Staphylococcal biofilm: penetration and bioavailability of vancomycin with or without rifampin.

We measured antibiotic penetration and bioavailability in staphylococcus biofilms using simulated humanized concentrations of fluorescent vancomycin plus or minus rifampin. Vancomycin percent recovery across biofilm layers was:upper = 46%, middle = 40%, and lower = 33%. Vancomycin plus rifampin was not significantly different (P = 0.65). Addition of rifampin did not improve vancomycin penetration across biofilm layers.

A rare case of gastric varices and splenic artery aneurysm secondary to splenic arteriovenous fistula.

A 33-year-old male with no relevant medical history presented with a few months of fatigue and reduced exercise tolerance and was found to have iron-deficiency anemia. An esophagogastroduodenoscopy revealed a cluster of isolated gastric fundal varices with high-risk stigmata. Serologic workup for cirrhosis was negative, and a FibroScan measured liver stiffness at 4.2 kilopascals. Computed tomography (CT) of his abdomen and pelvis showed non-cirrhotic portal hypertension, as well as the presence of a splenic arteriovenous (AV) fistula and splenic artery aneurysm (SAA). Resection of the fistula, SAA, and spleen completely resolved the gastric varices and anemia.

A MULTICENTER REVIEW EVALUATING THE RISK OF RHEGMATOGENOUS RETINAL DETACHMENT POST ENDOPHTHALMITIS: A Canadian Retina Research Network Investigation.

PURPOSE: To describe the characteristics of rhegmatogenous retinal detachments (RDs) that developed after endophthalmitis and to provide insight regarding incidence, management, and outcomes. METHODS: Retrospective chart review of consecutive patients diagnosed with endophthalmitis at two Canadian institutions and from one surgeon at a third center over a 10-year period. RESULTS: Three hundred sixteen eyes presented with endophthalmitis of which 32 (10%) were complicated by subsequent RD. The mean age (SD) of patients was 72.0 (13.77) years. Intravitreal injections (33%) and cataract surgery (31%) were the most common inciting events for the endophthalmitis. Cases were managed with tap and inject (16%), vitrectomy (30%), or both (47%). There were no differences in the rate of RD when comparing the inciting events, microbial growth, or management approaches. Baseline visual acuity was the only predictor of RD ( P = 0.009). There was an improvement in visual acuity following management of the RD (logarithm of the minimum angle of resolution 2.33 vs. 1.69 or Snellen hand motion vs. 20/980, P = 0.009), but final visual acuity in these patients was worse than in those who did not develop RD (logarithm of the minimum angle of resolution 1.69 vs. 1.27 or Snellen 20/980 vs. 20/372, P = 0.029). CONCLUSION: All patients with RD post endophthalmitis required additional surgery, and functional outcomes remained poor. Nevertheless, repair of these RDs can preserve some vision and be globe saving.

Long-Term Efficacy of a Treat-and-Extend Regimen with Ranibizumab in Patients with Neovascular Age-Related Macular Disease: An Open-Label 12-Month Extension to the CANTREAT Study.

INTRODUCTION: The objective of this study is to assess the long-term effectiveness of a treat-and-extend (T&E) anti-vascular endothelial growth factor regimen in patients with neovascular age-related macular degeneration who remain on T&E and those switched from once-monthly (OM) dosing to T&E (OM-T&E). METHODS: In this 12-month extension of the 2-year CANTREAT study, patients received intravitreal ranibizumab 0.5 mg in a T&E regimen. Main outcome measures included mean change in best-corrected visual acuity (BCVA) from baseline and from month 24 to month 36; percentages of patients who gained ≥5, ≥10, or ≥15 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters or lost ≥5, ≥10, or ≥15 letters from baseline and from month 24 to month 36; and number of injections administered from baseline and from month 24 to month 36 for both groups. RESULTS: Of the 139 patients (73 T&E, 66 OM-T&E) in the extension, 121 (68 T&E, 53 OM-T&E) completed 36 months. Mean (standard deviation [SD]) BCVA changes from baseline to the extension last visit (month 33-36) were +6.6 (11.4) letters in the T&E group and +4.8 (14.3) letters in the OM-T&E group, representing maintenance of 24-month gains. The mean (SD) numbers of injections during the extension were 7.3 (2.7) for T&E and 7.1 (2.8) for OM-T&E. DISCUSSION/CONCLUSION: These findings suggest that after 36 months of treatment, the mean BCVA improvement achieved at 24 months is maintained for both the patients exclusively treated with the T&E regimen and those that switched to T&E after 24 months in the OM regimen.

