The RAG Model: a new paradigm for genetic risk stratification in multiple myeloma

Molecular studies have shown that multiple myeloma is a highly genetically heterogonous disease which may manifest itself as any number of diverse subtypes each with variable clinicopathological features and outcomes. Given this genetic heterogeneity, a universal approach to treatment of myeloma is unlikely to be successful for all patients and instead we should strive for the goal of personalised therapy using rationally informed targeted strategies. Current DNA sequencing technologies allow for whole genome and exome analysis of patient myeloma samples that yield vast amounts of genetic data and provide a mutational overview of the disease. However, the clinical utility of this information currently lags far behind the sequencing technology which is increasingly being incorporated into clinical practice. This paper attempts to address this shortcoming by proposing a novel genetically based “traffic-light” risk stratification system for myeloma, termed the RAG (Red, Amber, Green) model, which represents a simplified concept of how complex genetic data may be compressed into an aggregate risk score. The model aims to incorporate all known clinically important trisomies, translocations, and mutations in myeloma and utilise these to produce a score between 1.0 and 3.0 that can be incorporated into diagnostic, prognostic, and treatment algorithms for the patient

Nurses\u27 attitudes to the nursing process

The nursing process was \u27introduced in Australia in the mid 1970s, as a teaching tool, however, with the advent of tertiary based education in the late 1970s, it was used as a problem solving approach to the practice of nursing. Acceptance of the nursing process has required changes\u27 in attitudes and practice. The objectives of the study were firstly, to describe nurses\u27 attitudes to the nursing process, and. secondly, to relate these attitudes to education and experience. The purpose of this study was to describe nurses\u27 attitudes to the nursing process because they are reported to influence the standards or client Care. In addition, better understanding of the problems experienced by nurses could aid in the planning of nursing education curricula and inservice programmes, and expose some impediments to successful clinical and managerial implementation. A descriptive survey was conducted at a metropolitan teaching hospital of a convenience sample of registered general nurses Responses to a twenty point questionnaire, developed by Bowman Thompson & Sutton (1983), were tabulated as percentage frequencies so that areas of positive and negative attitude could be identified. Demographic data was collected to enable correlation of number of years experience with attitude score, and to ascertain the influence of attitude by basic, inservice and postbasic nursing education in the nursing process by an analysis of variance procedure. The findings of the study indicated a moderately positive attitude held by the respondents there was no significant negative correlation between years of experience since basic nurse education and attitude scores there was a difference in attitude scores of nurses whose basic nurse education had included the nursing process and inservice and postbasic nursing process education had no significant influence on attitude scores. It was concluded that while nurses had a moderately positive attitude to the nursing process, the absence of an acknowledged link with improved nursing care in a significant number of respondents indicated a knowledge deficit, in addition, too much paperwork and lack of time were cited as major barriers to implementation, and there was an element of resignation to the use of the nursing process. The implications for the study lie in the educational provisions for nurses to facilitate translation from nursing theory to practice

The Role of Two Cognitive Constraints in the Management of Oral Narratives

The nature and supporting evidence for two well-known and frequently discussed cognitive processing principles, the CLOSURE and the GIVEN-NEW constraints, are reviewed. The two constraints are then evaluated against data from experiments dealing with the production of oral narratives under controlled conditions. It is concluded that the two constraints, for which the majority of supporting evidence has come from comprehension studies, are also operative in language production. CLOSURE is found to be highly salient and central in the production of such narratives, while the GIVEN-NEW constraint is shown to function in a somewhat more complex manner, depending on the type of narrative being produced. Possible reasons for the differences in salience are suggested

Legitimising Religion in Public

The English context for interreligious dialogue is shaped by the presence of an established church which is inclusive, geographically spread, and engages with the state. This article will trace the ways in which the presence of an established church, and the particular model of church-state settlement, provide a context to legitimise particular types of interreligious activity. The social role of religion, the representative function of religion, and religion as an inclusive category, will be highlighted as key elements in the role of religion in English public life and in how interreligious organisations have developed. This observation is analytically useful as it assists an understanding of how and why interreligious dialogue and other activity has at various points become significant for the state’s governance of religious diversity, how success is understood and managed, and what non-engagement with interreligious activity might indicate

Research ethics and teaching

Following the publication of the BASR Ethical Guidelines, it is timely to reflect on the significance of undergraduate understanding and engagement with ethical standards in religious studies research. Starting from a pedagogic rationale for engagement with research ethics and approval processes, this article will reflect on the experience of developing resources to support student engagement with research ethics in the study of religion. Some of the key issues facing students and seasoned researchers alike, including those related to research online, will be used to illustrate how research ethics can provide a structure for student engagement with theoretical issues in the study of religions

Extracellular Matrix Mineralization Promotes E11/gp38 Glycoprotein Expression and Drives Osteocytic Differentiation

