Treatment decisions and survival for people with small-cell lung cancer

Background: Chemotherapy improves survival for many patients with SCLC, and hence it is important to understand variations in practice and outcomes for this treatment strategy. Methods: We used the National Lung Cancer Audit and Hospital Episodes Statistics to determine the proportion of patients who received chemotherapy for SCLC, and assess the effects of patient and organisational factors on the odds of receiving chemotherapy and of completing four cycles. We calculated median survival and used Cox regression to determine factors that predicted survival. Results: Of 15 091 cases of SCLC, 70% received at least one cycle of chemotherapy. More deprived people were less likely to receive chemotherapy, but patients were more likely to receive chemotherapy, and to complete Xfour cycles, if they were referred to the lung cancer team by their GP. Median survival for those treated with chemotherapy was 12.9 months for limited and 7.3 months for extensive stage disease. Conclusions: The Linked NLCA and HES data provide real-life measures of survival in people treated with chemotherapy and show how this is influenced by patient and tumour characteristics. These data show the characteristics of patients who are less likely to complete a full course of treatment, an adverse predictor of survival

Cross-sectional associations between sleep duration, sedentary time, physical activity, and adiposity indicators among Canadian preschool-aged children using compositional analyses

Abstract Background Sleep duration, sedentary behaviour, and physical activity are three co-dependent behaviours that fall on the movement/non-movement intensity continuum. Compositional data analyses provide an appropriate method for analyzing the association between co-dependent movement behaviour data and health indicators. The objectives of this study were to examine: (1) the combined associations of the composition of time spent in sleep, sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) with adiposity indicators; and (2) the association of the time spent in sleep, sedentary behaviour, LPA, or MVPA with adiposity indicators relative to the time spent in the other behaviours in a representative sample of Canadian preschool-aged children. Methods Participants were 552 children aged 3 to 4 years from cycles 2 and 3 of the Canadian Health Measures Survey. Sedentary time, LPA, and MVPA were measured with Actical accelerometers (Philips Respironics, Bend, OR USA), and sleep duration was parental reported. Adiposity indicators included waist circumference (WC) and body mass index (BMI) z-scores based on World Health Organization growth standards. Compositional data analyses were used to examine the cross-sectional associations. Results The composition of movement behaviours was significantly associated with BMI z-scores (p = 0.006) but not with WC (p = 0.718). Further, the time spent in sleep (BMI z-score: γ sleep  = −0.72; p = 0.138; WC: γ sleep  = −1.95; p = 0.285), sedentary behaviour (BMI z-score: γ SB  = 0.19; p = 0.624; WC: γ SB  = 0.87; p = 0.614), LPA (BMI z-score: γ LPA  = 0.62; p = 0.213, WC: γ LPA  = 0.23; p = 0.902), or MVPA (BMI z-score: γ MVPA  = −0.09; p = 0.733, WC: γ MVPA  = 0.08; p = 0.288) relative to the other behaviours was not significantly associated with the adiposity indicators. Conclusions This study is the first to use compositional analyses when examining associations of co-dependent sleep duration, sedentary time, and physical activity behaviours with adiposity indicators in preschool-aged children. The overall composition of movement behaviours appears important for healthy BMI z-scores in preschool-aged children. Future research is needed to determine the optimal movement behaviour composition that should be promoted in this age group

Modelling production-consumption flows of goods in Europe: the trade model within Transtools3

The paper presents a new model for trade flows in Europe that is integrated with a logistics model for transport chain choice through Logsum variables. Logsums measures accessibility across an entire multi-modal logistical chain, and are calculated from a logistics model that has been estimated on disaggregated micro data and then used as an input variable in the trade model. Using Logsums in a trade model is new in applied large-scale freight models, where previous models have simply relied on the distance (e.g. crow-fly) between zones. This linkage of accessibility to the trade model makes it possible to evaluate how changes in policies on transport costs and changes in multi-modal networks will influence trade patterns. As an example the paper presents outcomes for a European-wide truck tolling scenario, which showcases to which extent trade is influenced by such a policy. The paper discusses how such a complex model can be estimated and considers the choice of mathematical formulation and the link between the trade model and logistics model. In the outcomes for the tolling scenario we decompose the total effects into effects from the trade model and effects from the logistics model

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

Clostridium septicum sepsis and colorectal cancer - a reminder

<p>Abstract</p> <p>Background</p> <p>Spontaneous clostridium septicum infections are rare and are associated with a high mortality. Association of clostridium infection with colorectal malignancies have been previously reported and most cases are described in tumours of the ascending colon. We report our experience of clostridium septicum infection in the presence of tumour perforation in a series of two patients as a reminder of its association with sepsis in the presence of colorectal malignancy.</p> <p>Case Presentation</p> <p>We isolated clostridium septicum infection in a series of two patients admitted as emergencies. One patient was found to have a perforated caecal tumour intraoperatively whilst the other had a perforated rectal tumour. The clinical outcome and management of each case are reported and underlying reasons for variations in outcome are discussed.</p> <p>Conclusion</p> <p>Although uncomman, the possibility of clostridium septicum sepsis should be borne in mind in patients who present with underlying malignancy and have sepsis. The cumulative effect of sepsis and malignant perforation is associated with a high morbidity and mortality. Awareness and early diagnosis of clostridium septicum may improve the prognosis of what is usually regarded as a fatal infection.</p

