Extensive Distribution Research Articles

Distributional modelling of positively skewed data via the flexible Weibull extension distribution

SummaryThe time until an event occurs is often known to have a skewed distribution. To model this, a statistical distribution called the two‐parameter flexible Weibull extension (FWE) has been proposed. In this paper, the FWE distribution is used to model datasets through the use of generalised additive models for location, scale and shape (GAMLSS) distributional regression. GAMLSS is the only regression technique that can examine the effects of both categorical and numeric predictors on all the parameters of the distribution used to fit the dependent variable. To make it easier to use the FWE distribution through GAMLSS, the RelDists R package is proposed. A simulation study shows that FWE modelling through GAMLSS provides reliable parameter estimates even in the presence of factors that affect the distribution.

Distributions of larvae and juveniles of Pacific saury Cololabis saira during winter in relation to oceanographic structures in the central and western North Pacific Ocean

AbstractFor small pelagic fish, the physical and feeding environments during the larval and juvenile periods significantly affect recruitment to standing stock. To understand the variation in environmental conditions experienced by larvae and juveniles, this study determined the distribution of larval and juvenile Pacific saury Cololabis saira over a distance of more than 6900 km in an east–west direction in relation to the ocean environment in winter. Specimens were collected from the western and central parts of the North Pacific Ocean, mainly in January and February 2018 and 2020. Larvae (≤39.9 mm) were broadly distributed around the Kuroshio Current and the Kuroshio Extension Current. Larval densities in the water masses around the Kuroshio Extension Current were as high as, or even significantly higher than, those around the Kuroshio Current, which is considered the main spawning ground. Most juveniles (≥40.0 mm) were captured north of the Kuroshio Extension Current, where sea surface temperatures were lower and chlorophyll a concentrations were higher. The generalized additive model analysis also suggested that, compared to larvae, juveniles tended to be distributed in areas with lower sea surface temperatures and in more eastern areas. The extensive distribution of Pacific saury larvae and juveniles indicates that it is necessary to focus not only on the marine environment around the Kuroshio region but also on the Kuroshio Extension region to understand the recruitment variability of this species.

Dynamic model in analyzing Indonesia’s agricultural sector’s macroeconomic performance

Indonesia, an emerging archipelagic nation, possesses abundant natural resources spanning marine, land (including forests and water sources), and diverse biological riches. The agricultural sector emerges as a pivotal driver of growth across the country, exhibiting extensive distribution. Consequently, there is an urgent imperative for comprehensive research to bolster and optimize the performance of this sector. This study aims to meticulously analyze and scrutinize macroeconomic variables aimed at enhancing Indonesia’s agricultural sector. Through the utilization of a dynamic panel model, the study zeroes in on crucial variables: economic growth in the agricultural sector, farmer terms of exchange, human development index, population density, inflation, average daily wages, and lagged economic growth data from each province in Indonesia. The best model for dynamic panel testing, employing both First Difference Generalized Method of Moments (FD-GMM) and Generalized Method of Moments System (SYS-GMM) approaches, is identified as the SYS-GMM model. This model exhibits unbiased and consistent estimation, as evidenced by the Arellano-Bond (AB) test and Sargan test results. The analysis conducted using this selected model reveals notable findings. Lagging agricultural sector performance, human capital measured by the Human Development Index (HDI), and farmers’ exchange rates are found to significantly and positively influence the economic growth of the agricultural sector. Conversely, inflation exerts a significant and negative impact on sectoral growth. However, wage levels and population density do not demonstrate a significant partial effect on the economic growth of the agricultural sector.

Divergent lineages in a young species: The case of datilillo (Yucca valida), a broadly distributed plant from the Baja California Peninsula.

