The national resurgence of human West Nile virus (WNV) disease in 2012 raised questions about the factors responsible for WNV outbreaks. Interannual climatic variations may influence WNV amplification and transmission to humans through multiple pathways, including mosquito breeding habitats, gonotrophic cycles, extrinsic incubation, avian communities, and human behavior. We examined the influences of temperature and precipitation anomalies on interannual variation in human WNV cases in three regions of the United States. There were consistent positive influences of winter temperatures, weaker and more variable positive effects of spring and summer temperatures, and highly variable precipitation effects that ranged from positive to negative. The overwintering period may be a particularly important climatic constraint on the dynamics of WNV in cold-temperate regions of North America. Geographic differences in the seasonal timing and relative importance of climatic drivers of WNV risk likely reflect underlying variability in key ecological and social characteristics. West Nile virus (WNV) is a prototypical emerging pathogen that was introduced to the Western Hemisphere in 1999 and has subsequently spread to all 48 conterminous United States and across much of North and South America. WNV has had a substantial public health impact at the national level. In total, 37,088 human WNV cases were reported to the Centers for Disease Control (CDC) through 2012, including 16,196 cases of severe neuroinvasive disease and 1,549 deaths. These effects have been spatially heterogeneous, with geographic clusters of persistently high WNV incidence in the Great Plains, the lower Mississippi Valley, and portions of the Intermountain West.4Climatic variation has long been hypothesized to influence the risk of vector-borne and zoonotic diseases through environmental influences on arthropod vectors, avian hosts, microbial pathogens, and human exposure.These associations are reflected in previous studies that have documented relationships between climatic variation and the spatial and temporal patterns of human WNV disease. Reisen and othersOne of the challenges to understanding the climatic triggers of WNV outbreaks is the broad range of environments in which the virus has become endemic. For example, the primary mosquito vectors of WNV vary across diverse regions of the United States, with the different species exhibiting a range of habitat associations, climatic sensitivities, and feeding preferences.To address this need, the primary of objective of this study was to explore the influences of temperature and precipitation on the interannual variation of human WNV disease in various parts of the United States. To examine these relationships, we used partial least squares (PLS) regression, a multivariate technique that accounts for the correlation structure of multiple climatic variables and provides an intuitive method for visualizing the distribution of human WNV risk in climatic space as biplots. The results showed consistent positive influences of winter temperatures on human WNV risk, weaker and more variable positive effects of spring and summer temperatures, and highly variable precipitation effects that ranged from positive to negative. These findings highlight the potential as well as the limitations of modeling future WNV risk based on temperature and precipitation and suggest future avenues of research to improve our understanding of the complex interactions between climatic variation and WNV.We focused on three regions containing the states that had the highest incidence rates during the resurgence of human WNV cases in 2012 ( in 2012 .http://diseasemaps.usgs.gov). The total number of reported human WNV cases per county, including both West Nile fever and West Nile neuroinvasive disease, was used as the dependent variable in the analyses. Human WNV incidence during the initial outbreak years from 1999 to 2003 was likely affected by immunologically naïve avian and human populations and dispersal limitations.WNV human case data were obtained from the US Geological Survey disease map archive  atmospheric forcing data . These dN = 387), 18 counties in the MW region (N = 162), and 57 counties in the SC region (N = 513). To quantify the interannual variability of WNV incidence for each county, we calculated the logarithm of the relative rate (LRR) of total WNV cases using the following equation:In the analyses, we included only counties with 18 or more cumulative WNV cases (a mean of 2 cases/year) during the 9-year study period (2004–2012) to focus on areas with the highest potential for measuring temporal variability in risk to humans. The study, thus, encompassed 43 counties in the NGP region  logarithm, ijLRR = 1 when ijO = iE. Values < 1 indicated a lower than expected number of cases, and values > 1 indicated a higher than expected number of cases for a given county.where We analyzed the relationship between county-level annual LRR values and climatic anomalies for the 12 months during and preceding the WNV transmission season. The WNV season in the three study regions occurs mainly between June and September. Therefore, for the LRR in a given year, predictor variables included climate anomalies from January to September of the same year and from October to December of the preceding year. Standardized monthly climatic anomalies from October of 2003 to September of 2012 were computed for temperature and precipitation using the following equation:k indexes months, ijkCLIM is the raw climatic variable (temperature or precipitation) for county i, year j, and month k, ikMCLIM is the mean, and ikSDCLIM is the SD of the climatic variable for county i and month k computed over all 30 years of the climatology (1981–2010).where Because of the potential for strong multicollinearity among the 24 monthly climatic anomaly variables, standard regression techniques are likely to yield inflated parameter variances and unstable parameter estimates. Although variable selection techniques, such as stepwise regression, can be applied to reduce the predictor variables to a smaller subset, these approaches are also sensitive to collinearity and can lead to biases in parameter estimation, inconsistencies in variable selection, and problems associated with multiple hypothesis testing.A separate PLS model was fitted for each of the three study areas. The PLS models were cross-validated by excluding each year (2004–2012) from the training dataset, using the remaining data to fit the PLS model, and comparing the excluded values with predicted values based on climate data for the excluded year. Cross-validation results were used to determine the number of latent factors to include in the final model. PLS regression coefficients were computed for these final models to identify the monthly climatic variables with the strongest effects on LRR. The cross-validation results were used to compute a jackknife estimate of the SE for each regression coefficient.x and y dimensions from the origin to the tips of the arrows represented the strengths and directions of the associations between the monthly climate variables and the latent variables. To improve the clarity of the biplots and better highlight the most important monthly variables for each latent variable, only variables with a standardized PLS regression coefficient of 0.075 or greater were displayed on the biplots. All analyses were carried out in the R statistical analysis environment.Biplots of the final models were used to visualize the associations between interannual variability in the rate of human WNV cases and climatic anomalies. The biplots were generated by constructing a scatterplot of the scores of each county/year combination along two latent factors from the PLS model. The relative positioning of points in this plot provided a graphical representation of the climatic similarity of the observations, with close points being more similar and distant points being more different. The size of each point was scaled to reflect the LRR for each county/year combination. Arrows radiating outward from the origin were plotted to illustrate the linear combination of monthly climate variables that comprised each of the latent variables. The distances in the Biplots provided two-dimensional representations of the distribution of county/year observations in a two-dimensional reduced climate space . Large sIn the NGP region, the first two latent factors of the PLS model accounted for 28.9% of the variance in the climatic variables and explained 50.1% of the variance in LRR. County/year observations with high LRR had high scores on axis 1 and were associated with higher-than-average temperatures in December, January, May, and June and lower-than-average precipitation in January and July. High LRR values during the 2007 outbreak had high scores on axis 2 and were associated with higher-than-average temperatures in December and higher-than-average precipitation in March and August.In the UM region, the first two latent factors of the PLS model accounted for 31.4% of the variance in the climatic variables and explained 64.2% of the variance in LRR. County/year observations with high LRR had high scores on axis 1 and were associated with higher-than-average January and July temperatures and higher-than-average July precipitation. High LRR values, particularly in 2006 and 2012, also had higher scores on axis 2 and were associated with higher-than-average January and February temperatures.In the SC region, the first two latent factors of the PLS model accounted for 23.4% of the variance in the climatic variables and explained 38.7% of the variance in LRR. County/year observations with high LRR had high scores on axis 1 and were associated with higher-than-average temperatures in January, February, and March. High LRR values also had higher scores on axis 2 and were associated with higher-than-average April and May temperatures and higher-than-average December precipitation.Cross-validation indicated that adding additional axes to the PLS solution beyond the first two increased the coefficient of variation in the model predictions. This result suggested that adding additional latent variables to the PLS solution resulted in overfitting, and therefore, standardized PLS regression coefficients were computed only for the first two latent variables to summarize climatic effects on LRR. The eight variables with the highest standardized PLS coefficients for each region were summarized in Culex tarsalis is the most important WNV vector in the NGP region,Cx. pipiens is the primary vector in the MW,Cx. quinquefasciatus is predominant in the SC region.Cx. tarsalis and Cx. pipiens can acquire WNV through vertical transmission, enter diapause, and carry the virus through the winter to infect avian hosts the next year.Cx. quinquefasciatus in the SC region does not enter true diapause, can become active during warm periods, and can maintain low levels of horizontal WNV transmission throughout the winter.7The strongest and most geographically consistent result from this study was the positive relationship between interannual variability in the rate of human WNV disease and temperature anomalies during the winter months, particularly December and January. This finding suggests that the overwintering phase of the WNV enzootic cycle is a climatically sensitive period that has the potential to influence virus amplification and ultimately, the risk to humans during the subsequent transmission season. However, overwintering is the least understood part of the WNV transmission cycle, and geographic variability in climate as well as mosquito species leads to regional differences in the winter ecology of WNV. Whereas Obtaining a better understanding of the overwintering period will be critical to furthering our understanding of climatic controls on WNV, a tropical virus that has become widely established in cold-temperate climates in North America.We also found positive relationships with temperature anomalies during the early amplification season from March to May, although the months with the strongest temperature influences were not consistent across regions. These effects are most likely the result of temperature effects on the gonotrophic cycle of the mosquito vector and the extrinsic incubation period of WNV, and they are in agreement with previous studies that have identified positive relationships between temperature and WNV risk.20Cx. tarsalis predominantly breeds in rural habitats in the NGP region,Cx. pipiens in the MW region and Cx. quinquefasciatus in the SC region are more closely linked with anthropogenic features, such as underground wastewater systems in urbanized environments.The geographically variable precipitation associations reflect the results of prior research that have found inconsistent relationships between precipitation and human WNV disease in different years and geographic locations.Although most studies of climatic influences on WNV have emphasized the effects of climate variability on mosquito populations, there are other mechanisms through which climate can affect the risk of WNV transmission to humans. For example, avian community composition has been shown to fluctuate from year to year in response to climatic variability.Along with extrinsic factors, such as temperature and precipitation, WNV outbreaks are also sensitive to intrinsic feedbacks within the WNV enzootic system. For example, WNV outbreaks are more likely when the level of herd immunity in avian communities is low, a situation that tends to occur after several seasons of relatively low WNV transmission.


Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow limitation and pose a huge burden to society. These obstructive lung diseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice versa. In order to understand the pathophysiology behind these diseases we need to integrate and understand changes occurring across these scales and this is the driving force for multiscale computational modeling.There is an urgent need for improved diagnosis and assessment of obstructive lung diseases. Standard clinical measures are based on global function tests which ignore the highly heterogeneous regional changes that are characteristic of obstructive lung disease pathophysiology. Advances in scanning technology such as hyperpolarized gas MRI has led to new regional measurements of ventilation, perfusion and gas diffusion in the lungs, while new image processing techniques allow these measures to be combined with information from structural imaging such as Computed Tomography (CT). However, it is not yet known how to derive clinical measures for obstructive diseases from this wealth of new data. Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods.Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone. Computational models offer a complementary method to unravel the structure-function relationships occurring within a multiscale, multiphysics system such as this. Here we review the current state-of-the-art in techniques developed for pulmonary image analysis, development of structural models of the respiratory system and predictions of function within these models. We discuss application of modeling techniques to obstructive lung diseases, namely asthma and emphysema and the use of models to predict response to therapy. Finally we introduce a large European project, AirPROM that is developing multiscale models to investigate structure-function relationships in asthma and COPD. Chronic obstructive lung diseases, the most prominent being that of asthma and chronic obstructive pulmonary disease (COPD), are common and exert a large burden on society . These dhttp://physiomeproject.org) started in 1997 with the aim of developing a framework for modeling the entire human body. The Virtual Physiological Human initiative (http://www.vph-institute.org) followed not long after with similar goals but with a particular emphasis on personalized medicine. These initiatives ultimately aim to bridge the gaps in physiology - bringing together data from disparate scales of biology and providing a means of interpreting or inferring alterations in regional properties across the biological scales from molecule to organ. Technical areas being addressed around the world as part of these initiatives include data handling, markup languages, model repositories, ontologies, computational tools as well as development of grid, middleware, and workflows [The Physiome project . However these measures are insufficient for current diagnostic needs because, although they can be used to attribute future risk of disease progression, future exacerbations and mortality in populations, they are poor predictors of patient outcomes for individuals . PFTs prEarly models of the lung utilized generic representations of the structure - for example, using symmetrically branching networks to represent airways and vessels . Rapid aState-of-the-art structural models used for 3D CFD are now fully patient specific consisting of high-resolution computational meshes of the central airways  containing in the order of millions of computational elements ,16. SmalBoth structural and functional information can be extracted from imaging and used to parameterize or validate computational models. Structural information is becoming relatively well established in the modeling pipeline. CT is the modality of choice for structural lung imaging due to its high spatial resolution and good signal-to-noise ratio . The CT Airway segmentation is commonly performed using threshold-based region-growing methods to detect the airway lumen . The cenLobe segmentation is typically performed by dividing the segmented lung volume through detection of the pulmonary fissures using various methods (see review by ). Some aThe regional assessment of obstructive disease can also be used to parameterize or validate computational models. A great deal of research has been carried out into automated assessment of COPD from CT images . The amoFunctional imaging offers a wealth of regional data for model parameterization and validation. In recent years, one of the biggest areas of development for functional imaging of the lung has been in hyperpolarized gas MR imaging (HP MRI) . MeasureModels of several different aspects of respiratory function have been developed including models of ventilation ,18,19,33There is a paucity of truly multiscale respiratory models. An excellent example of a multiscale model investigating lung disease is that of Donovan et al. ,11. ThisAnother example is the model developed by Venegas et al. which incorporated an airway network, the distribution of airflow, airway wall mechanics and ASM behavior . Only miVarious other modeling studies have presented novel outcomes through a combined imaging and modeling approach ,22. ThesThere have been far fewer modeling studies focusing on COPD, with most studies considering only emphysema. Models of emphysema have predominantly focused on the alterations occurring in the parenchymal tissue and the resultant change in tissue mechanical properties. The most common approach uses a network of springs to represent the lung parenchymal tissue ,44, withFunctional Respiratory Imaging (FRI) combines the computational modeling technique of 3D CFD with imaging to create patient-specific models of lung function. Pioneering studies by FLUIDDA, a small company based in Belgium, have applied this technique to provide a novel tool for phenotyping patients and monitoring the efficacy of novel respiratory drugs -9. ResulCT images at full inspiration and full expiration are required for this technique. Segmentation techniques are applied to extract the lobar volumes and central airway geometry. Patient-specific geometric models are created of the central airways and the patient-specific change in lobar volume from expiration to inspiration are applied in the CFD flow boundary conditions . FRI is Airway disease PRedicting Outcomes through patient-specific computational Modeling; http://www.airprom.eu) [In this section we will discuss a large European-wide project called AirPROM (prom.eu) . This isprom.eu) ). The ulThe clinical data consists of both asthmatic and COPD patients from aligned consortia EvA , UBIOPREFRI) simulation studies using the ANSYS software. 1D airway models are generated down to the gas exchange level using the VFB algorithm . Statistical models are being used to capture the structure and function of the lung as a whole. All of these models - large and small airways, macro and micro scale - will be linked together to provide a multiscale modeling framework to predict the evolution of disease and response to clinical interventions [A combined HP MRI measurement and modeling approach is being used to assess the structure and function of the small airways . In addiventions .These types of modeling approaches suffer from several limitations. The process of modeling requires several simplifying assumptions of the system being modeled to enable feasibility of solution; models will never replicate the complexity of reality. However, a model need only be as complicated as required to answer a specific question. It is paramount that implications of the simplifying assumptions used are carefully considered when analyzing outcomes and applying models. A large part of the Physiome/VPH-related modeling drive aims towards creating 'patient-specific' models. However, only parts of a model can be personalized to a given patient with many unknowns remaining . In addition, the link between genetics and environment for an individual seems a near impossible feat to include in models. Current models typically predict function at a narrow time point of life. Predictions of the longer time scale evolution of disease will be a very difficult property to integrate into a modeling framework. At this stage, the power of modeling is predominantly in generating new hypotheses that can be tested experimentally. As new knowledge emerges models and modeling techniques improve models will hopefully move forward in the areas described above.There is a pressing need for modelers and clinicians to work ever more closely to achieve the shared goal of patient-specific clinically relevant multiscale models. One of the major hurdles standing in the way of computational modeling and its clinical use is lack of model validation. Models need to be thoroughly tested to check the accuracy and reliability of the predictions before they will be accepted into the clinical environment. A recent paper by Pathmanathan and Gray  discusseHere we have presented the current state-of-the-art techniques in image processing and computational modeling of the lung. A combined approach using imaging and modeling together provides an extremely powerful tool to assess features of lung (dys)function unable to be measured in the clinic. The AirPROM project aims to develop multiscale models of the lung. In comparison, the Synergy-COPD project aims at a systems approach - integrating models across different organ systems in the body. The work being conducted within the AirPROM project will complement Synergy-COPD by contributing models and knowledge of the function within the lung in health and during asthma and COPD.CB has received grant income and consultancy from GSK, AZ/MedImmune, Novartis, Chiesi, Roche/Genentech and BI. KSB and TD have no competing interests.KSB developed the plan for the manuscript and provided expertise and text on computational modeling aspects within the paper and the AirPROM project. TD provided expertise and text on image-based techniques. CB provided expertise in respiratory medicine and the AirPROM project. All authors were involved in editing the final manuscript.,'


Current evidence suggests that screening and brief intervention (SBI) programs can be effective at reducing risky alcohol consumption. While validity and reliability have been demonstrated for existing screening instruments, little is known about how the diagnostic properties of an instrument influence the cost-effectiveness of SBI. We develop a decision theoretic framework to model this issue, and to measure the potential improvement in cost-effectiveness that could result from changes in screening instrument properties and other factors associated with SBI.To make use of our decision theoretic model, we obtain estimates of the input parameters by conducting a comprehensive review of the literature. In particular, we review the literature on the sensitivity and specificity of the Alcohol Use Disorders Identification Test (AUDIT), and then synthesize this evidence using meta-analytic methods. We also compile evidence on the cost of SBI, the QALY gains of SBI, and the prevalence of risky drinking among primary care patients. We assess uncertainty via Monte Carlo analysis. Finally, we conduct expected value of perfect information (EVPI) analyses to investigate the sources of decision uncertainty.When QALYs are valued at a conservative $1,000/QALY our decision theory indicates an optimal AUDIT threshold score of 5. Our model indicates that employing the recommended threshold score of 8 results in about $4.50 per patient in foregone benefits. This suggests large aggregate foregone benefits with even modest sized patient populations. Gender-specific results are qualitatively similar, but reveal that the optimal SBI program is dramatically different across genders.Despite the relatively sound psychometric properties of the AUDIT, small differences in the sensitivity and specificity can have large impacts on the cost-effectiveness of SBI. Differences in the AUDIT's performance across males and females, as well as differences in the prevalence of risky drinking across genders, contribute heavily to the cost-effectiveness of SBI as well.


