The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study.

BACKGROUND The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030. METHODS We developed a simulation model for HIV and applied it to each sub-Saharan African country. We used the WHO country intelligence database to estimate the number of adult patients receiving antiretroviral therapy from 2005 to 2014. We fitted the number of adult patients receiving antiretroviral therapy to observed estimates, and predicted first-line and second-line needs between 2015 and 2030. We present results for sub-Saharan Africa, and eight selected countries. We present 18 scenarios, combining the availability of viral load monitoring, speed of antiretroviral scale-up, and rates of retention and switching to second-line. HIV transmission was not included. FINDINGS Depending on the scenario, 8·7-25·6 million people are expected to receive antiretroviral therapy in 2020, of whom 0·5-3·0 million will be receiving second-line antiretroviral therapy. The proportion of patients on treatment receiving second-line therapy was highest (15·6%) in the scenario with perfect retention and immediate switching, no further scale-up, and universal routine viral load monitoring. In 2030, the estimated range of patients receiving antiretroviral therapy will remain constant, but the number of patients receiving second-line antiretroviral therapy will increase to 0·8-4·6 million (6·6-19·6%). The need for second-line antiretroviral therapy was two to three times higher if routine viral load monitoring was implemented throughout the region, compared with a scenario of no further viral load monitoring scale-up. For each monitoring strategy, the future proportion of patients receiving second-line antiretroviral therapy differed only minimally between countries. INTERPRETATION Donors and countries in sub-Saharan Africa should prepare for a substantial increase in the need for second-line drugs during the next few years as access to viral load monitoring improves. An urgent need exists to decrease the costs of second-line drugs. FUNDING World Health Organization, Swiss National Science Foundation, National Institutes of Health.

Evidence for Emergency Vaccination Having Played a Crucial Role to Control the 1965/66 Foot-and-Mouth Disease Outbreak in Switzerland.

Foot-and-mouth disease (FMD) is a highly contagious disease that caused several large outbreaks in Europe in the last century. The last important outbreak in Switzerland took place in 1965/66 and affected more than 900 premises and more than 50,000 animals were slaughtered. Large-scale emergency vaccination of the cattle and pig population has been applied to control the epidemic. In recent years, many studies have used infectious disease models to assess the impact of different disease control measures, including models developed for diseases exotic for the specific region of interest. Often, the absence of real outbreak data makes a validation of such models impossible. This study aimed to evaluate whether a spatial, stochastic simulation model (the Davis Animal Disease Simulation model) can predict the course of a Swiss FMD epidemic based on the available historic input data on population structure, contact rates, epidemiology of the virus, and quality of the vaccine. In addition, the potential outcome of the 1965/66 FMD epidemic without application of vaccination was investigated. Comparing the model outcomes to reality, only the largest 10% of the simulated outbreaks approximated the number of animals being culled. However, the simulation model highly overestimated the number of culled premises. While the outbreak duration could not be well reproduced by the model compared to the 1965/66 epidemic, it was able to accurately estimate the size of the area infected. Without application of vaccination, the model predicted a much higher mean number of culled animals than with vaccination, demonstrating that vaccination was likely crucial in disease control for the Swiss FMD outbreak in 1965/66. The study demonstrated the feasibility to analyze historical outbreak data with modern analytical tools. However, it also confirmed that predicted epidemics from a most carefully parameterized model cannot integrate all eventualities of a real epidemic. Therefore, decision makers need to be aware that infectious disease models are useful tools to support the decision-making process but their results are not equal valuable as real observations and should always be interpreted with caution.

Comparative cost-effectiveness of Option B+ for prevention of mother-to-child transmission of HIV in Malawi.

OBJECTIVE To estimate the cost-effectiveness of prevention of mother-to-child transmission (MTCT) of HIV with lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') compared with ART during pregnancy or breastfeeding only unless clinically indicated ('Option B'). DESIGN Mathematical modelling study of first and second pregnancy, informed by data from the Malawi Option B+ programme. METHODS Individual-based simulation model. We simulated cohorts of 10 000 women and their infants during two subsequent pregnancies, including the breastfeeding period, with either Option B+ or B. We parameterized the model with data from the literature and by analysing programmatic data. We compared total costs of antenatal and postnatal care, and lifetime costs and disability-adjusted life-years of the infected infants between Option B+ and Option B. RESULTS During the first pregnancy, 15% of the infants born to HIV-infected mothers acquired the infection. With Option B+, 39% of the women were on ART at the beginning of the second pregnancy, compared with 18% with Option B. For second pregnancies, the rates MTCT were 11.3% with Option B+ and 12.3% with Option B. The incremental cost-effectiveness ratio comparing the two options ranged between about US$ 500 and US$ 1300 per DALY averted. CONCLUSION Option B+ prevents more vertical transmissions of HIV than Option B, mainly because more women are already on ART at the beginning of the next pregnancy. Option B+ is a cost-effective strategy for PMTCT if the total future costs and lost lifetime of the infected infants are taken into account.

