Showing papers by "University of Newcastle published in 2012"

An assessment of the use of partial least squares structural equation modeling in marketing research

Abstract: Most methodological fields undertake regular critical reflections to ensure rigorous research and publication practices, and, consequently, acceptance in their domain. Interestingly, relatively little attention has been paid to assessing the use of partial least squares structural equation modeling (PLS-SEM) in marketing research—despite its increasing popularity in recent years. To fill this gap, we conducted an extensive search in the 30 top ranked marketing journals that allowed us to identify 204 PLS-SEM applications published in a 30-year period (1981 to 2010). A critical analysis of these articles addresses, amongst others, the following key methodological issues: reasons for using PLS-SEM, data and model characteristics, outer and inner model evaluations, and reporting. We also give an overview of the interdependencies between researchers’ choices, identify potential problem areas, and discuss their implications. On the basis of our findings, we provide comprehensive guidelines to aid researchers in avoiding common pitfalls in PLS-SEM use. This study is important for researchers and practitioners, as PLS-SEM requires several critical choices that, if not made correctly, can lead to improper findings, interpretations, and conclusions.

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib

Abstract: Approximately 50% of melanomas harbor activating (V600) mutations in the serine– threonine protein kinase B-RAF (BRAF). The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions in patients with BRAF V600– mutant metastatic melanoma in a phase 1 trial and improved overall survival in a phase 3 trial. METHODS We designed a multicenter phase 2 trial of vemurafenib in patients with previously treated BRAF V600–mutant metastatic melanoma to investigate the efficacy of vem urafenib with respect to overall response rate (percentage of treated patients with a tumor response), duration of response, and overall survival. The primary end point was the overall response rate as ascertained by the independent review committee; overall survival was a secondary end point. RESULTS A total of 132 patients had a median follow-up of 12.9 months (range, 0.6 to 20.1). The confirmed overall response rate was 53% (95% confidence interval [CI], 44 to 62; 6% with a complete response and 47% with a partial response), the median duration of response was 6.7 months (95% CI, 5.6 to 8.6), and the median progression-free survival was 6.8 months (95% CI, 5.6 to 8.1). Primary progression was observed in only 14% of patients. Some patients had a response after receiving vemurafenib for more than 6 months. The median overall survival was 15.9 months (95% CI, 11.6 to 18.3). The most common adverse events were grade 1 or 2 arthralgia, rash, photosensitivity, fatigue, and alopecia. Cutaneous squamous-cell carcinomas (the majority, keratoacanthoma type) were diagnosed in 26% of patients. CONCLUSIONS Vemurafenib induces clinical responses in more than half of patients with previously treated BRAF V600–mutant metastatic melanoma. In this study with a long follow-up, the median overall survival was approximately 16 months. (Funded by Hoffmann–La Roche; ClinicalTrials.gov number, NCT00949702.)

A critical look at the use of PLS-SEM in MIS Quarterly

Abstract: Wold’s (1974; 1982) partial least squares structural equation modeling (PLS-SEM) ap-proach and the advanced PLS-SEM algorithms by Lohmoller (Lohmoller 1989) have enjoyed steady popularity as a key multivariate analysis methods in management infor-mation systems (MIS) research (Gefen et al. 2011). Chin’s (1998b) scholarly work and technology acceptance model (TAM) applications (e.g., Gefen and Straub 1997) are milestones that helped to reify PLS-SEM in MIS research. In light of the proliferation of SEM techniques, Gefen et al. (2011), updating Gefen et al. (2000), presented a compre-hensive, organized, and contemporary summary of the minimum reporting requirements for SEM applications. Such guidelines are of crucial importance for advancing research for several reasons. First, researchers wishing to apply findings from prior studies or wanting to contribute to original research must comprehend other researchers’ decisions in order to under-stand the robustness of their findings. Likewise, when studies arrive at significantly different results, the natural course is to attempt explaining the differences in terms of the theory or concept employed, the empirical data used, and how the research method was applied. A lack of clarity on these issues, including the methodological applications, contradicts the goals of such studies (Jackson et al. 2009). Even worse, the misapplication of a technique may result in misinterpretations of empirical outcomes and, hence, false conclusions. Against this background, rigorous research has a long-standing tradition of critically reviewing prior practices of reporting standards and research method use (e.g., Boudreau et al. 2001). While the use of covariance-based SEM (CB-SEM) techniques has been well documented across disciplines (e.g., Medsker et al. 1994; Shook et al. 2004; Steenkamp and Baumgartner 2000), few reviews to date have investigated usage practices specific to PLS-SEM (see, however, Gefen et al. 2000). Previous reviews of such research practices were restricted to strategic management (Hulland 1999) and, more recently, marketing (Hair et al. 2012; Henseler et al. 2009), and accounting (Lee et al. 2011). The question arises as to how authors publishing in top IS journals such as MIS Quarterly have used PLS-SEM thus far, given the SEM recommendations of Gefen et al. (2011). By relating Gefen et al.’s (2011) reporting guidelines to actual practice, we attempt to identify potential problematic areas in PLS-SEM use, problems which may explain some of the criticism of how it has been applied (e.g., Marcoulides et al. 2009; Marcoulides and Saunders 2006). By reviewing previous PLS-SEM research in MIS Quarterly, we can hopefully increase awareness of established reporting standards. The results allow researchers to further improve the already good reporting practices that have been established in MIS Quarterly and other top journals and thus could become blueprints for conducting PLS-SEM analysis in other disciplines such as strategic management and marketing.

Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

Abstract: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

Guidelines for choosing between multi-item and single-item scales for construct measurement: a predictive validity perspective

Abstract: Establishing predictive validity of measures is a major concern in marketing research. This paper investigates the conditions favoring the use of single items versus multi-item scales in terms of predictive validity. A series of complementary studies reveals that the predictive validity of single items varies considerably across different (concrete) constructs and stimuli objects. In an attempt to explain the observed instability, a comprehensive simulation study is conducted aimed at identifying the influence of different factors on the predictive validity of single versus multi-item measures. These include the average inter-item correlations in the predictor and criterion constructs, the number of items measuring these constructs, as well as the correlation patterns of multiple and single items between the predictor and criterion constructs. The simulation results show that, under most conditions typically encountered in practical applications, multi-item scales clearly outperform single items in terms of predictive validity. Only under very specific conditions do single items perform equally well as multi-item scales. Therefore, the use of single-item measures in empirical research should be approached with caution, and the use of such measures should be limited to special circumstances.

Condition-Dependent Transcriptome Reveals High-Level Regulatory Architecture in Bacillus subtilis

Abstract: Bacteria adapt to environmental stimuli by adjusting their transcriptomes in a complex manner, the full potential of which has yet to be established for any individual bacterial species. Here, we report the transcriptomes of Bacillus subtilis exposed to a wide range of environmental and nutritional conditions that the organism might encounter in nature. We comprehensively mapped transcription units (TUs) and grouped 2935 promoters into regulons controlled by various RNA polymerase sigma factors, accounting for ~66% of the observed variance in transcriptional activity. This global classification of promoters and detailed description of TUs revealed that a large proportion of the detected antisense RNAs arose from potentially spurious transcription initiation by alternative sigma factors and from imperfect control of transcription termination.

Akt-Mediated Regulation of Autophagy and Tumorigenesis Through Beclin 1 Phosphorylation

Abstract: Aberrant signaling through the class I phosphatidylinositol 3-kinase (PI3K)-Akt axis is frequent in human cancer. Here, we show that Beclin 1, an essential autophagy and tumor suppressor protein, is a target of the protein kinase Akt. Expression of a Beclin 1 mutant resistant to Akt-mediated phosphorylation increased autophagy, reduced anchorage-independent growth, and inhibited Akt-driven tumorigenesis. Akt-mediated phosphorylation of Beclin 1 enhanced its interactions with 14-3-3 and vimentin intermediate filament proteins, and vimentin depletion increased autophagy and inhibited Akt-driven transformation. Thus, Akt-mediated phosphorylation of Beclin 1 functions in autophagy inhibition, oncogenesis, and the formation of an autophagy-inhibitory Beclin 1/14-3-3/vimentin intermediate filament complex. These findings have broad implications for understanding the role of Akt signaling and intermediate filament proteins in autophagy and cancer.

A randomized trial of tenecteplase versus alteplase for acute ischemic stroke.

Abstract: BackgroundIntravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, is an alternative thrombolytic agent. MethodsIn this phase 2B trial, we randomly assigned 75 patients to receive alteplase (0.9 mg per kilogram of body weight) or tenecteplase (0.1 mg per kilogram or 0.25 mg per kilogram) less than 6 hours after the onset of ischemic stroke. To favor the selection of patients most likely to benefit from thrombolytic therapy, the eligibility criteria were a perfusion lesion at least 20% greater than the infarct core on computed tomographic (CT) perfusion imaging at baseline and an associated vessel occlusion on CT angiography. The coprimary end points were the proportion of the perfusion lesion that was reperfused at 24 hours on perfusion-weighted magnetic resonance imaging and the extent of clinical improvement at 24 hours as assessed on the National Institutes of Health Stroke Scale (NIHSS, a 42-point scale ...

