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Myopic vitreopathy features precocious fibrous vitreous liquefaction and early posterior vitreous detachment (PVD). It is unclear whether visual function is affected by myopic vitreopathy and PVD. This study assessed the relationships among axial length, structural vitreous density, PVD, and visual function.Retrospective case-control study.Ultrasonography measurements were made of axial length, logMAR VA, contrast sensitivity function (CSF [Freiburg acuity contrast test]), and quantitative B-scan ultrasonography.Seventy-nine subjects (45 men and 34 women; mean age: 49 ± 14 years) were analyzed. Axial lengths ranged from 22 to 29.2 mm (mean: 24.9 ± 1.8 mm; myopic eyes: 26.35 ± 1.35 mm; and nonmyopic eyes: 23.45 ± 0.75 mm; P.001). With increasing axial length there was greater vitreous echodensity (R: 0.573; P.01) and degradation in CSF (R: 0.611; P.01). Subgroup analyses found that myopic eyes (- 3 diopters) had 37% more vitreous echodensity than nonmyopic eyes (762 ± 198 arbitrary units [AU] vs. 557 ± 171 AU, respectively; P.001) and that CSF was 53% worse in myopic eyes (3.30 ± 1.24 Weber index [%W]) than in nonmyopic eyes (2.16 ± .59 %W; P.001). Myopic eyes with PVD had 33% greater vitreous echodensity (815 ± 217 AU; P.001) and 62% degradation in CSF (3.63 ± 2.99 %W) compared to nonmyopic eyes with PVD (613 ± 159 AU; 2.24 ± 0.69 %W; P.001, each). Limited vitrectomy was performed in 11 of 40 cases (27.5%), normalizing vitreous echodensity and CSF in each case.Axial myopia is associated with increased fibrous vitreous liquefaction and echodensity, as well as profound degradation of CSF. PVD in myopic eyes is associated with even more structural and functional abnormalities, normalized by limited vitrectomy. These findings may explain some common complaints of myopic patients with respect to vision and quality of life.

Hepatocellular Carcinoma (HCC) and Cholangiocarcinoma (CCA) are the predominant forms of liver cancer, with a devastating combined incidence of 40,000 cases per year in the United States. Despite many differences between the cancers, liver transplant has found great success in treating both over traditional methods. However, up to 35% of patients’ cancer still recur within five years. Given the risk and resource intensiveness of this treatment, it is critical to identify factors that influence recurrence in these cancers. Previous studies have found the micro-environments of HCC tumors tend to be immune-active while those of CCA tumors tend to be immunosuppressive. Increased immune activity at the tumor level is associated with better patient outcomes, but the role and impact of the regional immune response in liver cancer is not well understood. Liver draining lymph node tissue was collected from patients undergoing orthotopic liver transplant (OLT) for HCC, CCA, or other reasons (control). Nanostring GeoMx Digital Spatial Profiler (DSP) was used to measure immune marker levelsWe found increased immune activity in the LNs of patients with HCC compared to CCA, showing significantly higher levels of lymphocytes and immune activity markers, matching previous tumor microenvironment findings. Additionally, comparing recurrent and non-recurrent HCC or CCA samples, we see generally increased immune activity in non-recurrent lymph nodes, also identifying specific immune markers in both cancer types that correlate with cancer recurrence or non-recurrence. These also reveal patterns of activity specific to both cancer type and recurrence status. Overall, this study provides novel insights into the regional immune response in liver cancers and identifies candidate proteins to serve as predictors of recurrence in liver cancer. We suggest CD163, CD66b, CD8, and CD56 as markers to predict post-OLT HCC recurrence and CD163, CD66b, ID01, and OX40L as candidate markers to predict post-OLT CCA recurrence using LN samples. Further spatial analysis of this data may further characterize immune activity in these lymph nodes, and future studies focusing on identified differences in immune activity may reveal factors affecting liver cancer aggressiveness and recurrence. Citation Format: Peyton Hickman, Aubrey E. Thompson, Justin Nguyen. The role of draining lymph nodes in the post-transplant recurrence of liver cancer: Examining immune response using spatial proteomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 624.

Visual perception plays a critical role in navigating 3D space and extracting semantic information crucial to survival. Even though visual stimulation on the retina is fundamentally 2D, we seem to perceive the world around us in vivid 3D effortlessly. This reconstructed 3D space is allocentric and faithfully represents the external 3D world. How can we recreate stable 3D visual space so promptly and reliably?To solve this mystery, we have developed new concepts MePMoS (Memory-Prediction-Motion-Sensing) and NHT (Neural Holography Tomography). These models state that visual signal processing must be primarily top-down, starting from memory and prediction. Our brains predict and construct the expected 3D space holographically using traveling alpha brainwaves. Thus, 3D space is represented by the three time signals in three directions.To test this hypothesis, we designed reaction time (RT) experiments to observe predicted space-to-time conversion, especially as a function of distance. We placed LED strips on a horizontal plane to cover distances from close up to 2.5 m or 5 m, either using a 1D or a 2D lattice. Participants were instructed to promptly report observed LED patterns at various distances. As expected, stimulation at the fixation cue location always gave the fastest RT. Additional RT delays were proportional to the distance from the cue. Furthermore, both covert attention (without eye movements) and overt attention (with eye movements) created the same RT delays, and both binocular and monocular views resulted in the same RTs. These findings strongly support our predictions, in which the observed RT-depth dependence is indicative of the spatiotemporal conversion required for constructing allocentric 3D space. After all, we perceive and measure 3D space by time as Einstein postulated a century ago.

