Packed red blood cells suppress myeloid dendritic cell and monocyte inflammatory responses in a whole blood model of transfusion

Purpose/Objective: The basis for poor outcomes in some patients post transfusion remains largely unknown. Despite leukodepletion, there is still evidence of immunomodulatory effects of transfusion that require further study. In addition, there is evidence that the age of blood components transfused significantly affects patient outcomes. Myeloid dendritic cell (DC) and monocyte immune function were studied utilising an in vitro whole blood model of transfusion. Materials and methods: Freshly collected (‘recipient’) whole blood was cultured with ABO compatible leukodepleted PRBC at 25% blood replacement-volume (6hrs). PRBC were assayed at [Day (D) 2, 14, 28and 42 (date-of expiry)]. In parallel, LPS or Zymosan (Zy) were added to mimic infection. Recipients were maintained for the duration of the time course (2 recipients, 4 PRBC units, n = 8).Recipient DC and monocyte intracellular cytokines and chemokines (IL-6, IL-10, IL-12,TNF-a, IL-1a, IL-8, IP-10, MIP-1a, MIP-1b, MCP-1) were measured using flow cytometry. Changes in immune response were calculated by comparison to a parallel no transfusion control (Wilcoxin matched pairs). Influence of storage age was calculated using ANOVA. Results: Significant suppression of DC and monocyte inflammatory responses were evident. DC and monocyte production of IL-1a was reduced following exposure to PRBC regardless of storage age (P < 0.05 at all time points). Storage independent PRBC mediated suppression of DC and monocyte IL-1a was also evident in cultures costimulated with Zy. In cultures co-stimulated with either LPS or Zy, significant suppression of DC and monocyte TNF-a and IL-6 was also evident. PRBC storage attenuated monocyte TNF-a production when co-cultured with LPS (P < 0.01 ANOVA). DC and monocyte production of MIP-1a was significantly reduced following exposure to PRBC (DC: P < 0.05 at D2, 28, 42; Monocyte P < 0.05 all time points). In cultures co-stimulated with LPS and zymosan, a similar suppression of MIP-1a production was also evident, and production of both DC and monocyte MIP-1b and IP-10 were also significantly reduced. Conclusions: The complexity of the transfusion context was reflected in the whole blood approach utilised. Significant suppression of these key DC and monocyte immune responses may contribute to patient outcomes, such as increased risk of infection and longer hospital stay, following blood transfusion.

End-of-life care in the critical care setting : nurses' practices and factors affecting these practices

