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Purpose: Accurate neural rim measurement based on optic disc imaging is important to glaucoma severity grading and often performed by trained glaucoma specialists. We aim to improve upon existing automated tools by building a fully automated system (RimNet) for direct rim identification in glaucomatous eyes and measurement of the minimum rim-to-disc ratio (mRDR) in intact rims, the angle of absent rim width (ARW) in incomplete rims, and the rim-to-disc-area ratio (RDAR) with the goal of optic disc damage grading. Design: Retrospective cross sectional study. Participants: One thousand and twenty-eight optic disc photographs with evidence of glaucomatous optic nerve damage from 1021 eyes of 903 patients with any form of primary glaucoma were included. The mean age was 63.7 (± 14.9) yrs. The average mean deviation of visual fields was −8.03 (± 8.59). Methods: The images were required to be of adequate quality, have signs of glaucomatous damage, and be free of significant concurrent pathology as independently determined by glaucoma specialists. Rim and optic cup masks for each image were manually delineated by glaucoma specialists. The database was randomly split into 80/10/10 for training, validation, and testing, respectively. RimNet consists of a deep learning rim and cup segmentation model, a computer vision mRDR measurement tool for intact rims, and an ARW measurement tool for incomplete rims. The mRDR is calculated at the thinnest rim section while ARW is calculated in regions of total rim loss. The RDAR was also calculated. Evaluation on the Drishti-GS dataset provided external validation (Sivaswamy 2015). Main Outcome Measures: Median Absolute Error (MAE) between glaucoma specialists and RimNet for mRDR and ARW. Results: On the test set, RimNet achieved a mRDR MAE of 0.03 (0.05), ARW MAE of 31 (89)°, and an RDAR MAE of 0.09 (0.10). On the Drishti-GS dataset, an mRDR MAE of 0.03 (0.04) and an mRDAR MAE of 0.09 (0.10) was observed. Conclusions: RimNet demonstrated acceptably accurate rim segmentation and mRDR and ARW measurements. The fully automated algorithm presented here would be a valuable component in an automated mRDR-based glaucoma grading system. Further improvements could be made by improving identification and segmentation performance on incomplete rims and expanding the number and variety of glaucomatous training images.

Abstract This study examines retinas from a rat glaucoma model for oxidized nucleosides 8OHdG and 8OHG, biomarkers for oxidative damage of DNA and RNA, respectively. Immunohistochemical data indicate a predominant localization of 8OHdG/8OHG in retinal ganglion cells (RGCs). The levels for these oxidized DNA/RNA products were 3.2 and 2.8 fold higher at 1 and 2 weeks after intraocular pressure elevation compared to control retinas, respectively. 8OHdG/8OHG were almost exclusively associated with mitochondrial DNA/RNA: ~ 65% of 8OHdG/8OHG were associated with RNA isolated from mitochondrial fraction and ~ 35% with DNA. Furthermore, we analyzed retinas of the rd10 mouse, a model for retinitis pigmentosa, with severe degeneration of photoreceptors to determine whether high levels of 8OHdG/8OHG staining intensity in RGCs of control animals is related to the high level of mitochondrial oxidative phosphorylation necessary to support light-evoked RGC activity. No significant difference in 8OHdG/8OHG staining intensity between control and rd10 mouse retinas was observed. The results of this study suggest that high levels of 8OHdG/8OHG in RGCs of wild-type animals may lead to cell damage and progressive loss of RGCs observed during normal aging, whereas ocular hypertension-induced increase in the level of oxidatively damaged mitochondrial DNA/RNA could contribute to glaucomatous neurodegeneration.

Purpose - The purpose of this study is to identify the learner characteristics attributable to the likelihood and the duration of programme completion in the Bachelor of Science (BSc) and Bachelor of Technology Honours in Engineering (BTech) degree programmes of the Open University of Sri Lanka (OUSL).

While greater yam provides food and income security for millions of people around the world, there are limited genomic resources available. Here, the authors report a chromosome-scale assembly of the greater yam genome as well as quantitative trait loci associated with anthracnose resistance and tuber traits.