Understanding and managing the interactive impacts of growth in urban land use and climate change on freshwater biota: A case study using the platypus (Ornithorhynchus anatinus).

Globally, urban expansion and climate change interact to threaten stream ecosystems and are accelerating the loss of aquatic biodiversity. Waterway managers urgently need tools to understand the potential combined impacts of urbanization and climate change and to identify effective mitigating management interventions for protecting freshwater biota. We address this challenge using the semi-aquatic mammal the platypus (Ornithorhynchus anatinus) as a focal species. We developed high-resolution environmental spatial data for stream networks and spatially explicit habitat suitability models (HSMs) to explore the impact of threats and to identify the combination of management actions most likely to maintain or improve habitat suitability over the next 50 years in greater Melbourne, Australia. We developed and evaluated platypus HSMs (males-and-females and females-only) including validation using an independent environmental DNA data set. Platypus occurred more commonly in larger, cooler streams with greater catchment-weighted discharge, following periods of greater stream flow. They were positively associated with near-stream forest cover and negatively associated with annual air temperature and urban stormwater runoff. Extensive reductions in suitable platypus habitat are predicted to occur under urbanization and climate change scenarios, with the greatest threat expected from reduced streamflows. This emphasizes the importance of maintaining flow regimes as part of conserving platypus in the region; however, substantial additional benefit is predicted by concurrent riparian revegetation and urban stormwater management efforts (that also have the potential to contribute to the streamflow objectives). Provision of adequate streamflows in a future with increasing water demands and water security requirements will likely require creative integrated water management solutions. Our high-resolution stream network and HSMs have allowed predictions of potential range-shifts due to urban expansion and climate change impacts at management-relevant scales and at the whole-of-landscape scale. This has enabled systematic strategic planning, priority action planning and target setting in strategic policy development.

Entomopathogenic nematode management of small hive beetles (Aethina tumida) in three native Alabama soils under low moisture conditions.

The goal was to determine the efficacy of entomopathogenic nematodes (EPNs) on Aethina tumida small hive beetle (SHB) in Alabama soils. The objectives were to (i) determine the pupation success of SHB wandering larvae; (ii) determine the efficacy of EPNs on SHB wandering larvae in natural and autoclaved soil; and (iii) determine the efficacy of EPNs on SHB wandering larvae in three Alabama soil types at typical low moisture levels. The Alabama soils were Kalmia loamy sand (KLS), Benndale fine sandy loam (BFSL), and Decatur silt loam (DSL). Heterorhabditis bacteriophora, H. indica, Steinernema carpocapsae, S. feltiae, S. kraussei, and S. riobrave were tested at population densities of 5, 10, 20, 40, and 80 third-stage infective EPN juveniles (IJ3) per 130 cm3 soil. Pupation success in SHB population densities of 5, 10, and 20 wandering larvae per Petri dish were similar. Of the six EPN species, S. carpocapsae achieved the highest efficacy across all EPN population densities in both natural and autoclaved soil. Steinernema riobrave and H. indica achieved the next highest efficacies; however, they were significantly less effective than S. carpocapsae. Steinernema carpocapsae parasitized 87% SHB wandering larvae across all population densities tested. Steinernema carpocapsae achieved the best efficacy colonizing 94% of the SHB in the KLS soil, 80% in the BFSL soil, and 47% in the DSL soil. In conclusions, S. carpocapsae is be a promising biological control EPN to implement into a management system on SHB.

Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse.

Efficacy of a Treat-and-Extend Regimen With Ranibizumab in Patients With Neovascular Age-Related Macular Disease: A Randomized Clinical Trial.

