The Cost-Effectiveness of Monitoring Strategies for Antiretroviral Therapy of HIV Infected Patients in Resource-Limited Settings: Software Tool.

BACKGROUND The cost-effectiveness of routine viral load (VL) monitoring of HIV-infected patients on antiretroviral therapy (ART) depends on various factors that differ between settings and across time. Low-cost point-of-care (POC) tests for VL are in development and may make routine VL monitoring affordable in resource-limited settings. We developed a software tool to study the cost-effectiveness of switching to second-line ART with different monitoring strategies, and focused on POC-VL monitoring. METHODS We used a mathematical model to simulate cohorts of patients from start of ART until death. We modeled 13 strategies (no 2nd-line, clinical, CD4 (with or without targeted VL), POC-VL, and laboratory-based VL monitoring, with different frequencies). We included a scenario with identical failure rates across strategies, and one in which routine VL monitoring reduces the risk of failure. We compared lifetime costs and averted disability-adjusted life-years (DALYs). We calculated incremental cost-effectiveness ratios (ICER). We developed an Excel tool to update the results of the model for varying unit costs and cohort characteristics, and conducted several sensitivity analyses varying the input costs. RESULTS Introducing 2nd-line ART had an ICER of US$1651-1766/DALY averted. Compared with clinical monitoring, the ICER of CD4 monitoring was US$1896-US$5488/DALY averted and VL monitoring US$951-US$5813/DALY averted. We found no difference between POC- and laboratory-based VL monitoring, except for the highest measurement frequency (every 6 months), where laboratory-based testing was more effective. Targeted VL monitoring was on the cost-effectiveness frontier only if the difference between 1st- and 2nd-line costs remained large, and if we assumed that routine VL monitoring does not prevent failure. CONCLUSION Compared with the less expensive strategies, the cost-effectiveness of routine VL monitoring essentially depends on the cost of 2nd-line ART. Our Excel tool is useful for determining optimal monitoring strategies for specific settings, with specific sex-and age-distributions and unit costs.

Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts.

BACKGROUND HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004-2013. METHODS Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. FINDINGS Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine VL, 1·21 (1·13-1·30) for targeted VL and 0·49 (0·43-0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114-133 cells/µl). INTERPRETATION Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing.

Monitoring the temporal development of natural hazard risks as a basis indicator for climate change adaptation.

The potential effects of climatic changes on natural risks are widely discussed. But the formulation of strategies for adapting risk management practice to climate changes requires knowledge of the related risks for people and economic values. The main goals of this work were (1) the development of a method for analysing and comparing risks induced by different natural hazard types, (2) highlighting the most relevant natural hazard processes and related damages, (3) the development of an information system for the monitoring of the temporal development of natural hazard risk and (4) the visualisation of the resulting information for the wider public. A comparative exposure analysis provides the basis for pointing out the hot spots of natural hazard risks in the province of Carinthia, Austria. An analysis of flood risks in all municipalities provides the basis for setting the priorities in the planning of flood protection measures. The methods form the basis for a monitoring system that periodically observes the temporal development of natural hazard risks. This makes it possible firstly to identify situations in which natural hazard risks are rising and secondly to differentiate between the most relevant factors responsible for the increasing risks. The factors that most influence the natural risks could be made evident.

Future water quality monitoring--adapting tools to deal with mixtures of pollutants in water resource management.

Environmental quality monitoring of water resources is challenged with providing the basis for safeguarding the environment against adverse biological effects of anthropogenic chemical contamination from diffuse and point sources. While current regulatory efforts focus on monitoring and assessing a few legacy chemicals, many more anthropogenic chemicals can be detected simultaneously in our aquatic resources. However, exposure to chemical mixtures does not necessarily translate into adverse biological effects nor clearly shows whether mitigation measures are needed. Thus, the question which mixtures are present and which have associated combined effects becomes central for defining adequate monitoring and assessment strategies. Here we describe the vision of the international, EU-funded project SOLUTIONS, where three routes are explored to link the occurrence of chemical mixtures at specific sites to the assessment of adverse biological combination effects. First of all, multi-residue target and non-target screening techniques covering a broader range of anticipated chemicals co-occurring in the environment are being developed. By improving sensitivity and detection limits for known bioactive compounds of concern, new analytical chemistry data for multiple components can be obtained and used to characterise priority mixtures. This information on chemical occurrence will be used to predict mixture toxicity and to derive combined effect estimates suitable for advancing environmental quality standards. Secondly, bioanalytical tools will be explored to provide aggregate bioactivity measures integrating all components that produce common (adverse) outcomes even for mixtures of varying compositions. The ambition is to provide comprehensive arrays of effect-based tools and trait-based field observations that link multiple chemical exposures to various environmental protection goals more directly and to provide improved in situ observations for impact assessment of mixtures. Thirdly, effect-directed analysis (EDA) will be applied to identify major drivers of mixture toxicity. Refinements of EDA include the use of statistical approaches with monitoring information for guidance of experimental EDA studies. These three approaches will be explored using case studies at the Danube and Rhine river basins as well as rivers of the Iberian Peninsula. The synthesis of findings will be organised to provide guidance for future solution-oriented environmental monitoring and explore more systematic ways to assess mixture exposures and combination effects in future water quality monitoring.