Background: Critical care units are designed and resourced to save lives, yet the provision of end-of-life care is a significant component of nursing work in these settings. Limited research has investigated the actual practices of critical care nurses in the provision of end-of-life care, or the factors influencing these practices. To improve the care that patients at the end of life and their families receive, and to support nurses in the provision of this care, further research is needed. The purpose of this study was to identify critical care nurses' end-of-life care practices, the factors influencing the provision of end-of-life care and the factors associated with specific end-of-life care practices. Methods: A three-phase exploratory sequential mixed-methods design was utilised. Phase one used a qualitative approach involving interviews with a convenience sample of five intensive care nurses to identify their end-of-life care experiences and practices. In phase two, an online survey instrument was developed, based on a review of the literature and the findings of phase one. The survey instrument was reviewed by six content experts and pilot tested with a convenience sample of 28 critical care nurses (response rate 45%) enrolled in a postgraduate critical care nursing subject. The refined survey instrument was used in phase three of this study to conduct a national survey of critical care nurses. Descriptive analyses, exploratory factor analysis and univariate general linear modelling was undertaken on completed survey responses from 392 critical care nurses (response rate 25%). Results: Six end-of-life care practice areas were identified in this study: information sharing, environmental modification, emotional support, patient and family-centred decision making, symptom management and spiritual support. The items most frequently identified as always undertaken by critical care nurses in the provision of end-of-life care were from the information sharing and environmental modification practice areas. Items least frequently identified as always undertaken included items from the emotional support practice area. Eight factors influencing the provision of end-of-life care were identified: palliative values, patient and family preferences, knowledge, preparedness, organisational culture, resources, care planning, and emotional support for nurses. Strong agreement was noted with items reflecting values consistent with a palliative approach and inclusion of patient and family preferences. Variation was noted in agreement for items regarding opportunities for knowledge acquisition in the workplace and formal education, yet most respondents agreed that they felt adequately prepared. A context of nurse-led practice was identified, with variation in access to resources noted. Collegial support networks were identified as a source of emotional support for critical care nurses. Critical care nurses reporting values consistent with a palliative approach and/or those who scored higher on support for patient and family preferences were more likely to be engaged in end-of-life care practice areas identified in this study. Nurses who reported higher levels of preparedness and access to opportunities for knowledge acquisition were more likely to report engaging in interpersonal practices that supported patient and family centred decision making and emotional support of patients and their families. A negative relationship was identified between the explanatory variables of emotional support for nurses and death anxiety, and the patient and family centred decision making practice area. Contextual factors had a limited influence as explanatory variables of specific end-of-life care practice areas. Gender was identified as a significant explanatory variable in the emotional and spiritual support practice areas, with male gender associated with lower summated scores on these practice scales. Conclusions: Critical care nurses engage in practices to share control with and support inclusion of families experiencing death and dying. The most frequently identified end-of-life care practices were those that are easily implemented, practical strategies aimed at supporting the patient at the end of life and the patient's family. These practices arguably require less emotional engagement by the nurse. Critical care nurses' responses reflected values consistent with a palliative approach and a strong commitment to the inclusion of families in end-of-life care, and these factors were associated with engagement in all end-of-life care practice areas. Perceived preparedness or confidence with the provision of end-of-life care was associated with engagement in interpersonal caring practices. Critical care nurses autonomously engage in the provision of end-of-life care within the constraints of an environment designed for curative care and rely on their colleagues for emotional support. Critical care nurses must be adequately prepared and supported to provide comprehensive care in all areas of end-of-life care practice. The findings of this study raise important implications, and informed recommendations for practice, education and further research.

Estimating the Burden of Malignant Neoplasm in Shandong Province [山东省恶性肿瘤疾病负担研究]

Objective To make a comprehensive estimation of the burden of malignant neoplasm in Shandong province by the means of disability- adjusted life year (DALY) for the first time. Methods DALYs were calculated following the procedures developed for the Global Burden of Disease (GBD) study to ensure comparability. We measured YLLs using the cancer mortality data of 19 Disease Surveillance Points (DSPs) in Shandong Province during 2000 and 2005. YLDs were estimated based on the cancer morbidity data of 6 Cancer Incidence Surveillance Points in Shandong Province in 2005. Results All cancers were responsible for 20.60 DALYs for every thousand population in Shandong Province (25.30 for men and 15.74 for women) . 94.3% of the losses were due to premature death and 5.7% to disability. 31.9% of the DALYs happened among 45~59 age group. The top 10 cancers for DALYs were lung cancer, liver cancer, stomach cancer, oesophagus cancer, colon/rectum cancer, breast cancer, leukemia, brain cancer, pancreas cancer and cervix uteri cancer in turn. The burden of major cancers such as lung cancer and liver cancer in Shandong were heavier than the global and national level. Conclusions he burden of disease of malignant neoplasm is mainly because of premature death. Lung cancer, liver cancer, stomach cancer and oesophagus cancer are the major cancers in Shandong Province and should be paid more attention to their prevention and control. Abstract in Chinese 目的 首次应用伤残调整寿命年(DALY)对山东省居民恶性肿瘤疾病负担进行综合评价. 方法 以2000-2005年山东省疾病监测系统的恶性肿瘤死亡资料和2005年山东省恶性肿瘤发病监测系统的发病资料为基础,利用世界卫生组织提供的专门公式,计算恶性肿瘤的YLLs、YLDs和DALYs,以此评价恶性肿瘤的疾病负担. 结果 山东省每千人每年因恶性肿瘤造成20.60个DALYs损失(男性25.30,女性15.74),其中,9413%为早死所致,5.7%因残疾所致:恶性肿瘤主要导致45～59岁人群的DALYs损失,占31.93%;恶性肿瘤疾病负担前10位依次为肺癌、肝癌、胃癌、食道癌、肠癌、乳腺癌、白血病、脑癌、胰腺癌和宫颈癌;山东省肺癌、肝癌等主要癌症疾病负担高于全球和全国水平. 结论 恶性肿瘤疾病负担主要由早死所致,肺癌、肝癌、胃癌和食道癌等主要癌症的防制地位十分突出.