Abstract Background Dengue is endemic in the Philippines. Aedes aegypti is the primary vector. This study aimed to determine the hatching behavior and viability of Ae. aegypti first-generation (F1) eggs when exposed to temperature and photoperiod regimes under laboratory conditions. Methods Parental eggs were collected from selected highland and lowland sites in the Philippine big islands (Luzon, Visayas, and Mindanao) during the wet (2017–2018) and dry (2018) seasons. F1 egg cohorts were exposed separately in environmental chambers at 18, 25, and 38 °C with respective photoperiods for 6 weeks. Phenotypes (percent pharate larvae [PPL], hatch rates [HRs], and reproductive outputs [ROs]) were determined. Results Results of multivariate analyses of variance (MANOVA) between seasons showed significant main effects of temperature, season, and big island on all phenotypes across all sites. Significant interaction effects between seasons on all phenotypes across sites were shown between or among (1) season and big island, (2) season and temperature, (3) big island and temperature, (4) season, big island, and temperature, (5) big island, altitude, and temperature, and (6) season, big island, altitude, and temperature. Factors associated with the big islands might include their ecology, available breeding sites, and day lengths due to latitudinal differences, although they were not measured in the field. MANOVA results within each season on all phenotypes across sites showed (1) significant main effects of big island and temperature, and (2) significant interaction effects between big island and temperature within the wet season and (3) between temperature and photoperiod within the dry season. PPL were highest at 18 °C and were formed even at 38 °C in both seasons. Pharate larvae might play an adaptive role in global warming, expanded distribution to highlands, and preponderance to transmit human diseases. HRs in both seasons were highest at 25 °C and lowest at 38 °C. ROs were highest at 25 °C in the wet season and at 18 °C in the dry season. Conclusions Temperature and latitude of Philippine big islands influenced the development-related phenotypes of Ae. aegypti in both seasons. The two seasons influenced the phenotypes and their interaction effects with big island and/or temperature and/or altitude. Recommendations include year-round enhanced 4S control strategies for mosquito vectors and water pipeline installation in rural highlands. Graphical Abstract

Abstract In this study, we designed two deep neural networks to encode 16 features for early seizure detection in intracranial EEG and compared them and their frequency responses to 16 widely used engineered metrics to interpret their properties: epileptogenicity index (EI), phase locked high gamma (PLHG), time and frequency domain Cho Gaines distance (TDCG, FDCG), relative band powers, and log absolute band powers (from alpha, beta, theta, delta, low gamma, and high gamma bands). The deep learning models were pretrained for seizure identification on the time and frequency domains of 1 s, single-channel clips of 127 seizures (from 25 different subjects) using “leave-one-out” (LOO) cross validation. Each neural network extracted unique feature spaces that were interpreted using spectral power modulations before being used to train a Random Forest Classifier (RFC) for seizure identification. The Gini Importance of each feature was calculated from the pretrained RFC, enabling the most significant features (MSFs) for each task to be identified. The MSFs were extracted to train another RFC for UPenn and Mayo Clinic’s Seizure Detection Kaggle Challenge. They obtained an AUC score of 0.93, demonstrating a transferable method to identify and interpret biomarkers for seizure detection.

UAVs need to communicate along three dimensions (3D) with other aerial vehicles, ranging from above to below, and often need to connect to ground stations. However, wireless transmission in 3D space significantly dissipates power, often hindering the range required for these types of links. Directional transmission is one way to efficiently use available wireless channels to achieve the desired range. While multiple-input multiple-output (MIMO) systems can digitally steer the beam through channel matrix manipulation without needing directional awareness, the power resources required for operating multiple radios on a UAV are often logistically challenging. An alternative approach to streamline resources is the use of phased arrays to achieve directionality in the analog domain, but this requires beam sweeping and results in search-time delay. The complexity and search time can increase with the dynamic mobility pattern of the UAVs in aerial networks. However, if the direction of the receiver is known at the transmitter, the search time can be significantly reduced. In this work, multi-antenna channels between two UAVs in A2A links are analyzed, and based on these findings, an efficient machine learning-based method for estimating the direction of a transmitting node using channel estimates of 4 antennas (2 × 2 MIMO) is proposed. The performance of the proposed method is validated and verified through in-field drone-to-drone measurements. Findings indicate that the proposed method can estimate the direction of the transmitter in the A2A link with 86% accuracy. Further, the proposed direction estimation method is deployable for UAV-based massive MIMO systems to select the directional beam without the need to sweep or search for optimal communication performance.

Burkina Faso is a sub-Saharan African country suffering from a high poverty rate. It has quadruplicated its population over the last twenty years, that is, from 4.5 to 18 million inhabitants. Such demographic changes, together with an intense migration process from rural areas to large cities, among other issues, are contributing to a rapid process of socio-cultural transformation. In this context, changes in both traditional and contemporary housing are analyzed for this article. To this aim, a thorough thermo-hygrometric evaluation is carried out by processing significant data from on-site measurements to shed new light on the adaptation of the said dwellings to the environmental and local cultural values. Preliminary results show that the introduction of land ownership linked to climate change and the increasing scarcity of natural resources are forcing native ethnic groups to modify their traditional ways of life, even threatening their subsistence. Consequently, we can prove that the new building typologies are not suitable in the least for the climatic conditions nor the rich cultural heritage of Burkina Faso. This fact negatively affects the possibility of revitalizing vernacular and environmentally oriented solutions for the contemporary world and the necessary advance towards a more sustainable architecture. With this research, we intent to start a reversal of such a deterioration process.

