"Cancer 2015": a prospective, population-based cancer cohort-phase 1: feasibility of genomics-guided precision medicine in the clinic

"Cancer 2015" is a longitudinal and prospective cohort. It is a phased study whose aim was to pilot recruiting 1000 patients during phase 1 to establish the feasibility of providing a population-based genomics cohort. Newly diagnosed adult patients with solid cancers, with residual tumour material for molecular genomics testing, were recruited into the cohort for the collection of a dataset containing clinical, molecular pathology, health resource use and outcomes data. 1685 patients have been recruited over almost 3 years from five hospitals. Thirty-two percent are aged between 61-70 years old, with a median age of 63 years. Diagnostic tumour samples were obtained for 90% of these patients for multiple parallel sequencing. Patients identified with somatic mutations of potentially "actionable" variants represented almost 10% of those tumours sequenced, while 42% of the cohort had no mutations identified. These genomic data were annotated with information such as cancer site, stage, morphology, treatment and patient outcomes and health resource use and cost. This cohort has delivered its main objective of establishing an upscalable genomics cohort within a clinical setting and in phase 2 aims to develop a protocol for how genomics testing can be used in real-time clinical decision-making, providing evidence on the value of precision medicine to clinical practice.

Evolution of a contagious cancer: epigenetic variation in devil facial tumour disease

The emergence of Devil Facial Tumour Disease (DFTD), a highly contagious cancer, is driving Tasmanian devils (Sarcophilus harrisii) to extinction. The cancer is a genetically and chromosomally stable clonal cell line which is transmitted by biting during social interactions. In the present study, we explore the Devil Facial Tumour (DFT) epigenome and the genes involved in DNA methylation homeostasis. We show that tumour cells have similar levels of methylation to peripheral nerves, the tissue from which DFTD originated. We did not observe any strain or region-specific epimutations. However, we revealed a significant increase in hypomethylation in DFT samples over time (p < 0.0001). We propose that loss of methylation is not because of a maintenance deficiency, as an upregulation of DNA methyltransferase 1 gene was observed in tumours compared with nerves (p < 0.005). Instead, we believe that loss of methylation is owing to active demethylation, supported by the temporal increase in MBD2 and MBD4 (p < 0.001). The implications of these changes on disease phenotypes need to be explored. Our work shows that DFTD should not be treated as a static entity, but rather as an evolving parasite with epigenetic plasticity. Understanding the role of epimutations in the evolution of this parasitic cancer will provide unique insights into the role of epigenetic plasticity in cancer evolution and progression in traditional cancers that arise and die with their hosts.

Individual differences in children's suggestibility : a comparison between intellectually disabled and mainstream samples

This study examined whether age, gender, intelligence, communication ability and shyness predict intellectually disabled children’s susceptibility to an interviewer’s misleading suggestions. Further, the study examined whether the relative influence of these factors differs between intellectually disabled and mainstream samples. Participants included 75 children with mild and borderline intellectual disabilities (aged 77–158 months) and 83 mainstream children (aged 68–152 months). All children were individually administered the Yield and Shift subscales of the Gudjonsson Suggestibility Scale (Form 2) as well as standardised measures of IQ, shyness and communication ability. For the intellectually disabled children, multiple regression analyses revealed that age, IQ and communication inversely predicted Yield suggestibility, however, none of the factors predicted Shift suggestibility. For the mainstream children, age made a significant independent contribution to both Yield and Shift suggestibility, while IQ was a significant predictor of Shift suggestibility. When comparing the relative impact of these factors across the samples, age had a significantly greater impact on mainstream (compared with intellectually disabled) children’s Shift suggestibility, while IQ had a significantly greater influence on intellectually disabled (compared with mainstream) children’s Yield scores. These findings highlight the limited generalisability of previous findings involving mainstream children’s suggestibility to intellectually disabled samples.