A process-oriented approach to supporting Off-site Manufacture in construction projects

It is well-known that the use of off-site manufacture (OSM) techniques can assist in timely completion of a construction project though the utilisation of such techniques may have other disadvantages. Currently, OSM uptake within the Australian construction industry is limited. To successfully incorporate OSM practices within a construction project, it is crucial to understand the impact of OSM adoption on the processes used during a construction project. This paper presents how a systematic process-oriented approach may be able to support OSM utilisation within a construction project. Process modelling, analysis and automation techniques which are well-known within the Business Process Management (BPM) discipline have been applied to develop a collection of construction process models that represent the end-to-end generic construction value chain. The construction value chain enables researchers to identify key activities, resources, data, and stakeholders involved in construction processes in each defined construction phase. The collection of construction process models is then used as a basis for identification of potential OSM intervention points in collaboration with domain experts from the Australian construction industry. This ensures that the resulting changes reflect the needs of various stakeholders within the construction industry and have relevance in practice. Based on the input from the domain experts, these process models are further refined and operational requirements are taken into account to develop a prototype process automation (workflow) system that can support and coordinate OSM-related process activities. The resulting workflow system also has the potential to integrate with other IT solutions used within the construction industry (e.g., BIM, Acconex). As such, the paper illustrates the role that process-oriented thinking can play in assisting OSM adoption within the industry.

Rapid quantification of free cholesterol in tears using direct insertion/electron ionization-Mass spectrometry

Purpose. To establish a simple and rapid analytical method, based on direct insertion/electron ionization-mass spectrometry (DI/EI-MS), for measuring free cholesterol in tears from humans and rabbits. Methods. A stable-isotope dilution protocol employing DI/EI-MS in selected ion monitoring mode was developed and validated. It was used to quantify the free cholesterol content in human and rabbit tear extracts. Tears were collected from adult humans (n = 15) and rabbits (n = 10) and lipids extracted. Results. Screening, full-scan (m/z 40-600) DI/EI-MS analysis of crude tear extracts showed that diagnostic ions located in the mass range m/z 350 to 400 were those derived from free cholesterol, with no contribution from cholesterol esters. DI/EI-MS data acquired using selected ion monitoring (SIM) were analyzed for the abundance ratios of diagnostic ions with their stable isotope-labeled analogues arising from the D6-cholesterol internal standard. Standard curves of good linearity were produced and an on-probe limit of detection of 3 ng (at 3:1 signal to noise) and limit of quantification of 8 ng (at 10:1 signal to noise). The concentration of free cholesterol in human tears was 15 ± 6 μg/g, which was higher than in rabbit tears (10 ± 5 μg/g). Conclusions. A stable-isotope dilution DI/EI-SIM method for free cholesterol quantification without prior chromatographic separation was established. Using this method demonstrated that humans have higher free cholesterol levels in their tears than rabbits. This is in agreement with previous reports. This paper provides a rapid and reliable method to measure free cholesterol in small-volume clinical samples. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