Triangles are an ever-present feature in nature, which the building construction industry duly echoes. However, an exact expression intended to supply the radiant field of any triangle in an upright or inclined position has not been identified by previous research. In this case, the author has been able to solve, via direct integration, the canonical expression of radiative transfer. This result alone confers a myriad of possibilities, that had been inconceivable before, for studying in detail the three-dimensional heat-transfer behavior of volumes and figures in which triangles manifest, such as fins, windows, roof-gables and louvers of various kinds. Typically, shading devices, when tilted, give rise in their extremes to rhomboidal shapes which were difficult to take into account or had to be subject to discretization and subsequent Monte Carlo methods in order to perform an approximate calculation of their emissions. This implied a lengthy and inexact procedure that induced many errors and consumed computing time. We can now avoid all these former downsides due to the advances hereby presented. As this novel expression can be converted into an algorithm, it will be advantageously employed for simulation. This significant finding dovetails into the intricate puzzle of radiated heat and we believe that its consequences will greatly affect the conception and design of HVAC devices, aircraft manufacturing and specifically the building or lighting industries, among others.

This article delves into the creation a fictional city solely for the development of Japanese American internment camps and the way in which sustainable arts and crafts played a significant role in ensuring survival in such a hostile environment. To this aim, we searched the literature and reviewed archives, primarily from the American West Coast. We demonstrate that beyond adaptation to the circumstances, the visual representation of the new city’s settlement, founding, and daily activities, instead of adding to the typical panoptic or sombre prison imagery, remains inscribed in the images selected by the inmates, and that the use of such images precisely fostered the inmates’ resiliency. This leads us to deduce that such ’city fiction’ was necessary in this case for survival and endurance, and that its artistic representation was primarily incorporated into the State’s ideological apparatus. On the other hand, occasional fissures subtly seethed with the violence exerted in the camps. In this way, we conclude that the artistic activity itself justified the city fiction, among other situations, revealing the conditions of systemic violence and oppression faced by the internees. Within this framework, we deem that the artworks hereby generated constitute a paramount historical document for resiliency’s sake. The arguments contained herein are still relevant, because everywhere around the world, situations of exclusion and confinement of displaced immigrants, or simply those considered misfits, are repeated time and time again. Nor have we alleviated the issue in any way today, since we disregard the lessons learned from the past.

Abstract Introduction Vital registration is an important element in health information systems which can inform policy and strengthen health systems. Mexico has a well-functioning vital registration system; however, there is still room for improvement, especially for deaths of children under 5. This study assesses the quality of the vital registration system in capturing deaths and evaluates the quality of cause of death certification in under-5 deaths in Yucatan, Mexico. Methods We collected information on under-5 deaths that occurred in 2015 and 2016 in Yucatan, Mexico. We calculated the Vital Statistics Performance Index (VSPI) to have a general assessment of the vital registration performance. We examined the agreement between vital registration records and medical records at the individual and population levels using the chance-corrected concordance (CCC) and cause-specific mortality fraction (CSMF) accuracy as quality metrics. Results We identified 966 records from the vital registry for all under-5 deaths, and 390 were linked to medical records of deaths occurring at public hospitals. The Yucatan vital registration system captured 94.8% of the expected under-5 deaths, with an overall VSPI score of 87.2%. Concordance between underlying cause of death listed in the vital registry and the cause determined by the medical record review varied substantially across causes, with a mean overall chance-corrected concordance across causes of 6.9% for neonates and 46.9% for children. Children had the highest concordance for digestive diseases, and neonates had the highest concordance for meningitis/sepsis. At the population level, the CSMF accuracy for identifying the underlying cause listed was 35.3% for neonates and 67.7% for children. Conclusions Although the vital registration system has overall good performance, there are still problems in information about causes of death for children under 5 that are related mostly to certification of the causes of death. The accuracy of information can vary substantially across age groups and causes, with causes reported for neonates being generally less reliable than those for older children. Results highlight the need to implement strategies to improve the certification of causes of death in this population.