Interstellar neutral helium in the heliosphere from Interstellar Boundary Explorer observations. III. Mach number of the flow, velocity vector, and temperature from the first six years of measurements

We analyzed observations of interstellar neutral helium (ISN He) obtained from the Interstellar Boundary Explorer (IBEX) satellite during its first six years of operation. We used a refined version of the ISN He simulation model, presented in the companion paper by Sokol et al. (2015b), along with a sophisticated data correlation and uncertainty system and parameter fitting method, described in the companion paper by Swaczyna et al. We analyzed the entire data set together and the yearly subsets, and found the temperature and velocity vector of ISN He in front of the heliosphere. As seen in the previous studies, the allowable parameters are highly correlated and form a four-dimensional tube in the parameter space. The inflow longitudes obtained from the yearly data subsets show a spread of similar to 6 degrees, with the other parameters varying accordingly along the parameter tube, and the minimum chi(2) value is larger than expected. We found, however, that the Mach number of the ISN He flow shows very little scatter and is thus very tightly constrained. It is in excellent agreement with the original analysis of ISN He observations from IBEX and recent reanalyses of observations from Ulysses. We identify a possible inaccuracy in the Warm Breeze parameters as the likely cause of the scatter in the ISN He parameters obtained from the yearly subsets, and we suppose that another component may exist in the signal or a process that is not accounted for in the current physical model of ISN He in front of the heliosphere. From our analysis, the inflow velocity vector, temperature, and Mach number of the flow are equal to lambda(ISNHe) = 255 degrees.8 +/- 0 degrees.5, beta(ISNHe) = 5 degrees.16 +/- 0 degrees.10, T-ISNHe = 7440 +/- 260 K, nu(SNHe) = 25.8 +/- 0.4 km s(-1), and M-ISNHe = 5.079 +/- 0.028, with uncertainties strongly correlated along the parameter tube.

Role of Neurogranin in the regulation of calcium binding to Calmodulin

Role of Neurogranin in the regulation of calcium binding to Calmodulin Anuja Chandrasekar, B.S Advisor: M. Neal Waxham, Ph.D The overall goal of my project was to gain a quantitative understanding of how the interaction between two proteins neurogranin (RC3) and calmodulin (CaM) alters a fundamental property of CaM. CaM, has been extensively studied for more than four decades due to its seminal role in almost all biological functions as a calcium signal transducer. Calcium signals in cardiac and neuronal cells are exquisitely precise and enable activation of some processes while down-regulating others. CaM, with its four calcium binding sites, serves as a central component of calcium signaling in these cells. It is aided in this role as a regulatory hub that differentially activates targets in response to a calcium flux by proteins that alter its calcium binding properties. Neurogranin, also known as RC3, is a member of a family of small neuronal IQ (SNIQ) domain proteins that was originally thought to play a ‘capacitive’ role by sequestering CaM until a calcium influx of sufficient intensity arrived. However, based on earlier work in our lab on neurogranin, we believe that this protein plays a more nuanced role in neurons than simply acting as a CaM buffer. We believe that neurogranin is one of the proteins which, by altering the kinetics of calcium binding allow CaM to decode a variety of signals with fine precision. To quantify the interaction between CaM, neurogranin and calcium, I used biophysical techniques and computational simulations. From my results, I conclude that neurogranin finely regulates the proportion of calcium-saturated CaM and thereby directs CaM’s target specificity.

