Discriminative vector quantization schemes such as learning vector quantization (LVQ) and extensions thereof offer efficient and intuitive classifiers based on the representation of classes by ...prototypes. The original methods, however, rely on the Euclidean distance corresponding to the assumption that the data can be represented by isotropic clusters. For this reason, extensions of the methods to more general metric structures have been proposed, such as relevance adaptation in generalized LVQ (GLVQ) and matrix learning in GLVQ. In these approaches, metric parameters are learned based on the given classification task such that a data-driven distance measure is found. In this letter, we consider full matrix adaptation in advanced LVQ schemes. In particular, we introduce matrix learning to a recent statistical formalization of LVQ, robust soft LVQ, and we compare the results on several artificial and real-life data sets to matrix learning in GLVQ, a derivation of LVQ-like learning based on a (heuristic) cost function. In all cases, matrix adaptation allows a significant improvement of the classification accuracy. Interestingly, however, the principled behavior of the models with respect to prototype locations and extracted matrix dimensions shows several characteristic differences depending on the data sets.
The extrinsic incubation period (EIP), defined as the time it takes for malaria parasites in a mosquito to become infectious to a vertebrate host, is one of the most influential parameters for ...malaria transmission but remains poorly understood. The EIP is usually estimated by quantifying salivary gland sporozoites in subsets of mosquitoes, which requires terminal sampling. However, assays that allow repeated sampling of individual mosquitoes over time could provide better resolution of the EIP.
We tested a non-destructive assay to quantify sporozoites of two rodent malaria species, Plasmodium chabaudi and Plasmodium berghei, expelled throughout 24-h windows, from sugar-soaked feeding substrates using quantitative-PCR.
The assay is able to quantify sporozoites from sugar-soaked feeding substrates, but the prevalence of parasite-positive substrates was low. Various methods were attempted to increase the detection of expelled parasites (e.g. running additional technical replicates; using groups rather than individual mosquitoes), but these did not increase the detection rate, suggesting that expulsion of sporozoites is variable and infrequent.
We reveal successful detection of expelled sporozoites from sugar-soaked feeding substrates. However, investigations of the biological causes underlying the low detection rate of sporozoites (e.g. mosquito feeding behaviour, frequency of sporozoite expulsion or sporozoite clumping) are needed to maximise the utility of using non-destructive assays to quantify sporozoite dynamics. Increasing detection rates will facilitate the detailed investigation on infection dynamics within mosquitoes, which is necessary to explain the highly variable EIP of Plasmodium and to improve understanding of malaria transmission dynamics.
Purpose
Recent developments in iterative image reconstruction enable absolute quantification of SPECT/CT studies by incorporating compensation for collimator–detector response, attenuation, and ...scatter as well as resolution recovery into the reconstruction process (Evolution; Q.Metrix package; GE Healthcare, Little Chalfont, UK). The aim of this experimental study is to assess its quantitative accuracy for potential clinical 99mTc‐sestamibi (MIBI)‐related SPECT/CT application in neoadjuvant chemotherapy response studies in breast cancer.
Methods
Two phantoms were filled with MIBI and acquired on a SPECT/CT gamma camera (Discovery 670 Pro; GE Healthcare), that is, a water cylinder and a NEMA body phantom containing six spheres that were filled with an activity concentration reflecting clinical MIBI uptake. Subsequently, volumes‐of‐interest (VOI) of each sphere were drawn (semi)automatically on SPECT using various isocontour methods or manually on CT. Finally, prone MIBI SPECT/CT scans were acquired 5 and 90 min p.i. in a locally advanced breast cancer patient.