The 10 Australian ecosystems most vulnerable to tipping points

We identify the 10 major terrestrial and marine ecosystems in Australia most vulnerable to tipping points, in which modest environmental changes can cause disproportionately large changes in ecosystem properties. To accomplish this we independently surveyed the coauthors of this paper to produce a list of candidate ecosystems, and then refined this list during a 2-day workshop. The list includes (1) elevationally restricted mountain ecosystems, (2) tropical savannas, (3) coastal floodplains and wetlands, (4) coral reefs, (5) drier rainforests, (6) wetlands and floodplains in the Murray-Darling Basin, (7) the Mediterranean ecosystems of southwestern Australia, (8) offshore islands, (9) temperate eucalypt forests, and (10) salt marshes and mangroves. Some of these ecosystems are vulnerable to widespread phase-changes that could fundamentally alter ecosystem properties such as habitat structure, species composition, fire regimes, or carbon storage. Others appear susceptible to major changes across only part of their geographic range, whereas yet others are susceptible to a large-scale decline of key biotic components, such as small mammals or stream-dwelling amphibians. For each ecosystem we consider the intrinsic features and external drivers that render it susceptible to tipping points, and identify subtypes of the ecosystem that we deem to be especially vulnerable. © 2011 Elsevier Ltd.

Electrical imaging and fluid modeling of convective fingering in a shallow water-table aquifer

Unstable density-driven flow can lead to enhanced solute transport in groundwater. Only recently has the complex fingering pattern associated with free convection been documented in field settings. Electrical resistivity (ER) tomography has been used to capture a snapshot of convective instabilities at a single point in time, but a thorough transient analysis is still lacking in the literature. We present the results of a 2 year experimental study at a shallow aquifer in the United Arab Emirates that was designed to specifically explore the transient nature of free convection. ER tomography data documented the presence of convective fingers following a significant rainfall event. We demonstrate that the complex fingering pattern had completely disappeared a year after the rainfall event. The observation is supported by an analysis of the aquifer halite budget and hydrodynamic modeling of the transient character of the fingering instabilities. Modeling results show that the transient dynamics of the gravitational instabilities (their initial development, infiltration into the underlying lower-density groundwater, and subsequent decay) are in agreement with the timing observed in the time-lapse ER measurements. All experimental observations and modeling results are consistent with the hypothesis that a dense brine that infiltrated into the aquifer from a surficial source was the cause of free convection at this site, and that the finite nature of the dense brine source and dispersive mixing led to the decay of instabilities with time. This study highlights the importance of the transience of free convection phenomena and suggests that these processes are more rapid than was previously understood.

Reliability of a wellness inventory for use among adolescent females aged 12-14 years

Background The wellness construct has application in a number of fields including education, healthcare and counseling, particularly with regard to female adolescents. The effective measurement of wellness in adolescents can assist researchers and practitioners in determining lifestyle behaviors in which they are lacking. Behavior change interventions can then be designed which directly aid in the promotion of these areas. Methods The 5-Factor Wellness Inventory (designed to measure the Indivisible Self model of wellness) is a popular instrument for measuring the broad aspects of wellness amongst adolescents. The instrument comprises 97 items contributing to 17 subscales, five dimension scores, four context scores, total wellness score, and a life satisfaction index. This investigation evaluated the test-retest (intra-rater) reliability of the 5 F-Wel instrument in repeated assessments (seven days apart) among adolescent females aged 12-14 years. Percentages of exact agreement for individual items, and the number of respondents who scored within +/-5, +/-7.5 and +/-10 points for total wellness and the five summary dimension scores were calculated. Results Overall, 46 (95.8%) participants responded with complete data and were included in the analysis. Item agreement ranged from 47.8% to 100% across the 97 items (median 69.9%, interquartile range 60.9%-73.9%). The percentage of respondents who scored within +/-5, +/-7.5 and +/-10 points for total wellness at the re-assessment was 87.0%, 97.8% and 97.8% respectively. The percentage of respondents who scored within +/-5, +/-7.5 and +/-10 for the domain scores at the reassessment ranged between 54.3-76.1%, 78.3-95.7% and 89.1-95.7% respectively across the five dimensions. Conclusions These findings suggest there was considerable variation in agreement between the two assessments on some individual items. However, the total wellness score and the five dimension summary scores remained comparatively stable between assessments.

