Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring

BACKGROUND: In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia. DESIGN AND METHODS: Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models. RESULTS: A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months [interquartile range (IQR) 10.1-26.6] in programmes with viral load monitoring and 21.8 months (IQR 14.0-21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/microl (IQR 77-265) in programmes with viral load monitoring and 102 cells/microl (44-181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7-18 after starting ART (aHR 1.38; 95% CI 0.97-1.98), similar during months 19-30 (aHR 0.97; 95% CI 0.58-1.60) and less common during months 31-42 (aHR 0.29; 95% CI 0.11-0.79). CONCLUSION: In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.

GRASP with Hybrid Path Relinking for Bi-Objective Winner Determination in Combinatorial Transportation Auctions

The procurement of transportation services via large-scale combinatorial auctions involves a couple of complex decisions whose outcome highly influences the performance of the tender process. This paper examines the shipper's task of selecting a subset of the submitted bids which efficiently trades off total procurement cost against expected carrier performance. To solve this bi-objective winner determination problem, we propose a Pareto-based greedy randomized adaptive search procedure (GRASP). As a post-optimizer we use a path relinking procedure which is hybridized with branch-and-bound. Several variants of this algorithm are evaluated by means of artificial test instances which comply with important real-world characteristics. The two best variants prove superior to a previously published Pareto-based evolutionary algorithm.

Egalitarianism under Earmark Constraints

Agents with single-peaked preferences share a resource coming from different suppliers; each agent is connected to only a subset of suppliers. Examples include workload balancing, sharing earmarked funds, and rationing utilities after a storm. Unlike in the one supplier model, in a Pareto optimal allocation agents who get more than their peak from underdemanded suppliers, coexist with agents who get less from overdemanded suppliers. Our Egalitarian solution is the Lorenz dominant Pareto optimal allocation. It treats agents with equal demands as equally as the connectivity constraints allow. Together, Strategyproofness, Pareto Optimality, and Equal Treatment of Equals, characterize our solution.

Shying away: An observer-based microprocess analysis of experiential avoidance and resource activation in outpatients with generalized anxiety spectrum disorder

Despite long-standing calls for patient-focused research on individuals with generalized anxiety spectrum disorder there is little systematized knowledge about the in-session behaviors of these patients. The primary objective of this study was to describe of in-session trajectories of the patients' level of explication (as an indicator of an elaborated exposure of negative emotionality) and the patients' focus on their own resources and how these trajectories are associated with post-treatment outcome. In respect to GAD patients, a high level of explication might be seen as an indicator of successful exposure of avoided negative emotionality during therapy sessions. Observers made minute-by-minute ratings of 1100 minutes of video of 20 patients-therapists dyads. The results indicated that a higher level of explication generally observed at a later stage during the therapy sessions and the patients' focus on competencies at an early stage was highly associated with positive therapy outcome at assessment at post treatment, independent of pretreatment distress, rapid response of well-being and symptom reduction, as well as the therapists' professional experience and therapy lengths. These results will be discussed under the perspective of emotion regulation of patients and therapist's counterregulation. It is assumed that GAD-Patients are especially skilled in masking difficult emotions. Explication level and emotion regulation are important variables for this patient group but there's relation to outcome is different.

Resource allocation with project management software

We present results of a benchmark test evaluating the resource allocation capabilities of the project management software packages Acos Plus.1 8.2, CA SuperProject 5.0a, CS Project Professional 3.0, MS Project 2000, and Scitor Project Scheduler 8.0.1. The tests are based on 1560 instances of precedence– and resource–constrained project scheduling problems. For different complexity scenarios, we analyze the deviation of the makespan obtained by the software packages from the best feasible makespan known. Among the tested software packages, Acos Plus.1 and Project Scheduler show the best resource allocation performance. Moreover, our numerical analysis reveals a considerable performance gap between the implemented methods and state–of–the–art project scheduling algorithms, especially for large–sized problems. Thus, there is still a significant potential for improving solutions to resource allocation problems in practice.

Batch scheduling in process industries: an application of resource-constrained project scheduling

The paper deals with batch scheduling problems in process industries where final products arise from several successive chemical or physical transformations of raw materials using multi–purpose equipment. In batch production mode, the total requirements of intermediate and final products are partitioned into batches. The production start of a batch at a given level requires the availability of all input products. We consider the problem of scheduling the production of given batches such that the makespan is minimized. Constraints like minimum and maximum time lags between successive production levels, sequence–dependent facility setup times, finite intermediate storages, production breaks, and time–varying manpower contribute to the complexity of this problem. We propose a new solution approach using models and methods of resource–constrained project scheduling, which (approximately) solves problems of industrial size within a reasonable amount of time.