Osteocytes are terminally differentiated osteoblasts which reside in a mineralized extracellular matrix (ECM). The factors that regulate this differentiation process are unknown. We have investigated whether ECM mineralization could promote osteocyte formation. To do this we have utilised MLO-A5 pre-osteocyte-like cells and western blotting and comparative RT-PCR to examine whether the expression of osteocyte-selective markers is elevated concurrently with the onset of ECM mineralization. Secondly, if mineralization of the ECM is indeed a driver of osteocyte formation, we reasoned that impairment of ECM mineralization would result in a reversible inhibition of osteocyte formation. Supplementation of MLO-A5 cell cultures with ascorbic acid and phosphate promoted progressive ECM mineralization as well as temporally associated increases in expression of the osteocyte-selective markers, E11/gp38 glycoprotein and sclerostin. Consistent with a primary role for ECM mineralization in osteocyte formation, we also found that inhibition of ECM mineralization, by omitting phosphate or adding sodium pyrophosphate, a recognized inhibitor of hydroxyapatite formation, resulted in a 15-fold decrease in mineral deposition that was closely accompanied by lower expression of E11 and other osteocyte markers such as Dmp1, Cd44 and Sost whilst expression of osteoblast markers Ocn and Col1a increased. To rule out the possibility that such restriction of ECM mineralization may produce an irreversible modification in osteoblast behaviour to limit E11 expression and osteocytogenesis, we also measured the capacity of MLO-A5 cells to re-enter the osteocyte differentiation programme. We found that the mineralisation process was re-initiated and closely allied to increased expression of E11 protein after re-administration of phosphate or omission of sodium pyrophosphate, indicating an ECM mineralization-induced restoration in osteocyte formation. These results emphasise the importance of cell-ECM interactions in regulating osteoblast behaviour and, more importantly, suggest that ECM mineralization exerts pivotal control during terminal osteoblast differentiation and acquisition of the osteocyte phenotype

Episodes as Memory Units in Discourse Representation: Anaphor Use in English and Mandarin

The present study investigates the relationship between cognitive constraints and discourse processing. In particular, it examines how the hierarchical structure of discourse is organized and presented, and what consequences that structure has for the linguistic coding employed during the dynamic time course of discourse processing. Special attention is directed to the distribution of full NPs and pronouns in discourse as a function of the location of episode boundaries. Results obtained from an experiment support the hypothesis that episode structure governs the alternative use of anaphora

High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types.

Understanding the distribution patterns of antibiotics at the site of infection is paramount to selecting adequate drug regimens and developing new antibiotics. Tuberculosis (TB) lung lesions are made of various immune cell types, some of which harbor persistent forms of the pathogen, Mycobacterium tuberculosis. By combining high resolution MALDI MSI with histology staining and quantitative image analysis in rabbits with active TB, we have mapped the distribution of a fluoroquinolone at high resolution, and identified the immune-pathological factors driving its heterogeneous penetration within TB lesions, in relation to where bacteria reside. We find that macrophage content, distance from lesion border and extent of necrosis drive the uneven fluoroquinolone penetration. Preferential uptake in macrophages and foamy macrophages, where persistent bacilli reside, compared to other immune cells present in TB granulomas, was recapitulated in vitro using primary human cells. A nonlinear modeling approach was developed to help predict the observed drug behavior in TB lesions. This work constitutes a methodological advance for the co-localization of drugs and infectious agents at high spatial resolution in diseased tissues, which can be applied to other diseases with complex immunopathology

Morphological and molecular evidence supports specific recognition of the recently extinct Bettongia anhydra (Marsupialia: Macropodidae)

In 1933, geologist and explorer Michael Terry collected the skull of a small macropodid captured by members of his party near Lake Mackay, western Northern Territory. In 1957, this skull was described as the sole exemplar of a distinct subspecies, Bettongia penicillata anhydra, but was later synonymized with B. lesueur and thereafter all but forgotten. We use a combination of craniodental morphology and ancient mitochondrial DNA to confirm that the Lake Mackay specimen is taxonomically distinct from all other species of Bettongia and recognize an additional specimen from a Western Australian Holocene fossil accumulation. B. anhydra is morphologically and genetically most similar to B. lesueur but differs in premolar shape, rostrum length, dentary proportions, and molar size gradient. In addition, it has a substantial mitochondrial cytochrome b pairwise distance of 9.6–12% relative to all other bettongs. The elevation of this recently extinct bettong to species status indicates that Australia’s mammal extinction record over the past 2 centuries is even worse than currently accepted. Like other bettongs, B. anhydra probably excavated much of its food and may have performed valuable ecological services that improved soil structure and water infiltration and retention, as well as playing an important role in the dispersal of seeds and mycorrhizal fungal spores. All extant species of Bettongia have experienced extensive range contractions since European colonization and some now persist only on island refugia. The near total loss of these ecosystem engineers from the Australian landscape has far-reaching ecological implications