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Supplementary Figure 4 from Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76–0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75–0.95; P = 0.006). Considering a multiple-testing–corrected significance threshold of P < 2.5 × 10−5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79–0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852–61. ©2013 AACR.

PDF file - 145K, Supplementary Table 1. Studies in the Ovarian Cancer Association Consortium (OCAC) are listed, as well as the abbreviation, location, type, and number of cases and controls for each study. Supplementary Table 2. The number of cases included in the analysis from each OCAC study site is listed by histologic subtype. Supplementary Table 3. Gene symbols and IDs are listed for NF-κB pathway genes that were tagged in this study, as well as chromosome position, number of SNPs tagged, and bin coverage of each gene using Hapmap or 1000 genomes as a reference. Supplementary Table 4. Reasons and numbers of samples excluded from the analysis following the sample quality control are described. Supplementary Table 5. We evaluated rs17561 and rs6785617 for interactions with known epidemiologic risk factors for risk of clear cell and LMP tumors, respectively, and report interaction p-values in the table below.

Supplementary Figure 5 from Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

Supplementary Tables 1-4 from Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

To evaluate anterior segment optical coherence tomography (AS-OCT) features of Descemet's membrane endothelial keratoplasty (DMEK) grafts associated with graft attachment worsening over time.Retrospective case series on patients who received uncomplicated DMEK surgery and for whom subsequent AS-OCT data were available for analysis. Patients' demographics and surgical details were collected. AS-OCT was analysed for graft detachment axial extension, presence of posterior stromal ripples, quadrant involvement (location and number), degree of detachment extension, peripheral roll, presence and amount of air in the anterior chamber (AC). Features associated with re-bubbling and graft detachment worsening over time were identified.A total of 147 patients with a mean age of 70.8 ± 9.8 years (63% females) were included. AS-OCT was performed at 2.9 ± 2.4 days after surgery. AS-OCT factors associated with re-bubbling were posterior stromal ripples (p = 0.004) and detachment axial extension (p 0.001). At first follow-up, of the 147 DMEK, 67 showed complete attachment and 80 partial detachment. In those cases of initially completely attached grafts, posterior stromal ripples were associated with the risk of subsequent graft detachment (p = 0.014) together with recipient age (p = 0.043), phaco-combined surgery (p = 0.018) and AS-OCT timing (p = 0.033); while, in the initially partially detached grafts, detachment worsening was associated with posterior stromal ripples (p = 0.025), detachment axial extension (p = 0.003), degrees of detachment involvement (p = 0.029), peripheral roll-in shape (p = 0.033) and presence of air in the AC (p = 0.032). Relative risk (RR) of graft detachment worsening in patients with moderate/severe posterior stromal ripples was 1.75 (95% CI = 1.09-2.81).Posterior stromal ripples and detachment axial extension1/3 of graft surface area were the main risk factors for detachment worsening over time, and patients showing these features should be monitored closely to identify the need for re-bubbling at an early stage, thus improving surgical outcomes.

AimTo investigate effect of patient age, gender, comorbidities and surgeon on refractive outcomes following cataract surgery.MethodsStudy population: patients on UK national ophthalmic cataract database on cataract operations undertaken between 1 April 2010 and 31 August 2018. Variables examined included gender, age, diabetic retinopathy, glaucoma, high myopia, inherited retinal disease, optic nerve disease, uveitis, pseudoexfoliation, vitreous opacities, retinal pathology, cataract type, previous surgery and posterior capsular rupture. A multivariate normal cross-classified model was fitted to the refractive outcome using Markov Chain Monte Carlo (MCMC) methods with diffuse priors to approximate maximum likelihood estimation. A MCMC chain was generated with a burn-in of 5000 iterations and a monitoring chain of 50 000 iterations.Results490 987 cataract operations were performed on 351 864 patients by 2567 surgeons. Myopic and astigmatic errors were associated with posterior capsule rupture (−0.38/+0.04×72), glaucoma (−0.10/+0.05×95), previous vitrectomy (−0.049/+0.03×66) and high myopia (−0.07/+0.03×57). Hyperopic and astigmatic errors were associated with diabetic retinopathy (+0.08/+0.03×104), pseudoexfoliation (+0.07/+0.01×158), male gender (+0.12/+0.05×91) and age (−0.01/+0.06×97 per increasing decade). Inherited retinal disease, optic nerve disease, previous trabeculectomy, uveitis, brunescent/white cataract had no significant impact on the error of the refractive outcome. The effect of patient gender and comorbidity was additive. Surgeons only accounted for 4% of the unexplained variance in refractive outcome.ConclusionPatient comorbidities and gender account for small but statistically significant differences in refractive outcome, which are additive. Surgeon effects are very small.

PURPOSE To assess the effect of an internal limiting membrane flap (IF) in macular hole surgery on the best-corrected visual acuity (BCVA) and integrity of the ellipsoid zone (EZ) and external limiting membrane. METHODS Patients were included who had successful surgery for macular hole