Globally, barriers triggered by climatic changes have caused habitat fragmentation and population allopatric divergence. Across North America, oscillations during the Quaternary have played important roles in the distribution of wildlife. Notably, diverse plant species from the Baja California Peninsula in western North America, isolated during the Pleistocene glacial-interglacial cycles, exhibit strong genetic structure and highly concordant divergent lineages across their ranges. A representative plant genus of the peninsula is Yucca, with Y. valida having the widest range. Although a dominant species, it has an extensive distribution discontinuity between 26° N and 27° N, suggesting restricted gene flow. Moreover, historical distribution models indicate the absence of an area with suitable conditions for the species during the Last Interglacial, making it an interesting model for studying genetic divergence. We assembled 4411 SNPs from 147 plants of Y. valida throughout its range to examine its phylogeography to identify the number of genetic lineages, quantify their genetic differentiation, reconstruct their demographic history and estimate the age of the species. Three allopatric lineages were identified based on the SNPs. Our analyses support that genetic drift is the driver of genetic differentiation among these lineages. We estimated an age of less than 1 million years for the common ancestor of Y. valida and its sister species. Habitat fragmentation caused by climatic changes, low dispersal, and an extensive geographical range gap acted as cumulative mechanisms leading to allopatric divergence in Y. valida.

Nitrogen fixation in the widely distributed marine γ-proteobacterial diazotroph Candidatus Thalassolituus haligoni.

The high diversity and global distribution of heterotrophic bacterial diazotrophs (HBDs) in the ocean has recently become apparent. However, understanding the role these largely uncultured microorganisms play in marine N2 fixation poses a challenge due to their undefined growth requirements and the complex regulation of the nitrogenase enzyme. We isolated and characterized Candidatus Thalassolituus haligoni, a member of a widely distributed clade of HBD belonging to the Oceanospirillales. Analysis of its nifH gene via amplicon sequencing revealed the extensive distribution of Cand. T. haligoni across the Pacific, Atlantic, and Arctic Oceans. Pangenome analysis indicates that the isolate shares >99% identity with an uncultured metagenome-assembled genome called Arc-Gamma-03, recently recovered from the Arctic Ocean. Through combined genomic, proteomic, and physiological approaches, we confirmed that the isolate fixes N2 gas. However, the mechanisms governing nitrogenase regulation in Cand. T. haligoni remain unclear. We propose Cand. T. haligoni as a globally distributed, cultured HBD model species within this understudied clade of Oceanospirillales.

Efficacy and safety of emodepside compared with albendazole in adolescents and adults with hookworm infection in Pemba Island, Tanzania: a double-blind, superiority, phase 2b, randomised controlled trial

Human hookworm is a cause of enormous global morbidity. Current treatments have insufficient efficacy and their extensive and indiscriminate distribution could also result in drug resistance. Therefore, we tested the efficacy and safety of emodepside, a strong anthelmintic candidate that is currently undergoing clinical development for onchocerciasis and soil-transmitted helminth infections. We conducted a double-blind, superiority, phase 2b, randomised controlled clinical trial comparing emodepside and albendazole. Participants in the emodepside group received six 5 mg tablets of emodepside (totalling 30 mg) and one placebo; participants in the albendazole group received one 400 mg tablet of albendazole and six placebos. Participants were recruited from four endemic villages and three secondary schools in Pemba Island, Tanzania. Participants aged 12-60 years were eligible for treatment if they were positive for hookworm infection, and they had 48 or more eggs per gram from four Kato-Katz thick smears and at least two slides had more than one hookworm egg present. Participants' treatment allocation was stratified by infection intensity and efficacy was measured by cure rate: participants who were hookworm positive and became hookworm negative after treatment. Adverse events were reported at 3 h, 24 h, 48 h, and 14-21 days post-treatment. The trial is registered at ClinicalTrials.gov, NCT05538767. From Sept 15 to Nov 8, 2022, and from Feb 15 to March 15, 2023, 1609 individuals were screened for hookworm. Of these, 293 individuals were treated: 147 with albendazole and 146 with emodepside. Emodepside demonstrated superiority, with an observed cure rate against hookworm of 96·6%, which was significantly higher compared with albendazole (cure rate 81·2%, odds ratio 0·14, 95% CI 0·04-0·35; p=0·0001). The most common adverse event in the emodepside treatment group was vision blur at 3 h after treatment (57 [39%] of 146). Other common adverse events were vision blur at 24 h after treatment (55 [38%]), and headache and dizziness at 3 h after treatment (55 [38%] for headache and 43 [30%] for dizziness). In the emodepside treatment group, 298 (93%) of the 319 adverse events were mild. The most commonly reported adverse events in the albendazole treatment group were headache and dizziness at 3 h after treatment (27 [18%] of 147 for headache and 14 [10%] for dizziness). No serious adverse events were reported. This phase 2b clinical trial confirms the high efficacy of emodepside against hookworm infections, solidifying emodepside as a promising anthelmintic candidate. However, although the observed safety events were generally mild in severity, considerations must be made to balance the strong efficacy outcomes with the increased frequency of adverse events compared with albendazole. European Research Council.

