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We will show that the 3-4-1 model with heavy right-handed neutrinos can explain the recent experimental data of $(g-2)_{e, \mu}$ anomalies of charged leptons and neutrino oscillations through the inverse seesaw mechanism. In addition, the model can predict large lepton flavor violating decay rates $\mu \to e\gamma$ and $\tau \to \mu\gamma, e\gamma$ up to the recent experimental sensitivities., Comment: Version accepted for publication by PTEP, 31 pages, 8 figures

SignificanceLipid deficiency due to meibomian gland (MG) dysfunction is believed to account for the vast majority of patients with dry eye compared with aqueous deficiency. Clinicians commonly evaluate MG length to determine a disease, but our research with isotretinoin users suggests that MG contrast is also an important characteristic to consider.PurposeThis study aimed to determine the sensitivity and specificity of MG contrast for the diagnosis of lipid-deficient dry eye (LDDE).MethodsThis case-control study used demographic data, Standard Patient Evaluation of Eye Dryness (SPEED) scores, average tear lipid layer thickness (TLLT), fluorescein tear breakup time (FTBUT), upper eyelid meibography images, and meibum quality and quantity scores for individuals with LDDE (SPEED score ≥10 and TLLT ≤35 interferometric color units) and normal individuals (SPEED ≤2 and TLLT ≥80 interferometric color units).ResultsThirty-one eyes of 22 controls (mean ± SD age, 22.7 ± 5.5 years) and 13 eyes of 12 cases (mean ± SD age, 43.9 ± 17.2 years) were included. Normalized MG contrast was significantly correlated with FTBUT (r = 0.35, P = .02), percent MG atrophy (r = -0.50, P < .001), and SPEED scores (r = -0.49, P < .001). The receiver operating characteristic curve for LDDE diagnosis classifiers MG contrast, MG atrophy, and meibum quantity score had areas under the curve of 0.83, 0.64, and 0.73, respectively. Meibomian gland contrast cutoff at 28.3 intensity units yielded optimal correct classification of subjects (84.1%; sensitivity, 0.69; specificity, 0.90). Cases had shorter FTBUT (P < .001), worse meibum quality (P = .02) and quantity (P = .02) scores, and lower MG contrast (P < .001) compared with controls. Subjects with low MG contrast (≤28.3) had 14.9 higher odds of having LDDE (95% confidence interval, 2.84 to 78.4) compared with subjects with high MG contrast (>28.3).ConclusionsMeibomian gland contrast correlates well with clinical parameters and symptoms, s

SignificanceLipid deficiency due to meibomian gland (MG) dysfunction is believed to account for the vast majority of patients with dry eye compared with aqueous deficiency. Clinicians commonly evaluate MG length to determine a disease, but our research with isotretinoin users suggests that MG contrast is also an important characteristic to consider.PurposeThis study aimed to determine the sensitivity and specificity of MG contrast for the diagnosis of lipid-deficient dry eye (LDDE).MethodsThis case-control study used demographic data, Standard Patient Evaluation of Eye Dryness (SPEED) scores, average tear lipid layer thickness (TLLT), fluorescein tear breakup time (FTBUT), upper eyelid meibography images, and meibum quality and quantity scores for individuals with LDDE (SPEED score ≥10 and TLLT ≤35 interferometric color units) and normal individuals (SPEED ≤2 and TLLT ≥80 interferometric color units).ResultsThirty-one eyes of 22 controls (mean ± SD age, 22.7 ± 5.5 years) and 13 eyes of 12 cases (mean ± SD age, 43.9 ± 17.2 years) were included. Normalized MG contrast was significantly correlated with FTBUT (r = 0.35, P = .02), percent MG atrophy (r = -0.50, P < .001), and SPEED scores (r = -0.49, P < .001). The receiver operating characteristic curve for LDDE diagnosis classifiers MG contrast, MG atrophy, and meibum quantity score had areas under the curve of 0.83, 0.64, and 0.73, respectively. Meibomian gland contrast cutoff at 28.3 intensity units yielded optimal correct classification of subjects (84.1%; sensitivity, 0.69; specificity, 0.90). Cases had shorter FTBUT (P < .001), worse meibum quality (P = .02) and quantity (P = .02) scores, and lower MG contrast (P < .001) compared with controls. Subjects with low MG contrast (≤28.3) had 14.9 higher odds of having LDDE (95% confidence interval, 2.84 to 78.4) compared with subjects with high MG contrast (>28.3).ConclusionsMeibomian gland contrast correlates well with clinical parameters and symptoms, s

Gina Wesley,1 Katherine Bickle,2 Johnathon Downing,3 Bret Fisher,4 Brennan Greene,5 Colton Heinrich,6 David Kading,7 Shane Kannarr,8 Jason Miller,9 Satish Modi,10 David Ludwick,11 Joseph Tauber,12 Thao N Yeh,13 Sruthi Srinivasan14 1Complete Eye Care of Medina, Hamel, MN, USA; 2ProCare Vision Center, Granville, OH, USA; 3East West Eye Institute, Los Angeles, CA, USA; 4Eye Center of N Florida, Panama City, FL, USA; 5The Eye Care Institute, Louisville, KY, USA; 6Clarke EyeCare Center, Wichita Falls, TX, USA; 7Specialty Eyecare Group, Bellevue, WA, USA; 8Kannarr Eye Care LLC, Pittsburg, KS, USA; 9Insight Research Clinic, Powell, OH, USA; 10Alterman, Modi & Wolter, Poughkeepsie, NY, USA; 11Ludwick Eye Center, Chambersburg, PA, USA; 12Tauber Eye Center, Kansas City, MO, USA; 13Alcon Vision, LLC, Fort Worth, TX, USA; 14Alcon Research, LLC, Johns Creek, GA, USACorrespondence: Sruthi Srinivasan, Alcon Research, LLC, 11460 Johns Creek Parkway, Johns Creek, GA, 30097, USA, Tel +1 678 415 5315, Email sruthi.srinivasan@alcon.comPurpose: This study aimed to demonstrate the effectiveness of Systane iLux, a thermal pulsation device, in patients with MGD, over 12 months post-single treatment.Methods: This is a post-hoc analysis of a previous prospective, assessor-masked, parallel-group, multicenter study (NCT03956225) that compared the effectiveness and safety of iLux with LipiFlow in subjects with MGD. The original study included subjects with meibomian gland score (MGS) ≤ 12 in lower eyelids, Impact of Dry Eye on Everyday Life-Symptom Bother (IDEEL-SB) module score > 16, and non-invasive tear break-up time (NITBUT) < 10 seconds. Subjects were randomized (1:1) to receive a single bilateral treatment of iLux or LipiFlow. In this post-hoc analysis, mean changes in MGS, NITBUT (first break-up; seconds), IDEEL-SB module score, and corneal staining, from baseline to 12 months were analyzed post-single treatment with iLux.Results: Data from 119 patients (n=238 eyes) treated w

PurposeMeibomian gland contrast may be a potential indicator of gland health, especially among isotretinoin users. We aimed to develop a repeatable and reliable method for measuring Meibomian gland contrast from meibography images.MethodsLower lid (LL) and upper lid (UL) meibography were captured with the OCULUS Keratograph 5M (OCULUS, Inc) at 2 visits under the following 4 conditions: face centered with room lights on (C), left-turned face (L), right-turned face (R), and face centered with room lights off (CLO). Contrast was measured with Fiji (v2.0.0-rc-59). Coefficient of repeatability and limits of agreement (LOA) were determined using Bland-Altman plots.ResultsA total of 512 meibography images from 16 subjects (age ± SD = 24.8 ± 5.2 years; 13 female patients) were collected. Coefficient of repeatability between visits was 10.5 for UL and 14.9 for LL. Lower and upper LOA, respectively, for UL, compared with condition C, were -10.9 [95% confidence interval (CI), -13.5 to -8.3] and 6.2 (95% CI, 3.6-8.8) for L; -11.0 (95% CI, -13.8 to -8.1) and 7.0 (95% CI, 4.2-9.8) for R; and -9.0 (95% CI, -11.6 to -6.5) and 7.2 (95% CI, 4.7-9.8) for CLO. Lower and upper LOA, respectively, for LL, compared with condition C, were -18.1 (95% CI, -22.6 to -13.5) and 11.0 (95% CI, 6.5-15.5) for L; -15.3 (95% CI, -19.2 to -11.3) and 9.9 (95% CI, 6.0-13.9) for R; and -12.0 (95% CI, -15.1 to -8.8) and 8.2 (95% CI, 5.0-11.3) for CLO.ConclusionsMeibomian gland contrast is a repeatable and reliable measure for changes in Meibomian gland contrast greater than 11 in the UL and 18 in the LL.

