Automated melanoma diagnosis system

An automated melanoma diagnosis system, the so-called Skin Polar-probe, was developed to improve the chances of early detection of skin cancers and help save the lives of melanoma victims. The system will offer unique benefits to aid early detection of melanoma - the key to reducing deaths caused by this cancer.

Toward a model for predicting magnetic susceptibility of bedrock regolith and soils

One of the Department of Defense's most pressing environmental problems is the efficient detection and identification of unexploded ordnance (UXO). In regions of highly magnetic soils, magnetic and electromagnetic sensors often detect anomalies that are of geologic origin, adding significantly to remediation costs. In order to develop predictive models for magnetic susceptibility, it is crucial to understand modes of formation and the spatial distribution of different iron oxides. Most rock types contain iron and their magnetic susceptibility is determined by the amount and form of iron oxides present. When rocks weather, the amount and form of the oxides change, producing concomitant changes in magnetic susceptibility. The type of iron oxide found in the weathered rock or regolith is a function of the duration and intensity of weathering, as well as the original content of iron in the parent material. The rate of weathering is controlled by rainfall and temperature; thus knowing the climate zone, the amount of iron in the lithology and the age of the surface will help predict the amount and forms of iron oxide. We have compiled analyses of the types, amounts, and magnetic properties of iron oxides from soils over a wide climate range, from semi arid grasslands, to temperate regions, and tropical forests. We find there is a predictable range of iron oxide type and magnetic susceptibility according to the climate zone, the age of the soil and the amount of iron in the unweathered regolith.

Characterization of frequency‐dependent magnetic susceptibility in UXO electromagnetic geophysics

Soils at many locations that have their origin in volcanic parent material and have undergone extensive weathering often exhibit strong frequency-dependent magnetic susceptibilities. The presence of such susceptibility has a profound effect on electromagnetic induction data acquired in such environments. Their transient electromagnetic response is characterized by a t-1 decay that is strong enough to mask UXO responses. In a field study and associated laboratory work on characterizing the frequency-dependent magnetic susceptibility and its influence on transient electromagnetic data, we collected soil samples on the surface and in soil pits from the Island of Kaho'olawe, Hawaii, and measured their frequency dependent magnetic susceptibilities. We present the details of the field investigation, confirm previous theoretical work with field and laboratory measurements, characterize the susceptibility with a Cole-Cole model, and investigate the response specific to the measured susceptibility.

Differential susceptibility to performance degradation across categories of facial emotion - a model confirmation

Patients with a number of psychiatric and neuropathological conditions demonstrate problems in recognising facial expressions of emotion. Research indicating that patients with schizophrenia perform more poorly in the recognition of negative valence facial stimuli than positive valence stimuli has been interpreted as evidence of a negative emotion specific deficit. An alternate explanation rests in the psychometric properties of the stimulus materials. This model suggests that the pattern of impairment observed in schizophrenia may reflect initial discrepancies in task difficulty between stimulus categories, which are not apparent in healthy subjects because of ceiling effects. This hypothesis is tested, by examining the performance of healthy subjects in a facial emotion categorisation task with three levels of stimulus resolution. Results confirm the predictions of the model, showing that performance degrades differentially across emotion categories, with the greatest deterioration to negative valence stimuli. In the light of these results, a possible methodology for detecting emotion specific deficits in clinical samples is discussed.

The transition to palliative care: A critical exploration in the context of metastatic melanoma

This research explored the transition to palliative care process through critical analysis of the experiences of patients diagnosed with metastatic melanoma, family carers and health professionals. The outcomes depict a complex intersection between acute care services and palliative care where the discipline of palliative care struggled to position itself within a highly specialised health system. The findings indicate uncertainty around scopes of practice with ambiguity and tension around the transition to palliative care. The research thus argues for stronger and more coherent partnerships and a critical and interdisciplinary conversation about the positioning of palliative care in the acute care sector.

