A machine learning-based, decision support, mobile phone application for diagnosis of common dermatological diseases.

BACKGROUND: The integration of machine learning algorithms in decision support tools for physicians is gaining popularity. These tools can tackle the disparities in healthcare access as the technology can be implemented on smartphones. We present the first, large-scale study on patients with skin of colour, in which the feasibility of a novel mobile health application (mHealth app) was investigated in actual clinical workflows. OBJECTIVE: To develop a mHealth app to diagnose 40 common skin diseases and test it in clinical settings. METHODS: A convolutional neural network-based algorithm was trained with clinical images of 40 skin diseases. A smartphone app was generated and validated on 5014 patients, attending rural and urban outpatient dermatology departments in India. The results of this mHealth app were compared against the dermatologists' diagnoses. RESULTS: The machine-learning model, in an in silico validation study, demonstrated an overall top-1 accuracy of 76.93 ± 0.88% and mean area-under-curve of 0.95 ± 0.02 on a set of clinical images. In the clinical study, on patients with skin of colour, the app achieved an overall top-1 accuracy of 75.07% (95% CI = 73.75-76.36), top-3 accuracy of 89.62% (95% CI = 88.67-90.52) and mean area-under-curve of 0.90 ± 0.07. CONCLUSION: This study underscores the utility of artificial intelligence-driven smartphone applications as a point-of-care, clinical decision support tool for dermatological diagnosis for a wide spectrum of skin diseases in patients of the skin of colour.

Photo-convertible fluorescent proteins as tools for fresh insights on subcellular interactions in plants.

Optical highlighters comprise photo-activatable, photo-switchable and photo-convertible fluorescent proteins and are relatively recent additions to the toolbox utilized for live cell imaging research. Here, we provide an overview of four photo-convertible fluorescent proteins (pcFP) that are being used in plant cell research: Eos, Kaede, Maple and Dendra2. Each of these proteins has a significant advantage over other optical highlighters since their green fluorescent nonconverted forms and red fluorescent converted forms are generally clearly visible at expression levels that do not appear to interfere with subcellular dynamics and plant development. These proteins have become increasingly useful for understanding the role of transient and sustained interactions between similar organelles. Tracking of single organelles after green-to-red conversion has provided novel insights on plastids and their stroma-filled extensions and on the formation of mega-mitochondria. Similarly colour recovery after photo-conversion has permitted the estimation of nuclear endo-reduplication events and is being developed further to image protein trafficking within the lumen of the endoplasmic reticulum. We have also applied photo-convertible proteins to create colour-differentiation between similar cell types to follow their development. Both the green and red fluorescent forms of these proteins are compatible with other commonly used single coloured FPs. This has allowed us to develop simultaneous visualization schemes for up to five types of organelles and investigate organelle interactivity. The advantages and caveats associated with the use of photo-convertible fluorescent proteins are discussed.

Cell growth: how to grow and where to grow.

Root hairs provide a model system for studying tip growth in plants. The recent cloning of genes required for tip growth has shed new light on the link between ionic regulation, cell wall assembly and the cytoskeleton in cell growth.

Cytoskeleton in plant development.

The plant cytoskeleton has crucial functions in a number of cellular processes that are essential for cell morphogenesis, organogenesis and development. These functions have been intensively investigated using single cell model systems. With the recent characterization of plant mutants that show aberrant organogenesis resulting from primary defects in cytoskeletal organization, an integrated understanding of the importance of the cytoskeleton for plant development has begun to emerge. Newly established techniques that allow the non-destructive visualization of microtubules or actin filaments in living plant cells and organs will further advance this understanding.

The influence of heavy water on boron requirements for neutron capture therapy.

