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Background Manual microscopy remains a widely-used tool for malaria diagnosis and clinical studies, but it has inconsistent quality in the field due to variability in training and field practices. Automated diagnostic systems based on machine learning hold promise to improve quality and reproducibility of field microscopy. The World Health Organization (WHO) has designed a 55-slide set (WHO 55) for their External Competence Assessment of Malaria Microscopists (ECAMM) programme, which can also serve as a valuable benchmark for automated systems. The performance of a fully-automated malaria diagnostic system, EasyScan GO, on a WHO 55 slide set was evaluated. Methods The WHO 55 slide set is designed to evaluate microscopist competence in three areas of malaria diagnosis using Giemsa-stained blood films, focused on crucial field needs: malaria parasite detection, malaria parasite species identification (ID), and malaria parasite quantitation. The EasyScan GO is a fully-automated system that combines scanning of Giemsa-stained blood films with assessment algorithms to deliver malaria diagnoses. This system was tested on a WHO 55 slide set. Results The EasyScan GO achieved 94.3 % detection accuracy, 82.9 % species ID accuracy, and 50 % quantitation accuracy, corresponding to WHO microscopy competence Levels 1, 2, and 1, respectively. This is, to our knowledge, the best performance of a fully-automated system on a WHO 55 set. Conclusions EasyScan GO’s expert ratings in detection and quantitation on the WHO 55 slide set point towards its potential value in drug efficacy use-cases, as well as in some case management situations with less stringent species ID needs. Improved runtime may enable use in general case management settings.

Knowledge of turbulence distribution along an experimental path can help in effective turbulence compensation and mitigation. Although scintillometers are traditionally used to measure the strength of turbulence, they provide a path-integrated measurement and have limited operational ranges. A technique to profile turbulence using time-lapse imagery of a distant target from spatially separated cameras is presented here. The method uses the turbulence induced differential motion between pairs of point features on a target, sensed at a single camera and between cameras to extract turbulence distribution along the path. The method is successfully demonstrated on a 511 m almost horizontal path going over half concrete and half grass. An array of Light-Emitting Diodes (LEDs) of non-uniform separation is imaged by a pair of cameras, and the extracted turbulence profiles are validated against measurements from 3D sonic anemometers placed along the path. A short-range experiment with a heat source to create local turbulence spike gives good results as well. Because the method is phase-based, it does not suffer from saturation issues and can potentially be applied over long ranges. Although in the present work, a cooperative target has been used, the technique can be used with non-cooperative targets. Application of the technique to images collected over slant paths with elevated targets can aid in understanding the altitude dependence of turbulence in the surface layer.

Distribution of substandard and falsified (SF) medicines is on the rise, and its impact on public health, particularly in low-resource countries, is becoming increasingly significant. Portable, nondestructive screening devices can support regulatory authorities in their defense against the spread of SF medicines. Vibrational spectroscopy is an ideal candidate due to its sampling ease and speed. In this work, five portable, among which four are considered low-cost, spectroscopic devices based on near-infrared (NIR), Raman, and mid-infrared (MIR) were evaluated to quantify active pharmaceutical ingredients (APIs) and formulation accuracy within simulated authentic, falsified, and substandard medicines. Binary sample mixtures containing a typical API in antimalarial, antiretroviral, or anti-tuberculosis medicines were assessed. In both univariate and multivariate analyses, the API quantification performance of the digital light processing (DLP) NIR spectrometer and a handheld Raman device consistently matched or exceeded that of the other NIR spectrometers and a scientific grade MIR spectrometer. In the formulation accuracy tests, data from all devices, other than the silicon photodiode array NIR spectrometer, were able to create regression models with less than 6% error. From this exploratory study, we conclude that certain portable NIR devices hold significant promise as cost-effective screening tools for falsified and potentially substandard medicines, and they warrant further investigation and development.

Poor-quality medicines are a major problem for health-care systems in resource-poor settings as identifying falsified medicines requires a complex laboratory infrastructure such as a Medicines Quality Control Laboratory. We report here an evaluation of a low-cost, handheld near-infrared spectrometer (NIRS) device by analyzing a library of artemisinin-based combination therapy (ACT) medicines to determine its usefulness as a drug-screening tool. The "SCiO" research prototype device was used to collect NIR spectra of a library of ACT and artesunate monotherapy medicine samples previously collected in Bioko Island and Equatorial Guinea and Kintampo, Ghana. The quality of these samples had been categorized as falsified, substandard, and quality assured based on the amount of stated active pharmaceutical ingredients detected using high-performance liquid chromatography photodiode array. Numerical analyses were performed on the NIR spectra to assess the usefulness of NIR to identify falsified and substandard medicines. The NIRS device was successful at detecting falsified medicines in all cases where the library contained both quality assured and falsified medicines of the same stated brand of medicines. The NIRS device was successful at identifying substandard amounts of artesunate but not amodiaquine in the ACT samples (N = 15) of artesunate-amodiaquine. This work reveals that this low-cost, portable NIRS device is promising for screening ACTs for falsified samples and could enable widespread drug screening at all points of the health system.