Estimación de la evapotranspiración real regional a partir de datos satelitales

El objetivo del presente trabajo fue determinar la Evapotranspiración real (ETR) a nivel regional utilizando la información del satélite meteorológico NOAA-AVHRR y comparar los resultados obtenidos con los calculados a partir de un modelo de simulación de balance hídrico. Para la estimación de la ETR se analizaron 30 imágenes que abarcan el oasis Norte de Mendoza. Con la información de los canales C1 (Visible) y C2 (IRC) se obtuvo el índice verde normalizado (NDVI), a través del cual se siguió la evolución anual de la vegetación y con la correspondiente al Infrarrojo térmico (C4 y C5) se calculó la Temperatura de superficie (Ts) por el método Split - Windows Luego se vinculó la Ts calculada por teledetección con la temperatura del aire (Ta), para finalmente calcular la suma acumulada de las diferencias entre Ts y Ta, conocida como SDD (stress degree day) que permite estimar globalmente las características de stress hídrico a nivel regional. Conociendo (Ts-Ta) se estimó la ETR a partir de la radiación neta y de los coeficientes A y B que se estimaron según las características de la cobertura vegetal, aplicando una relación simplificada a partir del balance de energía, desarrollado por Jackson (1977) y Seguin (1983) según la ecuación: ETR = Rn + A -B ( Ts - Ta ) Posteriormente, se incluyó en los cálculos los valores de Emisividad y se hizo variar el coeficiente B de acuerdo a la ocupación del suelo en cada uno de los polígonos en que fue dividida el área de estudio. En la etapa final se compararon estadísticamente los datos de ETR estimados por los distintos métodos con los simulados por el modelo y se obtuvo como conclusión final que: la estimación de la ETR a nivel regional mediante datos satelitales, se adapta muy bien a la mayoría de los casos y es sencilla de calcular, por lo que la metodología desarrollada es fácilmente extrapolable a otros oasis de la región.

El CIFOT como apoyo a la tarea empresarial : the CIFOT as support to the business task

Empresas como HEXA S.A. desean introducir SIG como elemento para incrementar el valor agregado de los proyectos de consultoría que realizan. Tal es el caso del trabajo encomendado por ellos al CIFOT titulado Esquema hidromorfológico de la cuenca del río Tunuyán Superior y clasificación de Usos del Suelo del Oasis Centro Oeste; Provincia de Mendoza. Se unifica en un único modelo digital una serie de cartas topográficas (IGM) digitalizan diversos niveles de información (curvas de nivel, hidrografía de la cuenca del río Tunuyán), red de caminos y su jerarquía. A partir de la base de datos lograda, se generan mapas temáticos de cada cuenca, apoyados con imágenes satelitales Landsat TM, que permiten identificar cobertura nivo- glacial y usos del suelo en el Oasis. Con esta información la empresa obtiene un modelo de simulación del Río Tunuyán para predecir el caudal que conduciría el río ante determinadas nevadas, por ejemplo. Se propone además un modelo de SIG para el monitoreo de la zona.

Producción de cerezo en Mendoza : viabilidad técnico-económica, basada en un modelo de simulación

Se plantea el problema de la correlación existente entre la factibilidad técnico-económica del cultivo del cerezo y su ubicación en las diferentes zonas de cultivo en la Provincia de Mendoza. El objetivo es la determinación de las localizaciones más convenientes. Se ha observado el comportamiento del cultivo del cerezo, en un periodo de 15 años, en varias zonas de la Provincia de Mendoza, analizando los resultados desde un enfoque de aptitud ecológica y de evaluación económica. Para ello, se ha elaborado un modelo de simulación que abarca las principales variables ecológicas y los resultados económicos de precios y costos de cosecha. Resalta, en los resultados, la contradicción entre aptitudes ecológicas y económicas. En las zonas tradicionales de cultivo se obtienen mejores rendimientos por ha, pero el ingreso neto es menor que en las más templadas y precoces del Este de Mendoza, implantadas recientemente con nuevos cultivares, como Marvin Brooks, New Star, Gardner, Celeste y otros que logran, como primicias, precios mucho más altos en el mercado. Este resultado permite aconsejar a los productores sobre los lugares y los cultivares más convenientes para los nuevos cerezales.

Simulating heterogeneous multinational firms

This paper develops a micro-simulation framework for multinational entry and sales activities across countries. The model is based on Eaton, Kortum, and Kramarz's (2010) quantitative trade model adapted towards multinational production. Using micro data on Japanese manufacturing firms, we first stylize the empirical regularities of multinational entry and sales activity and estimate the model's structural parameters with simulated method of moments. We then demonstrate that our adapted model is able to replicate important dimensions of the in-sample moments conditioned in our estimation strategy. Importantly, it is able to replicate activity under an economic period with a far different level of FDI barriers than was conditioned upon in our estimation sample. Overall, our research highlights the richness of the simulation framework for performing counterfactual analysis of various FDI policies.

Two-polar growth strategy in Myanmar : seeking "high" and "balanced" development

The Thein Sein government of Myanmar seeks higher and balanced economic growth. This is a challenge for the government since some economic literature identifies a trade-off between higher economic growth and better regional equality, especially for countries in the early stages of development. In this paper, we propose a two-polar growth strategy as one that includes both "high" and "balanced" growth. The first growth pole is Yangon, and the second is Mandalay. Nay Pyi Taw, the national capital, will develop as an administrative centre, not as an economic or commercial one. We also propose border development with enhanced connectivity with richer neighboring countries as a complementary strategy to the two growth poles. Effects of the two-polar growth strategy with border development are tested using a Geographical Simulation Model (GSM).

