Iterative image reconstruction algorithm analysis for optical CT radiochromic gel dosimetry.

Background.Modern radiation therapy technologies aim to enhance radiation dose precision to the tumor and utilize hypofractionated treatment regimens. Verifying the dose distributions associated with these advanced radiation therapy treatments remains an active research area due to the complexity of delivery systems and the lack of suitable three-dimensional dosimetry tools. Gel dosimeters are a potential tool for measuring these complex dose distributions. A prototype tabletop solid-tank fan-beam optical CT scanner for readout of gel dosimeters was recently developed. This scanner does not have a straight raypath from source to detector, thus images cannot be reconstructed using filtered backprojection (FBP) and iterative techniques are required.Purpose.To compare a subset of the top performing algorithms in terms of image quality and quantitatively determine the optimal algorithm while accounting for refraction within the optical CT system. The following algorithms were compared: Landweber, superiorized Landweber with the fast gradient projection perturbation routine (S-LAND-FGP), the fast iterative shrinkage/thresholding algorithm with total variation penalty term (FISTA-TV), a monotone version of FISTA-TV (MFISTA-TV), superiorized conjugate gradient with the nonascending perturbation routine (S-CG-NA), superiorized conjugate gradient with the fast gradient projection perturbation routine (S-CG-FGP), superiorized conjugate gradient with with two iterations of CG performed on the current iterate and the nonascending perturbation routine (S-CG-2-NA).Methods.A ray tracing simulator was developed to track the path of light rays as they traverse the different mediums of the optical CT scanner. Two clinical phantoms and several synthetic phantoms were produced and used to evaluate the reconstruction techniques under known conditions. Reconstructed images were analyzed in terms of spatial resolution, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), signal non-uniformity (SNU), mean relative difference (MRD) and reconstruction time. We developed an image quality based method to find the optimal stopping iteration window for each algorithm. Imaging data from the prototype optical CT scanner was reconstructed and analysed to determine the optimal algorithm for this application.Results.The optimal algorithms found through the quantitative scoring metric were FISTA-TV and S-CG-2-NA. MFISTA-TV was found to behave almost identically to FISTA-TV however MFISTA-TV was unable to resolve some of the synthetic phantoms. S-CG-NA showed extreme fluctuations in the SNR and CNR values. S-CG-FGP had large fluctuations in the SNR and CNR values and the algorithm has less noise reduction than FISTA-TV and worse spatial resolution than S-CG-2-NA. S-LAND-FGP had many of the same characteristics as FISTA-TV; high noise reduction and stability from over iterating. However, S-LAND-FGP has worse SNR, CNR and SNU values as well as longer reconstruction time. S-CG-2-NA has superior spatial resolution to all algorithms while still maintaining good noise reduction and is uniquely stable from over iterating.Conclusions.Both optimal algorithms (FISTA-TV and S-CG-2-NA) are stable from over iterating and have excellent edge detection with ESF MTF 50% values of 1.266 mm-1and 0.992 mm-1. FISTA-TV had the greatest noise reduction with SNR, CNR and SNU values of 424, 434 and 0.91 × 10-4, respectively. However, low spatial resolution makes FISTA-TV only viable for large field dosimetry. S-CG-2-NA has better spatial resolution than FISTA-TV with PSF and LSF MTF 50% values of 1.581 mm-1and 0.738 mm-1, but less noise reduction. S-CG-2-NA still maintains good SNR, CNR, and SNU values of 168, 158 and 1.13 × 10-4, respectively. Thus, S-CG-2-NA is a well rounded reconstruction algorithm that would be the preferable choice for small field dosimetry.

Iterative image reconstruction with polar coordinate discretized system matrix for optical CT radiochromic gel dosimetry.