Background Human papillomavirus vaccination and cervical screening are lacking in most lower resource settings, where approximately 80% of more than 500 000 cancer cases occur annually. Visual inspection of the cervix following acetic acid application is practical but not reproducible or accurate. The objective of this study was to develop a “deep learning”-based visual evaluation algorithm that automatically recognizes cervical precancer/cancer. Methods A population-based longitudinal cohort of 9406 women ages 18–94 years in Guanacaste, Costa Rica was followed for 7 years (1993–2000), incorporating multiple cervical screening methods and histopathologic confirmation of precancers. Tumor registry linkage identified cancers up to 18 years. Archived, digitized cervical images from screening, taken with a fixed-focus camera (“cervicography”), were used for training/validation of the deep learning-based algorithm. The resultant image prediction score (0–1) could be categorized to balance sensitivity and specificity for detection of precancer/cancer. All statistical tests were two-sided. Results Automated visual evaluation of enrollment cervigrams identified cumulative precancer/cancer cases with greater accuracy (area under the curve [AUC] = 0.91, 95% confidence interval [CI] = 0.89 to 0.93) than original cervigram interpretation (AUC = 0.69, 95% CI = 0.63 to 0.74; P Conclusions The results support consideration of automated visual evaluation of cervical images from contemporary digital cameras. If achieved, this might permit dissemination of effective point-of-care cervical screening.

We propose and demonstrate a purely optical approach to trap and align particles using the interaction of polarized light with periodic nanostructures to generate enhanced trapping force. With a weakly focused laser beam, we observed efficient trapping and transportation of polystyrene beads with sizes ranging from 10 mum down to 190 nm as well as cancer cell nuclei. In addition, alignment of non-spherical dielectric particles to a 1-D periodic nanostructure was achieved with low laser intensity without attachment to birefringent crystals. Bacterial cells were trapped and aligned with incident optical intensity as low as 17 microW/microm(2).

We propose a compact and low-cost design for a variable wave plate using tunable form-birefringent grating structures in polydimethylsiloxane (PDMS). The described device operates through PDMS deformation via electrostatically actuated transparent electrodes. The optical and mechanical properties of tunable form-birefringent structures are modeled using birefringence, rigorous coupled-wave analysis, and simple structural mechanics theory. The device is fabricated by a form of soft nanoimprint lithography. The optical properties are characterized for different structure geometries. Operating principles were verified through testing of the completed device. The experimental results and theoretical study show that an irregular grating structure performs better than a periodic subwavelength structure. [2007-0303].

Malaria remains a major global health burden, and new methods for low-cost, high-sensitivity, diagnosis are essential, particularly in remote areas with low-resource around the world. In this paper, a cost effective, optical cell-phone based transmission polarized light microscope system is presented for imaging the malaria pigment known as hemozoin. It can be difficult to determine the presence of the pigment from background and other artifacts, even for skilled microscopy technicians. The pigment is much easier to observe using polarized light microscopy. However, implementation of polarized light microscopy lacks widespread adoption because the existing commercial devices have complicated designs, require sophisticated maintenance, tend to be bulky, can be expensive, and would require re-training for existing microscopy technicians. To this end, a high fidelity and high optical resolution cell-phone based polarized light microscopy system is presented which is comparable to larger bench-top polarized microscopy systems but at much lower cost and complexity. The detection of malaria in fixed and stained blood smears is presented using both, a conventional polarized microscope and our cell-phone based system. The cell-phone based polarimetric microscopy design shows the potential to have both the resolution and specificity to detect malaria in a low-cost, easy-to-use, modular platform.

The equilibrium concentration (Co) of spinel was measured in 16 high-level waste (HLW) glasses as a function of temperature (T). Glasses were formulated by increasing or decreasing concentrations of Al2O3, Cr2O3, Fe2O3, Li2O, MgO, Na2O, or NiO, one-at-a-time, from a baseline composition. Data were fitted using the quasi-ideal-solution relationship between Co and T. The coefficients of this relationship were expressed as functions of glass composition using first-order approximation. All glass components had an effect on liquidus temperature (TL), but only NiO and Fe2O3 had a significant impact on spinel concentration below TL. The temperature at which Co had a given value was also expressed as a function of glass composition. These results can be used to optimize a HLW glass formulation to meet a constraint of either no spinel or a limited spinel fraction in the melter. In addition, the measurement of the size of spinel crystals and subsequent calculation of crystal number density (n) showed that Cr2O4 and Al2O3 increase n.

