The future burden of lung cancer attributable to current modifiable behaviours: a pooled study of seven Australian cohorts

BACKGROUND: Knowledge of preventable disease and differences in disease burden can inform public health action to improve health and health equity. We quantified the future lung cancer burden preventable by behavioural modifications across Australia. METHODS: We pooled seven Australian cohort studies (n = 367 058) and linked them to national registries to identify lung cancers and deaths. We estimated population attributable fractions and their 95% confidence intervals (CIs) for modifiable risk factors, using risk estimates from the cohort data and risk factor exposure distribution from contemporary national health surveys. RESULTS: During the first 10-year follow-up, there were 2025 incident lung cancers and 20 349 deaths. Stopping current smoking could prevent 53.7% (95% CI, 50.0-57.2%) of lung cancers over 40 years and 18.3% (11.0-25.1%) in 10 years. The smoking-attributable burden is highest in males, those who smoke <20 cigarettes per day, are <75 years of age, unmarried, of lower educational attainment, live in remote areas or are healthy weight. Increasing physical activity and fruit consumption, if causal, could prevent 15.6% (6.9-23.4%) and 7.5% (1.3-13.3%) of the lung cancer burden, respectively. Jointly, the three behaviour modifications could prevent up to 63.0% (58.0-67.5%) of lung cancers in 40 years, and 31.2% (20.9-40.1%) or 43 300 cancers in 10 years. The preventable burden is highest among those with multiple risk factors. CONCLUSIONS: Smoking remains responsible for the highest burden of lung cancer in Australia. The uneven burden distribution distinguishes subgroups that could benefit the most from activities to control the world's deadliest cancer

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Direct hospital costs of chest pain patients attending the emergency department: a retrospective study

BACKGROUND: Chest pain is one of the most common complaints in the Emergency Department (ED), but the cost of ED chest pain patients is unclear. The aim of this study was to describe the direct hospital costs for unselected chest pain patients attending the emergency department (ED). METHODS: 1,000 consecutive ED visits of patients with chest pain were retrospectively included. Costs directly following the ED visit were retrieved from the hospital economy system. RESULTS: The mean cost per patient visit was 26.8 thousand Swedish kronar (kSEK) (median 7.2 kSEK), with admission time accounting for 73% of all costs. Mean cost for patients discharged from the ED was 1.4 kSEK (median 1.3 kSEK), and for patients without ACS admitted 1 day or less 7.6 kSEK (median 6.9 kSEK). The practice in the present study to admit 67% of the patients, of whom only 31% proved to have ACS, was estimated to give a cost per additional life-year saved by hospital admission, compared to theoretical strategy of discharging all patients home, of about 350 kSEK (39 kEUR or 42 kUSD). CONCLUSION: Costs for chest pain patients are large and primarily due to admission time. The present admission practice seems to be cost-effective, but the substantial overadmission indicates that better ED diagnostics and triage could decrease costs considerably

Evaluation of Glycine max mRNA clusters

BACKGROUND: Clustering the ESTs from a large dataset representing a single species is a convenient starting point for a number of investigations into gene discovery, genome evolution, expression patterns, and alternatively spliced transcripts. Several methods have been developed to accomplish this, the most widely available being UniGene, a public domain collection of gene-oriented clusters for over 45 different species created and maintained by NCBI. The goal is for each cluster to represent a unique gene, but currently it is not known how closely the overall results represent that reality. UniGene's build procedure begins with initial mRNA clusters before joining ESTs. UniGene's results for soybean indicate a significant amount of redundancy among some sequences reported to be unique mRNAs. To establish a valid non-redundant known gene set for Glycine max we applied our algorithm to the clustering of only mRNA sequences. The mRNA dataset was run through the algorithm using two different matching stringencies. The resulting cluster compositions were compared to each other and to UniGene. Clusters exhibiting differences among the three methods were analyzed by 1) nucleotide and amino acid alignment and 2) submitting authors conclusions to determine whether members of a single cluster represented the same gene or not. RESULTS: Of the 12 clusters that were examined closely most contained examples of sequences that did not belong in the same cluster. However, neither the two stringencies of PECT nor UniGene had a significantly greater record of accuracy in placing paralogs into separate clusters. CONCLUSION: Our results reveal that, although each method produces some errors, using multiple stringencies for matching or a sequential hierarchical method of increasing stringencies can provide more reliable results and therefore allow greater confidence in the vast majority of clusters that contain only ESTs and no mRNA sequences

Comparative efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for early onset chronic depression: design and rationale of a multisite randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Effective treatment strategies for chronic depression are urgently needed since it is not only a common and particularly disabling disorder, but is also considered treatment resistant by most clinicians. There are only a few studies on chronic depression indicating that traditional psycho- and pharmacological interventions are not as effective as in acute, episodic depression. Current medications are no more effective than those introduced 50 years ago whereas the only psychotherapy developed specifically for the subgroup of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), faired well in one large trial. However, CBASP has never been directly compared to a non-specific control treatment.</p> <p>Methods/Design</p> <p>The present article describes the study protocol of a multisite parallel-group randomized controlled trial in Germany. The purpose of the study is to estimate the efficacy of CBASP compared to supportive psychotherapy in 268 non-medicated early-onset chronically depressed outpatients. The intervention includes 20 weeks of acute treatment with 24 individual sessions followed by 28 weeks of continuation treatment with another 8 sessions. Depressive symptoms are evaluated 20 weeks after randomisation by means of the 24-item Hamilton Rating Scale of Depression (HRSD). Secondary endpoints are depressive symptoms after 12 and 48 weeks, and remission after 12, 20, and 48 weeks. Primary outcome will be analysed using analysis of covariance (ANCOVA) controlled for pre-treatment scores and site. Analyses of continuous secondary variables will be performed using linear mixed models. For remission rates, chi-squared tests and logistic regression will be applied.</p> <p>Discussion</p> <p>The study evaluates the comparative effects of a disorder-specific psychotherapy and a well designed non-specific psychological approach in the acute and continuation treatment phase in a large sample of early-onset chronically depressed patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00970437">NCT00970437</a>).</p

