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Spatial interactions between cancer and immune cells, as well as the recognition of tumour antigens by cells of the immune system, play a key role in the immune response against solid tumours. The existing mathematical models generally focus only on one of these key aspects. We present here a spatial stochastic individual-based model that explicitly captures antigen expression and recognition. In our model, each cancer cell is characterised by an antigen profile which can change over time due to either epimutations or mutations. The immune response against the cancer cells is initiated by the dendritic cells that recognise the tumour antigens and present them to the cytotoxic T cells. Consequently, T cells become activated against the tumour cells expressing such antigens. Moreover, the differences in movement between inactive and active immune cells are explicitly taken into account by the model. Computational simulations of our model clarify the conditions for the emergence of tumour clearance, dormancy or escape, and allow us to assess the impact of antigenic heterogeneity of cancer cells on the efficacy of immune action. Ultimately, our results highlight the complex interplay between spatial interactions and adaptive mechanisms that underpins the immune response against solid tumours, and suggest how this may be exploited to further develop cancer immunotherapies.

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BACKGROUND: Saudi Arabia is developing very fast in all disciplines, especially in nursing and health. Only about five studies between 1990 and 2010 have been undertaken in Saudi Arabia concerning factors influencing job satisfaction of nurses, although a body of knowledge exists globally. AIM: The purpose of this research was to measure nurses' job satisfaction in Saudi Arabia in a university teaching hospital and to determine the influencing factors. METHODS: A quantitative, cross sectional method, self-administered questionnaire was used for this study. A systematic sample of N=189 nurses was used to collect data. The SPSS version 16.0. was used to analyze the data. An independent t-test and one-way analysis of variance were used to test hypotheses concerning different groups, and correlation tests (the Pearson's and Spearman's rank tests) were used to examine relationships between variables. RESULTS: Overall, nurses were neither satisfied nor dissatisfied with their jobs. However, nurses indicated satisfaction with supervision, co-workers and nature of work. The sources of dissatisfaction were with subscales such as pay, fringe benefits, contingent rewards and operating conditions. CONCLUSION: These findings indicate that there is a need to increase nurses' salaries and bonuses for extra duties. More training programmes and further education also should be encouraged for all nurses. Therefore, it is imperative that nursing managers and policy makers in Saudi Arabia consider these findings to improve nurses' job satisfaction.

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In April 2006 a new contract was introduced that governed how NHS General Dental Practitioners would be funded for the services they provide. This study looks at the impact that the contract has had in the three years since its introduction, evaluating its influence on the clinical care that patients receive and the clinical decisions that dentists are making. This qualitative service evaluation involved interviewing 12 dentists representative of a range of NHS dentists involved with the new NHS dental contract using a semi-structured approach. We found evidence that the new contract has led to dentists making different decisions in their daily practice and sometimes altering their treatment plans and referral patterns to ensure that their business is not disadvantaged. Access to care for some patients without a regular dentist can be compromised by the new contract as it can be financially challenging for a dentist to accept to care for a new patient who has an unknown and potentially large need for treatment. Cherry-picking of potentially more profitable patients may be common. The incentive is to watch borderline problems rather than to treat if a treatment band threshold has already been crossed and treatment may be delayed until a later course of treatment for the same reason. Dentists often feel that complex treatments (for example, endodontic treatments) are financially unviable. Some dentists are referring difficult cases that might previously have been treated 'in house', such as extractions, to another provider, as this enables offloading of costs while potentially retaining full fees. Younger and less experienced dentists may be further pressured.

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BACKGROUND AND AIMS: Familial benign hypocalciuric hypercalcaemia (FBHH) is a benign autosomal dominantly inherited condition which results in elevated serum calcium and low urinary calcium. This condition is of clinical interest because it can be mistakenly diagnosed as primary hyperparathyroidism (PHP). In most cases FBHH can be shown to be due to a mutation in the calcium sensing receptor (CASR) gene and we aimed to find the causative mutation in three Scottish kindreds with FBHH. METHODS: We used a combination of denaturing gradient gel electrophoresis and direct DNA sequencing to detect mutations in the CASR gene. RESULTS: We detected a mutation in the CASR gene in each of the three kindreds. Two different mutations were detected (the same one was present in two kindreds). Neither mutation has been reported previously. All hypercalcaemic individuals from each kindred had the appropriate mutation while all normocalcaemic individuals did not. CONCLUSION: In the vast majority of kindreds with FBHH which have been reported previously, the CASR mutation responsible is private to that kindred. In three Scottish kindreds we have identified two new mutations.

