitution of arginine for glutamine at codon 5345 which has been implicated in familial AMD.

Analysis of the ARMD1 locus: evidence that a mutation in HEMICENTIN-1 is associated with age-related macular degeneration in a large family.

Age-related macular degeneration (AMD) is a common cause of severe vision loss. Identification of the genes involved in AMD will lead to a better understanding of this disease at the molecular level, which will eventually lead to early detection, prevention and treatment. Previously, we mapped the ARMD1 gene to 1q25-31 in a large family with AMD.

Age-related macular degeneration--a genome scan in extended families.

We performed a genomewide scan and genetic linkage analysis, to identify loci associated with age-related macular degeneration (AMD). We collected 70 families, ranging from small nuclear families to extended multigenerational pedigrees and consisting of a total of 344 affected and 217 unaffected members available for genotyping. We performed linkage analyses using parametric and allele-sharing models.

Lack of an association of apolipoprotein E gene polymorphisms with familial age-related macular degeneration.

Background: Previously, the epsilon 4 allele of apolipoprotein E (APOE) was reported to have a significant association with a decreased risk of age-related macular degeneration (AMD). In addition, the epsilon 2 allele of APOE was reported to be possibly associated with an increased risk of AMD.

Objective: To determine if APOE polymorphisms, previously reported to be associated with AMD, affect its expression in medium to large families, as well as in unrelated patients with AMD.