[Health Status of Young Men in Switzerland: Monitoring Results from Conscription].

Abstract Due to their representativeness and consistent measurement standards the medical und sports data of the Swiss conscripts provide a valuable basis for a continuous health monitoring of young Swiss men. During three to four years, the prevalence of overweight and obesity seems to stabilise on a high level. After a longer period of decreasing performance at the endurance test between the 1980s and 2002, the level of physical performance in the fitness test does no longer decrease since 2006. However, health and health behaviour show significant regional and socioeconomic inequalities among young Swiss men. Besides economic resources and education, major driving factors behind these inequalities can be identified in health knowledge, values, and attitudes.

Measurement of isotopic uranium in water for compliance monitoring by liquid scintillation counting with alpha/beta discrimination

A simple and inexpensive method is described for analysis of uranium (U) activity and mass in water by liquid scintillation counting using $\alpha$/$\beta$ discrimination. This method appears to offer a solution to the need for an inexpensive protocol for monitoring U activity and mass simultaneously and an alternative to the potential inaccuracy involved when depending on the mass-to-activity conversion factor or activity screen.^ U is extracted virtually quantitatively into 20 ml extractive scintillator from a 1-$\ell$ aliquot of water acidified to less than pH 2. After phase separation, the sample is counted for a 20-minute screening count with a minimum detection level of 0.27 pCi $\ell\sp{-1}$. $\alpha$-particle emissions from the extracted U are counted with close to 100% efficiency with a Beckman LS6000 LL liquid scintillation counter equipped with pulse-shape discrimination electronics. Samples with activities higher than 10 pCi $\ell\sp-1$ are recounted for 500-1000 minutes for isotopic analysis. Isotopic analysis uses events that are automatically stored in spectral files and transferred to a computer during assay. The data can be transferred to a commercially available spreadsheet and retrieved for examination or data manipulation. Values for three readily observable spectral features can be rapidly identified by data examination and substituted into a simple formula to obtain $\sp{234}$U/$\sp{238}$U ratio for most samples. U mass is calculated by substituting the isotopic ratio value into a simple equation.^ The utility of this method for the proposed compliance monitoring of U in public drinking water supplies was field tested with a survey of drinking water from Texas supplies that had previously been known to contain elevated levels of gross $\alpha$ activity. U concentrations in 32 samples from 27 drinking water supplies ranged from 0.26 to 65.5 pCi $\ell\sp{-1}$, with seven samples exceeding the proposed Maximum Contaminant Level of 20 $\mu$g $\ell\sp{-1}$. Four exceeded the proposed activity screening level of 30 pCi $\ell\sp{-1}$. Isotopic ratios ranged from 0.87 to 41.8, while one sample contained $\sp{234}$U activity of 34.6 pCi $\ell\sp{-1}$ in the complete absence of its parent, $\sp{238}$U. U mass in the samples with elevated activity ranged from 0.0 to 103 $\mu$g $\ell\sp{-1}$. A limited test of screening surface and groundwaters for contamination by U from waste sites and natural processes was also successful. ^

