Biochemical prediction of response of bone metastases to treatment.

Assessment of response of skeletal metastases to systemic therapy is currently dependent on radiological evidence of bone healing. We have performed a prospective study of additional response criteria in patients with progressive bone metastases from breast cancer. Changes in these potential markers of response were correlated with the radiological response and the time to treatment failure (TTF). Successful systemic therapy typically led to a transient increase in osteoblast activity ('flare'), a reduction in osteoclast activity and symptomatic improvement. After 1 month a greater than 10% rise in serum osteocalcin (BGP) and alkaline phosphatase bone isoenzyme (ALP-BI) and a greater than 10% fall in urinary calcium excretion were seen in 14/16 patients with radiographic evidence of bone healing (UICC partial responders). In comparison similar biochemical changes at 1 month were seen in only 4/20 patients with progressive disease (P less than 0.001). The predictive value and diagnostic efficiency (DE) of changes at 1 month in biochemical measurements and symptom score has been calculated. The combination of a greater than 10% rise in ALPBI and BGP and a greater than 10% fall in urinary calcium excretion had a DE of 89% for discriminating response from progression, 88% for response from non-response (progressing + no change patients), and 76% for TTF of greater than 6 months from TTF of less than 6 months. Serum calcium, tartrate resistant acid phosphatase (TRP), urinary hydroxyproline excretion and bone scan changes were unhelpful in discriminating between patient groups. Independent confirmation is needed, but our results suggest there are reliable alternatives to plain radiography in the early assessment of response of bone metastases to treatment

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie

Assessing the diagnostic accuracy of the identification of hyperkinetic disorders following the introduction of government guidelines in England

<p>Abstract</p> <p>Background</p> <p>Previous studies have suggested that both underdiagnosis and overdiagnosis routinely occur in ADHD and hyperkinesis (hyperkinetic disorders). England has introduced governmental guidelines for these disorders' detection and treatment, but there has been no study on clinical diagnostic accuracy under such a regime.</p> <p>Methods</p> <p>All open cases in three Child and Adolescent Mental Health Services (CAMHS) in the South East of England were assessed for accuracy in the detection of hyperkinetic disorders, using a two-stage process employing the Strengths and Difficulties Questionnaire (SDQ) for screening, with the cut-off between "unlikely" and "possible" as the threshold for identification, and the Development And Well-Being Assessment (DAWBA) as a valid and reliable standard.</p> <p>Results</p> <p>502 cases were collected. Their mean age 11 years (std dev 3 y); 59% were clinically diagnosed as having a hyperkinetic disorder including ADHD. Clinicians had missed two diagnoses of hyperkinesis and six of ADHD. The only 'false positive' case was one that had become asymptomatic on appropriate treatment.</p> <p>Conclusion</p> <p>The identification of children with hyperkinetic disorders by three ordinary English CAMHS teams appears now to be generally consistent with that of a validated, standardised assessment. It seems likely that this reflects the impact of Governmental guidelines, which could therefore be an appropriate tool to ensure consistent accurate diagnosis internationally.</p

Permeating the social justice ideals of equality and equity within the context of Early Years: challenges for leadership in multi-cultural and mono-cultural primary schools

The ideology and commitment of social justice principles is central to Early Years practice, however, the term social justice in education is complex and remains contested. This paper explores the ideology of social justice through links between equality and equity and how it is embedded within Early Years, and what remain the potential challenges for leadership. Interviews in English multi-cultural and mono-cultural primary schools were conducted. Findings showed that the ideology of social justice, equality and equity was interpreted differently. Multi-cultural schools appear to use a greater variety of activities to embed social justice principles that involved their diverse communities more to enrich the curriculum. In mono-cultural schools leadership had to be more creative in promoting equality and equity given the smaller proportion of their diverse pupil and staff population. Tentative conclusions suggest that the vision for permeating equality and equity in Early Years, at best, is at early stages

Secondary school pupils' preferences for different types of structured grouping practices

The aim of this paper is to explore pupils’ preferences for particular types of grouping practices an area neglected in earlier research focusing on the personal and social outcomes of ability grouping. The sample comprised over 5,000 year 9 pupils (aged 13-14 years) in 45 mixed secondary comprehensive schools in England. The schools represented three levels of ability grouping in the lower school (years 7 to 9). Pupils responded to a questionnaire which explored the types of grouping that they preferred and the reasons for their choices. The majority of pupils preferred setting, although this was mediated by their set placement, type of school, socio-economic status and gender. The key reason given for this preference was that it enabled work to be matched to learning needs. The paper considers whether there are other ways of achieving this avoiding the negative social and personal outcomes of setting for some pupils

Increasing the satisfaction of general practitioners with continuing medical education programs: A method for quality improvement through increasing teacher-learner interaction