The present work is devoted to study the numerical simulation for unsteady MHD flow and heat transfer of a couple stress fluid over a rotating disk. A similarity transformation is employed to reduce the time dependent system of nonlinear partial differential equations (PDEs) to ordinary differential equations (ODEs). The Runge-Kutta method and shooting technique are employed for finding the numerical solution of the governing system. The influences of governing parameters viz. unsteadiness parameter, couple stress and various physical parameters on velocity, temperature and pressure profiles are analyzed graphically and discussed in detail. The flow problems of non-Newtonian fluids are attracted the interest of many researchers because of its significance in modern technology and industries. The natural and industrial applications of such fluids are volcanic lava, extrusion of polymer fluids, drilling mud, suspension solutions, cosmetic and food products, solidification of liquid crystals, cooling of metallic plates in a bath, exotic lubricants, colloidal and many others. In recent times, among various non-Newtonian fluid models, the couple stress fluid model has got the special status because of the spin field in the fluid which sets up an anti-symmetric stresses, known as couple stresses. The basic theory and constitutive equations for couple stress fluid initially developed by Stokes Magnetohydrodynamics (MHD) occurs when a conducting fluid flows in the presence of an electromagnetic field, such that the induced electromagnetic force affects the motion of the fluid. Some significant technological applications of MHD are, in experiments of controlled thermonuclear fusion where a strong magnetic field is used to confine rings or columns of hot plasma, to generate electricity where liquid metals are driven through a magnetic field, etc. Moreover, MHD principles are used in plasma accelerators for ion thrusters, for spacecraft propulsion and for light-ion-beam powered inertial confinement. Some remarkable attempts have been made to study the influence of MHD on various flow situations. The influences of MHD stagnation point flow was analyzed by Hayat et al. Rotating-disk flow of non-Newtonian fluids is intriguingly growing interest, as it is momentous in the study of engineering flows on rotating machineries, spin-coating, centrifugal pumps, rotational viscometers, computer storage devices and some aerodynamic related problems in fluid mechanics. Taking into account both industrial and technological applications, there have been a number of studies presented in literature on steady flow of various types of fluid over a rotating disks and sphere with and without considering magnetic effect Takhar et al. Consider the three dimensional, unsteady, laminar, incompressible, MHD flow and heat transfer of couple stress fluid over a rotating disk which rotates about the The governing partial differential equations areThe boundary conditions areHere, Using similarity transformationsThe equation of continuity yields the relationAnd Eqs. with boundary conditionsHere The shear stress of the fluid in the radial and axial directions can be found asThe heat transfer coefficient in terms of the Nusselt We use the result The dimensionless moment coefficient for a disk of radius The system of Eqs. It can be noticed that the Eqs. The resulting highly nonlinear system of ODEs The numerical solution of the problem has been computed via fourth order Runge-Kutta method based on shooting technique. The effect of various physical parameters namely the unsteadiness parameters luid see –15. The city see , whereasThe effects of tangential velocity ness see . Since tee . see .In gradient , while tadient ( .It is imperative to enlighten diverse limitations of this research. This discussion aims at assisting readers to comprehend this study, which ultimately, provide an opportunity to extend the current research. The following assumptions and limitations are considered.Flow is unsteady, incompressible and laminar.Flow is three dimensional and rotating over a disk about the A uniform magnetic field is applied in the direction normal to the surface of the disk which is assumed unchanging with a small magnetic Reynolds number It is assumed that the effect of dissipation in the energy equation is negligible.In this study we attempt to solve governing equations numerically for a fixed value of In this paper, the response of unsteady MHD flow of couple stress fluid over a rotating disk is discussed. The nonlinear differential equations have been solved numerically using Runge-Kutta method and shooting technique. The numerical formulas for radial and tangential shear stress, heat transfer coefficient in term of Nusselt number and dimensionless moment coefficient are presented. The influence of various physical parameters and couple stress parameter on the velocity field, temperature and pressure distributions are all examined numerically and discussed graphically. The following results can be drawn:The unsteadiness parameter decelerates the flow and temperature field over the rotating disk.The presence of couple stresses in the fluid enhances the fluid motion in tangential direction and weakens in radial and axial directions.The magnetic field opposes the fluid velocity in all directions i.e. radial, tangential and axial.There is a significant reduction in the temperature field due to an increase in Prandtl number and unsteadiness parameter.Pressure gradient decline while unsteadiness parameter, magnetic parameter and couple stress parameter increases.


Fractional calculus, in the understanding of its theoretical and real-world presentations in numerous regulations, for example, astronomy and manufacturing problems, is discovered to be accomplished of pronouncing phenomena owning long range memory special effects that are challenging to handle through traditional integer-order calculus. Nearby an increasing concentration has been in the modification of fractional calculus as a successful modelling instrument for complicated systems, contributing to innovative viewpoints in their dynamical investigation and regulator. This improvement in the methodical knowledge is established by an enormous quantity of evens developing on the subject, manuscripts, and presentations in the past years. Nevertheless, countless singularities still pose significant confronts to the apprehensive population and fractional calculus appears to be plausibly contestant to incorporate larger exemplars through detaching graceful dependent on the explanation of involvedness.This special issue contains papers about recent theoretical development and methods and applications results on the topics in almost all branches of sciences and engineering. We have received 56 papers during the submission period. Five were withdrawn; 34 were rejected including the papers submitted to the member of our editorial board. Only 17 good papers were accepted for publication.q-Sumudu transforms of q-analogues of Bessel functions, certain fractional integral formulas involving the product of generalized Bessel functions, and an expansion formula with higher-order derivatives for fractional operators of variable order were investigated in detail. A novel study underpinning construction of solution for fractional differential equations such as decomposition method for time fractional reactional-diffusion equation and high-order compact difference scheme for numerical solution of time fractional heat equation, a procedure to construct exact solutions of nonlinear fractional differential equations, were presented. An investigation on impulsive multiterm fractional differential equations and multiple positive solutions for nonlinear fractional boundary value problems were undertaken.The papers of this special issue cover some new algorithms and procedures designed to explore conventional, fractional, and time-scales differential equations of general interest. New understandings of existences and uniqueness theorems of some differential equations were also offered. In the following we give the brief summary of the content of the special issue. The existence and uniqueness theorems for impulsive fractional equations with the two-point and integral boundary conditions and sufficient condition on the fractional integral for the convergence of a function were presented. Besides the stability, boundedness, and Lagrange stability of fractional differential equation with initial time difference, stability of nonlinear Dirichlet BVPs governed by fractional Laplacian was proposed. A novel study on the singular perturbations fractional equations, analysis of a fractional-order couple model with acceleration in feelings, The editorial board trust that the set of nominated papers will offer readers an opportune renovate of significant investigation subjects and may also operate as a policy for encouraging additional contribution in this fast evolving ground.


