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A magnet has been developed to generate 30 T pulsed magnetic field with 100 ms flat-top at the Wuhan National High Magnetic Field Center (WHMFC). By adjusting the conductor height of each layer, this magnet has a typical bore with 20 mm diameter and a conical bore with 30 degree opening angle on the one side for X-ray diffraction and neutron scattering experiments. Fast cooling technique was used for better cooling performance, and eight stainless steel rods were placed in the cooling channel to resist the strong axial electromagnetic force. The magnet was connected in series with an auxiliary coil to extend the flat-top duration of the magnetic field, and energized with nineteen 1.25 MJ capacitor modules. The multiple capacitor modules are pre-charged to the set voltage, and then triggered in sequence. Peak field of 30 T with 90 ms flat-top and 1% flatness was obtained with optimized initial voltage and trigger time of each capacitor module.

The Zylon fiber-reinforced polymer (ZFRP) reinforcements of pulsed magnets often manifest transverse and shearing failure modes under ultrahigh magnetic fields, resulting in unintended disruptions of the magnet system. Nevertheless, the transverse tensile, compression, and in-plane shear behaviors of ZFRP remain insufficiently understood, impeding efforts to elucidate the underlying failure mechanisms and enhance magnet performance. To address this knowledge gap, this paper undertook a comprehensive mechanical tests of ZFRP. Specimen were fabricated using the autoclave-forming technique, followed by transverse tensile, compression and in-plane shear tests conducted at 213 K, 243 K, and 296 K. The elastic modulus and stress-strain response were both characterized, and the influence of the fiber-filling factor were also discussed.

IMPORTANCE: Calcium channel blocker (CCB) use has been associated with an increased risk of glaucoma in exploratory studies. OBJECTIVE: To examine the association of systemic CCB use with glaucoma and related traits among UK Biobank participants. DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography (OCT)–derived inner retinal layer thicknesses. Data analysis was conducted in January 2023. EXPOSURE: Calcium channel blocker use was assessed in a baseline touchscreen questionnaire and confirmed during an interview led by a trained nurse. MAIN OUTCOMES AND MEASURES: The primary outcome measures included glaucoma status, corneal-compensated IOP, and 2 OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell–inner plexiform layer [mGCIPL] thicknesses). We performed logistic regression and linear regression analyses to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively. RESULTS: This study included 427 480 adults. Their median age was 58 (IQR, 50-63) years, and more than half (54.1%) were women. There were 33 175 CCB users (7.8%). Participants who had complete data for glaucoma status (n = 427 480), IOP (n = 97 100), and OCT-derived inner retinal layer thicknesses (n = 41 023) were eligible for respective analyses. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001). Calcium channel blocker use was also associated with thinner mGCIPL (−0.34 μm [95% CI, −0.54 to −0.15 μm]; P = .001) and mRNFL (−0.16 μm [95% CI, −0.30 to −0.02 μm]; P = .03) thicknesses but not IOP (−0.01 mm Hg [95% CI, −0.09 to 0.07 mm Hg]; P = .84). CONCLUSIONS AND RELEVANCE: In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved. Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.

We have been translating laboratory findings into potential breakthroughs for patients, an effort that has been centered on the award of the new National Institute for Health Research Biomedical Research [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajo.2005.12.008 Byline: Winifred P. Nolan (a)(b), Tin Aung (a)(b)(c), David Machin (d), Peng T. Khaw (b)(e), Gordon J. Johnson (b)(f), Steve K.L. Seah (c), Paul J. Foster (b)(e) Abstract: To assess the performance of peripheral and central anterior chamber depth (ACD) measurements, and autorefraction, in identifying Chinese people with occludable drainage angles or established primary angle closure. Author Affiliation: (a) National University Hospital, Singapore (b) Institute of Ophthalmology, University College London, London, England (c) Singapore National Eye Centre, Singapore (d) Clinical Trials and Epidemiology Research Unit, Singapore (e) Glaucoma Research Unit, Moorfields Eye Hospital, London, England (f) London School of Tropical Medicine and Hygiene, London, England Article History: Accepted 8 December 2005 Article Note: (footnote) This study was supported by grants from the National Medical Research Council, Singapore, the International Glaucoma Association, London, England, and the British Council for the Prevention of Blindness, London; by grant G9330070 from The Medical Research Council, United Kingdom (P.T.K.); and by the Richard Desmond Charitable Trust, London, United Kingdom.

Managers in the three Chinese societies of Hong Kong, Taiwan and Mainland China are compared on the basis of cultural values shared by them and also the historical reasons that make them different from each other. All the three groups provide a degree of stability and certainty regarding appropriate ways to relate to others, based on clear status and hierarchical relationships due to the teachings of Confucianism and concepts that are common to them.

