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Sady Alpizar,1 Ayman Megally,2 Claudia Chen,3 Abhi Raj,4 John Downie,5 Gene Colice2 1Clinical Research Trials of Florida, Inc., Tampa, FL, USA; 2Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 3Biostatistics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 4Device Development, AstraZeneca, South San Francisco, CA, USA; 5Global Development Inflammation, Amgen, Thousand Oaks, CA, USACorrespondence: Ayman MegallyLate-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USATel +1703334-1796Fax +1301917-3211Email ayman.megally@astrazeneca.comBackground: Tezepelumab is an anti-thymic stromal lymphopoietin monoclonal antibody in development for the treatment of severe asthma. This study assessed the functionality and performance of an accessorized pre-filled syringe (APFS) and an autoinjector (AI) for administration of tezepelumab in the clinic and at home.Methods: This phase 3, multicenter, randomized, open-label, parallel-group study (PATH-HOME, ClinicalTrials.gov identifier: NCT03968978) was conducted in patients aged 12– 80 years with asthma that was uncontrolled despite treatment with medium- to high-dose inhaled corticosteroids plus at least one additional controller medication. Patients received six subcutaneous doses of tezepelumab 210 mg via APFS or AI. The first dose was administered by a healthcare professional, and patients or caregivers administered subsequent doses. First, second, third and final doses were administered in the clinic; fourth and fifth doses were administered at home. The primary endpoint was the proportion of successful administrations of tezepelumab. Secondary endpoints included the functionality and performance of the devices, Asthma Control Questionnaire (ACQ)-6 score, pharmacokinetics and safety.Results: Overall, 216 patients were randomized (APFS, n=111; AI, n=105). Tezepelumab was successfully administered via APFS by 91.7% of the participants (100/109) and via AI by 92.4% (97/105). Overall, 95.4– 97.1% of at-home administrations were successful across device groups. Malfunction occurred in 6 of 655 dispensed APFSs and 5 of 624 dispensed AIs. Clinically meaningful improvements in ACQ-6 score were observed after 24 weeks in 81.1% and 76.2% of the patients in the APFS and AI groups, respectively. Tezepelumab pharmacokinetics were consistent between device groups and with previous studies. The most common adverse event was nasopharyngitis (9.3%). Injection-site reactions occurred in 5.7% and 0% of the patients in the AI and APFS groups, respectively.Conclusion: This study demonstrated that the APFS and AI were functional and reliable, and performed equally well at home and in the clinic.Keywords: accessorized pre-filled syringe, at-home administration, autoinjector, severe asthma, tezepelumab

This paper investigates the benefit of using ultra-low-loss G.654.E fiber in the terrestrial section of PoP-PoP route in terms of GSNR improvement, higher fiber pair and cable capacity, and increased system value.

Purpose To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (TE intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 μm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome. Main Outcome Measures Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24. Results Of the 349 participants randomized (intensive arm, n = 174; relaxed arm, n = 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P = 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P = 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P = 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P = 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P = 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P = 0.005). Conclusions Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.