Modeling of protein signaling networks in clinical proteomics

Molecular interactions that underlie pathophysiological states are being elucidated using techniques that profile proteomicend points in cellular systems. Within the field of cancer research, protein interaction networks play pivotal roles in the establishment and maintenance of the hallmarks of malignancy, including cell division, invasion, and migration. Multiple complementary tools enable a multifaceted view of how signal protein pathway alterations contribute to pathophysiological states.One pivotal technique is signal pathway profiling of patient tissue specimens. This microanalysis technology provides a proteomic snapshot at one point in time of cells directly procured from the native context of a tumor micro environment. To study the adaptive patterns of signal pathway events over time, before and after experimental therapy, it is necessary to obtain biopsies from patients before, during, and after therapy. A complementary approach is the profiling of cultured cell lines with and without treatment. Cultured cell models provide the opportunity to study short-term signal changes occurring over minutes to hours. Through this type of system, the effects of particular pharmacological agents may be used to test the effects of signal pathway inhibition or activation on multiple endpoints within a pathway. The complexity of the data generated has necessitated the development of mathematical models for optimal interpretation of interrelated signaling pathways. In combination,clinical proteomic biopsy profiling, tissue culture proteomic profiling, and mathematical modeling synergistically enable a deeper understanding of how protein associations lead to disease states and present new insights into the design of therapeutic regimens.

Changes in teachers’ behaviour in secondary science education : implementing a standards-referenced national curriculum

There is substantial attention worldwide to the quality of secondary school teaching in STEM in Education. This paper reports on the use of Outcome Mapping (OM) as an approach to guide and monitor change in teacher practice and a visual tool, shaped as a Star, to benchmark and monitor this behaviour. OM and the visual tool were employed to guide and document three secondary teachers’ behaviour as they planned, implemented and assessed a science unit in the new Australian standards-referenced curriculum. Five key outcome markers in the teachers’ behaviour were identified together with progress markers — cumulative qualitative indicators — leading to these outcomes. The use of a Star to benchmark and track teachers’ behaviours was particularly useful because it showed teacher behaviour on multiple dimensions simultaneously at various points in time. It also highlighted priorities in need of further attention and provided a pathway to achievement. Hence, OM and the Star representation provide both theoretical and pragmatic approaches to enhancing quality in STEM teaching.

The Habitual Rhythms of Becoming-Involved: Insights into Participation Experiences in Urban Spaces by Children with Diverse Mobility

This chapter reports on a study that reveals the essence of participation in urban spaces by ten children who live with various physical conditions: Muscular Dystrophy, Cerebral Palsy, and Autoimmune Rheumatic Diseases. These conditions affect muscle and movement differently resulting in diverse ways in which children move through space (personal mobility). The children at the time of the research were 9-12 years of age residing in South-east Queensland, Australia. The approach and methods selected for this study, interpretive phenomenological inquiry and grounded theory, were chosen for their capacity to capture the complexity and multiple interactions of the child’s urban living. The confronting and poignant accounts by children and their families of their experiences produced a new way of understanding the concept of participation, as a ‘journey of becoming involved.’ Their accounts of performing everyday routines (e.g. leaving home, getting in and out of the car, and entering places) in urban spaces (neighbourhood streets, schools, open spaces, shopping centres, and hospitals) revealed differences in the way settings were experienced. These differences were associated with the interplay between the body, space and context. Where interplays were problematic, explicit decisions about children’s involvement were made. These decisions were described in terms of ‘avoid going’, ‘pick and choose’, ‘discontinue’, ‘accept’, or ‘contest.’ What these decisions mean is some spaces are avoided, some journeys are discontinued, and some barriers encountered in journeys are normalised as everyday experiences, i.e. ‘tolerable discrimination’. These actions resulted in experiences of non-participation or partial–tokenistic participation. The key substantive contribution of the research lies in the identification of points in children’s journeys that shape participation experience. These points identify where future interventions in policy, programming and design can be made to make real and sustaining changes to lives of children and their families in geographies crucial to urban living.