Abiotic drivers and plant traits explain landscape-scale patterns in soil microbial communities

Abstract: The controls on aboveground community composition and diversity have been extensively studied, but our understanding of the drivers of belowground microbial communities is relatively lacking, despite their importance for ecosystem functioning. In this study, we fitted statistical models to explain landscape-scale variation in soil microbial community composition using data from 180 sites covering a broad range of grassland types, soil and climatic conditions in England. We found that variation in soil microbial communities was explained by abiotic factors like climate, pH and soil properties. Biotic factors, namely community-weighted means (CWM) of plant functional traits, also explained variation in soil microbial communities. In particular, more bacterial-dominated microbial communities were associated with exploitative plant traits versus fungal-dominated communities with resource-conservative traits, showing that plant functional traits and soil microbial communities are closely related at the landscape scale.

The Contact Caveat Negative Contact Predicts Increased Prejudice More Than Positive Contact Predicts Reduced Prejudice

Abstract: Contact researchers have largely overlooked the potential for negative intergroup contact to increase prejudice. In Study 1, we tested the interaction between contact quantity and valence on prejudice toward Black Australians (n = 1,476), Muslim Australians (n = 173), and asylum seekers (n = 293). In all cases, the association between contact quantity and prejudice was moderated by its valence, with negative contact emerging as a stronger and more consistent predictor than positive contact. In Study 2, White Americans (n = 441) indicated how much positive and negative contact they had with Black Americans on separate measures. Although both quantity of positive and negative contact predicted racism and avoidance, negative contact was the stronger predictor. Furthermore, negative (but not positive) contact independently predicted suspicion about Barack Obama's birthplace. These results extend the contact hypothesis by issuing an important caveat: Negative contact may be more strongly associated with increased racism and discrimination than positive contact is with its reduction.

The brain–gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study

Abstract: Objective Psychological factors are known to be associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD). No prospective studies have evaluated whether it is the brain (eg, via anxiety) that drives gut symptoms, or whether gut dysfunction precipitates the central nervous system features such as anxiety. In a 12-year longitudinal, prospective, population-based study, we aimed to determine the directionality of the brain–gut mechanism in FGIDs. Design Participants (n=1775) were a random population sample from Australia who responded to a survey on FGIDs in 1997 and agreed to be contacted for future research; 1002 completed the 12-year follow-up survey (response rate =60%), with 217, 82 and 45 people meeting Rome II for new onset FGIDs, IBS and FD, respectively. Anxiety and depression were measured using the Delusions Symptom States Inventory at baseline and follow-up. Results Among people free of a FGID at baseline, higher levels of anxiety (OR 1.11; 95% CI 1.03 to 1.19, p=0.006) but not depression at baseline was a significant independent predictor of developing new onset FGIDs 12 years later. Among people who did not have elevated levels of anxiety and depression at baseline, those with a FGID at baseline had significantly higher levels of anxiety and depression at follow-up (mean difference coefficient 0.76, p Conclusions The central nervous system and gut interact bidirectionally in FGIDs.

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies.

Abstract: Summary Background Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.

People living with psychotic illness in 2010: the second Australian national survey of psychosis.

Abstract: Objective The 2010 Survey of High Impact Psychosis (SHIP) is Australia's second national psychosis survey. This paper provides an overview of its findings, including comparisons with the first psychosis survey and general population data. Methods The survey covered 1.5 million people aged 18-64 years, approximately 10% of Australians in this age group. A two-phase design was used. In phase 1, screening for psychosis took place in public mental health services and non-government organizations supporting people with mental illness. In phase 2, 1825 of those screen-positive for psychosis were randomly selected and interviewed. Data collected included symptomatology, substance use, functioning, service utilization, medication use, education, employment, housing, and physical health including fasting blood samples. Results The estimated 1-month treated prevalence of psychotic disorders in public treatment services was 3.1 people per 1000 population; the 12-month treated prevalence was 4.5 people per 1000. The majority (63.0%) of participants met ICD-10 criteria for schizophrenia/schizoaffective disorder. One-half (49.5%) reported attempting suicide in their lifetime and two-thirds (63.2%) were rated as impaired in their ability to socialize. Over half (54.8%) had metabolic syndrome. The proportion currently smoking was 66.1%. Educational achievement was low. Only 21.5% were currently employed. Key changes in the 12 years since the first survey included: a marked drop in psychiatric inpatient admissions; a large increase in the proportion attending community mental health clinics; increased use of rehabilitation services and non-government organizations supporting people with mental illness; a major shift from typical to atypical antipsychotics; and large increases in the proportions with lifetime alcohol or drug abuse/dependence. Conclusion People with psychotic illness face multiple challenges. An integrated approach to service provision is needed to ensure that their living requirements and needs for social participation are met, in addition to their very considerable mental and physical health needs.

