Rank regression for analyzing ordinal qualitative data for treatment comparison

Ordinal qualitative data are often collected for phenotypical measurements in plant pathology and other biological sciences. Statistical methods, such as t tests or analysis of variance, are usually used to analyze ordinal data when comparing two groups or multiple groups. However, the underlying assumptions such as normality and homogeneous variances are often violated for qualitative data. To this end, we investigated an alternative methodology, rank regression, for analyzing the ordinal data. The rank-based methods are essentially based on pairwise comparisons and, therefore, can deal with qualitative data naturally. They require neither normality assumption nor data transformation. Apart from robustness against outliers and high efficiency, the rank regression can also incorporate covariate effects in the same way as the ordinary regression. By reanalyzing a data set from a wheat Fusarium crown rot study, we illustrated the use of the rank regression methodology and demonstrated that the rank regression models appear to be more appropriate and sensible for analyzing nonnormal data and data with outliers.

A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers

Multiphenotype genome-wide association studies (GWAS) may reveal pleiotropic genes, which would remain undetected using single phenotype analyses. Analysis of large pedigrees offers the added advantage of more accurately assessing trait heritability, which can help prioritise genetically influenced phenotypes for GWAS analysis. In this study we performed a principal component analysis (PCA), heritability (h2) estimation and pedigree-based GWAS of 37 cardiovascular disease -related phenotypes in 330 related individuals forming a large pedigree from the Norfolk Island genetic isolate. PCA revealed 13 components explaining >75% of the total variance. Nine components yielded statistically significant h2 values ranging from 0.22 to 0.54 (P<0.05). The most heritable component was loaded with 7 phenotypic measures reflecting metabolic and renal dysfunction. A GWAS of this composite phenotype revealed statistically significant associations for 3 adjacent SNPs on chromosome 1p22.2 (P<1x10-8). These SNPs form a 42kb haplotype block and explain 11% of the genetic variance for this renal function phenotype. Replication analysis of the tagging SNP (rs1396315) in an independent US cohort supports the association (P = 0.000011). Blood transcript analysis showed 35 genes were associated with rs1396315 (P<0.05). Gene set enrichment analysis of these genes revealed the most enriched pathway was purine metabolism (P = 0.0015). Overall, our findings provide convincing evidence for a major pleiotropic effect locus on chromosome 1p22.2 influencing risk of renal dysfunction via purine metabolism pathways in the Norfolk Island population. Further studies are now warranted to interrogate the functional relevance of this locus in terms of renal pathology and cardiovascular disease risk.

Behçet's syndrome involving the gastrointestinal tract: a diagnostic dilemma in childhood

Behçet's syndrome is very rare in children, especially those under 10 years of age. Clinical and radiological features are described in 4 children, including 2 under the age of 5 years, with the syndrome. As in other pediatric cases reported, the incomplete form of Behçet's syndrome was present in each case. All 4 patients had oral and genital mucosal effects, arthritis and gastrointestinal and dermatological manifestations. Ophthalmological symptoms occurred in only 1 patient. Radiologically, the 4 cases demonstrated the spectrum of gastrointestinal involvement, from minimal irregularity and thickening of the terminal ileum to gross irregularity and deformity of the terminal ileum and cecum. Because of the difficulty in differentiating Behçet's syndrome from other forms of inflammatory bowel disease it is suggested that in children with gastrointestinal involvement, 3 major criteria be present before the diagnosis of Behçet's syndrome is made.

Osteopenia and rickets in the extremely low birth weight infant: A survey of the incidence and a radiological classification

A review was carried out of the radiographs of twenty-five infants with birth weights under 1000 G, who survived for more than twenty-eight days; eighteen of these had enough suitable films for a survey of the progressive bone changes which occur in these infants, including estimation of humeral cortical cross-sectional area. The incidence of the changes has been assessed and a typical progression of radiographic appearances has been shown, with a suggested system of staging. All infants showed some loss of bone mineral, with frank changes of rickets occurring in forty-four percent. Aetiological factors are mainly concerned with the difficulty of supplying and ensuring absorption of sufficient bone mineral (calcium and phosphate) and vitamin D. Liver immaturity may be another factor. Disease states additional to prematurity accentuate the problem. Rib fractures occurring around 80–90 days post-nataEy commonly draw attention to the bone disorder and are probably the major clinical factor of importance; there is a high incidence of associated lung disease of uncertain pathology. Attention is drawn to possible confusion with other bone disorders in the post-natal period.

