Aspirin use and survival after the diagnosis of breast cancer: a population-based cohort study.

BACKGROUND: Aspirin use has been associated with a reduced cancer incidence and fewer deaths from cancer. This study examined whether women with breast cancer prescribed aspirin postdiagnosis had improved survival. METHODS: An observational, population cohort study was undertaken using data linkage of cancer registry, dispensed prescriptions and death records in Tayside, Scotland. All community prescriptions for aspirin in women with breast cancer were extracted and use postdiagnosis for each individual examined using Cox's proportional hazard models. The main outcome measures were all-cause mortality and breast cancer-specific mortality. RESULTS: Four thousand six hundred and twenty-seven patients diagnosed with breast cancer between 1 January 1998 and 31 December 2008 were followed up until 28 February 2010. Median age at diagnosis was 62 (IQR 52-74). One thousand eight hundred and two (39%) deaths were recorded, with 815 (18%) attributed to breast cancer. One thousand and thirty-five (22%) patients were prescribed aspirin postdiagnosis. Such aspirin use was associated with lower risk of all-cause mortality (HR=0.53, 95% CI=0.45-0.63, P<0.001) and breast cancer-specific mortality (HR=0.42, 95% CI=0.31-0.55, P<0.001) after adjusting for age, socioeconomic status, TNM stage, tumour grade, oestrogen receptor status, surgery, radiotherapy, chemotherapy, adjuvant endocrine therapy and aspirin use prediagnosis. CONCLUSIONS: Aspirin use postdiagnosis of breast cancer may reduce both all-cause and breast cancer-specific mortality. Further investigation seeking a causal relationship and which subgroups of patients benefit most await ongoing randomised controlled trials.

Molecular epidemiology of Giardia and Cryptosporidium infections in dairy calves originating from three sources in Western Australia.

A longitudinal study was undertaken to determine the spread of naturally acquired Giardia and Cryptosporidium in dairy cattle in Western Australia. Samples were collected weekly from birth to weaning, and only calves that were sampled four or more times were included in the analysis. It was found that calves rapidly acquire infections with Cryptosporidium parvum and Giardia, with Cryptosporidium being the first to appear within 1-3 weeks after birth whereas Giardia was most prevalent in calves 4-7 weeks of age. Cryptosporidium and Giardia were detected in 48 and 89% of sampled calves, respectively. No significant association was observed in the present study between parasite occurrence and season or management practices (housing), and calf-to-calf contact appears to be the most likely source of transmission. Molecular characterization of isolates of Giardia and C. parvum recovered from calves demonstrated that only the occurrence Cryptosporidium represents a public health risk in terms of the potential for zoonotic transmission.

Action research to improve the pre-registration midwifery curriculum Part. 2: Case study evaluation in seven sites in England.

OBJECTIVE: To identify factors which facilitate and inhibit the effectiveness of current pre-registration midwifery programmes. DESIGN: The case study part of an action research project. SETTING: Seven case study institutions in England. PARTICIPANTS: Student midwives, midwives, midwifery managers/supervisors of midwives, midwife teachers, collaborators in the study. FINDINGS: It emerged, following a synthesis of all data, that the pre-registration midwifery curriculum should have five key outcomes: students should feel confident and competent as midwives; students must have achieved the statutory requirements for registration; students should be committed to undertaking the whole role and responsibilities of a midwife; students must be equipped to take responsibility and accept accountability for their actions; students must recognise the need for career long learning. Whilst overall these new programmes were considered to be effective in preparing students for their role as midwives, there was variability in the degree to which these five key outcomes were achieved by the case study students. IMPLICATIONS FOR PRACTICE: There needs to be agreement as to what constitutes fitness for practice at the point of registration; assessment schemes, particularly those relating to practice capabilities, need to be valid, reliable and robust with the benefit of the doubt being given in favour of childbearing women when students are 'borderline'; fitness for purpose requires clarification to avoid employers having unreal expectations of new qualifiers which may result in attrition due to excessive stress; review of curricula should take account of the importance of personal qualities and learning strategies which enable students to cope with complexity, uncertainty, decision making and 'being a midwife' before course completion.

Action research to improve the pre-registration midwifery curriculum Part. 3: Can fitness for practice be guaranteed? The challenges of designing and implementing an effective assessment in practice scheme.

