Shared component modelling as an alternative to assess geographical variations in medical practice: gender inequalities in hospital admissions for chronic diseases

<p>Abstract</p> <p>Background</p> <p>Small area analysis is the most prevalent methodological approach in the study of unwarranted and systematic variation in medical practice at geographical level. Several of its limitations drive researchers to use disease mapping methods -deemed as a valuable alternative. This work aims at exploring these techniques using - as a case of study- the gender differences in rates of hospitalization in elderly patients with chronic diseases.</p> <p>Methods</p> <p>Design and study setting: An empirical study of 538,358 hospitalizations affecting individuals aged over 75, who were admitted due to a chronic condition in 2006, were used to compare Small Area Analysis (SAVA), the Besag-York-Mollie (BYM) modelling and the Shared Component Modelling (SCM). Main endpoint: Gender spatial variation was measured, as follows: SAVA estimated gender-specific utilization ratio; BYM estimated the fraction of variance attributable to spatial correlation in each gender; and, SCM estimated the fraction of variance shared by the two genders, and those specific for each one.</p> <p>Results</p> <p>Hospitalization rates due to chronic diseases in the elderly were higher in men (median per area 21.4 per 100 inhabitants, interquartile range: 17.6 to 25.0) than in women (median per area 13.7 per 100, interquartile range: 10.8 to 16.6). Whereas Utilization Ratios showed a similar geographical pattern of variation in both genders, BYM found a high fraction of variation attributable to spatial correlation in both men (71%, CI95%: 50 to 94) and women (62%, CI95%: 45 to 77). In turn, SCM showed that the geographical admission pattern was mainly shared, with just 6% (CI95%: 4 to 8) of variation specific to the women component.</p> <p>Conclusions</p> <p>Whereas SAVA and BYM focused on the magnitude of variation and on allocating where variability cannot be due to chance, SCM signalled discrepant areas where latent factors would differently affect men and women.</p

Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis

Citation: Hanzlicek, G. A., Raghavan, R. K., Ganta, R. R., & Anderson, G. A. (2016). Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis. Plos One, 11(3), 13. doi:10.1371/journal.pone.0151924The space-time pattern and environmental drivers (land cover, climate) of bovine anaplasmosis in the Midwestern state of Kansas was retrospectively evaluated using Bayesian hierarchical spatio-temporal models and publicly available, remotely-sensed environmental covariate information. Cases of bovine anaplasmosis positively diagnosed at Kansas State Veterinary Diagnostic Laboratory (n = 478) between years 2005-2013 were used to construct the models, which included random effects for space, time and space-time interaction effects with defined priors, and fixed-effect covariates selected a priori using an univariate screening procedure. The Bayesian posterior median and 95% credible intervals for the space-time interaction term in the best-fitting covariate model indicated a steady progression of bovine anaplasmosis over time and geographic area in the state. Posterior median estimates and 95% credible intervals derived for covariates in the final covariate model indicated land surface temperature (minimum), relative humidity and diurnal temperature range to be important risk factors for bovine anaplasmosis in the study. The model performance measured using the Area Under the Curve (AUC) value indicated a good performance for the covariate model (>0.7). The relevance of climatological factors for bovine anaplasmosis is discussed

Plant Identity Influences Decomposition through More Than One Mechanism

Plant litter decomposition is a critical ecosystem process representing a major pathway for carbon flux, but little is known about how it is affected by changes in plant composition and diversity. Single plant functional groups (graminoids, legumes, non-leguminous forbs) were removed from a grassland in northern Canada to examine the impacts of functional group identity on decomposition. Removals were conducted within two different environmental contexts (fertilization and fungicide application) to examine the context-dependency of these identity effects. We examined two different mechanisms by which the loss of plant functional groups may impact decomposition: effects of the living plant community on the decomposition microenvironment, and changes in the species composition of the decomposing litter, as well as the interaction between these mechanisms. We show that the identity of the plant functional group removed affects decomposition through both mechanisms. Removal of both graminoids and forbs slowed decomposition through changes in the decomposition microenvironment. We found non-additive effects of litter mixing, with both the direction and identity of the functional group responsible depending on year; in 2004 graminoids positively influenced decomposition whereas in 2006 forbs negatively influenced decomposition rate. Although these two mechanisms act independently, their effects may be additive if both mechanisms are considered simultaneously. It is essential to understand the variety of mechanisms through which even a single ecosystem property is affected if we are to predict the future consequences of biodiversity loss

