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The mitogen-activated protein kinase (MAPK) pathway is particularly important for the survival and proliferation of melanoma cells. Somatic mutations in BRAF and NRAS are frequently observed in melanoma. Recently, the BRAF inhibitors vemurafenib and dabrafenib have emerged as promising agents for the treatment of melanoma patients with BRAF-activating mutations. However, as BRAF inhibitors induce RAF paradoxical activation via RAF dimerization in BRAF wild-type cells, rapid emergence of acquired resistance and secondary skin tumors as well as presence of few effective treatment options for melanoma bearing wild-type BRAF (including NRAS-mutant melanoma) are clinical concerns. Here, we demonstrate that the selective pan-RAF inhibitor TAK-632 suppresses RAF activity in BRAF wild-type cells with minimal RAF paradoxical activation. Our analysis using RNAi and TAK-632 in preclinical models reveals that the MAPK pathway of NRAS-mutated melanoma cells is highly dependent on RAF. We also show that TAK-632 induces RAF dimerization but inhibits the kinase activity of the RAF dimer, probably because of its slow dissociation from RAF. As a result, TAK-632 demonstrates potent antiproliferative effects both on NRAS-mutated melanoma cells and BRAF-mutated melanoma cells with acquired resistance to BRAF inhibitors through NRAS mutation or BRAF truncation. Furthermore, we demonstrate that the combination of TAK-632 and the MAPK kinase (MEK) inhibitor TAK-733 exhibits synergistic antiproliferative effects on these cells. Our findings characterize the unique features of TAK-632 as a pan-RAF inhibitor and provide rationale for its further investigation in NRAS-mutated melanoma and a subset of BRAF-mutated melanomas refractory to BRAF inhibitors.

The content and bioaccessibility of carotenoids from different chili peppers were analysed and the effects of typical domestic processing were investigated. Peppers were analysed before and after cooking by conventional boiling (10 min in 100 °C water) and also following a freezing period of four months in a domestic freezer (-20 °C). The content and bioaccessibility of the eight carotenoids quantified varied, depending on cultivar, species, colour and processing. Provitamin A carotenoids (β-carotene and β-cryptoxanthin) and capsanthin were present at highest concentrations in the samples before and after processing. In general, yellow and orange peppers were the best sources of lutein, zeaxanthin and neoxanthin. Xanthophyll carotenoids were more efficiently transferred to the micelles and, therefore, were also more bioavailable. Processing decreased the carotenoid content in certain samples; however, the micellar content was generally not lower for processed peppers; therefore the bioaccessibility of carotenoids from processed peppers is enhanced relative to unprocessed peppers., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Pesticides used in agriculture can be taken into worker homes and pose a potential risk for children and other family members. This study focused on identification of potential intervention points at the workplace., Methods: Workers (N = 46) recruited from two tree fruit orchards in Washington State were administered a 63-item pesticide safety questionnaire. Dust was collected from commuter vehicles and worker homes and analyzed for four organophosphorus (OP) pesticides (azinphosmethyl, phosmet, chlorpyrifos, malathion)., Results: Geometric mean azinphosmethyl concentrations in dust for three worker groups (16 pesticide handlers, 15 green fruit thinners, 15 organic orchard workers) ranged from 0.027-1.5 μg/g, with levels in vehicle dust higher than in house dust, and levels in house dust from handlers' homes higher than levels from tree fruit thinners' homes. Vehicle and house dust concentrations of azinphosmethyl were highly associated (R(2) = 0.44, P < 0.001). Significant differences were found across worker groups for availability of laundry facilities, work boot storage, frequency of hand washing, commuter vehicle use, parking location, and safety training., Conclusions: These findings support a focus on intervention activities to reduce take home pesticide exposure closer to the source of contamination; specifically, the workplace and vehicles used to travel to the workplace., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Mobile devices have become increasingly important to young people who now use them to access a wide variety of health-related information. Research and policy related to the integration of health information and support with this technology do not effectively consider the viewpoint of a younger patient. Views of young people with type 1 diabetes are vital in developing quality services and improving their own health-related quality of life (HRQOL), yet research on their lifestyle and use of Web and mobile technology to support their condition and in non-health-related areas is sparse., Objective: To develop insight into young people with type 1 diabetes and their current use of Web and mobile technology and its potential impact on HRQOL. This can be achieved by constructing an in-depth picture of their day-to-day experiences from qualitative interviewing and exploring how they make use of technology in their lives and in relation to their condition and treatment. The goal was then to build something to help them, using the researcher's technical expertise and seeking users' opinions during the design and build, utilizing sociotechnical design principles., Methods: Data were collected by semistructured, in-depth qualitative interviews (N=9) of young people with type 1 diabetes aged 18-21. Interviews were transcribed and loaded onto NVivo for theme identification. Data analysis was undertaken during initial interviews (n=4) to locate potential ideas and enhancements for technical development. Latter interviews (n=5) assisted in the iterative sociotechnical design process of the development and provided additional developmental ideas., Results: Six themes were identified providing an understanding of how participants lived with and experienced their condition and how they used technology. Four technological suggestions for improvement were taken forward for prototyping. One prototype was developed as a clinically approved app. A number of ideas for new mobile apps and enhancements to currently existing apps that did not satisfactorily cater to this age group's requirements for use in terms of design and functionality were suggested by interviewees but were not prototyped., Conclusions: This paper outlines the nonprototyped suggestions from interviewees and argues that young people with type 1 diabetes have a key role to play in the design and implementation of new technology to support them and improve HRQOL. It is vital to include and reflect on their suggestions as they have a radically different view of technology than either their parents or practitioners. We need to consider the relationship to technology that young people with type 1 diabetes have, and then reflect on how this might make a difference to them and when it might not be a suitable mechanism to use.