Abstract Background The Salud Mesoamérica Initiative (SMI) is a public-private collaboration aimed to improve maternal and child health conditions in the poorest populations of Mesoamerica through a results-based aid mechanism. We assess the impact of SMI on the staffing and availability of equipment and supplies for delivery care, the proportion of institutional deliveries, and the proportion of women who choose a facility other than the one closest to their locality of residence for delivery. Methods We used a quasi-experimental design, including baseline and follow-up measurements between 2013 and 2018 in intervention and comparison areas of Guatemala, Nicaragua, and Honduras. We collected information on 8754 births linked to the health facility closest to the mother’s locality of residence and the facility where the delivery took place (if attended in a health facility). We fit difference-in-difference models, adjusting for women’s characteristics (age, parity, education), household characteristics, exposure to health promotion interventions, health facility level, and country. Results Equipment, inputs, and staffing of facilities improved after the Initiative in both intervention and comparison areas. After adjustment for covariates, institutional delivery increased between baseline and follow-up by 3.1 percentage points (β = 0.031, 95% CI -0.03, 0.09) more in intervention areas than in comparison areas. The proportion of women in intervention areas who chose a facility other than their closest one to attend the delivery decreased between baseline and follow-up by 13 percentage points (β = − 0.130, 95% CI -0.23, − 0.03) more than in the comparison group. Conclusions Results indicate that women in intervention areas of SMI are more likely to go to their closest facility to attend delivery after the Initiative has improved facilities’ capacity, suggesting that results-based aid initiatives targeting poor populations, like SMI, can increase the use of facilities closest to the place of residence for delivery care services. This should be considered in the design of interventions after the COVID-19 pandemic may have changed health and social conditions.

Pineal parenchymal tumor of intermediate differentiation (PPTID) is a rare, primary tumor of the pineal gland. Due to its rarity, there is no consensus on optimal therapeutic strategies or standard characterization of the tumor’s behavior. Here, we report 2 new cases of PPTID and an extensive review of the literature involving the use and extent of radiation therapy. Patient 1 is a 54-year-old male who presented with PPTID and drop metastases in the spinal cord, received cranial spinal irradiation (CSI), and experienced recurrence 3.5 years after treatment. Stereotactic body radiation therapy (SBRT) helped the patient into remission for 9 months. Patient 2 is a 32-year-old male with a local PPTID at presentation who went on to receive surgical resection followed by focused adjuvant radiation therapy to the pineal tumor bed. He then presented 6 years after treatment with extensive disseminated recurrence and died due to leptomeningeal disease (LMD) about 4 years after recurrence. The available literature on PPTID is limited and reported cases of LMD with ongoing follow-up in PPTID are scarce. Our report adds to the current known PPTID cases, contributing to the information available regarding prognosis and treatment response. Although an optimal therapeutic strategy for PPTID still cannot be determined, data from the literature suggest that utilizing radiation therapy in patients with low-risk disease and gross total resections as well as the use of upfront CSI have the potential to improve patient progression and survival outcomes.

This paper is being written at a time when the recent pandemic, namely COVID-19, has shaken the entire world in a manner that has never been seen in modern history. The ecology, socio-economy and weak health systems make Africa an area favorable to the occurrence of various diseases and disease outbreaks. This paper explores forty-eight (48) years of disease outbreaks in the WHO African region of the World Health Organization (WHO). Twenty-five (25) Integrated Disease Surveillance and Response priority diseases were selected, and their outbreaks were described and analyzed. Using inferential spatial statistics, spatial clusters at the health district level, specifically hot spots of those outbreaks, were produced and analyzed. The Population at risk of those hot spots was estimated. Results show a consistent report of outbreaks during the selected period, with 52 outbreaks on average per year. Poliomyelitis, cholera, yellow fever, meningococcal disease and measles were the most reported outbreaks. Democratic Republic of the Congo (DRC) and Nigeria were the countries reporting the highest number of outbreaks (5 on average per year), with high number of people living in hot spots districts (85M). Despite efforts to limit their number, some disease outbreaks, such as cholera, malaria, and measles, continue to have a burden in terms of morbidity and mortality. In contrast, others, such as poliomyelitis, yellow fever and diarrhoeal disease, have shown a declining trend, and wild polio virus transmission has been eliminated in the region. Results suggest that concerted public health action may help reduce outbreaks in the region. Results can be used to inform preparedness and prevention activities. Priority public health actions should target DRC and Nigeria and identified hot spots and areas with existing risk factors within other countries.