Results
Activity concentration in the four largest spheres converged after nine iterations of evolution. Depending on the count statistics, the accuracy of the reconstructed activity concentration varied between −4.7 and −0.16% (VOI covering the entire phantom) and from 6.9% to 10% (8.8 cm ⌀ cylinder VOI placed in the center of the phantom). Recovery coefficients of SUVmax were 1.89 ± 0.18, 1.76 ± 0.17, 2.00 ± 0.38, 1.89 ± 0.35, and 0.90 ± 0.26 for spheres with 37, 28, 22, 17, and 13 mm ⌀, respectively. Recovery coefficients of SUVmean were 1.07 ± 0.06, 1.03 ± 0.09, 1.17 ± 0.21, 1.10 ± 0.20, and 0.52 ± 0.14 (42% isocontour); 1.10 ± 0.07, 1.02 ± 0.09, 1.13 ± 0.19, 1.06 ± 0.19, and 0.51 ± 0.13 (36% isocontour with local background correction); and 0.96, 1.09, 1.03, 1.03, and 0.29 (CT). Patient study results were concordant with the phantom validation.
Conclusions
Absolute SPECT/CT quantification of breast studies using MIBI seems feasible (<17% deviation) when a 42% isocontour is used for delineation for tumors of at least 17 mm diameter. However, with tumor shrinkage, response evaluation should be handled with caution, especially when using SUVmax.
Transmission reduction is a key component of global efforts to control and eliminate malaria; yet, it is unclear how the density of transmission stages (gametocytes) influences infection (proportion ...of mosquitoes infected). Human to mosquito transmission was assessed using 171 direct mosquito feeding assays conducted in Burkina Faso and Kenya. Plasmodium falciparum infects Anopheles gambiae efficiently at low densities (4% mosquitoes at 1/µl blood), although substantially more (>200/µl) are required to increase infection further. In a site in Burkina Faso, children harbour more gametocytes than adults though the non-linear relationship between gametocyte density and mosquito infection means that (per person) they only contribute slightly more to transmission. This method can be used to determine the reservoir of infection in different endemic settings. Interventions reducing gametocyte density need to be highly effective in order to halt human-mosquito transmission, although their use can be optimised by targeting those contributing the most to transmission. DOI:http://dx.doi.org/10.7554/eLife.00626.001.
Objectives The purpose of this study was to evaluate whether 123-iodine metaiodobenzylguanidine (123-I MIBG) imaging predicts ventricular arrhythmias causing appropriate implantable ...cardioverter-defibrillator (ICD) therapy (primary end point) and the composite of appropriate ICD therapy or cardiac death (secondary end point). Background Although cardiac sympathetic denervation is associated with ventricular arrhythmias, limited data are available on the predictive value of sympathetic nerve imaging with 123-I MIBG on the occurrence of arrhythmias. Methods Before ICD implantation, patients underwent 123-I MIBG and myocardial perfusion imaging. Early and late 123-I MIBG (planar and single-photon emission computed tomography SPECT) imaging was performed to assess cardiac innervation (heart-to-mediastinum ratio, cardiac washout rate, and 123-I MIBG SPECT defect score). Stress-rest myocardial perfusion imaging was performed to assess myocardial infarction and perfusion abnormalities (perfusion defect scores). During follow-up, appropriate ICD therapy and cardiac death were documented. Results One-hundred sixteen heart failure patients referred for ICD therapy were enrolled. During a mean follow-up of 23 ± 15 months, appropriate ICD therapy (primary end point) was documented in 24 (21%) patients and appropriate ICD therapy or cardiac death (secondary end point) in 32 (28%) patients. Late 123-I MIBG SPECT defect score was an independent predictor for both end points. Patients with a large late 123-I MIBG SPECT defect (summed score >26) showed significantly more appropriate ICD therapy (52% vs. 5%, p < 0.01) and appropriate ICD therapy or cardiac death (57% vs. 10%, p < 0.01) than patients with a small defect (summed score ≤26) at 3-year follow-up. Conclusions Cardiac sympathetic denervation predicts ventricular arrhythmias causing appropriate ICD therapy as well as the composite of appropriate ICD therapy or cardiac death.