A comparative analysis of hospital -based physician monitoring systems

The purpose of the multiple case-study was to determine how hospital subsystems (such as physician monitoring and credentialing; quality assurance; risk management; and peer review) were supporting the monitoring of physicians? Three large metropolitan hospitals in Texas were studied and designated as hospitals #1, #2, and #3. Realizing that hospital subsystems are a unique entity and part of a larger system, conclusions were made on the premises of a quality control system, in relation to the tools of government (particularly the Health Care Quality Improvement Act (HCQIA)), and in relation to itself as a tool of a hospital.^ Three major analytical assessments were performed. First, the subsystems were analyzed as to their "completeness"; secondly, the subsystems were analyzed for "performance"; and thirdly, the subsystems were analyzed in reference to the interaction of completeness and performance.^ The physician credentialing and monitoring and the peer review subsystems as quality control systems were most complete, efficient, and effective in hospitals #1 and #3. The HCQIA did not seem to be an influencing factor in the completeness of the subsystem in hospital #1. The quality assurance and risk management subsystem in hospital #2 was not representative of completeness and performance and the HCQIA was not an influencing factor in the completeness of the Q.A. or R.M. systems in any hospital. The efficiency (computerization) of the physician credentialing, quality assurance and peer review subsystems in hospitals #1 and #3 seemed to contribute to their effectiveness (system-wide effect).^ The results indicated that the more complete, effective, and efficient subsystems were characterized by (1) all defined activities being met, (2) the HCQIA being an influencing factor, (3) a decentralized administrative structure, (4) computerization an important element, and (5) staff was sophisticated in subsystem operations. However, other variables were identified which deserve further research as to their effect on completeness and performance of subsystems. They include (1) medical staff affiliations, (2) system funding levels, (3) the system's administrative structure, and (4) the physician staff "cultural" characteristics. Perhaps by understanding other influencing factors, health care administrators may plan subsystems that will be compatible with legislative requirements and administrative objectives. ^

Geochemical and nannofossil analyses of Cenomanian/Turonian sediments of DSDP Hole 75-530A

One of the key objectives of Deep Sea Drilling Project (DSDP) Leg 75 was to shed light on the underlying causes of Cretaceous oceanic anoxia in the South Atlantic by addressing two major hypotheses: productivity productivity-driven anoxia vs. enhanced ocean stratification leading to preservation of organic matter and black shale deposition. Here we present a detailed geochemical dataset from sediments deposited during the Cenomanian/Turonian (C/T) transition and the global oceanic anoxic event 2 (OAE 2) at DSDP Site 530A, located off-shore Namibia (southeast Angola Basin, north of Walvis Ridge). To characterise the succession of alternating black and green shales at this site and to reconstruct the evolution of their paleoenvironmental setting, we have combined data derived from investigations on bulk organic matter, biomarkers and the inorganic fraction. The location of the C/T boundary itself is biostratigraphically not well constrained due to the carbonate-poor (but organic matter-rich) facies of these sediments. The bulk d13Corg record and compound-specific d13C data, in combination with published as well as new biostratigraphic data, enabled us to locate more precisely the C/T boundary at DSDP Site 530A. The compound-specific d13C record is the first of this kind reported from C/T black shales in the South Atlantic. It is employed for paleoenvironmental reconstructions and chemostratigraphic correlation to other C/T sections in order to discuss the paleoceanographic aspects and implications of the observations at DSDP Site 530A in a broader context, e.g., with regard to the potential trigger mechanisms of OAE 2, global changes in black shale deposition and climate. On a stratigraphic level, an approximation and monitoring of the syndepositional degree of oxygen depletion within the sediments/bottom waters in comparison to the upper water column is achieved by comparing normalised concentrations of redox-sensitive trace elements with the abundance of highly source specific molecular compounds. These biomarkers are derived from photoautotrophic and simultaneously anoxygenic green sulphur bacteria (Chlorobiacea) and are interpreted as paleoindicators for events of photic zone euxinia. In contrast to a number of other OAE 2 sections that are characterised by continuous black shale sequences, DSDP Site 530A represents a highly dynamic setting where newly deposited black shales were repeatedly exposed to conditions of subtle bottom water re-oxidation, presumably leading to their progressive alteration into green shales. The frequent alternation between both facies and the related anoxic to slight oxygenated conditions can be best explained by variations in vertical extent of an oxygen minimum zone in response to changes in a highly productive western continental margin setting driven by upwelling.