Objective To determine the horizontal extent of the binocular visual field (BVF) in subjects with horizontal strabismus and whether the BVF falls below the driving standard. Methods and analysis Adults with congenital esotropia and infantile exotropia ≤45 Prism Dioptres (PD), and subjects with orthotropia were recruited. The manifest angle of deviation was measured using a simultaneous prism cover test. Monocular Visual Field (MVF) and BVF were measured using the Esterman visual field test. Subjects with diplopia or a manifest angle of strabismus that varied by>8PD or the present of a vertical tropia >8PD were excluded. Results Forty-nine subjects were included: 10 with orthotropia, 20 with exotropia and 19 with esotropia. The horizontal extent of BVF (degrees) was significantly smaller in esotropes (122.8 ± 18.8) than in orthotropes (141 ± 6.6) or exotropes (138.3 ± 8.3) (p p = 0.004) and 16.25 degrees (p = 0.045), respectively. The difference between the summation of MVFs and the BVF was significantly greater in orthotropes (100.6 ± 2.7) than in exotropes (68.9 ± 34.4) and esotropes (74.2 ± 20.7) (p Conclusion The horizontal extent of BVF is significantly smaller and more variable in adults with congenital esotropia and may fall below the driving standard. Strengths and limitations Largest study on visual fields in subjects with horizontal strabismus including an orthotropic control group who do not have diplopia and who would otherwise meet the driving standard. Visual field quality was high but limitation is that visual field repeatability was not undertaken. How this study might affect research, practice, or policy The findings of this study would suggest that people with an esotropia should be offered the opportunity to have a binocular visual field test before applying for a driving license. The DVLA may want to consider requesting people with an esotropia to have a binocular visual field test as is a requirement with other ophthalmic conditions such as glaucoma.

The opportunistic pathogen Pseudomonas aeruginosa is one of leading causes of disability and mortality worldwide and the world health organisation has listed it with the highest priority for the need of new antimicrobial therapies. P. aeruginosa strains responsible for the poorest clinical outcomes express either ExoS or ExoU, which are injected into target host cells via the type III secretion system (T3SS). ExoS is a bifunctional cytotoxin that promotes intracellular survival of invasive P. aeruginosa by preventing targeting of the bacteria to acidified intracellular compartments. ExoU is a phospholipase which causes destruction of host cell plasma membranes, leading to acute tissue damage and bacterial dissemination. Fluoroquinolones are usually employed as a first line of therapy as they have been shown to be more active against P. aeruginosa in vitrothan other antimicrobial classes. Their overuse over the past decade, however, has resulted in the emergence of antibiotic resistance. In certain clinical situations, aminoglycosides have been shown to be more effective then fluoroquinolones, despite their reduced potency towards P. aeruginosa in vitro. In this study, we evaluated the effects of fluoroquinolones (moxifloxacin and ciprofloxacin) and aminoglycosides (tobramycin and gentamycin) on T3SS expression and toxicity, in corneal epithelial cell infection models. We discovered that tobramycin disrupted T3SS expression and reduced both ExoS and ExoU mediated cytotoxicity, protecting infected HCE-t cells at concentrations below the minimal inhibitory concentration (MIC). The fluoroquinolones moxifloxacin and ciprofloxacin, however, up-regulated the T3SS and did not inhibit and may have increased the cytotoxic effects of ExoS and ExoU.

INTRODUCTION Serum eye drops (SED) are an important treatment for patients with chronic and severe ocular surface disease (OSD). Despite a long history of use, there is a paucity of information on patient-reported outcomes, particularly comparing autologous SED (Auto-SED) and allogeneic SED (Allo-SED). National Health Service Blood and Transplant is the national provider of SED service for patients in the UK. PURPOSE To evaluate and compare patient-reported outcome measures (PROMs) in patients receiving Auto-SED and Allo-SED for severe OSD. MATERIALS AND METHODS PROMs were retrospectively collected from all new patients commencing treatment with Auto-SED and Allo-SED between January 2017 and September 2018, using the Ocular Surface Disease Index (OSDI) 12-item questionnaire. A linear mixed model was used to evaluate the change in OSDI scores between baseline and follow-up. RESULTS During the study period, 279 patients who received either Auto-SED (n = 71) or Allo-SED (n = 208) were included in the analysis. Baseline and follow-up OSDI scores were available for 161 of these (49 Auto-SED and 112 Allo-SED). There was a significant reduction in mean OSDI score for both Auto-SED (59.06-24.63, p

Australia monitors its polio-free status by conducting surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years of age, as recommended by the World Health Organization (WHO). Cases of AFP in children are notified to the Australian Paediatric Surveillance Unit or the Paediatric Active Enhanced Disease Surveillance System, and faecal specimens are referred for virological investigation to the National Enterovirus Reference Laboratory. In 2021, no cases of poliomyelitis were reported from clinical surveillance and Australia reported 1.31 non-polio AFP cases per 100,000 children, thereby meeting the WHO’s performance criterion for a sensitive surveillance system. The non-polio enteroviruses coxsackievirus A4, coxsackievirus A10, coxsackievirus A13 and enterovirus A71 were identified from clinical specimens collected from AFP cases. Australia also performs enterovirus and environmental surveillance to complement the clinical system focussed on children. In 2021, there were five cases of wild poliovirus reported from the two remaining endemic countries: Afghanistan and Pakistan. Including Afghanistan and Pakistan, 22 countries also reported cases of AFP due to circulating vaccine-derived poliovirus.

Purpose: Royal College of Ophthalmologist recent guidance recommended delaying cross-linking services during the COVID-19 pandemic. This study investigates the effects of such delays in the delivery of cross-linking services in patients with keratoconus progression. Methods: Retrospective observational study of 46 patients with keratoconus progression, whose cross-linking was delayed due to the COVID-19 pandemic. Demographic and clinical details were obtained from assessments on the day of listing, and subsequent review on the day of the procedure. Topographic indices included keratometry of the posterior and anterior corneal surface, maximum keratometry ( Kmax), thinnest corneal thickness, ABCD progression and progression based on standard criteria recommendations (1.5 D Kmax & 20 microns thinning). Results: A total of 46 eyes were analysed with an average time between being listed for CXL and having the procedure done was 182 ± 65 days. The delay due to COVID-19 was of 3 months. In this time period they had a significant worsening of all keratometric indices and lost almost one line of visual acuity (0.19 ± 0.19 to 0.26 ± 0.18 LogMAR, p: 0.03). Thirty two eyes (70%) demonstrated progression in accordance with the ABCD progression criteria, while 18 eyes (39%) showed either an increase in Kmax of more than 1.5D or a thinning in corneal thickness of at least 20 μm. Conclusions: The treatment delay for the keratoconus patients caused further progression and vision worsening. We recommend that corneal collagen crosslinking needs to be considered as a high priority intervention.