Novel pterygotid sea scorpions from the Silurian and Devonian of Gondwana

Sea scorpions (eurypterids) are a group of extinct aquatic chelicerates that have a fossil record spanning the Ordovician through to the end Permian extinction. Due to their size and preservational potential, eurypterids have been well-documented in European and North American deposits, with less evidence from Gondwana. There is particularly limited evidence of the group from the Australian fossil record. To rectify this, we report new examples of pterygotid eurypterids from the late Silurian Wallace Shale and Early Devonian Merrimerriwa Formation, Mulga Downs Group in New South Wales. These specimens are assigned to Pterygotus sp. (Wallace Shale) and Jaekelopterus c.f. rhenaniae (Merrimerriwa Formation, Mulga Downs Group). The material is used to explore the extensive distribution and dispersal of these large, pelagic eurypterids and consider the position of the animals in their respective paleoecosystems. We conclude that these new records evidence the diversity of larger arthropods in Australian deposits and that ongoing documentation of these rare fossils is required to further understand the Paleozoic of Australia.

Classical And Bayesian Inferences of a New Additive Weibull Extension Distribution with Application

Classical And Bayesian Inferences of a New Additive Weibull Extension Distribution with Application

Human monkeypox disease prediction using novel modified restricted Boltzmann machine-based equilibrium optimizer

While the globe continues to struggle to recover from the devastation brought on by the COVID-19 virus's extensive distribution, the recent worrying rise in human monkeypox outbreaks in several nations raises the possibility of a novel worldwide pandemic. The symptoms of human monkeypox resemble those of chickenpox and traditional measles, with a few subtle variations like the various kinds of skin blisters. A range of deep learning techniques have demonstrated encouraging results in image-oriented tumor cell, Covid-19 diagnosis, and skin disease prediction tasks. Hence, it becomes necessary to perform the prediction of the new monkeypox disease using deep learning techniques. In this paper, an image-oriented human monkeypox disease prediction is performed with the help of novel deep learning methodology. Initially, the data is gathered from the standard benchmark dataset called Monkeypox Skin Lesion Dataset. From the collected data, the pre-processing is accomplished using image resizing and image normalization as well as data augmentation techniques. These pre-processed images undergo the feature extraction that is performed by the Convolutional Block Attention Module (CBAM) approach. The extracted features undergo the final prediction phase using the Modified Restricted Boltzmann Machine (MRBM), where the parameter tuning in RBM is accomplished by the nature inspired optimization algorithm referred to as Equilibrium Optimizer (EO), with the consideration of error minimization as the major objective function. Simulation findings demonstrate that the proposed model performed better than the remaining models at monkeypox prediction. The proposed MRBM-EO for the suggested human monkeypox disease prediction model in terms of RMSE is 75.68%, 70%, 60.87%, and 43.75% better than PSO-SVM, Xception-CBAM-Dense, ShuffleNet, and RBM respectively. Similarly, the proposed MRBM-EO for the suggested human monkeypox disease prediction model with respect to accuracy is 9.22%, 7.75%, 3.77%, and 10.90% better than PSO-SVM, Xception-CBAM-Dense, ShuffleNet, and RBM respectively.

Magnetic resonance imaging pattern recognition of metabolic and neurodegenerative encephalopathies in dogs and cats.