MMPs Regulate both Development and Immunity in the Tribolium Model Insect

BACKGROUND: Matrix metalloproteinases (MMPs) are evolutionarily conserved and multifunctional effector molecules in development and homeostasis. In spite of previous, intensive investigation in vitro and in cell culture, their pleiotrophic functions in vivo are still not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We show that the genetically amenable beetle Tribolium castaneum represents a feasible model organism to explore MMP functions in vivo. We silenced expression of three insect-type Tribolium MMP paralogs and their physiological inhibitors, TIMP and RECK, by dsRNA-mediated genetic interference (RNAi). Knock-down of MMP-1 arrested development during pupal morphogenesis giving phenotypes with altered antennae, compound eyes, wings, legs, and head. Parental RNAi-mediated knock-down of MMP-1 or MMP-2 resulted in larvae with non-lethal tracheal defects and with abnormal intestines, respectively, implicating additional roles of MMPs during beetle embryogenesis. This is different to findings from the fruit fly Drosophila melanogaster, in which MMPs have a negligible role in embryogenesis. Confirming pleiotrophic roles of MMPs our results also revealed that MMPs are required for proper insect innate immunity because systemic knock-down of Tribolium MMP-1 resulted in significantly higher susceptibility to the entomopathogenic fungus Beauveria bassiana. Moreover, mRNA levels of MMP-1, TIMP, and RECK, and also MMP enzymatic activity were significantly elevated in immune-competent hemocytes upon stimulation. To confirm collagenolytic activity of Tribolium MMP-1 we produced and purified recombinant enzyme and determined a similar collagen IV degrading activity as observed for the most related human MMP, MMP-19. CONCLUSIONS/SIGNIFICANCE: This is the first study, to our knowledge, investigating the in vivo role of virtually all insect MMP paralogs along with their inhibitors TIMP and RECK in both insect development and immunity. Our results from the Tribolium model insect indicate that MMPs regulate tracheal and gut development during beetle embryogenesis, pupal morphogenesis, and innate immune defense reactions thereby revealing the evolutionarily conserved roles of MMPs

Bayesian Spatio-Temporal Modeling of Schistosoma japonicum Prevalence Data in the Absence of a Diagnostic ‘Gold’ Standard

Schistosomiasis is a serious public health problem in the People's Republic of China and elsewhere, and mapping of risk areas is important for guiding control interventions. Here, a 10-year surveillance database from Dangtu County in the southeastern part of the People's Republic of China was utilized for modeling the spatial and temporal distribution of infections in relation to environmental features and socioeconomic factors. Disease surveillance was done on the basis of a serological test, and we explicitly considered the imperfect sensitivity and specificity of the test when modeling the ‘true’ infection prevalence of Schistosoma japonicum. We then produced a risk map for S. japonicum transmission, which can assist decision making for local control interventions. Our work emphasizes the importance of accounting for the uncertainty in the diagnosis of schistosomiasis, and the potential of predicting the spatial and temporal distribution of the disease when using a Bayesian modeling framework. Our study can therefore serve as a template for future risk profiling of neglected tropical diseases studies, particularly when exploring spatial and temporal disease patterns in relation to environmental and socioeconomic factors, and how to account for the influence of diagnostic uncertainty