OBJECTIVE: To design and implement a robust assessment scheme to more effectively identify student midwives' fitness for midwifery practice. DESIGN: Five inter-related action research cycles. Methods included: documentary analysis, interviews, observation, questionnaires, focus groups. SETTING: A large university in England. PARTICIPANTS: Student midwives, practising midwives and midwife teachers, childbearing women, course planning team and EME project team collaborators. FINDINGS: Whilst there was evidence that the majority of students are fit for midwifery practice by the end of the course, assessment schemes were found to be unreliable. In particular there was the potential for 'borderline' students to register as midwives if assessors were inadequately prepared for their responsibilities; assessment documentation was not 'user' friendly; evidence of competence was inadequately recorded or there was a lack of systematic monitoring by university teachers and examiners of the assessment in practice scheme. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The gap between curriculum aspirations and actual implementation needs to close. The assessment matrix, developed as part of the national evaluation study, could usefully be used as a framework when designing assessment schemes. The difficulties for midwife assessors in each locality need to be identified and solutions incorporated into workable but robust strategies. University midwife teachers/lectures have a responsibility to work in partnership with assessors and students to monitor assessment in practice schemes and, where local circumstances and confidence in reliability permit, grade and award credits for practice-based assessment of student capability.

Action research to improve the pre-registration midwifery curriculum--Part I: An appropriate methodology.

OBJECTIVE: To improve the pre-registration midwifery curriculum locally and influence national policy and guidelines for these programmes. DESIGN: Action research provided the framework for the study where a multi-method approach was largely qualitative to attempt to capture the context and complexity in which the midwifery programme operates. The study comprises a synthesis of two separate but interwoven research projects: a national study about the effectiveness of midwifery education (the EME project) and an evaluation and re-design of the three year pre-registration midwifery programme in a large multi-sited university in England. SETTING: A large university in England. PARTICIPANTS: The EME project 39 case study students, their teachers, practice-based mentors/assessors, preceptors and supervisors of midwives or managers; 50 students from the local university's midwifery programme, their teachers and practice-based mentors/assessors from six sites; 41 women who gave birth to their babies in a large teaching hospital in the East Midlands; and a professional network of experienced midwives whose role is to advise the statutory body regulating midwifery programmes in England. FINDINGS: Overall the three-year, pre-registration route into midwifery was found to be an effective preparation for contemporary midwifery practice as judged against a model of a competent midwife at the point of registration. However, there was evidence to suggest that not all students are equipped to practise competently and confidently in contexts of uncertainty and change in the National Health Service. Factors which emerged as influencing curriculum effectiveness related to: recruitment and selection; curriculum structure, appropriateness; and robustness of assessment schemes; the preparation of and support for assessors; and the role of the midwife teacher in assessment in practice settings. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Diagnosing problems and initiating actions as a collaborative process formed an important part of designing and implementing an 'ideal' curriculum in constrained health and higher education contexts. The need for on-going dialogue, critical reflection, and research to facilitate and assess learning more effectively in the 'caring' professions emerged as necessary to ensure that only competent practitioners have a license to practise.

Evaluation of genotoxic and immunotoxic activities of potential glucose biosensor components: ferrocenes.

Three ferrocenes used in glucose biosensor construction were tested in the aspect of genotoxic and immunotoxic activities. All three ferrocenes were not mutagenic in the standard bacterial Ames test. Equally in the Sister Chromatid Exchanges test in human lymphocyte cultures, the genotoxic action of tested ferrocenes could be excluded. However, all three significantly decreased the rate of lymphocyte proliferation and especially diminished the numbers of B-lymphocytes and NK-cells after 72 hours of in vitro culture. Marked differences between the ferrocenes in their immunotoxic activities were noticed, and we were able to select those which would be relatively safe and those which should be avoided in further investigation of the glucose biosensor construction. Our results indicate the necessity to estimate immunotoxic effects as well as genotoxic effects, especially in biosensor components potentially used in vivo.

Delphi technique: one cycle of an action research project to improve the pre-registration midwifery curriculum.