AimTo examine the associations of air pollution with both self-reported age-related macular degeneration (AMD), and in vivo measures of retinal sublayer thicknesses.MethodsWe included 115 954 UK Biobank participants aged 40–69 years old in this cross-sectional study. Ambient air pollution measures included particulate matter, nitrogen dioxide (NO2) and nitrogen oxides (NOx). Participants with self-reported ocular conditions, high refractive error (< −6 or > +6 diopters) and poor spectral-domain optical coherence tomography (SD-OCT) image were excluded. Self-reported AMD was used to identify overt disease. SD-OCT imaging derived photoreceptor sublayer thickness and retinal pigment epithelium (RPE) layer thickness were used as structural biomarkers of AMD for 52 602 participants. We examined the associations of ambient air pollution with self-reported AMD and both photoreceptor sublayers and RPE layer thicknesses.ResultsAfter adjusting for covariates, people who were exposed to higher fine ambient particulate matter with an aerodynamic diameter <2.5 µm (PM2.5, per IQR increase) had higher odds of self-reported AMD (OR=1.08, p=0.036), thinner photoreceptor synaptic region (β=−0.16 µm, p=2.0 × 10−5), thicker photoreceptor inner segment layer (β=0.04 µm, p=0.001) and thinner RPE (β=−0.13 µm, p=0.002). Higher levels of PM2.5absorbance and NO2were associated with thicker photoreceptor inner and outer segment layers, and a thinner RPE layer. Higher levels of PM10(PM with an aerodynamic diameter <10 µm) was associated with thicker photoreceptor outer segment and thinner RPE, while higher exposure to NOxwas associated with thinner photoreceptor synaptic region.ConclusionGreater exposure to PM2.5was associated with self-reported AMD, while PM2.5, PM2.5absorbance, PM10, NO2and NOxwere all associated with differences in retinal layer thickness.

Progression to exudative ‘wet’ age-related macular degeneration (exAMD) is a major cause of visual deterioration. In patients diagnosed with exAMD in one eye, we introduce an artificial intelligence (AI) system to predict progression to exAMD in the second eye. By combining models based on three-dimensional (3D) optical coherence tomography images and corresponding automatic tissue maps, our system predicts conversion to exAMD within a clinically actionable 6-month time window, achieving a per-volumetric-scan sensitivity of 80% at 55% specificity, and 34% sensitivity at 90% specificity. This level of performance corresponds to true positives in 78% and 41% of individual eyes, and false positives in 56% and 17% of individual eyes at the high sensitivity and high specificity points, respectively. Moreover, we show that automatic tissue segmentation can identify anatomical changes before conversion and high-risk subgroups. This AI system overcomes substantial interobserver variability in expert predictions, performing better than five out of six experts, and demonstrates the potential of using AI to predict disease progression.

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future.

Glaucoma is one of the leading causes of blindness, and there is an ongoing need for new therapies. Recent studies indicate that cell transplantation using Müller glia may be beneficial, but there is a need for novel sources of cells to provide therapeutic benefit. In this study, we have isolated Müller glia from retinal organoids formed by human induced pluripotent stem cells (hiPSCs) in vitro and have shown their ability to partially restore visual function in rats depleted of retinal ganglion cells by NMDA. Based on the present results, we suggest that Müller glia derived from retinal organoids formed by hiPSC may provide an attractive source of cells for human retinal therapies, to prevent and treat vision loss caused by retinal degenerative conditions. Stem Cells Translational Medicine2019;8:775&784 Purified populations of Müller glial cells were isolated from retinal organoids derived from human iPSC. Intra‐vitreal transplantation of these cells into rat eyes depleted of RGC by NMDA caused partial restoration of visual function, as assessed by improvement of the retinal electrophysiological responses. These findings highlight the potential of iPSC as a potential source of therapeutic cells for retinal degeneration.

Small tablets for implantation into the subconjunctival space in the eye are being developed to inhibit scarring after glaucoma filtration surgery (GFS). There is a need to evaluate drug dissolution at the molecular level to determine how the chemical structure of the active may correlate with dissolution in the nonsink conditions of the conjunctival space. We conducted molecular dynamics simulations to study the dissolution process of tablets derived from two drugs that can inhibit fibrosis after GFS, 5-fluorouracil (5-FU) and the matrix metalloprotease inhibitor (MMPi), ilomastat. The dissolution was simulated in the presence of simple point charge (SPC) water molecules, and the liquid turnover of the aqueous humor in the subconjunctival space was simulated by removal of the dissolved drug molecules at regular intervals and replacement by new water molecules. At the end of the simulation, the total molecular solvent accessible surface area of 5-FU tablets increased by 60 times more than that of ilomastat as a result of tablet swelling and release of molecules into solution. The tablet dissolution pattern shown in our molecular dynamic simulations tends to correlate with experimental release profiles. This work indicates that a series of molecular dynamic simulations can be used to predict the influence of the molecular properties of a drug on its dissolution profile and could be useful during preformulation where sufficient amounts of the drug are not always available to perform dissolution studies.