Background. Malaria is an entrenched global health challenge particularly in the sub-Saharan African countries. However, in Ghana, little is known about the determinants of malaria prevalence among under-five children. As such, this study sought to examine the sociodemographic factors that determine malaria among under-five children in Ghana. Methods. This paper used secondary data drawn from the 2008 Ghana Demographic and Health Survey. Bivariate analysis and complementary log-log regression models were used to examine the determinants of malaria prevalence among under-five children in Ghana for the study period. Results. The results therefore revealed that region of residence, age of child, and ownership of mosquito net were the key predictors of malaria cases among under-five children in Ghana for the five-year period preceding the survey. Conclusion. It is therefore imperative that special education on prevention of malaria should be intensified by the National Malaria Control Programme in all the regions in order to reduce malaria prevalence particularly among under-five children in Ghana. Malaria is a major public health concern in the world and more especially among pregnant women and children because of their vulnerability. As such, malaria has been described as an entrenched global health challenge . The disGlobally, there were 216 million cases of malaria in 106 endemic countries and territories in the world in 2010, out of which 86 percent of the victims were children under five years of age. The world malaria report of 2011 shows an estimated 655,000 malaria deaths in the world, majority of which were under-five children from Africa . The WorMalaria is also a major threat to public health in Ghana and the burden of the disease is a challenge to child survival. It is also the leading cause of morbidity and mortality among children under five years in the country . BesidesA number of studies have been conducted on malaria among under-five children and had attributed the disease to nonuse of insecticide treated nets (ITNs) by care givers . Ahorlu This paper used secondary data drawn from the 2008 Ghana Demographic and Health Survey (GDHS) children's data file. The GDHS is a nationally representative survey for all women aged 15–49 and all men aged 15–59. The sample points cover households sampled from all over the country. The survey collected detailed reliable information on fertility levels, marriage, sexual activities, malaria, fertility preferences, awareness and use of family planning methods, awareness and behaviour regarding AIDS and other sexually transmitted infections . In acquThe GDHS was carried out by the Ghana Statistical Service (GSS), the Ghana Health Service (GHS), and ICF Macro International. The survey was conducted between September 8 and November 25, 2008, on a nationally representative sample of 12,323 households . Out of The statistical package STATA (version 11) was used to process the data. Two main levels of analysis were done. Firstly, bivariate analysis was done to determine proportions of malaria cases within the various selected variables. Hence, results were presented in frequencies and proportions. Secondly, complementary log-log regression model was applied to study the factors that determine malaria cases among under-five children. It was also used to predict the odds of malaria cases among the under-five children; hence, results had been presented in odds ratios (OR). This was done in four chronological models by adding factors in stages in order to identify consistent and robust predictors or determinants of malaria. Complementary log-log regression model was used because of asymmetric distribution of data in terms of malaria cases  and the In terms of regional variations, the highest proportion of malaria was found among children from the Brong Ahafo Region (27%) while the Ashanti Region was the second highest (25%) and the Western Region had the least proportion of malaria with about 11 percent. For religious affiliation, the highest proportion of malaria was found among children whose mothers had no religion (26.7%) while children of mothers who professed to be traditionalists or spiritualists had the least proportion of malaria of about 12 percent. Concerning ethnicity, the Mole-Dagbani mothers and those from other ethnic groups reported the highest proportion of malaria among under-five children  while the lowest was reported by Ewe mothers and Ga-Dangme mothers . The results from On mother's education, the highest proportion of malaria among under-five children was reported among children whose mothers had primary school education (22.7%) while mothers with higher education reported the lowest malaria cases among children (17.4%). The results from To examine the background variables that determine malaria cases among children under the age of five, four sequential multivariate models of complementary log-log were constructed . In the P < 0.001), Volta Region , Ashanti Region , Brong Ahafo Region , the Northern Region , and the Upper East  and West Regions  were more likely to have malaria cases compared to their counterparts from the Western Region.In both models, 3 and 4, malaria in children showed a significant relationship with the Central Region, Volta Region, Ashanti Region, Brong Ahafo Region, the Northern Region, and the Upper East and West Regions except the Greater Accra and the Eastern Regions. Thus, in the final model, under-five children from the Central Region , 24–35 months , 36–47 months , and 48–59 months  compared to their counterparts who were aged less than 12 months. In terms of ownership of mosquito net, children from households which owned mosquito nets were 0.694 (P < 0.05) times less likely to contract malaria compared to their counterparts from households which owned no mosquito net. However, factors including mother's level of education, religious affiliation, ethnicity, wealth status of household, mother's marital status, mother's age, type of residence, and sex of child had no significant relationship with malaria prevalence among under-five children in Ghana for the five-year period preceding the survey.Child's age was also one of the factors that had significant relationship with malaria among under-five children. The odds of malaria were quite higher among children aged 12–23 months (OR = 2.514, This paper sought to examine the factors that determine or predict malaria cases among under-five children in Ghana using a nationally representative secondary data drawn from the 2008 Ghana Demographic and Health Survey. The study revealed that malaria cases were fewer among children less than one year. This may be as a result of the fact that children below one year are protected from malaria because of the antibodies they acquire from their mothers during pregnancy . Male chFurthermore, the study revealed that more children from the rural areas had malaria cases than children from the urban areas. In a similar study in Nigeria, Uzochukwu et al.  also revStable marriages have also been identified to provide children with the best physical health outcomes . This stWith regard to the determinants of malaria cases, region of residence was found to have significant effect on malaria cases with children from the majority of the regions being more likely to contract malaria compared to children from the Western Region. The likelihood of malaria cases was found to be higher among children aged one and beyond. This higher likelihood of malaria observed among children aged 12 to 59 months could be as a result of nutrient deficiency in their diet which may render them vulnerable to malaria than those below 12 months who were still likely to be exclusively breast-fed. This is because it has been observed that micronutrient deficiencies among infants could impinge on their immune system, increasing their risk for malaria .The use of mosquito net has also been found in this study as a protective factor against malaria cases among under-five children in Ghana. In another study in Nigeria, Yusuf et al.  found thRegion of residence, age of child, and ownership of mosquito net were the key determinants or predictors of malaria cases among under-five children in Ghana for the survey period. Ghana National Malaria Control Programme with the aid of the government should conduct more malaria prevalence surveys in the various regions to identify the malaria hot spots so that malaria intervention programmes can be targeted in order to reduce any new cases. Mothers should also be entreated to provide exclusive breastfeeding for infants and provide good nutrition for older children in order to boost their immunity against infectious diseases including malaria. The distribution and use of insecticide treated mosquito nets should also be encouraged and intensified.


Endoscopic repair is considered the treatment of choice in cerebrospinal fluid (CSF) rhinorrhea. The aim of our study was to analyze the etiopathogenesis of CSF rhinorrhea, the outcome of treatment and the causes of failure in a developing-country setting.A retrospective review of patients treated with endoscopic repair for CSF rhinorrhea at a tertiary care hospital in southern India from January 2002 to December 2009 identified 36 patients, the majority of them being women. The defects were closed in three layers using fat, fascia lata and nasal mucosa along with a fibrin sealant in the majority of the patients. Per-operatively, a subarachnoid drain was placed in all patients. Patients were followed up for 1 year. Spontaneous onset of CSF rhinorrhea was noted in 61% of patients. The most common site of leak was found to be the left cribriform plate area. Hence the most common cause of CSF rhinorrhea in our study was spontaneous and the second most common was post-traumatic. Our success rate on the first attempt at endoscopic repair was 100%, with a recurrence rate of 6%. A large defect, failure of localization of the defect, or other co-morbid conditions such as chronic cough may be the most likely causes of recurrence of leak.Accurate localization of the site of lesion using a high-resolution computed tomography (CT) scan with magnetic resonance imaging (MRI) and confirmation of the site of leak by intraoperative Valsalva maneuver along with multilayered closure of the dural defect and post-operative lumbar drain appear to be essential for the successful endoscopic repair of CSF rhinorrhea.  