Service liberalization in Lao PDR

Service liberalization is emerging as a high-priority issue in various parts of the world for mega free trade agreements as well as national policy. Lao PDR is no exception. To examine the level of service liberalization in Lao PDR, we first compare the Hoekman Indices of Lao PDR, Cambodia, and Vietnam on the ASEAN Framework Agreement on Services (AFAS 8). Lao PDR has lower commitment in many subsectors. In particular, we list the sectors in which Lao PDR made a lower commitment than Cambodia and Vietnam in Mode 3 (supply of services through commercial establishments abroad). Second, a simulation analysis using the Geographical Simulation Model (IDE-GSM) from the Institute of Developing Economies at the Japan External Trade Organization (IDE-JETRO) reveals how service liberalization benefits the economic development of Lao PDR. The two analyses clearly reveal that it is essential for Lao PDR to promote further service liberalization since such liberalization will contribute to the country's development.

Economic impacts of the Kra Canal : an application of the automatic calculation of sea distances by a GIS

A plan to construct a canal through the Kra Isthmus in Southern Thailand has been proposed many times since the 17th century. The proposed canal would become an alternative route to the over-crowded Straits of Malacca. In this paper, we attempt to utilize a Geographical Information System (GIS) to calculate the realistic distances between ports that would be affected by the Kra Canal and to estimate the economic impact of the canal using a simulation model based on spatial economics. We find that China, India, Japan, and Europe gain the most from the construction of the canal, besides Thailand. On the other hand, the routes through the Straits of Malacca are largely beneficial to Malaysia, Brunei, and Indonesia, besides Singapore. Thus, it is beneficial for all ASEAN member countries that the Kra Canal and the Straits of Malacca coexist and complement one another.

An investigation of the performance of a new Mechanical thrombectomy device using Bond Graph modelling: application to the extraction of blood clots in the middle cerebral artery

A number of thrombectomy devices using a variety of methods have now been developed to facilitate clot removal. We present research involving one such experimental device recently developed in the UK, called a ‘GP’ Thrombus Aspiration Device (GPTAD). This device has the potential to bring about the extraction of a thrombus. Although the device is at a relatively early stage of development, the results look encouraging. In this work, we present an analysis and modeling of the GPTAD by means of the bond graph technique; it seems to be a highly effective method of simulating the device under a variety of conditions. Such modeling is useful in optimizing the GPTAD and predicting the result of clot extraction. The aim of this simulation model is to obtain the minimum pressure necessary to extract the clot and to verify that both the pressure and the time required to complete the clot extraction are realistic for use in clinical situations, and are consistent with any experimentally obtained data. We therefore consider aspects of rheology and mechanics in our modeling.

Safety assessment of underground vehicles passing over highly resilient straight tracks in the presence of a broken rail

In this paper, vehicle-track interaction for a new slab track design, conceived to reduce noise and vibration levels has been analyzed, assessing the derailment risk for trains running on curved track when encountering a broken rail. Two different types of rail fastening systems with different elasticities have been analysed and compared. Numerical methods were used in order to simulate the dynamic behaviour of the train-track interaction. Multibody system (MBS) modelling techniques were combined with techniques based on the finite element method (FEM). MBS modelling was used for modelling the vehicle and FEM for simulating the elastic track. The simulation model was validated by comparing simulated results to experimental data obtained in field testing. During the simulations various safety indices, characteristic of derailment risk, were analysed. The simulations realised at the maximum running velocity of 110 km/h showed a similar behaviour for several track types. When reducing the running speed, the safety indices worsened for both cases. Although the worst behaviour was observed for the track with a greater elasticity, in none of the simulations did a derailment occur when running over the broken rail.

Improved design of an overhead rail current conductor for application in underground lines

Overhead rail current collector systems for railway traction offer certain features, such as low installation height and reduced maintenance, which make them predominantly suitable for use in underground train infrastructures. Due to the increased demands of modern catenary systems and higher running speeds of new vehicles, a more capable design of the conductor rail is needed. A new overhead conductor rail has been developed and its design has been patented [13]. Modern simulation and modelling techniques were used in the development approach. The new conductor rail profile has a dynamic behaviour superior to that of the system currently in use. Its innovative design permits either an increase of catenary support spacing or a higher vehicle running speed. Both options ensure savings in installation or operating costs. The simulation model used to optimise the existing conductor rail profile included both a finite element model of the catenary and a three-dimensional multi-body system model of the pantograph. The contact force that appears between pantograph and catenary was obtained in simulation. A sensitivity analysis of the key parameters that influence in catenary dynamics was carried out, finally leading to the improved design.