RNAi induced by double-stranded small interfering RNA (siRNA) molecules has attracted great attention as a naturally occurring approach to silence gene expression with high specificity. The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway is a master regulator of cytoskeletal gene expression and, thus, represents a promising target to prevent fibrosis. A major hurdle to implementing siRNA therapies is the method of delivery, and we have, thus, optimized lipid-peptide-siRNA (LPR) nanoparticles containing MRTF-B siRNAs as a targeted approach to prevent conjunctival fibrosis. We tested 15 LPR nanoparticle formulations with different lipid compositions, surface charges, and targeting or non-targeting peptides in human conjunctival fibroblasts. In vitro, the LPR formulation of the DOTMA/DOPE lipid with the targeting peptide Y (LYR) was the most efficient in MRTF-Bgene silencing and non-cytotoxic compared to the non-targeting formulation. In vivo, subconjunctival administration of LYR nanoparticles containing MRTF-B siRNAs doubled bleb survival in a pre-clinical rabbit model of glaucoma filtration surgery. Furthermore, MRTF-B LYR nanoparticles reduced the MRTF-BmRNA by 29.6% in rabbit conjunctival tissues, which led to significantly decreased conjunctival scarring with no adverse side effects. LYR-mediated delivery of siRNA shows promising results to increase bleb survival and to prevent conjunctival fibrosis after glaucoma filtration surgery.

IMPORTANCE: Identifing potential screening tests for future cognitive decline is a priority for developing treatments for and the prevention of dementia. OBJECTIVE: To examine the potential of retinal nerve fiber layer (RNFL) thickness measurement in identifying those at greater risk of cognitive decline in a large community cohort of healthy people. DESIGN, SETTING, AND PARTICIPANTS: UK Biobank is a prospective, multicenter, community-based study of UK residents aged 40 to 69 years at enrollment who underwent baseline retinal optical coherence tomography imaging, a physical examination, and a questionnaire. The pilot study phase was conducted from March 2006 to June 2006, and the main cohort underwent examination for baseline measures from April 2007 to October 2010. Four basic cognitive tests were performed at baseline, which were then repeated in a subset of participants approximately 3 years later. We analyzed eyes with high-quality optical coherence tomography images, excluding those with eye disease or vision loss, a history of ocular or neurological disease, or diabetes. We explored associations between RNFL thickness and cognitive function using multivariable logistic regression modeling to control for demographic as well as physiologic and ocular variation. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) for cognitive performance in the lowest fifth percentile in at least 2 of 4 cognitive tests at baseline, or worsening results on at least 1 cognitive test at follow-up. These analyses were adjusted for age, sex, race/ethnicity, height, refraction, intraocular pressure, education, and socioeconomic status. RESULTS: A total of 32 038 people were included at baseline testing, for whom the mean age was 56.0 years and of whom 17 172 (53.6%) were women. A thinner RNFL was associated with worse cognitive performance on baseline assessment. A multivariable regression controlling for potential confounders showed that those in the thinnest quintile of RNFL were 11% more likely to fail at least 1 cognitive test (95% CI, 2.0%-2.1%; P = .01). Follow-up cognitive tests were performed for 1251 participants (3.9%). Participants with an RNFL thickness in the 2 thinnest quintiles were almost twice as likely to have at least 1 test score be worse at follow-up cognitive testing (quintile 1: OR, 1.92; 95% CI, 1.29-2.85; P &lt; .001; quintile 2: OR, 2.08; 95% CI, 1.40-3.08; P &lt; .001). CONCLUSIONS AND RELEVANCE: A thinner RNFL is associated with worse cognitive function in individuals without a neurodegenerative disease as well as greater likelihood of future cognitive decline. This preclinical observation has implications for future research, prevention, and treatment of dementia.

The volume and complexity of diagnostic imaging is increasing at a pace faster than the availability of human expertise to interpret it. Artificial intelligence has shown great promise in classifying two-dimensional photographs of some common diseases and typically relies on databases of millions of annotated images. Until now, the challenge of reaching the performance of expert clinicians in a real-world clinical pathway with three-dimensional diagnostic scans has remained unsolved. Here, we apply a novel deep learning architecture to a clinically heterogeneous set of three-dimensional optical coherence tomography scans from patients referred to a major eye hospital. We demonstrate performance in making a referral recommendation that reaches or exceeds that of experts on a range of sight-threatening retinal diseases after training on only 14,884 scans. Moreover, we demonstrate that the tissue segmentations produced by our architecture act as a device-independent representation; referral accuracy is maintained when using tissue segmentations from a different type of device. Our work removes previous barriers to wider clinical use without prohibitive training data requirements across multiple pathologies in a real-world setting.

