Fine-needle aspiration cytology of Merkel cell carcinoma-A review of 69 cases

Background This study reviewed the clinical presentation, cytologic findings and the immunophenotype of 69 Merkel Cell Carcinoma (MCC) cases sampled by FNA. Methods Demographic and clinical data, the cytology findings and results of ancillary testing were reviewed. Results Median patient age was 78 years (37 – 104) with a 1:1.8 female to male ratio. The most common FNA sites sampled included lymph nodes in the neck, the axillary region, the inguinal region and the parotid gland. Most patients had a history of MCC (68%) &/or non-MCC malignancy (70%). The common cytologic pattern was a cellular smear with malignant cells arranged in a dispersed pattern with variable numbers of disorganised groups of cells. Cytoplasm was scant or absent and nuclei showed mild to moderate anisokaryosis, stippled chromatin, inconspicuous nucleoli and nuclear molding. Numerous apoptotic bodies were often present. Cell block samples (28 cases) were usually positive for cytokeratins in a perinuclear dot pattern, including 88% of cases with CK20 positivity. CD56 was the most sensitive (95%) neuroendocrine marker on cell blocks and was also positive with flow cytometry in 9 cases tested. Conclusions MCC is most commonly seen in FNA specimens from the head and neck of elderly patients, often with a history of previous skin lesions. Occasional cases present in younger patients and some may be mistaken for other round blue cell tumors, such as lymphoma. CD 56 may be a useful marker in cell block preparations and in flow cytometric analysis of MCC.

Progress towards understanding the genetics of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a complex syndrome that occurs following exposure to a potentially life threatening traumatic event. This review summarises the literature on the genetics of PTSD including gene–environment interactions (GxE), epigenetics and genetics of treatment response. Numerous genes have been shown to be associated with PTSD using candidate gene approaches. Genome-wide association studies have been limited due to the large sample size required to reach statistical power. Studies have shown that GxE interactions are important for PTSD susceptibility. Epigenetics plays an important role in PTSD susceptibility and some of the most promising studies show stress and child abuse trigger epigenetic changes. Much of the molecular genetics of PTSD remains to be elucidated. However, it is clear that identifying genetic markers and environmental triggers has the potential to advance early PTSD diagnosis and therapeutic interventions and ultimately ease the personal and financial burden of this debilitating disorder.

Genetic divergence and echolocation call frequency in cryptic species of Hipposideros larvatus s.l. (Chiroptera : Hipposideridae) from the Indo-Malayan region

The intermediate leaf-nosed bat (Hipposideros larvatus) is a medium-sized bat distributed throughout the Indo-Malay region. In north-east India, bats identified as H. larvatus captured at a single cave emitted echolocation calls with a bimodal distribution of peak frequencies, around either 85 kHz or 98 kHz. Individuals echolocating at 85 kHz had larger ears and longer forearms than those echolocating at 98 kHz, although no differences were detected in either wing morphology or diet, suggesting limited resource partitioning. A comparison of mitochondrial control region haplotypes of the two phonic types with individuals sampled from across the Indo-Malay range supports the hypothesis that, in India, two cryptic species are present. The Indian 98-kHz phonic bats formed a monophyletic clade with bats from all other regional populations sampled, to the exclusion of the Indian 85-kHz bats. In India, the two forms showed 12–13% sequence divergence and we propose that the name Hipposideros khasiana for bats of the 85-kHz phonic type. Bats of the 98-kHz phonic type formed a monophyletic group with bats from Myanmar, and corresponded to Hipposideros grandis, which is suggested to be a species distinct from Hipposideros larvatus. Differences in echolocation call frequency among populations did not reflect phylogenetic relationships, indicating that call frequency is a poor indicator of evolutionary history. Instead, divergence in call frequency probably occurs in allopatry, possibly augmented by character displacement on secondary contact to facilitate intraspecific communication.