Changes that may be expected in crocetin esters (crocins) upon digestion were examined in saffron aqueous extracts for the first time. Chemical characterization of total and individual crocins and other bioactive compounds was achieved by UV-vis spectrophotometry, RP-HPLC-DAD, and LC-ESI-MS. Antioxidant activity was evaluated using in vitro assays and the comet assay. The observed loss for both total and trans-crocins was higher in saffron (∼50%) than in gardenia extracts (∼30%), which were also examined for comparison. Loss was lower than that reported for hydrophobic carotenoids. cis-Isomers were less affected, leading to the hypothesis that trans/cis isomerization may occur in parallel to degradation reactions. Monitoring changes in the extracts at oral, gastric, or intestinal phases, separately, verified this view pointing out the critical effect of pH, temperature, and duration of process but not of digestive enzymes. No isomerization and less degradation (<20% loss) was evidenced when pure trans-crocetin (di-β-D-gentiobiosyl) ester was subjected to gastric or intestinal conditions.

A number of recent toxicity studies have highlighted the increased potency of oxygen analogs (oxons) of several organophosphorus (OP) pesticides. These findings were a major concern after environmental oxons were identified in environmental samples from air and surfaces following agricultural spray applications in California and Washington State. This paper reports on the validity of oxygen analog measurements in air samples for the OP pesticide, chlorpyrifos. Controlled environmental and laboratory experiments were used to examine artificial formation of chlorpyrifos-oxon using OSHA Versatile Sampling (OVS) tubes as recommended by NIOSH method 5600. Additionally, we compared expected chlorpyrifos-oxon attributable to artificial transformation to observed chlorpyrifos-oxon in field samples from a 2008 Washington State Department of Health air monitoring study using non-parametric statistical methods. The amount of artificially transformed oxon was then modeled to determine the amount of oxon present in the environment. Toxicity equivalency factors (TEFs) for chlorpyrifos-oxon were used to calculate chlorpyrifos-equivalent air concentrations. The results demonstrate that the NIOSH-recommended sampling matrix (OVS tubes with XAD-2 resin) was found to artificially transform up to 30% of chlorpyrifos to chlorpyrifos-oxon, with higher percentages at lower concentrations (< 30 ng/m3) typical of ambient or residential levels. Overall, the 2008 study data had significantly greater oxon than expected by artificial transformation, but the exact amount of environmental oxon in air remains difficult to quantify with the current sampling method. Failure to conduct laboratory analysis for chlorpyrifos-oxon may result in underestimation of total pesticide concentration when using XAD-2 resin matrices for occupational or residential sampling. Alternative methods that can accurately measure both OP pesticides and their oxygen analogs should be used for air sampling, and a toxicity equivalent factor approach should be used to determine potential health risks from exposures.

Translational research is needed to understand and predict the neurotoxic consequences associated with repeated occupational exposures to organophosphorus pesticides (OPs). In this report, we describe a research strategy for identifying biomarkers of OP neurotoxicity, and we characterize pesticide application workers in Egypt's Menoufia Governorate who serve as our anchor human population for developing a parallel animal model with similar exposures and behavioral deficits and for examining the influence of human polymorphisms in cytochrome P450 (CYP) and paraoxonase 1 (PON1) enzymes on OP metabolism and toxicity. This population has previously been shown to have high occupational exposures and to exhibit a broad range of neurobehavioral deficits. In addition to observational studies of work practices in the field, questionnaires on demographics, lifestyle and work practices were administered to 146 Egyptian pesticide application workers applying pesticides to the cotton crop. Survey results indicated that the application workforce uses standard operating procedures and standardized equipment provided by Egypt's Ministry of Agriculture, which provides a workforce with a stable work history. We also found that few workers report using personal protective equipment (PPE), which likely contributes to the relatively high exposures reported in these application workers. In summary, this population provides a unique opportunity for identifying biomarkers of OP-induced neurotoxicity associated with occupational exposure., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Chlorpyrifos exposures were assessed in 12 Egyptian cotton field workers., Methods: 3,5,6-trichloro-2-pyridinol (TCPy) was measured in 24-hour urine samples to estimate absorbed dose. Workshift air samples were used to calculate chlorpyrifos inhalation dose., Results: Patches on legs had the highest chlorpyrifos loading rates among body regions sampled. Geometric mean chlorpyrifos air concentrations were 5·1, 8·2, and 45·0 μg/m(3) for engineers, technicians, and applicators, respectively; peak TCPy urinary concentrations were 75-129, 78-261, and 487-1659 μg/l, respectively; geometric mean doses were 5·2-5·4, 8·6-9·7, and 50-57 μg/kg, respectively, considering TCPy excretion half-life values of 27 and 41 hours. All worker doses exceeded the acceptable operator exposure level of 1·5 μg/kg/day. An estimated 94-96% of the dose was attributed to dermal exposure, calculated as the difference between total dose and inhalation dose., Discussion: Interventions to reduce dermal exposure are warranted in this population, particularly for the hands, feet, and legs.

Purpose: Aurora A kinase is critical in assembly and function of the mitotic spindle. It is overexpressed in various tumor types and implicated in oncogenesis and tumor progression. This trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of MLN8054, a selective small-molecule inhibitor of Aurora A kinase., Methods: In this first-in-human, dose-escalation study, MLN8054 was given orally for 7, 14, or 21 days followed by a 14-day treatment-free period. Escalating cohorts of 3-6 patients with advanced solid tumors were treated until DLT was seen in ≥2 patients in a cohort. Serial blood samples were collected for pharmacokinetics and skin biopsies were collected for pharmacodynamics., Results: Sixty-one patients received 5, 10, 20, 30, or 40 mg once daily for 7 days; 25, 35, 45, or 55 mg/day in four divided doses (QID) for 7 days; or 55, 60, 70, or 80 mg/day plus methylphenidate or modafinil with daytime doses (QID/M) for 7-21 days. DLTs of reversible grade 3 benzodiazepine-like effects defined the estimated MTD of 60 mg QID/M for 14 days. MLN8054 was absorbed rapidly, exposure was dose proportional, and terminal half-life was 30-40 h. Three patients had stable disease for >6 cycles., Conclusions: MLN8054 dosing for up to 14 days of a 28-day cycle was feasible. Reversible somnolence was dose limiting and prevented achievement of plasma concentrations predicted necessary for target modulation. A recommended dose for investigation in phase 2 trials was not established. A second-generation Aurora A kinase inhibitor is in development.