PurposeMeibomian gland contrast may be a potential indicator of gland health, especially among isotretinoin users. We aimed to develop a repeatable and reliable method for measuring Meibomian gland contrast from meibography images.MethodsLower lid (LL) and upper lid (UL) meibography were captured with the OCULUS Keratograph 5M (OCULUS, Inc) at 2 visits under the following 4 conditions: face centered with room lights on (C), left-turned face (L), right-turned face (R), and face centered with room lights off (CLO). Contrast was measured with Fiji (v2.0.0-rc-59). Coefficient of repeatability and limits of agreement (LOA) were determined using Bland-Altman plots.ResultsA total of 512 meibography images from 16 subjects (age ± SD = 24.8 ± 5.2 years; 13 female patients) were collected. Coefficient of repeatability between visits was 10.5 for UL and 14.9 for LL. Lower and upper LOA, respectively, for UL, compared with condition C, were -10.9 [95% confidence interval (CI), -13.5 to -8.3] and 6.2 (95% CI, 3.6-8.8) for L; -11.0 (95% CI, -13.8 to -8.1) and 7.0 (95% CI, 4.2-9.8) for R; and -9.0 (95% CI, -11.6 to -6.5) and 7.2 (95% CI, 4.7-9.8) for CLO. Lower and upper LOA, respectively, for LL, compared with condition C, were -18.1 (95% CI, -22.6 to -13.5) and 11.0 (95% CI, 6.5-15.5) for L; -15.3 (95% CI, -19.2 to -11.3) and 9.9 (95% CI, 6.0-13.9) for R; and -12.0 (95% CI, -15.1 to -8.8) and 8.2 (95% CI, 5.0-11.3) for CLO.ConclusionsMeibomian gland contrast is a repeatable and reliable measure for changes in Meibomian gland contrast greater than 11 in the UL and 18 in the LL.

Background & aimsThe accumulation of neutral lipids within hepatocytes underlies non-alcoholic fatty liver disease (NAFLD), which affects a quarter of the world's population and is associated with hepatitis, cirrhosis, and hepatocellular carcinoma. Despite insights gained from both human and animal studies, our understanding of NAFLD pathogenesis remains limited. To better study the molecular changes driving the condition we aimed to generate a humanised NAFLD mouse model.MethodsWe generated TIRF (transgene-free Il2rg -/-/Rag2 -/-/Fah -/-) mice, populated their livers with human hepatocytes, and fed them a Western-type diet for 12 weeks.ResultsWithin the same chimeric liver, human hepatocytes developed pronounced steatosis whereas murine hepatocytes remained normal. Unbiased metabolomics and lipidomics revealed signatures of clinical NAFLD. Transcriptomic analyses showed that molecular responses diverged sharply between murine and human hepatocytes, demonstrating stark species differences in liver function. Regulatory network analysis indicated close agreement between our model and clinical NAFLD with respect to transcriptional control of cholesterol biosynthesis.ConclusionsThese NAFLD xenograft mice reveal an unexpected degree of evolutionary divergence in food metabolism and offer a physiologically relevant, experimentally tractable model for studying the pathogenic changes invoked by steatosis.Lay summaryFatty liver disease is an emerging health problem, and as there are no good experimental animal models, our understanding of the condition is poor. We here describe a novel humanised mouse system and compare it with clinical data. The results reveal that the human cells in the mouse liver develop fatty liver disease upon a Western-style fatty diet, whereas the mouse cells appear normal. The molecular signature (expression profiles) of the human cells are distinct from the mouse cells and metabolic analysis of the humanised livers mimic the ones observed in hu

SignificanceQuantifying meibomian gland morphology from meibography images is used for the diagnosis, treatment, and management of meibomian gland dysfunction in clinics. A novel and automated method is described for quantifying meibomian gland morphology from meibography images.PurposeMeibomian gland morphological abnormality is a common clinical sign of meibomian gland dysfunction, yet there exist no automated methods that provide standard quantifications of morphological features for individual glands. This study introduces an automated artificial intelligence approach to segmenting individual meibomian gland regions in infrared meibography images and analyzing their morphological features.MethodsA total of 1443 meibography images were collected and annotated. The dataset was then divided into development and evaluation sets. The development set was used to train and tune deep learning models for segmenting glands and identifying ghost glands from images, whereas the evaluation set was used to evaluate the performance of the model. The gland segmentations were further used to analyze individual gland features, including gland local contrast, length, width, and tortuosity.ResultsA total of 1039 meibography images (including 486 upper and 553 lower eyelids) were used for training and tuning the deep learning model, whereas the remaining 404 images (including 203 upper and 201 lower eyelids) were used for evaluations. The algorithm on average achieved 63% mean intersection over union in segmenting glands, and 84.4% sensitivity and 71.7% specificity in identifying ghost glands. Morphological features of each gland were also fed to a support vector machine for analyzing their associations with ghost glands. Analysis of model coefficients indicated that low gland local contrast was the primary indicator for ghost glands.ConclusionsThe proposed approach can automatically segment individual meibomian glands in infrared meibography images, identify ghost glands, and quant

SignificanceQuantifying meibomian gland morphology from meibography images is used for the diagnosis, treatment, and management of meibomian gland dysfunction in clinics. A novel and automated method is described for quantifying meibomian gland morphology from meibography images.PurposeMeibomian gland morphological abnormality is a common clinical sign of meibomian gland dysfunction, yet there exist no automated methods that provide standard quantifications of morphological features for individual glands. This study introduces an automated artificial intelligence approach to segmenting individual meibomian gland regions in infrared meibography images and analyzing their morphological features.MethodsA total of 1443 meibography images were collected and annotated. The dataset was then divided into development and evaluation sets. The development set was used to train and tune deep learning models for segmenting glands and identifying ghost glands from images, whereas the evaluation set was used to evaluate the performance of the model. The gland segmentations were further used to analyze individual gland features, including gland local contrast, length, width, and tortuosity.ResultsA total of 1039 meibography images (including 486 upper and 553 lower eyelids) were used for training and tuning the deep learning model, whereas the remaining 404 images (including 203 upper and 201 lower eyelids) were used for evaluations. The algorithm on average achieved 63% mean intersection over union in segmenting glands, and 84.4% sensitivity and 71.7% specificity in identifying ghost glands. Morphological features of each gland were also fed to a support vector machine for analyzing their associations with ghost glands. Analysis of model coefficients indicated that low gland local contrast was the primary indicator for ghost glands.ConclusionsThe proposed approach can automatically segment individual meibomian glands in infrared meibography images, identify ghost glands, and quant

Background & aimsThe accumulation of neutral lipids within hepatocytes underlies non-alcoholic fatty liver disease (NAFLD), which affects a quarter of the world's population and is associated with hepatitis, cirrhosis, and hepatocellular carcinoma. Despite insights gained from both human and animal studies, our understanding of NAFLD pathogenesis remains limited. To better study the molecular changes driving the condition we aimed to generate a humanised NAFLD mouse model.MethodsWe generated TIRF (transgene-free Il2rg -/-/Rag2 -/-/Fah -/-) mice, populated their livers with human hepatocytes, and fed them a Western-type diet for 12 weeks.ResultsWithin the same chimeric liver, human hepatocytes developed pronounced steatosis whereas murine hepatocytes remained normal. Unbiased metabolomics and lipidomics revealed signatures of clinical NAFLD. Transcriptomic analyses showed that molecular responses diverged sharply between murine and human hepatocytes, demonstrating stark species differences in liver function. Regulatory network analysis indicated close agreement between our model and clinical NAFLD with respect to transcriptional control of cholesterol biosynthesis.ConclusionsThese NAFLD xenograft mice reveal an unexpected degree of evolutionary divergence in food metabolism and offer a physiologically relevant, experimentally tractable model for studying the pathogenic changes invoked by steatosis.Lay summaryFatty liver disease is an emerging health problem, and as there are no good experimental animal models, our understanding of the condition is poor. We here describe a novel humanised mouse system and compare it with clinical data. The results reveal that the human cells in the mouse liver develop fatty liver disease upon a Western-style fatty diet, whereas the mouse cells appear normal. The molecular signature (expression profiles) of the human cells are distinct from the mouse cells and metabolic analysis of the humanised livers mimic the ones observed in hu