Cerebrospinal fluid (CSF) rhinorrhea has been reported to be spontaneous or secondary to head trauma, surgery, neoplastic invasion, congenital malfor- mations; the most common causes being post-traumatic according to some authors and iatrogenic according to others ,2. The rA retrospective study of patients who presented in our unit with CSF rhinorrhea and underwent endoscopic repair was performed. Etiopathogenesis, outcome of treatment and causes of failure were noted. Our experience is presented in this article. A retrospective inpatient chart audit was performed for all cases of CSF leak repairs carried out in the ear, nose and throat (ENT) unit at Christian Medical College and Vellore Hospital from January 2002 to December 2009. All cases were subjected to a detailed history, regarding the duration of leak, mode of onset, etiology and history of meningitis. Following this, diagnostic nasal endoscopy was performed to confirm the side of leak and to rule out other nasal pathologies. Nasal endoscopy was not useful in identifying the exact site of the leak. Nasal secretion was collected and sent for glucose concentration analysis to explore the likelihood of CSF rhinorrhea. All patients had a high-resolution computed tomography (CT) scan , with adPatients were subjected to hypotensive general anesthesia. A lumbar drain was inserted and kept closed until the site of leak was identified. Fat and fascia lata were then harvested from the lateral side of the thigh. All operations were performed using standard endoscopic sinus surgery equipment without computer-assisted surgical navigation. The middle turbinate was excised and the suspected site of leak in the skull base was denuded of mucosa. The bulla ethmoidalis was opened in cases where the defect was found to be extending into the fovea ethmoidalis. The site of the leak was localized. In a few patients where an active leak was not seen, it was noted by Valsalva maneuver. The margins of the bony defect were then delineated .At this stage, the lumbar drain was opened and fat was then inserted into the defect. The fascia lata was placed over the defect and a prepared fibrin sealant consisting of lyophilized vapor heated sealer human protein concentrate (TISSEEL) was injected onto the edges of the fascia. The mucosa from the middle turbinate was then spread over it, and the remaining fibrin sealant was again injected around the edge of the harvested middle turbinate mucosa. In two patients, a piece of the bone from the excised middle turbinate was used to seal the defect in addition to the fascia. Surgicel was then spread over the fascia/mucosa layer, and finally a Bismuth Iodoform Paraffin Paste pack was placed in position.th and 7th post-operative day, respectively. Thigh sutures were removed on the 10th day. An endoscopic inspection of the operative site with removal of crusts was performed on the same day, leaving the operative site untouched. All patients were followed up for 6–12 months. Postoperatively, patients were advised to adhere to strict bed rest. They were also given TED stockings and subcutaneous low molecular weight heparin for 5 days postoperatively to prevent deep vein thrombosis. Stool softeners were also given.A lumbar drain and nasal pack were removed on the 5A total of 36 patients were identified in whom endoscopic CSF rhinorrhea repair was performed from January 2002 to December 2009. One patient had an additional external approach for frontal sinus CSF leak repair. Most patients were in their 30s, with the youngest being 8 months old and the oldest being 64 years. Twenty-eight of the subjects were women, and eight were men.Fifteen of the 36 patients had a right-sided leak, 18 had a left-sided leak, and three had bilateral leaks. It is also interesting to note that most of the post-traumatic leaks were left-sided. Twenty-two patients had a spontaneous onset of the CSF leak, while nine patients had a post-traumatic leak. Five patients were post-surgical: following functional endoscopic sinus surgery (FESS), excision of astrocytoma, meningocele, arachnoid cyst and hemangiopericytoma maxilla and skull base, respectively . The most common site of leak was the cribriform plate (61%), followed by isolated fovea ethmoidalis, and involvement of both cribriform plate and fovea. One patient had a posterior table of frontal sinus involvement and another had a leak in the lateral recess of the sphenoid sinus .Two patients had recurrent CSF leak 3 months after the initial endoscopic repair (6%). In the first patient who had a recurrence, the size of the bony defect was 3.5 cm with an intervening sliver of bone. In the second patient, although the size of the leak was only 1.5 cm, there was an associated history of persistent cough which required treatment. Both patients had their site of leak identified in the fovea ethmoidalis on revision surgery.CSF rhinorrhea occurs as a consequence of breakdown in the dura, arachnoid and a bony skull base defect, resulting in a fistula between the sub-arachnoid space and the nasal cavity.CSF rhinorrhea may occur directly through the anterior cranial fossa or indirectly from the middle or posterior fossa via the Eustachian tube. The diagnosis and localization of the leak is crucial for surgical management. The endoscopic examination of the nose is invaluable in confirming the site of leak prior to surgery. Preoperative assessment for the site of leak is performed using a high-resolution CT scan of the paranasal sinuses and anterior skull base. This is currently accepted as the imaging technique of choice. Additional MRI (with T2- weighted sequences) is indicated when parenchymal or meningeal herniation is suspected .3 consider intrathecal fluorescein as the most accurate modality for identification of the site of the leak. Intrathecal fluorescein, however, is controversial due to multiple reported complications (Banks ications . Seth inications . Presuttications . In our 7,8 for repair of defects greater than 3-4 cm. Additionally, co-morbid conditions such as chronic cough may contribute to raised intracranial tension and failure of the repair. The size of the defect appears to impact the surgical outcome, with larger defects likely to result in failure of repair and recurrent leaks. Composite osteomucosal or chondromucosal flaps have also been advocatedPresutti, in their 5-year retrospective study of 52 patients with endoscopic closure of CSF leak , had an The most common etiology of CSF rhinorrhea in our study was spontaneous, unlike reports from the West, and the condition is more often seen among women. Better results can be achieved when the following factors are taken into consideration: exact localization of site on MRI/CT prior to surgery, with intraoperative demonstration of the leak by Valsalva maneuver; a three-layer closure technique with fat, fascia, mucosa and fibrin sealant interposition is preferred for small leaks and a meticulous four-layer closure with use of cartilage to give added strength in the repair of large defects.


Despite the increased interest about tele-rehabilitation, virtual reality and outcome measures for stroke rehabilitation, surprisingly little research has been done to map and summarize the most common outcome measures used in tele-rehabilitation. For this review, we propose to conduct a systematic search of the literature that reports outcome measures used in tele-rehabilitation or virtual reality for stroke rehabilitation. Specific objectives include: 1) to identify the outcome measures used in tele-rehabilitation studies; 2) to describe the psychometric properties of the outcome measures in the included studies; 3) to describe which parts of the International Classification of Functioning are measured in the studies. Methods: we will conduct a comprehensive search of relevant electronic databases . The scoping review will include all study designs. Two reviewers will pilot-test the data extraction forms and will independently screen all the studies and extract the data. Disagreements about inclusion or exclusion will be resolved by consensus or by consulting a third reviewer. The results will be synthesized and reported considering the implications of the findings within the clinical practice and policy context. Dissemination: we anticipate that this scoping review will contribute to inform researchers and end-users , regarding the most appropriate outcome measures for tele-rehabilitation or virtual reality as well as help to identify gaps in current measures. Results will be disseminated through reports and open access journals, conference presentations, as well as newsletters, podcasts and meetings targeting all the relevant stakeholders. Tele-rehabilitation (TR) and virtual reality (VR) are alternative and innovative approaches of delivering rehabilitation services for stroke survivors . Tele-reSeveral tools have been developed to evaluate the consequences of stroke and the effectiveness of virtual realityand telerehabilitation interventions on stroke outcomes . EvidencFormer systematic reviews on tele-rehabilitation and virtual reality addressed the difficulties of finding evidence coming from the small number of eligible studies. Scoping reviews may overcome this problem since their approach may address other questions beyond those related to intervention effectiveness, and generate findings that can complement the findings of clinical trials.The scoping review will use a methodologically rigorous approach, guided by the Arksey and O’Malley framework from the University of York . The YorWhich tele-rehabilitation and virtual reality outcome measures are used and when are they administrated  following a stroke?Which measures are psychometrically sound and what are the author(s) trying to measure? .Which parts of the International Classification of Functioning are measured in the outcome measures?  and structures , activities and participation  and environmental factors .A possible limitation of scoping reviews is the quality of the included studies since generally it’s not assessed; to overcome this limitation a quality assessment will be conducted in parallel to the stages of the scoping review, which will be based on the CASP tools . Results of this activity will be qualitatively summarized and added to the main findings of the studyThe scoping review will include studies: 1) involving stroke patients; 2) describing a rehabilitation intervention using tele-rehabilitation and/or virtual reality; 3) written in English, French, Spanish, Italian or Portuguese. The exclusion criteria are: articles published in other languages; articles not reporting the outcome measures or only reporting laboratory measures or only reporting the development of the technology. The search will not be limited by study design. Two authors will be in charge for the assessment of the retrieved papers; disagreement about inclusion or exclusion of a specific paper based on the review of its abstract will be resolved by reaching a motivated consensus or consulting a third reviewer.The literature search will be performed by a librarian expert in the field of rehabilitation. The search will include the major databases in which rehabilitation articles are found: PubMed (until December 2014), EMBASE (until December 2014), Cochrane Library-The Cochrane Central Register of Controlled Trials (until January 2015), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (until December 2014) and PEDRO (until January 2015) to identify potentially relevant records. A combination of medical sub-headings (MeSH) and or keywords will be adapted as needed for each database (the details of the search strategy are available upon request).Data collection process and charting the data within the selected studiesData-exstraction forms will be developed based on the current literature in the field and on the research questions. A pilot test will be conducted using a subset of articles covering the research questions; changes may be necessary in the data extraction form during this validation phase in order to reach a final version. We expect to collect data on: 1) articles’ authors, 2) year of publication, 3) objective(s) of the study, 5) study design, 6) country 7) outcome measures reported; 8) psychometric properties of measures reported, and 9) participants’ characteristics ; 10) relevant International Classification of Functioning domains.; 11) period of time at which the measure is taken ; 12) technology used ; 13) details on tele-rehabilitation and/or virtual reality intervention and 14) outcome improvement.The outcome measures will be organized according to the domains of the international classification of functioning.Based on the recommendations by The results of the proposed scoping review are addressed primarily to clinicians and researchers in rehabilitation. In addition, the results will be disseminated to a larger audience including clinicians, policy makers, researchers and stakeholders and those interested in standardizing outcome measures for stroke tele-rehabilitation and virtual reality. Our research team will ensure broad dissemination of our findings through numerous knowledge translation strategies including podcasts, publications in open-access and peer-reviewed journals, conference presentations, web seminars and meetings including diverse audiences such as clinicians, stakeholders, researchers, healthcare managers, policy-makers and citizens, among others.


