Richard A. Armstrong

When to use the Bonferroni correction

The Bonferroni correction adjusts probability (p) values because of the increased risk of a type I error when making multiple statistical tests. The routine use of this test has been criticised as deleterious to sound statistical judgment, testing the wrong hypothesis, and reducing the chance of a type I error but at the expense of a type II error; yet it remains popular in ophthalmic research. The purpose of this article was to survey the use of the Bonferroni correction in research articles published in three optometric journals, viz. Ophthalmic & Physiological Optics, Optometry & Vision Science, and Clinical & Experimental Optometry, and to provide advice to authors contemplating multiple testing.

Statistical guidelines for the analysis of data obtained from one or both eyes

Measurements obtained from the right and left eye of a subject are often correlated whereas many statistical tests assume observations in a sample are independent. Hence, data collected from both eyes cannot be combined without taking this correlation into account. Current practice is reviewed with reference to articles published in three optometry journals, viz., Ophthalmic and Physiological Optics (OPO), Optometry and Vision Science (OVS), Clinical and Experimental Optometry (CEO) during the period 2009–2012.

Overlap between neurodegenerative disorders

Neurodegenerative disorders are characterized by the formation of distinct pathological changes in the brain, including extracellular protein deposits, cellular inclusions, and changes in cell morphology. Since the earliest published descriptions of these disorders, diagnosis has been based on clinicopathological features, namely, the coexistence of a specific clinical profile together with the presence or absence of particular types of lesion. In addition, the molecular profile of lesions has become an increasingly important feature both in the diagnosis of existing disorders and in the description of new disease entities. Recent studies, however, have reported considerable overlap between the clinicopathological features of many disorders leading to difficulties in the diagnosis of individual cases and to calls for a new classification of neurodegenerative disease. This article discusses: (i) the nature and degree of the overlap between different neurodegenerative disorders and includes a discussion of Alzheimers disease, dementia with Lewy bodies, the fronto‐temporal dementias, and prion disease; (ii) the factors that contribute to disease overlap, including historical factors, the presence of disease heterogeneity, age‐related changes, the problem of apolipoprotein genotype, and the co‐occurrence of common diseases; and (iii) whether the current nosological status of disorders should be reconsidered.

Depression and tetrahydrobiopterin: The folate connection

Total biopterin, neopterin and creatinine were measured in spot urine samples from affective disorder patients on lithium therapy and control subjects. Folic acid was also measured in plasma in a sample of the patients. The mean neopterin: biopterin ratio was significantly higher in the 76 patients (3.2 +/- 0.5) than in the 61 controls (1.8 +/- 0.1). In female patients biopterin levels were significantly lower than in controls. In the control groups there was a significant correlation between the molar concentration of neopterin and biopterin. No such correlation was found in the patients. These data indicate that tetrahydrobiopterin (BH4) biosynthesis is reduced in this group. A significant positive correlation was found between plasma folate and urinary biopterin. It is suggested that folate deficiency may impair the synthesis of BH4, a cofactor essential for the synthesis of 5-HT and other monoamines that are involved in the pathogenesis of affective disorders.

β-Amyloid Plaques: Stages in Life History or Independent Origin?

Several types of discrete β-amyloid (Aβ) deposit or senile plaque have been identified in the brains of individuals with Alzheimer’s disease and Down’s syndrome. The majority of these plaques can be classified into four morphological types: diffuse, primitive, classic and compact. Two hypotheses have been proposed to account for these plaques. Firstly, that the diffuse, primitive, classic and compact plaques develop in sequence and represent stages in the life history of a single plaque type. Secondly, that the different Aβ plaques develop independently and therefore, unique factors are involved in the formation of each type. To attempt to distinguish between these hypotheses, the morphology, ultrastructure, composition, and spatial distribution in the brain of the four types of plaque were compared. Although some primitive plaques may develop from diffuse plaques, the evidence suggests that a unique combination of factors is involved in the pathogenesis of each plaque type and, therefore, supports the hypothesis that the major types of Aβ plaque develop independently.