We propose a predictive model based on the $SU(3)_C\times SU(3)_L\times U(1)_X$ gauge symmetry, which is supplemented by the $D_4$ family symmetry and several auxiliary cyclic symmetries whose spontaneous breaking produces the observed SM fermion mass and mixing pattern. The masses of the light active neutrinos are produced by an inverse seesaw mechanism mediated by three right handed Majorana neutrinos. To the best of our knowledge the model corresponds to the first implementation of the $D_4$ family symmetry in a $SU(3)_C\times SU(3)_L\times U(1)_X$ theory with three right handed Majorana neutrinos and inverse seesaw mechanism. Our proposed model successfully accommodates the experimental values of the SM fermion mass and mixing parameters, the muon anomalous magnetic moment as well as the Higgs diphoton decay rate and meson oscillations constraints. The consistency of our model with the muon anomalous magnetic moment requires charged exotic vector like leptons at the TeV scale., Comment: Version accepted for publication in European Physical Journal C

Long training time hinders the potential of the deep, large-scale Spiking Neural Network (SNN) with the on-chip learning capability to be realized on the embedded systems hardware. Our work proposes a novel connection pruning approach that can be applied during the on-chip Spike Timing Dependent Plasticity (STDP)-based learning to optimize the learning time and the network connectivity of the deep SNN. We applied our approach to a deep SNN with the Time To First Spike (TTFS) coding and has successfully achieved 2.1x speed-up and 64% energy savings in the on-chip learning and reduced the network connectivity by 92.83%, without incurring any accuracy loss. Moreover, the connectivity reduction results in 2.83x speed-up and 78.24% energy savings in the inference. Evaluation of our proposed approach on the Field Programmable Gate Array (FPGA) platform revealed 0.56% power overhead was needed to implement the pruning algorithm., Comment: 8 pages, 9 figures This paper has been accepted for publication in the International Conference on Neuromorphic Systems (ICONS) 2021

PurposeAssess potential risk factors for severe Meibomian gland atrophy (SMGA) in a young adult population.MethodsCross-sectional study using medical history and ocular surface examination to evaluate relationships with study outcomes: SMGA, tear lipid layer (TLL) thickness, non-invasive (NITBUT) and fluorescein (FTBUT) tear breakup times, and symptoms using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire.ResultsOne hundred one participants (101; 202 eyes; Age: mean±SD = 22.3±4.0 years) completed the study. Hormonal birth control (HBC) use was the only significant risk factor for SMGA (p = 0.028). Female HBC users had 4.8 times greater odds of having SMGA compared to female HBC non-users (p = 0.028), but the odds of having SMGA was similar between female HBC non-users and males (p = 0.885). Multivariable analysis suggested that the relationship between SMGA and TLL thickness was dependent on HBC use. Compared to female HBC non-users without SMGA, TLL thickness for HBC users was estimated to be 10 nm thinner if SMGA was absent (p = 0.007) and 21 nm thinner if SMGA was present (p<0.001). SMGA status had no significant impact on TLL thickness among female HBC non-users (p = 0.552). The effect of TLL thickness on FTBUT was small but significant (p = 0.026). TLL thickness was not significantly associated with NITBUT (p = 0.349). Neither FTBUT nor NITBUT was significantly associated with the SPEED score.ConclusionHBC use may be associated with SMGA, supporting the hypothesis that SMGA could lead to thinner TLL. However, less evidence was present to support that thin TLL could lead to clinically detectable tear film instability and subsequently to increased ocular dryness symptoms. Further investigation with a larger sample size is warranted to confirm these findings.

PurposeAssess potential risk factors for severe Meibomian gland atrophy (SMGA) in a young adult population.MethodsCross-sectional study using medical history and ocular surface examination to evaluate relationships with study outcomes: SMGA, tear lipid layer (TLL) thickness, non-invasive (NITBUT) and fluorescein (FTBUT) tear breakup times, and symptoms using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire.ResultsOne hundred one participants (101; 202 eyes; Age: mean±SD = 22.3±4.0 years) completed the study. Hormonal birth control (HBC) use was the only significant risk factor for SMGA (p = 0.028). Female HBC users had 4.8 times greater odds of having SMGA compared to female HBC non-users (p = 0.028), but the odds of having SMGA was similar between female HBC non-users and males (p = 0.885). Multivariable analysis suggested that the relationship between SMGA and TLL thickness was dependent on HBC use. Compared to female HBC non-users without SMGA, TLL thickness for HBC users was estimated to be 10 nm thinner if SMGA was absent (p = 0.007) and 21 nm thinner if SMGA was present (p<0.001). SMGA status had no significant impact on TLL thickness among female HBC non-users (p = 0.552). The effect of TLL thickness on FTBUT was small but significant (p = 0.026). TLL thickness was not significantly associated with NITBUT (p = 0.349). Neither FTBUT nor NITBUT was significantly associated with the SPEED score.ConclusionHBC use may be associated with SMGA, supporting the hypothesis that SMGA could lead to thinner TLL. However, less evidence was present to support that thin TLL could lead to clinically detectable tear film instability and subsequently to increased ocular dryness symptoms. Further investigation with a larger sample size is warranted to confirm these findings.

PurposeTo develop a deep learning approach to digitally segmenting meibomian gland atrophy area and computing percent atrophy in meibography images.MethodsA total of 706 meibography images with corresponding meiboscores were collected and annotated for each one with eyelid and atrophy regions. The dataset was then divided into the development and evaluation sets. The development set was used to train and tune the deep learning model, while the evaluation set was used to evaluate the performance of the model.ResultsFour hundred ninety-seven meibography images were used for training and tuning the deep learning model while the remaining 209 images were used for evaluations. The algorithm achieves 95.6% meiboscore grading accuracy on average, largely outperforming the lead clinical investigator (LCI) by 16.0% and the clinical team by 40.6%. Our algorithm also achieves 97.6% and 95.4% accuracy for eyelid and atrophy segmentations, respectively, as well as 95.5% and 66.7% mean intersection over union accuracies (mean IU), respectively. The average root-mean-square deviation (RMSD) of the percent atrophy prediction is 6.7%.ConclusionsThe proposed deep learning approach can automatically segment the total eyelid and meibomian gland atrophy regions, as well as compute percent atrophy with high accuracy and consistency. This provides quantitative information of the gland atrophy severity based on meibography images.Translational relevanceBased on deep neural networks, the study presents an accurate and consistent gland atrophy evaluation method for meibography images, and may contribute to improved understanding of meibomian gland dysfunction.

ZEB1 and ZEB2 are structurally related E-box binding homeobox transcription factors that induce epithelial to mesenchymal transitions during development and disease. As such, they regulate cancer cell invasion, dissemination and metastasis of solid tumors. In addition, their expression is associated with the gain of cancer stem cell properties and resistance to therapy. Using conditional loss-of-function mice, we previously demonstrated that Zeb2 also plays pivotal roles in hematopoiesis, controlling important cell fate decisions, lineage commitment and fidelity. In addition, upon Zeb2 overexpression, mice spontaneously develop immature T-cell lymphoblastic leukemia. Here we show that pre-leukemic Zeb2-overexpressing thymocytes are characterized by a differentiation delay at beta-selection due to aberrant activation of the interleukin-7 receptor signaling pathway. Notably, and in contrast to Lmo2-overexpressing thymocytes, these pre-leukemic Zeb2-overexpressing T-cell progenitors display no acquired self-renewal properties. Finally, Zeb2 activation in more differentiated T-cell precursor cells can also drive malignant T-cell development, suggesting that the early T-cell differentiation delay is not essential for Zeb2-mediated leukemic transformation. Altogether, our data suggest that Zeb2 and Lmo2 drive malignant transformation of immature T-cell progenitors via distinct molecular mechanisms.

OBJECTIVE: Stem cell-based regenerative therapies have been intensively studied with the aim to define an ideal cell type for the treatment of myocardial infarction. We tested systemically delivered, platelet-targeted induced vascular progenitor cells (iVPCs) to study their potential to salvage damaged myocardium after ischemia-reperfusion injury. METHODS: Using a mouse model of ischemia-reperfusion injury, we tested the potential of platelet-targeted iVPCs (1 × 106 targ-iVPCs) compared to non-targ-iVPCs and a saline control. Bioluminescence imaging, echocardiography, and histological analyses were performed. RESULTS: Four weeks after ischemia-reperfusion injury, systemic delivery of targ-iVPCs led to reduced fibrosis and infarct size (PBS: 25.7 ± 3.9 vs targ-iVPC: 18.4 ± 6.6 vs non-targ-iVPC: 25.1 ± 3.7%I/LV, P < 0.05), increased neovascularization, and restored cardiac function (PBS: 44.0 ± 4.2 vs targ-iVPC: 54.3 ± 4.5 vs non-targ-iVPC: 46.4 ± 3.8%EF, P < 0.01). Cell tracking experiments revealed entrapment of intravenously injected iVPCs in the pulmonary microvasculature in both cell-treated groups. CONCLUSIONS: Systemic delivery of iVPCs after cardiac ischemia-reperfusion injury is limited by pulmonary entrapment of the cells. Nevertheless, targ-iVPCs reduced infarct size, fibrosis, increased neovascularization, and most importantly retained cardiac function. These findings contribute to the mechanistic discussion of cell-based therapy and ultimately identify activated platelet-targeted iVPCs as candidates for cell therapy and also describe cell therapy benefits without the necessity of engrafting.

