(Review) World History for Behavior Analysts: Jared Diamond\u27s Guns, Germs, and Steel

The article examines two important messages for behavior analysts contained in the book Guns, Germs, and Steel: The Fates of Human Societies, by Jared Diamond. It provides an environmentalist explanation of the different fates of the world\u27s cultures that are compatible with the views of many behavior analysts. It details ways for behavior analysts to investigate the neglected forms of individual behavior

The epidemiology of vaccine preventable virus infections: studies of rubella virus and hepatitis B virus infections performed by oral fluid testing

This thesis presents studies on the epidemiology of vaccine preventable VIruS infections investigated by oral fluid testing. It involved studies of both rubella and hepatitis B virus infections by the detection of specific IgG in oral fluid and of rubella virus by PCR detection and genotyping of viral nucleic acid. To select an oral fluid collection device with optimal performance for these studies three (Orasure, Omni- SAL, Oracol) were compared. Each device collected oral fluid of sufficient quality for qualitative analysis of virus specific IgG, but DracoI was most acceptable to the subjects being tested. IgG capture ELISA (GACELISA) tests were developed for detection of rubella and anti-HBc specific IgG in oral fluid. Their sensitivity was less than that of corresponding serum ELiSAs, with sensitivity decreasing with increasing age of subjects. Whilst the performance of the rubella GACELISA was shown to be an improvement over the existing radioimmunoassay and was particularly sensitive with samples from paediatric populations, the performance of the anti-HBc GACELISA was not considered good enough for further use. The development of an RT-PCR assay targeting the El gene of rubella virus enabled the molecular epidemiology of rubella to be investigated using samples from the UK, China, Greece, and Brazil. By comparison to previously reported strains, the majority of strains were assigned to three banches of a phylogenetic tree. Those assigned to branches 1 (UK, Greece, China) and 2 (China) were not closely related to any previously reported strains. The timing of oral fluid collection and subsequent storage was critical for PCR detection. Ideally oral fluid samples should be collected within 14 days of the onset of symptoms and stored at least at -20°C prior to testing

Evaluation of a measles vaccine campaign by oral-fluid surveys in a rural Kenyan district: interpretation of antibody prevalence data using mixture models

We evaluated the effectiveness of a measles vaccine campaign in rural Kenya, based on oral-fluid surveys and mixture-modelling analysis. Specimens were collected from 886 children aged 9 months to 14 years pre-campaign and from a comparison sample of 598 children aged 6 months post-campaign. Quantitative measles-specific antibody data were obtained by commercial kit. The estimated proportions of measles-specific antibody negative in children aged 0–4, 5–9 and 10–14 years were 51%, 42% and 27%, respectively, pre- campaign and 18%, 14% and 6%, respectively, post-campaign. We estimate a reduction in the proportion susceptible of 65–78%, with ~85% of the population recorded to have received vaccine. The proportion of ‘weak’ positive individuals rose from 35% pre-campaign to 54% post-campaign. Our results confirm the effectiveness of the campaign in reducing susceptibility to measles and demonstrate the potential of oral-fluid studies to monitor the impact of measles vaccination campaigns

Improving sensitivity of oral fluid testing in IgG prevalence studies: application of mixture models to a rubella antibody survey

A method for the analysis of age-stratified antibody prevalence surveys is applied to a previously reported survey of antibody to rubella virus using oral fluid samples in which the sensitivity of the assay used was shown to be compromised. The age-specific distribution of the quantitative results of antibody tests using oral fluids is modelled as a mixture of strong positive, weak positive and negative components. This yields maximum likelihood estimates of the prevalence at each age and demonstrates that, when used in conjunction with mixture modelling techniques, the results of antibody prevalence studies using oral fluids accurately reflect those obtained using sera

Genetics of rheumatic disease

Many of the chronic inflammatory and degenerative disorders that present to clinical rheumatologists have a complex genetic aetiology. Over the past decade a dramatic improvement in technology and methodology has accelerated the pace of gene discovery in complex disorders in an exponential fashion. In this review, we focus on rheumatoid arthritis, systemic lupus erythematosus and ankylosing spondylitis and describe some of the recently described genes that underlie these conditions and the extent to which they overlap. The next decade will witness a full account of the main disease susceptibility genes in these diseases and progress in establishing the molecular basis by which genetic variation contributes to pathogenesis

Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) mutations are the second most common oncogenic driver event in non-small cell lung cancer (NSCLC). Classical activating mutations (exon 19 deletions and the L858R point mutation) comprise the vast majority of EGFR mutations and are well defined as strong predictors for good clinical response to EGFR tyrosine kinase inhibitors (EGFRi). However, low frequency mutations including point mutations, deletions, insertions and duplications occur within exons 18-25 of the EGFR gene in NSCLC and are associated with poorer responses to EGFRi. Despite an increased uptake of more sensitive detection methods to identify rare EGFR mutations in patients, our understanding of the biology of these rare EGFR mutations is poor compared to classical mutations. In particular, clinical data focused on these mutations is lacking due to their rarity and challenges in trial recruitment, resulting in an absence of effective treatment strategies for many low frequency EGFR mutations. In this review, we describe the structural and mechanistic features of rare EGFR mutations in NSCLC and discuss the preclinical and clinical evidence for EGFRi response for individual rare EGFR mutations. We also discuss EGFRi sensitivity for complex EGFR mutations, and conclude by offering a perspective on the outstanding questions and future steps required to make advances in the treatment of NSCLC patients that harbour rare EGFR mutations