Subtropical values and principles of subtropical design for the South East Queensland region : a report for the Office of Urban Management Queensland Government

The Office of Urban Management recognises that the values which characterise the SEQ region as 'subtropical' are important determinants of form in urban and regional planning. Subtropical values are those qualities on which our regional identity depends. A built environment which responds positively to these values is a critical ingredient for achieving a desirable future for the region. The Centre for Subtropical Design has undertaken this study to identify the particular set of values which characterises SEQ, and to translate theses values into design principals that will maintain and reinforce the value set. The principles not only apply to the overall balance between the natural environment and the built environment, but can be applied by local government authorities to guide local planning schemes and help shape specific built for outcomes.

A fast semi-implicit difference method for a nonlinear two-sided space-fractional diffusion equation with variable diffusivity coefficients

In this paper, we derive a new nonlinear two-sided space-fractional diffusion equation with variable coefficients from the fractional Fick’s law. A semi-implicit difference method (SIDM) for this equation is proposed. The stability and convergence of the SIDM are discussed. For the implementation, we develop a fast accurate iterative method for the SIDM by decomposing the dense coefficient matrix into a combination of Toeplitz-like matrices. This fast iterative method significantly reduces the storage requirement of O(n2)O(n2) and computational cost of O(n3)O(n3) down to n and O(nlogn)O(nlogn), where n is the number of grid points. The method retains the same accuracy as the underlying SIDM solved with Gaussian elimination. Finally, some numerical results are shown to verify the accuracy and efficiency of the new method.

Direct measurement as a tool for assessing the accuracy of inverse dynamics

The understanding of the loads generated within the prosthetic leg can aid engineers in the design of components and clinicians in the process of rehabilitation. Traditional methods to assess these loads have relied on inverse dynamics. This indirect method estimates the applied load using video recordings and force-plates located at a distance from the region of interest, such as the base of the residuum. The well-known limitations of this method are related to the accuracy of this recursive model and the experimental conditions required (Frossard et al., 2003). Recent developments in sensors (Frossard et al., 2003) and prosthetic fixation (Brånemark et al., 2000) permit the direct measurement of the loads applied on the residuum of transfemoral amputees. In principle, direct measurement should be an appropriate tool for assessing the accuracy of inverse dynamics. The purpose of this paper is to determine the validity of this assumption. The comparative variable used in this study is the velocity of the relative body center of mass (VCOM(t)). The relativity is used to align the static (w.r.t. position) force plate measurement with the dynamic load cell measurement.

Variation in the OC locus of Acinetobacter baumannii genomes predicts extensive structural diversity in the Lipooligosaccharide

Lipooligosaccharide (LOS) is a complex surface structure that is linked to many pathogenic properties of Acinetobacter baumannii. In A. baumannii, the genes responsible for the synthesis of the outer core (OC) component of the LOS are located between ilvE and aspS. The content of the OC locus is usually variable within a species, and examination of 6 complete and 227 draft A. baumannii genome sequences available in GenBank non-redundant and Whole Genome Shotgun databases revealed nine distinct new types, OCL4-OCL12, in addition to the three known ones. The twelve gene clusters fell into two distinct groups, designated Group A and Group B, based on similarities in the genes present. OCL6 (Group B) was unique in that it included genes for the synthesis of L-Rhamnosep. Genetic exchange of the different configurations between strains has occurred as some OC forms were found in several different sequence types (STs). OCL1 (Group A) was the most widely distributed being present in 18 STs, and OCL6 was found in 16 STs. Variation within clones was also observed, with more than one OC locus type found in the two globally disseminated clones, GC1 and GC2, that include the majority of multiply antibiotic resistant isolates. OCL1 was the most abundant gene cluster in both GC1 and GC2 genomes but GC1 isolates also carried OCL2, OCL3 or OCL5, and OCL3 was also present in GC2. As replacement of the OC locus in the major global clones indicates the presence of sub-lineages, a PCR typing scheme was developed to rapidly distinguish Group A and Group B types, and to distinguish the specific forms found in GC1 and GC2 isolates.

