Living Science: Three years in the Galapagos Islands.

The paper is an outline of work done from 1977-1979 by the authors, as visiting scientists at the Charles Darwin Research Station in the Galapagos Islands, Ecuador.They were funded for three years by the WWF (World Wildlife Fund)and the Bird Preservation Society of UK to study the breeding biology and ethology of Flightless cormorants and the Greater Flamingo. The presentation includes human aspects of living on and travelling between uninhabited islands.

Letter To Robert Lowell

Poem

A DRD2 and ANKK1 haplotype is associated with nicotine dependence

To test the importance of the dopamine D2 receptor (DRD2) region in nicotine dependence, 150 smokers and 228 controls were genotyped for the DRD2 C957T, -141delC and ANKK1 TaqIA polymorphisms (rs6277, rs1799732 and rs1800497, respectively). The -141delC SNP did not show any association but both the C957T and TaqIA SNPs showed association at the allele, genotype, haplotype and combined genotype levels. The 957C/TaqI A1 haplotype was more than 3.5 times as likely to be associated with nicotine dependence compared with the 957T/TaqI A1 haplotype (P = 0.003). Analysis of the combined genotypes of both SNPs revealed that individuals who were homozygous for the 957C-allele (CC) and had either one or two copies of the TaqI A1-allele were 3.3 times as likely to have nicotine dependence compared to all other genotype combinations (P = 0.0003) and that these genotypes accounted for approximately 13% of the susceptibility to nicotine addiction in our population. Our findings suggest that the DRD2 C957T polymorphism and the ANKK1 TaqIA polymorphism are key contributors to the genetic susceptibility to nicotine dependence.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

Cardiomyopathy classification : ongoing debate in the genomics era

Cardiomyopathies represent a group of diseases of the myocardium of the heart and include diseases both primarily of the cardiac muscle and systemic diseases leading to adverse effects on the heart muscle size, shape, and function. Traditionally cardiomyopathies were defined according to phenotypical appearance. Now, as our understanding of the pathophysiology of the different entities classified under each of the different phenotypes improves and our knowledge of the molecular and genetic basis for these entities progresses, the traditional classifications seem oversimplistic and do not reflect current understanding of this myriad of diseases and disease processes. Although our knowledge of the exact basis of many of the disease processes of cardiomyopathies is still in its infancy, it is important to have a classification system that has the ability to incorporate the coming tide of molecular and genetic information. This paper discusses how the traditional classification of cardiomyopathies based on morphology has evolved due to rapid advances in our understanding of the genetic and molecular basis for many of these clinical entities.

Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer

OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.

Recasting the theory of mosquito-borne pathogen transmission dynamics and control

Mosquito-borne diseases pose some of the greatest challenges in public health, especially in tropical and sub-tropical regions of theworld. Efforts to control these diseases have been underpinned by a theoretical framework developed for malaria by Ross and Macdonald, including models, metrics for measuring transmission, and theory of control that identifies key vulnerabilities in the transmission cycle. That framework, especially Macdonald’s formula for R0 and its entomological derivative, vectorial capacity, are nowused to study dynamics and design interventions for many mosquito-borne diseases. A systematic review of 388 models published between 1970 and 2010 found that the vast majority adopted the Ross–Macdonald assumption of homogeneous transmission in a well-mixed population. Studies comparing models and data question these assumptions and point to the capacity to model heterogeneous, focal transmission as the most important but relatively unexplored component in current theory. Fine-scale heterogeneity causes transmission dynamics to be nonlinear, and poses problems for modeling, epidemiology and measurement. Novel mathematical approaches show how heterogeneity arises from the biology and the landscape on which the processes of mosquito biting and pathogen transmission unfold. Emerging theory focuses attention on the ecological and social context formosquito blood feeding, themovement of both hosts and mosquitoes, and the relevant spatial scales for measuring transmission and for modeling dynamics and control.