BACKGROUND: Gel dosimeters are a potential tool for measuring the complex dose distributions that characterize modern radiotherapy. A prototype tabletop solid-tank fan-beam optical CT scanner for readout of gel dosimeters was recently developed. This scanner does not have a straight raypath from source to detector, thus images cannot be reconstructed using filtered backprojection (FBP) and iterative techniques are required. Iterative image reconstruction requires a system matrix that describes the geometry of the imaging system. Stored system matrices can become immensely large, making them impractical for storage on a typical desktop computer. PURPOSE: Here we develop a method to reduce the storage size of optical CT system matrices through use of polar coordinate discretization while accounting for the refraction in optical CT systems. METHODS: A ray tracing simulator was developed to track the path of light rays as they traverse the different mediums of the optical CT scanner. Cartesian coordinate discretized system matrices (CCDSMs) and polar coordinate discretized system matrices (PCDSMs) were generated by discretizing the reconstruction area of the optical CT scanner into a Cartesian pixel grid and a polar coordinate pixel grid, respectively. The length of each ray through each pixel was calculated and used to populate the system matrices. To ensure equal weighting during iterative reconstruction, the radial rings of PCDSMs were asymmetrically spaced such that the area of each polar pixel was constant. Two clinical phantoms and several synthetic phantoms were produced and used to evaluate the reconstruction techniques under known conditions. Reconstructed images were analyzed in terms of spatial resolution, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), signal nonuniformity (SNU), and Gamma map pass percentage. RESULTS: A storage size reduction of 99.72% was found when comparing a PCDSM to a CCDSM with the same total number of pixels. Images reconstructed with a PCDSM were found to have superior SNR, CNR, SNU, and Gamma (1 mm, 1%) pass percentage compared to those reconstructed with a CCDSM. Increasing spatial resolution in the radial direction with increasing radial distance was found in both PCDSM and CCDSM reconstructions due to the outer regions refracting light more severely. Images reconstructed with a PCDSM showed a decrease in spatial resolution in the azimuthal directions as radial distance increases, due to the widening of the polar pixels. However, this can be mitigated with only a slight increase in storage size by increasing the number of projections. A loss of spatial resolution in the radial direction within 5 mm radially from center was found when reconstructing with a PCDSM, due to the large innermost pixels. However, this was remedied by increasing the number of radial rings within the PCDSM, yielding radial spatial resolution on par with images reconstructed with a CCDSM and a storage size reduction of 99.26%. CONCLUSIONS: Discretizing the image pixel elements in polar coordinates achieved a system matrix storage size reduction of 99.26% with only minimal reduction in the image quality.

Rapid radiation of ant parasitic butterflies during the Miocene aridification of Africa.

Africa has undergone a progressive aridification during the last 20 My that presumably impacted organisms and fostered the evolution of life history adaptations. We test the hypothesis that shift to living in ant nests and feeding on ant brood by larvae of phyto-predaceous Lepidochrysops butterflies was an adaptive response to the aridification of Africa that facilitated the subsequent radiation of butterflies in this genus. Using anchored hybrid enrichment we constructed a time-calibrated phylogeny for Lepidochrysops and its closest, non-parasitic relatives in the Euchrysops section (Poloyommatini). We estimated ancestral areas across the phylogeny with process-based biogeographical models and diversification rates relying on time-variable and clade-heterogeneous birth-death models. The Euchrysops section originated with the emerging Miombo woodlands about 22 million years ago (Mya) and spread to drier biomes as they became available in the late Miocene. The diversification of the non-parasitic lineages decreased as aridification intensified around 10 Mya, culminating in diversity decline. In contrast, the diversification of the phyto-predaceous Lepidochrysops lineage proceeded rapidly from about 6.5 Mya when this unusual life history likely first evolved. The Miombo woodlands were the cradle for diversification of the Euchrysops section, and our findings are consistent with the hypothesis that aridification during the Miocene selected for a phyto-predaceous life history in species of Lepidochrysops, with ant nests likely providing caterpillars a safe refuge from fire and a source of food when vegetation was scarce.

Miocene Climate and Habitat Change Drove Diversification in Bicyclus, Africa's Largest Radiation of Satyrine Butterflies.