Guaiac versus immunochemical tests: Faecal occult blood test screening for colorectal cancer in a rural community

Objective: To describe patient participation and clinical performance in a colorectal cancer (CRC) screening program utilising faecal occult blood test (FOBT). Methods: A community-based intervention was conducted in a small, rural community in north Queensland, 2000/01. One of two FOBT kits – guaiac (Hemoccult-ll) or immunochemical (Inform) – was assigned by general practice and mailed to participants (3,358 patients aged 50–74 years listed with the local practices). Results: Overall participation in FOBT screening was 36.3%. Participation was higher with the immunochemical kit than the guaiac kit (OR=1.9, 95% Cl 1.6-2.2). Women were more likely to comply with testing than men (OR=1.4, 95% Cl 1.2-1.7), and people in their 60s were less likely to participate than those 70–74 years (OR=0.8, 95% Cl 0.6-0.9). The positivity rate was higher for the immunochemical (9.5%) than the guaiac (3.9%) test (χ2=9.2, p=0.002), with positive predictive values for cancer or adenoma of advanced pathology of 37.8% (95% Cl 28.1–48.6) for !nform and 40.0% (95% Cl 16.8–68.7) for Hemoccult-ll. Colonoscopy follow-up was 94.8% with a medical complication rate of 2–3%. Conclusions: An immunochemical FOBT enhanced participation. Higher positivity rates for this kit did not translate into higher false-positive rates, and both test types resulted in a high yield of neoplasia. Implications: In addition to type of FOBT, the ultimate success of a population-based screening program for CRC using FOBT will depend on appropriate education of health professionals and the public as well as significant investment in medical infrastructure for colonoscopy follow-up.

Retinal photography screening programs to prevent vision loss from diabetic retinopathy in rural and urban Australia: A review

Purpose This review assessed the effectiveness of diabetic retinopathy (DR) screening programs, using retinal photography in Australian urban and rural settings, and considered implications for public health strategy and policy. Methods An electronic search of MEDLINE, PubMed, and Embase for studies published between 1 January 1996 and the 30 June 2013 was undertaken. Key search terms were “diabetic retinopathy,” “screening,” “retinal photography” and “Australia.” Results Twelve peer-reviewed publications were identified. The 14 DR screening programs identified from the 12 publications were successfully undertaken in urban, rural and remote communities across Australia. Locations included a pathology collection center, and Indigenous primary health care and Aboriginal community controlled organizations. Each intervention using retinal photography was highly effective at increasing the number of people who underwent screening for DR. The review identified that prior to commencement of the screening programs a median of 48% (range 16–85%) of those screened had not undergone a retinal examination within the recommended time frame (every year for Indigenous people and every 2 years for non-Indigenous people in Australia). A median of 16% (range 0–45%) of study participants had evidence of DR. Conclusions This review has shown there have been many pilot and demonstration projects in rural and urban Australia that confirm the effectiveness of retinal photography-based screening for DR

The other country: A father's journey with autism

The memoir The Other Country and the essay Inspiration is Power examine i) contemporary experiences of autism and ii) the representation of autism disorder in scientific and autobiographical writing. The Other Country is a memoir of four years in the life of its author Michael Whelan, and his family, in the care of his son, Charlie. In February 1998, Charlie was diagnosed with autism, and in that moment Michael and his family's lives changed. The memoir describes in four parts a four-year journey through a father?s experiences: - Part 1, Welcome to Holland, the family's feelings of fear, grief and dislocation following diagnosis; - Part 2, Look at Me, the chaotic process of research and treatment, and intense early intervention programs; - Part 3, The Enchanted Cottage, the slow process of recovery that the family went through, and; - Part 4, The Long Way Home, the transformation of Charlie, Michael and his family and notions of home and normalcy. The title, The Other Country, in this context refers to the largely invisible parallel society inhabited by anyone who lives outside the mainstream. The accompanying critical essay, Inspiration is Power, examines the influence of the discourses of biomedical science and parental pathology on the representation and understanding of autism. Specifically, among autism narratives, the medical voice has an overwhelming authority and power in characterizing autistic disorder and experience for the lay reader. This discourse contests the moral authority of parental autobiographical writing, which, by contrast, characterizes autism as a personalized invading other and thief of their child. Through a critique of specific aspects of identity, narrative, evidence and authority, the essay suggests a register of rhetorical moves that may be employed to influence, and consequently empower, the reader of autism narratives.

