The efficacy of lymph node fine needle aspiration cytology

Fine needle aspiration cytology (FNAC) of lymph nodes is a safe, easy, cheap and quick diagnostic tool, which involves the examination of a random sample of cells from a lymph node. To assess the distribution of diagnostic categories and the efficacy of lymph node fine needle aspiration cytology at our institution. These were compared to the literature. Methodology: All of lymph node FNAC cases taken between the 1st January 2012 and the 31st December 2013 were retrieved from our Laboratory Information System. A total of 300 cases were retrieved and then placed into one of six categories; Category 1: Non-diagnostic, 2: Reactive, 3: Probably reactive but lymphoma cannot be excluded, 4: Non-Hodgkin lymphoma, 5: Hodgkin lymphoma, and 6: Metastasis. These were then correlated with the histology of the lymph node excision specimens. The proportion of diagnoses placed under categories 1, 2, 3, 4, 5 and 6 represent 14%, 53%, 4.3%, 5.7%, 1.7% and 21.3% of the total respectively. The overall efficacy of FNAC showed a sensitivity of 84.5%, specificity of 99.3%, a false negative rate of 10%, a false positive rate of 0.7%, accuracy of 93.1%, positive predictive value of 98.8% and negative predictive value of 89.9%. FNAC of lymph nodes is a very useful and effective tool in triaging patients with lymphadenopathy.peer-reviewe

Parathyroid carcinoma : clinical course, diagnosis and management

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism often resulting in severe hypercalcaemia. It tends to follow a rather aggressive course with a high propensity for locoregional spread and distant metastasis. En bloc resection is the mainstay of treatment, with surgery also playing a role in the palliation of hypercalcaemia for recurrent and metastatic disease. While adjuvant chemotherapy and radiotherapy have shown disappointing outcomes, bisphosphonates and calcimimetic agents are effective in the management of recalcitrant hypercalcaemia in parathyroid carcinoma. We report a case of parathyroid carcinoma in a lady who initially presented with a neck mass, severe hypercalcaemia, a bony swelling over the shin and elevated parathyroid hormone levels. The diagnosis was confirmed histologically following a thyroid lobectomy, isthmectomy and parathyroidectomy. In the three years which followed the patient received two courses of palliative radiotherapy, two thoracotomies for pulmonary metastatectomy, an extensive neck re-exploration and fashioning of a tracheostomy for aggressive local recurrence with invasion of the larynx.peer-reviewe

Simple, quick and green isolation of cannabinoids from complex natural product extracts using sustainable mesoporous materials (Starbon®)

The current process to purify CBD from C. sativa extract is long and intensive, requiring several steps such as winterification for 48 hours at -45 °C and high-temperature, high vacuum distillation. These processes are capital intensive and generate large amounts of toxic solvent waste. In contrast, the solid phase extraction (SPE) methodology proposed herein will change the way CBD is obtained, doing so in a single step that is fast and reusable. Furthermore, the new process is simple and easily implemented and does not require any intensive operator training. Starbon® A300 was successfully employed as the stationary phase in SPE taking Cannabis sativa extract in hexane to selectively physisorb the cannabinoids onto the surface, followed by ethanol to bring about desorption at up to 93% (by GC-FID). A similar one pot system was also proven, using Fedora hemp stem dust as feedstock, with extraction and adsorption in supercritical CO2 followed by desorption in ethanol

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Affect and engagement in STEM education

The current interest and focus on STEM education is largely a response to affective issues related to participation and engagement in mathematics and science. Concerns about low levels of interest and engagement are key factors in students opting out of these subjects, attaining low levels of achievement leading to declining enrolments and concerns about shortages in people taking up STEM-focused careers. This has created a sense of urgency and stakeholders have seen STEM education as a way to ameliorate these issues and concerns. However, the issues are, at least partially, fundamentally affective in nature, and so the response of educators to the current crisis must also be ‘affective’. In this chapter, we examine the philosophical and theoretical foundations of current STEM education approaches, and then interrogate current research relating to STEM education, with a particular focus on Australia, to examine whether affective issues are central in current STEM initiatives