The idea of women : representations of power in the work of Charles Bukowski

This thesis is a comparative textual analysis of Charles Bukowski's representations of power in relation to the idea of women. The exegesis explores Bukowski's idea of women and power as exemplified by the representational differences between his short stories for Hustler Magazine and his novel Women. The creative piece, a novel, "Many a Broken Hearted Woman" informed and was informed by this research.

Anglican Church knew clergyman Robert Waddington was a risk

AUSTRALIAN church officials knew of child-sex allegations in Britain against a senior clergymen when they pushed a victim into accepting a compensation payout on the basis that there was no evidence to back up his claims of abuse. Former Church of England investigator Ray Morris says he prepared a 2004 report about allegations in Britain and Australia - from the 1960s and 80s - against Robert Waddington. He sent it to north Queensland diocese officials, who were at the time involved in mediation with the Australian victim over his claims that he was abused weekly by Waddington between 1964 and 1968, who was headmaster of St Barnabas boarding school in Ravenshoe, southwest of Cairns.

Robert Waddington's cycle of abuse stretches beyond 50 years

THE Church of England banished serial pedophile priest Robert Waddington to Australia, where he abused children across a decade, after suspicions were raised about him molesting choirboys in his London parish. In an alleged church cover-up spanning almost 60 years, Waddington was suddenly and unexpectedly sent to a small school in regional Queensland in 1956 amid claims he was molesting the son of an English politician. Last month the Church of England ordered an independent inquiry into the handling of allegations against Waddington, after a joint investigation by The Australian and The Times of London. But it can now be revealed that Waddington - who died in 2007, facing allegations he abused students in Australia in the 1960s and English choirboys in the 80s and 90s - was molesting children as soon as he joined the church in 1953. The latest allegations have been made by Ray Munn, 70, who was recruited by Waddington, then a curate at St John's church in Bethnal Green, East London, to sing in the choir in 1953. He was almost immediately groomed by the Cambridge University-educated clergyman, who took him on holidays in the English countryside, before he began molesting the then 11-year-old.

Imaginative cinematic geographies of Australia : the mapped view in Charles Chauvel's Jedda and Baz Luhrmann's Australia

Cinema is central to the mediation of history and the construction of imaginative geographies that offer a politicized view of the land and its people. This article investigates cinematic representations of landscape and analyses the ways in which maps and journeys in Charles Chauvel’s film Jedda (1955) and Baz Luhrmann’s Australia (2008)—both set in the far North of Australia—articulate conceptions of “Australianness” in relationship to Indigeneity and the land. We argue the exotic tropics and arid outback regions of northern Australia function metonymically as representative of the nation in these films, working to naturalize ideological values and affirm dominant narratives of history, identity, and entitlement.

Entropic bounds for multi-scale and multi-physics coupling in earth sciences

The ability to understand and predict how thermal, hydrological,mechanical and chemical (THMC) processes interact is fundamental to many research initiatives and industrial applications. We present (1) a new Thermal– Hydrological–Mechanical–Chemical (THMC) coupling formulation, based on non-equilibrium thermodynamics; (2) show how THMC feedback is incorporated in the thermodynamic approach; (3) suggest a unifying thermodynamic framework for multi-scaling; and (4) formulate a new rationale for assessing upper and lower bounds of dissipation for THMC processes. The technique is based on deducing time and length scales suitable for separating processes using a macroscopic finite time thermodynamic approach. We show that if the time and length scales are suitably chosen, the calculation of entropic bounds can be used to describe three different types of material and process uncertainties: geometric uncertainties,stemming from the microstructure; process uncertainty, stemming from the correct derivation of the constitutive behavior; and uncertainties in time evolution, stemming from the path dependence of the time integration of the irreversible entropy production. Although the approach is specifically formulated here for THMC coupling we suggest that it has a much broader applicability. In a general sense it consists of finding the entropic bounds of the dissipation defined by the product of thermodynamic force times thermodynamic flux which in material sciences corresponds to generalized stress and generalized strain rates, respectively.