Neutron penetration in tissue is a major limitation of thermal NCT, as such much work has centered upon the epithermal neutron beam in an effort to improve this situation. Further gains in neutron flux penetration, and thus therapeutic ratios, are possible if natural water is replaced with heavy water prior to therapy. Applying MCNP to a heterogeneous ellipsoidal skull/brain model, advantage depth and therapeutic depth parameters are studied as a function of heavy water replacement for a range of tumor to blood boron ratios. Both thermal (0.025 eV) and epithermal (2-7 keV) ideal neutron beams are analyzed. Using 10B ratios in the range of documented human uptake, the thermal advantage depth improved by approximately 0.7 cm for 20% D2O replacement, however, the therapeutic depth increased by less than half this value. For the epithermal beam, both the advantage depth and the therapeutic depth increased by over 1 cm. Effects of heavy water replacement on 10B requirements to therapeutically treat the midline of the brain are also evaluated.

A new radiotherapy surface dose detector:the MOSFET.

Radiotherapy x-ray and electron beam surface doses are accurately measurable by use of a MOS-FET detector system. The MOSFET (Metal Oxide Semiconductor Field Effect Transistor) is approximately 200-microns in diameter and consists of a 0.5-microns Al electrode on top of a 1-microns SiO2 and 300-microns Si substrate. Results for % surface dose were within +/- 2% compared to the Attix chamber and within +/- 3% of TLD extrapolation results for normally incident beams. Detectors were compared using different energies, field size, and beam modifying devices such as block trays and wedges. Percentage surface dose for 10 x 10-cm and 40 x 40-cm field size for 6-MV x rays at 100-cm SSD using the MOSFET were 16% and 42% of maximum, respectively. Factors such as its small size, immediate retrieval of results, high accuracy attainable from low applied doses, and as the MOSFET records its dose history make it a suitable in vivo dosimeter where surface and skin doses need to be determined. This can be achieved within part of the first fraction of dose (i.e., only 10 cGy is required.)

Magnetic repulsion of linear accelerator contaminates.

Neodymium Iron Boron (NdFeB) rare earth permanent magnets have unique properties that enable them to fit easily onto the accessory mount of a clinical linear accelerator to partially sweep away electron contamination produced by the treatment head and block trays and thus increase skin sparing. Using such magnets the central axis entrance surface dose has been reduced by 11% for a 20 x 30 cm field size from 32% to 21% of maximum dose by the magnetic device. A reduction of 14% from 32% to 18% was seen for a 20 x 20 cm field size with a 6 mm perspex block tray positioned above the magnet. The magnetic device is light weight and thus clinically usable.

Teatment planning figures of merit in thermal and epithermal boron neutron capture therapy of brain tumours.

The boron neutron capture therapy (BNCT) figures of merit of advantage depth, therapeutic depth, modified advantage depth and maximum therapeutic depth have been studied as functions of 10B tumour to blood ratios and absolute levels. These relationships were examined using the Monte Carlo neutron photon transport code, MCNP, with an ideal 18.4 cm diameter neutron beam incident laterally upon all ellipsoidal neutron photon brain-equivalent model. Mono-energetic beams of 0.025 eV (thermal) and 35 eV (epithermal) were simulated. Increasing the tumour to blood 10B ratio predictably increases all figures of merit. concentration was also shown to have a strong bearing on the figures of merit when low levels were present in the system. This is the result of a non-10B dependent background dose. At higher levels however, the concentration of 10B has a diminishing influence. For boron sulphydryl (BSH), little advantage is gained by extending the blood 10B level beyond 30 ppm, whilst for D,L,-p-boronophenylalanine (BPA) this limit is 10 ppm. To achieve a therapeutic depth of 6 cm (brain mid-line from brain surface) using the thermal beam, a tumour to blood ratio of 25 with 10 ppm 10B in the blood is required for BPA. Similarly, a tumour to blood ratio of 8.5 with 30 ppm blood 10B is required for the maximum therapeutic depth of BSH to reach the brain mid-line. These requirements are five times above current values for these compounds in humans. Applying the epithermal beam under identical conditions, the therapeutic depth reaches the brain mid-line with a tumour to blood 10B ratio of only 5.7 for BPA. For BSH, the maximum therapeutic depth reaches the brain mid-line with a tumour to blood ratio of only 1.9 with 30 ppm in the blood. Human data for these compounds are very close to these requirements.

Radiochromic film as a radiotherapy surface-dose detector.

