OBJECTIVE: To report and analyse the pattern of end-of-life decision making for terminal Chinese cancer patients. DESIGN: Retrospective descriptive study. SETTING: A cancer clinical trials unit in a large teaching hospital. PATIENTS: From April 1992 to August 1997, 177 consecutive deaths of cancer clinical trial patients were studied. MAIN MEASUREMENT: Basic demographic data, patient status at the time of signing a DNR consent, or at the moment of returning home to die are documented, and circumstances surrounding these events evaluated. RESULTS: (...) DNR orders were written for 64.4% of patients. Patients in pain (odds ratio 0.45, 95% CI 0.22-0.89), especially if requiring opioid analgesia (odds ratio 0.40, 95% CI 0.21-0.77), were factors associated with a higher probability of such an order. Thirty-five patients were taken home to die, a more likely occurrence if the patient was over 75 years (odds ratio 0.12, 95% CI 0.04-0.34), had children (odds ratio 0.14, 95% CI 0.02-0.79), had Taiwanese as a first language (odds ratio 6.74, 95% CI 3.04-14.93), or was unable to intake orally (odds ratio 2.73, 95% CI 1.26-5.92). CPR was performed in 30 patients, none survived to discharge. CONCLUSIONS: DNR orders are instituted in a large proportion of dying Chinese cancer patients in a cancer centre, however, the order is seldom signed by the patient personally. This study also illustrates that as many as 20% of dying patients are taken home to die, in accordance with local custom. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

Background: Discussions about medical errors facilitate professional learning for physicians and may provide emotional support after an error, but little is known about physicians’ attitudes and practices regarding error discussions with colleagues.Methods: Survey of faculty and resident physicians in generalist specialties in Midwest, Mid-Atlantic and Northeast regions of the US to investigate attitudes and practices regarding error discussions, likelihood of discussing hypothetical errors, experience role-modelling error discussions and demographic variables.Results: Responses were received from 338 participants . In all, 73% of (...) respondents indicated they usually discuss their mistakes with colleagues, 70% believed discussing mistakes strengthens professional relationships and 89% knew at least one colleague who would be a supportive listener. Motivations for error discussions included wanting to learn whether a colleague would have made the same decision , wanting colleagues to learn from the mistake and wanting to receive support . Given hypothetical scenarios, most respondents indicated they would likely discuss an error resulting in no harm , minor harm or major harm . Fifty-seven percent of physicians had tried to serve as a role model by discussing an error and role-modelling was more likely among those who had previously observed an error discussion .Conclusions: Most generalist physicians in teaching hospitals report that they usually discuss their errors with colleagues, and more than half have tried to role-model discussions. However, a significant number of these physicians report that they do not usually discuss their errors and some do not know colleagues who would be supportive listeners. (shrink)

The Protein Ontology (PRO) provides a formal, logically-based classification of specific protein classes including structured representations of protein isoforms, variants and modified forms. Initially focused on proteins found in human, mouse and Escherichia coli, PRO now includes representations of protein complexes. The PRO Consortium works in concert with the developers of other biomedical ontologies and protein knowledge bases to provide the ability to formally organize and integrate representations of precise protein forms so as to enhance accessibility to results of protein (...) research. PRO (http://pir.georgetown.edu/pro) is part of the Open Biomedical Ontologies (OBO) Foundry. (shrink)

Neurosurgery for psychiatric disorders, also sometimes referred to as psychosurgery, is rapidly evolving, with new techniques and indications being investigated actively. Many within the field have suggested that some form of guidelines or regulations are needed to help ensure that a promising field develops safely. Multiple countries have enacted specific laws regulating NPD. This article reviews NPD-specific laws drawn from North and South America, Asia and Europe, in order to identify the typical form and contents of these laws and to (...) set the groundwork for the design of an optimal regulation for the field. Key challenges for this design that are revealed by the review are how to define the scope of the law, what types of regulations are required, and how to approach international harmonization given the potential migration of researchers and patients. (shrink)

A revised version of an essay awarded first prize by the Institut International des Sciences Théoriques. Despite its title, the book is less concerned with Eddington than with the British epistemological tradition.--J. C. H.

Originally published in 1933, in partnership with the Institute of Actuaries Students' Society, this book was written to provide actuarial students with an introduction to the operations of friendly societies. The text is highly accessible, avoiding references to external sources in favour of a more interconnected account of the subject. A concise bibliography is also included. This book will be of value to anyone with an interest in the history of friendly societies.

In orthodox quantum mechanics, it has virtually become the custom to identify properties of a physical system with operationally testable propositions about the system. The causes and consequences of this practice are explored mathematically in this paper. Among other things, it is found that such an identification imposes severe constraints on the admissible states of the physical system.

This article reviews the strengths and limitations of five major paradigms of medical computer-assisted decision making (CADM): (1) clinical algorithms, (2) statistical analysis of collections of patient data, (3) mathematical models of physical processes, (4) decision analysis, and (5) symbolic reasoning or artificial intelligence (Al). No one technique is best for all applications, and there is recent promising work which combines two or more established techniques. We emphasize both the inherent power of symbolic reasoning and the promise of artificial intelligence (...) and the other techniques to complement each other. (shrink)

In the recent past, several papers have pointed to the possibility that tumour removal generates a permissive environment in which tumour growth is potentiated. This phenomenon has been coined “perioperative tumour growth” and whilst it represents a departure in terms of our attitude to the surgical process, this concept was first hinted at by Paget1Sir James Paget (1814–1899) was a surgeon and physiologist who is widely held (along with Rudolph Virchow) to be the father of the science of pathology. Paget (...) described Paget's disease of the nipple as well as Paget's disease of bone. himself. Despite this, the time interval immediately before and after cancer surgery (i.e. the perioperative period) remains an underutilised interval during which chemotherapeutic regimens are rarely implemented. Herein, we present a summarised review of the literature that supports the concept that tumour removal may potentiate the growth of residual neoplastic disease. We also outline current knowledge regarding underlying mechanisms and in this manner highlight potential therapeutic entry points. Finally, we emphasise the urgent need for trials of agents that could protect patients against the harmful host–tumour interactions that may occur during the perioperative period. BioEssays 28: 433–437, 2006. © 2006 Wiley Periodicals, Inc. (shrink)