Patient classification system: An integrated method for measuring nursing intensity and optimizing resource allocation

A patient classification system was developed integrating a patient acuity instrument with a computerized nursing distribution method based on a linear programming model. The system was designed for real-time measurement of patient acuity (workload) and allocation of nursing personnel to optimize the utilization of resources.^ The acuity instrument was a prototype tool with eight categories of patients defined by patient severity and nursing intensity parameters. From this tool, the demand for nursing care was defined in patient points with one point equal to one hour of RN time. Validity and reliability of the instrument was determined as follows: (1) Content validity by a panel of expert nurses; (2) predictive validity through a paired t-test analysis of preshift and postshift categorization of patients; (3) initial reliability by a one month pilot of the instrument in a practice setting; and (4) interrater reliability by the Kappa statistic.^ The nursing distribution system was a linear programming model using a branch and bound technique for obtaining integer solutions. The objective function was to minimize the total number of nursing personnel used by optimally assigning the staff to meet the acuity needs of the units. A penalty weight was used as a coefficient of the objective function variables to define priorities for allocation of staff.^ The demand constraints were requirements to meet the total acuity points needed for each unit and to have a minimum number of RNs on each unit. Supply constraints were: (1) total availability of each type of staff and the value of that staff member (value was determined relative to that type of staff's ability to perform the job function of an RN (i.e., value for eight hours RN = 8 points, LVN = 6 points); (2) number of personnel available for floating between units.^ The capability of the model to assign staff quantitatively and qualitatively equal to the manual method was established by a thirty day comparison. Sensitivity testing demonstrated appropriate adjustment of the optimal solution to changes in penalty coefficients in the objective function and to acuity totals in the demand constraints.^ Further investigation of the model documented: correct adjustment of assignments in response to staff value changes; and cost minimization by an addition of a dollar coefficient to the objective function. ^

Impacts of a word-picture training on literacy skills in elementary school children and youths with intellectual disabilities

Objective: There is convincing evidence that phonological, orthographic and semantic processes influence children’s ability to learn to read and spell words. So far only a few studies investigated the influence of implicit learning in literacy skills. Children are sensitive to the statistics of their learning environment. By frequent reading they acquire implicit knowledge about the frequency of letter patterns in written words, and they use this knowledge during reading and spelling. Additionally, semantic connections facilitate to storing of words in memory. Thus, the aim of the intervention study was to implement a word-picture training which is based on statistical and semantic learning. Furthermore, we aimed at examining the training effects in reading and spelling in comparison to an auditory-visual matching training and a working memory training program. Participants and Methods: One hundred and thirty-two children aged between 8 and 11 years participated in training in three weekly session of 12 minutes over 8 weeks, and completed other assessments of reading, spelling, working memory and intelligence before and after training. Results: Results revealed in general that the word-picture training and the auditory-visual matching training led to substantial gains in reading and spelling performance in comparison to the working-memory training. Although both children with and without learning difficulties profited in their reading and spelling after the word-picture training, the training program led to differential effects for the two groups. After the word-picture training on the one hand, children with learning difficulties profited more in spelling as children without learning difficulties, on the other hand, children without learning difficulties benefit more in word comprehension. Conclusions: These findings highlight the need for frequent reading trainings with semantic connections in order to support the acquisition of literacy skills.

Resource-Constrained Project Scheduling with Project Management Information Systems

Most commercial project management software packages include planning methods to devise schedules for resource-constrained projects. As it is proprietary information of the software vendors which planning methods are implemented, the question arises how the software packages differ in quality with respect to their resource-allocation capabilities. We experimentally evaluate the resource-allocation capabilities of eight recent software packages by using 1,560 instances with 30, 60, and 120 activities of the well-known PSPLIB library. In some of the analyzed packages, the user may influence the resource allocation by means of multi-level priority rules, whereas in other packages, only few options can be chosen. We study the impact of various complexity parameters and priority rules on the project duration obtained by the software packages. The results indicate that the resource-allocation capabilities of these packages differ significantly. In general, the relative gap between the packages gets larger with increasing resource scarcity and with increasing number of activities. Moreover, the selection of the priority rule has a considerable impact on the project duration. Surprisingly, when selecting a priority rule in the packages where it is possible, both the mean and the variance of the project duration are in general worse than for the packages which do not offer the selection of a priority rule.

Oxygen isotope record of oceanic and high-pressure metasomatism: a P-T-time-fluid path for the Monviso eclogites (Italy)

Fluids are considered a fundamental agent for chemical exchanges between different rock types in the subduction system. Constraints on the sources and pathways of subduction fluids thus provide crucial information to reconstruct subduction processes. The Monviso ophiolitic sequence is composed of mafic, ultramafic and minor sediments that have been subducted to ~80 km depth. In this sequence, both localized fluid flow and channelized fluids along major shear zones have been documented. We investigate the timing and source of the fluids that affected the dominant mafic rocks using microscale U-Pb dating of zircon and oxygen isotope analysis of mineral zones (garnet, zircon and antigorite) in high pressure rocks with variable degree of metasomatic modification. In mafic eclogites, Jurassic zircon cores are the only mineralogical relicts of the protolith gabbros and retain δ18O values of 4.5–6 ‰, typical of mantle melts. Garnet and metamorphic zircon that grew during prograde to peak metamorphism display low δ18O values between 0.2 and 3.8 ‰, which are likely inherited from high-temperature alteration of the protolith on the sea floor. This is corroborated by δ18O values of 3.0 and 3.6 ‰ in antigorite from surrounding serpentinites. In metasomatised eclogites within the Lower Shear Zone, garnet rim formed at the metamorphic peak shows a shift to higher δ18O up to 6‰. The age of zircons in high-pressure veins and metasomatised eclogites constrains the timing of fluid flow at high pressure at around 45–46 Ma. Although the oxygen data do not contradict previous reports of interaction with serpentinite-derived fluids, the shift to isotopically heavier oxygen compositions requires contribution from sediment-derived fluids. The scarcity of metasediments in the Monviso sequence suggests that such fluids were concentrated and fluxed along the Lower Shear Zone in a sufficient amount to modify the oxygen composition of the eclogitic minerals.

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.