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OBJECTIVES: To determine if African Americans, Pacific Islanders and Gurkhas have a different incidence and severity of peripheral cold injury when compared to Caucasians in the British Army. METHOD: The design was a retrospective analysis of those British male army personnel aged over 18 assessed at the Institute of Naval Medicine Cold Injury Clinic. The participants were 311 patients assessed on first attendance at the UK Institute of Naval Medicine. RESULTS: After excluding those classed as normal, African Americans had a relative incidence of 30.36 (95% CI 25.82 -35.70) when compared to Caucasians; Pacific Islanders a relative incidence of 2.58 (CI 1.24 - 5.38), again against Caucasians. Being of Gurkha ethnicity proved protective, with no abnormal cases found on assessment. The African Americans were more severely affected than Caucasians, with mean scores of 5.39 (SD 1.767) against 4.24 (SD 1.994) for Caucasians. The severity of Pacific Islanders were similar to Caucasians. The ages of African Americans, Pacific Islander and Caucasians had similar means of 26.05, 26.30 and 26.68 respectively, but with a broader age range for Caucasians; SDs 3.428, 2.958 and 7.735. CONCLUSION: Young male African Americans in the British Army are at 30 times greater chance of developing peripheral cold injury and are more severely affected than their Caucasian counterparts following similar climatic exposure, using similar clothing and equipment. Pacific Islanders are at a 2.6 times increased risk, while being a Gurkha is protective.

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BACKGROUND: Symptoms of memory loss are a common complaint within the general population and a frequent reason for seeking medical advice. However, the clinical relevance of these symptoms to future development of neurodegenerative disease is uncertain. The aim of this study is to characterise a cohort of individuals with symptoms of memory loss and varying memory impairment, who will be followed longitudinally with serial neuropsychology and neuroimaging to evaluate the clinical relevance of symptoms of memory loss. METHOD: Fifty-eight subjects with symptoms of memory loss were recruited from the National Hospital for Neurology and Neurosurgery. All subjects underwent clinical assessment, APOE4 genotyping, neuroimaging and neuropsychological tests. RESULTS: Those with mild cognitive impairment (MCI) had an increased prevalence of the APOE4 allele, impaired performance on tests of memory, measures of IQ and naming compared to controls. Baseline brain volumes were decreased and ventricular size increased. Those with symptoms of memory loss but no cognitive impairment (SNCI) performed significantly worse on tests of memory than the control group. CONCLUSIONS: The MCI represent a group with multiple risk factors for progression to AD. The SNCI group may represent a heterogeneous group with some individuals in the early stages of AD whilst others' memory complaints are more likely linked to anxiety or personality traits.

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BACKGROUND: There is increasing interest in quality initiatives that are locally owned and delivered, team based, multiprofessional, and formative. The Royal College of General Practitioners' Quality Team Development (QTD) programme is one such initiative aimed at developing primary healthcare teams and their services. AIMS: To evaluate QTD from the perspective of participants and assessors. SETTING: UK primary health care. DESIGN AND METHOD: Twelve of 14 practices and all four primary care organisations (PCOs) approached agreed to participate. Thirty four semi-structured interviews were conducted with key stakeholders. The interviews were taped, transcribed, and analysed using the constant comparative method. RESULTS: The QTD programme appears to be highly valued by participating organisations. Practice based respondents perceived it as acceptable and feasible, and reported positive changes in teamwork and patient services. They valued its formative, participative, and multiprofessional nature, especially the peer review element. PCOs saw QTD as a method of delivering on prevailing national policies on clinical quality and modernization agendas as well as promoting interorganizational collaboration. The main concerns raised were the workload, particularly for assessors, and maintaining the quality of the assessments and the programme. CONCLUSION: This qualitative study suggests positive benefits for participants in the QTD programme. However, such practices are a self-selecting innovative minority. Further research is needed on more typical practices to identify barriers to their participation in QTD or other formative, team based quality improvement programmes.