Metabolic/neurodegenerative encephalopathies encompass a wide list of conditions that share similar clinical and magnetic resonance imaging (MRI) characteristics, challenging the diagnostic process and resulting in numerous tests performed in order to reach a definitive diagnosis. The aims of this multicentric, retrospective and descriptive study are: (I) to describe the MRI features of dogs and cats with metabolic/neurodegenerative encephalopathies; (II) to attempt an MRI recognition pattern classifying these conditions according to the involvement of grey matter, white matter or both; and (III) to correlate the MRI findings with previous literature. A total of 100 cases were recruited, comprising 81 dogs and 19 cats. These included hepatic encephalopathy (20 dogs and three cats), myelinolysis (five dogs), intoxications (seven dogs and one cat), thiamine deficiency (two dogs and seven cats), hypertensive encephalopathy (three dogs and two cats), neuronal ceroid lipofuscinosis (11 dogs and one cat), gangliosidosis (three dogs and two cats), fucosidosis (one dog), L-2-hydroxyglutaric aciduria (13 dogs and one cat), Lafora disease (11 dogs), spongiform leukoencephalomyelopathy (one dog) and cerebellar cortical degeneration (four dogs and two cats). None of the hepatic encephalopathies showed the previously described T1-weighted hyperintensity of the lentiform nuclei. Instead, there was involvement of the cerebellar nuclei (8/23), which is a feature not previously described. Dogs with myelinolysis showed novel involvement of a specific white matter structure, the superior longitudinal fasciculus (5/5). Thiamine deficiency affected numerous deep grey nuclei with novel involvement of the oculomotor nuclei (3/9), thalamic nuclei, subthalamus and cerebellar nuclei (1/9). Cats with hypertensive encephalopathy had a more extensive distribution of the white matter changes when compared to dogs, extending from the parietal and occipital lobes into the frontal lobes with associated mass effect and increased brain volume. Lysosomal storage disease showed white matter involvement only, with neuronal ceroid lipofuscinosis characterised by severe brain atrophy when compared to gangliosidosis and fucosidosis. All patients with L-2-hydroxyglutaric aciduria had a characteristic T2-weighted hyperintense swelling of the cerebral and cerebellar cortical grey matter, resulting in increased brain volume. Lafora disease cases showed either normal brain morphology (5/11) or mild brain atrophy (6/11). Dogs with cerebellar cortical degeneration had more marked cerebellar atrophy when compared to cats. This study shows the important role of MRI in distinguishing different metabolic/neurodegenerative encephalopathies according to specific imaging characteristics.

The Main Controlling Factors of the Cambrian Ultra-Deep Dolomite Reservoir in the Tarim Basin

The genesis of deep-to-ultra-deep dolomite reservoirs in the Tarim Basin is crucial for exploration and development. The Cambrian subsalt dolomite reservoirs in the Tarim Basin are widely distributed, marking significant prospects for ultra-deep reservoir exploration. Based on big data methodologies, this study collects and analyzes porosity and permeability data of carbonate reservoirs in the western Tarim Basin, specifically targeting the Cambrian deep-oil and gas-reservoir research. Through an examination of the sedimentary evolution and distribution of carbonate–evaporite sequences, and considering sedimentary facies, stratigraphic sediment thickness, fault zone distribution, and source-reservoir assemblages as primary reference factors, the study explores the macro-distribution patterns of porosity and permeability, categorizing three favorable reservoir zones. The controlling factors for the development of Cambrian carbonate reservoirs on the western part of the Tarim Basin are analyzed from the perspectives of sedimentary and diagenetic periods. Factors such as tectonic activity, depositional environment, microbial activity, and pressure dissolution are analyzed to understand the main causes of differences in porosity and permeability distribution. Comprehensive analysis reveals that the porosity and permeability of the Series2 carbonate reservoirs are notably high, with extensive distribution areas, particularly in the Bachu–Tazhong and Keping regions. The geological pattern of “Three Paleo-uplifts and Two Depressions” facilitated the formation of inner-ramp and intra-platform shoals, creating conducive conditions for the emergence of high-porosity reservoirs. The characteristics of reservoir development are predominantly influenced by diagenetic and tectonic activities. The Miaolingian is chiefly affected by diagenesis, featuring high permeability but lower porosity and smaller distribution range; dolomitization, dissolution, and filling processes under a dry and hot paleoclimate significantly contribute to the formation and preservation of reservoir spaces. In the Furongian, the Keping and Bachu areas display elevated porosity and permeability levels, along with substantial sedimentary thickness. The conservation and development of porosity within thick dolomite sequences are mainly governed by high-energy-particulate shallow-shoal sedimentary facies and various dissolution actions during diagenesis, potentially indicating larger reserves.