Modified MLVA for genotyping Queensland invasive Streptococcus pneumoniae

Background Globally, over 800 000 children under five die each year from infectious diseases caused by Streptococcus pneumoniae. To understand genetic relatedness between isolates, study transmission routes, assess the impact of human interventions e.g. vaccines, and determine infection sources, genotyping methods are required. The ‘gold standard’ genotyping method, Multi-Locus Sequence Typing (MLST), is useful for long-term and global studies. Another genotyping method, Multi-Locus Variable Number of Tandem Repeat Analysis (MLVA), has emerged as a more discriminatory, inexpensive and faster technique; however there is no universally accepted method and it is currently suitable for short-term and localised epidemiology studies. Currently Australia has no national MLST database, nor has it adopted any MLVA method for short-term or localised studies. This study aims to improve S. pneumoniae genotyping methods by modifying the existing MLVA techniques to be more discriminatory, faster, cheaper and technically less demanding than previously published MLVA methods and MLST. Methods Four different MLVA protocols, including a modified method, were applied to 317 isolates of serotyped invasive S. pneumoniae isolated from sterile body sites of Queensland children under 15 years from 2007–2012. MLST was applied to 202 isolates for comparison. Results The modified MLVA4 is significantly more discriminatory than the ‘gold standard’ MLST method. MLVA4 has similar discrimination compared to other MLVA techniques in this study). The failure to amplify particular loci in previous MLVA methods were minimised in MLVA4. Failure to amplify BOX-13 and Spneu19 were found to be serotype specific. Conclusion We have modified a highly discriminatory MLVA technique for genotyping Queensland invasive S. pneumoniae. MLVA4 has the ability to enhance our understanding of the pneumococcal epidemiology and the changing genetics of the pneumococcus in localised and short-term studies.

The future of outsourcing in the Asia-Pacific region: Implications for research and practice—panel report from PACIS 2014

This paper summarizes a panel discussion held at the 18th Pacific Asia Conference on Information Systems (PACIS) in Chengdu, China, 2014, with the same title. The panel discussed the future of outsourcing in the Asia-Pacific region (specifically the importance of outsourcing, new trends, and issues in outsourcing). This paper provides directions for future research that surpasses regional specificity (i.e., the Asia-Pacific region), and contributes to research interests on outsourcing in general.

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10−14, odds ratio = 0.86, 95% confidence interval = 0.82–0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.

Numerical treatment of a two-dimensional variable-order fractional nonlinear reaction-diffusion model

A two-dimensional variable-order fractional nonlinear reaction-diffusion model is considered. A second-order spatial accurate semi-implicit alternating direction method for a two-dimensional variable-order fractional nonlinear reaction-diffusion model is proposed. Stability and convergence of the semi-implicit alternating direct method are established. Finally, some numerical examples are given to support our theoretical analysis. These numerical techniques can be used to simulate a two-dimensional variable order fractional FitzHugh-Nagumo model in a rectangular domain. This type of model can be used to describe how electrical currents flow through the heart, controlling its contractions, and are used to ascertain the effects of certain drugs designed to treat arrhythmia.

Anti-tumour effects of antibodies targeting the extracellular cysteine-rich region of the receptor tyrosine kinase EphB4

EphB4 is a membrane-bound receptor tyrosine kinase (RTK) commonly over-produced by many epithelial cancers but with low to no expression in most normal adult tissues. EphB4 over-production promotes ligand-independent signaling pathways that increase cancer cell viability and stimulate migration and invasion. Several studies have shown that normal ligand-dependent signaling is tumour suppressive and therefore novel therapeutics which block the tumour promoting ligand-independent signaling and/or stimulate tumour suppressive ligand-dependent signaling will find application in the treatment of cancer. An EphB4-specific polyclonal antibody, targeting a region of 200 amino acids in the extracellular portion of EphB4, showed potent in vitro anti-cancer effects measured by an increase in apoptosis and a decrease in anchorage independent growth. Peptide exclusion was used to identify the epitope targeted by this antibody within the cysteine-rich region of the EphB4 protein, a sequence defined as a potential ligand interacting interface. Addition of antibody to cancer cells resulted in phosphorylation and subsequent degradation of the EphB4 protein, suggesting a mechanism that is ligand mimetic and tumour suppressive. A monoclonal antibody which specifically targets this identified extracellular epitope of EphB4 significantly reduced breast cancer xenograft growth in vivo confirming that EphB4 is a useful target for ligand-mimicking antibody-based anti-cancer therapies.