Objectives The West London lung screening pilot aimed to identify early-stage lung cancer by targeting low-dose CT (LDCT) to high risk participants. Successful implementation of screening requires maximising participant uptake and identifying those at highest risk. As well as reporting pre-specified baseline screening metrics, additional objectives were to 1) compare participant uptake between a mobile and hospital-based CT scanner and 2) evaluate the impact on cancer detection using two lung cancer risk models. Methods From primary care records, ever-smokers aged 60–75 were invited to a lung health check at a hospital or mobile site. Participants with PLCOM2012 6-yr risk ≥1.51 % and/or LLPv2 5-yr risk ≥2.0 % were offered a LDCT. Lung cancer detection rate, stage, and recall rates are reported. Participant uptake was compared at both sites (chi-squared test). LDCT eligibility and cancer detection rate were compared between those recruited under each risk model. Results Of 8366 potential participants invited, 1047/5135 (20.4 %) invitees responded to an invitation to the hospital site, and 702/3231 (21.7 %) to the mobile site (p = 0.14). The median distance travelled to the hospital site was less than to the mobile site (3.3 km vs 6.4 km, p Conclusion Targeted screening is effective in detecting early-stage lung cancer. Similar levels of participant uptake at a mobile and fixed site scanner were demonstrated, indicating that uptake was driven by factors in addition to scanner location. The LLPv2 model was more permissive; recruitment with PLCOM2012 alone would have missed several cancers.

Air curtains are produced by thin vertical planar air jets and are used to prevent exchange flows between two fluids with a horizontal density gradient. They have been shown to work effectively provided the deflection modulus (DM) is greater than a critical value (DM = 0.14). Herein, results are presented from an experimental and modeling study of the initial transient development of the buoyancy distribution within an enclosure containing a round buoyant turbulent plume that is segmented by a co-flowing planar turbulent jet. A theoretical model based on filling box theory is developed to predict the leakage of buoyant fluid across the planar jet and the time at which the planar jet is no longer able to contain the buoyant plume outflow. Results from a series of analog salt-bath experiments are also presented that show that the model accurately predicts the rate of transport of buoyant fluid across the planar jet up until DM falls below the critical value of 0.14. The experiments show that, following the breakdown of the model there is a transition period after which the horizontal distribution of buoyant fluid throughout the enclosure is the same as it would be in the absence of the planar jet.

The ability of green roof systems to impact stormwater runoff from buildings has been covered in many research studies. However, a lot of these studies looked at long-term retention, with much less work focused on how to model a green roof's response to larger design storms. Work that has examined flow routing for individual rainfall events has focused on empirical routing models that are tuned to the specific roof being modelled. This paper presents a new physics-based model for flow routing based on the green roof module geometry and soil properties, which requires only a single discharge coefficient to be measured. The results of this model were compared with the results of a series of experiments to quantify a modular green roof system's hydraulic response to drawdown and steady rainfall.

Purpose To describe a method to visualize and manage a completely detached Descemet membrane endothelial keratoplasty (DMEK) tissue scroll in the anterior chamber. Methods A 56-year-old male patient with pseudophakic bullous keratopathy, who underwent uncomplicated DMEK surgery, had a complete graft detachment diagnosed at 1-week follow-up. The graft was reattached using a new technique, that is, the free-floating graft was stained in the anterior chamber with trypan blue, immediately followed by air injection to separate the host stroma from the dye. The stained DMEK graft was opened by gentle tapping and attached to the host stroma by air tamponade. Result This technique allowed sufficient staining of DMEK tissue to further evaluate and correct the graft orientation inside the anterior chamber without compromising the stroma. The DMEK graft was attached 1 week after the reattachment procedure. The cornea cleared confirming the functionality of the endothelial cells. Conclusions The technique described may be useful in the cases of complete detachment of DMEK tissue and poor visualization of the DMEK tissue orientation. Staining with trypan blue under a "protective" air bubble can provide sufficient visualization to ensure the unfolding of DMEK tissue and reduce the risk of host stromal staining.

Satellite measurements of lake surface temperature can benefit several environmental applications such as estimation of lake evaporation, predictions of lake overturning, and meteorological forecasts. Using a one-dimensional lake simulation that incorporates satellite measurements of lake surface temperature, the average diurnal variation in lake surface temperature was obtained. The satellite measurements were obtained from the MODIS instrument aboard the Aqua and Terra satellites. Herein the functional form for the diurnal variation in surface temperature is presented for each of the five major lakes in the Savannah River Basin, which are located in South Carolina and Georgia: Lakes Jocassee, Keowee, Hartwell, Russell, and Thurmond. Differences in the diurnal variation in surface temperature between each of these lakes are identified and potential explanations for these differences are presented.