IMPORTANCE: Postsurgical fibrosis is a critical determinant of the long-term success of glaucoma surgery, but no reliable biomarkers are currently available to stratify the risk of scarring. OBJECTIVE: To compare the clinical phenotype of patients with conjunctival fibrosis after glaucoma surgery with candidate gene expression tissue biomarkers of fibrosis. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, 42 patients were recruited at the time of glaucoma surgery at the Moorfields Eye Hospital from September 1, 2014, to September 1, 2016. The participants were divided into those with fibrosis and those without fibrosis. MAIN OUTCOMES AND MEASURES: Genotype-phenotype correlations of the IL6 or PRG4 gene and detailed clinical phenotype. The IL6 and PRG4 protein expression in conjunctival tissues was also assessed using in situ immunohistochemical analysis. Central bleb area, maximal bleb area, and bleb height were graded on a scale of 1 to 5 (1 indicating 0%; 2, 25%; 3, 50%; 4, 75%; and 5, 100%). Bleb vascularity was graded on a scale of 1 to 5 (1 indicating avascularity; 2, normal; 3, mild; 4, moderate; and 5, severe hyperemia). RESULTS: A total of 42 patients were recruited during the study period; 28 participants (67%) had previously undergone glaucoma surgery (fibrotic group) (mean [SD] age, 43.8 [3.6 years]; 16 [57%] female; 22 [79%] white), and 14 participants (33%) had not previously undergone glaucoma surgery (nonfibrotic group) (mean [SD] age, 47.7 [6.9] years; 4 [29%] female; 9 [64%] white). The fibrotic group had marked bleb scarring and vascularization and worse logMAR visual acuity. The mean (SD) grades were 1.4 (0.1) for central bleb area, 1.4 (0.1) for bleb height, and 3.4 (0.2) for bleb vascularity. The IL6 gene was upregulated in fibrotic cell lines (mean, 0.040) compared with nonfibrotic cell lines (mean, 0.011) (difference, 0.029; 95% CI, 0.015-0.043; P = .003). The PRG4 gene was also downregulated in fibrotic cell lines (0.002) compared with nonfibrotic cell lines (mean, 0.109; difference, 0.107; 95% CI, 0.104-0.110; P = .03). The study found a strong correlation between the IL6 gene and the number of glaucoma operations (r = 0.94, P &lt; .001) and logMAR visual acuity (r = 0.64, P = .03). A moderate correlation was found between the PRG4 gene and the number of glaucoma operations (r = −0.72, P = .005) and logMAR visual acuity (r = −0.62, P = .03). CONCLUSIONS AND RELEVANCE: IL6 and PRG4 represent potential novel tissue biomarkers of disease severity and prognosis in conjunctival fibrosis after glaucoma surgery. Future longitudinal studies with multiple postoperative measures are needed to validate the effect of these potential biomarkers of fibrosis.

Autoantibodies recognizing 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) are associated with statin exposure, the HLA allele DRB1*11:01, and necrotizing muscle biopsies in adult myositis patients. The aim of this study was to characterize the features of juvenile anti‐HMGCR‐positive myositis patients. The sera of 440 juvenile myositis patients were screened for anti‐HMGCR autoantibodies. Demographic and clinical features, responses to therapy, and HLA alleles were assessed. The features of anti‐HMGCR‐positive patients were compared to those of previously described adult patients with this autoantibody and to children with other myositis‐specific autoantibodies (MSAs). Five of 440 patients (1.1%) were anti‐HMGCR‐positive; none had taken statin medications. Three patients had rashes characteristic of juvenile dermatomyositis and 2 patients had immune‐mediated necrotizing myopathies. The median highest creatine kinase (CK) level of anti‐HMGCR‐positive subjects was 17,000 IU/liter. All patients had severe proximal muscle weakness, distal weakness, muscle atrophy, joint contractures, and arthralgias, which were all more prevalent in HMGCR‐positive subjects compared to MSA‐negative patients or those with other MSAs. Anti‐HMGCR‐positive patients had only partial responses to multiple immunosuppressive medications, and their disease often took a chronic course. The DRB1*07:01 allele was present in all 5 patients, compared to 26.25% of healthy controls (corrected P= 0.01); none of the 5 juvenile patients had DRB1*11:01. Compared to children with other MSAs, muscle disease appears to be more severe in those with anti‐HMGCR autoantibodies. Like adults, children with anti‐HMGCR autoantibodies have severe weakness and high CK levels. In contrast to adults, in anti‐HMGCR‐positive children, there is a strong association with HLA–DRB1*07:01.

Cancer stem cells (CSCs), which are a rare population in any type of cancer, including colon cancer, are tumorigenic and responsible for cancer recurrence and metastasis. CSCs have been isolated from a number of different solid tumors recently, although the isolation of CSCs in colon cancer is still challenging. We cultured colon cancer cells in stem cell medium to obtain colonosphere cells. These cells possessed the characteristics of CSCs, with a high capacity of tumorigenicity, migration and invasion in vitroand in vivo. The isolation and identification of CSCs have provided new targets for the therapeutics. Oncolytic herpes simplex viruses (oHSV) are an effective strategy for killing colon cancer cells in preclinical models. Here, we examined the efficacy of an oncolytic herpes simplex virus type 2 (oHSV2) in killing colon cancer cells and colon cancer stem-like cells (CSLCs). oHSV2 was found to be highly cytotoxic to the adherent and sphere cells in vitro, and oHSV2 treatment in vivosignificantly inhibited tumor growth. This study demonstrates that oHSV2 is effective against colon cancer cells and colon CSLCs and could be a promising strategy for treating colon cancer patients.