Facilitating a unified interpretation of new or re-designed curricula can be problematic in multi-sited universities. This paper discusses the use of the Delphi technique when implementing an innovative pre-registration midwifery curriculum. It formed one of the action research cycles of the author's doctoral study and was used in an attempt to seek the views of all midwife teachers and achieve a critical mass consensus. The most important issues that emerged from the Delphi process were grouped into four categories. These four categories (the teacher's base site, communications, staff development and administration issues) formed the agenda for a staff away day. The outcome of the process was the generation of a list of priorities and actions for curriculum implementation and the identification of ways in which staff development needs might be met more effectively. An unexpected, but equally important, outcome was the way it helped with team building and agreement on positive actions for its further development.

Women's perceptions of midwifery care: a longitudinal study to shape curriculum development.

BACKGROUND: Health and education services are increasingly expected to focus on the consumer. The perceptions of childbearing women should be incorporated into midwifery curricula, but often they are given minimal attention or not sought for this purpose. This study was designed to enable the views and experiences of local women to influence curriculum development in a large university in England. METHODS: A descriptive, longitudinal, qualitative study was conducted using semistructured and unstructured interviews with women, and data from their maternity records. Forty-one pregnant women were recruited and interviewed during pregnancy, in the early postpartum period in hospital, and in their homes 2 to 3 weeks after the birth. RESULTS: Themes were clustered into three categories: the characteristics and qualities of the caregivers, the individualized nature of care, and the clinical competence of the caregivers. Continuity of caregiver was desired but accepted as probably unrealistic by many. Developing a "special" trusting relationship with a female midwife was perceived as essential to promoting a positive childbirth experience. Clinical competence was expected and largely experienced. Negative feelings related to individual caregivers more than the type of care given. CONCLUSIONS: Most women had positive experiences, finding midwives and doctors with good knowledge, interpersonal skills, and abilities. Examples of poor communication skills and interprofessional conflict indicated a need to give priority to developing and assessing students' interpersonal skills. Evidence of interprofessional conflict acted as the catalyst to merge midwifery with the department of obstetrics in the university to enhance interprofessional learning.

Stoichiometric CO reductive titrations of acetyl-CoA synthase (Carbon monoxide dehydrogenase) from Clostridium thermoaceticum.

Acetyl-CoA synthase (carbon monoxide dehydrogenase) from Clostridium thermoaceticum was stoichiometrically titrated under CO(2) with CO and thionin. Resulting EPR titration curves were simulated assuming different redox descriptions of the enzyme. Samples began slightly reduced, with approximately 20% of the C-cluster reduced to the C(red1) state. With increasing CO intensities, the intensity of C(red1) increased to a maximum, and then declined as the intensities of C(red2), B(red), and A(red)-CO increased and plateaued. Simulations revealed that only a fraction of the A-, B-, and C-centers in the enzyme were redox-active and that, within the probed potentials (-0.2 to -0.45 V), there are probably no other redox sites in the enzyme. Oxidative processes occurred at higher potentials, but they are catalytically irrelevant. Additional low-potential redox sites may be present, but this could not be assessed from the titrations. Best-fit E degrees (C)()ox(/C)()red1 = -0.12 +/- 0.04 V, 0.1 V less negative than under Ar. Titrated samples accepted from 3.5 to 5.0 equiv/alphabeta in accordance with the intensity of the sample's EPR signals. A similar titration under Ar revealed a different pattern of reduction. The intensity of B(red) increased first; then C(red1) converted to C(red2), and then A(red)-CO developed. The sample accepted approximately 4 equiv/alphabeta. The heterogeneity in the enzyme is summarized as follows. About forty percent of A(ox) can be reduced by one electron and bound with CO, yielding A(red)-CO. The remaining A(ox) cannot be reduced. All B(ox) can be reduced, most ( approximately 65%) to the S = (1)/(2) state and the remainder to the S = (3)/(2) state. About 40% of C(ox) are reduced by one electron to C(red1) and then by two more electrons to C(red2). The remaining C(ox) clusters are reduced by one electron to an S = (3)/(2) form. Possible origins of this heterogeneity are discussed.

Evidence for a proposed intermediate redox state in the CO/CO(2) active site of acetyl-CoA synthase (Carbon monoxide dehydrogenase) from Clostridium thermoaceticum.