To describe the changes in corneal graft thickness following ultrathin Descemet's Stripping Automated Endothelial Keratoplasty (UT-DSAEK) comparing pre- and postoperative values over a 24-month period.In this retrospective single-center case series, patients who received eye bank-prepared tissues for UT-DSAEK surgery were included. Preoperative and postoperative graft thickness measurements were determined in the eye bank and in clinic using anterior segment optical coherence tomography (AS-OCT) images. Graft thickness measurements and their percentage change between preoperative values and values at 1 day, 1 week and 1, 6, 12, 24 months were calculated.In total, 47 eyes of 47 patients with a mean age of 69 ± 11 years (29 males) were included. Twnty-three patients had Fuchs' endothelial dystrophy (49%) and the remaining 24 had pseudophakic bullous keratopathy (51%). In total, 29/47 eyes underwent UT-DSAEK alone (62%) and 18/47 received combined cataract surgery as a triple procedure (38%). Preoperative donor graft thickness was 92 ± 28 μm. Compared to preoperative values, where graft thickness increased to 194 ± 101.3 μm at 1 day, 151.1 ± 71.4 μm at 1 week, and 108.4 ± 52.5 μm at 1 month. Graft thickness continued to gradually decrease over time until 6 months (91.7 ± 33.6 μm), and then plateaued at 12 months (83.9 ± 25.0 μm), showing minimal changes at 2 years (101.4 ± 37.5 μm).Preoperative DSAEK graft thickness measurements as reported by the eye bank are a valid approximation of DSAEK graft thickness at 6 months after surgery and these measurements tend to stabilize over time up to 2 years after surgery.

The opportunistic pathogen Pseudomonas aeruginosa is a leading cause of disability and mortality worldwide and the World Health Organisation has listed it with the highest priority for the need of new therapies. P. aeruginosa strains that express ExoU are implicated in the worst clinical outcomes. ExoU is phospholipase that is secreted by P. aeruginosa directly into the cytoplasm of target host cells, where its catalytic activity, directed towards plasma membranes, causes rapid cell lysis. Inhibition of ExoU may be a novel strategy to combat acutely cytotoxic ExoU expressing P. aeruginosa infections. Using an in vitro phospholipase assay, we performed a high throughput screen to identify compounds that might be repurposed as therapeutic ExoU inhibitors. We discovered a panel of compounds that appeared to inhibit ExoU through distinct mechanisms. Compound C prevented ExoU membrane localisation in HEK293T cells and caused colocalization with lysosomes, whereas compound D prevented PIP2 dependent oligomerisation of ExoU in vitro suggestive of synergistic action. Indeed, the concentrations required by compounds C and D to inhibit in vitro ExoU catalytic activity, when used in combination, was in the nanomolar region. In corneal scratch and infection assays, these compounds reduced ExoU mediated cytotoxicity, as assessed by fluorescence microscopy and lactate dehydrogenase release assays.

Effective suturing remains key to achieving successful outcomes in corneal surgery, especially anterior lamellar keratoplasty and full thickness transplantation. Limitations in the technique may result in complications such as wound leak, infection, or high astigmatism post corneal graft. By using a systematic approach, this study reviews articles and conducts content analysis based on update 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria). The aim of this paper is to summarize the state of the art of corneal suturing techniques for every type of corneal transplant and patient age and also their outcomes regarding astigmatism and complications. Future developments for corneal transplantation will be also discussed. This is important because especially the young surgeon must have knowledge of the implications of every suture performed in order to achieve consistent and predictable post-operative outcomes and also be aware of all the possible complications.

Extracellular vesicles (EVs), specifically exosomes, carry a cell-type dependent cargo that is transported to the recipient cell and translated in the presence of a required machinery. Differences in the cargo carried by the corneal and conjunctival-derived EVs could be the agent that triggers the transdifferentiation of these two cell populations. Therefore, this study investigates the role of EVs in triggering the plasticity of corneal and conjunctival epithelial cells and identifies prospective miRNA and genes responsible for maintaining ocular surface homeostasis. The EVs were extracted from the conditioned media (after starving) of corneal epithelial (hTCEpi) and conjunctival (HCjE-Gi) cell lines using ultracentrifugation. HCjE-Gi cells were cultured with hTCEpi-derived EVs and vice-versa. The EVs were characterized as exosomes using Nanosight and Flow cytometry. KRT3 and KRT12 were used as associated corneal markers, whereas KRT7 and KRT13 were used as associated conjunctival markers with ΔNp63 as a differentiation marker. Shift of these markers was an indication of transdifferentiation. The cargo of the extracted exosomes from both the cell types was explored using next-generation sequencing. The hTCEpi-derived EVs induced conjunctival epithelial cells to express the corneal-associated markers KRT3 and KRT12, losing their conjunctival phenotype at both the mRNA and protein level. Simultaneously, HCjE-Gi-derived EVs induced corneal epithelial cells to express the conjunctival associated markers KRT7 and KRT13, losing their corneal phenotype. This process of differentiation was accompanied by an intermediate step of cell de-differentiation showed by up-regulation in the expression of epithelial stem cell marker ΔNp63, also shown on the ex vivo human cadaveric donor corneas. miRNA molecules (total of 11 including precursor and mature) with significant differences in their relative abundance between the two populations (p < 0.05) were found and investigated. miR-9-5p expression was higher in HCjE-Gi cells and HCjE-Gi-derived EVs when compared to hTCEpi cells and hTCEPi-derived EVs (p < 0.001). The results suggest that EVs released by the two cell types have the ability to influence the transdifferentiation of human conjunctival and corneal epithelial cells. miR-9-5p could have a role in stem cell homeostasis and cell differentiation via HES-1 gene.