Introduction:A variety of inflammatory disorders influence the serum white blood cell (WBC) count. Elevated systemic inflammatory insult may contribute to impaired lung function, such as obstructive or restrictive lung disease. The aim of our study is to investigate the correlation between WBC count and pulmonary function.Material and Methods:Eligible participants aged ≥ 18 years (n = 16 312) were enrolled from the United States National Health and Nutrition Examination Survey III, 1988–1994. Pertinent information including pulmonary function test, demographics, WBC count, glucose, C-reactive protein and a personal health questionnaire were obtained for subjects without known pulmonary diseases. White blood cell counts were classified into quartiles over the normal range. Multiple hierarchical regression models and trends testing were used to assess the correlation between WBC counts and pulmonary function tests.Results:In the unadjusted mode of quartile-based analysis, the beta coefficients interpreted as the differences in FEV1% predicted upon comparing subjects in the upper three quartiles of WBC count to those in the lowest quartile were − 0.007, − 0.022 and − 0.041 (P < 0.001). After adjusting for multiple pertinent covariates, inverse association between quartiles of WBC count and FEV1% predicted remained essentially unchanged. The negative trends between FEV1% predicted and WBC count quartiles in the stratified comparison with extended-model approach were statistically significant (Pfor trends < 0.001) in quartile-based multiple linear regression.Conclusions:Elevated WBC count is independently associated with declined pulmonary function. It may be a simple, accessible and inexpensive indicator of changes in pulmonary function.

To evaluate the impact of age, glaucoma-specific diagnosis, and history of prior glaucoma surgery on outcomes in pediatric patients treated with latanoprost monotherapy.

Vascular endothelial growth factor A (VEGF-A) is a validated therapeutic target in several angiogenic- and vascular permeability–related pathological conditions, including certain cancers and potentially blinding diseases, such as age-related macular degeneration and diabetic retinopathy. We and others have shown that VEGF-A also plays an important role in neuronal development and neuroprotection, including in the neural retina. Antagonism of VEGF-A function might therefore present a risk to neuronal survival as a significant adverse effect. Herein, we demonstrate that VEGF-A acts directly on retinal ganglion cells (RGCs) to promote survival. VEGF receptor-2 signaling via the phosphoinositide-3-kinase/Akt pathway was required for the survival response in isolated RGCs. These results were confirmed in animal models of staurosporine-induced RGC death and experimental hypertensive glaucoma. Importantly, we observed that VEGF-A blockade significantly exacerbated neuronal cell death in the hypertensive glaucoma model. Our findings highlight the need to better define the risks associated with use of VEGF-A antagonists in the ocular setting.

OBJECTIVE To determine whether the timing of cataract surgery after trabeculectomy has an effect on trabeculectomy function in terms of intraocular pressure control. METHODS This was a cohort study nested within a randomized clinical trial. There were 235 participants with glaucoma who had a single previous trabeculectomy augmented with either intraoperative 5-fluorouracil or placebo. Cataract surgery with intraocular lens implantation was performed on participants judged to have significant lens opacity. Cox regression was performed to evaluate the effect of time between trabeculectomy and cataract surgery on the time to trabeculectomy failure, after adjusting for other relevant risk factors. The main outcome measure was time to failure of trabeculectomy, defined as an intraocular pressure of greater than 21 mm Hg. RESULTS Of the 235 participants, 124 (52.7%) underwent subsequent cataract surgery. The median time from trabeculectomy to cataract surgery for these patients was 21.7 months (range, 4.6-81.9 months). The median follow-up period was 60 months (range, 28-84 months) for the cataract surgery group and 48 months (range, 12-84 months) for the non–cataract surgery group. Cox regression showed that the time from trabeculectomy to cataract surgery was significantly associated with time to trabeculectomy failure (hazard ratio, 1.73 [95% CI, 1.05-2.85]; P = .03). The adjusted declining hazard ratios for risk of subsequent trabeculectomy failure when cataract surgery was performed 6 months, 1 year, and 2 years after trabeculectomy were 3.00 (95% CI, 1.11-8.14), 1.73 (95% CI, 1.05-2.85), and 1.32 (95% CI, 1.02-1.69), respectively. CONCLUSIONS Cataract surgery after trabeculectomy increases the risk of trabeculectomy failure, and this risk is increased if the time between trabeculectomy and cataract surgery is shorter.

A new type of photodegradable poly(vinyl chloride)‐bismuth oxyiodide/TiO2(PVC‐BiOI/TiO2) nanocomposite film was prepared by embedding a nano‐TiO2photocatalyst modified by BiOI into the commercial PVC plastic. The solid‐phase photocatalytic degradation behavior of the as‐prepared film was investigated in ambient air at room temperature under UV light irradiation, with the aid of UV‐Vis spectroscopy, weight loss monitoring, scanning electron microscopy, and FT‐IR spectroscopy. Compared to the PVC‐TiO2nanocomposite film, the PVC‐BiOI nanocomposite film and the pure PVC film, the PVC‐BiOI/TiO2nanocomposite film exhibited a higher photocatalytic degradation activity. The optimal mass ratio of BiOI to TiO2was found to be 0.75 %. The weight loss rate of the PVC‐BiOI/TiO2nanocomposite film reached 30.8 % after 336 h of irradiation, which is 1.5 times higher than that of the PVC‐TiO2nanocomposite film under identical conditions. The solid‐phase photocatalytic degradation mechanism of the nanocomposite films was briefly discussed.