Bacillus thuringiensis israelensis (Bti) use against malaria and other vector species, larval source management could see a revival in the upcoming years. In this project we analyze the ecologic and health impacts as well as the cost effectiveness of larval source management under different larviciding scenarios in a health district in Burkina Faso.Malaria control is based on early treatment of cases and on vector control. The current measures for malaria vector control in Africa are mainly based on long-lasting insecticide treated nets (LLINs) and to a much smaller extent on indoor residual spraying (IRS). A third pillar in the fight against the malaria vector, larval source management (LSM), has virtually not been used in Africa since the ban of DDT in the 1960s. Within the light of recent WHO recommendations for The project is designed as prospective intervention study with duration of three years (2013–2015). Its spatial scale includes three arms of interventions and control, comprising a total of 127 villages and the district capital Nouna in the extended HDSS  of the Kossi province. Baseline data on mosquito abundance, parasitemia in U5 children, and malaria related morbidity and mortality are gathered over the project duration. Besides the outcome on ecologic and health parameters, the economic costs are seized and valued against the achieved health benefits.Risk map based, guided larvicide application might be a possibility to further decrease economic cost of LSM and facilitate its faster incorporation to integrated malaria control programs. Given the limited resources in many malaria endemic countries, it is of utmost importance to relate the costs of novel strategies for malaria prevention to their effect on the burden of the disease. Occurring costs and the impact on the health situation will be made comparable to other, existing intervention strategies, allowing stakeholders and policymakers decision making. Malaria is causing severe health and economic damage in Africa. An estimated 1.2 billion people worldwide were at high risk in 2012 , living mostly in the African Region (47%) and the Southeast Asia Region 37%) (7% (3). TAnopheles mosquito in malaria transmission was discovered more than 100 years ago, different control and eradication attempts have been undertaken. Besides adult vector control and exposure reduction, several strategies are based on vector larvae reduction such as habitat drainage or by targeting the vector larvae directly via insecticides or microbials. A promising approach that came up some 30 years ago is the use of bacteria-produced toxins such as Bacillus sphaericus (Bs) and Bacillus thuringiensis israelensis (Bti) that, if digested, kill the larval stages of vulnerable mosquito species  (VectoBac®).An approach elaborated within the project “Ecologic Malaria Reduction for Africa” (EMIRA) aims on complementing the commonly used integrated malaria control measures (Insecticide Treated Nets (ITNs), DDT residual spraying in houses against resting mosquitoes on walls, intermittent preventive treatment in pregnancy (IPTp), early diagnosis and treatment of malaria cases, and seasonal malaria chemoprevention) by treatment of mosquito breeding grounds with biological larvicides namely Bti based LSM, namely the treatment of habitats where larvae are immobile and concentrated, we try to proof feasible and efficient in the typical setting of a rural, sub Saharan area. We expect to reduce malaria transmission by decreasing vector abundance and achieve an impact on the malaria-induced morbidity and mortality. Furthermore, we hope to generate evidence that the incorporation of novel approaches, such as selective larviciding of the most productive breeding sites guided by remote-sensing-derived risk maps, can contribute to lower economic costs and hence increase opportunities for their use.These known advantages and possibilities of Lack of implementation of integrated malaria vector control strategies in sub-Saharan AfricaBti-based LSM in rural environmentsInsufficient data on the additional health benefit of Lack of reliable data on implementation costs of LSM in rural sub-Saharan Africa allowing per capita cost comparison with measures that are already in place (e.g. impregnated bed nets)Lack of implementation and testing of spatio-temporal malaria risk models in actual intervention measuresBti-based larviciding intervention in a complete health district in a developing country.It is feasible to run a The incurring costs per capita will be similar to those for the distribution of ITNs.There will be a significant health benefit to reflect in several outcome indicators.The use of remote sensing for selective larviciding in the most productive breeding sites can further cut back on intervention costs.Bti-based LSM on malaria vector densities, the transmission of malaria and burden of the disease. Evaluate the cost-effectiveness of satellite-based risk maps for a guided treatment of vector breeding sites  . RoutineThe project is designed as a prospective intervention study with a duration of 3 years (2013–2015). Its spatial scale includes three arms of interventions and control, comprising a total of 127 villages and the district capital Nouna in the extended HDSS of the Kossi province . BaselinExhaustive treatment of all detected breeding sites in and around 42 villages and the semi-urban district capital Nouna during the rainy season (extended for prevailing breeding sites). Larvicide application is performed using detailed maps of the villages and knowledge of the terrain.Guided treatment using remote-sensing-derived risk maps for 42 villages. The 50% of most productive breeding sites regarding their larval densities are treated selectively. Maps for steered treatment are based on a prediction model using high spatial resolution satellite imagery , 26. A 5Control arm with no performed larval control for 43 villages but collection of impact evaluation parameters .The three arms are distinguished by their level of intervention as follows:Bti every 10 days to reduce the number of emerging adult vectors. The larviciding runs as an added component to complement the integrated malaria control that is uniformly implemented in the study region . During the rainy season (June-September), local village-based teams perform the larvicide application and the ground surveillance of its efficacy. Teams of sprayers and entomologic technicians treat the breeding sites in a repetition cycle of 10 days. Existing infrastructures of other anti-malaria measures such as bed net distribution and basic medical treatment on the district level  facilitate an implementation and integration of this method. Information on proximity of houses to breeding sites is available via GIS databases that comprise the position of breeding sites and the geo-coordinates of all households within the HDSS area.The mosquito breeding sites are treated with All 127 rural study villages are regrouped into a total of nine clusters . These aAnopheles larval growth, while pollution, strong turbidity, and complete vegetation cover is a hindering factor. In the investigation area, there are pools and tarns during the rainy season, which can be of different appropriateness for vector breeding. In research projects prior to EMIRA in Burkina Faso and Senegal, methods to classify breeding sites by their anopheline larval productivity using satellite imagery were developed  that are positioned in four villages in each cluster. In each village, three sample points are chosen with one outdoor and one indoor light trap each. Data collection is performed every 14 days from May to November and collected mosquitoes are determined to species level.Measuring parasitemia in children aged less than 5 years: Two rounds of testing for malaria parasites are performed every year. Rapid Diagnostic Test (RDT) sets are used in children with increased temperature to test for malaria. For positive cases, a microscopy test is performed in the district hospital to determine blood parasite rates. The activity is carried out once before the onset of the rainy season and once during the time of highest infection, in August. A total of 19,700 children under five live within the total population, and sampling is performed in the calculated sample size of 385 children.Cases of death and morbidity reported by the HDSS and additional Community Key Informants (CKI). The HDSS data allow comparing death cases and morbidity attributable to malaria between study years and between treated and untreated villages in the same year. The HDSS data are provided on a regular basis three times per year. Morbidity cases are collected from the consultation registers in the health facilities since origins of patients are not available from the database of the health district.The effectiveness of the intervention measures is examined by the following key figures:The registration of incurred costs for baseline data collection and LSM implementation is conducted alongside the study. This study analyzes two different scenarios, full and guided partial larviciding, and compares those against each other. The analysis for full and guided intervention captures all resources used, comprising material, transport, and costs for scientific and field personnel. Furthermore, the inclusion of opportunity costs allows attribution of available means . The overall cost for running the project in a research setting will be equally captured as the pure LSM implementation costs. Assessment of the latter is important to calculate per capita cost for LSM and to compare its resource exigencies to other interventions such as impregnated bed nets. Cost efficiency of full and guided LSM will be evaluated by comparing with the registered health outcome parameters.The LSM is accompanied by a qualitative study component researching the perception and acceptability of LSM within the population. The perceived reduction in mosquito abundance and nuisance will be compared with the number of mosquitoes caught with light traps. Furthermore, the general acceptance and will of participation in a larviciding program will be registered to improve information and participation strategies.Malaria as the leading cause of death in wide parts of sub-Saharan Africa is in the scope of the global health priorities. EMIRA's cooperative and multidisciplinary approach is designed to evaluate the feasibility, added health benefit, and cost-effectiveness of novel tools for larval source management in these environments. With the current success of ITN programs in many parts of Africa, more and more areas that have previously been highly burdened with malaria, now show characteristics of low and focal malaria transmission and hence offer great opportunities for the implementation of LSM. Risk map-based, guided larvicide application might be a possibility to further decrease economic cost of LSM and facilitate its faster incorporation to integrated malaria control programs. Given the limited resources in many malaria endemic countries, it is of utmost importance to relate the costs of novel strategies for malaria prevention to their effect on the burden of the disease. Occurring costs and the impact on the health situation will be made comparable to other, existing intervention strategies, allowing stakeholders and policymakers decision-making. The project results, in particular the costs incurred and the expected positive effect on the health situation, are monitored and remitted to the Ministry of Health. Based on the outcomes of this project, the national authorities may solicit funds from other donors for the long-term implementation and scale-up for public policies in a later step.