Background Patients with severe, uncontrolled asthma, particularly those with a non-eosinophilic phenotype, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine. In the PATHWAY phase 2b study (NCT02054130), tezepelumab reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline eosinophilic inflammatory status. This article reports the design and objectives of the phase 2 CASCADE study. Methods CASCADE is an ongoing exploratory, phase 2, randomized, double-blind, placebo-controlled, parallel-group study aiming to assess the anti-inflammatory effects of tezepelumab 210 mg administered subcutaneously every 4 weeks for 28 weeks in adults aged 18–75 years with uncontrolled, moderate-to-severe asthma. The primary endpoint is the change from baseline to week 28 in airway submucosal inflammatory cells (eosinophils, neutrophils, T cells and mast cells) from bronchoscopic biopsies. Epithelial molecular phenotyping, comprising the three-gene-mean technique, will be used to assess participants’ type 2 (T2) status to enable evaluation of the anti-inflammatory effect of tezepelumab across the continuum of T2 activation. Other exploratory analyses include assessments of the impact of tezepelumab on airway remodelling, including reticular basement membrane thickening and airway epithelial integrity. At the onset of the COVID-19 pandemic, the protocol was amended to address the possibility that site visits would be limited. The amendment allowed for: at-home dosing of study drug by a healthcare professional, extension of the treatment period by up to 6 months so patients are able to attend an onsite visit to undergo the end-of-treatment bronchoscopy, and replacement of final follow-up visits with a virtual or telephone visit. Discussion CASCADE aims to determine the mechanisms by which tezepelumab improves clinical asthma outcomes by evaluating the effect of tezepelumab on airway inflammatory cells and remodelling in patients with moderate-to-severe, uncontrolled asthma. An important aspect of this study is the evaluation of the anti-inflammatory effect of tezepelumab across patients with differing levels of eosinophilic and T2 inflammation. Trial registration NCT03688074 (ClinicalTrials.gov). Registered 28 September 2018.

Background Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. The efficacy, safety and oral corticosteroid-sparing potential of tezepelumab are being investigated in two ongoing, phase 3, randomized, double-blind, placebo-controlled studies (NAVIGATOR [NCT03347279] and SOURCE [NCT03406078]). DESTINATION (NCT03706079) is a long-term extension (LTE) of these studies. Methods DESTINATION is a randomized, double-blind, placebo-controlled LTE study in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. The study population will comprise patients who complete the 52- and 48-week NAVIGATOR and SOURCE studies, respectively. Patients who were randomized to receive tezepelumab 210 mg every 4 weeks (Q4W) in either predecessor study will continue to receive this regimen for 1 year; those who were previously randomized to receive placebo will be re-randomized (1:1) to receive either tezepelumab 210 mg Q4W or placebo for 1 year. Patients will receive their prescribed controller medications throughout DESTINATION and study physicians will have the opportunity to down- or up-titrate dosage of these medications, if appropriate. The primary objective is to evaluate the long-term safety and tolerability of tezepelumab over 104 weeks (inclusive of the treatment period of either predecessor study). The secondary objective is to assess the long-term effect of tezepelumab on asthma exacerbations. Patients recruited from SOURCE will be followed up post-treatment for 12 weeks. Patients recruited from NAVIGATOR who complete 100 weeks of tezepelumab treatment will be eligible for either 12 weeks of follow-up or a 36-week extended follow-up during which the clinical benefit of tezepelumab after treatment cessation will be investigated. Discussion DESTINATION will evaluate the long-term safety, tolerability and efficacy of tezepelumab versus placebo with continued dosing for up to 2 years. DESTINATION will also evaluate the clinical effect of tezepelumab after treatment cessation. This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma. Trial registration NCT03706079 (ClinicalTrials.gov). Registered 15 October 2018.

Purpose To present the visual and safety outcomes of surgery for primary idiopathic macular holes including predictors of visual acuity and the impact of combined phacovitrectomy surgery. Design Registry-style, prospective, nonrandomized, observational cohort study. Participants Patients with idiopathic macular holes undergoing primary surgery. Methods Surgeons were invited to submit clinical details of all macular hole cases receiving surgery. Baseline demographic and clinical information, and details of surgical intervention were collected. Primary follow-up data were collected at 3 months postoperatively or before revision surgery, and surgeons were also asked to submit data at 12 and 24 months postoperatively. Main Outcome Measures Visual acuity improvement ≥15 letters and ≥0 letters, change in mean visual acuity, visual acuity ≥70 letters (20/40), retinal detachment, and endophthalmitis. Results A total of 2455 eyes of 2366 patients were included in the study, and hole closure was achieved in 95.6% of eyes with a single procedure. Mean baseline vision was 48.3 letters. The proportion of successful eyes improving ≥15 letters at 3, 12, and 24 months was 59.1%, 69.4%, and 68.2%, respectively. The mean improvement in acuity at 3, 12, and 24 months was 16.0, 19.2, and 23.6 letters, and 92.4%, 93.4%, and 95.8% improved ≥0 letters at 3, 12, and 24 months, respectively. Eyes receiving SF6 gas had better visual acuities at all time points postoperatively (adjusted effect 3.4, 3.1, and 4.6 letters better at 3, 12, and 24 months vs. longer-acting gas, respectively). Combined phacovitrectomy in phakic eyes was associated with better corrected visual acuity postoperatively (vs. vitrectomy surgery alone), a difference that vanished when eyes went on to have subsequent cataract surgery. The rate of retinal detachment postoperatively was 1.3%, and the odds of detachment were greater in eyes receiving longer-acting gases versus SF6 gas (adjusted odds ratio, 2.2; 95% confidence interval, 1.04–4.77; P = 0.039). There were no reported cases of endophthalmitis. Conclusions Macular hole surgery substantially improved acuity in approximately two thirds of patients and was seldom associated with loss of vision. SF6 gas was associated with better visual outcomes, an effect that warrants further study.