Purpose To investigate if donor to recipient gender or H-Y mismatching was associated with graft rejection or failure following Descemet stripping automated endothelial keratoplasty (DSAEK) in patients with Fuchs endothelial corneal dystrophy (FECD). Design Clinical Cohort study. Methods We used multi-center registry including patients older than 18 years who had undergone their first DSAEK for FECD between January 2008 and March 2018. The impact of donor and recipient gender incompatibility (including H-Y mismatches) on corneal graft rejection and failure was evaluated using Kaplan–Meier curves and univariable and multivariable Cox models. Results Outcome data from 4341 eyes (3915 from the UK and 426 from Italy) were analyzed. Graft failure at 2-year follow-up occurred in 477 (11.0%) cases. Graft rejection at 2-year follow-up occurred in 175 cases (4.0%); 58 (1.3%) of whom developed graft failure. There was no significant effect of gender or H-Y mismatching on either rejection (p=0.12, p=0.06) or failure (p=0.28, p=0.14), respectively. Conclusions In patients with FECD undergoing DSAEK, we found no significant influence of gender and or H-Y mismatch on graft rejection or failure.

To summarize the graft loading, transporting and delivery devices used for endothelial keratoplasty (EK).A literature search of electronic databases was performed.New techniques and devices have been introduced and implemented to prepare, load, transport and transplant the grafts for EK. The advantages are not only limited to the surgical theatre but also widely spread across the eye banking field. Investigation of advanced materials and designs have been rapidly growing with continuous evolution in the field of eye banking and corneal transplantation. Innovative techniques and modern devices have been evaluated to reduce the endothelial cell loss and increase the precision of the transplant in order to benefit both surgeons and the patients.It is extremely important to reduce any potential wastage and optimize the use of every available donor cornea due to the limited availability of healthy cadaveric donor corneas required for transplants. As a result, the use of pre-cut and pre-loaded grafts supplied by the eye banks in calibrated devices have been gaining momentum. Innovation in the field of bioengineering for the development of new devices that facilitate excellent clinical outcomes along with reduction in learning curve has shown promising results.

Purpose To evaluate the difference in Descemet Membrane Endothelial Keratoplasty (DMEK) graft detachment rate comparing superior versus temporal main incision approach. Methods Retrospective comparative study on patients who underwent DMEK surgery for Fuchs endothelial dystrophy or bullous keratopathy with main wound incision performed at either 90° in the superior approach, or at 180°/0° in the temporal approach. All main incisions were secured with a single 10–0 nylon suture at the end of surgery. Data collected were donor age and gender, endothelial cell counts, graft diameter, recipient age and gender, indication for transplant, surgeon grade, re-bubbling rate, air fill in the anterior chamber (AC) at day one and intra- and early postoperative complications. Results 187 eyes were included in the study. 99 eyes had DMEK surgery with superior approach, while 88 eyes had temporal approach. The two groups had no differences in donor age and sex, endothelial cell counts, graft diameter, recipient age and sex, indication for transplant, surgeon grade, and air fill in the anterior chamber at day one. Re-bubbling rate was 38.4% for surgeries performed with superior access and 29.5% for those with temporal access(p = 0.186). After exclusion of patients with intraoperative and/or postoperative complication, the difference in re-bubbling rate was higher, although non-significant (37.5% and 25% for superior and temporal approach respectively, p = 0.098). Conclusion The temporal approach in DMEK showed a trend towards a clinically significant lower rate of post-operative re-bubbling compared to the superior approach, however, no statistically significant difference was noted comparing the two approaches, which both remain feasible options in DMEK surgery.

ObjectiveTo determine whether patients who receive corneas from the same donor have similar risks of endothelial failure and rejection.Methods and AnalysisPatients with Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK) who received their first corneal transplant between 1999 and 2016 were analysed. Patients receiving corneas from donors who donated both corneas for the same indication were defined as ‘paired’. Gray’s test was used to compare the cumulative incidence of endothelial failure and rejection within 5 years post-transplant for ‘paired’ and ‘unpaired’ groups. Cox regression models were fitted to determine whether there was an association between recorded donor characteristics (endothelial cell density (ECD), age and sex and endothelial graft failure and rejection.Results10 838 patients were analysed of whom 1536 (14%) were paired. The unpaired group comprised 1837 (69%) recipients of single corneal donors and 7465 (69%) donors who donated both corneas for another indication. ECD was lower for unpaired single cornea donors (p0.16 for ECD, p>0.32 for donor age, p>0.14 for sex match and p>0.17 for the donor effect).ConclusionThe absence of a significant difference in graft outcome for corneal transplants for FED and PBK between paired and unpaired donors may reflect a homogeneous donor pool in the UK.

Purpose To determine if sex is associated with corneal epithelial wound healing time in patients with persistent corneal epithelial defects (PCEDs). Methods Retrospective case series on patients with PCED from November 2014 to January 2019. Records of 127 patients with diagnosis of PCED were reviewed. Patients with an epithelial defect that lasted more than two weeks in the absence of an active corneal infection were included. Main outcome was corneal epithelial wound healing time. Results 55 patients (29 males) with a mean age of 65.3 ± 16.5 years were included. No difference was found between female and male patients in terms of risk factors, age, treatment strategies or intervals between visits (median of 15 days in females and 12 days in males; p = 0.24). Median duration of the PCED was 51 days (IQR 32-130), with a median number of 5 clinical visits (IQR 4-8). Female patients had significantly longer healing times (p = 0.004) and a corresponding increase in the number of clinical visits (median of 7 visits vs. 5 clinical visits in males, p = 0.012). Conclusion Results from this study suggest female patients with PCED might have a longer corneal epithelial wound healing duration and may therefore require earlier intervention.