Recruiting in public places : A strategy to increase diversity in qualitative research samples

For some research projects, recruiting in public places is an invaluable addition to sampling strategies. It complements the more traditional recruitment strategies by providing researchers with' opportunities to include people in the research who would otherwise be excluded. One of the limitations of selective and snowball sampling is that participants often come from the same social group. Participants from these social groups often share similar experiences and ways of thinking about those experiences. The aim of recruiting in public places is to move beyond this 'in group' to ensure a wider perspective. This paper illustrates how recruiting in public places can provide greater sample diversity for theoretical strength. The paper begins with a brief overview of recruiting in public places. It then describes the theoretical considerations associated with this recruiting strategy. The paper demonstrates how recruiting in public places facilitates grounded theory by providing comparisons that are informed by diverse experiences. Using examples and a case study, we illustrate how recruiting in public places can complement selective, snowball and theoretical sampling to ensure a more comprehensive sample.

Determination of glyphosate mono-isopropylamine salt in process samples using flow injection analysis with tris(2,2`-bipyridyl)ruthenium(II) chemiluminescence detection

The mono-isopropylamine salt of glyphosate was selectively determined directly in industrial and commercial formulations using flow injection analysis with tris(2,2′-bipyridyl)ruthenium(II) chemiluminescence detection without the need for separation. Glyphosate and its mono-isopropylamine salt furnished detection limits of 7×10⁻⁹ and 3.5×10⁻¹⁰ M and relative standard deviations of 0.4% at 1×10⁻⁷ M and 0.8% at 5×10⁻⁸ M, respectively. The methodology is robust and reliable with samples subjected only to aqueous dilution prior to analysis.

The determination of urea in soil extracts and related samples - a review

Although the dominant methods for the determination of urea in clinical applications incorporate selective enzymatic hydrolysis of urea, the determination of urea in soil extracts is complicated by the presence of urease inhibitors. The spectrophotometric determination of urea with an acidic solution diacetyl monoxime and semicarbazide is a viable option but traditional manual procedures are time-consuming. New variations on these procedures, based on microplates or flow-injection analysis methodologies, allow a far greater number of samples to be analysed with high precision and sensitivity.

Youth alcohol and other drug use in the United States and Australia: a cross-national comparison of three state-wide samples

Although youth drug and alcohol harm minimization policies in Australia are often contrasted with the abstinence and zero tolerance policies adopted in the United States, there has been little research directly comparing youth substance use behaviour in the two countries. Three state representative samples in Victoria, Australia (n = 7898) and in the US states of Oregon (n = 15 224) and Maine (n = 16 245) completed a common cross-sectional student survey. Rates of alcohol use (lifetime alcohol use, recent use in the past 30 days), alcohol use exceeding recommended consumption limits (binge drinking: five or more drinks in a session), other licit drug use (tobacco use), and norm-violating substance use (substance use at school, use in the past 30 days of marijuana or other illicit drug use) were compared for males and females at ages 12-17. Rates were lower (odds ratios 0.5-0.8) for youth in Maine and Oregon compared to Victoria for lifetime and recent alcohol use, binge drinking and daily cigarette smoking. However, rates of recent marijuana use and recent use of other illicit drugs were higher in Maine and Oregon, as were reports of being drunk or high at school. In contradiction of harm minimization objectives, Victoria, relative to the US states of Oregon and Maine, demonstrated higher rates of alcohol use exceeding recommended consumption limits and daily tobacco use. However, findings suggested that aspects of norm-violating substance use (substance use at school, marijuana use and other illicit drug use) were higher in the US states compared to Victoria.

Methodology for extracting quasi-random samples from world wide web domains

The purpose of this paper is to describe a process for sampling specific domain name zones on the World Wide Web. Because of the size of the Web, sampling strategies must be employed in order to effectively model and study the Web business environment.  This paper discusses Various efforts employed to sample the Web, which ranged from random generation of Internet Protocol Addresses and domain names, to the process finally
employed to create descriptive models of the dot-com domain name zones. The paper suggests that sampling the Web Top Level Domains offers a reasonable alternative for business researchers because it requires only familiarity with the use of the simple Web utilities such as File Transfer
Protocols to obtain initial domain name listings.