The mitotic kinase Aurora A is an important therapeutic target for cancer therapy. This study evaluated new mechanism-based pharmacodynamic biomarkers in cancer patients in two phase I studies of MLN8054, a small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received MLN8054 orally for 7 consecutive days in escalating dose cohorts, with skin and tumor biopsies obtained before and after dosing. Skin biopsies were evaluated for increased mitotic cells within the basal epithelium. Tumor biopsies were assessed for accumulation of mitotic cells within proliferative tumor regions. Several patients in the highest dose cohorts showed marked increases in the skin mitotic index after dosing. Although some tumors exhibited increases in mitotic cells after dosing, others displayed decreases, a variable outcome consistent with dual mechanisms of mitotic arrest and mitotic slippage induced by antimitotics in tumors. To provide a clearer picture, mitotic cell chromosome alignment and spindle bipolarity, new biomarkers of Aurora A inhibition that act independently of mitotic arrest or slippage, were assessed in the tumor biopsies. Several patients, primarily in the highest dose cohorts, had marked decreases in the percentage of mitotic cells with aligned chromosomes and bipolar spindles after dosing. Evidence existed for an exposure-effect relationship for mitotic cells with defects in chromosome alignment and spindle bipolarity that indicated a biologically active dose range. Outcomes of pharmacodynamic assays from skin and tumor biopsies were concordant in several patients. Together, these new pharmacodynamic assays provide evidence for Aurora A inhibition by MLN8054 in patient skin and tumor tissues.

In this article we offer an existential theory of well-being that is guided by Heidegger's later writings on "homecoming". We approach the question of what it is about the essence of well-being that makes all kinds of well-being possible. Consistent with a phenomenological approach, well-being is both a way of being-in-the-world, as well as a felt sense of what this is like as an experience. Drawing on Heidegger's notion of Gegnet (abiding expanse), we characterise the deepest possibility of existential well-being as "dwelling-mobility". This term indicates both the "adventure" of being called into expansive existential possibilities, as well as "being-at-home-with" what has been given. This deepest possibility of well-being carries with it a feeling of rootedness and flow, peace and possibility. However, we also consider how the separate notions of existential mobility and existential dwelling as discrete emphases can be developed to describe multiple variations of well-being possibilities.

Background: Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice., Methods/design: This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change., Discussion: This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research., Trial Registration: Current Controlled Trials ISRCTN76517470.

Neurobehavioral deficits have been reported in Egyptian pesticide application teams using organophosphorus (OP) pesticides, but whether these effects are related to OP pesticide exposures has yet to be established. In preparation for a comprehensive study of the relationship between OP pesticide dose and neurobehavioral deficits, we assessed exposure within this population. We conducted occupational surveys and workplace observations, and collected air, dermal patch and biological samples from applicators, technicians and engineers involved in chlorpyrifos applications during cotton production to test the hypotheses that: (1) dermal exposure was an important contributor to internal dose and varied across body regions; and (2) substantial differences would be seen across the three job categories. Applicators were substantially younger and had shorter exposure histories than did technicians and engineers. Applicators and technicians were observed to have relatively high levels of skin or clothing contact with pesticide-treated foliage as they walked through the fields. Both dermal patch loadings of chlorpyrifos and measurements of a chlorpyrifos-specific metabolite (TCPy) in urine confirmed substantial exposure to and skin absorption of chlorpyrifos that varied according to job category; and dermal patch loading was significantly higher on the thighs than on the forearms. These findings support our hypotheses and support the need for research to examine neurobehavioral performance and exposures in this population. More importantly, the exposures reported here are sufficiently high to recommend urgent changes in work practices amongst these workers., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objectives: (i) To develop a group-based intervention for the management of multiple sclerosis (MS) fatigue incorporating energy effectiveness and cognitive behavioural approaches and (ii) to undertake a process and preliminary evaluation., Methods: Drawing upon a literature search, a local model of good practice and the views of service users and health professionals, a manualised group-based fatigue management programme was developed, designed to be delivered by health professionals. A process and preliminary outcome evaluation was undertaken. Sixteen participants attended across two iterations. Participant feedback, obtained via a focus group and evaluation questionnaires, was used to refine the programme. Outcomes were collected pre- and post-programme (including fatigue severity, quality of life, self-efficacy)., Results: Focus group feedback suggested the programme was well received, reflected in high attendance and positive ratings on evaluation questionnaires. At follow-up, despite the small sample size, there were significant improvements in perceived self-efficacy for managing fatigue., Conclusion: An evidence-based fatigue management intervention has been developed and preliminary findings look promising. In the next phase we will examine whether the programme transfers satisfactorily to other centres and collect data in preparation for a randomised controlled trial (RCT)., Practice Implications: Implications for practice will emerge when the results of our RCT are published., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

In this paper we offer an appreciation and critique of patient-led care as expressed in current policy and practice. We argue that current patient-led approaches hinder a focus on a deeper understanding of what patient-led care could be. Our critique focuses on how the consumerist/citizenship emphasis in current patient-led care obscures attention from a more fundamental challenge to conceptualise an alternative philosophically informed framework from where care can be led. We thus present an alternative interpretation of patient-led care that we call 'lifeworld-led care', and argue that such lifeworld-led care is more than the general understanding of patient-led care. Although the philosophical roots of our alternative conceptualisation are not new, we believe that it is timely to re-consider some of the implications of these perspectives within current discourses of patient-centred policies and practice. The conceptualisation of lifeworld-led care that we develop includes an articulation of three dimensions: a philosophy of the person, a view of well-being and not just illness, and a philosophy of care that is consistent with this. We conclude that the existential view of well-being that we offer is pivotal to lifeworld-led care in that it provides a direction for care and practice that is intrinsically and positively health focused in its broadest and most substantial sense.

