Chromosomal radiosensitivity in G2-phase lymphocytes identifies breast cancer patients with distinctive tumour characteristics

A substantial proportion of women with breast cancer exhibit an abnormally high radiosensitivity as measured by the frequency of chromatid breaks induced in G2-phase, PHA stimulated lymphocytes. Chromatid break frequencies were compared for a cohort of previously untreated sporadic breast cancer patients and hospital outpatient controls. In the breast cancer group 46% showed high radiosensitivity compared to 14% of controls (P< 0.001). Comparison of those breast cancer patients with a high G2radiosensitivity (G2RS) versus those with a low G2RS showed no difference in menopausal status or age but the high G2RS group had on average a lower score on the Nottingham Prognostic Index. Predicted survival in the high G2RS group at 15 years was 55% compared to 36% for the low G2RS group. Furthermore, 81% of tumours from the high G2RS were oestrogen receptor positive compared to 45% from the low G2RS group. Thus high G2RS identifies a sub-population of patients with distinctive tumour characteristics and with a predicted improved prognosis as compared with those in the low G2RS group. Our findings imply that besides influencing risk of breast cancer the genetic factors determining G2radiosensitivity also influence the tumour characteristics and prognosis in these patients. © 2001 Cancer Research Campaign  http://www.bjcancer.co

Primary care services co-located with Emergency Departments across a UK region: early views on their development

Background Co-location of primary care services with Emergency Departments (ED) is one initiative aiming to reduce the burden on EDs of patients attending with non-urgent problems. However, the extent to which these services are operating within or alongside EDs is not currently known. This study aimed to create a typology of co-located primary care services in operation across Yorkshire and Humber (Y&H) as well as identify early barriers and facilitators to their implementation and sustainability. Methods A self-report survey was sent to the lead consultant or other key contact at 17 EDs in the Y&H region to establish the extent and configuration of co-located primary care services. Semi-structured interviews were then conducted with urgent and unscheduled care stakeholders across five hospital sites to explore the barriers and facilitators to the formation and sustainability of these services. Results Thirteen EDs completed the survey and interviews were carried out with four ED consultants, one ED nurse and three general practitioners (GPs). Three distinct models were identified: ‘Primary Care Services Embedded within the ED’ (seven sites), ‘Co-located Urgent Care Centre’ (two sites) and ‘GP out-of-hours’ (nine sites). Qualitative data were analysed using framework analysis. Four interview themes emerged (justification for the service, level of integration, referral processes and sustainability) highlighting some of the challenges in implementing these co-located primary care services. Conclusion Creating a service within or alongside the ED in which GPs can use their distinct skills and therefore add value to the existing skill mix of ED staff is an important consideration when setting up these systems. Effective triage arrangements should also be established to ensure appropriate patients are referred to GPs. Further research is required to identify the full range of models nationally and to carry out a rigorous assessment of their impact

A modified agar pad method for mycobacterial live-cell imaging

<p>Abstract</p> <p>Background</p> <p>Two general approaches to prokaryotic live-cell imaging have been employed to date, growing bacteria on thin agar pads or growing bacteria in micro-channels. The methods using agar pads 'sandwich' the cells between the agar pad on the bottom and a glass cover slip on top, before sealing the cover slip. The advantages of this technique are that it is simple and relatively inexpensive to set up. However, once the cover slip is sealed, the environmental conditions cannot be manipulated. Furthermore, desiccation of the agar pad, and the growth of cells in a sealed environment where the oxygen concentration will be in gradual decline, may not permit longer term studies such as those required for the slower growing mycobacteria.</p> <p>Findings</p> <p>We report here a modified agar pad method where the cells are sandwiched between a cover slip on the bottom and an agar pad on top of the cover slip (rather than the reverse) and the cells viewed from below using an inverted microscope. This critical modification overcomes some of the current limitations with agar pad methods and was used to produce time-lapse images and movies of cell growth for <it>Mycobacterium smegmatis </it>and <it>Mycobacterium bovis </it>BCG.</p> <p>Conclusions</p> <p>This method offers improvement on the current agar pad methods in that long term live cell imaging studies can be performed and modification of the media during the experiment is permitted.</p

The frequency distribution of presenting symptoms in children aged six months to six years to primary care.

