“The Dashing Subaltern”: Sir Richard Turner in Retrospect

When war came to Canada in August 1914, thousands rallied to the call to arms. Colonel Sam Huges the charismatic and controversial Minister of Militia and Defence scrapped his department’s meticulous plans for mobilizing the nation’s militia and assumed control with amazing, almost fortuitous, results. By September, 33,000 recruits were training at a hastily constructed Camp Valcartier, Quebec. A month later the first contingent of the legendary Canadian Expeditionary Force (CEF) sailed for England (the largest military force ever to cross the Atlantic up to that time)

The effect on survival of early detection of breast cancer in South Australia

Early detection of breast cancer is an important public health policy. Programs of regular screening examinations have been widely established in an attempt to detect the disease when the primary tumour diameter is small. In South Australia, BreastScreen SA suggests that women between the ages of 50 and 70 years be screened every 24 months. Our aim in this paper is to make assessments of various screening procedures by using statistical models with parameters estimated exclusively from South Australian data. We establish a relationship between primary tumour diameter and ultimate survival time. We estimate an advantage of 2.9 (.7) years in median survival time for those women detected with the disease by BreastScreen SA, compared with an unscreened population. We construct a computer model from which we determine the consequences of using a 12 month screening interval, and also the effect of beginning screening at the age of 40 rather than the current conventional commencement age of 50 years

La paradoja balear: ¿por qué las islas fueron colonizadas tan tarde?

Research on Mediterranean islands has pushed the evidence for initial human presence backwardsin time, with 75% occupied by the 4th millennium BC. Yet data from the Balearics suggest that themost likely window for human arrival there is in the last half, and perhaps the final third, of the 3rdmillennium BC. We refer to this disparity as the “Balearic paradox”—why were these large islandscolonized so late? We contextualize the Balearic data, suggesting that “push” and “pull” factors wouldhave affected the willingness of mainland-based agropastoralists to undertake colonization endeavors.We consider the need for improved understanding of socioeconomic, environmental, and climaticfactors in likely colonist source areas.La investigación sobre las islas mediterráneas ha hecho retroceder en el tiempo las primeras evidenciasde ocupación humana, con un 75% de ellas ocupadas en el IV milenio aC. Sin embargo, enlas Baleares los datos sugieren la llegada de los primeros humanos en la segunda mitad, o tal vez elúltimo cuarto, del III milenio aC. Nos referimos a esta disparidad como la «paradoja balear»; ¿porqué fueron estas grandes islas colonizadas tan tarde? En esta contribución, contextualizamos losdatos de las Baleares y sugerimos que diversos factores de atracción y expulsión habrían afectado lavoluntad de las comunidades agropastoriles de tierra firme por emprender esfuerzos colonizadores.Consideramos necesario mejorar nuestra comprensión de los factores socioeconómicos, medioambientalesy climáticos en las posibles áreas de origen de las colonizaciones

Recognition of skin malignancy by general practitioners: observational study using data from a population-based randomised controlled trial

Skin malignancy is an important cause of mortality in the United Kingdom and is rising in incidence every year. Most skin cancer presents in primary care, and an important determinant of outcome is initial recognition and management of the lesion. Here we present an observational study of interobserver agreement using data from a population-based randomised controlled trial of minor surgery. Trial participants comprised patients presenting in primary care and needing minor surgery in whom recruiting doctors felt to be able to offer treatment themselves or to be able to refer to a colleague in primary care. They are thus relatively unselected. The skin procedures undertaken in the randomised controlled trial generated 491 lesions with a traceable histology report: 36 lesions (7%) from 33 individuals were malignant or pre-malignant. Chance-corrected agreement (κ) between general practitioner (GP) diagnosis of malignancy and histology was 0.45 (0.36–0.54) for lesions and 0.41 (0.32–0.51) for individuals affected with malignancy. Sensitivity of GPs for the detection of malignant lesions was 66.7% (95% confidence interval (CI), 50.3–79.8) for lesions and 63.6% (95% CI, 46.7–77.8) for individuals affected with malignancy. The safety of patients is of paramount importance and it is unsafe to leave the diagnosis and treatment of potential skin malignancy in the hands of doctors who have limited training and experience. However, the capacity to undertake all of the minor surgical demand works demanded in hospitals does not exist. If the capacity to undertake it is present in primary care, then the increased costs associated with enhanced training for general medical practitioners (GPs) must be borne

Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function

Bacterial neonatal meningitis results in high mortality and morbidity rates for those affected. Although improvements in diagnosis and treatment have led to a decline in mortality rates, morbidity rates have remained relatively unchanged. Bacterial resistance to antibiotics in this clinical setting further underlines the need for developing other technologies, such as phage therapy. We exploited an in vitro phage therapy model for studying bacterial neonatal meningitis based on Escherichia coli (E. coli) EV36, bacteriophage (phage) K1F and human cerebral microvascular endothelial cells (hCMECs). We show that phage K1F is phagocytosed and degraded by constitutive- and PAMP-dependent LC3-assisted phagocytosis and does not induce expression of inflammatory cytokines TNFα, IL-6, IL-8 or IFNβ. Additionally, we observed that phage K1F temporarily decreases the barrier resistance of hCMEC cultures, a property that influences the barrier permeability, which could facilitate the transition of immune cells across the endothelial vessel in vivo. Collectively, we demonstrate that phage K1F can infect intracellular E. coli EV36 within hCMECs without themselves eliciting an inflammatory or defensive response. This study illustrates the potential of phage therapy targeting infections such as bacterial neonatal meningitis and is an important step for the continued development of phage therapy targeting antibiotic-resistant bacterial infections generally

Population policies and education: exploring the contradictions of neo-liberal globalisation

The world is increasingly characterised by profound income, health and social inequalities (Appadurai, 2000). In recent decades development initiatives aimed at reducing these inequalities have been situated in a context of increasing globalisation with a dominant neo-liberal economic orthodoxy. This paper argues that neo-liberal globalisation contains inherent contradictions regarding choice and uniformity. This is illustrated in this paper through an exploration of the impact of neo-liberal globalisation on population policies and programmes. The dominant neo-liberal economic ideology that has influenced development over the last few decades has often led to alternative global visions being overlooked. Many current population and development debates are characterised by polarised arguments with strongly opposing aims and views. This raises the challenge of finding alternatives situated in more middle ground that both identify and promote the socially positive elements of neo-liberalism and state intervention, but also to limit their worst excesses within the population field and more broadly. This paper concludes with a discussion outling the positive nature of middle ground and other possible alternatives

DNA Ligase C and Prim-PolC participate in base excision repair in mycobacteria

Prokaryotic Ligase D is a conserved DNA repair apparatus processing DNA double-strand breaks in stationary phase. An orthologous Ligase C (LigC) complex also co-exists in many bacterial species but its function is unknown. Here, we show that the LigC complex interacts with core BER enzymes in vivo and demonstrate that together these factors constitute an excision repair apparatus capable of repairing damaged bases and abasic sites. The polymerase component, which contains a conserved C-terminal structural loop, preferentially binds to and fills-in short gapped DNA intermediates with RNA and LigC ligates the resulting nicks to complete repair. Components of the LigC complex, like LigD, are expressed upon entry into stationary phase and cells lacking either of these pathways exhibit increased sensitivity to oxidising genotoxins. Together, these findings establish that the LigC complex is directly involved in an excision repair pathway(s) that repairs DNA damage with ribonucleotides during stationary phase

Subcellular distribution of nuclear import-defective isoforms of the promyelocytic leukemia protein

<p>Abstract</p> <p>Background</p> <p>The promyelocytic leukemia (PML) protein participates in a number of cellular processes, including transcription regulation, apoptosis, differentiation, virus defense and genome maintenance. This protein is structurally organized into a tripartite motif (TRIM) at its N-terminus, a nuclear localization signal (NLS) at its central region and a C-terminus that varies between alternatively spliced isoforms. Most PML splice variants target the nucleus where they define sub-nuclear compartments termed PML nuclear bodies (PML NBs). However, PML variants that lack the NLS are also expressed, suggesting the existence of PML isoforms with cytoplasmic functions. In the present study we expressed PML isoforms with a mutated NLS in U2OS cells to identify potential cytoplasmic compartments targeted by this protein.</p> <p>Results</p> <p>Expression of NLS mutated PML isoforms in U2OS cells revealed that PML I targets early endosomes, PML II targets the inner nuclear membrane (partially due to an extra NLS at its C-terminus), and PML III, IV and V target late endosomes/lysosomes. Clustering of PML at all of these subcellular locations depended on a functional TRIM domain.</p> <p>Conclusions</p> <p>This study demonstrates the capacity of PML to form macromolecular protein assemblies at several different subcellular sites. Further, it emphasizes a role of the variable C-terminus in subcellular target selection and a general role of the N-terminal TRIM domain in promoting protein clustering.</p