There is abundant evidence of the benefits of breastfeeding. In the UK, supplementation in hospital has consistently been shown to be associated with shortened duration of breastfeeding. This paper reports on a subset of the data from an ethnographic study that explored the expectations, beliefs and experiences of mothers and health professionals concerning supplementation, using a variety of methods, of breastfed babies in an English maternity unit in 2002. This paper aims to describe the expectations, beliefs and experiences of mothers and health professionals concerning supplementation by nasogastric (NG) tube on the post-natal ward. Participant observation was carried out on day and night shifts and at weekends over 9 months. Mothers, midwives, neonatal nurses, health care assistants and senior paediatricians were interviewed. Categories and themes were generated. The researchers' constructs of 'the essential method', when the tube was the method needed for medical reasons, and 'the chosen method', when other methods of oral feeding should have been possible, emerged. The latter included time pressures and the avoidance of any form of oral activity that might perhaps make return to the breast more difficult. The data concerning the use of NG tubes for supplementation yielded the specific theme of parental distress. In the absence of evidence that supplementation by NG tube on the post-natal ward is associated with greater breastfeeding success than other methods, the use of the tube to avoid any form of 'oral confusion' should be discontinued. Its use primarily to save time should not be considered acceptable.

To compare the perspectives of adult childhood cancer survivors and their parents in terms of: (1) parental involvement in the survivor's healthcare, (2) thoughts and discussion about their own or their son's/daughter's childhood cancer, (3) concern about the survivor's current health status, and (4) perceived benefits of follow-up care. Forty-two adult survivors and their parents completed a semistructured audio-taped interview via the phone responding to a parallel set of questions. Thirty-eight percent of survivors reported that one of their parents attended the adult survivor clinic with them; in 41% of patient-parent dyads the parent expressed more concern than their child about the child's health status; 45% of the parents reported thinking about the cancer experience more often than their child. The results suggest that some parents continue to worry about their child's health status into adulthood, and in turn may choose to stay involved in their adult child's healthcare. Additional research is needed to understand the survivorship needs of the adult survivor and their family. Including parents in important healthcare decisions and discussions may be a consideration when caring for this unique population of patients.

The publisher regrets that this article is an accidental duplication of an article that has already been published in the International Journal of Nursing Studies, volume 45 (2008) 971-974, doi:10.1016/S0020-7489(08)00116-8. The duplicate article has therefore been withdrawn.

The unsaponifiable lipid fraction of plant-based foods is a potential source of bioactive components such as phytosterols, squalene, and tocopherols. The objective of the present study was to determine the levels of phytosterols, and squalene, as well as tocopherols (alpha and beta + gamma) in selected grains, seeds, and legumes. The method comprised acid hydrolysis and lipid extraction followed by alkaline saponification, prior to analysis by HPLC. In addition, the fatty acid profile of the foods was determined via total lipid extraction, fatty acid derivitisation and GC analysis. In general, beta-sitosterol was the most prevalent phytosterol, ranging in concentration from 24.9 mg/100 g in pumpkin seed to 191.4 mg/100 g in peas. Squalene identified in all foods examined in this study, was particularly abundant in pumpkin seed (89.0 mg/100 g). The sum of alpha- and beta+ gamma-tocopherols ranged from 0.1 mg/100 g in rye to 15.9 mg/100 g in pumpkin seeds. Total oil content ranged from 0.9% (w/w) in butter beans to 42.3% (w/w) in pumpkin seed and the type of fat, in all foods examined, was predominantly unsaturated. In conclusion, seeds, grains, and legumes are a rich natural source of phytosterols. Additionally, they contain noticeable amounts of squalene and tocopherols, and in general, their fatty acid profile is favorable.

Aurora A is a serine/threonine protein kinase essential for normal mitotic progression. Aberrant increased expression of Aurora A, which occurs frequently in human cancers, results in abnormal mitoses leading to chromosome instability and possibly tumorigenesis. Consequently, Aurora A has received considerable attention as a potential target for anticancer therapeutic intervention. Aurora A coordinates several essential mitotic activities through phosphorylation of a variety of proteins, including TACC3, which modulates microtubule stabilization of the mitotic spindle. Recent studies identified a conserved serine in Xenopus (Ser(626)) and Drosophila (Ser(863)) TACC3 orthologues that is phosphorylated by Aurora A. We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner. Furthermore, oral administration of MLN8054 to nude mice bearing HCT-116 human tumor xenografts caused a dose-dependent mislocalization of TACC3 away from spindle poles that correlated with tumor growth inhibition. As TACC3 localization to mitotic spindles depends on Aurora A-mediated phosphorylation, quantifying TACC3 mislocalization represents a novel pharmacodynamic approach for measuring Aurora A activity in cancer patients treated with inhibitors of Aurora A kinase.

In this paper, we describe the value and philosophy of lifeworld-led care. Our purpose is to give a philosophically coherent foundation for lifeworld-led care and its core value as a humanising force that moderates technological progress. We begin by indicating the timeliness of these concerns within the current context of citizen-oriented, participative approaches to healthcare. We believe that this context is in need of a deepening philosophy if it is not to succumb to the discourses of mere consumerism. We thus revisit the potential of Husserl's notion of the lifeworld and how lifeworld-led care could provide important ideas and values that are central to the humanisation of healthcare practice. This framework provides a synthesis of the main arguments of the paper and is finally expressed in a model of lifeworld-led care that includes its core value, core perspectives, relevant indicative methodologies and main benefits. The model is offered as a potentially broad-based approach for integrating many existing practices and trends. In the spirit of Husserl's interest in both commonality and variation, we highlight the central, less contestable foundations of lifeworld-led care, without constraining the possible varieties of confluent practices.