Vision degrading myodesopsia (VDM) results from clinically significant vitreous opacities that reduce contrast sensitivity (CS) and visual quality of life (VQOL). Previous studies with a single clinical system for quantitative ultrasonography (QUS) found correlations with CS and VQOL as measured by the N.E.I. Visual Function Questionnaire (VFQ). Here, we evaluated a cohort of patients to determine if VDM as evaluated by QUS is machine independent. 28 eyes from 14 patients (age 56 ± 14 years) experiencing VDM were scanned with two different clinical ophthalmic ultrasound systems in succession: one with a 15-MHz single element transducer (23mm focal length, 7 mm aperture) and one with a 20 MHz annular array (five elements, 22 mm focal length, 9 mm total aperture). Images were acquired as a longitudinal plane through premacular vitreous in temporal gaze. Three QUS parameters and a composite score were computed from the vitreous region within each set of log-compressed envelope data and averaged over artifact-free frames. A linear regression comparing QUS parameters computed fromeach system showed statistically significant correlations (R ≥ 0.86, p

INTRODUCTION AND OBJECTIVE:Time from symptom onset of testicular torsion to detorsion predicts likelihood of testicular salvage. We aimed to reduce time from door-to-incision to under 120 minutes a...

INTRODUCTION AND OBJECTIVE:Urinary tract infections (UTI) are a common complication following office-based lower urinary tract procedures. While the American Urological Association Best Practice St...

Automating traffic monitoring and management can materially contribute to the realization of Smart Cities, but this demands detailed, accurate and timely characterization of traffic flows. Current methods employ video capture (high installation and operating costs), pneumatic-tube-based counters (limited detail about vehicle types and often only installed temporarily), or manual data capture (high human cost).We have developed an intelligent, inexpensive, pavement-mountable device capable of collecting information about vehicle types and speeds using an embedded, power-optimized neural network. The device is designed to fit within a raised pavement marker (RPM). RPMs are deployed throughout the world as lane markers. Packaging our sensing technology into RPMs offers the potential to significantly improve the spatial and temporal resolution of traffic flow information across a city.We outline our methodology for energy-optimized machine learning on a small, resource-constrained sensor device. We present the results of our work in terms of accuracy (96% classifying vehicle type and 89% classifying vehicle speed) and battery life (three years).

Background The personal health and professional impact of physician pregnancy requires further study. We performed a comprehensive scoping review of physician pregnancy to synthesize and assess the evidence to aid decision-making for relevant stakeholders. Methods A search of 7 databases resulted in 3733 citations. 407 manuscripts were included and scored for evidence level. Data were extracted into themes using template analysis. Results Physician pregnancy impacted colleagues through perceived increased workload and resulted in persistent stigmatization and discrimination despite work productivity and academic metrics being independent of pregnancy events. Maternity leave policies were inconsistent and largely unsatisfactory. Women physicians incurred occupational hazard risk and had high rates of childbearing delay, abortion, and fertility treatment; obstetric and fetal complication rates compared to controls are conflicting. Conclusions Comprehensive literature review found that physician pregnancy impacts colleagues, elicits negative perceptions of productivity, and is inadequately addressed by current parental leave policies. Data are poor and insufficient to definitively determine the impact of physician pregnancy on maternal and fetal health. Prospective risk-matched observational studies of physician pregnancy should be pursued.