Ambivalent connections: a qualitative study of the care experiences of non-psychotic chronic patients who are perceived as 'difficult' by professionals

Contains fulltext : 90688.pdf (publisher's version ) (Open Access)Background: Little is known about the perspectives of psychiatric patients who are perceived as 'difficult' by clinicians. The aim of this paper is to improve understanding of the connections between patients and professionals from patients' point of view. Methods: A Grounded Theory study using interviews with 21 patients from 12 outpatient departments of three mental health care facilities. Results: Patients reported on their own difficult behaviours and their difficulties with clinicians and services. Explanations varied but could be summarized as a perceived lack of recognition. Recognition referred to being seen as a patient and a person - not just as completely 'ill' or as completely 'healthy'. Also, we found that patients and professionals have very different expectations of one another, which may culminate in a difficult or ambivalent connection. In order to explicate patient's expectations, the patient-clinician contact was described by a stage model that differentiates between three stages of contact development, and three stages of substantial treatment. According to patients, in each stage there is a therapeutic window of optimal clinician behaviour and two wider spaces below and above that may be qualified as 'toxic' behaviour. Possible changes in clinicians' responses to 'difficult' patients were described using this model. Conclusions: The incongruence of patients' and professionals' expectations may result in power struggles that may make professionals perceive patients as 'difficult'. Explication of mutual expectations may be useful in such cases. The presented model gives some directions to clinicians how to do this.11 p

Gene Conversion Transfers the GAF-A Domain of Phosphodiesterase TbrPDEB1 to One Allele of TbrPDEB2 of Trypanosoma brucei

Cyclic nucleotide specific phosphodiesterases are important regulators of cyclic nucleotide signalling in eukaryotes. In many organisms, including humans and trypanosomes, some of these enzymes contain specific domains (GAF domains) that bind cyclic nucleotides, and that are involved in the regulation of the catalytic domain. In the parasitic protozoon that causes human sleeping sickness, Trypanosoma brucei, two closely related phosphodiesterases each contain two such GAF domains, GAF-A and GAF-B. Their genes are tandemly located on chromosome 9, spaced by only a few thousand nucleotides. We here show that a gene conversion event has exchanged the region that codes for the GAF-A domain of the downstream gene by the closely similar corresponding sequence of the upstream gene. This domain exchange has no effect on intracellular localization of the two enzymes. The gene conversion event has occurred in one particular strain of trypanosomes (Lister427) and is found in all its derivatives, but not in any other strain or isolate. The presence or absence of this gene conversion represents a useful analytical marker for the stringent discrimination of Lister427 derivatives from other trypanosome strains

Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case-control study

INTRODUCTION: Vitamin D receptor (VDR) polymorphisms have been inconsistently associated with breast cancer risk. Whether risk is influenced by polymorphisms in other vitamin D metabolism genes and whether calcium or vitamin D intake modifies risk by genotype have not been evaluated. METHODS: We conducted a nested case-control study within the Cancer Prevention Study II Nutrition Cohort of associations between breast cancer and four VDR single-nucleotide polymorphisms (SNPs), Bsm1,Apa1,Taq1, and Fok1, a poly(A) microsatellite, and associated haplotypes (baTL and BAtS). We also examined one SNP in the 24-hydroxylase gene (CYP24A1) and two in the vitamin D-binding protein (group-specific component [GC]) gene. Participants completed a questionnaire on diet and medical history at baseline in 1992. This study includes 500 postmenopausal breast cancer cases and 500 controls matched by age, race/ethnicity, and date of blood collection. RESULTS: Incident breast cancer was not associated with any genotype examined. However, women with the Bsm1 bb SNP who consumed greater than the median intake of total calcium (≥902 mg/day) had lower odds of breast cancer compared to women with the Bb or BB genotype and less than the median calcium intake (odds ratio 0.61, 95% confidence interval 0.38 to 0.96; p(interaction )= 0.01). Similar interactions were observed for Taq1 (T allele) and the poly(A) (LL) repeat. CONCLUSION: We found no overall association between selected vitamin D pathway genes and postmenopausal breast cancer risk. However, certain VDR gene polymorphisms were associated with lower risk in women consuming high levels of calcium, suggesting that dietary factors may modify associations by VDR genotype

Economic Impacts of Non-Native Forest Insects in the Continental United States

Reliable estimates of the impacts and costs of biological invasions are critical to developing credible management, trade and regulatory policies. Worldwide, forests and urban trees provide important ecosystem services as well as economic and social benefits, but are threatened by non-native insects. More than 450 non-native forest insects are established in the United States but estimates of broad-scale economic impacts associated with these species are largely unavailable. We developed a novel modeling approach that maximizes the use of available data, accounts for multiple sources of uncertainty, and provides cost estimates for three major feeding guilds of non-native forest insects. For each guild, we calculated the economic damages for five cost categories and we estimated the probability of future introductions of damaging pests. We found that costs are largely borne by homeowners and municipal governments. Wood- and phloem-boring insects are anticipated to cause the largest economic impacts by annually inducing nearly $1.7 billion in local government expenditures and approximately$830 million in lost residential property values. Given observations of new species, there is a 32% chance that another highly destructive borer species will invade the U.S. in the next 10 years. Our damage estimates provide a crucial but previously missing component of cost-benefit analyses to evaluate policies and management options intended to reduce species introductions. The modeling approach we developed is highly flexible and could be similarly employed to estimate damages in other countries or natural resource sectors