Saint Anselm of Canterbury and Charismatic Authority

The early career of Archbishop Anselm of Canterbury (c. 1033–1109) provides an opportunity to explore the operation of charismatic authority in a monastic setting. It is argued that the choice of Anselm for the archiepiscopal see of Canterbury in 1093 was the result of his growing reputation cultivated during his years as prior and abbot of the influential Norman monastery of Bec. The article explores various aspects of Anselm’s charismatic authority including his performance of charisma, the charisma derived from his fame as a scholar, and his reputation as a miracle-working holy man

Blastomycosis in Ontario, 1994–2003

Clinicians in Ontario should be aware of symptoms and areas where disease is endemic

Overdiagnosis and overtreatment of early detected prostate cancer

Early detection of prostate cancer is associated with the diagnosis of a considerable proportion of cancers that are indolent, and that will hardly ever become symptomatic during lifetime. Such overdiagnosis should be avoided in all forms of screening because of potential adverse psychological and somatic side effects. The main threat of overdiagnosis is overtreatment of indolent disease. Men with prostate cancer that is likely to be indolent may be offered active surveillance. Evaluation of active surveillance studies and validation of new biological parameters for risk assessment are expected

Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement

BACKGROUND: This study was performed to test the hypothesis that expression of small heat shock protein Hsp-27 is, at diagnosis, a reliable predictive biomarker of clinically aggressive prostate cancer. METHODS: A panel of tissue microarrays constructed from a well-characterised cohort of 553 men with conservatively managed prostate cancer was stained immunohistochemically to detect Hsp-27 protein. Hsp-27 expression was compared with a series of pathological and clinical parameters, including outcome. RESULTS: Hsp-27 staining was indicative of higher Gleason score (P7, the presence of Hsp-27 retained its power to independently predict poor clinical outcome (P<0.002). Higher levels of Hsp-27 staining were almost entirely restricted to cancers lacking ERG rearrangements (chi2 trend=31.4, P<0.001), although this distribution did not have prognostic significance. INTERPRETATION: This study has confirmed that, in prostate cancers managed conservatively over a period of more than 15 years, expression of Hsp-27 is an accurate and independent predictive biomarker of aggressive disease with poor clinical outcome (P<0.001). These findings suggest that apoptotic and cell-migration pathways modulated by Hsp-27 may contain targets susceptible to the development of biologically appropriate chemotherapeutic agents that are likely to prove effective in treating aggressive prostate cancers

Treatment of local-regional prostate cancer detected by PSA screening: Benefits and harms according to prognostic factors

Background:Men with screen-detected prostate cancer can choose to undergo immediate curative treatment or enter into an expectant management programme. We quantified how the benefits and harms of immediate treatment vary according to the prognostic factors of clinical T-stage, Gleason score, and patient age.Methods:A microsimulation model based on European Randomized Study of Screening for Prostate Cancer data was used to predict the benefits and harms of immediate treatment versus delayed treatment of local-regional prostate cancer in men aged 55-74 years. Benefits included life-years gained and reduced probability of death from prostate cancer. Harms included lead time and probability of overdiagnosis.Results:The ratio of mean lead time to mean life-years gained ranged from 1.8 to 31.2, and the additional number of treatments required per prostate cancer death prevented ranged from 0.3 to 11.6 across the different prognostic groups. Both harm-benefit ratios were lowest, most favourable, for men aged 55-59 years and diagnosed with moderate-risk prostate cancer. Ratios were high for men aged 70-74 years regardless of clinical T-stage and Gleason score.Conclusion:Men aged 55-59 years with moderate-risk prostate cancer are predicted to derive greatest benefit from immediate curative treatment. Immediate treatment is least favourable for men aged 70-74 years with either low-risk or high-risk prostate cancer

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis

Killing them softly: A review on snake translocation and an Australian case study

Human-wildlife conflicts with ‘nuisance’ snakes are becoming more frequent around the world as urbanisation continues to encroach on remaining habitats. In an attempt to mitigate this issue, snakes are often translocated in an uncontrolled fashion, with little to no conservation value. To determine the most appropriate methods of translocation we reviewed the available primary literature on studies performing translocations of snakes. We found two types of translocation: long and short-distance. Based on the welfare of the animals involved and difficulty of achieving success with long-distance translocations, we deduced that short-distance translocations are the most favourable. We also reviewed the literature on a third method-repatriating wild populations of snakes with captive-bred or captive-reared individuals, the results of which were very similar to those of long-distance translocations. In conjunction with a mark recapture study carried out by snake catchers in Darwin, Australia, we use our findings to make suggestions on the most appropriate course of action for the mitigation-based snake catching activities in Australia. The difficulty of ensuring successful outcomes for long distance translocations along with a high mortality rate meant we cannot suggest this as an appropriate method for managing ‘nuisance’ snakes. Instead, we argue that short distance translocations are the most suitable for the welfare of the snakes involved. Nevertheless, no outcome will be more favourable for the snakes than to be simply released within their home range accompanied by a change in attitude of the general public towards a willingness to coexist. Although we focus primarily on Australia our suggested framework can be applied in any country where there is conflict with snakes. Furthermore, should our suggestions be implemented, they are merely a temporary solution to an ongoing problem and we are in desperate need for further research to devise a long-term management plan