Intra-cluster correlation structure in longitudinal data analysis: Selection criteria and misspecification tests

Selection criteria and misspecification tests for the intra-cluster correlation structure (ICS) in longitudinal data analysis are considered. In particular, the asymptotical distribution of the correlation information criterion (CIC) is derived and a new method for selecting a working ICS is proposed by standardizing the selection criterion as the p-value. The CIC test is found to be powerful in detecting misspecification of the working ICS structures, while with respect to the working ICS selection, the standardized CIC test is also shown to have satisfactory performance. Some simulation studies and applications to two real longitudinal datasets are made to illustrate how these criteria and tests might be useful.

The bentiromide test using plasma p-aminobenzoic acid for diagnosing pancreatic insufficiency in young children. The effect of two different doses and a liquid meal

The bentiromide test was evaluated using plasma p-aminobenzoic acid as an indirect test of pancreatic insufficiency in young children between 2 months and 4 years of age. To determine the optimal test method, the following were examined: (a) the best dose of bentiromide (15 mg/kg or 30 mg/kg); (b) the optimal sampling time for plasma p-aminobenzoic acid, and; (c) the effect of coadministration of a liquid meal. Sixty-nine children (1.6 ± 1.0 years) were studied, including 34 controls with normal fat absorption and 35 patients (34 with cystic fibrosis) with fat maldigestion due to pancreatic insufficiency. Control and pancreatic insufficient subjects were studied in three age-matched groups: (a) low-dose bentiromide (15 mg/kg) with clear fluids; (b) high-dose bentiromide (30 mg/kg) with clear fluids, and; (c) high-dose bentiromide with a liquid meal. Plasma p-aminobenzoic acid was determined at 0, 30, 60, and 90 minutes then hourly for 6 hours. The dose effect of bentiromide with clear liquids was evaluated. High-dose bentiromide best discriminated control and pancreatic insufficient subjects, due to a higher peak plasma p-aminobenzoic acid level in controls, but poor sensitivity and specificity remained. High-dose bentiromide with a liquid meal produced a delayed increase in plasma p-aminobenzoic acid in the control subjects probably caused by retarded gastric emptying. However, in the pancreatic insufficient subjects, use of a liquid meal resulted in significantly lower plasma p-aminobenzoic acid levels at all time points; plasma p-aminobenzoic acid at 2 and 3 hours completely discriminated between control and pancreatic insufficient patients. Evaluation of the data by area under the time-concentration curve failed to improve test results. In conclusion, the bentiromide test is a simple, clinically useful means of detecting pancreatic insufficiency in young children, but a higher dose administered with a liquid meal is recommended.

Serum immunoreactive pancreatic lipase and cationic trypsinogen for the assessment of exocrine pancreatic function in older patients with cystic fibrosis

Indirect and qualitative tests of pancreatic function are commonly used to screen patients with cystic fibrosis for pancreatic insufficiency. In an attempt to develop a more quantitative assessment, we compared the usefulness of measuring serum pancreatic lipase using a newly developed enzyme-linked immunosorbent immunoassay with that of cationic trypsinogen using a radioimmunoassay in the assessment of exocrine pancreatic function in patients with cystic fibrosis. Previously, we have shown neither lipase nor trypsinogen to be of use in assessing pancreatic function prior to 5 years of age because the majority of patients with cystic fibrosis in early infancy have elevated serum levels regardless of pancreatic function. Therefore, we studied 77 patients with cystic fibrosis older than 5 years of age, 41 with steatorrhea and 36 without steatorrhea. In addition, 28 of 77 patients consented to undergo a quantitative pancreatic stimulation test. There was a significant difference between the steatorrheic and nonsteatorrheic patients with the steatorrheic group having lower lipase and trypsinogen values than the nonsteatorrheic group (P < .001). Sensitivities and specificities in detecting steatorrhea were 95% and 86%, respectively, for lipase and 93% and 92%, respectively, for trypsinogen. No correlations were found between the serum levels of lipase and trypsinogen and their respective duodenal concentrations because of abnormally high serum levels of both enzymes found in some nonsteatorrheic patients. We conclude from this study that both serum lipase and trypsinogen levels accurately detect steatorrhea in patients with cystic fibrosis who are older than 5 years but are imprecise indicators of specific pancreatic exocrine function above the level needed for normal fat absorption.