Meaning of home : a comparison of the meaning of home as identified by samples of Victorians with, and without, an intellectual disability

This phenomenological study of the meaning of home from the perspectives of people with and without an intellectual disability sought to identify, (a) any common ‘essence’ of meaning held by and, (b) the nature of any differences of perception between, the groups. Purposive samples of 18 people with an intellectual disability and 21 non-disabled people were surveyed using a semi-structured interview to ascertain their experiences of home and 'non-homes'. Inductive analysis of the data revealed a shared understanding of the meaning of home at a fundamental level. This shared meaning of home was found to comprise: the ability to exert control over an area; having a personalised space; feeling content with the living situation; a sense of familiarity with the setting; a set of behaviours and routines usually only enacted when at home; common names and uses for rooms; socialising at home with others; the importance of a positive social atmosphere in the home; and, recognition of places as non-homes because they lacked one or more of these attributes. Further analysis revealed the essence of home is its experience as the place where stress is most reduced or minimised for the individual. The study demonstrates that the concept of stress is superordinate to previously identified concepts considered fundamental to home such as privacy, control and non-homes. Major differences between the two samples were largely differences of degree with people who have an intellectual disability reporting the same fundamental attributes of home as people who do not have an intellectual disability, but in a less elaborated form. Principal among these differences of degree was the notion of control over the home and its derivative elements which encompassed the whole dwelling including its setting for people without an intellectual disability but was very restricted for people with an intellectual disability being largely confined to the person's bedroom. Socialising in or from the home was also very limited for people with an intellectual disability in comparison with that experienced by non-disabled informants with the former group conveying an impression of leading significantly socially isolated lives at home. The major implications of this study are related to the meaning of home per se, to residential service provision to people with an intellectual disability, and to future research.

Anti-tumour necrosis factor-α therapy for severe enteropathy in patients with common variable immunodeficiency (CVID)

We present three common variable immunodeficiency (CVID) patients with
severe inflammatory bowel disease of unknown aetiology, resistant to steroid
treatment, treated with infliximab.After exclusion of any infection, infliximab
was given at a dose of 5 mg/kg every 4 weeks for a 3 month induction followed
by every 4–8 weeks depending on clinical response. Two of these patients had
predominantly small bowel disease; they both showed clinical response to
infliximab with weight gain and improvement of quality of life scores. The
third patient had large bowel involvement with profuse watery diarrhea; this
patient improved dramatically within 48 hours of having infliximab
treatment. All three patients have been maintained on infliximab treatment
for between 5 and 53 months (mean 37 months) with no evidence of increased
susceptibility to infections in the patients with small bowel disease, although
the third patient developed two urinary tract infections and a herpes zoster
infection following therapy. This is the first small case series to show that
infliximab is a useful addition to current therapy in this rare group of patients
with potentially life threatening enteritis.

Obstructive jaundice secondary to neuroendocrine tumour in a patient with von Recklinghausen's disease

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, with variable clinical manifestations and unpredictable course, associated with an increased incidence of various tumours. Plexiform neurofibromas are hallmark lesions of NF1; they are slow-growing tumours, which account for substantial morbidity, including disfigurement and functional impairment, and may even be life-threatening. Neuroendocrine tumours (NETs), a rare diverse group of neoplasms, are occasionally associated with neurofibromatosis. Pancreatic NETs are tumours with an incidence of less than 1/100 000 population/year and complex patterns of behaviour, which often need complicated strategies for optimal management. We present the case of a young adult with NF1, having a unique concurrence of plexiform neurofibroma involving the liver with an ampullary NET, and we discuss step by step the management in a specialist centre.