Purpose Lamellar macular holes (LMHs) can been subdivided into tractional and degenerative subtypes. This cross-sectional cohort study compared structural and functional characteristics in these subtypes hypothesizing that tractional LMH has a higher prevalence of vitreopapillary adhesion and tangential traction (macular pucker), whereas degenerative LMH has more ellipsoid zone disruption and worse vision, measured three different ways. Methods Tractional LMH (n = 22) and degenerative LMH (n = 15) were distinguished by optical coherence tomography criteria. Separate spectral domain optical coherence tomography scanning of the macula and optic disk was performed. Visual acuity, contrast sensitivity function (Weber Index, %W), and the degree of visual distortions (3-dimensional threshold Amsler grid; % volume lost [%VL]) were quantified. Results Vitreopapillary adhesion was present in 14/22 (64%) tractional, but in only 3/15 (20%) degenerative LMH (P = 0.006). Macular pucker was present in 19/22 (86%) tractional, but in only 8/15 (53%) degenerative LMH (P = 0.011). Ellipsoid zone disruption was present in 13/15 (87%) degenerative, but in only 2/22 (9%) tractional LMH (P = 0.0001). Visual acuity was better in tractional than degenerative LMH (P = 0.006), as was contrast sensitivity function (tractional = 3.44 ± 1.07 %W, degenerative = 4.66 ± 1.73 %W; P = 0.015). Visual distortions were less in tractional (0.33 ± 0.61 %VL) than in degenerative (0.85 ± 0.68 %VL) LMH (P = 0.014). Conclusion Structure and visual function differ significantly in subtypes of LMH. Tractional LMH has 3-fold higher prevalence of vitreopapillary adhesion and 2-fold higher prevalence of macular pucker. Degenerative LMH has 9-fold more ellipsoid zone disruption, worse visual acuity and contrast sensitivity function, and 3-fold more distortions. Thus, outer retinal integrity seems more closely correlated with vision than anterior structural abnormalities in LMH.

Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment is performed on vitreous floaters, but studies of structural and functional effects with objective outcome measures are lacking. This study evaluated Nd:YAG laser effects by comparing participants with vitreous floaters who previously underwent laser treatment with untreated control participants and healthy persons without vitreous floaters using quantitative ultrasonography to evaluate vitreous structure and by measuring visual acuity and contrast sensitivity function to assess vision.Retrospective, comparative study.One eye was enrolled for each of 132 participants: 35 control participants without vitreous floaters, 59 participants with untreated vitreous floaters, and 38 participants with vitreous floaters previously Nd:YAG-treated. Of these, 25 were dissatisfied and sought vitrectomy; 13 were satisfied with observation.The 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-39) to assess participant visual well-being, quantitative ultrasonography (QUS) to measure vitreous echodensity, and best-corrected visual acuity (BCVA) and contrast sensitivity function (CSF) to evaluate vision.Results of NEI-VFQ-39, QUS, BCVA, and CSF.Compared with control participants without vitreous floaters, participants with untreated vitreous floaters showed worse NEI-VFQ-39 results, 57% greater vitreous echodensity, and significant (130%) CSF degradation (P0.001 for each). Compared with untreated eyes with vitreous floaters, Nd:YAG-treated eyes had 23% less vitreous echodensity (P0.001), but no differences in NEI-VFQ-39 (P = 0.51), BCVA (P = 0.42), and CSF (P = 0.17) results. Of 38 participants with vitreous floaters who previously were treated with Nd:YAG, 25 were dissatisfied and seeking vitrectomy, whereas 13 were satisfied with observation. Participants seeking vitrectomy showed 24% greater vitreous echodensity (P = 0.018) and 52% worse CSF (P = 0.006). Multivariate linear regression models confirmed these findings.As a group, participants previously treated with Nd:YAG laser for bothersome vitreous floaters showed less dense vitreous, but similar visual function as untreated control participants with vitreous floaters. Because some treated eyes showed less dense vitreous and better visual function than those of untreated control participants, a prospective randomized study of Nd:YAG laser treatment of vitreous is warranted, using uniform laser treatment parameters and objective quantitative outcome measures.

The utility of Multiparametric magnetic resonance imaging (mpMRI) guided prostate biopsy among patients with prostate cancer (CaP) managed with active surveillance (AS) with low-suspicion lesions remains unsettled.We performed a retrospective analysis of 415 men with low-risk CaP managed with active surveillance. We selected men with mpMRI visible index lesions scored as 2 or 3 according to Prostate Imaging Reporting and Data System (PI-RADS) version 2. The primary outcome was detection of clinically significant prostate cancer (csCaP) was defined as Gleason grade group ≥ 2. We assessed the diagnostic accuracy of biopsy approaches using area under the receiver operator characteristic (ROC) curve and evaluated factors associated with csCaP in these patients using multivariate logistic regression.CsCaP was identified in 22 of 125 patients (17.6%) with PI-RADS 2 or 3 index lesions during surveillance prostate biopsies. These included 10 (45.5%) diagnosed by systematic biopsy alone, 9 (40.9%) by targeted alone, and 3 (13.6%) by both approaches. On multivariable analysis, the only significant variable predicting the detection of csCaP in men with low-risk imaging mpMRI characteristics was higher PSAD (OR per 0.1 unit=2.26, 95% CI 1.25-4.06, P = 0.007. A PSAD cutoff of 0.1, 0.12 and 0.15 resulted in a negative predictive value (NPV) of 90.9%, 87.1% and 86.2%, respectively. When stratified by PI-RADS score, a PSAD cutoff of 0.1, 0.12 and 0.15 resulted in NPV of 96.2%, 90.6% and 89.7% and 86.2%, 84.2% and 83.3% for detection of csCaP in PI-RADS 2 and 3 lesions, respectively. In patients with PIRDAS 2 lesions, using a PSAD of 0.1 would potentially allow 51% of patients to avoid biopsy with only a 3.8% chance of missing csCaP.In men with clinical low-risk prostate cancer on active surveillance with PI-RADS 2 and 3 lesions, there is an almost 18% risk of upgrade to csCaP. Integration of PSAD may be a useful adjunctive tool in identifying patients at highest risk for upgrade despite favorable imaging findings. In men with PIRADS 2 lesions with PSAD ≤0.12 biopsy can be avoided. For men with PIRADS 2 lesions with PSAD ≤0.15 informed decision making regarding the AS intensity should include that these patients have a low risk (10%) of developing csCaP. In men with PIRADS 3 lesions with PSAD0.1, shared decision making should include discussion of a10% miss rate of csCaP.