Selection at a single locus leads to widespread expansion of toxoplasma gondii lineages that are virulent in mice

The determinants of virulence are rarely defined for eukaryotic parasites such as T. gondii, a widespread parasite of mammals that also infects humans, sometimes with serious consequences. Recent laboratory studies have established that variation in a single secreted protein, a serine/threonine kinase known as ROPO18, controls whether or not mice survive infection. Here, we establish the extent and nature of variation in ROP18among a collection of parasite strains from geographically diverse regions. Compared to other genes, ROP18 showed extremely high levels of diversification and changes in expression level, which correlated with severity of infection in mice. Comparison with an out-group demonstrated that changes in the upstream region that regulates expression of ROP18 led to an historical increase in the expression and exposed the protein to diversifying selective pressure. Surprisingly, only three atypically distinct protein variants exist despite marked genetic divergence elsewhere in the genome. These three forms of ROP18 are likely adaptations for different niches in nature, and they confer markedly different virulence to mice. The widespread distribution of a single mouse-virulent allele among geographically and genetically disparate parasites may have consequences for transmission and disease in other hosts, including humans

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change &#8805;2) and significantly altered in GBM (p &#8804; 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

A genome-wide assessment of the role of untagged copy number variants in type 1 diabetes.

Genome-wide association studies (GWAS) for type 1 diabetes (T1D) have successfully identified more than 40 independent T1D associated tagging single nucleotide polymorphisms (SNPs). However, owing to technical limitations of copy number variants (CNVs) genotyping assays, the assessment of the role of CNVs has been limited to the subset of these in high linkage disequilibrium with tag SNPs. The contribution of untagged CNVs, often multi-allelic and difficult to genotype using existing assays, to the heritability of T1D remains an open question. To investigate this issue, we designed a custom comparative genetic hybridization array (aCGH) specifically designed to assay untagged CNV loci identified from a variety of sources. To overcome the technical limitations of the case control design for this class of CNVs, we genotyped the Type 1 Diabetes Genetics Consortium (T1DGC) family resource (representing 3,903 transmissions from parents to affected offspring) and used an association testing strategy that does not necessitate obtaining discrete genotypes. Our design targeted 4,309 CNVs, of which 3,410 passed stringent quality control filters. As a positive control, the scan confirmed the known T1D association at the INS locus by direct typing of the 5' variable number of tandem repeat (VNTR) locus. Our results clarify the fact that the disease association is indistinguishable from the two main polymorphic allele classes of the INS VNTR, class I-and class III. We also identified novel technical artifacts resulting into spurious associations at the somatically rearranging loci, T cell receptor, TCRA/TCRD and TCRB, and Immunoglobulin heavy chain, IGH, loci on chromosomes 14q11.2, 7q34 and 14q32.33, respectively. However, our data did not identify novel T1D loci. Our results do not support a major role of untagged CNVs in T1D heritability

Waist Circumference as Compared with Body-Mass Index in Predicting Mortality from Specific Causes

Background Whether waist circumference provides clinically meaningful information not delivered by body-mass index regarding prediction of cause-specific death is uncertain. Methods We prospectively examined waist circumference (WC) and body-mass index (BMI) in relation to cause-specific death in 225,712 U.S. women and men. Cox regression was used to estimate relative risks and 95% confidence intervals (CI). Statistical analyses were conducted using SAS version 9.1. Results During follow-up from 1996 through 2005, we documented 20,977 deaths. Increased WC consistently predicted risk of death due to any cause as well as major causes of death, including deaths from cancer, cardiovascular disease, and non-cancer/non-cardiovascular diseases, independent of BMI, age, sex, race/ethnicity, smoking status, and alcohol intake. When WC and BMI were mutually adjusted in a model, WC was related to 1.37 fold increased risk of death from any cancer and 1.82 fold increase risk of death from cardiovascular disease, comparing the highest versus lowest WC categories. Importantly, WC, but not BMI showed statistically significant positive associations with deaths from lung cancer and chronic respiratory disease. Participants in the highest versus lowest WC category had a relative risk of death from lung cancer of 1.77 (95% CI, 1.41 to 2.23) and of death from chronic respiratory disease of 2.77 (95% CI, 1.95 to 3.95). In contrast, subjects in the highest versus lowest BMI category had a relative risk of death from lung cancer of 0.94 (95% CI, 0.75 to 1.17) and of death from chronic respiratory disease of 1.18 (95% CI, 0.89 to 1.56). Conclusions Increased abdominal fat measured by WC was related to a higher risk of deaths from major specific causes, including deaths from lung cancer and chronic respiratory disease, independent of BMI