OBJECTIVES To develop and validate a novel ex vivo model of conjunctival contraction. METHODS Ex vivo segments of conjunctiva were maintained in culture for 4 weeks in permeable support plates. Digital images were obtained twice a week to monitor contraction using tissue area changes and weekly weight measurements. Investigated were the effects of known contraction stimulators (fetal bovine serum and transforming growth factor β2) and of the matrix metalloproteinase inhibitor GM6001. Microscopic contraction, tissue organization, and cell viability (using the cell vital dye carboxyfluorescein diacetate) were monitored by confocal reflection and 2-photon microscopy, revealing detailed real-time kinetics of tissue remodeling. RESULTS Fetal bovine serum and transforming growth factor β2 induced significant tissue contraction in conjunctiva segments, with no changes in cell viability. This correlated with dramatic and specific degradation of the collagen component in the tissue. Contraction and collagen degradation were reduced in the presence of GM6001. CONCLUSIONS Ex vivo segments of conjunctiva can be used as an integral model system to provide a higher level of understanding about the efficacy of antiscarring therapies and can help bridge the current gap between in vitro and in vivo models. CLINICAL RELEVANCE Scarring leads to the failure of several ocular surgical procedures. This novel ex vivo model recapitulates tissue contraction (with kinetics close to that of in vivo scarring) and allows for a more physiological analysis of conjunctival scarring, which could better evaluate potential therapeutic targets.Arch Ophthalmol. 2011;129(5):619-627--

Crystal structure of 4H-SiC was refined from room-temperature X-ray powder diffraction data using the Rietveld refinement method. The refined lattice constants were determined to be a=b=3.079 93(0) ?, c=10.082 22(2) ?, and the refined overall temperature factor B=0.383(3) ?2. Using the Debye approximation, the Debye temperature was successfully determined to be 1194.8 K.

The article looks into the significance of morality and its various interpretations. The author emphasizes that the absence of morality makes society more likely to be unjust, inhuman and unfair when dealing with existing inequities. Several cultural and religious traditions have different answers to the question of the right moral conduct that include the Five Constitutional Relations of Confucianism, Ten Commandments from Judaism, and the Seven Principles of Unitarian-Universalism.

Urinary tract infections are the most common infection in renal transplant patients and Escherichia coli (E. coli) is the most common clinical isolate. Although acute allograft injury (AAI) secondary to urinary tract infection (UTI) has been reported, the incidence of AAI associated with UTI, the virulence factors express by uropathic E. coli and whether virulence factors are associated with renal allograft outcome have not been described. We collected E. coli from our renal transplant patients with UTI, determined O:H serotypes, P and Dr fimbriae expression and the clinical presentation and allograft function during the UTI and post-UTI period. Pyelonephritis occurred in 40% of our patients, 82% of which had AAI (>20% increase in SCr). Sixty-two percent of E. coli isolates that expressed P fimbriae were associated with AAI, whereas only 29% that did not express P fimbriae had AAI (p = 0.03). The pattern of P fimbriae and O serotypes differed from reported isolates, as the P fimbriae PapG class II and the O25 serotype were the most common. Dr adhesin was expressed on 7 isolates, including 2 of 3 with urosepsis. We propose a unique pattern of uropathogenic serotypes and adherence factors contribute to acute allograft injury in renal transplant patients with UTI.

Urinary tract infections are the most common infection in renal transplant patients and Escherichia coli(E. coli) is the most common clinical isolate. Although acute allograft injury (AAI) secondary to urinary tract infection (UTI) has been reported, the incidence of AAI associated with UTI, the virulence factors express by uropathic E. coliand whether virulence factors are associated with renal allograft outcome have not been described. We collected E. colifrom our renal transplant patients with UTI, determined O:H serotypes, P and Dr fimbriae expression and the clinical presentation and allograft function during the UTI and post-UTI period. Pyelonephritis occurred in 40% of our patients, 82% of which had AAI (>20% increase in SCr). Sixty-two percent of E. coliisolates that expressed P fimbriae were associated with AAI, whereas only 29% that did not express P fimbriae had AAI (p = 0.03). The pattern of P fimbriae and O serotypes differed from reported isolates, as the P fimbriae PapG class II and the O25 serotype were the most common. Dr adhesin was expressed on 7 isolates, including 2 of 3 with urosepsis. We propose a unique pattern of uropathogenic serotypes and adherence factors contribute to acute allograft injury in renal transplant patients with UTI.

