Identifying genes that contribute most to good classification in microarrays

BACKGROUND: The goal of most microarray studies is either the identification of genes that are most differentially expressed or the creation of a good classification rule. The disadvantage of the former is that it ignores the importance of gene interactions; the disadvantage of the latter is that it often does not provide a sufficient focus for further investigation because many genes may be included by chance. Our strategy is to search for classification rules that perform well with few genes and, if they are found, identify genes that occur relatively frequently under multiple random validation (random splits into training and test samples). RESULTS: We analyzed data from four published studies related to cancer. For classification we used a filter with a nearest centroid rule that is easy to implement and has been previously shown to perform well. To comprehensively measure classification performance we used receiver operating characteristic curves. In the three data sets with good classification performance, the classification rules for 5 genes were only slightly worse than for 20 or 50 genes and somewhat better than for 1 gene. In two of these data sets, one or two genes had relatively high frequencies not noticeable with rules involving 20 or 50 genes: desmin for classifying colon cancer versus normal tissue; and zyxin and secretory granule proteoglycan genes for classifying two types of leukemia. CONCLUSION: Using multiple random validation, investigators should look for classification rules that perform well with few genes and select, for further study, genes with relatively high frequencies of occurrence in these classification rules

Estimating the cumulative risk of false positive cancer screenings

BACKGROUND: When evaluating cancer screening it is important to estimate the cumulative risk of false positives from periodic screening. Because the data typically come from studies in which the number of screenings varies by subject, estimation must take into account dropouts. A previous approach to estimate the probability of at least one false positive in n screenings unrealistically assumed that the probability of dropout does not depend on prior false positives. METHOD: By redefining the random variables, we obviate the unrealistic dropout assumption. We also propose a relatively simple logistic regression and extend estimation to the expected number of false positives in n screenings. RESULTS: We illustrate our methodology using data from women ages 40 to 64 who received up to four annual breast cancer screenings in the Health Insurance Program of Greater New York study, which began in 1963. Covariates were age, time since previous screening, screening number, and whether or not a previous false positive occurred. Defining a false positive as an unnecessary biopsy, the only statistically significant covariate was whether or not a previous false positive occurred. Because the effect of screening number was not statistically significant, extrapolation beyond 4 screenings was reasonable. The estimated mean number of unnecessary biopsies in 10 years per woman screened is .11 with 95% confidence interval of (.10, .12). Defining a false positive as an unnecessary work-up, all the covariates were statistically significant and the estimated mean number of unnecessary work-ups in 4 years per woman screened is .34 with 95% confidence interval (.32, .36). CONCLUSION: Using data from multiple cancer screenings with dropouts, and allowing dropout to depend on previous history of false positives, we propose a logistic regression model to estimate both the probability of at least one false positive and the expected number of false positives associated with n cancer screenings. The methodology can be used for both informed decision making at the individual level, as well as planning of health services

Relationship of dental practitioners to rural primary care networks

Abstract still to be addedResidents of rural and remote communities have poorer oral health and less access to oral health services than people living in major cities. The populations of many rural and remote centres are not large enough to support a resident dentist and, in the absence of community oral health services, rural residents may present to non-dental primary care providers with oral health problems. The aim of this study was to describe strategies that can be used by primary care practitioners to improve the provision of oral health services to rural and remote communities. The specific objectives were to (i) map oral health services practices in rural communities across primary care providers (ii) assess the extent to which oral health problems impact on service provision by primary health care providers; (iii) assess the extent to which primary care networks could be more effectively utilised to improve the provision of oral health services to rural communities and to identify what interventions/strategies were most likely to be effective.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy

The paradox of going hungry when there is so much food : the perspective of vulnerable youth and their caseworkers

This study aimed to examine the food security challenges experienced among vulnerable youth in North West Tasmania. An exploratory, descriptive design was used to collect data through face-to-face interviews and focus group discussions with 22 young residents and with five stakeholders and representatives from different community and state organisations. The most significant finding of the study was that a proportion of young residents in the North West Coast of Tasmania were threatened by food insecurity, which was caused by a combination of factors including patterns of food consumption and dietary behaviours. Those with higher financial difficulty due to the lack of a stable job were significantly more vulnerable to food insecurity and faced a higher chance of having health problems. The findings of the project have many implications to improve the food security and lives of vulnerable youth

A light-front description of electromagnetic form factors for J≤3/2J \leq {3/2} hadrons

A review of the hadron electromagnetic form factors obtained in a light-front constituent quark model, based on the eigenfunctions of a mass operator, is presented. The relevance of different components in the q-q interaction for the description of hadron experimental form factors is analysed.Comment: 6 pages, Latex, 3 Postscript figures included. Proceedings of "Nucleon 99", Frascati, June 1999. To appear in Nucl. Phys.