Successful translation ofin vivoexperimental data to human patients is an unmet need and a bottleneck in the development of effective therapeutics. micro technology aims to address this need with significant advancements reported recently that enable modeling of organ level function. These microengineered chips enable researcher to recreate critical elements such asin vivorelevant tissue-tissue interface, air-liquid interface, and mechanical forces, such as mechanical stretch and fluidic shear stress, are crucial in emulating tissue level functions. Here, we present the development of a new, comprehensive 3D cell-culture system, where we combined our proprietary Organ-Chip technology with recent advantages in three-dimensional organotypic culture. Leveraging microfabrication techniques, we engineered a flexible chip that consists of a channel containing an organotypic epithelium surrounded by two vacuum channels that can be actuated to stretch the hydrogel throughout its thickness. Furthermore, the ceiling of this channel is a removable lid with a built-in microchannel that can be perfused with liquid or air and removed as needed for direct access to the tissue. The floor of this channel is a porous flexible membrane in contact with a microfluidic channel that provides diffusive mass transport to and from the channel. This additional microfluidic channel can be coated with endothelial cells to emulate a blood vessel and capture endothelial interactions. Our results show that the Open-Top Chip design successfully addresses common challenges associated with the Organs-on-Chips technology, including the capability to incorporate a tissue-specific extracellular matrix gel seeded with primary stromal cells, to reproduce the architectural complexity of tissues by micropatterning the gel, that can be extracted for H&E staining. We provide proof-of-concept data on the feasibility of the system using skin and alveolar epithelial primary cells and by simulating alveolar inflammation.

Context A 2009 systematic review synthesized data between 1987 and 2007 and revealed a higher prevalence of smoking among sexual minority populations than among heterosexuals. Subsequently, growing attention to tobacco use among sexual minority populations has spurred more literature on this issue because higher tobacco use prevalence has been found in certain sexual minority subgroups relative to others. However, a population-level synthesis of tobacco use prevalence by sexual minority subgroup has not been done for the past decade. Evidence acquisition Investigators conducted a meta-analysis by searching MEDLINE, Web of Science, EMBASE, and PsycINFO for U.S.-based studies published between 2007 and 2020 that specifically reported tobacco use prevalence among adults and separated the sexes and gays/lesbians versus bisexuals. Using random-effects models, meta-prevalence estimates, 95% CIs, and heterogeneity (I2) were calculated for each sexual minority subgroup. Evidence synthesis A total of 30 studies were included in the meta-analysis. The highest current cigarette use prevalence estimates were found among bisexual women (37.7%), followed by lesbians (31.7%), gay men (30.5%), and bisexual men (30.1%). Heterosexual men (21.0%) and women (16.6%) had the lowest prevalence. Conclusions Tobacco use prevalence among sexual minorities during 2007–2020 remained at similarly high levels as those during 1987–2007, and tobacco use disparity between sexual minorities and heterosexuals persisted in the past decade. Significant heterogeneity existed in tobacco use across sexual minority subgroups, with bisexual women having the highest prevalence. These findings are critical for increasing decision maker's awareness and action to address sexual minorities’ persistent high prevalence of tobacco use, particularly among bisexual women.

Clinical development of Hu5c8, a monoclonal antibody against CD40L intended for treatment of autoimmune disorders, was terminated due to unexpected thrombotic complications. These life-threatening side effects were not discovered during preclinical testing due to the lack of predictive models. In the present study, we describe the development of a microengineered system lined by human endothelium perfused with human whole blood, a "Vessel-Chip." The Vessel-Chip allowed us to evaluate key parameters in thrombosis, such as endothelial activation, platelet adhesion, platelet aggregation, fibrin clot formation, and thrombin anti-thrombin complexes in the Chip-effluent in response to Hu5c8 in the presence of soluble CD40L. Importantly, the observed prothrombotic effects were not observed with Hu5c8-IgG2σ designed with an Fc domain that does not bind the FcγRIIa receptor, suggesting that this approach may have a low potential risk for thrombosis. Our results demonstrate the translational potential of Organs-on-Chips, as advanced microengineered systems to better predict human response.