Age-related alterations in immunoreactive pancreatic lipase and cationic trypsinogen in young children with cystic fibrosis

Serum immunoreactive pancreatic lipase and cationic trypsinogen are elevated in young infants with cystic fibrosis (CF) and may be useful neonatal screening tests for CF. We compared lipase measured by a recently developed ELISA immunoassay with trypsinogen measured by radioimmunoassay in 70 children (ages 0.1 to 9.9 years) with CF who had various degrees of pancreatic dysfunction and in 79 similarly aged children without CF (controls). In the control children, lipase activity increased with advancing age, whereas trypsinogen showed no age-related trend. Lipase and trypsinogen were significantly elevated in the infants with CF who were younger than 1 year, irrespective of pancreatic function (trypsinogen, P<0.001; lipase, P<0.05). Sensitivities in detecting CF were 76% and 90% for lipase and trypsinogen, respectively. After the first year of life, lipase and trypsinogen values declined toward normal, the rate of decline of lipase being greater than that of trypsinogen; 67% of lipase values were within or below the normal range by 3 years, whereas 67% of trypsinogen values continued to be elevated. We conclude that trypsinogen is an excellent screening test for CF in young infants regardless of pancreatic function, and that the addition of a serum pancreatic lipase determination does not improve the accuracy of trypsinogen as a screening test for cystic fibrosis.

Trapping to monitor tephritid movement: Results, best practice, and assessment of alternatives

Movement of tephritid flies underpins their survival, reproduction, and ability to establish in new areas and is thus of importance when designing effective management strategies. Much of the knowledge currently available on tephritid movement throughout landscapes comes from the use of direct or indirect methods that rely on the trapping of individuals. Here, we review published experimental designs and methods from mark-release-recapture (MRR) studies, as well as other methods, that have been used to estimate movement of the four major tephritid pest genera (Bactrocera, Ceratitis, Anastrepha, and Rhagoletis). In doing so, we aim to illustrate the theoretical and practical considerations needed to study tephritid movement. MRR studies make use of traps to directly estimate the distance that tephritid species can move within a generation and to evaluate the ecological and physiological factors that influence dispersal patterns. MRR studies, however, require careful planning to ensure that the results obtained are not biased by the methods employed, including marking methods, trap properties, trap spacing, and spatial extent of the trapping array. Despite these obstacles, MRR remains a powerful tool for determining tephritid movement, with data particularly required for understudied species that affect developing countries. To ensure that future MRR studies are successful, we suggest that site selection be carefully considered and sufficient resources be allocated to achieve optimal spacing and placement of traps in line with the stated aims of each study. An alternative to MRR is to make use of indirect methods for determining movement, or more correctly, gene flow, which have become widely available with the development of molecular tools. Key to these methods is the trapping and sequencing of a suitable number of individuals to represent the genetic diversity of the sampled population and investigate population structuring using nuclear genomic markers or non-recombinant mitochondrial DNA markers. Microsatellites are currently the preferred marker for detecting recent population displacement and provide genetic information that may be used in assignment tests for the direct determination of contemporary movement. Neither MRR nor molecular methods, however, are able to monitor fine-scale movements of individual flies. Recent developments in the miniaturization of electronics offer the tantalising possibility to track individual movements of insects using harmonic radar. Computer vision and radio frequency identification tags may also permit the tracking of fine-scale movements by tephritid flies by automated resampling, although these methods come with the same problems as traditional traps used in MRR studies. Although all methods described in this chapter have limitations, a better understanding of tephritid movement far outweighs the drawbacks of the individual methods because of the need for this information to manage tephritid populations.

