Malaria and Economic Evaluation Methods: Challenges and Opportunities.

There is a growing evidence base on the cost effectiveness of malaria interventions. However, certain characteristics of malaria decision problems present a challenge to the application of healthcare economic evaluation methods. This paper identifies five such challenges. The complexities of (i) declining incidence and cost effectiveness in the context of an elimination campaign; (ii) international aid and its effect on resource constraints; and (iii) supranational priority setting, all affect how health economists might use a cost-effectiveness threshold. Consensus and guidance on how to determine and interpret cost-effectiveness thresholds in the context of internationally financed elimination campaigns is greatly needed. (iv) Malaria interventions are often complimentary and evaluations may need to construct intervention bundles to represent relevant policy positions as sets of mutually exclusive alternatives. (v) Geographic targeting is a key aspect of malaria policy making that is only beginning to be addressed in economic evaluations. An approach to budget-based geographic resource allocation is described in an accompanying paper in this issue and addresses some of these methodological challenges

Evolution of Static Allometry and Constraint on Evolutionary Allometry in a Fossil Stickleback

Allometric scaling describes the relationship of trait size to body size within and among taxa. The slope of the population-level regression of trait size against body size (i.e. static allometry) is typically invariant among closely related populations and species. Such invariance is commonly interpreted to reflect a combination of developmental and selective constraints that delimit a phenotypic space into which evolution could proceed most easily. Thus, understanding how allometric relationships do eventually evolve is important to understanding phenotypic diversification. In a lineage of fossil Threespine Stickleback (Gasterosteus doryssus), we investigated the evolvability of static allometric slopes for nine traits (five armour and four non-armour) that evolved significant trait differences across 10 samples over 8500 years. The armour traits showed weak static allometric relationships and a mismatch between those slopes and observed evolution. This suggests that observed evolution in these traits was not constrained by relationships with body size, perhaps because prior, repeated adaptation to freshwater habitats by Threespine Stickleback had generated strong selection to break constraint. In contrast, for non-armour traits, we found stronger allometric relationships. Those allometric slopes did evolve on short time scales. However, those changes were small and fluctuating and the slopes remained strong predictors of the evolutionary trajectory of trait means over time (i.e. evolutionary allometry), supporting the hypothesis of allometry as constraint

Analisis Risiko Implementasi Digital Gold Pada Transaksi Emas Retail

Penelitian ini mengeksplorasi PT XYZ Tbk., perusahaan pertambangan yang juga memasarkan produk logam mulia seperti emas dan perak. Metode penelitian kuantitatif digunakan untuk mengumpulkan data dan mengukur risiko dengan rumus R = P × D. Hasil penelitian menunjukkan bahwa risiko meliputi kesalahan input data oleh konsumen, kesalahan input oleh Customer Service, dan risiko hilangnya barang saat pengiriman oleh pihak ketiga. Perusahaan berkomitmen untuk mendigitalisasi proses penjualan emas dengan implementasi "Digital Gold," namun mereka juga harus memitigasi risiko yang mungkin muncul seiring dengan digitalisasi, terutama terkait dengan keamanan data dan layanan online. Penelitian ini memberikan wawasan berharga dalam mengelola risiko transaksi online dalam bisnis penjualan emas retail dan menyoroti pentingnya keamanan data dalam lingkungan bisnis yang semakin digital

Dispersal of Galactic Magnetic Fields into Intracluster Space

Little is known about the origin and basic properties of magnetic fields in clusters of galaxies. High conductivity in magnetized interstellar plasma suggests that galactic magnetic fields are (at least partly) ejected into intracluster (IC) space by the same processes that enrich IC gas with metals. We explore the dispersal of galactic fields by hydrodynamical simulations with our new {\em Enzo-Galcon} code, which is capable of tracking a large number galaxies during cluster assembly, and modeling the processes that disperse their interstellar media. Doing so we are able to describe the evolution of the mean strength of the field and its profile across the cluster. With the known density profile of dispersed gas and an estimated range of coherence scales, we predict the spatial distribution of Faraday rotation measure and find it to be consistent with observational data

Using Weak Lensing Dilution to Improve Measurements of the Luminous and Dark Matter in A1689