Importance: Although the Canadian Treat-and-Extend Analysis Trial With Ranibizumab in Patients With Neovascular Age-Related Macular Disease (CANTREAT) reported herein and the Treat and Extend study provided data to show noninferiority of treat-and-extend (T&E) at 12 months, to date there are few data on 24-month T&E trials compared with monthly dosing. Objective: To compare the efficacy of ranibizumab using a T&E regimen to monthly dosing in treatment-naive patients with neovascular age-related macular degeneration (nAMD) after 24 months. Design, Setting, and Participants: A randomized, open-label, multicenter, noninferiority intention-to-treat trial with a margin of -5 letters in best-corrected visual acuity (BCVA) from baseline to 12 months between groups was conducted at 27 treatment centers in Canada. Participants included 580 patients with treatment-naive choroidal neovascularization secondary to AMD. The study was conducted from May 8, 2013, to August 28, 2018, and data analysis was performed between August 29 and September 12, 2018. Interventions: Patients with nAMD were randomized 1:1 to receive intravitreal ranibizumab, 0.5 mg, in either a T&E or monthly dosing regimen. Main Outcomes and Measures: Mean change in BCVA in Early Treatment of Diabetic Retinopathy Study letters from baseline to month 24. Results: Of the 580 randomized patients, 350 were women (60.3%) and 547 were white (94.3%). Mean (SD) age was 78.8 (7.8) years. By the end of month 24, 466 of the 580 randomized patients (80.3%) had completed the study and participants in the T&E arm received a mean of 17.6 injections compared with 23.5 injections for the monthly arm, for a difference of 5.9 injections and visits over 2 years (95% CI, 5.4-6.5; P < .001). The mean (SD) BCVA improvement was not worse with the T&E arm, 6.8 (14.1) letters vs 6.0 (12.6) letters, compared with the monthly arm (difference, 0.9; 95% CI, -1.6 to 3.3; P = .21). There was a gain of 15 or more letters in 25.5% of the T&E group and 23.1% of the monthly treatment group (difference, 2.4%; 95% CI, -6.8% to 11.6%; P = .59) and a loss of 15 or more letters in 6.5% of the T&E group and 5.8% of the monthly treatment group (difference, -0.7%; 95% CI, -9.9% to 8.5%; P = .85). Conclusions and Relevance: These findings suggest that change in vision from baseline is not worse with a T&E compared with a monthly regimen of ranibizumab for nAMD through 24 months, achieving clinically meaningful improvements in BCVA despite fewer injections and visits. Trial Registration: ClinicalTrials.gov identifier: NCT02103738.

OUTCOMES OF VITRECTOMY IN TERSON SYNDROME: A Multicenter Canadian Perspective.

PURPOSE: To characterize the presentation of Terson syndrome, the occurrence of a vitreous hemorrhage in association with intracranial hemorrhage, and report on the outcomes of vitrectomy at two major centers in Canada. METHODS: Retrospective chart review of consecutive patients with Terson syndrome undergoing vitrectomy by retina specialists over the last 10 years. Primary outcome was the change in best-corrected visual acuity (BCVA) at 3 months from baseline. Secondary outcomes included the association between baseline BCVA and final BCVA, and the association between final BCVA and timing of surgery (early vs. later than 90 days). RESULTS: A total of 14 eyes of 11 patients were included. The mean time between observation of intraocular hemorrhage and vitrectomy was 160 days. Baseline preoperative BCVA was logarithm of the minimum angle of resolution 1.57 ± 1.03 (Snellen 20/740), which improved to logarithm of the minimum angle of resolution 0.53 ± 0.82 (Snellen 20/70) at the final postoperative follow-up, P = 0.01. Baseline BCVA was not significantly correlated with final BCVA, Spearman's rho = 0.016, P = 0.957. Final BCVA did not significantly differ between those who had surgery before 90 days compared with after 90 days, P = 0.087. CONCLUSION: Vitrectomy is safe and effective and should be considered for nonclearing vitreal bleeding due to Terson syndrome. Ocular hemorrhaging in Terson syndrome can be observed conservatively for spontaneous improvement without the risk of reduced visual potential. Ophthalmic evaluation should be considered promptly after intracranial hemorrhage.

The platypus: evolutionary history, biology, and an uncertain future.