In response to US colleagues' concerns about the NHS, we undertook a comparison of mortality rates in England and Wales and the US. Figures for 1974-2000 were obtained from World Health Organization data on all-cause and cancer mortality rates. Overall rates fell in all three countries but there was a more significant drop in England and Wales over the period. This is a summary: the full paper can be accessed at nursingtimes.net.

Nuts contain bioactive constituents that elicit cardio-protective effects including phytosterols, tocopherols and squalene. The objective of the present study was to determine the total oil content, peroxide value, fatty acid composition and levels of tocopherols, squalene and phytosterols in oil extracted from freshly ground brazil, pecan, pine, pistachio and cashew nuts. The total oil content of the nuts ranged from 40.4 to 60.8% (w/w) while the peroxide values ranged from 0.14 to 0.22 mEq O2/kg oil. The most abundant monounsaturated fatty acid was oleic acid (C18:1), while linoleic acid (C18:2) was the most prevalent polyunsaturated fatty acid. The levels of total tocopherols ranged from 60.8 to 291.0 mg/g. Squalene ranged from 39.5 mg/g oil in the pine nut to 1377.8 mg/g oil in the brazil nut. beta-Sitosterol was the most prevalent phytosterol, ranging in concentration from 1325.4 to 4685.9 mg/g oil. In conclusion, the present data indicate that nuts are a good dietary source of unsaturated fatty acids, tocopherols, squalene and phytosterols.

Background: The unpredictable, variable nature of Multiple Sclerosis (MS), and the possibility of increasing disability, means that a diagnosis can have substantial psychological consequences., Objectives: To assess the effectiveness of psychological interventions for people with MS., Search Strategy: We searched 19 databases up to December 2004; Cochrane MS Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsychINFO, CINAHL and 14 others. We searched reference lists of articles, wrote to corresponding authors of the 13 papers identified by June 2004, and searched for trials in progress using 3 research registers., Selection Criteria: Randomised controlled trials of interventions described as wholly or mostly based on psychological theory and practice, in people with MS. Primary outcome measures were disease specific and general quality of life, psychiatric symptoms, psychological functioning, disability, and cognitive outcomes. Secondary outcome measures were number of relapses, pain, fatigue, health care utilisation, changes in medication, and adherence to other therapies., Data Collection and Analysis: Pertinent studies were identified from abstracts by one author. Full papers were independently compared to selection criteria by four authors. Key details were extracted from relevant papers using a standard format, and studies scored on three dimensions of quality. The review is organised into four mini-reviews (MR) dependent on the intervention's target population; people with cognitive impairments (MR1), people with moderate to severe disability (MR2), people with MS (no other criteria) (MR3), and people with depression (MR4)., Main Results: Overall 16 studies were identified and included. MR1: three trials (n=145). Some evidence of effectiveness of cognitive rehabilitation on cognitive outcomes, although this was difficult to interpret because of the large number of outcome measures used. MR2: three trials (n=80). One small trial suggesting psychotherapy may help with depression. MR3: seven studies (n=688). Some evidence that cognitive behavioural therapy may help people adjust to, and cope with, having MS (three trials). The other trials were diverse in nature and some difficult to interpret because of multiple outcome measures. MR4: three trials (n=93). Two small studies of cognitive behavioural therapy showed significant improvements in depression., Authors' Conclusions: The diversity of psychological interventions identified indicates the many ways in which they can potentially help people with MS. No definite conclusions can be made from this review. However there is reasonable evidence that cognitive behavioural approaches are beneficial in the treatment of depression, and in helping people adjust to, and cope with, having MS.

In view of the reported potential anti-inflammatory activity of the New Zealand green lipped mussel (NZGLM), we aimed to compare the effect of low dose marine oil supplementation, from mussels and fish, in reducing blood markers of inflammation. Thirty apparently healthy males and females were recruited from the general public in Melbourne, Australia to participate in a double blind, randomised, parallel intervention study. Subjects were consuming approximately 73 mg of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) daily in their background diet prior to the commencement of the intervention. Subjects were randomly assigned to consume either 2 mL/day of the NZGLM oil preparation (mixed with olive oil and dl-alpha-tocopherol) or fish oil preparation (also mixed with olive oil and dl-alpha-tocopherol) for six weeks. Two mL of the oils contained 241 mg and 181 mg of n-3 LCPUFA, respectively. Neutrophil phospholipid fatty acids, serum thromboxane B2 (TXB2), stimulated monocyte production of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNFalpha) were measured. During the intervention, the total intakes of n-3 LCPUFA from the background diet and the supplements were 199 mg/d and 173 mg/day for the NZGLM and FO groups, respectively. Following six weeks of supplementation, both groups showed a small, but significant increase in neutrophil phospholipid proportion of eicosapentaenoic acid. The NZGLM group also showed a significant increase in docosahexaenoic acid levels. There were no significant changes with time or treatment for TXB2, PGE2, IL-1 beta or TNFalpha. This study showed that low dose supplementation with n-3 LCPUFA from two different marine oil preparations showed no difference in inflammatory markers in this group of healthy individuals. Further studies are warranted including dose response trials and studies in populations with inflammatory conditions.

This article reports 1 theme from an ethnographic study that aimed to describe the experiences, expectations, and beliefs of mothers and health care professionals concerning supplementation in a UK maternity unit. Observation was conducted on the postnatal ward and the newborn infant unit, and 30 mothers, 17 midwives, 4 neonatal nurses, 3 health care assistants, 3 senior house officers, and 3 senior pediatricians gave in-depth interviews during a 9-month period in 2002. One of the major themes that emerged was the cup-versus-bottle debate. There were 3 categories strongly linked to this theme: difficulties returning to the breast, ease of use, and necessary skills and knowledge. It appears there is an urgent need to determine which is the best method of giving supplementary feeds, so that full, accurate information can be given to mothers, appropriate policies be devised, and the necessary resources and staff training be provided.