Random Breath Testing Operation and Effectiveness in 1987

• In December 1986 funds were approved to double the intensity of random breath testing (RBT) and provide publicity support for police efforts. These changes were considered necessary to make RBT effective. • RBT methods were changed in the metropolitan area to enable block testing (pulling over a block of traffic rather than one or two cars), deployment of police to cut off escape routes, and testing by traffic patrols in all police subdivisions. Additional operators were trained for country RBT. • A publicity campaign was developed, aimed mainly at male drivers aged 18-50. The campaign consisted of the “cardsharp” television commercials, radio commercials, newspaper articles, posters and pamphlets. • Increased testing and the publicity campaigns were launched on 10 April 1987. • Police tests increased by 92.5% in May – December 1987, compared with the same period in the previous four years. • The detection rate for drinking drivers picked up by police who were cutting off escape routes was comparatively high, indicating that drivers were attempting to avoid RBT, and that this police method was effective at detecting these drivers. • A telephone survey indicated that drivers were aware of the messages of the publicity campaign. • The telephone survey also indicated that the target group had been exposed to high levels of RBT, as planned, and that fear of apprehension was the major factor deterring them from drink driving. • A roadside survey of driver blood alcohol concentrations (BACs) by the University of Adelaide’s Road Accident Research Unit (RARU) showed that, between 10p.m. and 3a.m., the proportion of drivers in Adelaide with a BAC greater than or equal to 0/08 decreased by 42%. • Drivers under 21 were identified as a possible problem area. • Fatalities in the twelve month period commencing May 1987 decreased by 18% in comparison with the previous twelve month period, and by 13% in comparison with the average of the previous two twelve month periods (commencing May 1985 and May 1986). There are indications that this trend is continuing. • It is concluded that the increase in RBT, plus publicity, was successful in achieving its aims of reductions in drink driving and accidents.

No genetic support for a contribution of prostaglandins to the aetiology of androgenetic alopecia

MADAM, Androgenetic alopecia (AGA) is a common age-dependent trait, characterized by a progressive loss of hair from the scalp. The hair loss may commence during puberty and up to 80% of white men experience some degree of AGA during their lifetime.1 Research has established that two essential aetiological factors for AGA are a genetic predisposition and the presence of androgens (male sex hormones).1,2 A recent meta-analysis of genome-wide association studies (GWAS) has increased the number of identified loci associated with this trait at the molecular level to a total of eight.3 However, despite these successes, a large fraction of the genetic contribution remains to be identified. One way to identify further genetic loci is to combine the resource of GWAS datasets with knowledge about specific biological factors likely to be involved in the development of disease. The focused evaluation of a limited number of candidate genes in GWAS datasets avoids the necessity for extensive correction for multiple testing, which typically limits the power for detecting genetic loci at a genome-wide level.4 Because the presence of genetic association suggests that candidate genes are likely to operate early in the causative chain of events leading to the phenotype, this approach may also function to favour biological pathways for their importance in the development of AGA.

Genome-wide meta-analysis of common variant differences between men and women

The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 x 10(-8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across ~115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.

Quick abnormal-bid-detection method for construction contract auctions

Non-competitive bids have recently become a major concern in both Public and Private sector construction contract auctions. Consequently, several models have been developed to help identify bidders potentially involved in collusive practices. However, most of these models require complex calculations and extensive information that is difficult to obtain. The aim of this paper is to utilize recent developments for detecting abnormal bids in capped auctions (auctions with an upper bid limit set by the auctioner) and extend them to the more conventional uncapped auctions (where no such limits are set). To accomplish this, a new method is developed for estimating the values of bid distribution supports by using the solution to what has become known as the German tank problem. The model is then demonstrated and tested on a sample of real construction bid data and shown to detect cover bids with high accuracy. This work contributes to an improved understanding of abnormal bid behavior as an aid to detecting and monitoring potential collusive bid practices.