When samples of the enzyme in the C(red1) state were reduced with Ti(3+) citrate, the C-cluster stabilized in an EPR-silent state. Subsequent treatment with CO or dithionite yielded C(red2). The EPR-silent state formed within 1 min of adding Ti(3+) citrate, while C(red2) formed after 60 min. Ti(3+) citrate appeared to slow the rate by which C(red2) formed from C(red1) and stabilize the C-cluster in the previously proposed C(int) state. This is the first strong evidence for C(int), and it supports the catalytic mechanism that required its existence. This mechanism is analogous to those used by flavins and hydrogenases to convert between n = 2 and n = 1 processes. Ti(3+) citrate had a different effect on enzyme in a CO(2) atmosphere; it shifted reduction potentials of metal centers (relative to those obtained using CO) and did not stabilize C(int). Different redox behavior was also observed when methyl viologen and benzyl viologen were used as reductants. This variability was exploited to prepare enzyme samples in which EPR from C(red2) was present without interfering signals from B(red). The saturation properties of B(red) depended upon the redox state of the enzyme. Three saturation "modes", called Sat1-Sat3, were observed. Sat1 was characterized by a sharp g = 1.94 resonance and low-intensity g = 2. 04 and 1.90 resonances, and was observed in samples poised at slightly negative potentials. Sat2 was characterized by weak intensity from all three resonances, and was strictly associated with intermediate redox states and the presence of CO(2). Sat3 was characterized by strong broad resonances with normalized intensities essentially unchanged relative to nonsaturating conditions, and was observed at the most negative potentials. Each mode probably reflects different spatial relationships among magnetic components in the enzyme.

Eliciting the views of experienced midwives about the assessment of competence in midwifery.

OBJECTIVE: to investigate the views of the English National Board for Nursing, Midwifery and Health Visiting (ENB) Professional Midwifery Advisory Network (PMAN) members about the assessment of competence in midwifery. DESIGN: initial questionnaire followed by a group discussion of a summary of the data from the completed questionnaires. PARTICIPANTS: 54 PMAN midwives representing education, management, research, practice and supervision; plus six ENB Education Officers (midwifery). FINDINGS: the response rate to the questionnaires was 75%. In the group discussion the PMAN members commented particularly on: the large number of items identified as needing assessment in practice and by written work; lack of total agreement on the assessment in practice of normal delivery; differences in practitioners' perceptions of assessment; the number and range of areas to be assessed; differences in expectation of 'task' assessment versus 'holistic' assessment; lack of assessment in simulation; heavy reliance on written work in assessment. CONCLUSIONS: the group's discussion of the questionnaire data revealed further interesting data, which added considerably to the initial analysis and overview. Some participants had misinterpreted the instructions and found that what they had filled in did not accurately reflect their beliefs about assessment. General consensus was reached on the need for a national standard or framework for assessment and more emphasis to be placed on assessing students in the practice setting whilst ensuring this includes knowledge and understanding and not merely psycho-motor skills. The major implications include effective preparation of assessors and more teacher involvement in practice to support the midwife assessors.

Pre-registration midwifery programmes: a case study evaluation of the non-midwifery placements.

OBJECTIVE: to evaluate the effectiveness of non-midwifery placements in enabling pre-registration (direct entry) student midwives to learn about caring for childbearing women with medical, surgical or mental health problems and needs. DESIGN: case study. SETTING: a large midwifery education department and three acute general hospitals in England. PARTICIPANTS: 15 student midwives in the first intake of one college's three-year diploma programme in midwifery plus the practitioners involved in their education. MAIN OUTCOME MEASURES: the learning needs of student midwives, who have no previous health-care experience, to enable them to care effectively for women with medical/surgical/mental health problems; the teaching processes and learning opportunities related to these aspects of care; how the views of teachers and practice placement staff compare with those of the students; the factors that influence the teaching and learning processes and experiences for pre-registration student midwives. FINDINGS: the broad range of experiences in medical/surgical/metal health placements enabled students to increase in maturity, and confidence and develop their communication skills. The variety of placements enhanced student understanding of the multi-disciplinary team's contribution to health care, students learned new practical skills which were transferable to maternity care contexts and all students had opportunities to care for adults with most of the medical/surgical/mental health problems seen in childbearing women. CONCLUSION: this action research project provided data for curriculum development and helped to avoid premature reaction to individual staff and student response. The value of the medical/surgical/mental health placements and the importance of staff and student preparation for effective learning was established. Whilst it might be essential to identify what and where student midwives should learn, it would appear that developing each student must be an equal, if not greater, priority for curriculum designers.

Glucose oxidase mediation by soluble and immobilized electroactive detergents.

