Historical Perspective: What Constitutes Discovery (of a New Virus)?

A historic review of the discovery of new viruses leads to reminders of traditions that have evolved over 118 years. One such tradition gives credit for the discovery of a virus to the investigator(s) who not only carried out the seminal experiments but also correctly interpreted the findings (within the technological context of the day). Early on, ultrafiltration played a unique role in "proving" that an infectious agent was a virus, as did a failure to find any microscopically visible agent, failure to show replication of the agent in the absence of viable cells, thermolability of the agent, and demonstration of a specific immune response to the agent so as to rule out duplicates and close variants. More difficult was "proving" that the new virus was the etiologic agent of the disease ("proof of causation")-for good reasons this matter has been revisited several times over the years as technologies and perspectives have changed. One tradition is that the discoverers get to name their discovery, their new virus (unless some grievous convention has been broken)-the stability of these virus names has been a way to honor the discoverer(s) over the long term. Several vignettes have been chosen to illustrate several difficulties in holding to the traditions (vignettes chosen include vaccinia and variola viruses, yellow fever virus, and influenza viruses. Crimean-Congo hemorrhagic fever virus, Murray Valley encephalitis virus, human immunodeficiency virus 1, Sin Nombre virus, and Ebola virus). Each suggests lessons for the future. One way to assure that discoveries are forever linked with discoverers would be a permanent archive in one of the universal virus databases that have been constructed for other purposes. However, no current database seems ideal-perhaps members of the global community of virologists will have an ideal solution.

Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease.

Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the 'gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies.

Genus Coltivirus (family Reoviridae): genomic and morphologic characterization of Old World and New World viruses.

We report a genomic and morphologic study of the European Eyach (EYA) virus (genus Coltivirus, family Reoviridae) and a comparative analysis with the American Colorado tick fever (CTF) virus (the type species of the genus). The previously established, but distant, antigenic relationship between these viruses was strengthened by genetic findings (presence of cognate genes, amino acid identity between 55 and 88%, similar conserved terminal motifs, suspected read-through phenomenon in segment 9 of both viruses) and by indistinguishable ultramicroscopic morphologies. Moreover, putative constitutive modifying enzyme activities were suspected to be carried out by homologous viral proteins (RNA-dependent RNA polymerase, methyl/guanylyl transferase, NTPase). These findings, together with the comparative analysis to genomes of southeast Asian isolates, support the recent classification of arboviruses with 12 segments of dsRNA within two distinct genera (genus Coltivirus and genus Seadornavirus) and raise interesting questions about the evolutionary origins of coltiviruses. The previously proposed hypothesis that EYA virus was derived from an ancestral virus introduced in Europe with the migration of lagomorphs from North-America, would imply a divergence date between American and European isolates of over 50 million years ago (MYA). This analysis allows for the first time to propose an evolutionary rate for virus dsRNA genomes which was found to be in the order of 10(-8) to 10(-9) mutations/nt/year, a rate similar to that of dsDNA genomes.

Sexual dimorphism and developmental expression of signal-transduction machinery in the vomeronasal organ.

We have explored the use of a new model to study the transduction of chemosignals in the vomeronasal organ (VNO), for which the functional pathway for chemical communication is incompletely understood. Because putative vomeronasal receptors in mammalian and other vertebrate models belong to the superfamily of G-protein-coupled receptors, the objective of the present study was to define which G-protein subunits were present in the VNO of Sternotherus odoratus (stinkpot or musk turtle) in order to provide directionality for future functional studies of the downstream signaling cascades. The turtle vomeronasal epithelium (VNE) was found to contain the G-proteins G(beta) and G(alphail-3) at the microvillar layer, the presumed site of signal tranduction in these neurons, as evidenced by immunocytochemical techniques. G(alphao) labeled the axon bundles in the VNE and the somata of the vomeronasal sensory neurons but not the microvillar layer. Densitometric analysis of Western blots indicated that the VNO from females contained greater concentrations of G(alphai1-3) compared with males. Sexually immature (juvenile) turtles showed intense immunolabeling for all three subunits (G(beta), G(alphai1-3), and G(alphao)) in the axon bundles and an absence of labeling in the microvillar layer. Another putative signaling component found in the microvilli of mammalian VNO, transient receptor potential channel, was also immunoreactive in S. odoratus in a gender-specific manner, as quantified by Western blot analysis. These data demonstrate the utility of Sternotherus for discerning the functional signal transduction machinery in the VNO and may suggest that gender and developmental differences in effector proteins or cellular signaling components may be used to activate sex-specific behaviors.