This research arose out of a collaboration between a service user (M) and two researchers. Following M's invitation to us to explore issues surrounding a carer's experience of Alzheimer's, we jointly agreed a research strategy in which we would engage in a series of interviews with M, with the aim of developing insight into how the intimate carer's complex journey can support and benefit other family caregivers faced with similar challenges. Using a broadly hermeneutic-phenomenological method, three essential themes emerged to describe the carer's journey: (i) something is wrong; (ii) the challenging shared journey: being the carer; (iii) coping through meaning-making: advocacy. We arrive at a position which considers the unique role of an intimate carer as a 'liminal' figure between the private world of an Alzheimer's sufferer and the public world of health and social care systems. The paper concludes with a consideration of how the unique role of the intimate carer as mediator could be more respectfully involved as an ongoing knowledge source for care planning and treatment decisions. Specific areas of consideration in this regard include mechanisms for such user involvement in policy making, day-to-day care delivery, and developments in the support of other carers. We hope to highlight the 'intimacy' of this position and the distinctive benefits and challenges of such intimacy in providing a crucial level of user knowledge and 'evidence' for ongoing treatment decisions. We also hope to highlight the value and power of single-case study in generating useful insights for practice.

The objective of this study was to determine the effect of type of conserved forage and concentrate composition on the quality of beef held in overwrapped (aerobic) or modified atmosphere packaging under simulated retail display for 17 d. Friesian steers (n = 45) were assigned randomly to one of five dietary treatments: 1) extensively fermented grass silage plus silage concentrate (EFS); 2) restricted fermented grass silage plus silage concentrate (RFS); 3) starch-based concentrate plus wheat straw (SC); 4) nonstarch-based concentrate plus wheat straw (NSC); or 5) zero-grazed perennial ryegrass plus grass concentrate (RYE). Meat quality was determined by measuring color, lipid oxidation (TBARS), alpha-tocopherol concentrations, and fatty acid composition. In aerobically packaged beef, there was a display x diet interactive effect (P < 0.001) on Hunter a* values, with steaks from the EFS group having higher (P < 0.05) a* values than all other dietary groups from d 6 through d 17. Moreover, during the last 12 d of display, beef from the EFS group had the lowest (P < 0.01) proportion of metmyoglobin (display day x diet; P < 0.001). Under aerobic packaging, the SC and NSC groups produced steaks with higher (P < 0.05) TBARS values than RFS, EFS, and RYE groups, which did not differ from each other (display day x diet; P < 0.01). The SC and NSC groups had higher (P < 0.05) oxidation levels than RFS, EFS, and RYE groups, which did not differ from each other. Beef from the EFS group had (P < 0.05) higher concentrations of alpha-tocopherol than from the SC, NSC, and RYE groups. Beef from EFS-fed steers had a higher (P < 0.05) proportion of saturated fatty acids than the SC and NSC groups. It was concluded that the method of grass conservation influenced beef color, whereas concentrate composition did not. Color of aerobically packaged beef was improved by feeding animals silage that had undergone extensive fermentation. Conversely, oxidative stability was decreased by feeding animals starch- and nonstarch-based concentrate diets.

Nuts are high in fat but have a fatty acid profile that may be beneficial in relation to risk of coronary heart disease. Nuts also contain other potentially cardioprotective constituents including phytosterols, tocopherols and squalene. In the present study, the total oil content, peroxide value, composition of fatty acids, tocopherols, phytosterols and squalene content were determined in the oil extracted from freshly ground walnuts, almonds, peanuts, hazelnuts and the macadamia nut. The total oil content of the nuts ranged from 37.9 to 59.2%, while the peroxide values ranged from 0.19 to 0.43 meq O2/kg oil. The main monounsaturated fatty acid was oleic acid (C18:1) with substantial levels of palmitoleic acid (C16:1) present in the macadamia nut. The main polyunsaturated fatty acids present were linoleic acid (C18:2) and linolenic acid (C18:3). alpha-Tocopherol was the most prevalent tocopherol except in walnuts. The levels of squalene detected ranged from 9.4 to 186.4 microg/g. beta-Sitosterol was the most abundant sterol, ranging in concentration from 991.2 to 2071.7 microg/g oil. Campesterol and stigmasterol were also present in significant concentrations. Our data indicate that all five nuts are a good source of monounsaturated fatty acid, tocopherols, squalene and phytosterols.

* The aim of this study was to explore and describe parents' perceptions of staff competency in a neonatal intensive care unit (NICU). The study set out to use a grounded theory approach that was modified because of a number of constraints. Eight parents whose babies met a number of inclusion criteria were interviewed using focused conversational interviews. They were then transcribed and thematically analysed. The research approach was modified as the study developed because of practical and ethical access reasons: the sampling strategy and lack of opportunity to exploit fully the constant comparative method. * Four key themes which conceptualize competency as caring emerged from the data: parents are facilitated to integrate into the unit and do not feel a burden; parents feel in control whilst in the unit; parents have a choice to opt out from observing tasks and procedures on their baby; parents and the interprofessional team communicate well and provide appropriate information. These are discussed in the context of available literature. * In conclusion, the results of the study serve to highlight how parents' perceptions of competence in a professional are not based solely on skills and tasks but on many caring behaviours. The grounded theory approach has generated a number of areas for exploration, in particular, ideas about the conceptual basis of caring in an NICU context and its links to competence. The caring behaviours involve learning to share responsibility with families. The findings suggest that when there is 'a handing over' of control to parents and a greater emphasis on parent support, they feel less like 'guests'. These ideas are supported by the available literature. A number of methodological issues are raised.