Congenital heart defects (CHD) are the most common cause of death in children under the age of 1. Tetralogy of Fallot (TOF) is a severe CHD that results from developmental defects in the conotruncal outflow tract. Recently, a tissue-specific gene expression template (GET) was derived from microarray data that accurately characterized multiple normal human tissues. We used the GET to examine spatial, temporal, and a pathological condition (TOF) within a single organ, the heart. The GET, as previously defined, generally identified temporal and spatial differences in the cardiac tissue. Differences in the stoichiometry of the GET reflected the severe developmental disturbance associated with TOF. Our analysis suggests that the homoeostatic equilibrium assessed by the GET at the inter-organ level is generally maintained at the intra-organ level as well. With the advent of tools for whole transcriptome analysis, there has been great interest in defining the gene expression profile of normal tissues as well as pathological states in order to understand the genetic regulation of development and identify potential therapeutic targets -5. TheseCongenital heart defects (CHD) are the most common birth defect and are the highest cause of mortality in children under the age of 1. Tetralogy of Fallot (TOF) is a severe constellation of defects that results from a disruption of the communication pathways between the first and second heart fields at about 20 days of gestation. A multitude of genes and genetic networks contribute to the spatial and temporal specification required for proper embryological heart formation -11. VariThe complexity of the cardiac regulatory system controlling heart development is challenging, but it was recently shown that a gene expression template (GET) containing only 56 genes could be used as a molecular signature to accurately specify at least 24 different disease-free tissues , includiWe wondered if the expression pattern of the 56 genes comprising the GET defined by Hwang et al.  would prHwang et al.  used Afft test with Benjamini-Hochburg correction for multiple testing) in pairwise assessments among groups in order to determine what genes and/or pathways were driving divergence among sets of tissues  clearly demonstrated that the variability between the tissues (colon vs. heart) was greater than the intra-tissue variability Figure A. The PCWe analyzed ten randomly assembled groups of 54 genes to determine if their expression pattern might also reflect group differences. We saw no discernible pattern in the dendrograms generated from the random sets of genes and none of the groups were appropriately clustered (data not shown). Thus, the sensitivity of the previously derived GET to reflect tissue specificity and pathological conditions appears to also discriminate anatomically distinct regions within the heart.We compared the expression of the GET between adult RV and adult LV. There were just 18 genes with significant changes in expression between the two tissues , normally developing infant right ventricular tissue, and adult right ventricular tissue. The clustering algorithm accurately placed the right ventricular samples into their appropriate groups Figure . The fetTaken together, there were 32 genes that differed in expression in at least one of the comparisons among the three different normally developing RV datasets . Interestingly, the TOF RV tissues were more closely associated with adult LV and RV than to the age-matched controls. The TOF tissue was distinctly different from similarly aged, normally developing RV with 33 of the 54 genes examined having a statistically significant change in expression .Based on our analysis, the GET can be applied to pathologic tissues as well as normal tissues with great accuracy. Most interesting is the difference between the TOF RV and control-matched infant RV. This comparison has the most genes in the GET with a significant change in expression , eight infants with normally developing hearts, and three fetal samples . LifeNet Health is a non-profit regenerative medicine company that provides bioimplants and organs for transplantation. The comparison samples were matched for age to the study population, and all control subjects expired due to non-cardiac related causes as described in detail previously [Our subjects were children less than 1 year of age with TOF requiring surgical reconstruction. The diagnosis and anatomy were obtained by echocardiography and angiography and confirmed at the time of surgery. All microarray analyses were run on samples from sixteen infants with TOF who had normal chromosomes .In addition, exon array data was downloaded from the GEO derived from the right ventricular tissue of 4 adult subjects  and the We generated exon array data for this study using RNA extracted from the right ventricular tissue from 16 infants with tetralogy of Fallot, right ventricle from 8 typically developing age- and sex-matched comparison infants, and right ventricle from three fetal hearts . The exon arrays were all Affymetrix HuEx-1_0-st-v2 and gene expression levels were generated as a mean of all probes within the coding sequence of the gene. The raw data from our arrays have been deposited in the GEO (accession number to be supplied upon acceptance). Our arrays were run at the University of Kansas Medical Center-Microarray Facility (KUMC-MF) according to the manufacturer's protocols. The KUMC-MF is supported by the Kansas University-School of Medicine, KUMC Biotechnology Support Facility, the Smith Intellectual and Developmental Disabilities Research Center (HD02528), and the Kansas IDeA Network of Biomedical Research Excellence (RR016475). All of our array data has been deposited in the GEO and will be available after July 2014. However, we make the data available prior to this date upon request.a priori grouping was applied. We tested several algorithms for accuracy in clustering: average linkage with squared euclidian distance (averaged point-to-point distances to define cluster to cluster distance), complete linkage without squared euclidian distance , and single linkage (point-to-point distance of closest neighbors). The complete clustering algorithm without squaring the euclidian distance produced the best dendrogram, accurately reflecting group relationships with only one TOF sample associated with the normal infant RV. The average linkage algorithm correctly clustered most of the groups, but split the LV samples into two subgroups, one group with ten samples that were most closely associated with the TOF samples and four samples that were most closely associated with the RV samples. Adding colon samples also had the effect of causing separation of the LV samples regardless of the clustering algorithm .Click here for fileHierarchical clustering based on 54 genes of the gene expression template (GET). The clustering algorithm used a complete linkage algorithm without squaring the euclidian distance to establish the dendrogram.Click here for file


Africa bears 24% of the global burden of disease but has only 3% of the world’s health workers. Substantial variation in health worker performance adds to the negative impact of this significant shortfall. We therefore sought to identify interventions implemented in sub-Saharan African aiming to improve health worker performance and the contextual factors likely to influence local effectiveness.A systematic search for randomised controlled trials of interventions to improve health worker performance undertaken in sub-Saharan Africa identified 41 eligible trials. Data were extracted to define the interventions’ components, calculate the absolute improvement in performance achieved, and document the likelihood of bias. Within-study variability in effect was extracted where reported. Statements about contextual factors likely to have modified effect were subjected to thematic analysis. Interventions to improve health worker performance can be very effective. Two of the three trials assessing mortality impact showed significant reductions in death rates . Eight of twelve trials focusing on prescribing had a statistically significant positive effect, achieving an absolute improvement varying from 9% to 48%. However, reported range of improvement between centres within trials varied substantially, in many cases exceeding the mean effect. Nine contextual themes were identified as modifiers of intervention effect across studies; most frequently cited were supply-line failures, inadequate supervision or management, and failure to follow-up training interventions with ongoing support, in addition to staff turnover.Interventions to improve performance of existing staff and service quality have the potential to improve patient care in underserved settings. But in order to implement interventions effectively, policy makers need to understand and address the contextual factors which can contribute to differences in local effect. Researchers therefore must recognise the importance of reporting how context may modify effect size. Africa bears 24% of the global burden of disease but has only 3% of the world’s health workers . This reAn overview of strategies to maintain and improve health worker performance in low and middle income countries was previously published , but a sA number of Cochrane reviews address the effectiveness of specific interventions to improve healthcare systems and delivery. While some focus on low and middle-income countries, most include studies conducted in high income western countries and so their applicability to sub-Saharan Africa is questionable . A recenWe have therefore systematically identified trials carried out in sub-Saharan Africa and extracted available data on context, as well as absolute effect, to facilitate the use of the evidence by policy makers. By context, we mean local issues  reported by authors as having impacted on the effectiveness of the intervention assessed.In conducting the review we adhered to PRISMA guidelines . The aimThe initial electronic search is detailed in The Cochrane EPOC Group classification of interventions was used to categorise the components of each intervention . Risk ofA small number of trials were multi-arm, comparing a number of interventions, often cumulative (i.e. each extra intervention arm including the interventions in other arms). For these studies we report the comparison between the most and least intensive intervention. Many of the studies reported more than one outcome. In selecting the outcome to report in this analysis we applied the following criteria: the stated main objective of the study, the objectivity of the measurement of performance (e.g. observed performance was preferred to self-reported), and the anticipated impact . Three authors  independently identified the outcomes which they felt most closely reflected the stated objective and, if more than one, the most serious outcome in terms of impact. Initial inter-rater agreement in this assessment was high (35/41 studies complete agreement). If outcome at more than one time point was reported, we used the last time point in reporting effect.In line with our intention to make our findings useful to policy makers, we reported and defined four unique measures. The baseline performance is the pre-intervention performance in the intervention arm . The absolute change in the intervention group is the difference in the pre- and post-intervention performance in the intervention arm. The absolute difference between the change in the intervention group and the change in the control group is the difference in pre-and post-intervention performance or, if not measured, the difference in end performance. The within study range of change is the minimum and maximum change in performance in the different study sites where reported .Extracted data were entered and analysed using Microsoft Excel (2010). The statistical significance reported is the 2-tailed p-value calculated by the authors of the original paper to assess the likelihood that the observed difference in performance between the intervention and control arms could have arisen by chance. The precise value given therefore reflects the way in which the authors chose to report the chosen outcome  and so is an approximation of the statistical significance of the difference between baseline and absolute improvement in performance reported in the tables. However, in all but two trials this p-value was adjusted for