Diverse and ecologically unique mesophotic coral ecosystems in the central Indian Ocean

Research on Mesophotic Coral Ecosystems (MCEs; 30–150 m) has grown exponentially in the last few decades, highlighting their rich diversity and extensive distribution. However, they are still largely underexplored compared to shallow-water coral reefs and frequently remain under-protected and under-represented in marine spatial planning. One reason for the imbalance between the high ecological value of MCEs and the limited levels of protection may be that baseline data on MCEs are largely missing to date, yet are crucial to provide evidence-based information for management actions. Here, we present data on the alpha and beta diversity of the benthic communities within MCEs in the Chagos Archipelago, Indian Ocean. Using imagery collected from Remotely Operated Vehicle surveys, benthic invertebrate megafauna were surveyed along the entire depth gradient from shallow to lower mesophotic depths (15–160 m). The diversity of the benthic communities decreased with increasing depth, from shallow water to the lower mesophotic zone. Nevertheless, the deepest parts of MCEs in the Archipelago displayed higher species richness values than several other shallow subtropical regions. In addition, the benthic communities showed high dissimilarity along the depth gradient, indicating that the key driver of community composition change with depth is species turnover (species replacement), revealing the uniqueness of MCEs. This study presents novel findings on MCEs in the central Indian Ocean, demonstrating that they host a high and unique benthic diversity, and highlighting the need to protect these ecosystems to preserve the overall biodiversity of coral reefs.

Asian Mus musculus: subspecies divergence, genetic diversity, and historical biogeography

Abstract The House Mouse, Mus musculus, is a model organism that has greatly contributed to evolutionary research. Despite its significance, there remain gaps in our understanding of its phylogeography and population genetic structure in Asian regions. This comprehensive study aims to elucidate the evolutionary history, genetic diversity, and distribution patterns of M. musculus. A diverse data set of 281 M. musculus samples was collected from across Asia, covering 101 localities in 19 countries. Phylogenetic analysis using Cytochrome b and D-Loop region unveiled well-supported lineages. These lineages correspond to: M. m. musculus, M. m. domesticus, M. m. castaneus, and M. m. bactrianus. Also, validity of M. m. bactrianus was questioned. The analysis suggests a monophyletic origin of these subspecies approximately 0.59 million years ago (Mya), followed by 2 main lineages—one consisting of M. m. domesticus (~0.59 Mya) and the other comprising M. m. castaneus, M. m. bactrianus, and M. m. musculus (~0.56 Mya). Genetic diversity varied among subspecies, with M. m. domesticus exhibiting the highest diversity due to its extensive global distribution and M. m. bactrianus exhibiting the lowest diversity due to restriction in southwest Asia. Pairwise genetic distances and Fst values confirmed significant genetic differentiation among the subspecies, underlining their historical isolation. Additionally, a Mantel test indicated that geographical distance played a pivotal role in shaping genetic differentiation. Demographic analysis revealed evidence of population expansions in M. m. domesticus, M. m. musculus, and M. m. castaneus, while M. m. bactrianus showed characteristics of neutral selection and genetic drift. Species distribution modeling, assessing both Current Conditions and the Last Glacial Maximum, indicated habitat shifts and losses during glacial periods, particularly in the eastern and northern regions of Asia. However, each subspecies displayed unique responses to climatic changes, reflecting their distinct ecological adaptations. Historical biogeography analysis pointed to complex origins and a network of dispersal and vicariance events that led to the contemporary distribution of subspecies. Deserts and xeric shrublands emerged as critical areas for diversification and speciation. This study contributes to our understanding of the phylogeography and population genetics of M. musculus in Asia, highlighting the significance of geographical factors and climatic fluctuations in shaping its evolutionary history and genetic diversity.