Australia monitors its polio-free status by conducting surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years of age, as recommended by the World Health Organization (WHO). Cases of AFP in children are notified to the Australian Paediatric Surveillance Unit or the Paediatric Active Enhanced Disease Surveillance System and faecal specimens are referred for virological investigation to the National Enterovirus Reference Laboratory. In 2020, no cases of poliomyelitis were reported from clinical surveillance; Australia reported 1.09 non-polio AFP cases per 100,000 children, thereby meeting the WHO’s performance criterion for a sensitive surveillance system. The non-polio enteroviruses coxsackievirus A10 and coxsackievirus A16 were identified from clinical specimens collected from AFP cases. Australia also performs enterovirus surveillance and environmental surveillance to complement the clinical system focussed on children. In 2020, there were 140 cases of wild poliovirus reported from the two remaining endemic countries: Afghanistan and Pakistan. Another 28 countries reported cases of circulating vaccine-derived poliovirus.

Infection from the opportunistic pathogen Pseudomonas aeruginosa is one of leading causes of disability and mortality worldwide and the world health organisation has listed it with the highest priority for the need of new antimicrobial therapies. P. aeruginosa strains responsible for the poorest clinical outcomes express either ExoS or ExoU, which are injected into target host cells via the type III secretion system (T3SS). ExoS is a bifunctional cytotoxin that promotes intracellular survival of invasive P. aeruginosa by preventing targeting of the bacteria to acidified intracellular compartments and lysosomal degradation. ExoU is a potent phospholipase which causes rapid destruction of host cell plasma membranes, leading to acute tissue damage and bacterial dissemination. Fluoroquinolones are usually employed as a first line of therapy as they have been shown to be more active against P. aeruginosa in vitro than other antimicrobial classes. However, their overuse over the past decade has caused alarming rates of antibiotic resistance to emerge. In certain clinical situations, aminoglycosides have been shown to be more effective then fluoroquinolones, despite their reduced potency towards P. aeruginosa in vitro. In this study, we evaluated the effects of fluoroquinolones (moxifloxacin and ciprofloxacin) and aminoglycosides (tobramycin and gentamycin) on T3SS expression and toxicity, in corneal epithelial cell infection models. We discovered tobramycin disrupted T3SS expression and inhibited both ExoS and ExoU mediated cytotoxicity, protecting infected HCE-T cells even at concentrations below the minimal inhibitory concentrations (MIC). Fluoroquinolones moxifloxacin and ciprofloxacin, however, upregulated the T3SS and in particular did not subvert the cytotoxic effects of ExoS and ExoU.

Concurrent outbreaks of circulating vaccine-derived poliovirus serotypes 1 and 2 (cVDPV1, cVDPV2) were confirmed in the Republic of the Philippines in September 2019 and were subsequently confirmed in Malaysia by early 2020. There is continuous population subgroup movement in specific geographies between the two countries. Outbreak response efforts focused on sequential supplemental immunization activities with monovalent Sabin strain oral poliovirus vaccine type 2 (mOPV2) and bivalent oral poliovirus vaccines (bOPV, containing Sabin strain types 1 and 3) as well as activities to enhance poliovirus surveillance sensitivity to detect virus circulation. A total of six cVDPV1 cases, 13 cVDPV2 cases, and one immunodeficiency-associated vaccine-derived poliovirus type 2 case were detected, and there were 35 cVDPV1 and 31 cVDPV2 isolates from environmental surveillance sewage collection sites. No further cVDPV1 or cVDPV2 have been detected in either country since March 2020. Response efforts in both countries encountered challenges, particularly those caused by the global COVID-19 pandemic. Important lessons were identified and could be useful for other countries that experience outbreaks of concurrent cVDPV serotypes.

This paper examines the relationship between the flow rate and outflow depth for flow in a rectangular pipe with the outflow running partially full of a free nappe through a series of compu...

Quantifying evaporative loss from reservoirs plays a critical role in sound water-availability management plans and in reservoir management. Various methods are used to quantify reservoir evaporation; however, each method carries a degree of uncertainty that propagates to model predictions of available water within a reservoir or a reservoir network. Herein, we explore the impact of uncertainty in reservoir evaporation on model outputs of historical and future water availability throughout the five major reservoirs in the Savannah River Basin in South Carolina, USA, using four different evaporation methods. Variability in the total available water is evaluated using the United States Army Corps of Engineers (USACE) 2006 Drought Contingency Plan hydrologic model of the Savannah River Basin, which incorporates recent water-management plans and reservoir controls. Results indicate that, during droughts, reservoir evaporation plays a large role in water-availability predictions, and uncertainty in evaporative losses produces significant uncertainty in modeled water availability for extreme events. For example, the return period for an event in which the availability of water in Lake Hartwell was reduced to 50% of full pool capacity varied from 38.2 years to 53.4 years, depending on the choice of evaporation parameterization. This is a variation of 40% in the return period, depending on the choice of evaporation method.