Axenfeld‐Rieger Syndrome (ARS) is a genetically heterogeneous birth defect characterized by malformation of the anterior segment of the eye associated with glaucoma. Mutation of the PITX2 homeobox gene has been identified as a cause of ARS. We report a novel Arg5Trp missense mutation in the PITX2 homeodomain, which is associated with brain abnormalities. One patient had a small sella turcica likely to reflect hypoplasia of the pituitary gland and consistent with the critical role identified for Pitx2 in pituitary development in mice. Two patients had an enlarged cisterna magna, one with a malformed cerebellum, and two had executive skills deficits one in isolation and one in association with a below average intellectual capacity. The mutation caused a typical ARS ocular phenotype. All affected had iris hypoplasia, anterior iris to corneal adhesions, and corectopia. The ocular phenotype varied significantly in severity and showed some asymmetry. All affected also had redundant peri‐umbilical skin, a hypoplastic maxilla, microdontia, and hypodontia missing between 20 and 27 teeth with an unusual pattern of tooth loss. Dental phenotypes were documented as they are often poorly characterized in ARS patients. All affected individuals showed an absence of first permanent molars with variable absence of other rarely absent teeth: the permanent upper central incisors, maxillary and mandibular first and second molars, and the mandibular canines. Based on the distinctive dental anomalies, we suggest that the dental phenotype can assist in predicting the presence of a PITX2 mutation and the possibility of brain abnormalities. © 2006 Wiley‐Liss, Inc.

Since the first description of matrix metalloproteinase (MMP)-1 as an interstitial collagenase, great importance has been ascribed to this enzyme in extracellular matrix remodeling during tumoral, inflammatory, and angiogenic processes. As more evidence for the role of MMPs in targeting nonmatrix substrates emerges, casual observations that intracellular MMP-1 is found in vitroand in vivoprompt investigation of the role that MMP-1 may play on basic cell functions such as cell division and apoptosis. Here we show for the first time that MMP-1 not only has extracellular functions but that it is strongly associated with mitochondria and nuclei and accumulates within the cells during the mitotic phase of the cell cycle. On induction of apoptosis, MMP-1 co-localized with aggregated mitochondria and accumulated around fragmented nuclei. Inhibition of this enzyme by RNA interference or treatment with a broad MMP inhibitor caused faster degradation of lamin A, activation of caspases, and fragmentation of DNA when compared with untreated cells. These observations strongly suggest that intracellular association of MMP-1 to mitochondria and nuclei confers resistance to apoptosis and may explain the well-known association of this enzyme with tumor cell survival and spreading.

To describe the intraocular pressure (IOP) changes resulting from scleral flap suture and scleral flap manipulation in an experimental model of conventional guarded filtration surgery.

Al2O3microtubules with ca. 60–600 μm in lengths and 2–16 μm in outer diameter have been prepared using water‐soluble ammonium tartrate crystal as a template in a sol‐gel method using aluminum sec‐butoxide (ASB) as starting materials, which may have potential application in catalytic materials, electronic science or separation technology.

No abstract.

The UV‐curable urethane‐acrylates based on 2‐hydroxyethyl methacrylate (HEMA)‐terminated polyurethane (PU) for lithographic and coating applications are investigated in this study. Series of PU prepolymers were made from 4,4‐diphenyl methane diisocyanate (MDI), poly(propylene oxide) glycol (PPG 400), poly(butylene adipate)glycol (PBA 500), or poly(tetramethylene oxide) glycol (PTMO 1000) and are terminated with HEMA. The 2,2‐azobisisobutyronitrile (AIBN) was used as a UV‐initiator under air atmosphere. The curing kinetics of HEMA‐terminated PU film were studied. The curing analysis, using FTIR and reaction kinetics, indicate the reaction rate equation correlates well with the film thickness [T], initiator concentration [I], unreacted double bond concentration [CC], and exposed energy [E] of the reaction system. The kinetic rate equation for the UV‐curable reaction can be written as © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 3162–3166, 2004

Excessive cell-mediated tissue contraction after injury can lead to morbid contractile scarring in the body. In the eye this can cause blindness because of posterior capsule opacification, proliferative vitroretinopathy, failure of glaucoma filtration surgery, and corneal haze. During repair, transforming growth factor (TGF)-β and connective tissue growth factor (CTGF) genes are co-ordinately expressed. Although TGF-β and CTGF stimulate new matrix deposition, their role and regulation during contractile scarring is unknown. In this study, an in vitromodel of collagen matrix contraction culminating from tractional forces generated by fibroblasts showed that both TGF-β1and CTGF-stimulated contraction. Using a specific anti-sense oligodeoxynucleotide to CTGF the procontractile activity of TGF-β1was found to be mediated by CTGF. During contraction fibroblasts produced similar levels of matrix metalloproteinases (MMPs)-2 and -9 with TGF-β1or CTGF and a modest increase in MMP-1 with CTGF only (indicated by zymography and enzyme-linked immunosorbent assay). The requirement of MMPs for contraction was demonstrated using a broad-spectrum synthetic inhibitor. This study demonstrates a new function for CTGF in mediating matrix contraction by fibroblasts involving MMPs and suggests a novel regulatory mechanism for TGF-β-stimulated contraction. Inhibition of CTGF activity or gene transcription could be a suitable target for anti-scarring therapies.