The impact of Hashimoto's thyroiditis on the clinical outcome of papillary thyroid cancer after radioactive iodine therapy: a propensity score matching study.

The potential association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) has been studied from different perspectives for many years. This study was aimed to evaluate the impact of HT on the clinical outcomes of PTC patients after radioactive iodine (RAI) therapy. We conducted a retrospective study on consecutive patients with PTC who underwent RAI therapy from April 2017 to May 2020. The diagnosis of HT was based on pathological examination, and patients were divided into the HT and non-HT group. Distributions of age, gender, ultrasound features, papillary variants, extrathyroidal extension, and other histopathological characteristics were observed. Propensity score matching (PSM) was used to compare the clinical features and outcomes between the two groups at 1 and 3-year follow-up. In total, 782 patients with PTC were enrolled (570 women, 212 men). HT was presented in 130 (16.6%) patients, and was associated with younger age, smaller primary tumors, less extrathyroidal extension, and less lymph node metastasis at presentation. On review of the images, only calcification and blood flow distribution were significantly different among the US features (P < 0.05). At the end of follow-up (three years), the responses to RAI therapy were significantly different between the two groups (ER: 76.9% vs 64.9%; IDR:11.5% vs 17.2%; BIR: 4.6% vs 10.7%; SIR: 6.9% vs 7.2%, P = 0.03). Patients with HT had less frequently evidence of disease (11.6% vs 17.9%). When compared with the matched groups, 123 pairs of patients were successfully matched, PTC patients with HT were found to have a better response to RAI therapy. PTC patients with HT had less aggressive characteristics at presentation. Importantly, the presence of HT not only had a significant association with the outcome, but was also protective from the risk of recurrence.

The distribution of Apis laboriosa revisited: range extensions, biogeographic affinities, and species distribution modelling

IntroductionApis laboriosa, the Himalayan giant honeybee, inhabits the foothills of Himalaya and neighboring mountainous regions. Here we revise its distribution in light of recent reports and discoveries, review the ecozones it inhabits, and reassess its likely distribution through species distribution modeling.MethodsWe revised the range map for A. laboriosa by mapping locality records from various sources: refereed research publications, museum specimens, records with identifiable images of bees in publicly available databases, personal observations of the authors, and photos/videos and their coordinates submitted to the authors by honey-hunters, beekeepers, and extension workers. We then used that map to determine the ecozones in which the species occurs. The geographical coordinates of the data localities were used to estimate the potential suitable areas for the bee with MaxEnt modeling.ResultsOur research filled in several previously identified gaps in the distribution of A. laboriosa: in western Nepal; mountainous regions of Myanmar, northwestern Thailand, and northern Laos; several river valleys in Xizang and Yunnan, China; and northeastern Pakistan. Over most of its range this bee species primarily occupies subtropical broadleaf forests with strong Himalayan affinities. However, in the western part of its range it extends into zones dominated by conifers. The sites where A. laboriosa has been recorded closely match the predicted range of the species. Two variables, mean temperature of the coldest quarter and temperature seasonality, contributed most (76%) to the species distribution model.DiscussionApis laboriosa has a more extensive distribution in the foothills of the Himalaya and neighboring mountainous regions than has been previously recognized. The range now extends from longitude 74.4°–105.9°E, a linear distance of 3300 km, and from latitude 19.2°N–34.8°N. We have documented nesting on tree branches in northern Vietnam. Future research is warranted on its elevational migrations along river valleys, population differentiation, and ecological role as a pollinator in the different ecological zones it inhabits.