PurposeTo develop a deep learning approach to digitally segmenting meibomian gland atrophy area and computing percent atrophy in meibography images.MethodsA total of 706 meibography images with corresponding meiboscores were collected and annotated for each one with eyelid and atrophy regions. The dataset was then divided into the development and evaluation sets. The development set was used to train and tune the deep learning model, while the evaluation set was used to evaluate the performance of the model.ResultsFour hundred ninety-seven meibography images were used for training and tuning the deep learning model while the remaining 209 images were used for evaluations. The algorithm achieves 95.6% meiboscore grading accuracy on average, largely outperforming the lead clinical investigator (LCI) by 16.0% and the clinical team by 40.6%. Our algorithm also achieves 97.6% and 95.4% accuracy for eyelid and atrophy segmentations, respectively, as well as 95.5% and 66.7% mean intersection over union accuracies (mean IU), respectively. The average root-mean-square deviation (RMSD) of the percent atrophy prediction is 6.7%.ConclusionsThe proposed deep learning approach can automatically segment the total eyelid and meibomian gland atrophy regions, as well as compute percent atrophy with high accuracy and consistency. This provides quantitative information of the gland atrophy severity based on meibography images.Translational relevanceBased on deep neural networks, the study presents an accurate and consistent gland atrophy evaluation method for meibography images, and may contribute to improved understanding of meibomian gland dysfunction.

Iron deficiency (ID) defined as plasma ferritin <12 µg/L is associated with delayed cognitive development in early childhood and increased incidence of infections, however the longitudinal association between early life factors and ID in 18-month-old children in Denmark is unknown. This study aimed to determine the prevalence of ID and to describe risk factors associated with ID in healthy 18-month-old Danish children. Blood samples, anthropometric measurements and self-reported questionnaire data had been obtained in the birth cohort, Odense Child Cohort (OCC). The questionnaires were modified from those used in the DNBC, Danish National Birth Cohort. Plasma ferritin and C-reactive protein in venous, non-fasting samples were analysed in the final sample size of 370 children after exclusion of 79 children due to chronic disease, acute infection, C-reactive protein >10 mg/L, twin birth or prematurity. Associations with ID were analysed by logistic regression, adjusting for sex, maternal education, duration of partial breastfeeding and current intake of milk, fish and meat. Overall, 56 children had ID (15.1%). Factors associated with increased risk were exclusive breastfeeding beyond 4 months (OR 5.97, 95%CI [1.63; 21.86]) and no intake of oral iron supplements from 6-12 months (OR 3.99, 95%CI [1.33; 11.97]. Duration of partial breastfeeding and current diet were not associated with ID. In conclusion, the ID prevalence was 15.1%, and both exclusive breastfeeding beyond 4 months and no intake of oral iron supplements from 6-12 months were associated with increased risk for ID in 18-month-old children.

Iron deficiency (ID) defined as plasma ferritin <12 µg/L is associated with delayed cognitive development in early childhood and increased incidence of infections, however the longitudinal association between early life factors and ID in 18-month-old children in Denmark is unknown. This study aimed to determine the prevalence of ID and to describe risk factors associated with ID in healthy 18-month-old Danish children. Blood samples, anthropometric measurements and self-reported questionnaire data had been obtained in the birth cohort, Odense Child Cohort (OCC). The questionnaires were modified from those used in the DNBC, Danish National Birth Cohort. Plasma ferritin and C-reactive protein in venous, non-fasting samples were analysed in the final sample size of 370 children after exclusion of 79 children due to chronic disease, acute infection, C-reactive protein >10 mg/L, twin birth or prematurity. Associations with ID were analysed by logistic regression, adjusting for sex, maternal education, duration of partial breastfeeding and current intake of milk, fish and meat. Overall, 56 children had ID (15.1%). Factors associated with increased risk were exclusive breastfeeding beyond 4 months (OR 5.97, 95%CI [1.63; 21.86]) and no intake of oral iron supplements from 6-12 months (OR 3.99, 95%CI [1.33; 11.97]. Duration of partial breastfeeding and current diet were not associated with ID. In conclusion, the ID prevalence was 15.1%, and both exclusive breastfeeding beyond 4 months and no intake of oral iron supplements from 6-12 months were associated with increased risk for ID in 18-month-old children.

Purpose:There has been interest in determining whether lid wiper epitheliopathy (LWE) plays a key role in causing ocular discomfort. Conflicting reports have made it difficult to discern whether LWE is more prevalent in certain populations, what characteristics are associated with its severity, and what its role is in symptomology. This cross-sectional study on a large and diverse population attempts to answer these questions. Methods:Subjects were asked to complete questionnaires related to dry eye and to ocular discomfort. A comprehensive set of ocular surface parameters were assessed, including LWE length and width, tear-film lipid layer thickness, fluorescein tear breakup time (FTBUT), lid-parallel conjunctival folds (LIPCOF), and corneal staining. Results:A total of 287 subjects participated in the study. LWE was observed in 45% of the study cohort and was twice as prevalent in Asians than non-Asians (P < 0.005). LWE was more likely to present in contact lens wearers than non-contact lens wearers (P = 0.03). Decreased FTBUT was associated with increased LWE length and width (P < 0.005 and P = 0.01, respectively), although only a small effect size was noted. Presence of LIPCOF was linked with a 0.25-grade increase in LWE width (P = 0.01). Only LWE width was associated with greater symptoms in contact lens wearers. Conclusions:LWE was associated with decreased tear-film stability, contact lens wear, lid anatomy, and LIPCOF. LWE was not associated with symptoms in non-contact lens wearers. LWE width was associated with greater symptoms in contact lens wearers but was only clinically significant with moderate to severe LWE width.

Atacama Large Millimetre/sub-millimetre Array (ALMA) observations of the CO(1-0) and CO(2-1) emissions from the circumstellar envelope of the Asymptotic Giant Branch (AGB) star EP Aqr have been made with four times better spatial resolution than previously available. They are analysed with emphasis on the de-projection in space of the effective emissivity and flux of matter using as input a prescribed configuration of the velocity field, assumed to be radial. The data are found to display an intrinsic axi-symmetry with respect to an axis making a small angle with the line of sight. A broad range of wind configurations, from prolate (bipolar) to oblate (equatorial) has been studied and found to be accompanied by significant equatorial emission. Qualitatively, the effective emissivity is enhanced near the equator to produce the central narrow component observed in the Doppler velocity spectra and its dependence on star latitude generally follows that of the wind velocity with the exception of an omni-present depression near the poles. In particular, large equatorial expansion velocities produce a flared disc or a ring of effective emissivity and mass loss. The effect on the determination of the orientation of the star axis of radial velocity gradients and possibly competing rotation and expansion in the equatorial disc is discussed. In general, the flux of matter is found to reach a broad maximum at distances of the order of 500 au from the star. Arguments are given that may be used to prefer one wind velocity distribution to another. As a result of the improved quality of the data, a deeper understanding of the constraints imposed on morphology and kinematics has been obtained., Comment: 17 pages, 11 figures, accepted for publication in RAA

Observations by the Atacama Large Millimeter/sub-millimeter Array of the dust continuum and $^{13}$CO(3-2) millimeter emissions of the triple stellar system GG Tau A are analysed, giving evidence for a rotating gas disc and a concentric and coplanar dust ring. The present work complements an earlier analysis (Tang et al. 2016) by exploring detailed properties of the gas disc. A 95% confidence level upper limit of 0.24 arcsec (34 au) is placed on the disc scale height at a distance of 1 arcsec (140 au) from the central stars. Evidence for Keplerian rotation of the gas disc is presented, the rotation velocity reaching ~3.1 kms$^{-1}$ at 1 arcsec from the central stars, and a 99% confidence level upper limit of 9% is placed on a possible in-fall velocity relative contribution. Variations of the intensity across the disc area are studied in detail and confirm the presence of a hot spot in the south-eastern quadrant. However several other significant intensity variations, in particular a depression in the northern direction, are also revealed. Variations of the intensity are found to be positively correlated to variations of the line width. Possible contributions to the measured line width are reviewed, suggesting an increase of the disc temperature and opacity with decreasing distance from the stars., Comment: 15 pages, 15 figures, 2 tables and 7 references, accepted for publication in RAA