Radiochromic film is shown to be a useful surface-dose detector for radiotherapy x-ray beams. Central-axis percentage surface-dose results as measured by Gafchromic film for a 6 MVp x-ray beam produced by a Varian 2100C Linac at 100 cm SSD are 16%, 25%, 35%, 41% for 10, 20, 30 and 40 cm square field sizes, respectively. Using a simple, uniform light source and a CCD camera connected to an image analysis system, quantitative 3D surface doses are accurately attainable in real time as either numerical data, a black-and-white image or a colour-enhanced image.

Monte Carlo calculations of epithermal boron neutron capture therapy with heavy water.

Much work over the past decade has centred upon the development of epithermal neutron beams for boron neutron capture therapy (BNCT) in an effort to increase thermal-neutron flux penetration and dose homogeneity throughout the brain. While heavy water has been used extensively to improve neutron penetration associated with thermal neutron beams, the effects of heavy water with epithermal neutron beams remain largely unexplored. Applying the Monte Carlo code MCNP to a heterogenous ellipsoidal skull/brain model, the effects of heavy-water replacement are studied for the JRC/ECN Petten HFR epithermal neutron beam. Thermal neutron flux and induced gamma depth dose distributions are calculated for 20% D2O replacement in comparison to standard brain and skull materials. Results are presented for both unilateral and bilateral irradiation. With bilateral irradiation, thermal-neutron flux homogeneity is substantially increased with 20% D2O replacement, thus improving the potential to give lethal doses to boron-10-loaded, disseminated cancer cells whilst avoiding local 'hot spots' to healthy tissue. Additionally, the induced gamma dose is reduced by up to 30%, substantially lowering the background dose to healthy tissue. With bilateral irradiation, 20% D2O replacement increases the therapeutic ratio from 2.25 to 2.75 for over 4 cm depth centred at the midline of the brain. These calculations use documented tumour and blood 10B concentrations for boronophenylalanine (BPA) in humans and recently documented neutron relative biological effectiveness (RBE) values.

Effect of interaction of thenoyltrifluoroacetone with neutral oxo-donors in the synergistic extraction of tervalent actinides.

The interaction of HTTA with TBP, DOSO, DBBP and TOPO in xylene has been studied by a spectrophotometric method. The complex species formed is HTTA. S (where S is a neutral donor) and the equilibrium constants for the formation of the species follow the order TOPO > DBBP > DOSO > TBP. After application of a correction for the HTTA-S interaction, the free HTTA and S concentrations in the organic phase were calculated. Plots of log D vs. log [HTTA] for the tervalent actinides Am, Cm, Bk and Cf gave straight lines with a slope of 3 only after application of the interaction correction, otherwise curves with slopes varying from 3 to 2 were found. The equilibrium constants of the organic phase synergistic reactions of the tervalent actinides are found to be approximately 10% higher after application of the HTTA-S interaction correction.

Extraction of actinides and fission products by octyl(phenyl)-N,N-diisobutylcarbamoylmethyl-phosphine oxide from nitric acid media.

Extraction of promethium(III), uranium(VI), plutonium(IV), americium(III), zirconium(IV), ruthenium(III), iron(III) and palladium(II) has been carried out with a mixture of octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO) and tributyl phosphate (TBP) in dodecane. The effects of nitric acid, TBP and CMPO concentrations on the extraction of these metal ions have been studied. The nature of the species of the above metal ions extracted into the organic phase has been suggested.

ICP-AES determination of silver after chemical separation from uranium matrix.

The separation of silver from a uranium matrix has been carried out using Cyanex-471X (triisobutylphosphine sulphide) in xylene. The effects of various parameters such as the Cyanex-471X concentration, the nitric acid molarity, the contact time and the nitrate ion concentration on the extraction of silver have been studied. The silver metal ion species extracted into the organic phase was found to be Ag(NO(3)).2S (where S is Cyanex-471X). The stripping of silver into an aqueous medium was carried out with 5% NaHSO(3), followed by its determination using ICP-AES.

Determination of trace impurities in uranium, thorium and plutonium matrices by solvent extraction and inductively coupled plasma atomic emission spectrometry.