Diagnostic values for skin temperature assessment to detect diabetes-related foot complications

Background Skin temperature assessment is a promising modality for early detection of diabetic foot problems, but its diagnostic value has not been studied. Our aims were to investigate the diagnostic value of different cutoff skin temperature values for detecting diabetes-related foot complications such as ulceration, infection, and Charcot foot and to determine urgency of treatment in case of diagnosed infection or a red-hot swollen foot. Materials and Methods The plantar foot surfaces of 54 patients with diabetes visiting the outpatient foot clinic were imaged with an infrared camera. Nine patients had complications requiring immediate treatment, 25 patients had complications requiring non-immediate treatment, and 20 patients had no complications requiring treatment. Average pixel temperature was calculated for six predefined spots and for the whole foot. We calculated the area under the receiver operating characteristic curve for different cutoff skin temperature values using clinical assessment as reference and defined the sensitivity and specificity for the most optimal cutoff temperature value. Mean temperature difference between feet was analyzed using the Kruskal–Wallis tests. Results The most optimal cutoff skin temperature value for detection of diabetes-related foot complications was a 2.2°C difference between contralateral spots (sensitivity, 76%; specificity, 40%). The most optimal cutoff skin temperature value for determining urgency of treatment was a 1.35°C difference between the mean temperature of the left and right foot (sensitivity, 89%; specificity, 78%). Conclusions Detection of diabetes-related foot complications based on local skin temperature assessment is hindered by low diagnostic values. Mean temperature difference between two feet may be an adequate marker for determining urgency of treatment.

Measuring the expressed emotion in Chinese family caregivers of persons with dementia: Validation of a Chinese version of the Family Attitude Scale

- Background Expressed emotion (EE) captures the affective quality of the relationship between family caregivers and their care recipients and is known to increase the risk of poor health outcomes for caregiving dyads. Little is known about expressed emotion in the context of caregiving for persons with dementia, especially in non-Western cultures. The Family Attitude Scale (FAS) is a psychometrically sound self-reporting measure for EE. Its use in the examination of caregiving for patients with dementia has not yet been explored. - Objectives This study was performed to examine the psychometric properties of the Chinese version of the FAS (FAS-C) in Chinese caregivers of relatives with dementia, and its validity in predicting severe depressive symptoms among the caregivers. - Methods The FAS was translated into Chinese using Brislin's model. Two expert panels evaluated the semantic equivalence and content validity of this Chinese version (FAS-C), respectively. A total of 123 Chinese primary caregivers of relatives with dementia were recruited from three elderly community care centers in Hong Kong. The FAS-C was administered with the Chinese versions of the 5-item Mental Health Inventory (MHI-5), the Zarit Burden Interview (ZBI) and the Revised Memory and Behavioral Problem Checklist (RMBPC). - Results The FAS-C had excellent semantic equivalence with the original version and a content validity index of 0.92. Exploratory factor analysis identified a three-factor structure for the FAS-C (hostile acts, criticism and distancing). Cronbach's alpha of the FAS-C was 0.92. Pearson's correlation indicated that there were significant associations between a higher score on the FAS-C and greater caregiver burden (r = 0.66, p < 0.001), poorer mental health of the caregivers (r = −0.65, p < 0.001) and a higher level of dementia-related symptoms (frequency of symptoms: r = 0.45, p < 0.001; symptom disturbance: r = 0.51, p < 0.001), which serves to suggest its construct validity. For detecting severe depressive symptoms of the family caregivers, the receiving operating characteristics (ROC) curve had an area under curve of 0.78 (95% confidence interval (CI) = 0.69–0.87, p < 0.0001). The optimal cut-off score was >47 with a sensitivity of 0.720 (95% CI = 0.506–0.879) and specificity of 0.742 (95% CI = 0.643–0.826). - Conclusions The FAS-C is a reliable and valid measure to assess the affective quality of the relationship between Chinese caregivers and their relatives with dementia. It also has acceptable predictability in identifying family caregivers with severe depressive symptoms.