Collaborating with practitioners in teaching and research: a model for developing the role of the nurse lecturer in practice areas.

Collaborating with practitioners in teaching and research: a model for developing the role of the nurse lecturer in practice areas The integration of nurse education with higher education in the United Kingdom, has highlighted an uncertainty over the clinical role of nurse lecturers. Although benefits have been identified from lecturers maintaining strong links with clinical practice, the evidence suggests that nurse lecturer participation in practice areas is limited. This paper reports a strategy for developing the clinical role of the nurse lecturer through collaborating with practitioners in teaching and research. An action research project designed to implement and evaluate a teaching programme for pre-registration nursing students was developed. The research aimed to evaluate the programme and identify the benefits for students, practitioners and the nurse lecturer in collaborating in teaching on the programme. Ethical approval was granted from the local research ethics committee. Data were collected in three ways: questionnaires to 17 students; focused interviews with nine practitioners; and analysis of the reflective diary kept by the lecturer. Findings identified the success of the teaching programme and also revealed substantial benefits for students, practitioners and the lecturer. Selected findings are used to demonstrate how the liaison, teaching, clinical practice and research elements of the nurse lecturer's clinical role could be developed. The project was small scale and grounded within a specific context and thus may not be applicable to other settings. However, it is suggested that collaboration between nurse educationalists and practitioners in this way offers a potential model for developing the clinical role of the nurse lecturer.

The evolution of viruses, the emergence of viral diseases: a synthesis that Martinus Beijerinck might enjoy.

The relentless production of viral variants and their selection for improved "fit" are seen from the perspective of the infectious disease sciences as ever-changing viral phenotypes and emerging disease risks. In the Darwinian cause:effect equation, we can characterize very well the effects of mutation and selection--these are catalogued as new viral phenotypes or pathotypes. However, the selective forces themselves driving such changes remain rather mysterious. Many selective forces must be at work, acting on the virus, the host, the host population and the environment. In some instances the virus seems to test new unoccupied niches in the absence of any apparent environmental change, but usually it is clear that changes are driven by human activity. Most important must be the ever increasing density of human, domestic animal and crop plant populations and the consequent increased opportunities for transmission of viral variants. Also important must be the great changes affecting all ecosystems--these especially favor the emergence of new zoonotic viruses and viral "species jumpers." The great increase in human travel and transport carries exotic viruses, vectors and hosts around the world, again favoring viral occupation of new niches. The rise of bioterrorism adds yet another threat. Increasing numbers of emerging viral disease episodes seem to be linked to a decline in global resources for proven public health programs, agricultural extension programs, and the like, programs that have stood in the way of the spread and evolution of viral pathogens. If the relationship between viral evolution and the emergence of new viral diseases is rooted firstly in the host and the host population, then more research and resources must be directed to intervention at these levels rather than at the level of the viruses themselves.

The experience of early miscarriage from a male perspective.

In the literature there is increasing awareness of the psychological consequences of early miscarriage for women. However, there is little on the feelings, needs and experiences of men whose partner has had an early miscarriage. This paper aims to describe the experience of early miscarriage from a male perspective using a phenomenological approach. Seven categories related to the experience of early miscarriage are discussed: Feelings, Loss, Characteristics and differences between men and women, Staff action and attitudes, What to do?, Coping and time. Based on an awareness of the needs of both partners, it is suggested that nurses have a key role to play in delivering effective interventions after early miscarriage.