Consumer preferences for teledermoscopy screening to detect melanoma early

- Introduction ‘Store and forward’ teledermoscopy is a technology with potential advantages for melanoma screening. Any large-scale implementation of this technology is dependent on consumer acceptance. - Aim To investigate preferences for melanoma screening options compared to skin selfexamination in adults considered to be at increased risk of developing skin cancer. - Methods A discrete choice experiment (DCE) was completed by 35 consumers, all of whom had prior experience with the use of teledermoscopy, in Queensland, Australia. Participants made 12 choices between screening alternatives described by seven attributes including monetary cost. A mixed logit model was used to estimate the relative weights that consumers place on different aspects of screening, along with the marginal willingness to pay for teledermoscopy as opposed to screening at a clinic. - Results Overall, participants preferred screening/diagnosis by a health professional rather than skin self-examination. Key drivers of screening choice were for results to be reviewed by a dermatologist; a higher detection rate; fewer non-cancerous moles being removed in relation for every skin cancer detected; and less time spent away from usual activities. On average, participants were willing to pay AU$110 to have teledermoscopy with dermatologist review available to them as a screening option. - Discussion & Conclusions Consumers preferentially value aspects of care that are more feasible with a teledermoscopy screening model, as compared to other skin cancer screening and diagnosis options. This study adds to previous literature in the area which has relied on the use of consumer satisfaction scales to assess the acceptability of teledermoscopy.

Melanoma cell colony expansion parameters revealed by approximate Bayesian computation

In vitro studies and mathematical models are now being widely used to study the underlying mechanisms driving the expansion of cell colonies. This can improve our understanding of cancer formation and progression. Although much progress has been made in terms of developing and analysing mathematical models, far less progress has been made in terms of understanding how to estimate model parameters using experimental in vitro image-based data. To address this issue, a new approximate Bayesian computation (ABC) algorithm is proposed to estimate key parameters governing the expansion of melanoma cell (MM127) colonies, including cell diffusivity, D, cell proliferation rate, λ, and cell-to-cell adhesion, q, in two experimental scenarios, namely with and without a chemical treatment to suppress cell proliferation. Even when little prior biological knowledge about the parameters is assumed, all parameters are precisely inferred with a small posterior coefficient of variation, approximately 2–12%. The ABC analyses reveal that the posterior distributions of D and q depend on the experimental elapsed time, whereas the posterior distribution of λ does not. The posterior mean values of D and q are in the ranges 226–268 µm2h−1, 311–351 µm2h−1 and 0.23–0.39, 0.32–0.61 for the experimental periods of 0–24 h and 24–48 h, respectively. Furthermore, we found that the posterior distribution of q also depends on the initial cell density, whereas the posterior distributions of D and λ do not. The ABC approach also enables information from the two experiments to be combined, resulting in greater precision for all estimates of D and λ.

Common variants in the CYP2C19 gene are associated with susceptibility to endometriosis

Objective: To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. Design Case-control study. Setting Academic research. Subject(s) The cases comprised 2,271 women with surgically confirmed endometriosis; the controls comprised 939 women with self-report of no endometriosis and 1,770 unscreened population samples. Intervention(s) Sequencing of the CYP2C19 region and follow-up of 80 single nucleotide polymorphisms (SNPs) in two case-control samples. Main Outcome Measure(s) Allele frequency differences between cases and controls. Result(s) Sequencing of the CYP2C19 gene region resulted in the detection of a large number of known and novel SNPs. Genotyping of 80 polymorphic SNPs in 901 endometriosis cases and 939 controls resulted in study-wide significant association signals for SNPs in moderate or complete linkage disequilibrium with rs4244285, a functional SNP in exon 5 that abrogates CYP2C19 function through the creation of an alternative splice site. Evidence of association was also detected for another functional SNP in the CYP2C19 promoter, rs12248560, which was highlighted in our previous study. Conclusion(s) Functional variants in CYP2C19 may contribute to endometriosis susceptibility in both familial and sporadic cases. © 2014 by American Society for Reproductive Medicine.