Improving deep groundwater aquifer characterization with deep learning inversion of audio-frequency magnetotelluric data

Deep groundwater is a crucial resource for drinking, industry, and ecosystems. However, its extensive subsurface distribution poses challenges for traditional hydrological sampling methods. Audio-frequency Magnetotelluric (AMT) is commonly used to image shallow subsurface resistivity distribution, but its application for quantifying deep groundwater aquifers is challenging. In this study, we propose a two-step strategy deep learning (DL) to estimate subsurface water information from AMT data. First, we employ an inversion DL network to directly predict subsurface resistivity distribution from AMT data. To assess the impact of data and prior information on DL inversions, we progressively include more input data during training, from apparent resistivity to apparent resistivity, phase, and Bostick transformed initial models. In the second step, we use another DL network to predict subsurface structure from AMT inversion results. We then estimate water content based on unit-specific petrophysical relationships. Evaluating our algorithm with synthetic cases, we find that including more information generally improves network performance, particularly when incorporating initial Bostick transformed models. Applying the algorithm to a field hydrogeological survey, we compare the inversion network trained with apparent resistivity, phase, and Bostick transformed initial models to traditional regularization inversions. The new approach shows better consistency with borehole data. Another network extracts structure information, enabling the estimation of subsurface water content and gaining valuable hydrogeological insights. To summarize, our study presents a novel DL-based approach to quantitatively delineate deep groundwater aquifers using AMT data. The proposed algorithm demonstrates promising performance in estimating subsurface hydrologic properties, providing valuable insights for hydrogeological investigations.

Determining tissue distribution of the oral antileishmanial agent miltefosine: a physiologically-based pharmacokinetic modeling approach.

Miltefosine (MTS) is the only approved oral drug for treating leishmaniasis caused by intracellular Leishmania parasites that localize in macrophages of the liver, spleen, skin, bone marrow, and lymph nodes. MTS is extensively distributed in tissues and has prolonged elimination half-lives due to its high plasma protein binding, slow metabolic clearance, and minimal urinary excretion. Thus, understanding and predicting the tissue distribution of MTS help assess therapeutic and toxicologic outcomes of MTS, especially in special populations, e.g., pediatrics. In this study, a whole-body physiologically-based pharmacokinetic (PBPK) model of MTS was built on mice and extrapolated to rats and humans. MTS plasma and tissue concentration data obtained by intravenous and oral administration to mice were fitted simultaneously to estimate model parameters. The resulting high tissue-to-plasma partition coefficient values corroborate extensive distribution in all major organs except the bone marrow. Sensitivity analysis suggests that plasma exposure is most susceptible to changes in fraction unbound in plasma. The murine oral-PBPK model was further validated by assessing overlay of simulations with plasma and tissue profiles obtained from an independent study. Subsequently, the murine PBPK model was extrapolated to rats and humans based on species-specific physiological and drug-related parameters, as well as allometrically scaled parameters. Fold errors for pharmacokinetic parameters were within acceptable range in both extrapolated models, except for a slight underprediction in the human plasma exposure. These animal and human PBPK models are expected to provide reliable estimates of MTS tissue distribution and assist dose regimen optimization in special populations.

First zoeal stage of the Indian Ocean hydrothermal vent crab, Austinograea rodriguezensis Tsuchida &amp; Hashimoto, 2002 (Decapoda: Brachyura: Bythograeidae)

First stage zoeas of the vent crab Austinograea rodriguezensis Tsuchida &amp; Hashimoto, 2002 (Decapoda, Brachyura, Bythograeidae) were collected by a remotely operated vehicle from the Kairei Hydrothermal Vent, Central Indian Ridge, in January 2016 during the INDEX2016 cruise of the French registered RV Pourquoi Pas? The zoeal appendages are illustrated using confocal laser scanning microscopy and described. A comparison between first stage zoeal morphology of Gandalfus yunohana (Takeda, Hashimoto &amp; Ohta, 2000) and A. rodriguezensis is made and, although remarkably similar, they can be distinguished by dorsal pleonal spinulation. Tdhe number of possible zoeal stages of A. rodriguezensis is discussed and considered to be four. Several deep-water brachyuran zoea 1 have been described with distinct elongated dorsal carapace and pleonal spinulation, including A. rodriguezensis, G. yunohana, Calocarcinus africanus Calman, 1909, Dorhynchus thomsoni Thomson, 1873. These are compared with the zoeas of three species of Geryoninae Colosi, 1924 for which the larval phases are described. These geryonine crabs are also deep-water species, but their zoeas are only described with rostral, dorsal and lateral carapace spines and are without the elongated dorsal spinulation of the carapace and pleomeres. This is attributed to the fact these geryonines have an extensive distribution range compared to those of A. rodriguezensis, G. yunohana, C. africanus and D. thomsoni, which are restricted to discrete habitats. The elongated dorsal spinulation of the carapace and pleomeres of these latter four species is attributed to the fact that the length of these spines increases the effective size of these without extra cost of growth and help the dispersal of the zoeal stages. Videos of A. rodriguezensis female behaviour with respect to aeration of eggs and the subsequent hatching near vent plumes are provided as supplementary information.