BACKGROUND: Continuing medical education (CME) for general practitioners relies on specialist-based teaching methods in many settings. Formal lectures by specialists may not meet the learning needs of practitioners and may cause dissatisfaction with traditional CME. Increasing learner involvement in teaching programs may improve learner satisfaction. METHODS: A quality improvement program for CME for 18 general practitioners in the Tel Aviv region was designed as a result of dissatisfaction with traditional CME activities. A two-step strategy for change was developed. The CME participants first selected the study topics relevant to them from a needs assessment and prepared background material on the topics. In the second step, specialist teachers were invited to answer questions arising from the preparation of selected topics. Satisfaction with the traditional lecture program and the new participatory program were assessed by a questionnaire. The quality criteria included the relevance, importance and applicability of the CME topic chosen to the participant's practice, the clarity of the presentation and the effective use of teaching aids by the lecturer and the potential of the lecturer to serve as a consultant to the participant. RESULTS: The participatory model of CME significantly increased satisfaction with relevance, applicability and interest in CME topics compared to the traditional lecture format. CONCLUSIONS: Increased learner participation in the selection and preparation of CME topics, and increased interaction between CME teachers and learners results in increased satisfaction with teaching programs. Future study of the effect of this model on physician performance is required

Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) has few effective treatments. Immunotherapy, an attractive alternative strategy, remains challenging with the lack of knowledge on the tumor-infiltrating lymphocyte (TIL) landscape in PDAC. To generate a reference of T-cell subpopulations, we profiled 80,000 T cells from 57 PDAC samples, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on T-cell receptor clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical analysis suggested that certain TIL states, such as dysfunctional and inhibitory populations, often occurred together. Finally, analysis of cultured TIL revealed that high-frequency clones from effector populations were preferentially expanded. These data provide a framework for understanding the PDAC TIL landscape for future TIL use in immunotherapy for PDAC

Obesity management and continuing medical education in primary care: results of a Swiss survey

ABSTRACT: BACKGROUND: The worldwide increase in obesity is becoming a major health concern. General practitioners (GPs) play a central role in managing obesity. We aimed to examine Swiss GPs self-reported practice in diagnosis and treatment of obesity with a special focus on the performance of waist measurement.. METHODS: A structured self-reported questionnaire was mailed to 323 GPs recruited from four urban physician networks in Switzerland. Measures included professional experience, type of practice, obesity-related continuing medical education (CME) and practice in dealing with obesity such as waist measurement. We assessed the association between the performance of waist measurement and obesity-related CME by multivariate ordered logistic regression controlling for GP characteristics as potential confounders. RESULTS: A total of 187 GPs responded to the questionnaire. More than half of the GPs felt confident in managing obesity. The majority of the GPs (73%) spent less than 4 days in the last 5 years on obesity-related CME. More than half of GPs gave advice to reduce energy intakes (64%), intakes of high caloric and alcoholic drinks (56%) and to increase the physical activity (78%). Half of the GPs seldom performed waist measurement and documentation. The frequency of obesity-related CME was independently associated with the performance of waist measurement when controlled for GPs' characteristics by multivariate ordered logistic regression. CONCLUSIONS: The majority of GPs followed guideline recommendations promoting physical activity and dietary counselling. We observed a gap between the increasing evidence for waist circumference assessment as an important measure in obesity management and actual clinical practice. Our data indicated that specific obesity-related CME might help to reduce this gap

A Method for Determining Skeletal Lengths from DXA Images

<p>Abstract</p> <p>Background</p> <p>Skeletal ratios and bone lengths are widely used in anthropology and forensic pathology and hip axis length is a useful predictor of fracture. The aim of this study was to show that skeletal ratios, such as length of femur to height, could be accurately measured from a DXA (dual energy X-ray absorptiometry) image.</p> <p>Methods</p> <p>90 normal Caucasian females, 18–80 years old, with whole body DXA data were used as subjects. Two methods, linear pixel count (LPC) and reticule and ruler (RET) were used to measure skeletal sizes on DXA images and compared with real clinical measures from 20 subjects and 20 x-rays of the femur and tibia taken in 2003.</p> <p>Results</p> <p>Although both methods were highly correlated, the LPC inter- and intra-observer error was lower at 1.6% compared to that of RET at 2.3%. Both methods correlated positively with real clinical measures, with LPC having a marginally stronger correlation coefficient (r²= 0.94; r²= 0.84; average r²= 0.89) than RET (r²= 0.86; r²= 0.84; average r²= 0.85) with X-rays and real measures respectively. Also, the time taken to use LPC was half that of RET at 5 minutes per scan.</p> <p>Conclusion</p> <p>Skeletal ratios can be accurately and precisely measured from DXA total body scan images. The LPC method is easy to use and relatively rapid. This new phenotype will be useful for osteoporosis research for individuals or large-scale epidemiological or genetic studies.</p