Primary care providers and researchers wishing to estimate study recruitment rates need estimates of illness frequency in primary care. Previous studies of children's symptoms have found that presentations are most common for the symptoms: cough, fever, earache, rash, diarrhoea and vomiting. Since 2000, primary care provision in the United Kingdom has changed with the introduction of Walk-in-Centres (WICs) and new Out of Hours (OoHs) providers. To describe the type and frequency of parent-reported presenting symptoms at a range of primary care sites between 2005 and 2007. Parent-reported presenting symptoms, recorded in their own words, were extracted from data collected from all children aged six months to six years during recruitment to a randomised controlled trial. Presenting symptoms were coded and presented as frequency per 100 'consulting sessions' by type of primary care site. Results were evaluated from 2491 episodes of illness at 35 sites. When grouped by primary care site, respiratory symptoms were the most common at OoHs centres, the WIC and general practitioner (GP) surgeries. Trauma symptoms were common in the Emergency Department, but unexpectedly, diarrhoea and vomiting were more common in the Emergency Department and skin presenting symptoms more common at the WIC than at GP sites. We report the relative frequency of acute symptoms by type of primary care provider. These data may be useful to those planning recruitment to primary care paediatric studies and policy makers for planning primary care service provision

Patient-reported outcomes of periacetabular osteotomy from the prospective ANCHOR cohort study

BACKGROUND: Current literature describing the periacetabular osteotomy (PAO) is mostly limited to retrospective case series. Larger, prospective cohort studies are needed to provide better clinical evidence regarding this procedure. The goals of the current study were to (1) report minimum 2-year patient-reported outcomes (pain, hip function, activity, overall health, and quality of life), (2) investigate preoperative clinical and disease characteristics as predictors of clinical outcomes, and (3) report the rate of early failures and reoperations in patients undergoing contemporary PAO surgery. METHODS: A large, prospective, multicenter cohort of PAO procedures was established, and outcomes at a minimum of 2 years were analyzed. A total of 391 hips were included for analysis (79% of the patients were female, and the average patient age was 25.4 years). Patient-reported outcomes, conversion to total hip replacement, reoperations, and major complications were documented. Variables with a p value of ≤0.10 in the univariate linear regressions were included in the multivariate linear regression. The backward stepwise selection method was used to determine the final risk factors of clinical outcomes. RESULTS: Clinical outcome analysis demonstrated major clinically important improvements in pain, function, quality of life, overall health, and activity level. Increasing age and a body mass index status of overweight or obese were predictive of improved results for certain outcome metrics. Male sex and mild acetabular dysplasia were predictive of lesser improvements in certain outcome measures. Three (0.8%) of the hips underwent early conversion to total hip arthroplasty, 12 (3%) required reoperation, and 26 (7%) experienced a major complication. CONCLUSIONS: This large, prospective cohort study demonstrated the clinical success of contemporary PAO surgery for the treatment of symptomatic acetabular dysplasia. Patient and disease characteristics demonstrated predictive value that should be considered in surgical decision-making. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

In silico peptide-directed ligand design complements experimental peptide-directed binding for protein–protein interaction modulator discovery

Using the protein–protein interaction of Mcl-1/Noxa, two methods for efficient modulator discovery are directly compared. In silico peptide-directed ligand design is evaluated against experimental peptide-directed binding, allowing for the discovery of two new inhibitors of Mcl-1/Noxa with cellular activity. In silico peptide-directed ligand design demonstrates an in vitro hit rate of 80% (IC50 < 100 μM). The two rapid and efficient methods demonstrate complementary features for protein–protein interaction modulator discovery

Reduction rules for the maximum parsimony distance on phylogenetic trees

In phylogenetics, distances are often used to measure the incongruence between a pair of phylogenetic trees that are reconstructed by different methods or using different regions of genome. Motivated by the maximum parsimony principle in tree inference, we recently introduced the maximum parsimony (MP) distance, which enjoys various attractive properties due to its connection with several other well-known tree distances, such as tbr and spr. Here we show that computing the MP distance between two trees, a NP-hard problem in general, is fixed parameter tractable in terms of the tbr distance between the tree pair. Our approach is based on two reduction rules – the chain reduction and the subtree reduction – that are widely used in computing tbr and spr distances. More precisely, we show that reducing chains to length 4 (but not shorter) preserves the MP distance. In addition, we describe a generalization of the subtree reduction which allows the pendant subtrees to be rooted in different places, and show that this still preserves the MP distance. On a slightly different note we also show that Monadic Second Order Logic (MSOL), posited over an auxiliary graph structure known as the display graph (obtained by merging the two trees at their leaves), can be used to obtain an alternative proof that computation of MP distance is fixed parameter tractable in terms of tbr-distance. We conclude with an extended discussion in which we focus on similarities and differences between MP distance and TBR distance and present a number of open problems. One particularly intriguing question, emerging from the MSOL formulation, is whether two trees with bounded MP distance induce display graphs of bounded treewidth