Purpose:There has been interest in determining whether lid wiper epitheliopathy (LWE) plays a key role in causing ocular discomfort. Conflicting reports have made it difficult to discern whether LWE is more prevalent in certain populations, what characteristics are associated with its severity, and what its role is in symptomology. This cross-sectional study on a large and diverse population attempts to answer these questions. Methods:Subjects were asked to complete questionnaires related to dry eye and to ocular discomfort. A comprehensive set of ocular surface parameters were assessed, including LWE length and width, tear-film lipid layer thickness, fluorescein tear breakup time (FTBUT), lid-parallel conjunctival folds (LIPCOF), and corneal staining. Results:A total of 287 subjects participated in the study. LWE was observed in 45% of the study cohort and was twice as prevalent in Asians than non-Asians (P < 0.005). LWE was more likely to present in contact lens wearers than non-contact lens wearers (P = 0.03). Decreased FTBUT was associated with increased LWE length and width (P < 0.005 and P = 0.01, respectively), although only a small effect size was noted. Presence of LIPCOF was linked with a 0.25-grade increase in LWE width (P = 0.01). Only LWE width was associated with greater symptoms in contact lens wearers. Conclusions:LWE was associated with decreased tear-film stability, contact lens wear, lid anatomy, and LIPCOF. LWE was not associated with symptoms in non-contact lens wearers. LWE width was associated with greater symptoms in contact lens wearers but was only clinically significant with moderate to severe LWE width.

We perform a comprehensive analysis of several phenomenological aspects of the renormalizable extension of the inert 3-3-1 model with sequentially loop-generated SM fermion mass hierarchy. Special attention is paid to the study of the constraints arising from the experimental data on the $\rho$ parameter, as well as those ones resulting from the charged lepton flavor violating process $\mu\to e\gamma$ and dark matter. We also study the single $Z'$ production via Drell-Yan mechanism at the LHC. We have found that $Z'$ gauge bosons heavier than about $4$ TeV comply with the experimental constraints on the oblique $\rho$ parameter as well as with the collider constraints. In addition, we have found that the constraint on the charged lepton flavor violating decay $\mu\rightarrow e\gamma$ sets the sterile neutrino masses to be lighter than about $1.12$ TeV. In addition the model allows charged lepton flavor violating processes within reach of the forthcoming experiments. The scalar potential and the gauge sector of the model are analyzed and discussed in detail. Our model successfully accommodates the observed Dark matter relic density., Comment: Version accepted for publication in PRD

The electroweak phase transition (EWPT) is considered in the framework of 3-3-1-1 model for Dark Matter. The phase structure within three or two periods is approximated for the theory with many vacuum expectation values (VEVs) at TeV and Electroweak scales. In the mentioned model, there are two pictures. The first picture containing two periods of EWPT, has a transition $SU(3) \rightarrow SU(2)$ at 6 TeV scale and another is $SU(2) \rightarrow U(1)$ transition which is the like-standard model EWPT. The second picture is an EWPT structure containing three periods, in which two first periods are similar to those of the first picture and another one is the symmetry breaking process of $U(1)_N$ subgroup. Our study leads to the conclusion that EWPTs are the first order phase transitions when new bosons are triggers and their masses are within range of some TeVs. Especially, in two pictures, the maximum strength of the $SU(2) \rightarrow U(1)$ phase transition is equal to 2.12 so this EWPT is not strong. Moreover, neutral fermions, which are candidates for Dark Matter and obey the Fermi-Dirac distribution, can be a negative trigger for EWPT. However, they do not make lose the first-order EWPT at TeV scale. Furthermore, in order to be the strong first-order EWPT at TeV scale, the symmetry breaking processes must produce more bosons than fermions or the mass of bosons must be much larger than that of fermions., Comment: 32 pages, 6 figures, PRD Journal version

Atacama Large Millimetre/sub-millimetre Array (ALMA) observations of the CO(1-0) and CO(2-1) emissions from the circumstellar envelope of the Asymptotic Giant Branch (AGB) star EP Aqr have been made with four times better spatial resolution than previously available. They are analysed with emphasis on the de-projection in space of the effective emissivity and flux of matter using as input a prescribed configuration of the velocity field, assumed to be radial. The data are found to display an intrinsic axi-symmetry with respect to an axis making a small angle with the line of sight. A broad range of wind configurations, from prolate (bipolar) to oblate (equatorial) has been studied and found to be accompanied by significant equatorial emission. Qualitatively, the effective emissivity is enhanced near the equator to produce the central narrow component observed in the Doppler velocity spectra and its dependence on star latitude generally follows that of the wind velocity with the exception of an omni-present depression near the poles. In particular, large equatorial expansion velocities produce a flared disc or a ring of effective emissivity and mass loss. The effect on the determination of the orientation of the star axis of radial velocity gradients and possibly competing rotation and expansion in the equatorial disc is discussed. In general, the flux of matter is found to reach a broad maximum at distances of the order of 500 au from the star. Arguments are given that may be used to prefer one wind velocity distribution to another. As a result of the improved quality of the data, a deeper understanding of the constraints imposed on morphology and kinematics has been obtained., Comment: 17 pages, 11 figures, accepted for publication in RAA

Observations by the Atacama Large Millimeter/sub-millimeter Array of the dust continuum and $^{13}$CO(3-2) millimeter emissions of the triple stellar system GG Tau A are analysed, giving evidence for a rotating gas disc and a concentric and coplanar dust ring. The present work complements an earlier analysis (Tang et al. 2016) by exploring detailed properties of the gas disc. A 95% confidence level upper limit of 0.24 arcsec (34 au) is placed on the disc scale height at a distance of 1 arcsec (140 au) from the central stars. Evidence for Keplerian rotation of the gas disc is presented, the rotation velocity reaching ~3.1 kms$^{-1}$ at 1 arcsec from the central stars, and a 99% confidence level upper limit of 9% is placed on a possible in-fall velocity relative contribution. Variations of the intensity across the disc area are studied in detail and confirm the presence of a hot spot in the south-eastern quadrant. However several other significant intensity variations, in particular a depression in the northern direction, are also revealed. Variations of the intensity are found to be positively correlated to variations of the line width. Possible contributions to the measured line width are reviewed, suggesting an increase of the disc temperature and opacity with decreasing distance from the stars., Comment: 15 pages, 15 figures, 2 tables and 7 references, accepted for publication in RAA

PurposeTo examine the relationships among tear osmolarity, tear film stability, and several measures of dry eye (DE) symptoms in a multivariable analysis.MethodsA cross-sectional study was conducted with 137 subjects (68 non-contact lens [CL] wearers and 69 soft CL wearers) recruited from a university campus. Tear breakup time (TBUT) was measured noninvasively (NITBUT) and with fluorescein (FTBUT). Tear osmolarity was measured by an osmometer. Dry eye symptoms were assessed using the Dry Eye Flow Chart and several different questionnaires.ResultsSubjects ranged in age from 18 to 67 years, with a mean of 28 years. Subjects had a mean (SD) osmolarity of 293 (10) mOsm/L, NITBUT of 14.1 (10.9) seconds, and FTBUT of 14.8 (12.6) seconds. Shorter NITBUT and FTBUT were significantly associated with female sex (p = 0.001 and p = 0.027, respectively) and Asian ethnicity (p = 0.030 and p = 0.004, respectively). There were no clinically significant relationships between tear osmolarity and FTBUT, NITBUT, or DE symptoms. Higher Dry Eye Flow Chart score (i.e., worse symptoms) was associated with older age (p < 0.001), female sex (p = 0.014), CL wear (p < 0.001), shorter NITBUT (p < 0.001), and shorter FTBUT (p = 0.028). The sensitivities and specificities for using clinical measurements to diagnose moderate to severe DE were as follows: osmolarity, 0.67 and 0.46, respectively; NITBUT, 0.72 and 0.52, respectively; and FTBUT, 0.68 and 0.57, respectively.ConclusionsIn a population of asymptomatic, mild and moderate DE patients, increased tear osmolarity was not significantly associated with reported symptom severity and frequency. Tear osmolarity, NITBUT, and FTBUT exhibited similar sensitivities and specificities when used to diagnose moderate to severe DE.