Next generation sequencing identifies novel CACNA1A gene mutations in Episodic Ataxia type 2

Episodic Ataxia type 2 (EA2) is a rare autosomal dominantly inherited neurological disorder characterized by recurrent disabling imbalance, vertigo and episodes of ataxia lasting minutes to hours. EA2 is caused most often by loss of function mutations of the calcium channel gene CACNA1A. In addition to EA2, mutations in CACNA1A are responsible for two other allelic disorders: familial hemiplegic migraine type1 (FHM1) and spinocerebellar ataxia type 6 (SCA6). Herein, we have utilised Next Generation Sequencing (NGS) to screen the coding sequence, exon-intron boundaries and UTRs of five genes where mutation is known to produce symptoms related to EA2, including CACNA1A. We performed this screening in a group of 31 unrelated patients with EA2 symptoms. Both novel and known mutations were detected through NGS technology, and confirmed through Sanger sequencing. Genetic testing showed in total 15 mutation bearing patients (48%), of which 9 were novel mutations (6 missense and 3 small frameshift deletion mutations) and six known mutations (4 missense and 2 nonsense).These results demonstrate the efficiency of our NGS-panel for detecting known and novel mutations for EA2 in the CACNA1A gene, also identifying a novel missense mutation in ATP1A2 which is not a normal target for EA2 screening.

Automatic wildfire detection and simulation using optical information from unmanned aerial systems

In many parts of the world, uncontrolled fires in sparsely populated areas are a major concern as they can quickly grow into large and destructive conflagrations in short time spans. Detecting these fires has traditionally been a job for trained humans on the ground, or in the air. In many cases, these manned solutions are simply not able to survey the amount of area necessary to maintain sufficient vigilance and coverage. This paper investigates the use of unmanned aerial systems (UAS) for automated wildfire detection. The proposed system uses low-cost, consumer-grade electronics and sensors combined with various airframes to create a system suitable for automatic detection of wildfires. The system employs automatic image processing techniques to analyze captured images and autonomously detect fire-related features such as fire lines, burnt regions, and flammable material. This image recognition algorithm is designed to cope with environmental occlusions such as shadows, smoke and obstructions. Once the fire is identified and classified, it is used to initialize a spatial/temporal fire simulation. This simulation is based on occupancy maps whose fidelity can be varied to include stochastic elements, various types of vegetation, weather conditions, and unique terrain. The simulations can be used to predict the effects of optimized firefighting methods to prevent the future propagation of the fires and greatly reduce time to detection of wildfires, thereby greatly minimizing the ensuing damage. This paper also documents experimental flight tests using a SenseFly Swinglet UAS conducted in Brisbane, Australia as well as modifications for custom UAS.

Investigating limitations of SURF approach for thermal imaging analysis and mapping

Wildlife conservation involves an understanding of a specific animal, its environment and the interaction within a local ecosystem. Unmanned Aerial Vehicles (UAVs) present cost effective, non-intrusive solution for detecting animals over large areas and the use thermal imaging cameras offer the ability detect animals that would otherwise be concealed to visible light cameras. This report examines some of limitations on using SURF for the development of large maps using multiple stills images extracted from the thermal imaging video camera which contain wildlife (eg. Koala in them).

Clinical application of biomarkers in prostate cancer in men with metabolic syndrome project: Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in diagnosing localised prostate cancer

Localised prostate cancer is a heterogenous disease and a multi-modal approach is required to accurately diagnose and stage the disease. Whilst the use of magnetic resonance imaging (MRI) has become more common, small volume and multi-focal disease are oft en diffi cult to characterise. Prostate specifi c membrane antigen is a cell surface protein, which is expressed in nearly all prostate cancer cells. Its expression is signifi cantly higher in high grade prostate cancer cells. In this study, we compare multi-parametric magnetic resonance imaging and 68-Gallinium-PSMA PET with whole-mount pathology of the prostate to evaluate the applicability of multiparameteric (MP) MRI and 68Ga-PSMA PET in detecting and locating tumour foci in patients with localised prostate cancer.