Triumphs and tribulations in the psychotherapy of schizophrenia : reflections on a pilot study of metacognitive narrative psychotherapy

Schizophrenia results in a profound disruption of one’s capacity to make sense of mental states, coherently narrate self-experiences, and meaningfully relate to others. While current treatment options for people with schizophrenia tend to be symptom-focused, experience in designing and implementing a study focusing on enhancing sense of self demonstrates the feasibility of developing and implementing models of treatment that prioritize the subjective distress and self-experience of people with schizophrenia. There is emerging research evidence, based upon dialogical theory of self, that posits the potential of people with deficits of self to engage in meaningful therapeutic relationships and work toward greater integrity of self and degrees of recovery. The challenge is to translate these ideas into a research methodology that can be successfully applied within therapeutic contexts with people who meet the diagnostic criteria for schizophrenia. Based upon dialogical theory, we developed a principle-based manual for metacognitive narrative psychotherapy: a psychological approach to the treatment of people with schizophrenia, which aims to enhance metacognitive capacity and ability to narrate self-experiences. Five phases of treatment were identified: (1) developing a therapeutic relationship, (2) eliciting narratives, (3) enhancing metacognitive capacity, (4) enriching narratives, and (5) living enriched stories. Proscribed practices were also identified. We then implemented the manual within a university clinic context. Six therapists were trained to implement the model and, in turn, provided therapy to 11 patients who completed 12 to 24 months of treatment. Participants were assessed on metacognitive capacity, narrative coherence, narrative richness, self-reported recovery, and symptomatology at three points in time over the course of therapy. Contrary to expectations, participants were highly engaged in the therapeutic process, with minimal dropout. Overall, over 75% of participants evidenced improvement in their level of recovery over the course of therapy. The manualization and outcome findings demonstrate the feasibility of applying such interventions to a broader clinical population.

Corporatizing the 'intellectual machinery' of government : the case of educational policy in Australia

This article analyses what it describes as the corporatization of the ‘intellectual machinery’ of government: the theories, knowledges, research and ‘know how’ utilized by political authorities to render the world thinkable, programmable and subject to intervention. Through an analysis of two key nodal points in national policy on teacher professional standards in Australia over the last decade, the article discloses a shift in the relation between expertise and politics. This is manifested, it is argued, in an increased reliance by policy authorities on corporatized forms of research produced by national and international private consulting firms, Think Tanks, and ‘policy entrepreneurs’ and a concomitant decrease in their reliance on free research produced largely by academics in institutions of higher education. The article seeks to account for this shift in terms of the ‘advanced liberal’ formula for rule which now characterizes government in contemporary Western polities.

Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.

In search of Nirvana : why Nirvana : the True Story could never be "true"

In my book Nirvana: The True Story (2006), I undertake an autoethnographical approach to biography, attempting to impart an understanding of my chosen subject - the rock band Nirvana - via discussion of my own experiences. On numerous occasions, I veer off into tangential asides, frequently using extensive footnotes to explain obscure musical references. Personal anecdotes are juxtaposed with "insider" information; at crucial points in the story (notable concerts, the first meeting of singer Kurt Cobain with his future wife Courtney Love, the news of Cobain's suicide), the linear thread of the narrative spills over into a multi-faceted approach, with several different (and sometimes opposing) voices given equal prominence. Despite my firsthand experience of the band, however, Nirvana: The True Story is not considered authoritative, even within its own field. This article considers the reasons why this may be the case.In my book Nirvana: The True Story (2006), I undertake an autoethnographical approach to biography, attempting to impart an understanding of my chosen subject - the rock band Nirvana - via discussion of my own experiences. On numerous occasions, I veer off into tangential asides, frequently using extensive footnotes to explain obscure musical references. Personal anecdotes are juxtaposed with "insider" information; at crucial points in the story (notable concerts, the first meeting of singer Kurt Cobain with his future wife Courtney Love, the news of Cobain's suicide), the linear thread of the narrative spills over into a multi-faceted approach, with several different (and sometimes opposing) voices given equal prominence. Despite my firsthand experience of the band, however, Nirvana: The True Story is not considered authoritative, even within its own field. This article considers the reasons why this may be the case.