The E/SO sequence of a cluster defines a boundary redward of which a reliable weak lensing signal can be obtained from background galaxies, uncontaminated by cluster members. For bluer colors, both background and cluster members are present, reducing the distortion signal by the proportion of unlensed cluster members. In deep Subaru and HST/ACS images of A1689 the tangential distortion of galaxies with bluer colors falls rapidly toward the cluster center relative to the lensing signal of the red background. We use this dilution effect to derive the cluster light profile and luminosity function to large radius, with the advantage that no subtraction of far-field background counts is required. The light profile declines smoothly to the limit of the data, r<2Mpc/h, with a constant slope, dlog(L)/dlog(r)=-1.12+-0.06, unlike the lensing mass profile which steepens continuously with radius, so that M/L peaks at an intermediate radius, ~100kpc/h. A flatter behavior is found for the more physically meaningful ratio of dark-matter to stellar-matter, when accounting for the color-mass relation of cluster members. The cluster luminosity function has a flat slope, alpha=-1.05+-0.07, independent of radius and with no faint upturn to M_i'<-12. We establish that the very bluest objects are negligibly contaminated by the cluster V-i'<0.2, because their distortion profile rises towards the center following the red background, but offset higher by ~20%. This larger amplitude is consistent with the greater estimated depth of the faint blue galaxies, z~=2.0 compared to z~=0.85 for the red background, a purely geometric effect related to cosmological parameters. Finally, we improve upon our earlier mass profile by combining both the red and blue background populations, clearly excluding low concentration CDM profiles.Comment: 17 pages, 21 figures, revised version in response to referee comments,(added some discussion, references), conclusions unchanged. Accepted for publication in Ap

How context can impact clinical trials : a multi-country qualitative case study comparison of diagnostic biomarker test interventions

Background Context matters for the successful implementation of medical interventions, but its role remains surprisingly understudied. Against the backdrop of antimicrobial resistance, a global health priority, we investigated the introduction of a rapid diagnostic biomarker test (C-reactive protein, or CRP) to guide antibiotic prescriptions in outpatient settings and asked, “Which factors account for cross-country variations in the effectiveness of CRP biomarker test interventions?” Methods We conducted a cross-case comparison of CRP point-of-care test trials across Yangon (Myanmar), Chiang Rai (Thailand), and Hanoi (Vietnam). Cross-sectional qualitative data were originally collected as part of each clinical trial to broaden their evidence base and help explain their respective results. We synthesised these data and developed a large qualitative data set comprising 130 interview and focus group participants (healthcare workers and patients) and nearly one million words worth of transcripts and interview notes. Inductive thematic analysis was used to identify contextual factors and compare them across the three case studies. As clinical trial outcomes, we considered patients’ and healthcare workers’ adherence to the biomarker test results, and patient exclusion to gauge the potential “impact” of CRP point-of-care testing on the population level. Results We identified three principal domains of contextual influences on intervention effectiveness. First, perceived risks from infectious diseases influenced the adherence of the clinical users (nurses, doctors). Second, the health system context related to all three intervention outcomes (via the health policy and antibiotic policy environment, and via health system structures and the ensuing utilisation patterns). Third, the demand-side context influenced the patient adherence to CRP point-of-care tests and exclusion from the intervention through variations in local healthcare-seeking behaviours, popular conceptions of illness and medicine, and the resulting utilisation of the health system. Conclusions Our study underscored the importance of contextual variation for the interpretation of clinical trial findings. Further research should investigate the range and magnitude of contextual effects on trial outcomes through meta-analyses of large sets of clinical trials. For this to be possible, clinical trials should collect qualitative and quantitative contextual information for instance on their disease, health system, and demand-side environment. Trial registration: ClinicalTrials.gov Identifiers NCT02758821 and NCT01918579

Cost effectiveness and resource allocation of Plasmodium falciparum malaria control in Myanmar: a modelling analysis of bed nets and community health workers.

BACKGROUND: Funding for malaria control and elimination in Myanmar has increased markedly in recent years. While there are various malaria control tools currently available, two interventions receive the majority of malaria control funding in Myanmar: (1) insecticide-treated bed nets and (2) early diagnosis and treatment through malaria community health workers. This study aims to provide practical recommendations on how to maximize impact from investment in these interventions. METHODS: A simple decision tree is used to model intervention costs and effects in terms of years of life lost. The evaluation is from the perspective of the service provider and costs and effects are calculated in line with standard methodology. Sensitivity and scenario analysis are undertaken to identify key drivers of cost effectiveness. Standard cost effectiveness analysis is then extended via a spatially explicit resource allocation model. FINDINGS: Community health workers have the potential for high impact on malaria, particularly where there are few alternatives to access malaria treatment, but are relatively costly. Insecticide-treated bed nets are comparatively inexpensive and modestly effective in Myanmar, representing a low risk but modest return intervention. Unlike some healthcare interventions, bed nets and community health workers are not mutually exclusive nor are they necessarily at their most efficient when universally applied. Modelled resource allocation scenarios highlight that in this case there is no "one size fits all" cost effectiveness result. Health gains will be maximized by effective targeting of both interventions

Profiles of Dark Matter Velocity Anisotropy in Simulated Clusters

We report statistical results for dark matter (DM) velocity anisotropy, \beta, from a sample of some 6000 cluster-size halos (at redshift zero) identified in a \Lambda CDM hydrodynamical adaptive mesh refinement simulation performed with the Enzo code. These include profiles of \beta\ in clusters with different masses, relaxation states, and at several redshifts, modeled both as spherical and triaxial DM configurations. Specifically, although we find a large scatter in the DM velocity anisotropy profiles of different halos (across elliptical shells extending to at least ~$1.5 r_{vir}$), universal patterns are found when these are averaged over halo mass, redshift, and relaxation stage. These are characterized by a very small velocity anisotropy at the halo center, increasing outward to about 0.27 and leveling off at about $0.2 r_{vir}$. Indirect measurements of the DM velocity anisotropy fall on the upper end of the theoretically expected range. Though measured indirectly, the estimations are derived by using two different surrogate measurements - X-ray and galaxy dynamics. Current estimates of the DM velocity anisotropy are based on very small cluster sample. Increasing this sample will allow testing theoretical predictions, including the speculation that the decay of DM particles results in a large velocity boost. We also find, in accord with previous works, that halos are triaxial and likely to be more prolate when unrelaxed, whereas relaxed halos are more likely to be oblate. Our analysis does not indicate that there is significant correlation (found in some previous studies) between the radial density slope, \gamma, and \beta\ at large radii, $0.3 r_{vir} < r < r_{vir}$.Comment: 12 pages, 17 figures, accepted to Ap

Quantification of Uncertainty in the Measurement of Magnetic Fields in Clusters of Galaxies

We assess the principal statistical and physical uncertainties associated with the determination of magnetic field strengths in clusters of galaxies from measurements of Faraday rotation (FR) and Compton-synchrotron emissions. In the former case a basic limitation is noted, that the relative uncertainty in the estimation of the mean-squared FR will generally be at least one third. Even greater uncertainty stems from the crucial dependence of the Faraday-deduced field on the coherence length scale characterizing its random orientation; we further elaborate this dependence, and argue that previous estimates of the field are likely to be too high by a factor of a few. Lack of detailed spatial information on the radio emission--and the recently deduced nonthermal X-ray emission in four clusters--has led to an underestimation of the mean value of the field in cluster cores. We conclude therefore that it is premature to draw definite quantitative conclusions from the previously-claimed seemingly-discrepant values of the field determined by these two methods.Comment: 31 pages including 3 figures; accepted for publication in the Astrophysical Journal as paper #5497

Geographic Resource Allocation Based on Cost Effectiveness: An Application to Malaria Policy.

Healthcare services are often provided to a country as a whole, though in many cases the available resources can be more effectively targeted to specific geographically defined populations. In the case of malaria, risk is highly geographically heterogeneous, and many interventions, such as insecticide-treated bed nets and malaria community health workers, can be targeted to populations in a way that maximises impact for the resources available. This paper describes a framework for geographically targeted budget allocation based on the principles of cost-effectiveness analysis and applied to priority setting in malaria control and elimination. The approach can be used with any underlying model able to estimate intervention costs and effects given relevant local data. Efficient geographic targeting of core malaria interventions could significantly increase the impact of the resources available, accelerating progress towards elimination. These methods may also be applicable to priority setting in other disease areas