A general method for a new, hindered lithium diadamantylamide (LDAM) base-promoted insertion of arynes into Si-P, Si-S, Si-N, and C-C bonds is described. Arynes are generated from easily available aryl triflates and halides. Subsequent reaction of the aryne with silylated phosphines, sulfides, or amines affords the insertion products. Furthermore, a one-step synthesis of anthracenes from aryl halides and aryl ketones is also demonstrated. Cyano, aryl, alkyl, trifluoromethyl, vinyl, methoxy, chloro, fluoro, and even formyl moieties are compatible with the reaction conditions. The new lithium amide affords higher yields compared with lithium tetramethylpiperidide (LiTMP)-promoted reactions. Furthermore, the bulkiness of LDAM base essentially suppresses aryne reaction with base, allowing use of aryl halides and triflates as the limiting reagents.

Contrast sensitivity function (CSF) declines with age. When unassociated with cataracts, this is hypothesized to be due to macular ganglion cell complex (GCC) thinning. However, other studies found associations with increased vitreous echodensity and posterior vitreous detachment (PVD). We investigate the relationship between CSF, vitreous echodensity, PVD, and GCC thickness as related to age in the same subjects. Age, CSF (Weber index: %W), vitreous echodensity (quantitative ultrasonography [QUS]), lens status (phakia or pseudophakia), best-corrected visual acuity (BCVA), and GCC thickness (SD-OCT) were evaluated in 57 eyes of 57 subjects with (n = 32, mean age = 62 years) and without (n = 25, mean age = 44 years) PVD (P

Successful translation of in vivo experimental data to human patients is an unmet need and a bottleneck in the development of effective therapeutics. Organ-on-Chip technology aims to address this need by leveraging recent significant advancements in microfabrication and biomaterials, which enable modeling of organs and their functionality. These microengineered chips offer researchers the possibility to recreate critical elements of native tissue architecture such as in vivo relevant tissue-tissue interface, air-liquid interface, and mechanical forces, including mechanical stretch and fluidic shear stress, which are crucial to recapitulate tissue level functions. Here, we present the development of a new, comprehensive 3D cell-culture system, where we combined our proprietary Organ-Chip technology with the advantages offered by three-dimensional organotypic culture. Leveraging microfabrication techniques, we engineered a flexible chip that consists of a chamber containing an organotypic epithelium, surrounded by two vacuum channels that can be actuated to stretch the hydrogel throughout its thickness. Furthermore, the ceiling of this chamber is a removable lid with a built-in microchannel that can be perfused with liquid or air and removed as needed for direct access to the tissue. The bottom part of this chamber is made from a porous flexible membrane which allows diffusive mass transport to and from the microfluidic channel positioned below the membrane. This additional microfluidic channel can be coated with endothelial cells to emulate a blood vessel and recapitulate endothelial interactions. Our results show that the Open-Top Chip design successfully addresses common challenges associated with the Organs-on-Chip technology, including the capability to incorporate a tissue-specific extracellular matrix gel seeded with primary stromal cells, to reproduce the architectural complexity of tissues by micropatterning the gel, and to extract the gel for H&E staining. We also provide proof-of-concept data on the feasibility of using the system with primary human skin and alveolar epithelial cells.

A computational model of vitreous oxygen consumption and transport predicts that limited vitrectomy will result in lower retrolental oxygen levels than extensive vitrectomy, and that higher retrolental oxygen would promote cataractogenesis. This study compared the incidence and timing of cataract surgery after limited versus extensive vitrectomy for vitreous opacities.Ninety-six phakic eyes in 75 patients (aged 55±14 years) underwent limited 25 G vitrectomy with preservation of 3 to 4 mm of retrolental vitreous and without surgical posterior vitreous detachment induction. Of these 96 eyes, 48 eyes in 37 patients (aged 56±14 years) had a minimum of 24 months' follow-up and were compared with 23 eyes from 18 patients (aged 63±8 years) who underwent extensive vitrectomy.Limited vitrectomy patients were older than extensive vitrectomy patients (P0.015), yet only 17 of 96 eyes (18%) required cataract surgery after limited vitrectomy (mean follow-up = 20±17 months). In eyes with a minimum follow-up of 24 months, 17 of 48 eyes (35%; age = 53-81 years) with limited vitrectomy required cataract surgery, versus 20 of 23 eyes (87%; age = 50-75 years) with extensive vitrectomy (P0.0001). Just before cataract surgery, visual acuity was comparable in each group (0.47±0.18 in the limited vitrectomy group vs. 0.54±0.30 in the extensive vitrectomy group; P = 0.23). Cataract surgery occurred an average of 12.4±5.1 months after limited vitrectomy, compared with 7.3±3.9 months after extensive vitrectomy (P0.002).The incidence of cataract surgery was lower after limited vitrectomy, which had a longer interval until cataract surgery compared with extensive vitrectomy. These findings are consistent with the computational model of oxygen consumption and transport and suggest clinical strategies to mitigate postvitrectomy cataractogenesis.