Abstract Background Little is known regarding the rate and clinical outcomes of asymptomatic carriers of SARS‐CoV‐2 among patients with cancer. Detection of asymptomatic carriers is important in this population given the use of myelosuppressive and immunomodulating therapies. Understanding the asymptomatic carrier rate will help to develop mitigation strategies in this high‐risk cohort. Methods Retrospective cohort analysis of an asymptomatic screening protocol which required patients receiving infusional anti‐cancer therapy to undergo a symptom/exposure screen and SARS‐CoV‐2 PCR testing 24–96 h prior to their infusion. The primary outcome of this analysis was the rate of asymptomatic SARS‐CoV‐2 infection. Secondary outcomes included the rate of COVID‐19‐related hospitalization and mortality and delays in oncologic therapy. Results Among a cohort of 2691 cancer patients who underwent asymptomatic screening, 1.6% (N = 43/2691) of patients were found to be SARS‐CoV‐2 positive on asymptomatic screening. 11.6% (N = 5/43) of the cohort ultimately developed COVID‐19‐related symptoms. Four patients required hospitalization for complications of COVID‐19 infection. No patient died from COVID‐related complications. 97.7% (N = 42/43) had their anti‐cancer therapy delayed or deferred with a median delay of 21 days (range: 7–77 days). Conclusions Overall, among a cohort of active cancer patients receiving anti‐cancer therapy, an asymptomatic SARS‐CoV2 PCR‐based screening protocol detected a small cohort of asymptomatic carriers. The majority of these patients remained asymptomatic on long‐term follow‐up and outcomes were much more favorable compared to previously described outcomes of cancer patients with symptomatic COVID‐19 infection.

Measurable residual disease (MRD) is the most powerful independent predictor of risk of relapse and long-term survival in adults and children with acute lymphoblastic leukemia (ALL). For almost all patients with ALL there is a reliable method to evaluate MRD, which can be done using multi-color flow cytometry, quantitative polymerase chain reaction to detect specific fusion transcripts or immunoglobulin/T-cell receptor gene rearrangements, and high-throughput next-generation sequencing. While next-generation sequencing-based MRD detection has been increasingly utilized in clinical practice due to its high sensitivity, the clinical significance of very low MRD levels (

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra region of the midbrain. Diagnostic criteria for PD require that at least two of three motor signs are observed: tremor, rigidity, and/or bradykinesia. The most common and effective treatment for PD is Levodopa (L-DOPA) which is readily converted to DA and has been the primary treatment since the 1960’s. Dopamine agonists have also been developed but are less effective than L-DOPA. Although the lack of a model system to study PD has hampered efforts to identify treatments, diverse screening strategies have been proposed for identification of new pharmaceutical candidates. Here, we describe a pilot screen to identify candidate molecules from a bioactive compound library, that might increase formation, maintenance and/or survival of DA neurons in vitro. The screen used a previously characterized reporter construct consisting of the luciferase gene inserted downstream of the endogenous tyrosine hydroxylase (TH) gene and neurons differentiated from human pluripotent stem cells for 18 days. The reporter mimics expression of TH and includes a secreted luciferase whose activity can be measured non-invasively over multiple timepoints. Screening of the bioactive compound library resulted in the identification of a single molecule, SGC0946, that is an inhibitor of DOT1L (Disruptor Of Telomeric silencing 1-Like) which encodes a widely-conserved histone H3K79 methyltransferase that is able to both activate and repress gene transcription. Our results indicate that SGC0946 increased reporter luciferase activity with a single treatment for 48-h post-plating being equivalent to continuous treatment. Moreover, data suggested that the total number of neurons differentiated in the assays was comparable from experiment to experiment under different SGC0946 treatments over time. In contrast, data suggested that the survival and/or maintenance of DA neurons might be specifically enhanced by SGC0946 treatment. These results document the feasibility of a set of tools for further exploration of small molecules that may impact DA neuron differentiation, maintenance and/or survival. Results provide evidence in support of other reports that indicate inhibition of DOT1L may play an important role in maintenance and survival of neural progenitor cells (NPCs) and their lineage-specific differentiation.

Background: The humeral head osteotomy during shoulder arthroplasty influences humeral component height, version and possibly neck-shaft angle. These parameters all potentially influence outcomes of anatomic and reverse shoulder replacement to a variable degree. Patient-specific guides and navigation have been studied and utilized clinically for glenoid component placement. Little, however, has been done to evaluate these techniques for humeral head osteotomies. The purpose of this study, therefore, was to evaluate the use of patient-specific guides and surgical navigation for executing a planned humeral head osteotomy. Methods: The DICOM images of 10 shoulder computed tomography scans (5 normal and 5 osteoarthritic) were used to print 3D polylactic models of the humerus. Each model was duplicated, such that there were 2 identical groups of 10 models. After preoperative planning of a humeral head osteotomy, Group 1 underwent osteotomy via a patient-specific guide, while group 2 underwent a real time navigated osteotomy with an optically tracked sagittal saw. The cut height (millimeters), version (degrees) and neck-shaft angle (degrees) were recorded and statistically compared between groups. Results: There were no statistically significant differences between patient-specific guides and navigation for osteotomy cut height (P = .45) and humeral version (P = .059). Navigation, however, resulted in significantly less neck-shaft angle error than the patient specific guides (P = .023). Subgroup analysis of the osteoarthritic cases showed statistical significance for navigation resulting in less version error than the patient specific guides (P = .048). Conclusion: No significant differences were found between patient specific guides and navigation for recreation of the preoperatively planned humeral head cut height and version. Neck-shaft angle, however, had significantly less deviation from the preoperative plan when conducted with navigation.