Most malaria (Plasmodium spp.) parasite species undergo asexual replication synchronously within the red blood cells of their vertebrate host. Rhythmicity in this intraerythrocytic developmental ...cycle (IDC) enables parasites to maximise exploitation of the host and align transmission activities with the time of day that mosquito vectors blood feed. The IDC is also responsible for the major pathologies associated with malaria, and plasticity in the parasite's rhythm can confer tolerance to antimalarial drugs. Both the severity of infection (virulence) and synchrony of the IDC vary across species and between genotypes of Plasmodium; however, this variation is poorly understood. The theory predicts that virulence and IDC synchrony are negatively correlated, and we tested this hypothesis using two closely related genotypes of the rodent malaria model Plasmodium chabaudi that differ markedly in virulence. We also test the predictions that, in response to perturbations to the timing (phase) of the IDC schedule relative to the phase of host rhythms (misalignment), the virulent parasite genotype recovers the correct phase relationship faster, incurs less fitness losses and so hosts benefit less from misalignment when infected with a virulent genotype. Our predictions are partially supported by results suggesting that the virulent parasite genotype is less synchronous in some circumstances and recovers faster from misalignment. While hosts were less anaemic when infected by misaligned parasites, the extent of this benefit did not depend on parasite virulence. Overall, our results suggest that interventions to perturb the alignment between the IDC schedule, and host rhythms and increase synchrony between parasites within each IDC, could alleviate disease symptoms. However, virulent parasites, which are better at withstanding conventional antimalarial treatment, would also be intrinsically better able to tolerate such interventions.
Fitness costs of disrupting circadian rhythms in malaria parasites O'Donnell, Aidan J.; Schneider, Petra; McWatters, Harriet G. ...
Proceedings - Royal Society. Biological sciences/Proceedings - Royal Society. Biological Sciences,
08/2011, Letnik:
278, Številka:
1717
Journal Article
Recenzirano
Odprti dostop
Circadian biology assumes that biological rhythms maximize fitness by enabling organisms to coordinate with their environment. Despite circadian clocks being such a widespread phenomenon, ...demonstrating the fitness benefits of temporal coordination is challenging and such studies are rare. Here, we tested the consequences—for parasites—of being temporally mismatched to host circadian rhythms using the rodent malaria parasite, Plasmodium chabaudi. The cyclical nature of malaria infections is well known, as the cell cycles across parasite species last a multiple of approximately 24 h, but the evolutionary explanations for periodicity are poorly understood. We demonstrate that perturbation of parasite rhythms results in a twofold cost to the production of replicating and transmission stages. Thus, synchronization with host rhythms influences in-host survival and between-host transmission potential, revealing a role for circadian rhythms in the evolution of host–parasite interactions. More generally, our results provide a demonstration of the adaptive value of circadian rhythms and the utility of using an evolutionary framework to understand parasite traits.
The transmission of malaria to mosquitoes depends on the presence of gametocytes that circulate in the peripheral blood of infected human hosts. Sensitive estimates of the densities of female ...gametocytes (FG) and male gametocytes (MG) may allow the prediction of infectivity to mosquitoes and thus a molecular estimate of the human infectious reservoir for transmission.
A novel multiplex qRT-PCR assay with intron-spanning primers was developed for the parallel quantification of FG and MG. CCp4 (PF3D7_0903800) transcripts specific for FG and PfMGET (PF3D7_1469900) transcripts specific for MG were quantified in total nucleic acids. The assay was validated on sex-sorted gametocytes from culture material and on samples from clinical trials with gametocytocidal drugs. Synthetic RNA standards were generated for the two targets genes and calibrated against known gametocyte quantities.
The limit of detection was determined at 0.1 male and 0.1 female gametocyte/µL, which was equal to the limit of quantification (LOQ) for MG, while the LOQ for FG was 1 FG/µL. Results from previously reported clinical trials that used separate gametocyte qRT-PCR assays for FG (targeting Pfs25) and MG (targeting PfMGET) were reproduced with the multiplex assay. High levels of agreement between separate assays and the multiplex approach were observed (R
= 0.9473, 95% CI 0.9314-0.9632, for FG measured by transcript levels of Pfs25 in qRT-PCR or CCp4 in multiplex; R
= 0.8869, 95% CI 0.8541-0.9197, for MG measured by PfMGET in either single or multiplex qRT-PCR). FG and MG transcripts were detected in pure ring stage parasites at 10,000- and 100,000-fold reduced frequency for CCp4 and PfMGET, respectively. The CCp4 and PfMGET transcripts were equally stable under suboptimal storage conditions.