Lithium 1,1-diadamantylamide (LDAM) base-promoted insertion of arynes into disulfide S–S bonds is described. After generation of arynes from readily available aryl halides and triflates, reactions with diaryl and diisopropyl disulfides afford the insertion products in moderate to excellent yields. Use of 1-cyclohexenyl triflate gave an excellent yield of 1,2-bis(phenylthio)cyclohexene.

Purpose To evaluate the effect of posterior vitreous detachment (PVD) on contrast sensitivity function (CSF) in previously normal eyes, with the hypothesis that PVD reduces CSF. Design Prospective observational case series. Methods At a single clinical practice 28 eyes were evaluated: 8 eyes of 8 adults (mean age 54.4 ± 10.1 years; range 39–68 years) with normal CSF documented by Freiburg Acuity Contrast Testing (Weber index: %W) who subsequently experienced PVD, as confirmed by ultrasonography and optical coherence tomography; 8 fellow eyes without PVD; and 12 control eyes: 9 eyes with PVD in patients who chose observation and 3 fellow eyes without PVD. Results At study entry there was no significant difference in CSF of fellow eye controls (mean 1.44 ± 0.27 %W; range 1.06–2.00 %W) and eyes that subsequently developed PVD (1.81 ± 0.61 %W; P = .146; range 1.01–2.69 %W). Following PVD there was a 52.5% reduction in CSF (2.76 ± 0.30 %W; P = .001; range 2.25–3.14 %W). CSF in the patients who chose limited vitrectomy (2.51 ± 0.46 %W; range 2.03–3.06 %W) was 41.8% worse than in the eyes with PVD of patients who chose observation (1.46 ± 0.21 %W; P = .001; range 1.08–1.87 %W). After vitrectomy, CSF improved by an average of 43.2%, normalizing in each case at 1 month (CSF 1.51 ± 0.28 %W; P = .001; range 1.14–2.00 %W), 3 months (1.38 ± 0.10 %W; P = .0002; range 1.28–1.51 %W), and 12 months (1.34 ± 0.34 %W; P = .0001; range 1.01–1.89 %W, n = 5) postoperatively, attaining the same CSF as the control fellow eyes (1.34 ± 0.20 %W; range 1.06–1.56 %W). Conclusion PVD is associated with significant reduction in CSF of previously normal eyes. This quantifiable negative impact on visual function can distinguish patients who are not significantly bothered by vitreous floaters from those with clinically significant symptoms.

To measure the effects of macular pucker (MP) on macular structure and quantify function by measuring visual acuity (VA), contrast sensitivity (CS), and distortions. The effects of surgery were quantitatively evaluated using these measures.Prospective, comparative case series.Fifty-three patients with unilateral MP and normal fellow eyes: 24 operated MP subjects, 17 unoperated controls, and 12 reproducibility subjects.Posterior vitreous detachment was diagnosed by ultrasound and ellipsoid zone disruption (EZD) was determined by OCT, which also measured macular thickness and volume. Vision was assessed, by measuring VA (logMAR) and CS (Freiburg acuity contrast testing: Weber index, %W). A visual distortions index (%DI) was calculated using 3-dimensional threshold Amsler grid testing. Comparisons to controls were performed before surgery and at 1, 3, 6, and 12 months after vitrectomy/membrane peel without chromodissection.Posterior vitreous detachment (ultrasound), EZD (OCT), macular thickness and volume (OCT), VA (logMAR), CS (%W), distortions (%DI).Posterior vitreous detachment was present in 90% of MP eyes, but only 50% of fellow eyes (P 0.001). All structural and functional indices were worse (28% to 5-fold) in the 24 operated MP eyes than the 17 unoperated MP eyes (P0.001). Before surgery, EZD was present in 33% of operated MP eyes but none of the unoperated MP eyes (P0.02). The macula was thicker (514±85 μm vs. 257±59 μm; P0.001) with greater volume (3.22±0.56 μl vs. 2.14±0.22 μl; P0.001) in operated MP eyes than normal fellow eyes. Before surgery, MP eyes had VA = 0.53 logMAR (Snellen equivalent, 20/67) vs. controls = 0.21 (20/32); P0.001; CS was 8.61±5.36 %W vs. controls = 3.71±1.47 %W (P0.001); and distortions were 7.61±12.6 %DI vs. controls = 0.13±0.61 %DI (P0.001). EZD was associated with worse VA (P0.01) and CS (P0.03) before and after surgery. Each outcome measure improved progressively at 1, 3, 6, and 12 months after surgery, but only %DI and macular volume normalized.These quantitative measures characterize the impact of MP on macular structure and function. All indices improved after surgery, but only distortions and macular volume normalized. Contrast sensitivity measurements and quantification of distortions can objectively assess visual dysfunction in MP and may be useful outcome measures of therapy.