Studies on the determination of trace metallic impurities in nuclear materials such as uranium, thorium and plutonium are described. The bulk of the matrix is separated by batch extraction from their nitric acid solutions using 2-ethylhexyl hydrogen 2-ethylhexyl phosphonate (KSM-17, equivalent to PC88-A). The final aqueous phase containing the metallic impurities is fed to a high-temperature source inductively coupled plasma and the analysis is carried out employing a computer-controlled multichannel direct-reading spectrometer. The studies also included the recovery of impurities at various acidities and spectral interferences of the above matrices over the analyte elements. Based on the above studies, methods were standardized for the determination of 19 elements, viz. Al, B, Be, Ca, Cd, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Si, Zn, Ce, Dy, Eu, Gd and Sm, in U/Th/Pu solutions. The relative standard deviation for various elements is in the range 1-5%.

Recovery of plutonium and americium from laboratory acidic waste solutions using tri-n-octylamine and octylphenyl-N-N- diisobutylcarbamoylmethylphosphine oxide.

Plutonium from acidic waste solutions has been recovered quantitatively using tri-n-octylamine (TnOA) in xylene and americium using a mixture of octylphenyl-N-N- diisobutylcarbamoylmethylphosphine oxide (CMPO) and TBP in dodecane by extraction and extraction chromatographic methods. The Pu ( IV ) TnOA species extracted into the organic phase from higher nitric acid concentrations has been confirmed as (R(3)NH)(2)Pu(NO(3))(6) (where R(3)N = TnOA by employing slope analysis as well as spectrophotometric studies.

The influence of various carbon and nitrogen sources on oil production by Fusarium oxysporum.

The oil-synthesizing capacity of Fusarium oxysporum, cultivated on basal nutrient medium, was evaluated using different carbon and nitrogen sources. In one of the media, molasses was also used as a principal carbon source. Media containing glucose and ammonium nitrate were found to be most efficient for oil production. Fatty acid profile of the fungal oil indicated the presence of a wide range of fatty acids ranging from C8 to C24. Fatty acid composition largely depends on the type of carbon and nitrogen sources.

Fatty acid composition of oil synthesized by Aspergillus nidulans.

The filamentous fungus Aspergillus nidulans Eidam strain 300 was found to be capable of synthesizing 24.9% oil or remarkably low free fatty acidity, in a chemically defined medium with 34% glucose as sole carbon source. although the total content of oil synthesized was less, utilization of the carbon source is better as shown by the high (8.4) fat coefficient. The major component fatty acids of the oil were palmitic, stearic, oleic and linoleic and are influenced by the source of carbon. Palmitoleic acid is present in traces, confirming thereby the general observation that high oil formers produce oil of low hexadecenoic acid content. The relatively high stearic acid content of the oil distinguishes it from those of other microorganisms and resembles the oil produced by certain tropical plants, such as Madhuca latifolia.

Blood histaminase in phlyctenulosis.

Blood Histaminase estimations were done in 42 cases of phlyctenulosis and 25 normal subjects. Significantly higher level of blood Histaminase was found in patients of phlyctenulosis, which may be a consequence of its induction secondary to increased release of histamine in the early phase of disease.

Study of serum amylase in acute viral hepatitis.

Serum total Amylase and its heat stable fraction (HSF) were studied in 10 healthy controls, and 20 patients of Viral hepatitis. A highly significant (p < 0.001) elevation in the levels of total and HSF of Serum amylase was found in acute viral hepatitis, mainly due to the HSF which originates from hepatitis. The levels declined significantly after 10 days when the disease regressed and there was evidence of improvement in clinical and functional status of the liver. Hence an estimation of total and HSF of Serum amylase proved to have some diagnostic and prognostic importance.

Effect of pinealectomy on daily rhythm of blood glucose in rabbits.

Daily rhythm of blood glucose was studied in superior cervical ganglionectomized (SCGX), sham operated and normal rabbits. A typical daily rhythm was observed in normal animals which was not influenced by surgical procedures. However, ganglionectomy, which tantamount to physiological elimination of pineal gland, caused complete reversal of this rhythm. Probable role of pineal gland in controlling blood glucose daily rhythm is suggested.