The platypus (Ornithorhynchus anatinus) is one of the world's most evolutionarily distinct mammals, one of five extant species of egg-laying mammals, and the only living species within the family Ornithorhynchidae. Modern platypuses are endemic to eastern mainland Australia, Tasmania, and adjacent King Island, with a small introduced population on Kangaroo Island, South Australia, and are widely distributed in permanent river systems from tropical to alpine environments. Accumulating knowledge and technological advancements have provided insights into many aspects of its evolutionary history and biology but have also raised concern about significant knowledge gaps surrounding distribution, population sizes, and trends. The platypus' distribution coincides with many of Australia's major threatening processes, including highly regulated and disrupted rivers, intensive habitat destruction, and fragmentation, and they were extensively hunted for their fur until the early 20th century. Emerging evidence of local population declines and extinctions identifies that ecological thresholds have been crossed in some populations and, if threats are not addressed, the species will continue to decline. In 2016, the IUCN Red Listing for the platypus was elevated to "Near Threatened," but the platypus remains unlisted on threatened species schedules of any Australian state, apart from South Australia, or nationally. In this synthesis, we review the evolutionary history, genetics, biology, and ecology of this extraordinary mammal and highlight prevailing threats. We also outline future research directions and challenges that need to be met to help conserve the species.

Lid splinting eyelid retraction technique: a minimised sterile approach for intravitreal injections.

BACKGROUND/AIMS: To describe an alternative technique for avoiding contact with the lids and lashes, without the use of a lid speculum, during intravitreal anti-vascular endothelial growth factor injections. METHODS: Retrospective case series of all patients undergoing intravitreal injections of bevacizumab and ranibizumab, with the lid splinting retraction technique from January 2010 to December 2015. Injections performed by six vitreoretinal specialists were included. The key preinjection ocular surface preparation includes topical anaesthetic, 5% povidone-iodine and a subconjunctival injection of 2% lidocaine with epinephrine. A second instillation of 5% povidone-iodine is given and the intravitreal injection is then performed. No lid speculum is used. A search of the electronic medical records identified patients diagnosed with postinjection endophthalmitis and charts were reviewed to ensure inclusion criteria were met. The main outcome measure was incidence of postinjection endophthalmitis. RESULTS: A total of 78 009 consecutive intravitreal injections were performed, of which 22 207 were bevacizumab and 55 802 were ranibizumab. In this cohort of patients (n=6320), 12 cases of endophthalmitis developed, corresponding to a rate of 0.015%. CONCLUSIONS: The technique of eyelid retraction for intravitreal injection has a low rate of endophthalmitis, similar to the reported rates using a metal lid speculum. This is beneficial for both the physician and the patient as it minimises patient discomfort as well as the duration of the procedure. To our knowledge, this is one of the largest studies performed to date evaluating intravitreal injection-related endophthalmitis.

Reliability of EUS indices to detect inflammation in ulcerative colitis.

BACKGROUND AND AIMS: EUS is a potentially useful modality to assess severity of inflammation in ulcerative colitis (UC). We assessed the reliability of existing EUS indices and correlated them with endoscopic and histologic scores. METHODS: Four blinded endosonographers assessed 58 endoscopic and EUS videos in triplicate, from patients with UC. Intrarater and interrater reliability of the hyperemia and Tsuga scores were estimated by using intra-class correlation coefficients (ICCs). Correlation with the Mayo endoscopy score, modified Baron score (MBS), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Geboes histopathology score (GHS) were calculated by using bootstrapping methods. A RAND consensus process led to development of standardized definitions and a revised EUS-UC score. RESULTS: ICCs for intrarater reliability were 0.76 (95% confidence interval [CI], 0.71-0.80) for the hyperemia score and 0.85 (95% CI, 0.79-0.89) for the Tsuga score. Corresponding values for interrater reliability were 0.34 (95% CI, 0.25-0.42) and 0.36 (95% CI, 0.24-0.46). Correlation between hyperemia and Tsuga scores to Mayo scoring system, MBS, UCEIS, and the GHS were 0.39 (95% CI, 0.15-0.61) and 0.28 (95% CI, 0.04-0.51), 0.38 (95% CI, 0.16-0.57) and 0.25 (95% CI, -0.01-0.48), 0.41 (95% CI, 0.16-0.62) and 0.27 (95% CI, 0.01-0.50), 0.37 (95% CI, -0.01-0.48) and 0.24 (95% CI, 0.13-0.57), respectively. The revised EUS-UC score included bowel wall thickening, depth of inflammation, and hyperemia. CONCLUSIONS: Although substantial to almost perfect intrarater agreement existed for EUS indices in UC, interrater agreement was fair. Standardization of item definitions with development of a revised evaluative instrument has potential application as an evaluative and prognostic tool for UC. (Clinical trial registration number: NCT01852760.).

A web portal for in-silico action potential predictions.

INTRODUCTION: Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models are proposed as one way of predicting the integrated compound effects on whole-cell electrophysiology, to provide an improved indication of pro-arrhythmic risk. METHODS: We have developed open source software to run cardiac electrophysiology simulations to predict the overall effect of compounds that block IKr, ICaL, INa, IKs, IK1 and Ito to varying degrees, using a choice of mathematical electrophysiology models. To enable safety pharmacology teams to run and evaluate these simulations easily, we have also developed an open source web portal interface to this simulator. RESULTS: The web portal can be found at https://chaste.cs.ox.ac.uk/ActionPotential. Users can enter details of compound affinities for ion channels in the form of IC50 or pIC50 values, run simulations, store the results for later retrieval, view summary graphs of the results, and export data to a spreadsheet format. DISCUSSION: This web portal provides a simple interface to reference versions of mathematical models, and well-tested state-of-the-art equation solvers. It provides safety teams easy access to the emerging technology of cardiac electrophysiology simulations for use in the drug-discovery process.

Confronting Auditory Hallucinations Using Virtual Reality: The Avatar Therapy.

The AVATAR therapy is a computer-based intervention which aims to reduce the frequency and severity of voices. The approach is based on computer technology which enables each patient to create an avatar of the entity (human or non-human) that they believe is talking to them. The therapist promotes a dialogue between the patient and the avatar in which the avatar progressively comes under the patient's control. Using real-time voice conversion delivery software, the therapist can modify the relationship between the patient and his/her voice. The innovation of this new intervention is discussed in the present paper as well as the advantages of using a computer based system. The subjective view of the technology from a participant's point of view is also presented.

Evaluation of an in silico cardiac safety assay: using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge.

INTRODUCTION: Drugs that prolong the QT interval on the electrocardiogram present a major safety concern for pharmaceutical companies and regulatory agencies. Despite a range of assays performed to assess compound effects on the QT interval, QT prolongation remains a major cause of attrition during compound development. In silico assays could alleviate such problems. In this study we evaluated an in silico method of predicting the results of a rabbit left-ventricular wedge assay. METHODS: Concentration-effect data were acquired from either: the high-throughput IonWorks/FLIPR; the medium-throughput PatchXpress ion channel assays; or QSAR, a statistical IC50 value prediction model, for hERG, fast sodium, L-type calcium and KCNQ1/minK channels. Drug block of channels was incorporated into a mathematical differential equation model of rabbit ventricular myocyte electrophysiology through modification of the maximal conductance of each channel by a factor dependent on the IC50 value, Hill coefficient and concentration of each compound tested. Simulations were performed and agreement with experimental results, based upon input data from the different assays, was evaluated. RESULTS: The assay was found to be 78% accurate, 72% sensitive and 81% specific when predicting QT prolongation (>10%) using PatchXpress assay data (77 compounds). Similar levels of predictivity were demonstrated using IonWorks/FLIPR data (121 compounds) with 78% accuracy, 73% sensitivity and 80% specificity. QT shortening (<-10%) was predicted with 77% accuracy, 33% sensitivity and 90% specificity using PatchXpress data and 71% accuracy, 42% sensitivity and 81% specificity using IonWorks/FLIPR data. Strong quantitative agreement between simulation and experimental results was also evident. DISCUSSION: The in silico action potential assay demonstrates good predictive ability, and is suitable for very high-throughput use in early drug development. Adoption of such an assay into cardiovascular safety assessment, integrating ion channel data from routine screens to infer results of animal-based tests, could provide a cost- and time-effective cardiac safety screen.

Canadian expert consensus: optimal treatment of neovascular age-related macular degeneration.