To describe our institutional experience with cytoreductive/consolidative radical cystectomy (CCRC) for metastatic urothelial carcinoma (UC) and to investigate clinicopathologic features predicting prolonged cancer specific survival (CSS) following CCRC. We performed IRB-approved review of our cystectomy database, and identified 43 patients with metastatic UC who underwent CCRC. Baseline demographics, chemotherapy regimen, clinicopathologic features, and perioperative complications were collected. Progression-free survival (PFS) and CSS were estimated from the time of CCRC. Univariate and multivariate Cox regression models were used to identify predictors of improved CSS after CCRC. Of the 43 patients, 32 (74.4%) had clinical evidence of distant metastases, while 11 harbored occult metastases on the surgical specimen. The most common site of metastasis was the retroperitoneal lymph nodes, found in 30 patients. Solitary metastases were found in 22 patients (51.1%). Forty-one (95%) patients received chemotherapy prior to CCRC. Disease progression was detected in 35 patients after CCRC (median PFS 5.9 months), and 34 died of metastatic cancer (median CSS 12.3 months). On multivariate analysis, patients with solitary metastases were found to have improved CSS compared to those with multiple metastases (HR 2.62, 95% CI 1.16–5.90, p = 0.02), with median CSS of 26.0 months vs. 7.9 months (p

Vitreous floaters can lower visual acuity (VA) and degrade contrast sensitivity function (CSF). Limited vitrectomy improves VA and normalizes CSF, but long-term results in a large series with objective quantitative outcome measures are lacking.Case series.One hundred ninety-five eyes of 145 patients (87 men, age = 57.6 ± 4.3 years; 58 women, age = 61.5 ± 12.0 years) reporting bothersome vitreous floaters were compared to 70 age-matched controls. Posterior vitreous detachment (PVD) alone was the cause in 96/195 (49.2%), myopic vitreopathy alone was the cause in 30/195 (15.4%), PVD with myopic vitreopathy was the cause in 56/195 (28.7%), and asteroid hyalosis was the cause in 13/195 eyes (6.7%).Limited vitrectomy with 25-gauge instruments was performed without surgical PVD induction, preserving 3 to 4 mm of retrolental vitreous in phakic eyes. Follow-up averaged 32.6 ± 23.5 months (range, 3-115 months), with 2 years or more in 144 eyes, 3 years or more in 69 eyes, 4 years or more in 51 eyes, and 5 years or more in 24 eyes.Visual acuity, 39-item National Eye Institute Visual Function Questionnaire (VFQ) results, CSF (Weber index), and quantitative ultrasonography results.After surgery, vitreous echodensity decreased by 94.1% (P0.0001) and VFQ results improved by 19.3% (P0.0001). Preoperative VA was 0.68 ± 0.21, improving to 0.77 ± 0.19 after surgery (P0.0001). Preoperative CSF was degraded by 91.3% compared with controls (P0.0001), normalizing at 1, 3, 6, 12, 24, 36, and 48 months after surgery (P0.00005 for each). There were no cases of endophthalmitis. There were 3 retinal tears and 3 retinal detachments that underwent successful repair. Clinically significant vitreous hemorrhage developed in 2 patients, clearing spontaneously. Two macular puckers and 4 recurrent floaters from new PVD were cured by re-operation. Cataract surgery occurred in 21 of 124 patients (16.9%; mean age, 64 ± 7 years; none younger than 53 years), an average of 13.1 ± 6.8 months after vitrectomy.Limited vitrectomy for Vision Degrading Vitreopathy decreases vitreous echodensity, improves patient well-being, improves VA, and normalizes CSF. The long-term efficacy and safety profiles suggest this may be a safe and effective treatment for clinically significant vitreous floaters, warranting a prospective randomized trial.

Background: Epigenetic dysregulation is involved in the etiology and progression of various human diseases. Formalin-fixed paraffin-embedded (FFPE) samples represent the gold standard for archiving pathology samples, and thus FFPE samples are a major resource of samples in clinical research. However, chromatin-based epigenetic assays in the clinical settings are limited to fresh or frozen samples and are hampered by low chromatin yield in FFPE samples due to the lack of reliable and efficient chromatin preparation methods. Here, we introduce a new chromatin extraction method from FFPE tissues (Chrom-EX PE) for chromatin-based epigenetic assays. Results: During rehydration of FFPE tissues, applying tissue-level cross-link reversal to the deparaffinized tissue at 65°C dramatically increased chromatin yield in the soluble fraction. We found the resulting chromatin to be compatible with ChIP-qPCR and ChIP-seq analysis of histone marks (H3K4me3, H3K27me3, and H3K27Ac) and RNA polymerase II. The chromatin prepared by Chrom-EX PE showed a gradual fragmentation pattern with varying incubation temperature. At temperatures below 37°C, the majority of soluble chromatin was over 1 kb in size. The soluble chromatin prepared at 45-60°C showed a typical nucleosomal pattern shown in cell lines and frozen tissues. The majority of the chromatin prepared at 65°C is close to mononucleosomal size. These observations indicate that chromatin preparation from FFPE samples can be controlled for downstream chromatin-based epigenetic assays. Conclusions: Our method achieves efficient extraction of high-quality chromatin from FFPE samples suitable for targeted and genome-wide epigenetic assays while minimizing degradation and damages. This approach provides a new platform for developing chromatin-based assays applicable to archived FFPE samples to circumvent the over-fixed nature of FFPE tissues. This work was supported, in part, by National Institutes of Health grant P01DK068055 and the Mayo Clinic Center for Individualized Medicine Epigenomics Program. Citation Format: Jian Zhong, Zhenqing Ye, Chad Clark, Samuel Lenz, Justin Nguyen, Huihuang Yan, Keith Robertson, Gianrico Farrugia, Zhiguo Zhang, Tamas Ordog, Jeong-Heon Lee. Enhanced and controlled chromatin extraction for chromatin-based epigenetic assays in FFPE tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5180.