A series of novel, surface-active, inorganometallic complexes of osmium were synthesized and then characterized (using electrochemical techniques) as electron transfer mediators for glucose oxidase (EC 1.1.3.4, GOD) from Aspergillus niger. The mediators contain a dipyridylamine ligand bearing (on the amine nitrogen) a saturated alkyl chain (typically C5 to C12), omega-terminated with either a methyl group or a functional group such as carboxyl or hydroxyl. Such compounds displayed subtle differences in their interactions with GOD. The presence of a omega-functional group tended to diminish a mediator's micelle-forming activity, but also concomitantly decreased the denaturing action of the mediator towards the protein structure of GOD. However, the presence of an ionised carboxyl group slowed GOD mediation relative to that of a similar mediator bearing a methyl-terminated long alkyl chain, probably because of the additional negative charge. The omega-carboxyl functionality allowed covalent coupling of mediators to NH2-bearing graphite electrodes. GOD was co-immobilized and the resulting, reagentless, glucose-sensitive electrodes were characterized. Immobilization of the mediator did not appear to affect unduly the ability to mediate GOD. Additionally, complexes were directly coupled to lysine groups of GOD to give a self-mediating enzyme.

Towards an integrated model of competence in midwifery.

Currently in the UK, there is no consensus as to what constitutes an adequate definition of a competent midwife. Yet, given the rapidly changing midwifery needs of childbearing women and society, such clarification has never been more important. In this paper some concepts of competence taken from a review of midwifery, nursing, educational and industrial literature are reviewed, and it is hoped that discussion leading to conceptualisation of an integrated model of competence in midwifery will be stimulated. Questions raised include--What is it that makes midwives competent? Can competence be inferred from performance? How can capability be recognised? Can competence be broken into elements for assessment without losing meaning?

Novel redox surfactants and their interactions with glucose oxidase of Aspergillus niger.

A number of novel redox surfactants (based on mixed bipyridine/dipyridylamine complexes of osmium (II) where the dipyridylamine ligands bears a saturated C(8), C(10), C(12), C(14), or C(16) alkyl chain) were synthesized and characterized electrochemically and biochemically as mediators for glucose oxidase (EC 1.1.3.4, GOD) of Aspergillus niger. These compounds exhibited critical micelle concentrations (CMCs) in phosphate-buffered saline solution (pH 7.4) in the range 10(-4) 10 10(-3) M, the value decreasing with increasing chain length. Dependence of a number of properties (speed of mediation, redox potential, denaturing action on the enzyme, adsorption on an electrode surface) on the length of the mediator alkyl chain was observed. The presence of an alkyl chain decreased the rate of mediation relative to otherwise similar nonsurfactant mediators, and the longer alkyl chain, the slower the rate of mediation. For each compound, mediation above the CMC was about tenfold slower than that observed below the CMC. However, for the cases of mediator absorbed on an electrode surface with GOD, longer chains give increased physisorption of mixed micelles of enzyme and mediator. The compounds were incidentally found to inhibit the glucose oxidase activity of GOD in a complex manner; inhibition increased with increasing chain length and the deactivation, for any given compound, was more pronounced below the CMC than above. Glucose oxidase activity assays and study of the action of surfactants and mediators on the fluorescent properties of carboxy-fluorescein-labeled GOD led to the consideration of a model for redox surfactant-GOD interaction where three mechanisms may operate: first, a selective interaction of mediators with the GOD active site; second, a nondenaturing association of short-chain (

Mirages with atmospheric gravity waves.

The temperature inversions that produce superior mirages are capable of supporting gravity (buoyancy) waves of very low frequency and long wavelength. This paper describes the optics of single mode gravity waves that propagate in a four-layer atmosphere. Images calculated by ray tracing show that (1) relatively short waves add a fine structure to the basic static mirage, and (2) long waves produce cyclic images, similar to those observed in the field, that display significant variation from a base image.

Dilated cardiomyopathy associated with chronic overuse of an adrenaline inhaler.

Endogenous catecholamines in excess are known to cause dilated cardiomyopathy. A patient presented with dilated cardiomyopathy after many years of overusing an adrenaline inhaler. Pathological features and a considerable improvement in myocardial function after withdrawal implicated the exogenous catecholamine excess in the pathogenesis of the cardiomyopathy.