Continental Limousin and Charolais crossbred steers (n=66) were assigned to one of six diets: (1) high herbage allowance (18 kg grass dry matter), zero concentrate (HH0C), (2) high herbage allowance and 2.5 kg concentrate (HHLC), (3) high herbage allowance and 5 kg concentrate (HHHC), (4) low herbage allowance (6 kg grass DM) and 5 kg concentrate (LHHC), (5) medium herbage allowance (12 kg grass DM) and 2.5 kg concentrate (MHLC) or (6) concentrates ad-libitum+1 kg straw (CON). Colour was assessed in steaks (n=5) chosen at random from each dietary group and held in overwrapped and/or modified atmosphere packaging (MAP) (80 O(2):20 CO(2)) under simulated retail display conditions for 17 days. When the HH0C and the CON groups were compared, there was no significant difference in colour under overwrapped conditions, however under MAP, surface redness was significantly (P<0.01) higher (greatest Hunter "a" values) in the HH0C group. When the other four diets were compared to the HH0C and CON groups, there was no significant difference in colour under both forms of packaging. Lipid oxidation was highest for the dietary group CON compared to all other dietary groups examined. There was no significant difference in vitamin E levels between the six dietary groups, levels ranged from 1.7 to 2.5 μg/g meat.

The need for new innovations in nurse education is clear. Ways to help nursing students learn to reflect that can be used once qualified are being experimented with. The use of reflective practice as a learning tool for education is growing. Action learning groups (ALGs) help nurses reflect on their own personal development and the sharing of that development. Focus groups were used to examine students' perspectives on ALGs and the influence on their education. Students saw ALGs as a vital part of their course. Although the functioning of the group was dependent upon the lecturer's abilities and the dynamics of the group in general, ALGs were perceived by the majority of the students as an important component of their training. ALGs were seen as the common factor throughout the course and as the mechanism that linked theory to practice.

This article describes a floating support scheme, provided by a local housing association, which enables single vulnerable people to live independently in their own homes. The study aimed to explore the impact of the scheme from the perspectives of clients, floating support workers and representatives from health, social care and voluntary agencies. It was found that the majority of clients had long-term mental health problems and were supported by a range of professionals. Floating support was flexible in responding to individual needs. A number of themes of relevance to interprofessional working emerged from the data. These included: floating support as a community resource, links with other agencies and confidentiality, information sharing and risk management. Floating support workers worked closely with professionals from health, social care, voluntary and educational services. Although the scheme's contribution to client care was highly valued, a number of barriers to effective interagency working were evident. This study highlighted the need for discussion and presented a forum for developing an ongoing collaborative process to address the specific issues which emerged in focus group discussions.

A perceptible shift has begun, away from mass lectures towards more flexible, novel and adaptable methods of teaching and learning. A variety of terms (open, distance, flexible) have been used to describe such instructional methods, a key characteristic of which is that they do not require constant and/or synchronous contact between teacher and learner. This paper explores students' views of a distributed learning initiative within a University in the South of England. The initiatives were in response to increase in the number of students in each intake which was just one of the recent changes called for by the Government. This evaluation consisted of a longitudinal research project following two cohorts of nursing students (n=288) through the first two years of their education (and will continue in the final year). The study assessed the perceived influence of distributed learning (DL) on their academic education and professional training as well as their satisfaction with the workbooks. The evaluation used a mixture of qualitative and quantitative data collection, questionnaires and focus groups. DL was seen as a flexible way of studying for students. Students were able to study a topic area at their own pace and at a time convenient to them. The activities in the workbook stimulated discussions and triggered ideas and thoughts for both students and lecturers. With the commencement of the workbooks lecturers were given the opportunity to reflect on their teaching styles and were encouraged to utilise a number of different teaching and learning methodologies.

In the United Kingdom the election of the 1997-2001 Labour government led to rapid development of drug treatment interventions in the criminal justice sector. One type of drug treatment intervention is arrest referral and this is the most developed and researched form of intervention within the United Kingdom (Arrest referral: emerging lessons from research, paper 23. London: Home Office; 1998). However, much of the published literature reports upon evaluations of working styles and practices of individual arrest referral schemes (ARS). This paper reports a follow-up study on the impact that intervention by an ARS had upon a group of drug-misusing arrestees, 18 months after their initial contact with the ARS. The findings from the follow-up study demonstrate that the intervention had had a positive impact on both drug misuse and offending among the sample. Sixty-four per cent had entered treatment and remained 'clean' following an intervention by the ARS. Analysis of the police national computer records for the sample demonstrated that 88% of those who remained 'clean' also ceased criminal activity. Additionally, the study highlighted other factors relevant to the treatment of drug misusers. Most of the sample had been in contact with health professionals during their misusing careers but the perceived negative attitude on the part of health professionals towards drug misusers and the lack of proactive, health-led interventions indicated that mainstream health care provision had failed this sample of problematic drug misusers. Another key factor to emerge from the study was the relevance of aftercare to the recovery process, which was needed to offer wide-ranging support to drug misusers in recovery, such as help with accommodation, learning basic life skills and constructing a new lifestyle without drugs. The study therefore has a dual outcome in demonstrating the positive impact of the ARS and in turn the rationale for the Government's 10-year anti-drugs strategy but it also highlights the weakness as aftercare is not a prominent feature of the strategy (Tackling drugs to build a better Britain, the government's ten year strategy for tackling drugs. London: The Stationery Office; 1998).