The purpose of this project is to test the effectiveness of using polyvinyl chloride (PVC) structural angles to increase the capacity of reinforced concrete (RC) beams. Two ½-scale beams with different reinforcement configurations were loaded to approximately twice the yield displacement, unloaded, and subsequently repaired and reloaded to failure. Results indicate that the PVC attachments increased the capacity of the beams by 10-15%. While the increase in strength was modest, it may be sufficient for cases in which only minor improvement is necessary and thus does not justify the high cost of other repair techniques.

Vertically aligned carbon nanotubes (VACNTs) present a uniform pore size as compared to activated carbon or nonaligned carbon nanotubes, increasing the available surface area for electric double layer formation. In this study, we fabricate VACNTs grown directly on thin aluminum foils using only conductive support layers in a scalable, low-pressure chemical vapor deposition (LPCVD) process. These highly flexible and conductive electrodes were optimized by utilizing combinations of diffusion barrier layers and catalyst support layers to alter the electrode porosity and available surface area. Specific capacitances for five growth times (5, 10, 15, 20 and 25 min) were measured to be 30–79 F g −1 and compare favorably to similar studies. Power densities for all supercapacitor sheets exceeded 3 MW kg −1 and consistently exceeded other VACNT supercapacitor studies. Our study demonstrates the benefits and applicability of fabricating VACNTs on metal substrates using scalable techniques for flexible and conductive supercapacitors.

Smudge, a bacteriophage enriched from soil using Bacillus thuringiensis DSM-350 as the host, had its complete genome sequenced. Smudge is a myovirus with a genome consisting of 292 genes and was identified as belonging to the C1 cluster of Bacillus phages.

524 Background: The strategy of surgical extirpation of the primary tumor in the setting of metastatic disease has gained acceptance for a variety of solid tumors. The role of cytoreductive/consolidative radical cystectomy (CCRC) for metastatic urothelial cancer (UC) is unknown. We aimed to describe our institutional experience with CCRC for metastatic UC and to investigate clinicopathologic features predicting prolonged cancer specific survival (CSS) following CCRC. Methods: We performed IRB approved review of our bladder cancer database, and identified 32 patients with metastatic cancer originating from the lower urinary tract who underwent CCRC. Of these, two patients had non−UC histology. Baseline demographics, regimen of chemotherapy, clinicopathologic features, and perioperative complications were collected. Progression free survival (PFS) and cancer specific survival (CSS) were estimated from the time of CCRC. Univariate and multivariate Cox regression models were used to identify predictors of improved CSS after CCRC. Results: Of the 32 patients, 19 (59%) had clinical evidence of distant metastases, while 13 were found to harbor occult metastases on the surgical specimen. The most common site of metastasis was the retroperitoneal lymph nodes, found in 17 patients. Solitary metastases were found in 19 patients (59%). Twenty−eight (88%) patients received chemotherapy prior to CCRC. Disease progression was detected in 29 patients after CCRC (median PFS 4.5 mo), while 28 died of metastatic cancer (median CSS 11.7 mo). On multivariate analysis, patients with solitary metastases were found to have improved CSS compared to those with multiple metastases (HR 2.51, 95% CI 1.06−5.92, p = 0.04), with median CSS of 16.9 mo vs. 5.6 mo (p = 0.003). Median postoperative LOS was 10 days. Overall, 59% suffered postoperative complications, including one perioperative mortality. Conclusions: CCRC is feasible in the setting of metastatic UC, with comparable perioperative morbidity and mortality to RC with curative intent. Patients with solitary metastasis demonstrated longer CSS than those with multiple metastases, and should be considered candidates for future trials evaluating the role of CCRC for metastatic UC.

The strategy for the collection of information (i.e., data) for model development is called experimental design. Optimal design seeks to maximize the information content under constraints of time and sampling. In the system identification literature the dominant strategy has been the method of pseudo random sequences (PRS). However, this work demonstrates that statistical design of experiments (SDOE) can provide greater information content as quantitatively measured by the D-optimal criterion.