PurposeTo examine the relationships among tear osmolarity, tear film stability, and several measures of dry eye (DE) symptoms in a multivariable analysis.MethodsA cross-sectional study was conducted with 137 subjects (68 non-contact lens [CL] wearers and 69 soft CL wearers) recruited from a university campus. Tear breakup time (TBUT) was measured noninvasively (NITBUT) and with fluorescein (FTBUT). Tear osmolarity was measured by an osmometer. Dry eye symptoms were assessed using the Dry Eye Flow Chart and several different questionnaires.ResultsSubjects ranged in age from 18 to 67 years, with a mean of 28 years. Subjects had a mean (SD) osmolarity of 293 (10) mOsm/L, NITBUT of 14.1 (10.9) seconds, and FTBUT of 14.8 (12.6) seconds. Shorter NITBUT and FTBUT were significantly associated with female sex (p = 0.001 and p = 0.027, respectively) and Asian ethnicity (p = 0.030 and p = 0.004, respectively). There were no clinically significant relationships between tear osmolarity and FTBUT, NITBUT, or DE symptoms. Higher Dry Eye Flow Chart score (i.e., worse symptoms) was associated with older age (p < 0.001), female sex (p = 0.014), CL wear (p < 0.001), shorter NITBUT (p < 0.001), and shorter FTBUT (p = 0.028). The sensitivities and specificities for using clinical measurements to diagnose moderate to severe DE were as follows: osmolarity, 0.67 and 0.46, respectively; NITBUT, 0.72 and 0.52, respectively; and FTBUT, 0.68 and 0.57, respectively.ConclusionsIn a population of asymptomatic, mild and moderate DE patients, increased tear osmolarity was not significantly associated with reported symptom severity and frequency. Tear osmolarity, NITBUT, and FTBUT exhibited similar sensitivities and specificities when used to diagnose moderate to severe DE.

We present high resolution ALMA observations of the CO(3-2) and 350 GHz continuum emissions of the debris disc of 49 Ceti, known to be particularly rich in molecular gas in spite of its age. The main new results are: i) both CO and dust discs share a same position angle and a same inclination but the gas disc is more homogeneous, more central and thinner than the dust disc; ii) evidence is obtained for a significant deficit of observed CO(3-2) emission at Doppler velocities differing from the star systemic velocity by less than 1 \kms; iii) gas velocities are accurately measured and found Keplerian over a broad range of disc radii; iv) the observed CO(3-2) line width is dominated by Keplerian shear and upper limits are obtained to the intrinsic line width. Simple phenomenological models of both CO(3-2) and \mbox{350 GHz} continuum emissions are presented, requiring the use of only very few parameters. The results are discussed in the frame of currently favoured models., Comment: 15 pages, 11 figures, accepted for publication in MNRAS

We show that the economical 3-3-1 model poses a very high new physics scale of the order of 1000~TeV due to the constraint on the flavor-changing neutral current. The implications of the model for neutrino masses, inflation, leptogenesis, and superheavy dark matter are newly recognized. Alternatively, we modify the model by rearranging the third quark generation differently from the first two quark generations, as well as changing the scalar sector. The resultant model now predicts a consistent new physics at TeV scale unlike the previous case and may be fully probed at the current colliders. Particularly, due to the minimal particle contents, the models under consideration manifestly accommodate dark matter candidates and neutrino masses, with novel and distinct production mechanisms. The large flavor-changing neutral currents that come from the ordinary and exotic quark mixings can be avoided due to the approximate $B-L$ symmetry., Comment: 21 pages; english writing improved, dark matter stability stated, and references added; matches journal version

The lepton flavor violating decay of the Standard Model-like Higgs boson (LFVHD), h->\mu\tau, is discussed in seesaw models at the one-loop level. Based on particular analytic expressions of Passarino-Veltman functions, the two unitary and 't Hooft Feynman gauges are used to compute the branching ratio of LFVHD and compare with results reported recently. In the minimal seesaw (MSS) model, the branching ratio was investigated in the whole valid range 10^{-9}-10^{15} GeV of new neutrino mass scale m_{n_6}. Using the Casas-Ibarra parameterization, this branching ratio enhances with large and increasing m_{n_6}. But the maximal value can reach only order of 10^{-11}. Interesting relations of LFVHD predicted by the MSS and inverse seesaw (ISS) model are discussed. The ratio between two LFVHD branching ratios predicted by the ISS and MSS is simply m^2_{n_6}\mu^{-2}_X, where \mu_X is the small neutrino mass scale in the ISS. The consistence between different calculations is shown precisely from analytical approach., Comment: 4 figures, 26 pages, some analytic formulas and statements are corrected. Main results are unchanged. New references added. Version published in NPB

We present high resolution ALMA observations of the CO(3-2) and 350 GHz continuum emissions of the debris disc of 49 Ceti, known to be particularly rich in molecular gas in spite of its age. The main new results are: i) both CO and dust discs share a same position angle and a same inclination but the gas disc is more homogeneous, more central and thinner than the dust disc; ii) evidence is obtained for a significant deficit of observed CO(3-2) emission at Doppler velocities differing from the star systemic velocity by less than 1 \kms; iii) gas velocities are accurately measured and found Keplerian over a broad range of disc radii; iv) the observed CO(3-2) line width is dominated by Keplerian shear and upper limits are obtained to the intrinsic line width. Simple phenomenological models of both CO(3-2) and \mbox{350 GHz} continuum emissions are presented, requiring the use of only very few parameters. The results are discussed in the frame of currently favoured models., Comment: 15 pages, 11 figures, accepted for publication in MNRAS

PurposeTo investigate the effects of 30 nights of overnight orthokeratology (OOK) on corneal epithelial permeability (Pdc) and corneal biomechanical properties.MethodsBE Retainer and Paragon CRT lenses were used. Visits were scheduled approximately 4 hours after awakening at baseline and after 1, 5, 10, 14, and 30 days of treatment. Pdc was measured at baseline and at day 30, whereas corneal biomechanical properties and visual acuities (VAs) were measured at all visits.ResultsThirty-nine neophytes and soft contact lens wearers completed the study. There was no difference in Pdc between baseline (ln[Pdc] [95% confidence interval (CI)] = -2.65 [-2.80 to -2.50]) and day 30 (ln[Pdc][CI] = -2.68 [-2.85 to -2.50]) (P = 0.88). Corneal hysteresis (CH) and corneal resistance factor (CRF) reduced significantly from baseline (CH [CI] = 10.89 [10.59-11.19] mm Hg and CRF [CI] = 10.35 [9.99-10.72] mm Hg) to day 30 (CH [CI] = 10.59 [10.31-10.87] mm Hg and CRF [CI] = 9.58 [9.26-9.89] mm Hg) (P = 0.001 for CH and P < 0.001 for CRF). Posttreatment VA did not reach baseline targets, and the difference was worse with low-contrast letters. Asian individuals (n = 18) had significantly worse VA than non-Asian individuals (n = 21) under most conditions through day 5, and the difference extended through day 14 with low-contrast letters under mesopic conditions. The percentage of participants who achieved 20/20 uncorrected was 17% Asian and 40% non-Asian individuals after day 1 and reached 69% Asian and 83% non-Asian individuals at day 30.ConclusionsThirty nights of OOK did not alter Pdc when measured 4 hours after awakening. OOK caused CH and CRF to decrease, but the changes were not clinically significant compared with diseased and postsurgical cases. Asian individuals, who had lower baseline CH in this study, responded slower to OOK based on early uncorrected VA and overrefraction measurements.

PurposeTo investigate the effects of 30 nights of overnight orthokeratology (OOK) on corneal epithelial permeability (Pdc) and corneal biomechanical properties.MethodsBE Retainer and Paragon CRT lenses were used. Visits were scheduled approximately 4 hours after awakening at baseline and after 1, 5, 10, 14, and 30 days of treatment. Pdc was measured at baseline and at day 30, whereas corneal biomechanical properties and visual acuities (VAs) were measured at all visits.ResultsThirty-nine neophytes and soft contact lens wearers completed the study. There was no difference in Pdc between baseline (ln[Pdc] [95% confidence interval (CI)] = -2.65 [-2.80 to -2.50]) and day 30 (ln[Pdc][CI] = -2.68 [-2.85 to -2.50]) (P = 0.88). Corneal hysteresis (CH) and corneal resistance factor (CRF) reduced significantly from baseline (CH [CI] = 10.89 [10.59-11.19] mm Hg and CRF [CI] = 10.35 [9.99-10.72] mm Hg) to day 30 (CH [CI] = 10.59 [10.31-10.87] mm Hg and CRF [CI] = 9.58 [9.26-9.89] mm Hg) (P = 0.001 for CH and P < 0.001 for CRF). Posttreatment VA did not reach baseline targets, and the difference was worse with low-contrast letters. Asian individuals (n = 18) had significantly worse VA than non-Asian individuals (n = 21) under most conditions through day 5, and the difference extended through day 14 with low-contrast letters under mesopic conditions. The percentage of participants who achieved 20/20 uncorrected was 17% Asian and 40% non-Asian individuals after day 1 and reached 69% Asian and 83% non-Asian individuals at day 30.ConclusionsThirty nights of OOK did not alter Pdc when measured 4 hours after awakening. OOK caused CH and CRF to decrease, but the changes were not clinically significant compared with diseased and postsurgical cases. Asian individuals, who had lower baseline CH in this study, responded slower to OOK based on early uncorrected VA and overrefraction measurements.