BACKGROUND: New therapeutic approaches, particularly anti-vascular endothelial growth factor (anti-VEGF) therapies, prevent, and in some cases reverse, vision damage caused by age-related macular degeneration (AMD). Unequal access to care across Canada remains a problem for many retina specialists and their patients. OBJECTIVE: To develop a consensus concerning the management of patients with exudative age-related macular degeneration (AMD). DESIGN: Consensus document. PARTICIPANTS: Ten Canadian retina specialists. METHODS: The development of a consensus among Canadian experts concerning optimal treatment of AMD began with a review of the clinical evidence, daily practices, existing guidelines, and current national and international approvals and policies. The experts met on June 29, 2010, in Quebec City to discuss their findings and to propose strategies for consensus. RESULTS: The result of this expert panel is a consensus proposal for Canadian ophthalmologists and retina specialists who are treating patients with or at risk for developing neovascular AMD. CONCLUSIONS: The consensus provides guidelines to aid retina specialists in managing exudative AMD. Currently, ranibizumab is the only agent with sufficient Level I evidence and a Health Canada-approved indication for the treatment of wet AMD. Bevacizumab has been shown to be noninferior in preserving and improving visual acuity when compared to ranibizumab. Potential safety differences between the 2 drugs remain to be elucidated. The positioning of ranibizumab in this therapeutic area will be further defined as additional data for existing and emerging therapies become available. Until then, this agent remains the therapy of choice for individuals with neovascular AMD.

Exciton diffusion in polyfluorene copolymer thin films: kinetics, energy disorder and thermally assisted hopping.

A series of {(9,9-dioctylfluorene)(0.7-x)-(dibenzothiophene-S,S-dioxide)(0.3)-[4,7-bis(2-thienyl)-2,1,3-benzothiadiazole](x)} (PFS(30)-TBTx), where x represents the minor percentage of the red emitter 4,7-bis(2-thienyl)-2,1,3-benzothiadiazole (TBT) randomly incorporated into the copolymer backbone, is investigated in order to follow the energy transfer from PFS(30) to TBT moieties. The emission of the donor poly[(9,9-dioctylfluorene)(0.7)-(dibenzothiophene-S,S-dioxide)(0.3) identified by PFS(30) and peaking at 450 nm, is clearly quenched by the presence of the red TBT chromophore emitting at 612 nm, with an isoemissive point observed when the spectra are collected as a function of temperature. A plot of the ratio between the TBT and PFS(30) emissions as a function of the reciprocal of temperature gives a clear linear trend between 290 and 200 K, with an activation energy of 20 meV and showing a turn over to a non-activated regime below 200 K. Picosecond time-resolved fluorescence decays collected at the PFS(30) and TBT emission wavelengths, show a decay of the PFS(30) emission and a fast build-in, followed by a decay, of the TBT emission, confirming that the population of the TBT excited state occurs during the PFS(30) lifetime (approximately 600 ps). The population of the TBT excited state occurs on a time regime around 150 ps at 290 K, showing an energy barrier of 20 meV that turns over to a non-activated regime below 200 K in clear agreement with the steady-state data. The origin of the activation barrier is attributed to the presence of physical and energetic disorder, affected by fast thermal fluctuations that dynamically change the energy landscape and control the exciton migration through the polymer density of states.

Telemedicine approach to screening for severe retinopathy of prematurity: a pilot study.

PURPOSE: To evaluate the use of remote reading of digital retinal photographs in the diagnosis of severe (referral-warranted) retinopathy of prematurity (ROP) during longitudinal screening for ROP. STUDY DESIGN: Prospective, longitudinal cohort study. SUBJECTS: Forty-four consecutive premature infants at risk for ROP. METHODS: All infants were examined longitudinally, over a series of examinations, by indirect ophthalmoscopy (gold standard) and digital photography using the RetCam-120 Digital Retinal Camera (Massie Research Laboratories Inc., Dublin, CA) equipped with an ROP lens. Images were stored and read remotely by a masked reader. Referral-warranted ROP was defined as ROP in zone 1, the presence of plus disease or the presence of any stage 3 ROP. We determined whether and when referral-warranted ROP was diagnosed for each eye, of each infant, on each examination, during the course of each of the infant's screening. RESULTS: Severe (referral-warranted) ROP was diagnosed in 23 eyes by indirect ophthalmoscopy during their series of examinations. Digital photography had a sensitivity of 100% and a specificity of 96% in detecting referral-warranted ROP. The positive predictive value of digital photography was 92%, and the negative predictive value was 100%. In 87% of eyes, referral-warranted ROP was diagnosed by digital photography before or at the same time as indirect ophthalmoscopy. CONCLUSIONS: Longitudinal remote reading of digital photographs using the RetCam-120 system has excellent specificity and sensitivity in detecting referral-warranted ROP. This pilot study has shown that remote reading of digital photographs has promise for telemedicine strategies in ROP screening.