Compared to other regions, the drivers of diversification in Africa are poorly understood. We studied a radiation of insects with over 100 species occurring in a wide range of habitats across the Afrotropics to investigate the fundamental evolutionary processes and geological events that generate and maintain patterns of species richness on the continent. By investigating the evolutionary history of Bicyclus butterflies within a phylogenetic framework, we inferred the group's origin at the Oligo-Miocene boundary from ancestors in the Congolian rainforests of central Africa. Abrupt climatic fluctuations during the Miocene (ca. 19-17 Ma) likely fragmented ancestral populations, resulting in at least eight early-divergent lineages. Only one of these lineages appears to have diversified during the drastic climate and biome changes of the early Miocene, radiating into the largest group of extant species. The other seven lineages diversified in forest ecosystems during the late Miocene and Pleistocene when climatic conditions were more favorable-warmer and wetter. Our results suggest changing Neogene climate, uplift of eastern African orogens, and biotic interactions have had different effects on the various subclades of Bicyclus, producing one of the most spectacular butterfly radiations in Africa. [Afrotropics; biodiversity; biome; biotic interactions; Court Jester; extinction; grasslands; paleoclimates; Red Queen; refugia forests; dependent-diversification; speciation.].

Amino acid-enriched plant-based RUTF treatment was not inferior to peanut-milk RUTF treatment in restoring plasma amino acid levels among patients with oedematous or non-oedematous malnutrition.

Ready-to-use therapeutic food (RUTF) with adequate quality protein is used to treat children with oedematous and non-oedematous severe acute malnutrition (SAM). The plasma amino acid (AA) profile reflects the protein nutritional status; hence, its assessment during SAM treatment is useful in evaluating AA delivery from RUTFs. The objective was to evaluate the plasma AAs during the treatment of oedematous and non-oedematous SAM in community-based management of acute malnutrition (CMAM) using amino acid-enriched plant-based RUTFs with 10% milk (MSMS-RUTF) or without milk (FSMS-RUTF) compared to peanut milk RUTF (PM-RUTF). Plasma AA was measured in a non-blinded, 3-arm, parallel-group, simple randomized controlled trial conducted in Malawi. The RUTFs used for SAM were FSMS-RUTF, MSMS-RUTF or PM-RUTF. A non-inferiority hypothesis was tested to compare plasma AA levels from patients treated with FSMS-RUTF or MSMS-RUTF with those from patients treated with PM-RUTF at discharge. For both types of SAM, FSMS-RUTF and MSMS-RUTF treatments were non-inferior to the PM-RUTF treatment in restoration of the EAA and cystine except that for FSMS-RUTF, methionine and tryptophan partially satisfied the non-inferiority criteria in the oedematous group. Amino-acid-enriched milk-free plant-source-protein RUTF has the potential to restore all the EAA, but it is possible that enrichment with amino acids may require more methionine and tryptophan for oedematous children.

To mate, or not to mate: The evolution of reproductive diapause facilitates insect radiation into African savannahs in the Late Miocene.

Many tropical environments experience cyclical seasonal changes, frequently with pronounced wet and dry seasons, leading to a highly uneven temporal distribution of resources. Short-lived animals inhabiting such environments often show season-specific adaptations to cope with alternating selection pressures. African Bicyclus butterflies show strong seasonal polyphenism in a suite of phenotypic and life-history traits, and their adults are thought to undergo reproductive diapause associated with the lack of available larval host plants during the dry season. Using 3 years of longitudinal field data for three species in Malawi, dissections demonstrated that one forest species reproduces continuously, whereas two savannah species undergo reproductive diapause in the dry season, either with or without pre-diapause mating. Using additional data from field-collected and museum samples, we then documented the same three mating strategies for a further 37 species. Phylogenetic analyses indicated that the ancestral state was a non-diapausing forest species, and that habitat preference and mating strategy evolved in a correlated fashion. Bicyclus butterflies underwent rapid diversification during the Late Miocene, coinciding with expansions into more open savannah habitat. We conclude that the ability to undergo reproductive diapause was a key trait that facilitated colonization and eventual radiation into savannahs in the Late Miocene.