clustering and co-variance when appropriate. If the authors reported only confidence intervals, the p-value was calculated from the standard error implicit in the reported intervals .Contextual effect modifiers were identified when authors incidentally reported factors beyond the intervention, which may have led to differences in outcome between randomisation units  within the trial, or contributed to the overall reported trial effect size. Data were identified from the results or discussion text of the reports. In five instances where study authors referred to qualitative publications, they were accessed to confirm and provide additional contextual data. For one identified trial, a post-hoc analysis report was also accessed , and relWe report the characteristics of trials, the main trial outcome data, and the contextual data reported by authors. We then present a qualitative analysis of themes emerging from the extracted contextual data.The 42 manuscripts reporting the 41 eligible trials identified are shown in Although seven trials were hospital-based, the majority of trials were conducted in primary care facilities, including some private clinics or dispensaries and some specialist clinics . The analysis of the elements of the intervention according to the EPOC classification shows that just over half the interventions (23/41) were multi-faceted, including three or more elements. The most frequent elements were educational material and meetings. About one-third (17/41) of the trials reported some form of prior assessment of local context to customise the intervention, but only in five was a formal theory of change presented. Five of the trials referred to a total of six accompanying qualitative papers in their discussions, of which four were available for analysis –61. We aHalf of the trials (23/41) were conducted in South Africa or Kenya with most of the rest in other East African countries . Only eiThere was substantial variation in the effect of these interventions ; for exaThe most frequent contextual factors cited by authors as influencing outcome were staff motivation, supervision and turnover. None of these studies reported the within-study heterogeneity between centres.There was again substantial variation in effect , rangingFive of the studies reported within study heterogeneity. Where the range of difference between paired intervention and control sites was reported ,44, thisTwo interventions to improve health worker performance achieved important reductions in mortality –in childThe within-study variability was reported for five trials. Where reported, the range in the difference between intervention and control sites in different strata exceeded mean effect ,31. The The results of the thematic analysis of contextual effect modifiers are summarised in …inadequately supported training, supervision and follow-up, which has resulted in their infrequent use by the prescribers”  were adapted to the [local] environment and... used locally relevant graphics to enhance engagement with low-literate women” [The poor effect in [regional] hospitals outside the capital could be due to potential contamination bias” [The environmental themes identified related to: material resources, patient and community factors, and concurrent health system interventions. The most frequently cited issue was “stock-outs”, such as failure of the supply chain for drugs (“ulation” ) althouge women” ). Finallon bias” ).Our review shows three important things. Firstly, it is possible to improve the performance of existing health workers serving in under-resourced health systems. Secondly, the success of an intervention in improving performance depends very much on local context, with differences reported between centres within trials. Thirdly, few trials have been undertaken in sub-Saharan Africa and even fewer have adopted methodologies which allow the effect of local context to be assessed (e.g. only a minority applied a theory of change model or reported difference in effect between participating centres).The wide range of interventions assessed and outcomes measured in very different settings means that a simple comparison of relative effect has limited policy relevance. However, the positive performance of interventions to improve prescribing in 8/12 included trials is policy relevant (even if this is because it is a straightforward care function to target and measure). The parallel contextual observation that drug “stock-outs” were a frequent cause of variation in the within-study effect also emphasises the policy importance of securing the medicines supply-chain.The fact that the range of performance improvement exceeded the mean in many trials reporting this information is perhaps the most important observation. However, we are not the first to note the modifying effect of local context on outcome and the limited policy utility of focusing on mean effect. Others have previously stressed that triallists should give better information on contextual effects  and toolThe informal way in which contextual data were reported in our included trials weakens the generalisability of our findings while also reflecting the lack of systematic effort to report and understand aspects of context which influence the effect of interventions. We could only extract what was reported incidentally, and this is likely to be incomplete. Despite this, the frequency with which the same contextual issues recurred in different manuscripts is consistent with the existing literature and echoes the context elements of the PARIHS framework . The theIn order to know what will work locally, and to implement any intervention effectively, policy makers need to understand and address the specific contextual factors which contribute to differences in effect sizes seen in trials. To implement the “knowledge to action cycle” promoted by the Canadian Institute of Health Research, it is essential to identify the local barriers and facilitators likely to impact on the effectiveness of an intervention , and to In other words, those who undertake trials need to recognise the importance of providing sufficient evidence to make clear whether intervention X will work in setting Y. Our results show that interventions to improve the performance of existing health workers have the potential to impact very positively on patient morbidity and mortality in an underserved sub-Saharan context. The importance of local contextual influence in intervention trials should be reflected in both trial reporting, and in intervention planning and design.An initial protocol for the review was registered with PROSPERO 2014:CRD42014007391.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOC)Click here for additional data file.S1 Text(PDF)Click here for additional data file.S2 Text(DOCX)Click here for additional data file.


The urogenital tract is a rare origin of laryngeal metastasis; transitional cell carcinoma with laryngeal metastases had never been reported previously. In this paper, we describe the clinical and pathological characteristics, evolution, and treatment of the first reported case of a laryngeal metastasis of a TCC followed by a brief review of the literature. Transitional cell carcinoma (TCC) of the renal pelvis accounts for approximately 5–7% of all urothelial tumors . It usuaA 70-year-old male patient was referred to our clinic for a new onset of hematuria, fatigue, and weight loss. Clinical exam was strictly normal. Contrast enhanced abdominal and pelvic CT scan demonstrated a renal mass classified Bosniak V. Total left nephrectomy revealed a necrotic mass determined as stage III TCC . Subsequently, the patient received adjuvant chemotherapy of Gemcitabine and Cisplatin. One month later, the patient reported a progressive onset of low grade dysphonia and dysphagia, without signs of systemic symptoms. Clinical exam revealed a solid and painless cervical mass in contact with the right thyroid lobe. Initial laboratory testing showed no abnormalities. Cervical CT scan demonstrated an erosion of the right thyroid cartilage at the level of the glottis and the supraglottic regions attributed to a mass arising from the right lateral laryngeal wall. This lesion was solely metabolically hyperactive (SUV = 6.6) on PET-CT scan. Transcutaneous Trucut biopsy revealed a well differentiated TCC with prominent pleomorphic nuclei on hematoxylin and eosin stain. Immunohistochemistry was diffusely positive for CK 5/6/7, thus closely resembling the bladder tumor pattern of our patient. Salvage chemotherapy with vinflunine was initiated. Unfortunately, the disease progressed with aggravation of the dyspnea until the patient's death three weeks later.Tumors of the urogenital tract are a rare origin of laryngeal metastasis but may occur even years after complete remission. This is attributed to the high metastatic potential of this tumor in the presence of a highly vascularized tissue. The literature describes rare cases of renal cell carcinoma metastasizing to the larynx but reports of TCC with laryngeal metastasis are inexistent . LaryngeMetastasis to the larynx is determined by its anatomic characteristics. Effectively, the anatomic distribution of the vascular and lymphatic circulation accounts for the rare occurrence of laryngeal seeding and renders the supraglottic and subglottic region the most common sites of metastases . DescribTreatment of metastatic kidney cancers relies mainly on the site of metastasis and the performance status of the patient . WhereasTo our knowledge, this is the first case of laryngeal metastasis from TCC of the renal pelvis to be reported in the literature. The particularity of this case resides in the presence of a solitary laryngeal metastasis where such a finding may be mistaken for a primary tumor of the larynx. The core tip of this case is to maintain a high index of suspicion for laryngeal metastasis in patients with laryngeal symptoms and a past history of cancer. Early detection allows appropriate treatment of this unusual metastatic site.


Kawasaki disease is the second most common systemic vasculitis of childhood and may result in life-threatening coronary artery abnormalities in up to 25% of untreated patients. Adolescents often present with an atypical/incomplete presentation of KD with a delayed diagnosis. Kawasaki Shock syndrome (KDSS) is a rare KD presentation and has been recently defined as the presence of any of the following conditions: systolic hypotension (< -2 SD blood pressure defined for age and sex), a decrease in systolic blood pressure from baseline of >20% or clinical signs of poor perfusion with accompanying features of KD .To describe a case of KDSS and to increase awareness for this rare condition among paediatric rheumatologist and intensivists.We report the case of 15-year-old boy presenting with atypical KD complicated by severe shock syndrome and successfully treated with high-dose intravenous immunoglobulins (IVIG).A 15-year-old boy presented to another hospital after four days of high-grade fever, diffuse abdominal pain, diarrhoea and a maculo-papular cutaneous rash. He received antibiotic therapy and underwent laparoscopic abdominal exploration in the suspicion of acute appendicitis, which was ruled out. The postoperative period was complicated by fever persistence and a by general clinical worsening with clinical signs of shock and of left ventricular dysfunction; a presumptive diagnosis of viral myocarditis was made and the boy was transferred to our ICU where he required mechanical ventilation, fluid resuscitation and inotropic support. Microbiological test failed to identify any infectious agent. Because of the persistence of high grade fever, the sequential appearance of other four KD criteria  and the demonstration of left coronary artery hyperechogenicity, a diagnosis of KDSS was made and he was administered two courses of IVIG with rapid improvement. Eventually he was discharged with low-dose aspirin; two weeks later he showed periungual peeling of fingers and toes. No further complications appeared, and at last follow up visit, 24 months after diagnosis, he was completely asymptomatic with normal laboratory tests and echo-cardiogram.KDSS is a rare aetiology for shock in childhood; the diagnosis could be missed because of its atypical presentation. Because of the need for proper diagnosis and rapid treatment, paediatricians and paediatric intensivists should maintain a high index of suspicion.None declared