Observations by the Atacama Large Millimetre/sub-millimetre Array of the 358 GHz continuum emission of the gravitationally lensed quasar host RX J0911.4+0551 have been analysed. They complement earlier Plateau de Bure Interferometer observations of the CO(7-6) emission. The good knowledge of the lensing potential obtained from Hubble Space Telescope observations of the quasar makes a joint analysis of the three emissions possible. It gives evidence for the quasar source to be concentric with the continuum source within 0.31 kpc and with the CO(7-6) source within 1.10 kpc. It also provides a measurement of the size of the continuum source, 0.76 $\pm$ 0.04 kpc FWHM, making RX J0911.4+0551 one of the few high redshift galaxies for which the dust and gas components are resolved with dimensions being measured. Both are found to be very compact, the former being smaller than the latter by a factor of $\sim$3.4$\pm$0.4. Moreover, new measurements of the CO ladder $-$ CO(10-9) and CO(11-10) $-$ are presented that confirm the extreme narrowness of the CO line width (107$\pm$20 km s$^{-1}$ on average). Their mere detection implies higher temperature and/or density than for typical quasar hosts at this redshift and suggests a possible contribution of the central AGN to gas and dust heating. The results are interpreted in terms of current understanding of galaxy evolution at the peak of star formation. They suggest that RX J0911.4+0551 is a young galaxy in an early stage of its evolution, having experienced no recent major mergers, star formation being concentrated in its centre., Comment: 13 pages, 11 figures, accepted for publication in MNRAS

Using ALMA observations of the C$^{18}$O(2-1) line emission of the gas envelope of protostar L1527, we have reconstructed its morphology and kinematics under the assumption of axisymmetry about the west-east axis. The main original contribution to our understanding of the formation process of L1527 is the presentation of a simple 3D parameterisation based solely on regions that are not dominated by absorption. In the explored range ($\sim$0.7 to 5 arcsec from the star) the model reproduces observations better than earlier attempts. The main results include: a measurement of the rotation velocity that confirms its evolution to Keplerian toward short distances; a measurement of the mean in-fall velocity, 0.43$\pm$0.10 kms$^{-1}$, lower than free fall velocity, with no evidence for the significant $r$-dependence suggested by an earlier analysis; a measurement of the central mass, 0.23$\pm$0.06 M$_{\odot}$ within a distance of 1.5 arcsec from the star, in agreement with earlier estimates obtained from a different range of distances; evidence for a strong disc plane depression of the in-falling flux resulting in an $X$ shaped flow possibly caused by the freeze-out of CO molecules on dust grains; a measurement of the accretion rate, 3.5$\pm$1.0 10$^{-7}$ M$_{\odot}$yr$^{-1}$ at a distance of 1 arcsec (140 au) from the star; evidence for a 10$^\circ$ tilt of the symmetry plane of the envelope about the line of sight, cancelling below $\sim$3 arcsec from the star, but matching infrared observations and being also apparent on the sky map of the mean Doppler velocity., Comment: 11 pages, 12 figures, MNRAS accepted

We analyse ALMA observations of the 12CO(3-2) emission of the circumstellar envelope (CSE) of the Mira variable binary star W Aql. These provide, for the first time, spatially resolved Doppler velocity spectra of the CSE up to angular distances to the central star of ~ 5" (meaning some 2000 AU). The exploratory nature of the observations (only five minutes in each of two different configurations) does not allow for a detailed modelling of the properties of the CSE but provides important qualitative information on its morphology and kinematics. Emission is found to be enhanced along an axis moving from east/west to north-east/south-west when the angular distance from the central star projected on the plane of the sky increases from zero to four arcseconds. In parallel, the Doppler velocity distribution displays asymmetry along an axis moving from east/west to north-west/south-east. The results are discussed in the context of earlier observations, in particular of the dust morphology., Comment: 11 pages, 12 figures

Observations of the $^{12}$CO(3-2) emission of the circumstellar envelope (CSE) of the variable star $\pi^1$ Gru using the compact array (ACA) of the ALMA observatory have been recently made accessible to the public. An analysis of the morphology and kinematics of the CSE is presented with a result very similar to that obtained earlier for $^{12}$CO(2-1) emission by Chiu et al. (2006) using the Sub-Millimeter Array. A quantitative comparison is made using their flared disk model. A new model is presented that provides a significantly better description of the data, using radial winds and smooth evolutions of the radio emission and wind velocity from the stellar equator to the poles., Comment: accepted for publication in Research in Astronomy and Astrophysics (RAA)

The unprecedented quality of the observations available from the Atacama Large Millimetre/sub-millimetre Array (ALMA) calls for analysis methods making the best of them. Reconstructing in space the morphology and kinematics of radio sources is an underdetermined problem that requires imposing additional constraints for its solution. The hypothesis of rotational invariance about a well-defined star axis, which is a good approximation to the description of the gas envelopes of many evolved stars and protostars, is particularly efficient in this role. In the first part of the article, a systematic use of simulated observations allows for identifying the main problems and for constructing quantities aimed at solving them. In particular the evaluation of the orientation of the star axis in space and the differentiation between expansion along the star axis and rotation about it are given special attention. The use of polar rather than Cartesian sky coordinates is shown to better match the morphology and kinematics of actual stars. The radial dependence of the gas density and temperature and the possible presence of velocity gradients are briefly considered. In the second part, the results obtained in the first part are applied to a few stars taken as examples with the aim of evaluating their usefulness when applied to concrete cases. A third part takes stock of what precedes and formulates some guidelines for modelling the radio emission of axisymmetric radio sources, limited however to the mathematics and geometry of the problem, physics considerations being ignored., Comment: 21 pages, 19 figures, published MNRAS 461, 4276 (2016)

Observations of 12CO(3-2) emission of the circumbinary envelope of Mira Ceti, made by ALMA are analysed. The observed Doppler velocity distribution is made of three components: a blue-shifted south-eastern arc, which can be described as a ring in slow radial expansion, ~1.7 km/s, making an angle of ~50 deg with the plane of the sky and born some 2000 years ago; a few arcs, probably born at the same epoch as the blue-shifted arc, all sharing Doppler velocities red-shifted by approximately 3 +/- 2 km/s with respect to the main star; the third, central region dominated by the circumbinary envelope, displaying two outflows in the south-western and north-eastern hemispheres. At short distances from the star, up to ~1.5", these hemispheres display very different morphologies: the south-western outflow covers a broad solid angle, expands radially at a rate between 5 and 10 km/s and is slightly red shifted; the north-eastern outflow consists of two arms, both blue-shifted, bracketing a broad dark region where emission is suppressed. At distances between ~1.5" and ~2.5" the asymmetry between the two hemispheres is significantly smaller and detached arcs, particularly spectacular in the north-eastern hemisphere are present. Close to the stars, we observe a mass of gas surrounding Mira B, with a size of a few tens of AU, and having Doppler velocities with respect to Mira B reaching +/-1.5 km/s, which we interpret as gas flowing from Mira A toward Mira B., Comment: 16 pages, 21 figures

Observations by the Atacama Large Millimetre/sub-millimetre Array of the 358 GHz continuum emission of the gravitationally lensed quasar host RX J0911.4+0551 have been analysed. They complement earlier Plateau de Bure Interferometer observations of the CO(7-6) emission. The good knowledge of the lensing potential obtained from Hubble Space Telescope observations of the quasar makes a joint analysis of the three emissions possible. It gives evidence for the quasar source to be concentric with the continuum source within 0.31 kpc and with the CO(7-6) source within 1.10 kpc. It also provides a measurement of the size of the continuum source, 0.76 $\pm$ 0.04 kpc FWHM, making RX J0911.4+0551 one of the few high redshift galaxies for which the dust and gas components are resolved with dimensions being measured. Both are found to be very compact, the former being smaller than the latter by a factor of $\sim$3.4$\pm$0.4. Moreover, new measurements of the CO ladder $-$ CO(10-9) and CO(11-10) $-$ are presented that confirm the extreme narrowness of the CO line width (107$\pm$20 km s$^{-1}$ on average). Their mere detection implies higher temperature and/or density than for typical quasar hosts at this redshift and suggests a possible contribution of the central AGN to gas and dust heating. The results are interpreted in terms of current understanding of galaxy evolution at the peak of star formation. They suggest that RX J0911.4+0551 is a young galaxy in an early stage of its evolution, having experienced no recent major mergers, star formation being concentrated in its centre., Comment: 13 pages, 11 figures, accepted for publication in MNRAS