Soya, maize and sorghum ready-to-use therapeutic foods are more effective in correcting anaemia and iron deficiency than the standard ready-to-use therapeutic food: randomized controlled trial.

BACKGROUND: The prevalence of anaemia and iron deficiency (ID) among children with severe acute malnutrition (SAM) and their correction during nutritional rehabilitation are not well documented. This study assessed anaemia and ID prevalence and their predictors at start of SAM treatment, and the efficacy of their treatment and effect on gut health of two novel Ready-To-Use Therapeutic foods (RUTF) prepared from soybean, maize and sorghum (SMS) with (MSMS-RUTF) or without added milk (FSMS-RUTF) compared to those of the standard formulation prepared from peanut and milk (PM-RUTF). METHODS: This was a 3-arms parallel groups, simple randomised, controlled non-inferiority trial in 6-59 months old Central Malawian children with SAM. Anaemia was defined using altitude- and ethnicity-adjusted haemoglobin. Iron status was defined using soluble transferrin receptor (sTfR) and body iron stores (BIS). We used Pearson's chi-square test, t-test for paired or unpaired data, Kruskal-Wallis test for between-arm differences as appropriate and logistic regression to identify independent predictors of anaemia or iron deficiency anaemia (IDA). RESULTS: The sample size was 389. At admission, the prevalence [%(95%CI)] of anaemia was 48.9(41.4-56.5)% while that of ID and IDA were 55.7(48.6-62.5)% and 34.3(28.2-41.0)% when using sTfR criterion and 29.1(24.4-34.4)% and 28.9(23.7-34.9)% when using BIS criterion, respectively. At discharge, nutrition rehabilitation with SMS-RUTF was associated with the lowest prevalence of anaemia [12.0(6.9-20.3)% for FSMS-RUTF, 18.2(11.9-26.8)% for MSMS-RUTF and 24.5(15.8-35.9)% for PM-RUTF; p = 0.023] and IDA [7.9(3.4-17.3)% for FSMS-RUTF, 10.9(4.8-22.6)% for MSMS-RUTF and 20.5(10.7-35.5)% for PM-RUTF; p = 0.028]. SMS-RUTF was also associated with the highest increase in BIS [Change in BIS (95%CI)] among the iron deplete at admission [6.2 (3.7; 8.6), 3.2 (0.8; 5.6), 2.2 (0.2; 4.3) for the same study arms; Anova p = 0.045]. Compared to P-RUTF, FSMS-RUTF had the highest adjusted recovery rate [OR (95%CI = 0.3 (0.2-0.5) with p < 0.001 for FSMS-RUTF and 0.6 (0.3-1.0) with p = 0.068 for MSMS-RUTF]. No effect of iron content on risk of iron overload or gut inflammation was observed. CONCLUSIONS: Anaemia and ID are common among children with SAM. FSMS-RUTF is more efficacious in treating anaemia and correcting BIS among this group than PM-RUTF. TRIAL REGISTRATION: This study was registered on 15 April 2015 ( PACTR201505001101224 ).

A neo-W chromosome in a tropical butterfly links colour pattern, male-killing, and speciation.

Sexually antagonistic selection can drive both the evolution of sex chromosomes and speciation itself. The tropical butterfly the African Queen, Danaus chrysippus, shows two such sexually antagonistic phenotypes, the first being sex-linked colour pattern, the second, susceptibility to a male-killing, maternally inherited mollicute, Spiroplasma ixodeti, which causes approximately 100% mortality in male eggs and first instar larvae. Importantly, this mortality is not affected by the infection status of the male parent and the horizontal transmission of Spiroplasma is unknown. In East Africa, male-killing of the Queen is prevalent in a narrow hybrid zone centred on Nairobi. This hybrid zone separates otherwise allopatric subspecies with different colour patterns. Here we show that a neo-W chromosome, a fusion between the W (female) chromosome and an autosome that controls both colour pattern and male-killing, links the two phenotypes thereby driving speciation across the hybrid zone. Studies of the population genetics of the neo-W around Nairobi show that the interaction between colour pattern and male-killer susceptibility restricts gene flow between two subspecies of D. chrysippus Our results demonstrate how a complex interplay between sex, colour pattern, male-killing, and a neo-W chromosome, has set up a genetic 'sink' that keeps the two subspecies apart. The association between the neo-W and male-killing thus provides a 'smoking gun' for an ongoing speciation process.