Emerging zoonoses.

In the past few years, emergent disease episodes have increased; nearly all have involved zoonotic or species-jumping infectious agents. Because there is no way to predict when or where the next important new zoonotic pathogen will emerge or what its ultimate importance might be, investigation at the first sign of emergence of a new zoonotic disease is particularly important. Such investigation may be described in terms of a discovery-to-control continuum: from recognition of a new disease in a new setting to complex phases involving the hard science disciplines pertaining to discovery, the epidemiologic sciences pertaining to risk assessment, and activities pertaining to risk management. Today, many activities involving zoonotic disease control are at risk because of a failed investigative infrastructure or financial base. Because zoonotic diseases are distinct, their prevention and control will require unique strategies, based more on fundamental research than on traditional approaches. Such strategies require that we rebuild a cadre of career-committed professionals with a holistic appreciation of several medical and biologic sciences.

Applying lexical and semantic analysis to the exploration of free-text data.

A substantial study of primary nursing involving the authors ( 1 , 2 ) generated, in addition to the pre-coded data, a large number of free-text responses. We decided to investigate whether these less structured data could help to categorise and understand the leadership styles of ward sisters in the sample.

Characterization of a novel syncytium-inducing baboon reovirus.

A syncytium-inducing reovirus was recently isolated from brain homogenates of a baboon suffering from acute, progressive meningoencephalo myelitis. This baboon reovirus (BRV) was classified as a member of the genus Orthoreovirus, family Reoviridae, on the basis of the characteristic capsid morphology and genome and protein profiles. We have assessed the relationship between BRV and the other syncytium-inducing reoviruses in order to determine whether the emergence of this virus represents a host range or pathogenic alteration in a previously described isolate or the appearance of a novel entity. BRV was compared to representative members of the prototype mammalian reoviruses, avian reoviruses, and Nelson Bay virus on the basis of electropherotype, protein profile, and antigenic similarity as measured by immunoprecipitation using homologous and heterologous antisera. In spite of similarities between the genome and protein profiles of BRV and the other orthoreoviruses, migration-rate polymorphisms indicate that BRV has diverged extensively from the previously described syncytium-inducing orthoreoviruses. Most importantly, the limited epitope conservation suggests that BRV has existed in genetic isolation from other reoviruses for quite some time. We conclude that BRV represents a novel syncytium-inducing mammalian reovirus, which is of particular interest in view of its association with disease in nonhuman primates during natural infections and its unusual syncytial phenotype.

One step along the way: the introduction of supernumerary status for RGN students in Foresterhill College, Aberdeen.

This article describes the introduction of supernumerary status for RGN students. A revised modular scheme was implemented and the main aims were to introduce supernumerary status and to provide the students with an identified 'mentor'. The changes were evaluated from teacher, student and ward staff perspectives. Supernumerary status was introduced successfully but mentorship less so. Finally, the significant change is reflected upon in light of current and future changes in nurse education.

Unilateral versus bilateral thyroid resection in differentiated thyroid carcinoma.

Risk-group definitions have been developed recently in an attempt to clarify which operation to do for whom in differentiated thyroid carcinoma. The authors attempted to confirm the validity of an age-based risk-group definition for identifying patients at high risk of death from thyroid carcinoma and to test whether the degree of surgical resection in either high- or low-risk groups affected patient survival. An age-based risk-group definition was used in the retrospective analysis of 161 patients with differentiated thyroid carcinoma seen at the Saskatoon Cancer Centre, University of Saskatchewan, between 1933 and 1964. A significant difference was found in the death rate between low- and high-risk groups (4.3% versus 47% respectively). This confirms the validity of such an age-based risk-group definition. Although a long-term survival benefit was suggested with the use of bilateral thyroid resection in high-risk patients, the difference was not significant. In low-risk patients, there was no difference in the survival rate between patients who underwent unilateral or bilateral thyroid resection, followed up for as long as 55 years.