Gametocyte densities and their sex ratios can be determined in the presented one-step multiplex assay with higher throughput than single assays. The interpretation of low gametocyte densities at asexual parasite densities above 1000 parasites/µL requires caution to avoid false positive gametocyte signals from spurious transcript levels in ring stage parasites.
Urbanization processes in Asia are still ongoing; thus, aggregate demand is expected to increase in following years. Even though construction and demolition waste is a source for secondary building ...materials in industrialized countries, it is not yet an alternative construction material source in Vietnam as the urbanization process is still ongoing. Thus, there is a need for river sand and aggregates alternatives in concrete, namely manufactured sand (m-sand) from primary solid rock materials and secondary waste materials. The focus in the present study for Vietnam was on m-sand sand as alternative for river sand, and different ashes as alternatives for cement in concrete. The investigations comprised concrete lab tests according to the formulations of concrete strength class C 25/30 in accordance with DIN EN 206, followed by a lifecycle assessment study in order to identify the environmental impact of the alternatives. In total 84 samples were investigated, consisting of 3 reference samples, 18 samples with primary substitutes, 18 samples with secondary substitutes, and 45 samples with cement substitutes. This kind of holistic investigation approach comprising material alternatives and accompanying LCA was the first study for Vietnam, and even for Asia, and represents a substantial added value for future policy development in order to cope with resource scarcity. The results show that with the exception of metamorphic rocks, all m-sands meet the requirements for quality concrete. In terms of cement replacement, the mixes showed that a higher percentage of ash reduces the compressive strength. The compressive strength values of the mixes with up to 10% coal filter ash or rice husk ash were equivalent to the C25/30 standard concrete formulation. Higher ash contents up to 30% lead to the reduction of the concrete quality. The LCA study's results highlighted the better environmental footprints across environmental impact categories in the 10% substitution material in comparison to the use of primary materials. The LCA analysis results showed that cement as a component in concrete holds the highest footprint. The use of secondary waste as alternative for cement provides significant environmental advantage.
The Halda River and Haor basins are considered unique breeding habitats for carps in Bangladesh. The purpose of the study was to evaluate the natural spawning environment of carp species, with an ...emphasis on the hydrological conditions of the Halda River, the Surma River, and Tanguar Haor. This study, which covers the years 2021 and 2022, considered two spawning seasons. The results revealed that temperature, total dissolved solids (TDS), salinity, turbidity, conductivity, and pH were significantly different in the Halda River to the Surma River and Tanguar Haor. However, sudden rainfall and upstream runoff in 2021 were deemed as major factors causing an increment in TDS and electrical conductivity. The water pollution index was excellent in the Surma River and Tanguar Haor, and good in the Halda River. The study reported moderately reduced IMC fry production in 2021 because of inconsistent turbidity, high conductivity, and increased salinity which interrupted the ideal spawning habitat. However, in 2022, the spawning environment was favorable in the Halda River, while the Surma River and Tanguar Haor were considered to be comparatively favorable in both years. Differences were also found in the climatic and meteorological conditions, which revealed uneven rainfall, higher temperatures, decreasing water discharge, and low water levels. The meteorological data also revealed that the overall rainfall showed a decreasing trend for all sites in the last 20 years causing an interrupted water discharge. It was discovered that the amount of carp spawn obtained in the Halda River was greater than that obtained in the Surma River and Tanguar Haor. In terms of hydrological conditions and spawning performance, the Surma River and Tanguar Haor were reported to have significant differences, which may be due to their geographical location.
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