BackgroundSelective lamellar corneal transplantation (keratoplasty) has overtaken full thickness penetrating keratoplasty as the graft choice for endothelial failure. Even more recently eye bank prepared tissues are becoming increasing popular as a way to reduce the risks of tissue loss and stress during endothelial keratoplasty preparation in the surgical theatre. This study compares costs between surgeon and eye bank prepared tissues for Descemet’s stripping automated endothelial keratoplasty (DSAEK) and Descemet’s membrane endothelial keratoplasty (DMEK).MethodsRetrospective study conducted at the Royal Liverpool University Hospital including endothelial keratoplasties with a minimum of 6 months follow-up time. Cost analysis included surgical expenses, tissue acquisition fees, cost of patient’s ward admission and out-patient expenses, including cost of re-bubbling procedures, costs of visits, anterior segment imaging and optometrist visits within the first 6 months follow-up.ResultsNinety-eight eyes of 98 patients were included in the study of which 42 underwent DSAEK surgery and 56 DMEK surgery. Cost analysis of surgical expenses in the DSAEK group showed a significant difference between using surgeon prepared and eye bank prepared tissue (£3866 ± 296 and £4389 ± 360, respectively;p p ConclusionsAt the Royal Liverpool University Hospital, eye bank prepared tissues had higher surgical expenses compared to those prepared by the surgeon, while the post-operative care expenses were similar between the two groups.

PURPOSE To describe a method to center a Descemet stripping automated endothelial keratoplasty lamellar graft and address interface folds. METHODS A novel technique to center a Descemet stripping automated endothelial keratoplasty graft without undue manipulation of endothelial surface using a STC-6 needle passed obliquely through the anterior corneal surface to engage and progress the lenticule along the posterior surface after injection of air. RESULT Centration of graft achieved and macroscopic folds resolved. CONCLUSIONS Here, we describe an atraumatic and reproducible method for graft centration.

To investigate the role of an internal limiting membrane (ILM) flap in macular hole (MH) surgery on closure rate, visual acuity, and integrity of the outer retinal layers.Retrospective, nonrandomized interventional analysis in which 117 eyes of 117 patients were included who had undergone pars-plana vitrectomy (PPV) and gas tamponade for primary idiopathic MH400 µm with either conventional ILM peeling or with inverted ILM flap technique at The Royal Liverpool University Hospital between January 2016 and April 2018. Main outcome measures were closure of MH, best-corrected visual acuity (BCVA) at 3, 6, and 12 months, and restoration of external limiting membrane and ellipsoid zone (EZ) using optical coherence tomography.Macular hole closure rate was significantly higher in patients with an ILM flap (67/68; 98.53%) than in those with conventional ILM peeling (43/49; 87.76%) (P = 0.02). Both groups showed significant improvements in their preoperative to postoperative BCVA at 3 months from 1.07 (0.43) logarithm of the minimum angle of resolution (logMAR) (20/235 Snellen) to 0.71 (0.34) logMAR (20/103 Snellen) (P0.001), but there was no significant difference between the two groups (P = 0.45, P = 0.71). We found significant associations between postoperative BCVA and preoperative BCVA (P0.01) and the integrity of the EZ (P0.01). In 35 patients who had follow-up to 12 months, there was a significant improvement in BCVA between 3, 6, and 12 months from 0.73 (0.45) logMAR (20/107 Snellen) to 0.53 (0.24) logMAR (20/68 Snellen) and to 0.35 (0.18) logMAR (20/45 Snellen), respectively (P0.01). There was no significant difference at these time periods between the two groups (P = 0.62, P = 0.21, P = 0.31). The integrity of the EZ also improved significantly between 3, 6, and 12 months (P = 0.01), irrespective of the presence of an ILM flap (P = 0.58), but with a trend toward delay in restoration in those patients with an ILM flap. The improvement in BCVA at 12 months, taking into account the age of the patient, size and duration of the MH, presence of an ILM flap, and preoperative BCVA was dependent on the state of the EZ (P = 0.01).In patients undergoing primary pars-plana vitrectomy for MH400 µm, the presence of an inverted ILM flap was associated with a significantly higher closure rate than a conventional ILM peeling. Best-corrected visual acuity showed a strong correlation with the integrity of the EZ and both improved significantly between 3, 6, and 12 months, irrespective of the presence of an ILM flap.

Candida parapsilosis has been considered an emerging pathogen with increasing incidence reported in the literature. As a normal commensal of human skin, it is likely that Candida species could gain access to soft tissues of the hand and wrist by direct inoculation, resulting in an infectious tenosynovitis. With the increased prevalence of intravenous drug use (IVDU), users are at increasing risk for musculoskeletal infections including soft tissue abscesses, cellulitis, tenosynovitis, and septic arthritis. Chronic tenosynovitis, with rice body formation in particular, is a comparatively rare musculoskeletal infection. Knowledge of this entity, the related pathogens, imaging findings, and the treatment plan is important not only to the treating clinician, but also to radiologists as the physiological and anatomic consequences can be detrimental to patient recovery. Keywords: Candida Parapsilosis, Extensor tendon, Wrist, Intravenous drug use

AimsTo investigate the relative risk of pretransplant corneal vascularisation on rate of rejection and graft failure within 5 years of surgery when categorised by indication for transplantation.We analysed all adults recorded in the UK transplant registry who had a first cornea transplant for keratoconus (KC), pseudophakic bullous keratopathy (PBK) or previous infection (viral/bacterial/fungal/protozoan) between 1999 and 2017. We analysed the number of quadrants of the recipient cornea vascularised before transplant and type of vascularisation, the interval post-transplant to rejection, if any, and the outcome at 5 years post-transplant. Risk factors for rejection and transplant failure were modelled by multivariable risk-adjusted Cox regression.ResultsCorneal vascularisation was recorded in 10%, 25% and 67% of patients with KC, PBK and infection, respectively. Individuals with PBK had an increased hazard of transplant rejection only when there were more than two quadrants of vascularisation (HR 1.5, p=0.004) when either superficial and/or deep vascularisation was present (HR 1.3 and 1.4, respectively, p=0.004). Individuals who had a transplant for previous infection had an increased hazard of rejection with four quadrants of vascularisation (HR 1.6, p=0.003). There was no risk-adjusted increase in transplant failure associated with vascularisation in any group. There was weak evidence of reduction in risk of rejection and/or failure associated with lamellar compared with penetrating transplantation in KC and PBK in vascularised recipient corneas.ConclusionVascularisation is a risk factor for corneal allograft rejection within 5 years. The indication for transplantation has a clinically significant effect on the magnitude of this risk.