Intravitreal injection is the most widely used injection technique for ocular gene delivery. However, vector diffusion is attenuated by physical barriers and neutralizing antibodies in the vitreous. The 13-lined ground squirrel (13-LGS), as in humans, has a larger relative vitreous body volume than the more common rodent models such as rats and mice, which would further reduce transduction efficiency with the intravitreal injection route. We report here a “pre-retinal” injection approach that leads to detachment of the posterior hyaloid membrane and delivers vector into the space between vitreous and inner retina. Vectors carrying a ubiquitously expressing mCherry reporter were injected into the deep vitreous or pre-retinal space in adult wild-type 13-LGSs. Then, adeno-associated virus (AAV)-mediated mCherry expression was evaluated with non-invasive imaging, immunofluorescence, and flow cytometry. Compared to deep vitreous delivery, pre-retinal administration achieved pan-retinal gene expression with a lower vector dose volume and significantly increased the number of transduced cone photoreceptors. These results suggest that pre-retinal injection is a promising tool in the development of gene therapy strategies in animal models and is a potential approach for use in human research, particularly in younger individuals with an intact posterior hyaloid membrane and stable vitreous.

Summary:. Concomitant with such a shift toward competency-based curricula, there has been increasing adoption of surgical simulation coupled with virtual, mixed, and augmented reality. These technologies have become more commonplace across multiple surgical disciplines, in domains such as preoperative planning, surgical education, and intraoperative navigation. However, there is a relative paucity of literature pertaining to the application of this technology to plastic surgery education. This review outlines the advantages of mixed and augmented reality in the pursuit of an ideal simulation environment, their benefits for the education of plastic surgery trainees, and their role in standardized assessments. In addition, we offer practical solutions to commonly encountered problems with this technology. Augmented reality has tremendous untapped potential in the next phase of plastic surgery education, and we outline steps toward broader implementation to enhance the learning environment for our trainees and to improve patient outcomes.

The impact of pre-existing immunity on the efficacy of artemisinin combination therapy is largely unknown. We performed in-depth profiling of serological responses in a therapeutic efficacy study [comparing artesunate-mefloquine (ASMQ) and artemether-lumefantrine (AL)] using a proteomic microarray. Responses to over 200 Plasmodium antigens were significantly associated with ASMQ treatment outcome but not AL. We used machine learning to develop predictive models of treatment outcome based on the immunoprofile data. The models predict treatment outcome for ASMQ with high (72–85%) accuracy, but could not predict treatment outcome for AL. This divergent treatment outcome suggests that humoral immunity may synergize with the longer mefloquine half-life to provide a prophylactic effect at 28–42 days post-treatment, which was further supported by simulated pharmacokinetic profiling. Our computational approach and modeling revealed the synergistic effect of pre-existing immunity in patients with drug combination that has an extended efficacy on providing long term treatment efficacy of ASMQ.

Purpose: To investigate spatiotemporal correlations among ganglion cell complex (GCC) superpixel thickness measurements and explore underlying patterns of longitudinal change across the macular region. Design: Longitudinal cohort study. Subjects: One hundred eleven eyes from 111 subjects from the Advanced Glaucoma Progression Study with ≥ 4 visits and ≥ 2 years of follow-up. Methods: We further developed our proposed Bayesian hierarchical model for studying longitudinal GCC thickness changes across macular superpixels in a cohort of glaucoma patients. Global priors were introduced for macular superpixel parameters to combine data across superpixels and better estimate population slopes and intercepts. Main Outcome Measures: Bayesian residual analysis to inspect cross-superpixel correlations for subject random effects and residuals. Principal component analysis (PCA) to explore underlying patterns of longitudinal macular change. Results: Average (standard deviation [SD]) follow-up and baseline 10-2 visual field mean deviation were 3.6 (0.4) years and −8.9 (5.9) dB, respectively. Superpixel-level random effects and residuals had the greatest correlations with nearest neighbors; correlations were higher in the superior than in the inferior region and strongest among random intercepts, followed by random slopes, residuals, and residual SDs. PCA of random intercepts showed a first large principal component (PC) across superpixels that approximated a global intercept, a second PC that contrasted the superior and inferior macula, and a third PC, contrasting inner and nasal superpixels with temporal and peripheral superpixels. PCs for slopes, residual SDs, and residuals were remarkably similar to those of random intercepts. Conclusions: Introduction of cross-superpixel random intercepts and slopes is expected to improve estimation of population and subject parameters. Further model enhancement may be possible by including cross-superpixel random effects and correlations to address spatiotemporal relationships in longitudinal data sets.