Polymorphisms in the vascular endothelial growth factor gene and the risk of familial endometriosis

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic protein suspected to be involved in the pathogenesis of endometriosis by establishing a new blood supply to the human exfoliated endometrium. Several transcription factor-binding sites are found in the VEGF 5'-untranslated region and variation within the region increases the transcriptional activity. Six previous studies which tested between one and three single nucleotide polymorphisms (SNPs) in samples comprising 105-215 cases and 100-219 controls have produced conflicting evidence for association between the SNPs in the VEGF region and endometriosis. To further investigate the reported association between VEGF variants and endometriosis, we tested the four VEGF polymorphisms (-2578 A/C, rs699947; -460 T/C, rs833061; +405 G/C, rs2010963 and +936 C/T, rs3025039) in a large Australian sample of 958 familial endometriosis cases and 959 controls. We also conducted a literature-based review of all relevant association studies of these VEGF SNPs in endometriosis and performed a meta-analysis. There was no evidence for association between endometriosis and the VEGF polymorphisms genotyped in our study. Combined association results from a meta-analysis did not provide any evidence for either genotypic or allelic association with endometriosis. Our detailed review and meta-analysis of the VEGF polymorphisms suggests that genotyping assay problems may underlie the previously reported associations between VEGF variants and endometriosis.

Latent class and genetic analysis does not support migraine with aura and migraine without aura as separate entities

Latent class and genetic analyses were used to identify subgroups of migraine sufferers in a community sample of 6,265 Australian twins (55% female) aged 25-36 who had completed an interview based on International Headache Society (IHS) criteria. Consistent with prevalence rates from other population-based studies, 703 (20%) female and 250 (9%) male twins satisfied the IHS criteria for migraine without aura (MO), and of these, 432 (13%) female and 166 (6%) male twins satisfied the criteria for migraine with aura (MA) as indicated by visual symptoms. Latent class analysis (LCA) of IHS symptoms identified three major symptomatic classes, representing 1) a mild form of recurrent nonmigrainous headache, 2) a moderately severe form of migraine, typically without visual aura symptoms (although 40% of individuals in this class were positive for aura), and 3) a severe form of migraine typically with visual aura symptoms (although 24% of individuals were negative for aura). Using the LCA classification, many more individuals were considered affected to some degree than when using IHS criteria (35% vs. 13%). Furthermore, genetic model fitting indicated a greater genetic contribution to migraine using the LCA classification (heritability, h(2)=0.40; 95% CI, 0.29-0.46) compared with the IHS classification (h(2)=0.36; 95% CI, 0.22-0.42). Exploratory latent class modeling, fitting up to 10 classes, did not identify classes corresponding to either the IHS MO or MA classification. Our data indicate the existence of a continuum of severity, with MA more severe but not etiologically distinct from MO. In searching for predisposing genes, we should therefore expect to find some genes that may underlie all major recurrent headache subtypes, with modifying genetic or environmental factors that may lead to differential expression of the liability for migraine.

Dominant negative ATM mutations in breast cancer families

BACKGROUND: The ATM gene encoding a putative protein kinase is mutated in ataxia-telangiectasia (A-T), an autosomal recessive disorder with a predisposition for cancer. Studies of A-T families suggest that female heterozygotes have an increased risk of breast cancer compared with noncarriers. However, neither linkage analyses nor mutation studies have provided supporting evidence for a role of ATM in breast cancer predisposition. Nevertheless, two recurrent ATM mutations, T7271G and IVS10-6T-->G, reportedly increase the risk of breast cancer. We examined these two ATM mutations in a population-based, case-control series of breast cancer families and multiple-case breast cancer families. METHODS: Five hundred twenty-five or 262 case patients with breast cancer and 381 or 68 control subjects, respectively, were genotyped for the T7271G and IVS10-6T-->G ATM mutations, as were index patients from 76 non-BRCA1/2 multiple-case breast cancer families. Linkage and penetrance were analyzed. ATM protein expression and kinase activity were analyzed in lymphoblastoid cell lines from mutation carriers. All statistical tests were two-sided. RESULTS: In case and control subjects unselected for family history of breast cancer, one case patient had the T7271G mutation, and none had the IVS10-6T-->G mutation. In three multiple-case families, one of these two mutations segregated with breast cancer. The estimated average penetrance of the mutations was 60% (95% confidence interval [CI] = 32% to 90%) to age 70 years, equivalent to a 15.7-fold (95% CI = 6.4-fold to 38.0-fold) increased relative risk compared with that of the general population. Expression and activity analyses of ATM in heterozygous cell lines indicated that both mutations are dominant negative. CONCLUSION: At least two ATM mutations are associated with a sufficiently high risk of breast cancer to be found in multiple-case breast cancer families. Full mutation analysis of the ATM gene in such families could help clarify the role of ATM in breast cancer susceptibility.