Invited review article: high-speed flexure-guided nanopositioning: mechanical design and control issues.

Abstract: Recent interest in high-speed scanning probe microscopy for high-throughput applications including video-rate atomic force microscopy and probe-based nanofabrication has sparked attention on the development of high-bandwidth flexure-guided nanopositioning systems (nanopositioners). Such nanopositioners are designed to move samples with sub-nanometer resolution with positioning bandwidth in the kilohertz range. State-of-the-art designs incorporate uniquely designed flexure mechanisms driven by compact and stiff piezoelectric actuators. This paper surveys key advances in mechanical design and control of dynamic effects and nonlinearities, in the context of high-speed nanopositioning. Future challenges and research topics are also discussed.

Predictability of biomass burning in response to climate changes

Abstract: Climate is an important control on biomass burning, but the sensitivity of fire to changes in temperature and moisture balance has not been quantified. We analyze sedimentary charcoal records to show that the changes in fire regime over the past 21,000 yrs are predictable from changes in regional climates. Analyses of paleo- fire data show that fire increases monotonically with changes in temperature and peaks at intermediate moisture levels, and that temperature is quantitatively the most important driver of changes in biomass burning over the past 21,000 yrs. Given that a similar relationship between climate drivers and fire emerges from analyses of the interannual variability in biomass burning shown by remote-sensing observations of month-by-month burnt area between 1996 and 2008, our results signal a serious cause for concern in the face of continuing global warming.

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Abstract: Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.

Evidence that Microglia Mediate the Neurobiological Effects of Chronic Psychological Stress on the Medial Prefrontal Cortex

Abstract: Psychological stress contributes to the development of clinical depression. This has prompted many preclinical studies to investigate the neurobiology of this relationship, however, the effects of stress on glia remain unclear. In this study, we wished to determine, first, how exposure to chronic psychological stress affects microglial activity within the prefrontal cortex (PFC) and, second, whether the observed changes were meaningfully related to corresponding changes in local neuronal activity and PFC-regulated behavior. Therefore, we examined markers of microglial activation, antigen presentation, apoptosis, and persistent neuronal activation within the PFC after exposure to repeated restraint stress. We also examined the effect of stress on spatial working memory, a PFC-dependent function. Finally, we tested the ability of a microglial activation inhibitor (minocycline) to alter the impact of chronic stress on all of these endpoints. Stressor exposure produced positively correlated increases in microglial and long-term neuronal activation in the PFC but not antigen presentation or apoptosis. As expected, it also impaired spatial working memory. Importantly, minocycline reduced the impact of stress on neuronal activation and working memory, as well as microglial activation. These results suggest a role for microglia in mediating the effects of stress on PFC neuronal function and PFC-regulated behavior.

Advanced Control Strategy of DFIG Wind Turbines for Power System Fault Ride Through

Abstract: This paper presents an advanced control strategy for the rotor and grid side converters of the doubly fed induction generator (DFIG) based wind turbine (WT) to enhance the low-voltage ride-through (LVRT) capability according to the grid connection requirement. Within the new control strategy, the rotor side controller can convert the imbalanced power into the kinetic energy of the WT by increasing its rotor speed, when a low voltage due to a grid fault occurs at, e.g., the point of common coupling (PCC). The proposed grid side control scheme introduces a compensation term reflecting the instantaneous DC-link current of the rotor side converter in order to smooth the DC-link voltage fluctuations during the grid fault. A major difference from other methods is that the proposed control strategy can absorb the additional kinetic energy during the fault conditions, and significantly reduce the oscillations in the stator and rotor currents and the DC bus voltage. The effectiveness of the proposed control strategy has been demonstrated through various simulation cases. Compared with conventional crowbar protection, the proposed control method can not only improve the LVRT capability of the DFIG WT, but also help maintaining continuous active and reactive power control of the DFIG during the grid faults.