Purpose To investigate if the peripheral corneal endothelium that is discarded after the preparation of preloaded Descemet membrane endothelial keratoplasty (DMEK) grafts for transplantation could be successfully used for corneal endothelial cell culture. Methods Complete Descemet membrane-endothelial complex (11.00 mm) was peeled from research-grade tissues (n = 15). The periphery (2.75 mm) of clinical-grade tissues (n = 15) deemed for preloaded DMEK transplants was gently peeled and preserved for 48 hours in tissue culture media, followed by centrifugation at 1000 rpm for 5 minutes. After enzymatic digestion, the cells from each group were plated in 2 different wells of an 8-well chamber slide. Media were refreshed and the confluence rate was monitored every alternate day. Live/dead staining and the expression of ZO-1, Tag1A3, Tag2A12, and Ki-67 markers were used to assess the viability, morphology, tight-junctions, cell area, and number of proliferative cells. The Wilcoxon and Student's t test were applied, where P Results Average endothelial cell density at confluence was 2,352 cells/mm2 from complete endothelium and 2,510 cells/mm from peripheral endothelium (P = 0.0351). The confluence rate (%), hexagonality (%), polymorphism (%), cell area (μm), and Ki-67 positivity (%) did not differ between both groups (P > 0.05). All the antibodies were expressed in both groups at confluence. Conclusions The discarded peripheral endothelial cells obtained after preparing a preloaded DMEK graft for clinical application has a huge reservoir of healthy endothelial cells having proliferative potential. Using these discarded tissue pieces from donor tissues will significantly increase the primary source of healthy donor endothelial cells for regenerative treatments, which are otherwise difficult to obtain.

We assessed the effectiveness of an integrated engineering public-speaking class relative to a traditionally taught public-speaking class. The integrated class was designed to meet the grow...

Purpose To investigate the effect of dehydration on human donor corneal stroma for biobanking. Methods Epithelium and endothelium of research-grade human donor corneas (n = 12) were scraped off, leaving a bare stroma with attached sclera. The tissues were placed in a large Petri dish prefilled with silica gel in the periphery and stored at room temperature for 14 days. At the end of preservation, the tissues were rehydrated by being submerged in phosphate-buffered saline for 15 minutes. Transparency (using a custom-built device) and thickness (using optical coherence tomography) measurements were recorded before dehydration, after dehydration, and after rehydration of the tissues. Periodic acid-Schiff and alpha-smooth muscle actin (α-SMA) staining before dehydration and after rehydration were performed to determine the presence of keratocytes and expression of α-SMA. Tensile stress-strain before dehydration and after rehydration was performed to evaluate the biomechanical properties. Results No difference in corneal transparency before dehydration (69.57 ± 6.41%) and after rehydration (67.37 ± 2.82%), P = 0.36, was observed. The corneas were more compact after dehydration. A significant change in thickness between before dehydration (625.8 ± 75.58 μm) and after rehydration (563.6 ± 15.77 μm) stage, P = 0.03, was noticed. The thickness was reduced to 147.6 ± 3.71 μm when dehydrated. Periodic acid-Schiff staining showed presence of stromal keratocytes and α-SMA protein expressed in control, dehydrated, and rehydrated corneas. There was no significant difference in the stiffness between control (27.86 ± 11.65 MPa) and rehydrated corneas (31.46 ± 11.41 MPa). Conclusions Human donor corneal stroma can be biobanked for up to 2 weeks in a dehydrated condition without losing their molecular or biomechanical properties after rehydration.

Purpose To compare methods for evaluating refractive outcomes after cataract surgery to detect outliers. Design Case series database study of the evaluation of diagnostic technology. Participants Consecutive patients who had uneventful cataract operations over a 5-year period. Methods The intended and postoperative refractive outcome and differences between these were analyzed as a spherical equivalent, cylinder, and spherocylinder. The average keratometry and differences between steep and flat keratometric meridians were used to calculate the intended refractive error. Main Outcome Measures Outliers were defined as patients for whom the difference between the intended and postoperative refractive errors was more than 3 standard deviations (SDs) away from the mean. Results A total of 9000 patients were included. Twelve patients had missing data and were excluded. The mean intended refractive outcome was −0.12+0.12×2 (95% lower confidence limit [LCL], −1.94+1.06×44; 95% upper confidence limit [UCL], +0.77+1.05×140). The actual postoperative refractive error was −0.30+0.47×6 (95% LCL, −2.36+1.31×36; 95% UCL, +1.00+1.18×148) with a difference from the intended of −0.18+0.35×7 (95% LCL, −1.91+1.22×38; 95% UCL, +0.75+1.09×145). Treating the components of the refractive error independently, outliers were observed in 82 eyes (0.91%) based on the sphere, 46 eyes (0.51%) based on the spherical equivalent, 115 eyes (1.28%) based on treating the cylinder as a scalar, and 76 eyes (0.85%) based on treating the cylinder as a vector. When the differences between the intended and postoperative refractive errors were calculated as a compound spherocylinder, outliers were observed for 233 eyes (2.59%). Conclusions Treating the intended refractive outcome as a spherocylinder improves the precision for detecting clinically significant refractive outliers.