Writing quality scale (WQS) : HE version. Administration and scoring guide

Writing is an important skill that takes time to master. Berninger and Amtmann’s (2003) ‘Simple view of writing’ is a useful framework for understanding the different skills; language, cognitive, and motor processes involved in writing and how they interact. In early childhood the focus is on mastering the ‘transcription’ skills of how to form the letters and words required to represent language in its written form. Once this essential skill is mastered, then the focus moves to ‘text generation’ and how to use written language effectively to convey information. Writing skills are important throughout education with handwritten work continuing to be used as a method of assessment. However, for some students, writing continues to present challenges in higher education (HE), with difficulties experienced in the accuracy and fluency of writing letters or spelling words (transcription skills) and/or in the planning and composition of ideas and thoughts into written text (text generation skills). This includes students with specific learning difficulties (SpLDs) such as dyslexia and in 2021-22 students with SpLDs accounted for 6.15% of the higher education (HE) student population in the UK and for 33% of the student population with a known disability (Higher Education Statistics Authority, 2023). Various tools are available to measure aspects of transcription. For example, the standardised Detailed Assessment of Speed of Handwriting (DASH, Barnett et al., 2007; DASH17+, Barnett et al., 2010) measures handwriting speed across a range of writing tasks. Handwriting legibility can be assessed with the criterion referenced Handwriting Legibility Scale (HLS; Barnett et al., 2018). However, tools for measuring writing quality are limited, particularly for use with students in HE. The development of the Writing Quality Scale (WQS; Stuart & Barnett, 2023) arose out of the needs of specialist teacher assessors working in HE. The aim was to develop a quick, simple, and practical criterion referenced tool to help in gathering information about the difficulties that a student may experience in writing in HE and to help inform decisions about the support that they may need. The WQS has been designed to be used with the free writing task from the DASH 17+ 1(Barnett et al., 2010). The WQS uses an analytic scoring measure that provides an overall score for writing quality based on scores given for six individual criteria. The six criteria target areas known to predict writing quality in HE academic assignments (Crossley, 2020; Crossley et al., 2014) as well as the areas in which students with SpLDs (such as dyslexia) often have difficulty with when writing (Connelly et al., 2006; Galbraith et al., 2012; Sumner & Connelly, 2020). Within an overall score for writing quality (which can be categorised as: low, medium, high), the WQS indicates where areas of relative strength and difficultly lie and where support might best be targeted. The WQS was designed for use by a range of professionals, including specialist teacher assessors and educational psychologists, to identity students whose writing quality may be a cause for concern and require appropriate support. The WQS does not require the need for specialised or subject specific language and/or knowledge to administer it. The aim of the WQS is to help identify students (aged 17-25) in HE who have poor written expression or writing quality

Brain Volumetrics, Regional Cortical Thickness and Radiographic Findings in Adults with Cyanotic Congenital Heart Disease

AbstractBackgroundChronic cyanosis in adults with congenital heart disease (CHD) may cause structural brain changes that could contribute to impaired neurological functioning. The extent of these changes has not been adequately characterized.HypothesisWe hypothesized that adults with cyanotic CHD would have widespread changes including abnormal brain volumetric measures, decreased cortical thickness and an increased burden of small and large vessel ischemic changes.MethodsTen adults with chronic cyanosis from CHD (40±4years) and mean oxygen saturations of 82±2% were investigated using quantitative MRI. Hematological and biochemical parameters were also assessed. All subjects were free from major physical or intellectual impairment. Brain volumetric results were compared with randomly selected age- and sex-matched controls from our database of normal subjects.ResultsFive of 10 cyanotic subjects had cortical lacunar infarcts. The white matter (WM) hyperintensity burden was also abnormally high (Scheltens Scale was 8±2). Quantitative MRI revealed evidence of extensive generalized WM and gray matter (GM) volumetric loss; global GM volume was reduced in cyanosed subjects (630±16 vs. 696±14mL in controls, p=0.01) as was global WM volume (471±10 vs. 564±18mL, p=0.003). Ventricular cerebrospinal fluid volume was increased (35±10 vs. 26±5mL, p=0.002). There were widespread regions of local cortical thickness reduction observed across the brain. These changes included bilateral thickness reductions in the frontal lobe including the dorsolateral prefrontal cortex and precentral gyrus, the posterior parietal lobe and the middle temporal gyrus. Sub-cortical volume changes were observed in the caudate, putamen and in the thalamus (p≤0.005 for all regions). Cortical GM volume negatively correlated with brain natriuretic peptide (R=−0.89, p=0.009), high sensitivity C-reactive protein (R=−0.964, p<0.0001) and asymmetric dimethylarginine (R=−0.75, p=0.026) but not with oxygen saturations, packed cell volume or viscosity.ConclusionsWe present the first comprehensive analysis of brain structure in adults with chronic neurocyanosis due to congenital heart disease. We demonstrate clear evidence for marked macro- and microvascular injury. Cyanotic patients show global evidence for reduced brain volume as well as specific foci of cortical thickness reduction. The GM volume loss correlated with hsCRP, BNP and ADMA suggesting that inflammation, neurohormonal activation and endothelial dysfunction may have important roles in its pathogenesis