Psychosis that occurs over the course of Alzheimer’s disease (AD) is associated with increased caregiver burden and a more rapid cognitive and functional decline. To find new treatment targets, studies modeling psychotic conditions traditionally employ agents known to induce psychosis, utilizing outcomes with cross-species relevance, such as locomotive activity and sensorimotor gating, in rodents. In AD, increased burdens of tau pathology (a diagnostic hallmark of the disease) and treatment with anticholinergic medications have, separately, been reported to increase the risk of psychosis. Recent evidence suggests that muscarinic antagonists may increase extracellular tau. Preclinical studies in AD models have not previously utilized muscarinic cholinergic antagonists as psychotomimetic agents. In this report, we utilize a human–mutant–tau model (P301L/COMTKO) and an over-expressed non-mutant human tau model (htau) in order to compare the impact of antimuscarinic (scopolamine 10 mg/kg/day) treatment with dopaminergic (reboxetine 20 mg/kg/day) treatment, for 7 days, on locomotion and sensorimotor gating. Scopolamine increased spontaneous locomotion, while reboxetine reduced it; neither treatment impacted sensorimotor gating. In the P301L/COMTKO, scopolamine treatment was associated with decreased muscarinic M4 receptor expression, as quantified with RNA-seq, as well as increased dopamine receptor D2 signaling, as estimated with Micro-PET [11C] raclopride binding. Scopolamine also increased soluble tau in the striatum, an effect that partially mediated the observed increases in locomotion. Studies of muscarinic agonists in preclinical tau models are warranted to determine the impact of treatment—on both tau and behavior—that may have relevance to AD and other tauopathies.

To explore the temporal profile of retinal proteomes specific to primary and secondary retinal ganglion cell (RGC) loss. Unilateral partial optic nerve transection (pONT) was performed on the temporal side of the rat optic nerve. Temporal and nasal retinal samples were collected at 1, 4 and 8 weeks after pONT (n = 4 each) for non-biased profiling with a high-resolution hybrid quadrupole time-of-flight mass spectrometry running on label-free SWATHTM acquisition (SCIEX). An information-dependent acquisition ion library was generated using ProteinPilot 5.0 and OneOmics cloud bioinformatics. Combined proteome analysis detected 2531 proteins with a false discovery rate of p < 0.05, FC ≥ 1.4 or ≤0.7). Eight proteins (ALDH1A1, TRY10, GFAP, HBB-B1, ALB, CDC42, SNCG, NEFL) were differentially expressed for at least two time points. The expressions of ALDH1A1 and SNCG at nerve fibers were decreased along with axonal loss. Increased ALDH1A1 localization in the inner nuclear layer suggested stress response. Increased GFAP expression demonstrated regional reactivity of astrocytes and Muller cells. Meta-analysis of gene ontology showed a pronounced difference in endopeptidase and peptidase inhibitor activity. Temporal proteomic profiling demonstrates established and novel protein targets associated with RGC damage.

The classic equations used to find the form factor inside fragments of spheres are often unassailable. The main difficulties that they present lie in iterative integrations effected over curved surfaces. The typical simulation software for this kind of issue is not capable of tackling the drawbacks that appear in the process, among them we could cite the impossibility of discretizing curved shapes with equal matching tiles, whether triangles or rectangles, especially when we arrive at the contour elements. The current type of cylindrical tiles employed for the calculation of spheres, due to incoherence in curvature, presents a significant array of gaps that render the whole procedure inadequate and inconsistent. To countermeasure this drawback, the recent finding of some innovative principles by the present author has provided a sure and exact path towards the solution of the problem in the frequent case of a volume enclosed within a spherical fragment and two limiting sections of the said sphere placed at arbitrary positions. The coherent application of such postulates by virtue of form factor algebra leads to an encompassing expression which solely requires the input of the surface areas of the involved shapes and, thus, avoids the lengthy resort to integration. A relevant number of cases in radiative heat transfer simulation, that cannot be solved by any other method, become feasible and accurate. Since the new tool can be implemented as an algorithm for simulation software, pivotal advances emerge in the complex domain of radiation which are applicable for the lighting industry, building simulations, and aerospace technologies, among others.