Reactive Oxygen Species and Sperm Function—In Sickness and In Health

Abstract: The ability of spermatozoa to generate reactive oxygen species (ROS) has been appreciated since the 1940s. It is a universal property of mature spermatozoa from all mammalian species and a major contributor to the oxidative stress responsible for defective sperm function. The mechanisms by which oxidative stress limits the functional competence of mammalian spermatozoa involve the peroxidation of lipids, the induction of oxidative DNA damage, and the formation of protein adducts. ROS production in these cells involves electron leakage from the sperm mitochondria, triggered by a multitude of factors that impede electron flow along the electron transport chain. The net result of mitochondrial ROS generation is to damage these organelles and initiate an intrinsic apoptotic cascade, as a consequence of which spermatozoa lose their motility, DNA integrity, and vitality. This pathway of programmed senescence also results in the exteriorization of phosphatidylserine, which may facilitate the silent phagocytosis of these cells in the aftermath of insemination, in turn influencing the female tract immune response to sperm antigens and future fertility. Despite the vulnerability of sperm to oxidative stress, it is also clear that normal sperm function depends on low levels of ROS generation in order to promote the signal transduction pathways associated with capacitation. Modulators of ROS generation by spermatozoa may therefore have clinical utility in regulating the fertilizing capacity of these cells and preventing the development of antisperm immunity. Achievement of these objectives will require a systematic evaluation of pro- and antioxidant strategies in vivo and in vitro.

An atlas-based electron density mapping method for magnetic resonance imaging (MRI)-alone treatment planning and adaptive MRI-based prostate radiation therapy.

Abstract: Purpose Prostate radiation therapy dose planning directly on magnetic resonance imaging (MRI) scans would reduce costs and uncertainties due to multimodality image registration. Adaptive planning using a combined MRI-linear accelerator approach will also require dose calculations to be performed using MRI data. The aim of this work was to develop an atlas-based method to map realistic electron densities to MRI scans for dose calculations and digitally reconstructed radiograph (DRR) generation. Methods and Materials Whole-pelvis MRI and CT scan data were collected from 39 prostate patients. Scans from 2 patients showed significantly different anatomy from that of the remaining patient population, and these patients were excluded. A whole-pelvis MRI atlas was generated based on the manually delineated MRI scans. In addition, a conjugate electron-density atlas was generated from the coregistered computed tomography (CT)-MRI scans. Pseudo-CT scans for each patient were automatically generated by global and nonrigid registration of the MRI atlas to the patient MRI scan, followed by application of the same transformations to the electron-density atlas. Comparisons were made between organ segmentations by using the Dice similarity coefficient (DSC) and point dose calculations for 26 patients on planning CT and pseudo-CT scans. Results The agreement between pseudo-CT and planning CT was quantified by differences in the point dose at isocenter and distance to agreement in corresponding voxels. Dose differences were found to be less than 2%. Chi-squared values indicated that the planning CT and pseudo-CT dose distributions were equivalent. No significant differences ( p > 0.9) were found between CT and pseudo-CT Hounsfield units for organs of interest. Mean ± standard deviation DSC scores for the atlas-based segmentation of the pelvic bones were 0.79 ± 0.12, 0.70 ± 0.14 for the prostate, 0.64 ± 0.16 for the bladder, and 0.63 ± 0.16 for the rectum. Conclusions The electron-density atlas method provides the ability to automatically define organs and map realistic electron densities to MRI scans for radiotherapy dose planning and DRR generation. This method provides the necessary tools for MRI-alone treatment planning and adaptive MRI-based prostate radiation therapy.

Preventable deaths due to problems in care in English acute hospitals: a retrospective case record review study

Abstract: Introduction Monitoring hospital mortality rates is widely recommended. However, the number of preventable deaths remains uncertain with estimates in England ranging from 840 to 40 000 per year, these being derived from studies that identified adverse events but not whether events contributed to death or shortened life expectancy of those affected. Methods Retrospective case record reviews of 1000 adults who died in 2009 in 10 acute hospitals in England were undertaken. Trained physician reviewers estimated life expectancy on admission, to identified problems in care contributing to death and judged if deaths were preventable taking into account patients' overall condition at that time. Results Reviewers judged 5.2% (95% CI 3.8% to 6.6%) of deaths as having a 50% or greater chance of being preventable. The principal problems associated with preventable deaths were poor clinical monitoring (31.3%; 95% CI 23.9 to 39.7), diagnostic errors (29.7%; 95% CI 22.5% to 38.1%), and inadequate drug or fluid management (21.1%; 95% CI 14.9 to 29.0). Extrapolating from these figures suggests there would have been 11 859 (95% CI 8712 to 14 983) adult preventable deaths in hospitals in England. Most preventable deaths (60%) occurred in elderly, frail patients with multiple comorbidities judged to have had less than 1 year of life left to live. Conclusions The incidence of preventable hospital deaths is much lower than previous estimates. The burden of harm from preventable problems in care is still substantial. A focus on deaths may not be the most efficient approach to identify opportunities for improvement given the low proportion of deaths due to problems with healthcare.