To assess the prevalence of optic disc hemorrhage in Asian patients with established glaucoma using a recently described, highly sensitive detection method.

Titania microtubules with high specific surface areas and well-developed framework mesopores forming the tubular walls by a surfactant-mediated template in the sol−gel process were fabricated in a laurylamine hydrochloride (LAHC)/tetra-n-butyl-orthotitanate (TBOT) system. The outer diameter and the wall thickness of titania microtubules are 2−8 and 0.2−2 μm, respectively. The walls of the microtubules consisted of nanochannels with exceptionally uniform pore size. This technique is a convenient and facile procedure for fabricating hierarchical ordered hollow tubules. The possible mechanism of the formation of the microtubules in the present system was discussed in detail.

A set of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors was investigated with the aim of developing 3D-QSAR models using the Flexible Atom Receptor Model (FLARM) method. Some 3D-QSAR models were built with high correlation coefficients, and the FLARM method predicted the biological activities of compounds in test set well. The FLARM method also gave the pseudoreceptor model, which indicates the possible interactions between the receptor and the ligand. The possible interactions include two hydrogen bonds, one hydrophobic interaction, and one sulfur−aromatic interaction, which are in accord with those in the pharmacophore model given by the scientists at Novartis. This shows that the FLARM method can bridge 3D-QSAR and receptor modeling in computer-aided drug design. Pharmacophore can be obtained according to these results, and 3D searching can then be done with databases to find the lead compound of EGFR tyrosine kinase inhibitors.

To investigate the effects of needle perforation of proximal Molteno tubes on intraluminal pressure in a constant flow system.

Glial Müller cells are known to undergo functional and morphological changes during retinal proliferative disorders, but very little is known of the contribution of these cells to extracellular matrix deposition during retinal wound healing and gliosis. This study constitutes the first demonstration that retinal Müller cells express two major matrix metalloproteinases (MMPs), gelatinase A (MMP-2) and gelatinase B (MMP-9), implicated in cell migration and matrix degradation. Although mRNA and gelatinolytic activity of MMP-2 remained unchanged in cultured Müller cells, basal levels of MMP-9 mRNA observed after subculture at 24 hours, markedly declined after 48 or 72 hours. This correlated with the expression of MMP-9 gelatinolytic activity that peaked at 24 hours, but gradually decreased at 48 and 72 hours. Tumor necrosis factor-α, in both a soluble form or bound to collagen and fibronectin, increased MMP-9 mRNA and gelatinolytic activity, but not MMP-2 expression, and its effect could be blocked by anti-tumor necrosis factor-α antibodies. The results suggest that Müller cells may aid in the local control of extracellular matrix deposition during retinal proliferative disorders, and that interaction of these cells with matrix-bound cytokine may influence their pathological behavior. Control of Müller cell production of MMP-9 may constitute an important target for the design of new therapeutic approaches to treat and prevent retinal proliferative disease.

The development of East Asian Chinese societies in recent decades has led to observed change in leadership styles among business managers. This study examines the relationship between societal changes, especially the change in culture, and the change in leadership styles. The subjects of this study are Chinese managers in four major Oriental Chinese societies: Mainland China, Hong Kong, Singapore, and Taiwan. It is argued that, due to different political, economical, and cultural developments in recent decades, the leadership styles in these Chinese societies have also changed in different directions. Based on data from the Global Leadership and Organizational Behavior Effectiveness Program (GLOBE) study, our findings show some significant and interesting differences in leadership style among business leaders in these Chinese societies. The implications of the findings are discussed.

Polyferrocenyldimethylsilanes with different molecular weights were prepared via thermal ring-opening polymerization of the corresponding strained, silicon-bridged ferrocenophanes. The electrochemical behavior of the resultant polymers in different media were investigated by cyclic voltammetry. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 3258–3261, 2001

The most common cause of failure of retinal reattachment surgery is formation of fibrocellular contractile membranes on both surfaces of the neuroretina. This intraocular fibrosis, known as proliferative vitreoretinopathy, results in a blinding tractional retinal detachment because of the contractile nature of the membrane. Contractility is a cell-mediated event that is thought to be dependent on locomotion and adhesion to the extracellular matrix. Interactions between cells and the extracellular matrix can be influenced by matrix metalloproteinases (MMPs) and we investigated the role of MMPs in two in vitromodels (two- and three-dimensional) of human retinal pigment epithelial (RPE) cell-mediated contraction. MMP activity was detected using enzyme-linked immunosorbent assays and zymography techniques that revealed MMP-1, -2, -3, and -9 positivity during the collagen matrix contraction assays. RPE-populated collagen matrix contraction (three-dimensional) was inhibited using a cocktail of anti-MMP antibodies and with Galardin (a broad-spectrum MMP inhibitor). Galardin inhibition was dose-dependent, reversible, and dependent on cell number. MMP inhibitors had no effect on contraction when RPEs were seeded on two-dimensional collagen matrices or on cellular adhesion to collagen type I. Our results suggest that MMP activity may be required for three-dimensional but not two-dimensional RPE-collagen matrix contraction.