The effects of three preslaughter diets on heifer beef quality were investigated. Heifers (n = 45) were divided into three groups and fed for ad libitum consumption either maize silage, grass silage, or a 50:50 mixture of maize silage and grass silage. Meat quality was determined by measuring color, lipid oxidation, alpha-tocopherol levels, and fatty acid composition. Beef from the maize silage group had poorest color stability (P < 0.05), whereas beef from the grass silage diet had best (P < 0.05) color stability. The visual panel least preferred the maize silage group after 2 or more days of display, and lipid oxidation was significantly (P < 0.001) higher in this group compared to the 50:50 maize:grass silage and grass silage groups. There was a significant (P < 0.001) difference in the alpha-tocopherol levels detected in the meat from the three dietary groups. Alpha-tocopherol levels increased in the order: maize silage < 50:50 maize:grass silage < grass silage, at levels of 2.08, 2.95, and 3.84 microg/g meat, respectively. Fatty acid analysis indicated 18:3 was significantly (P < 0.001) lower in the maize silage-fed group than in the maize:grass silage and grass silage groups. However, 18:3 was significantly (P < 0.001) higher in the grass silage group than in the other two groups. There were no significant differences in all other fatty acids among the three dietary groups. It was concluded that beef from grass silage-fed animals had better overall quality in terms of color, lipid oxidation, and alpha-tocopherol levels than beef from maize silage fed animals.

This paper describes an action research study in a community setting. A group of residents from a local housing estate and a number of local workers used participative methods to explore local child care issues with the aim of developing initiatives for improved child care. The paper describes the study processes and reflects on lessons learnt. A discussion of implications for interprofessional working concludes the paper and includes emphasis of the need to focus on shared objectives, and develop appropriate organizational structures and educational provision.

The use of complementary therapies is fast growing in the UK, but their place within health care is still unclear. This study explored the views of families using a specific complementary therapy in the care of their brain-injured children, and of professionals involved in the care of the children. The findings revealed an interesting comparison of views about the use of complementary therapies and attitudes towards their use.

This study evaluated the impact of a nurse-led health education programme on the behaviour, nicotine dependence and nicotine withdrawal in patients who smoke and suffer from peripheral vascular disease, based in a large teaching hospital in the north of England. Smoking behaviour was measured by self report, end-expired carbon monoxide and urinary cotinine. Nicotine dependence and withdrawal were measured using a nicotine dependence scale and a nicotine withdrawal scale. The findings demonstrated that the programme did have some impact on behaviour. The study raised issues concerning the measurement of physiological markers for smoking as nursing outcomes. Issues about the measurement of nicotine dependence and withdrawal are highlighted.

This study explores the issues of working and training together for nurses and operating department assistants and practitioners (ODAs/ODPs), based on experiences in an operating department. Interviews and focus groups with nurses, ODAs/ODPs and medical staff were the means of collecting data.

A number of Citizens Advice Bureaux (CAB) have entered into partnerships with Health Authorities in order to provide advice in general practice surgeries as part of the health care services offered by the primary health care team. This illuminative evaluation has involved an exploration of the impacts of the service from the perspective of its users, the CAB advisers and the referral agents. Data was collected from questionnaires, individual interviews and focus group interviews from participants in both a rural and urban setting. The findings of the study suggest that locating CAB advisers in GP surgeries facilitates access for people who would otherwise be effectively excluded by reason of age, poor health, poverty or lack of transport. Overall, consultations with the CAB advisers were perceived very positively. This study would suggest that Citizens Advice Bureaux in GP surgeries are a viable and useful adjunct to primary health care teams in terms of information-giving, social support, up-take of benefits and co-ordination of services.

The effect of dietary vitamin E supplementation on cholesterol oxidation in vacuum packaged, cooked, refrigerated and frozen beef steaks, was investigated. Steers (Friesian×Charolais×Black Hereford) were fed diets providing 20 or 3000 mg α-tocopheryl acetate/head/day for 135 days prior to slaughter. α-Tocopherol concentrations in M. psoas major (PM) and M. longissimus dorsi (LD) were significantly (p<0.05) increased by supplementation and were significantly (p<0.05) higher in PM than LD. Cholesterol oxidation (monitored by measuring 7-ketocholesterol formation) increased during refrigerated and frozen storage in some, but not all, groups, and tended to be higher in PM than LD. Dietary vitamin E did not affect 7-ketocholesterol formation in LD, but significantly (p<0.05) reduced concentrations in PM during refrigerated and frozen storage. Supplementation significantly (p<0.05) reduced TBARS in PM and LD, indicating that vitamin E improved oxidative stability in both muscles. The results show that dietary vitamin E supplementation inhibits cholesterol oxidation in vacuum packaged, cooked beef during refrigerated and frozen storage, but may be influenced by muscle type.

The 1999/2000 winter demands on the NHS have once again highlighted deficits in UK critical care provision (Daily Telegraph, 2000; London Evening Standard, 2000) Recent years have seen the development of the role of health care support workers in the NHS; some critical care units now employ health care support workers This research examined the views of critical care unit staff on the introduction of health care support workers into the critical care unit It is concluded that the role is viable within the setting of this study A framework is outlined that could form the basis for a critical care health care support worker training programme

Primary care is developing rapidly with significant impacts on the nursing team. Such changes have brought inter-professional team-working into sharper focus, particularly community care and collaborative working. This paper: examines the nursing roles within a general practice; describes the perspectives of service users; identifies areas of change; clarifies core and specialist skills; defines new roles among the primary health care nursing team; proposes a new model of working; and identifies appropriate education. The project was set in a general practice in south-west England and used an action research methodology. The objectives were to create a change in practice and to develop and refine existing theory to underpin nursing roles. Throughout the research regular team meetings allowed reflection and discussion about research findings and progress. Data were collected from multiple sources, including team workshops, patient focus group interviews, and individual interviews with GPs, practice managers and area managers. Reflective diaries and a patient survey were also used. The analysis of the quantitative and qualitative data collected from patients formed a basis for practice development and facilitated the team's reflection on the areas of change. Overall high satisfaction with services and care was expressed in the patient interviews and the questionnaire. The themes from the data highlighted areas important for patients and helped in shaping the new roles and responsibilities for team members. Regarding the team perspective, the data indicated many areas that could be considered for development. The community nursing team decided to concentrate on three key areas: child health, leg ulcer management, and cardiovascular health. The research concludes that action research presents some problems and challenges but is a useful approach to developing team-working in primary health care.