Ready-to-use therapeutic food with elevated n-3 polyunsaturated fatty acid content, with or without fish oil, to treat severe acute malnutrition: a randomized controlled trial.

BACKGROUND: Ready-to-use therapeutic foods (RUTF) are lipid-based pastes widely used in the treatment of acute malnutrition. Current specifications for RUTF permit a high n-6 polyunsaturated fatty acid (PUFA) content and low n-3 PUFA, with no stipulated requirements for preformed long-chain n-3 PUFA. The objective of this study was to develop an RUTF with elevated short-chain n-3 PUFA and measure its impact, with and without fish oil supplementation, on children's PUFA status during treatment of severe acute malnutrition. METHODS: This randomized controlled trial in children with severe acute malnutrition in rural Kenya included 60 children aged 6 to 50 months who were randomized to receive i) RUTF with standard composition; ii) RUTF with elevated short chain n-3 PUFA; or iii) RUTF with elevated short chain n-3 PUFA plus fish oil capsules. Participants were followed-up for 3 months. The primary outcome was erythrocyte PUFA composition. RESULTS: Erythrocyte docosahexaenoic acid (DHA) content declined from baseline in the two arms not receiving fish oil. Erythrocyte long-chain n-3 PUFA content following treatment was significantly higher for participants in the arm receiving fish oil than for those in the arms receiving RUTF with elevated short chain n-3 PUFA or standard RUTF alone: 3 months after enrollment, DHA content was 6.3% (interquartile range 6.0-7.3), 4.5% (3.9-4.9), and 3.9% (2.4-5.7) of total erythrocyte fatty acids (P <0.001), respectively, while eicosapentaenoic acid (EPA) content was 2.0% (1.5-2.6), 0.7% (0.6-0.8), and 0.4% (0.3-0.5) (P <0.001). RUTF with elevated short chain n-3 PUFA and fish oil capsules were acceptable to participants and carers, and there were no significant differences in safety outcomes. CONCLUSIONS: PUFA requirements of children with SAM are not met by current formulations of RUTF, or by an RUTF with elevated short-chain n-3 PUFA without additional preformed long-chain n-3 PUFA. Clinical and growth implications of revised formulations need to be addressed in large clinical trials. TRIAL REGISTRATION: Clinicaltrials.gov NCT01593969. Registered 4 May 2012.

A review of methods to detect cases of severely malnourished children in the community for their admission into community-based therapeutic care programs.

BACKGROUND: The complexity and cost of measuring weight-for-height make it unsuitable for use by community-based volunteers. This has led community therapeutic care programs to adopt a two-stage screening and admission procedure in which mid-upper-arm circumference (MUAC) is used for referral and weight-for-height is used for admission. Such a procedure results in many individuals being referred for care on the basis of MUAC but subsequently being refused treatment because they do not meet the weight-for-height admission criterion. This "problem of rejected referrals" has proved to be a major barrier to program uptake. OBJECTIVE: To systematically review methods to detect cases of severely malnourished children in the community for their admission into community-based therapeutic care programs. METHODS: Clinical and anthropometric methods for case detection of severely malnourished children in the community were reviewed with regard to their ability to reflect both mortality risk and nutritional status. RESULTS: MUAC, with the addition of the presence of bipedal edema, was found to be the indicator best suited to screening and case detection of malnutrition in the community. The case definition "MUAC < 110 mm OR the presence of bipedal edema," with MUAC measured by a color-banded strap, is suitable for screening and case detection of malnutrition in the community for children aged between 6 and 59 months. Monitoring and discharge criteria were also reviewed. CONCLUSIONS: There is no compelling evidence to support a move away from using weight in combination with clinical criteria for monitoring and discharge.