Background: The haemozoin crystal continues to be investigated extensively for its potential as a biomarker for malaria diagnostics. In order for haemozoin to be a valuable biomarker, it must be present in detectable quantities in the peripheral blood and distinguishable from false positives. Here, dark-field microscopy coupled with sophisticated image processing algorithms is used to characterize the abundance of detectable haemozoin within infected erythrocytes from field samples in order to determine the window of detection in peripheral blood. Methods: Thin smears from Plasmodium falciparum-infected and uninfected patients were imaged in both dark field (DF) unstained and bright field (BF) Giemsa-stained modes. The images were co-registered such that each parasite had thumbnails in both BF and DF modes, providing an accurate map between parasites and DF objects. This map was used to find the abundance of haemozoin as a function of parasite stage through careful parasite staging and correlation with DF objects. An automated image-processing and classification algorithm classified the bright spots in the DF images as either haemozoin or non-haemozoin objects. Results: The algorithm distinguishes haemozoin from non-haemozoin objects in DF images with an object-level sensitivity of 95% and specificity of 97%. Ring stages older than about 6 hours begin to show detectable haemozoin, and rings between 10–16 hours reliably contain detectable haemozoin. However, DF microscopy coupled with the image-processing algorithm detect no haemozoin in rings younger than six hours. Discussion: Although this method demonstrates the most sensitive detection of haemozoin in field samples reported to date, it does not detect haemozoin in ring-stage parasites younger than six hours. Thus, haemozoin is a poor biomarker for field samples primarily composed of young ring-stage parasites because the crystal is not present in detectable quantities by the methods described here. Based on these results, the implications for patient-level diagnosis and recommendations for future work are discussed.

Avalanche concentration, a rapid, long-range accumulation of particles around a laser spot in a liquid sample, is demonstrated and characterized for various nanoparticles (NPs). The effect is driven by a convective flow in the sample, caused by efficient heating of NPs with high absorption efficiencies. Several types of concentration behavior were observed and characterized. Control of optical power and initial particle density was found to be effective in determining the assembly process. VO(2) nanowires, carbon nanotube (CNT), and quantum dot (QD) electrode gap bridges were assembled with a variety of sizes and geometries to show the utility of the method for nano-assembly. Bridges were assembled from as many as thousands to as few as one NP and were found to form solid electrical contact between the electrodes, as verified by measuring the current--voltage (I-V) characteristic.

Plasmonics, a rapidly emerging subdiscipline of nanophotonics, is aimed at exploiting surface plasmons for important applications, including sensing, waveguiding, and imaging. Parallel to these research efforts, technology yielding enhanced scattering and absorption of localized surface plasmons (LSPs) provides promising routes for trapping and manipulation of micro and nano scale particles, as well as biomolecules with low laser intensity due to high energy conversion efficiency under resonant excitation. In this paper, we show that the LSP-induced scattering field from a self-assembled gold nanoparticle array can be used to sustain trapping of single micron-sized particles with low laser intensity. Moreover, we demonstrate for the first time efficient localized concentration of sub-micron sized particles and DNAs of various sizes through photothermal effect of plasmonics.

We propose and demonstrate a dark-field imaging technique capable of automated identification of individual bacteria. An 87-channel multispectral system capable of angular and spectral resolution was used to measure the scattering spectrum of various bacteria in culture smears. Spectra were compared between various species and between various preparations of the same species. A 15-channel system was then used to prove the viability of bacterial identification with a relatively simple microscope system. A simple classifier was able to identify four of six bacterial species with greater than 90% accuracy in bacteria-by-bacteria testing.

The scattering characteristics of the malaria byproduct hemozoin, including its scattering distribution and depolarization, are modeled using Discrete Dipole Approximation (DDA) and compared to those of healthy red blood cells. Scattering (or dark-field) spectroscopy and imaging are used to identify hemozoin in fresh rodent blood samples. A new detection method is proposed and demonstrated using dark-field in conjunction with cross-polarization imaging and spectroscopy. SNRs greater than 50:1 are achieved for hemozoin in fresh blood without the addition of stains or reagents. The potential of such a detection system is discussed.

This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (