Gel versus capillary electrophoresis genotyping for categorizing treatment outcomes in two anti-malarial trials in Uganda

Abstract Background Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure) or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Methods Samples were genotyped using both gel and capillary electrophoresis from randomized trials of artemether-lumefantrine (AL) vs. dihydroartemisinin-piperaquine (DP) performed in two areas of Uganda: Kanungu, where transmission is moderate, and Apac, where transmission is very high. Both gel and capillary methods evaluated polymorphic regions of the merozoite surface protein 1 and 2 and glutamine rich protein genes. Results Capillary electrophoresis detected more alleles and provided higher discriminatory power than agarose gel electrophoresis at both study sites. There was only moderate agreement between classification of outcomes with the two methods in Kanungu (kappa = 0.66) and poor agreement in Apac (kappa = 0.24). Overall efficacy results were similar when using gel vs. capillary methods in Kanungu (42-day risk of treatment failure for AL: 6.9% vs. 5.5%, p = 0.4; DP 2.4% vs. 2.9%, p = 0.5). However, the measured risk of recrudescence was significantly higher when using gel vs. capillary electrophoresis in Apac (risk of treatment failure for AL: 17.0% vs. 10.7%, p = 0.02; DP: 8.5% vs. 3.4%, p = 0.03). Risk differences between AL and DP were not significantly different whether gel or capillary methods were used. Conclusions Genotyping with gel electrophoresis overestimates the risk of recrudescence in anti-malarial trials performed in areas of high transmission intensity. Capillary electrophoresis provides more accurate outcomes for such trials and should be performed when possible. In areas of moderate transmission, gel electrophoresis appears adequate to estimate comparative risks of treatment failure

An application of hybrid life cycle assessment as a decision support framework for green supply chains

In an effort to achieve sustainable operations, green supply chain management has become an important area for firms to concentrate on due to its inherent involvement with all the processes that provide foundations to successful business. Modelling methodologies of product supply chain environmental assessment are usually guided by the principles of life cycle assessment (LCA). However, a review of the extant literature suggests that LCA techniques suffer from a wide range of limitations that prevent a wider application in real-world contexts; hence, they need to be incorporated within decision support frameworks to aid environmental sustainability strategies. Thus, this paper contributes in understanding and overcoming the dichotomy between LCA model development and the emerging practical implementation to inform carbon emissions mitigation strategies within supply chains. Therefore, the paper provides both theoretical insights and a practical application to inform the process of adopting a decision support framework based on a LCA methodology in a real-world scenario. The supply chain of a product from the steel industry is considered to evaluate its environmental impact and carbon ‘hotspots’. The study helps understanding how operational strategies geared towards environmental sustainability can be informed using knowledge and information generated from supply chain environmental assessments, and for highlighting inherent challenges in this process

Development of Transition Edge Sensor Detectors Optimized for Single-Photon Spectroscopy in the Optical and Near-Infrared

The search for biosignatures in the atmospheres of exoplanets will be a key focus of future space telescopes that operate in the ultraviolet, visible, and near-infrared bands. Detection of biosignatures requires an instrument with moderate spectral resolving power ($R \sim 100$) and a large bandwidth ($\sim 400$ nm -- $\sim 1.8$ $\mu$m). Additionally, biosignature detection is a photon-starved science; instruments designed for these measurements would ideally combine high optical efficiency with quantum-limited photon detectors (i.e., detectors that exhibit zero dark current). In this work, we report on our efforts to develop energy resolving transition edge sensor (TES)-based detectors designed for biosignature detection. TESs operated as microcalorimeters are compelling detectors for this application. Unlike semiconductor detectors, TESs eliminate the need for dispersive optics and are truly single photon detectors -- fundamental TES noise yields uncertainty in the energies of detected photons, not in the number of detected photons. We introduce TESs designed for this application and discuss the path toward realizing a TES-based dispersionless spectrometer optimized for biosignature detection

The Neon Nova. III. The Infrared Light Curves of Nova QU Vulpeculae (Nova Vul 1984 #2)

We report 1.25 to 19.5 µm broadband infrared (IR) photometric measurements acquired during an eight year period on the prototypical ONeMg “neon nova” QU Vulpeculae (Nova Vul 1984 #2). The energy distribution of the ejecta evolved through several phases. An early free-free emission phase was followed by an IR coronal phase characterized by the appearance of strong emission lines from forbidden atomic transitions. The lines of [Ne Vi] at 7.6 /xm, and [Ne il] at 12.8 µm were especially strong during the coronal phase. A small amount of silicate dust condensed in the ejecta after about a year. The evidence provided by our IR observations for high abundances of metals in the ejecta of QU Vul is reviewed. We present the IR light curves of QU Vul, and show that the temporal development of its persistent IR coronal emission phase was evident in the broadband K (2.3 µm) and L (3.6 µm) photometry. Using data from our previous studies of classical novae, we suggest that K and L photometry can distinguish between the slower ONeMg novae with persistent IR coronal activity and CO novae that produce copious quantities of circumstellar dust. The most striking signature is produced in the L band, which contains emission from [Mg Vlll] at 3.02 µm, [A1 Vi] at 3.66 µm, and [Si ix] at 3.92 µm. We comment on the peculiar tendency of the IR light curves of novae to decay exponentially

Vδ2+ T cell response to malaria correlates with protection from infection but is attenuated with repeated exposure.

Vδ2+ γδ T cells are semi-innate T cells that expand markedly following P. falciparum (Pf) infection in naïve adults, but are lost and become dysfunctional among children repeatedly exposed to malaria. The role of these cells in mediating clinical immunity (i.e. protection against symptoms) to malaria remains unclear. We measured Vδ2+ T cell absolute counts at acute and convalescent malaria timepoints (n = 43), and Vδ2+ counts, cellular phenotype, and cytokine production following in vitro stimulation at asymptomatic visits (n = 377), among children aged 6 months to 10 years living in Uganda. Increasing age was associated with diminished in vivo expansion following malaria, and lower Vδ2 absolute counts overall, among children living in a high transmission setting. Microscopic parasitemia and expression of the immunoregulatory markers Tim-3 and CD57 were associated with diminished Vδ2+ T cell pro-inflammatory cytokine production. Higher Vδ2 pro-inflammatory cytokine production was associated with protection from subsequent Pf infection, but also with an increased odds of symptoms once infected. Vδ2+ T cells may play a role in preventing malaria infection in children living in endemic settings; progressive loss and dysfunction of these cells may represent a disease tolerance mechanism that contributes to the development of clinical immunity to malaria

Estimating malaria parasite prevalence from community surveys in Uganda: a comparison of microscopy, rapid diagnostic tests and polymerase chain reaction.

BACKGROUND: Household surveys are important tools for monitoring the malaria disease burden and measuring impact of malaria control interventions with parasite prevalence as the primary metric. However, estimates of parasite prevalence are dependent on a number of factors including the method used to detect parasites, age of the population sampled, and level of immunity. To better understand the influence of diagnostics, age, and endemicity on estimates of parasite prevalence and how these change over time, community-based surveys were performed for two consecutive years in three settings and the sensitivities of microscopy and immunochromatographic rapid diagnostic tests (RDTs) were assessed, considering polymerase chain reaction (PCR) as the gold standard. METHODS: Surveys were conducted over the same two-month period in 2012 and 2013 in each of three sub-counties in Uganda: Nagongera in Tororo District (January-February), Walukuba in Jinja District (March-April), and Kihihi in Kanungu District (May-June). In each sub-county, 200 households were randomly enrolled and a household questionnaire capturing information on demographics, use of malaria prevention methods, and proxy indicators of wealth was administered to the head of the household. Finger-prick blood samples were obtained for RDTs, measurement of hemoglobin, thick and thin blood smears, and to store samples on filter paper. RESULTS: A total of 1200 households were surveyed and 4433 participants were included in the analysis. Compared to PCR, the sensitivity of microscopy was low (65.3% in Nagongera, 49.6% in Walukuba and 40.9% in Kihihi) and decreased with increasing age. The specificity of microscopy was over 98% at all sites and did not vary with age or year. Relative differences in parasite prevalence across different age groups, study sites, and years were similar for microscopy and PCR. The sensitivity of RDTs was similar across the three sites (range 77.2-82.8%), was consistently higher than microscopy (p < 0.001 for all pairwise comparisons), and decreased with increasing age. The specificity of RDTs was lower than microscopy (76.3% in Nagongera, 86.3% in Walukuba, and 83.5% in Kihihi) and varied significantly by year and age. Relative differences in parasite prevalence across age groups and study years differed for RDTs compared to microscopy and PCR. CONCLUSION: Malaria prevalence estimates varied with diagnostic test, age, and transmission intensity. It is important to consider the effects of these parameters when designing and interpreting community-based surveys

Follow-Up Near-infrared Spectroscopy of Ultraluminous Infrared Galaxies observed by ISO

We present low resolution near-infrared spectroscopy of an unbiased sample of 24 ultraluminous infrared galaxies (ULIRGs), selected from samples previously observed spectroscopically in the mid-infrared with the Infrared Space Observatory (ISO). Qualitatively, the near-infrared spectra resemble those of starbursts. Only in one ULIRG, IRAS 04114-5117E, do we find spectroscopic evidence for AGN activity. The spectroscopic classification in the near-infrared is in very good agreement with the mid-infrared one. For a subset of our sample for which extinction corrections can be derived from Pa-alpha and Br-gamma, we find rather high Pa-alpha luminosities, in accordance with the powering source of these galaxies being star formation.[Fe] emission is strong in ULIRGs and may be linked to starburst and superwind activity. Additionally, our sample includes two unusual objects. The first, IRAS F00183-7111, exhibits extreme [Fe] emission and the second, IRAS F23578-5307, is according to our knowledge one of the most luminous infrared galaxies in H2 rotation-vibration emission.Comment: Accepted for publication in A&A (12 pages, 4 figures). See http://www.mpia-hd.mpg.de/homes/dannerb/ for a version with higher quality figure