Time trends in municipal distribution patterns of cancer mortality in Spain

BACKGROUND: New disease mapping techniques widely used in small-area studies enable disease distribution patterns to be identified and have become extremely popular in the field of public health. This paper reports on trends in the geographical mortality patterns of the most frequent cancers in Spain, over a period of 20 years. METHODS: We studied the municipal spatial pattern of stomach, colorectal, lung, breast, prostate and urinary bladder cancer mortality in Spain across four quinquennia, spanning the period 1989-2008. Case data were broken down by town (8073 municipalities), period and sex. Expected cases for each town were calculated using reference rates for each five-year period. For map plotting purposes, smoothed municipal relative risks were calculated using the conditional autoregressive model proposed by Besag, York and Mollié, with independent data for each quinquennium. We evaluated the presence of spatial patterns in maps on the basis of models, calculating the variance in relative risk corresponding to the structured spatial component and the unstructured component, as well as the proportion of variance explained by the structured spatial component. RESULTS: The mortality patterns observed for stomach, colorectal and lung cancer were maintained over the 20 years covered by the study. Prostate cancer and the tumours studied in women showed no defined spatial pattern, with the single exception of stomach cancer. The trend in spatial fractional variance indicated the possibility of a change in the spatial pattern in breast, bladder and colorectal cancer in women during the last five-year period. The paper goes on to discuss ways in which spatio-temporal data are depicted in the case of cancer, and review the risk factors that may possibly influence the respective tumours’ spatial patterns. CONCLUSION: In men, the marked geographical patterns of stomach, colorectal, lung and bladder cancer remained stable over time. Breast, colorectal and bladder cancer in women show signs of the possible appearance of a spatial pattern in Spain and should therefore be monitored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2407-14-535) contains supplementary material, which is available to authorized users

Global fire emissions buffered by the production of pyrogenic carbon

Landscape fires burn 3–5 million km2 of the Earth’s surface annually. They emit 2.2 Pg of carbon per year to the atmosphere, but also convert a significant fraction of the burned vegetation biomass into pyrogenic carbon. Pyrogenic carbon can be stored in terrestrial and marine pools for centuries to millennia and therefore its production can be considered a mechanism for long-term carbon sequestration. Pyrogenic carbon stocks and dynamics are not considered in global carbon cycle models, which leads to systematic errors in carbon accounting. Here we present a comprehensive dataset of pyrogenic carbon production factors from field and experimental fires and merge this with the Global Fire Emissions Database to quantify the global pyrogenic carbon production flux. We found that 256 (uncertainty range: 196–340) Tg of biomass carbon was converted annually into pyrogenic carbon between 1997 and 2016. Our central estimate equates to 12% of the annual carbon emitted globally by landscape fires, which indicates that their emissions are buffered by pyrogenic carbon production. We further estimate that cumulative pyrogenic carbon production is 60 Pg since 1750, or 33–40% of the global biomass carbon lost through land use change in this period. Our results demonstrate that pyrogenic carbon production by landscape fires could be a significant, but overlooked, sink for atmospheric CO2

Personalized therapy for mycophenolate:Consensus report by the international association of therapeutic drug monitoring and clinical toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.</p

Temperature sensitivity of soil enzymes along an elevation gradient in the Peruvian Andes

Soil enzymes are catalysts of organic matter depolymerisation, which is of critical importance for ecosystem carbon (C) cycling. Better understanding of the sensitivity of enzymes to temperature will enable improved predictions of climate change impacts on soil C stocks. These impacts may be especially large in tropical montane forests, which contain large amounts of soil C. We determined the temperature sensitivity (Q 10) of a range of hydrolytic and oxidative enzymes involved in organic matter cycling from soils along a 1900 m elevation gradient (a 10 °C mean annual temperature gradient) of tropical montane forest in the Peruvian Andes. We investigated whether the activity (V max) of selected enzymes: (i) exhibited a Q 10 that varied with elevation and/or soil properties; and (ii) varied among enzymes and according to the complexity of the target substrate for C-degrading enzymes. The Q 10 of V max for β-glucosidase and β-xylanase increased with increasing elevation and declining mean annual temperature. For all other enzymes, including cellobiohydrolase, N-acetyl β-glucosaminidase and phosphomonoesterase, the Q 10 of V max did not vary linearly with elevation. Hydrolytic enzymes that degrade more complex C compounds had a greater Q 10 of V max, but this pattern did not apply to oxidative enzymes because phenol oxidase had the lowest Q 10 value of all enzymes studied here. Our findings suggest that regional differences in the temperature sensitivities of different enzyme classes may influence the terrestrial C cycle under future climate warming