Current treatment for prostate cancer is dependent on the stages of the cancer, recurrence, and genetic factors. Treatment varies from active surveillance or watchful waiting to prostatectomy, chemotherapy, and radiation therapy in combination or alone. Although radical prostate cancer therapy reduces the advancement of the disease and its mortality, the increased disease treatment associated morbidity, erectile dysfunction, and incontinence affect the quality of life of cancer survivors. To overcome these problems, photodynamic therapy (PDT) has previously been investigated using PhotofrinTM as a photosensitizer (PS). However, Photofrin-PDT has shown limitations in treating prostate cancer due to its limited tumor-specificity and the depth of light penetration at 630 nm (the longest wavelength absorption of PhotofrinTM). The results presented herein show that this limitation can be solved by using a near infrared (NIR) compound as a photosensitizer (PS) for PDT and the same agent also acts as a sonosensitizer for SDT (using ultrasound to activate the compound). Compared to light, ultrasound has a stronger penetration ability in biological tissues. Exposing the PS (or sonosensitizer) to ultrasound (US) initiates an electron-transfer process with a biological substrate to form radicals and radical ions (type I reaction). In contrast, exposure of the PS to light (PDT) generates singlet oxygen (type II reaction). Therefore, the reactive oxygen species (ROS) produced by SDT and PDT follow two distinct pathways, i.e., type I (oxygen independent) and type II (oxygen dependent), respectively, and results in significantly enhanced destruction of tumor cells. The preliminary in vitro and in vivo results in a PC3 cell line and tumor model indicate that the tumor specificality of the therapeutic agent(s) can be increased by targeting galectin-1 and galectin-3, known for their overexpression in prostate cancer.

Radiant heat interchanges are pivotal to assessing the energy use of buildings and facilities that channel some sort of solar radiation. Form factor integrals are needed for an accurate simulation of the main features of the envelope of such buildings. However, the expressions required when the space under analysis is curved, for instance, in domes and vaults, are not feasible. The calculation process of algorithms is usually addressed by cumbersome analytical deductions or else by rough statistical approximations included in the simulations, such as ray-tracing methods. Neither of which works properly under curved geometries. The following article deals with an innovative methodology for employing an exact property that solves any spherical configuration of the radiant surfaces. The newly found relationship is validated by comparison with other solutions previously deducted by the author and by numerical simulations when available. Since there is no other exact method of calculating radiation exchanges within spherical fragments, we consider that this finding represents an advance which contributes to overcoming a variety of unexplained and practical problems of radiative heat transfer applicable to architectural developments, lighting elements and aircraft components.

Lung cancer (LC) is the leading cause of cancer‐related mortality. However, the molecular mechanisms associated with the development of metastasis are poorly understood. Understanding the biology of LC metastasis is critical to unveil the molecular mechanisms for designing targeted therapies. We developed two genetically engineered LC mouse models KrasG12D/+; Trp53R172H/+; Ad‐Cre (KPA) and KrasG12D/+; Ad‐Cre (KA). Survival analysis showed significantly (P = 0.0049) shorter survival in KPA tumor‐bearing mice as compared to KA, suggesting the aggressiveness of the model. Our transcriptomic data showed high expression of N‐acetylgalactosaminide alpha‐2, 6‐sialyltransferase 1 (St6galnac‐I) in KPA compared to KA tumors. ST6GalNAc‐I is an O‐glycosyltransferase, which catalyzes the addition of sialic acid to the initiating GalNAc residues forming sialyl Tn (STn) on glycoproteins, such as mucins. Ectopic expression of species‐specific p53 mutants in the syngeneic mouse and human LC cells led to increased cell migration and high expression of ST6GalNAc‐I, STn, and MUC5AC. Immunoprecipitation of MUC5AC in the ectopically expressing p53R175H cells exhibited higher affinity toward STn. In addition, ST6GalNAc‐I knockout (KO) cells also showed decreased migration, possibly due to reduced glycosylation of MUC5AC as observed by low STn on the glycoprotein. Interestingly, ST6GalNAc‐I KO cells injected mice developed less liver metastasis (P = 0.01) compared to controls, while colocalization of MUC5AC and STn was observed in the liver metastatic tissues of control mice. Collectively, our findings support the hypothesis that mutant p53R175H mediates ST6GalNAc‐I expression, leading to the sialyation of MUC5AC, and thus contribute to LC liver metastasis.

Pecan is an important specialty crop that has experienced extensive interspecific hybridization and nearly-obligate outcrossing. Here, the authors assemble diploid genomes of four outbred genotypes, identify interspecific introgressions through comparative genomics analyses, and map QTLs associated with pest resistance.