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OBJECTIVE: To examine the perceived effect of teaching clinical skills and associated teacher training programmes on general practitioners' morale and clinical practice. DESIGN: Qualitative semistructured interview study. SETTING: General practices throughout north London. SUBJECTS: 30 general practitioners who taught clinical skills were asked about the effect of teaching and teacher training on their morale, confidence in clinical and teaching skills, and clinical practice. RESULTS: The main theme was a positive effect on morale. Within teacher training this was attributed to developing peer and professional support; improved teaching skills; and revision of clinical knowledge and skills. Within teaching this was attributed to a broadening of horizons; contact with enthusiastic students; increased time with patients; improved clinical practice; improved teaching skills; and an improved image of the practice. Problems with teaching were due to external factors such as lack of time and space and anxieties about adequacy of clinical cover while teaching. CONCLUSION: Teaching clinical skills can have a positive effect on the morale of general practitioner teachers as a result of contact with students and peers, as long as logistic and funding issues are adequately dealt with.

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Reindeer inhabit a severe arctic or subarctic environment, with the young born in early spring under adverse weather conditions. The extreme northern climate imposes a major thermal challenge to the newborn, and in the present study we have examined fetal, neonatal, and young (from 2 wk before birth to 16 mo postpartum) semidomesticated reindeer from northern Finland for the presence of thermogenic brown adipose tissue. Adipose tissues were removed, mitochondria were prepared, and the proteins were separated by molecular weight and blotted onto nitrocellulose membranes. The membranes were then probed for the presence of the 32,000-relative molecular weight mitochondrial uncoupling protein (UCP) unique to brown fat by use of a rabbit anti-(ground squirrel UCP) serum. Immunoreactivity at the molecular weight characteristic of UCP was present in perirenal, abdominal, inter(pre)scapular, sternal, intralumbar, vertebral, tracheal, inguinal, and omental-mesenteral adipose tissues of newborn reindeer (0-2 days of age). No immunoreactivity was detected in coronary adipose tissue. UCP was found at high levels in interscapular and perirenal adipose tissues of fetal reindeer at 2 wk before birth. Although the protein was present during the first few days postpartum, little immunoreactivity was found at 1 mo of age, and none was evident by 2 mo. UCP and its mRNA were also apparent in perirenal adipose tissue of the newborn of another species of Cervidae, the red deer. It is concluded, on the basis of the immunologic identification of UCP, that most adipose tissues of newborn reindeer represent functional brown fat but that there is a subsequent conversion to white adipose tissue by the 2nd mo of life.(ABSTRACT TRUNCATED AT 250 WORDS)

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Speech therapists trained in the use of hypnosis were asked to identify the client groups with whom hypnosis was used and the main benefits of hypnosis in the management of these clients. Thirty-six (42%) of the questionnaires produced usable data. The majority of respondents use hypnosis in the treatment of voice or fluency disorders although hypnosis is used in the treatment of acquired neurological disorders too. Respondents were less inclined to use hypnosis with children than with adults. The major use of hypnosis in fluency and voice disorders is as a means of achieving relaxation and of encouraging self-esteem in the client. Of respondents 87% use autohypnosis. Problems encountered in the use of hypnosis and autohypnosis are explored. The results suggest that a closer examination of the purpose and efficacy of hypnosis is called for.

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We have analyzed the regulation of expression of the human beta-globin gene by DNA mediated gene transfer in MEL cells and microinjection in fertilized mouse eggs. The results show that the beta-globin gene contains two regulatory elements: one element in the promoter, that is required for full transcriptional activity and, secondly, a tissue and developmental specific enhancer 3' to the gene.

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