Electromagnetic analysis of periodic structures under a waveguide viewpoint

The fundamental objective of this Ph. D. dissertation is to demonstrate that, under particular circumstances which cover most of the structures with practical interest, periodic structures can be understood and analyzed by means of closed waveguide theories and techniques. To that aim, in the first place a transversely periodic cylindrical structure is considered and the wave equation, under a combination of perfectly conducting and periodic boundary conditions, is studied. This theoretical study runs parallel to the classic analysis of perfectly conducting closed waveguides. Under the light shed by the aforementioned study it is clear that, under certain very common periodicity conditions, transversely periodic cylindrical structures share a lot of properties with closed waveguides. Particularly, they can be characterized by a complete set of TEM, TE and TM modes. As a result, this Ph. D. dissertation introduces the transversely periodic waveguide concept. Once the analogies between the modes of a transversely periodic waveguide and the ones of a closed waveguide have been established, a generalization of a well-known closed waveguide characterization method, the generalized Transverse Resonance Technique, is developed for the obtention of transversely periodic modes. At this point, all the necessary elements for the consideration of discontinuities between two different transversely periodic waveguides are at our disposal. The analysis of this type of discontinuities will be carried out by means of another well known closed waveguide method, the Mode Matching technique. This Ph. D. dissertation contains a sufficient number of examples, including the analysis of a wire-medium slab, a cross-shaped patches periodic surface and a parallel plate waveguide with a textured surface, that demonstrate that the Transverse Resonance Technique - Mode Matching hybrid is highly precise, efficient and versatile. Thus, the initial statement: ”periodic structures can be understood and analyzed by means of closed waveguide theories and techniques”, will be corroborated. Finally, this Ph. D. dissertation contains an adaptation of the aforementioned generalized Transverse Resonance Technique by means of which the analysis of laterally open periodic waveguides, such as the well known Substrate Integrated Waveguides, can be carried out without any approximation. The analysis of this type of structures has suscitated a lot of interest in the recent past and the previous analysis techniques proposed always resorted to some kind of fictitious wall to close the structure. vii Resumen El principal objetivo de esta tesis doctoral es demostrar que, bajo ciertas circunstancias que se cumplen para la gran mayoría de estructuras con interés práctico, las estructuras periódicas se pueden analizar y entender con conceptos y técnicas propias de las guías de onda cerradas. Para ello, en un primer lugar se considera una estructura cilíndrical transversalmente periódica y se estudia la ecuación de onda bajo una combinación de condiciones de contorno periódicas y de conductor perfecto. Este estudio teórico y de caracter general, sigue el análisis clásico de las guías de onda cerradas por conductor eléctrico perfecto. A la luz de los resultados queda claro que, bajo ciertas condiciones de periodicidad (muy comunes en la práctica) las estructuras cilíndricas transversalmente periódicas guardan multitud de analogías con las guías de onda cerradas. En particular, pueden ser descritas mediante un conjunto completo de modos TEM, TE y TM. Por ello, ésta tesis introduce el concepto de guía de onda transversalmente periódica. Una vez establecidas las similitudes entre las soluciones de la ecuación de onda, bajo una combinación de condiciones de contorno periódicas y de conductor perfecto, y los modos de guías de onda cerradas, se lleva a cabo, con éxito, la adaptación de un conocido método de caracterización de guías de onda cerradas, la técnica de la Resonancia Transversal Generalizada, para la obtención de los modos de guías transversalmente periódicas. En este punto, se tienen todos los elementos necesarios para considerar discontinuidades entre guías de onda transversalmente periódicas. El analisis de este tipo de discontinuidades se llevará a cabo mediante otro conocido método de análisis de estructuras cerradas, el Ajuste Modal. Esta tesis muestra multitud de ejemplos, como por ejemplo el análisis de un wire-medium slab, una superficie de parches con forma de cruz o una guía de placas paralelas donde una de dichas placas tiene cierta textura, en los que se demuestra que el método híbrido formado por la Resonancia Transversal Generalizada y el Ajuste Modal, es tremendamente preciso, eficiente y versátil y confirmará la validez de el enunciado inicial: ”las estructuras periódicas se pueden analizar y entender con conceptos y técnicas propias de las guías de onda cerradas” Para terminar, esta tésis doctoral incluye también una modificación de la técnica de la Resonancia Transversal Generalizada mediante la cual es posible abordar el análisis de estructuras periódica abiertas en los laterales, como por ejemplo las famosas guías de onda integradas en sustrato, sin ninguna aproximación. El análisis de este tipo de estructuras ha despertado mucho interés en los últimos años y las técnicas de análisis propuestas hasta ix el momento acostumbran a recurrir a algún tipo de pared ficticia para simular el carácter abierto de la estructura.

Integrated phased array transducer for on-board structural health monitoring

Permanently bonded onto a structure, an integrated Phased Array (PhA II) transducer that can provide reliable electromechanical connection with corresponding sophisticated miniaturized ?all in one? SHM electronic device installed directly above it, without need for any interface cabling, during all aerospace structure lifecycle phases and for a huge variety of real harsh service environments of structures to be monitored is presented. This integrated PhA II transducer [1], as a key component of the PAMELA SHM? (Phased Array Monitoring for Enhanced Life Assessment) system, has two principal tasks at the same time, reliably transceive elastic waves in real aerospace service environments and serves as a reliable sole carrier or support for associated integrated on-board SHM electronic device attached above. The PhA II transducer successfully accomplished both required task throughout extensive test campaigns which included low to high temperature tests, temperature cycling, mechanical loading, combined thermo- mechanical loading and vibration resistance, etc. both with and without SHM device attached above due to RTCA DO-160F.