Using ALMA observations of the C$^{18}$O(2-1) line emission of the gas envelope of protostar L1527, we have reconstructed its morphology and kinematics under the assumption of axisymmetry about the west-east axis. The main original contribution to our understanding of the formation process of L1527 is the presentation of a simple 3D parameterisation based solely on regions that are not dominated by absorption. In the explored range ($\sim$0.7 to 5 arcsec from the star) the model reproduces observations better than earlier attempts. The main results include: a measurement of the rotation velocity that confirms its evolution to Keplerian toward short distances; a measurement of the mean in-fall velocity, 0.43$\pm$0.10 kms$^{-1}$, lower than free fall velocity, with no evidence for the significant $r$-dependence suggested by an earlier analysis; a measurement of the central mass, 0.23$\pm$0.06 M$_{\odot}$ within a distance of 1.5 arcsec from the star, in agreement with earlier estimates obtained from a different range of distances; evidence for a strong disc plane depression of the in-falling flux resulting in an $X$ shaped flow possibly caused by the freeze-out of CO molecules on dust grains; a measurement of the accretion rate, 3.5$\pm$1.0 10$^{-7}$ M$_{\odot}$yr$^{-1}$ at a distance of 1 arcsec (140 au) from the star; evidence for a 10$^\circ$ tilt of the symmetry plane of the envelope about the line of sight, cancelling below $\sim$3 arcsec from the star, but matching infrared observations and being also apparent on the sky map of the mean Doppler velocity., Comment: 11 pages, 12 figures, MNRAS accepted

Observations of 12CO(3-2) emission of the circumbinary envelope of Mira Ceti, made by ALMA are analysed. The observed Doppler velocity distribution is made of three components: a blue-shifted south-eastern arc, which can be described as a ring in slow radial expansion, ~1.7 km/s, making an angle of ~50 deg with the plane of the sky and born some 2000 years ago; a few arcs, probably born at the same epoch as the blue-shifted arc, all sharing Doppler velocities red-shifted by approximately 3 +/- 2 km/s with respect to the main star; the third, central region dominated by the circumbinary envelope, displaying two outflows in the south-western and north-eastern hemispheres. At short distances from the star, up to ~1.5", these hemispheres display very different morphologies: the south-western outflow covers a broad solid angle, expands radially at a rate between 5 and 10 km/s and is slightly red shifted; the north-eastern outflow consists of two arms, both blue-shifted, bracketing a broad dark region where emission is suppressed. At distances between ~1.5" and ~2.5" the asymmetry between the two hemispheres is significantly smaller and detached arcs, particularly spectacular in the north-eastern hemisphere are present. Close to the stars, we observe a mass of gas surrounding Mira B, with a size of a few tens of AU, and having Doppler velocities with respect to Mira B reaching +/-1.5 km/s, which we interpret as gas flowing from Mira A toward Mira B., Comment: 16 pages, 21 figures

The unprecedented quality of the observations available from the Atacama Large Millimetre/sub-millimetre Array (ALMA) calls for analysis methods making the best of them. Reconstructing in space the morphology and kinematics of radio sources is an underdetermined problem that requires imposing additional constraints for its solution. The hypothesis of rotational invariance about a well-defined star axis, which is a good approximation to the description of the gas envelopes of many evolved stars and protostars, is particularly efficient in this role. In the first part of the article, a systematic use of simulated observations allows for identifying the main problems and for constructing quantities aimed at solving them. In particular the evaluation of the orientation of the star axis in space and the differentiation between expansion along the star axis and rotation about it are given special attention. The use of polar rather than Cartesian sky coordinates is shown to better match the morphology and kinematics of actual stars. The radial dependence of the gas density and temperature and the possible presence of velocity gradients are briefly considered. In the second part, the results obtained in the first part are applied to a few stars taken as examples with the aim of evaluating their usefulness when applied to concrete cases. A third part takes stock of what precedes and formulates some guidelines for modelling the radio emission of axisymmetric radio sources, limited however to the mathematics and geometry of the problem, physics considerations being ignored., Comment: 21 pages, 19 figures, published MNRAS 461, 4276 (2016)

Observations of the $^{12}$CO(3-2) emission of the circumstellar envelope (CSE) of the variable star $\pi^1$ Gru using the compact array (ACA) of the ALMA observatory have been recently made accessible to the public. An analysis of the morphology and kinematics of the CSE is presented with a result very similar to that obtained earlier for $^{12}$CO(2-1) emission by Chiu et al. (2006) using the Sub-Millimeter Array. A quantitative comparison is made using their flared disk model. A new model is presented that provides a significantly better description of the data, using radial winds and smooth evolutions of the radio emission and wind velocity from the stellar equator to the poles., Comment: accepted for publication in Research in Astronomy and Astrophysics (RAA)

We analyse ALMA observations of the 12CO(3-2) emission of the circumstellar envelope (CSE) of the Mira variable binary star W Aql. These provide, for the first time, spatially resolved Doppler velocity spectra of the CSE up to angular distances to the central star of ~ 5" (meaning some 2000 AU). The exploratory nature of the observations (only five minutes in each of two different configurations) does not allow for a detailed modelling of the properties of the CSE but provides important qualitative information on its morphology and kinematics. Emission is found to be enhanced along an axis moving from east/west to north-east/south-west when the angular distance from the central star projected on the plane of the sky increases from zero to four arcseconds. In parallel, the Doppler velocity distribution displays asymmetry along an axis moving from east/west to north-west/south-east. The results are discussed in the context of earlier observations, in particular of the dust morphology., Comment: 11 pages, 12 figures

General self-reported rates of violence and studies identifying risk factors for delinquency and serious violence have been limited for Asian, particularly Southeast Asian youth. Additionally, the role of psychosocial-cultural related factors such as individualism/collectivism, intergenerational/intercultural conflict, and ethnic identity in delinquency has largely been neglected. In a sample of 329 Cambodian, Chinese, Lao/Mien, and Vietnamese youth, robust risk factors for serious violence (aggravated assault, robbery, gang, rape) included peer delinquency, prior arrest, and victimization. In addition, cultural factors such as second generation status, individualism, and intergenerational/intercultural conflict also significantly increased the odds of serious violence, whereas factors that decreased the odds included collectivism and school achievement. For family/partner violence (hit a family member or boyfriend/girlfriend), the strongest risk factors were victimization and parent discipline. Demographics, individual, and peer domains contributed more explanatory variance for serious violence, while individual and parental domains contributed more explanatory variance for family/partner violence. Consistent with official statistics, rates of serious violence among Southeast Asian youth were higher than for Chinese youth.

The CO(1-0) and (2-1) emission of the circumstellar envelope of the AGB star EP Aqr has been observed using the IRAM PdBI and the IRAM 30-m telescope. The line profiles reveal the presence of two distinct components centered on the star velocity, a broad component extending up to ~10 km/s and a narrow component indicating an expansion velocity of ~2 km/s. An early analysis of these data was performed under the assumption of isotropic winds. The present study revisits this interpretation by assuming instead a bipolar outflow nearly aligned with the line of sight. A satisfactory description of the observed flux densities is obtained with a radial expansion velocity increasing from ~2 km/s at the equator to ~10 km/s near the poles. The angular aperture of the bipolar outflow is ~45 deg with respect to the star axis, which makes an angle of ~13 deg with the line of sight. A detailed study of the CO(1-0) to CO(2-1) flux ratio reveals a significant dependence of the temperature on the star latitude, smaller and steeper at the poles than at the equator at large distances from the star. Under the hypothesis of radial expansion and of rotation invariance about the star axis, the effective density has been evaluated in space as a function of star coordinates. Evidence is found for an enhancement of the effective density in the northern hemisphere of the star at angular distances in excess of ~3" and covering the whole longitudinal range. The peak velocity of the narrow component is observed to vary slightly with position on the sky, a variation consistent with the model and understood as the effect of the inclination of the star axis with respect to the line of sight. While the phenomenological model presented here reproduces well the general features of the observations, significant differences are also revealed, which would require a better spatial resolution to be properly described., Comment: accepted for publication in Astronomy & Astrophysics