Characterization of the organellar genomes of Mazzaella laminarioides and Mazzaella membranacea (Gigartinaceae, Rhodophyta).

Mazzaella, a genus with no genomic resources available, has extensive distribution in the cold waters of the Pacific, where they represent ecologically and economically important species. In this study, we aimed to sequence, assemble, and annotate the complete mitochondrial and chloroplast genomes from two Mazzaella spp. and characterize the intraspecific variation among them. We report for the first time seven whole organellar genomes (mitochondria: OR915856, OR947465, OR947466, OR947467, OR947468, OR947469, OR947470; chloroplast: OR881974, OR909680, OR909681, OR909682, OR909683, OR909684, OR909685) obtained through high-throughput sequencing for six M. laminarioides sampled from three Chilean regions and one M. membranacea. Sequenced Mazzaella mitogenomes have identical gene number, gene order, and genome structure. The same results were observed for assembled plastomes. A total of 52 genes were identified in mitogenomes, and a total of 235 genes were identified in plastomes. Although the M. membranacea plastome included a full-length pbsA gene, in all M. laminarioides samples, the pbsA gene was split in three open reading frames (ORFs). Within M. laminarioides, we observed important plastome lineage-specific variations, such as the pseudogenization of the two hypothetical protein-coding genes, ycf23 and ycf45. Nonsense mutations in the ycf23 and ycf45 genes were only detected in the northern lineage. These results are consistent with phylogenetic reconstructions and divergence time estimation using concatenated coding sequences that not only support the monophyly of M. laminarioides but also underscore that the three M. laminarioides lineages are in an advanced stage of divergence. These new results open the question of the existence of still undisclosed species in M. laminarioides.

Factors at the initial visit associated with poor visual outcomes in patients with acute retinal necrosis.

Acute retinal necrosis (ARN) is a vision-threatening disease caused by herpesvirus infection. This study aimed to investigate the visual prognostic factors that could be determined at the initial visit. This retrospective study included 34 patients with ARN. Logistic regression analysis was employed to evaluate the associations between poor final visual outcomes and various factors, including poor initial visual acuity, presence of retinal detachment at the initial visit, posterior extension of necrotizing retinitis, and circumferential extension of necrotizing retinitis. Posterior extension was evaluated with three zonings, from the periphery (zone 3), mid-periphery (zone 2), and macula (zone 1). Circumferential extension was evaluated according to the degree of necrotizing retinitis lesions using ultra-wide fundus imaging. The mean logarithm of the minimum angle of resolution was 0.63 ± 0.68 at the initial visit and 0.83 ± 0.65 at 12 months after the initial visit. Seven patients had a retinal detachment. The distribution of posterior extension at the initial visit was 5 in zone 1, 20 in zone 2, and 9 in zone 3. The average of necrotizing retinitis lesion angle was 249 ± 115°. The logistic regression analysis revealed that participants with wide angles of necrotizing retinitis were associated with final poor vision, with an odds ratio of 1.28 per 30° increase (95%CI: 1.00-1.65, p = 0.03). Assessment of the widespread circumferential extension of white necrotizing retinal lesions at the initial visit is a crucial risk factor for the visual prognosis in ARN.