Concentrations of phthalates and DINCH metabolites in pooled urine from Queensland, Australia

Dialkyl phthalate esters (phthalates) are ubiquitous chemicals used extensively as plasticizers, solvents and adhesives in a range of industrial and consumer products. 1,2-Cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is a phthalate alternative introduced due to a more favourable toxicological profile, but exposure is largely uncharacterised. The aim of this study was to provide the first assessment of exposure to phthalates and DINCH in the general Australian population. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n = 24 pools of 100). Concentrations of free and total species were measured using online solid phase extraction isotope dilution high performance liquid chromatography tandem mass spectrometry. Concentrations ranged from 2.4 to 71.9 ng/mL for metabolites of di(2-ethylhexyl)phthalate, and from < 0.5 to 775 ng/mL for all other metabolites. Our data suggest that phthalate metabolites concentrations in Australia were at least two times higher than in the United States and Germany; and may be related to legislative differences among countries. DINCH metabolite concentrations were comparatively low and consistent with the limited data available. Ongoing biomonitoring among the general Australian population may help assess temporal trends in exposure and assess the effectiveness of actions aimed at reducing exposures.

Monitoring exposure to polycyclic aromatic hydrocarbons in an Australian population using pooled urine samples

Integrated exposure to polycyclic aromatic hydrocarbons (PAHs) can be assessed through monitoring of urinary mono-hydroxylated PAHs (OH-PAHs). The aim of this study was to provide the first assessment of exposure to PAHs in a large sample of the population in Queensland, Australia including exposure to infant (0-4. years). De-identified urine specimens, obtained from a pathology laboratory, were stratified by age and sex, and pooled (n. =. 24 pools of 100) and OH-PAHs were measured by gas chromatography-isotope dilution-tandem mass spectrometry. Geometric mean (GM) concentrations ranged from 30. ng/L (4-hydroxyphenanthrene) to 9221. ng/L (1-naphthol). GM of 1-hydroxypyrene, the most commonly used PAH exposure biomarker, was 142. ng/L. The concentrations of OH-PAHs found in this study are consistent with those in developed countries and lower than those in developing countries. We observed no association between sex and OH-PAH concentrations. However, we observed lower urinary concentrations of all OH-PAHs in samples from infants (0-4. years), children (5-14. years) and the elderly (>. 60. year old) compared with samples from other age groups (15-29, 30-44 and 45-59. years) which may be attributed to age-dependent behaviour-specific exposure sources.

Peritoneal washing cytology

Peritoneal washing cytology (PWC) is a useful indicator of ovarian surface involvement and peritoneal dissemination by ovarian tumours. It may identify subclinical peritoneal spread and thus provide valuable staging and prognostic information, particularly for non-serous ovarian tumours. The role of PWC as a prognostic indicator for endometrial carcinoma is less clear, due in part to the questionable significance of identifying endometrial tumour cells in the peritoneum. Detection of metastatic carcinoma in PWC is based on recognition of non-mesothelial cell characteristics, however a number of conditions such as reactive mesothelial cells, endometriosis and endosalpingiosis may mimic this appearance. Cells from these conditions may have a similar presentation in PWC to that of serous borderline tumours and low grade serous carcinoma. The presence of cilia, lack of single atypical cells, prominent cytoplasmic vacuolation, marked nuclear atypia or two distinct cell populations are features favouring a benign process. Attention to these features along with close correlation with clinical history and the results of surgical pathology should help avoid errors. Additional assistance may be provided by the use of cell blocks and special stains.

Use of pooled samples to assess human exposure to parabens, benzophenone-3 and triclosan in Queensland, Australia

Parabens, benzophenone-3 and triclosan are common ingredients used as preservatives, ultraviolet radiation filters and antimicrobial agents, respectively. Human exposure occurs through consumption of processed food and use of cosmetics and consumer products. The aim of this study was to provide a preliminary characterisation of exposure to selected personal care product chemicals in the general Australian population. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n= 24 pools of 100). Concentrations of free and total (sum of free plus conjugated) species of methyl, ethyl, propyl and butyl paraben, benzophenone-3 and triclosan were quantified using isotope dilution tandem mass spectrometry; with geometric means 232, 33.5, 60.6, 4.32, 61.5 and 87.7. ng/mL, respectively. Age was inversely associated with paraben concentration, and females had concentrations approximately two times higher than males. Total paraben and benzophenone-3 concentrations are significantly higher than reported worldwide, and the average triclosan concentration was more than one order of magnitude higher than in many other populations. This study provides the first data on exposure of the general Australian population to a range of common personal care product chemical ingredients, which appears to be prevalent and warrants further investigation.