Visual Symptoms in Parkinson's Disease

Parkinsons disease (PD) is a common disorder of middle-aged and elderly people in which degeneration of the extrapyramidal motor system causes significant movement problems. In some patients, however, there are additional disturbances in sensory systems including loss of the sense of smell and auditory and/or visual problems. This paper is a general overview of the visual problems likely to be encountered in PD. Changes in vision in PD may result from alterations in visual acuity, contrast sensitivity, colour discrimination, pupil reactivity, eye movements, motion perception, visual field sensitivity, and visual processing speeds. Slower visual processing speeds can also lead to a decline in visual perception especially for rapidly changing visual stimuli. In addition, there may be disturbances of visuospatial orientation, facial recognition problems, and chronic visual hallucinations. Some of the treatments used in PD may also have adverse ocular reactions. The pattern electroretinogram (PERG) is useful in evaluating retinal dopamine mechanisms and in monitoring dopamine therapies in PD. If visual problems are present, they can have an important effect on the quality of life of the patient, which can be improved by accurate diagnosis and where possible, correction of such defects.

Methods to evaluate pesticide damage to the biomass of the soil microflora

Respiratory methods to estimate the amount of C in the soil microbial biomass and the relative contributions of prokaryotes and eukaryotes in the biomass were used to evaluate the influence of pesticides on the soil microflora. Experiments were conducted with 5 and 50 micrograms per gram of three fungicides, captan, thiram and verdesan. At 5 micrograms per gram they caused significant decreases (40%) in the biomass; the organomercury fungicide verdesan also caused a shift from fungal to bacterial dominance. Within 8 days, biomass in captan- and thiram-amended soils had recovered to that of controls. Although the fungal to bacterial balance was restored in verdesan-amended soils, biomass recovery was not complete. At 50 micrograms per gram the fungicides caused long-term decreases in the biomass and altered the relative proportions of the bacterial and fungal populations. Verdesan had the greatest effect on soil microbial biomass and competition.

Infection and colonization of trout eggs by Saprolegniaceae

Saprolegia diclina and Saprolegnia ferax zoospores only infected dead trout eggs, in particular eggs sited downstream of the fungi. Susceptibility of dead eggs to infection appears to be associated with nutrient loss after shocking. Living and dead eggs were colonized by hyphae of both species although the saprophyte S. ferax was the more aggressive colonizer.

Is the clustering of neurofibrillary tangles in Alzheimer's patients related to the cells of origin of specific cortico-cortical projections?

The spatial pattern of cellular neurofibrillary tangles (NFT) was studied in the supra- and infragranular layers of various cortical regions in cases of Alzheimers disease (AD). The objective was to test the hypothesis that NFT formation was associated with the cells of origin of specific cortico-cortical projections. The novel feature of the study was that pattern analysis enabled the dimension and spacing of NFT clusters along the cortical ribbon to be estimated. In the majority of brain regions studied, NFT occurred in clusters of neurons which were regularly spaced along the cortical strip. This pattern is consistent with the predicted distribution of the cells of origin of specific cortico-cortico projections. Mean NFT cluster size varied from 250 to > 12800 microns in different cortical tissues suggesting either variation in the size of the cell clusters or a dynamic process in the development of NFT in relation to these cell clusters. The formation of NFT in cell clusters which may give rise to the feed-forward and feed-back cortico-cortical projections suggests a possible route of spread of NFT pathology in AD between cortical regions and from the cortex to subcortical areas.

The Pathogenesis of Alzheimer's Disease: A Reevaluation of the “Amyloid Cascade Hypothesis”

The most influential theory to explain the pathogenesis of Alzheimers disease (AD) has been the “Amyloid Cascade Hypothesis” (ACH) first formulated in 1992. The ACH proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD leading to the formation of senile plaques (SPs) and then to neurofibrillary tangles (NFTs) death of neurons, and ultimately dementia. This paper examines two questions regarding the ACH: (1) is there a relationship between the pathogenesis of SPs and NFTs, and (2) what is the relationship of these lesions to disease pathogenesis? These questions are examined in relation to studies of the morphology and molecular determinants of SPs and NFTs, the effects of gene mutation, degeneration induced by head injury, the effects of experimentally induced brain lesions, transgenic studies, and the degeneration of anatomical pathways. It was concluded that SPs and NFTs develop independently and may be the products rather than the causes of neurodegeneration in AD. A modification to the ACH is proposed which may better explain the pathogenesis of AD, especially of late-onset cases of the disease.