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

Molecular genetic investigation of mitochondrial dysfunction in relation to migraine susceptibility

The aim of this research was to assess the role of genetic variation in mitochondrial function and how this relates to migraine pathophysiology. Using our unique Norfolk Island population, a custom in-house next generation sequencing methodology was developed. This data for the first time showed that there is a molecular genetic link between mitochondrial dysfunction and migraine susceptibility. This work has provided the foundation for further studies aimed at utilising the identified markers in improved migraine diagnostic and therapeutic strategies.

Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: A human pharmacological magnetic resonance imaging study at 1.5 and 4 T

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level. © 2005 Wiley-Liss, Inc.

Identity-by-Descent Mapping to Detect Rare Variants Conferring Susceptibility to Multiple Sclerosis

Genome-wide association studies (GWAS) have identified around 60 common variants associated with multiple sclerosis (MS), but these loci only explain a fraction of the heritability of MS. Some missing heritability may be caused by rare variants that have been suggested to play an important role in the aetiology of complex diseases such as MS. However current genetic and statistical methods for detecting rare variants are expensive and time consuming. 'Population-based linkage analysis' (PBLA) or so called identity-by-descent (IBD) mapping is a novel way to detect rare variants in extant GWAS datasets. We employed BEAGLE fastIBD to search for rare MS variants utilising IBD mapping in a large GWAS dataset of 3,543 cases and 5,898 controls. We identified a genome-wide significant linkage signal on chromosome 19 (LOD = 4.65; p = 1.9×10-6). Network analysis of cases and controls sharing haplotypes on chromosome 19 further strengthened the association as there are more large networks of cases sharing haplotypes than controls. This linkage region includes a cluster of zinc finger genes of unknown function. Analysis of genome wide transcriptome data suggests that genes in this zinc finger cluster may be involved in very early developmental regulation of the CNS. Our study also indicates that BEAGLE fastIBD allowed identification of rare variants in large unrelated population with moderate computational intensity. Even with the development of whole-genome sequencing, IBD mapping still may be a promising way to narrow down the region of interest for sequencing priority. © 2013 Lin et al.

Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with Multiple Sclerosis susceptibility

Multiple sclerosis (MS) is a debilitating, chronic demyelinating disease of the central nervous system affecting over 2 million people worldwide. The TAM family of receptor tyrosine kinases (TYRO3, AXL and MERTK) have been implicated as important players during demyelination in both animal models of MS and in the human disease. We therefore conducted an association study to identify single nucleotide polymorphisms (SNPs) within genes encoding the TAM receptors and their ligands associated with MS. Analysis of genotype data from a genome-wide association study which consisted of 1618 MS cases and 3413 healthy controls conducted by the Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) revealed several SNPs within the MERTK gene (Chromosome 2q14.1, Accession Number NG_011607.1) that showed suggestive association with MS. We therefore interrogated 28 SNPs in MERTK in an independent replication cohort of 1140 MS cases and 1140 healthy controls. We found 12 SNPs that replicated, with 7 SNPs showing p-values of less than 10-5 when the discovery and replication cohorts were combined. All 12 replicated SNPs were in strong linkage disequilibrium with each other. In combination, these data suggest the MERTK gene is a novel risk gene for MS susceptibility. © 2011 Ma et al.

Whole-genome screening in ankylosing spondylitis: Evidence of non-MHC genetic-susceptibility loci

Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonparametric linkage analysis was performed. Regions were identified showing "suggestive" or stronger linkage with the disease on chromosomes 1p, 2q, 6p, 9q, 10q, 16q, and 19q. The MHC locus was identified as encoding the greatest component of susceptibility, with an overall LOD score of 15.6. The strongest non-MHC linkage lies on chromosome 16q (overall LOD score 4.7). These results strongly support the presence of non-MHC genetic-susceptibility factors in AS and point to their likely locations.

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.