Purpose: To evaluate the efficacy and safety of early pars plana vitrectomy (PPV) for the treatment of acute infective endophthalmitis, and identify prognostic factors for better visual outcome. Design: Retrospective cohort study. Methods: Consecutive patients who underwent early PPV within 72 hours of presentation for the treatment of acute infective bacterial endophthalmitis and presented to a large tertiary referral center in New South Wales, Australia, between January 2009 and December 2013 were included. Changes in best-corrected visual acuity (VA) from baseline to 1 year were examined. Results: A total of 64 patients were included. The inciting events were cataract surgery (53%), intravitreal injection (36%), trabeculectomy (3%), and endogenous (3%). The mean VA improved from 3.1 logMAR (hand motion) at baseline to 1.02 (approximately 20/200) at 1 year, with 42% achieving final VA equal to or better than 0.477 logMAR (20/60) following early PPV. Positive prognostic factors were negative microbial cultures (P < 0.01) and etiology of post-cataract surgery (P < 0.01). In multivariable analyses adjusting for age and prognostic factors, patients with baseline VA of light perception and hand motion achieved greater visual gains than those with counting fingers, with gains of logMAR of -2.68, -2.09, and -0.85, respectively (P < 0.0001). Conclusions: Most patients who undergo early PPV experience substantial VA improvement. Negative microbial cultures and endophthalmitis after cataract surgery were associated with better final visual outcome. Patients with presenting VA of light perception or hand motion achieved higher visual gains than those with counting fingers, suggesting the possibility that early PPV may be beneficial in both groups.

Purpose Tezepelumab is an anti–thymic stromal lymphopoietin monoclonal antibody therapeutic in development for patients with severe, uncontrolled asthma. In ongoing Phase III studies, tezepelumab is administered via subcutaneous (SC) injections using a vial-and-syringe (V–S). This study compared the pharmacokinetic (PK) parameters, safety, and tolerability of tezepelumab administered subcutaneously via V–S versus via an accessorized prefilled syringe (APFS) or autoinjector (AI). Methods This single-center, randomized, open-label, parallel-group study was conducted in healthy volunteers aged 18–65 years. Participants, stratified according to weight (50 to Findings A total of 315 adults were randomized to treatment. Geometric mean ratios for comparisons between device groups of Cmax, AUC0–∞, and AUC0–last were close to 1, with 90% CIs all within the range of 0.8–1.25, meeting bioequivalence criteria. PK variables were also similar between devices across injection sites and weight categories. Across devices, thigh injection resulted in slightly higher exposure than upper arm injection, and abdomen injection resulted in exposure similar to or slightly lower than thigh injection; however, these differences were not clinically meaningful. Treatment-emergent anti-tezepelumab antibodies were present in 3 (2.9%), 1 (1.0%), and 0 participants in the V–S, APFS, and AI groups, respectively. Treatment-related adverse events were reported in 15.0% of participants overall (V–S, 10.7%; APFS, 18.1%; AI, 16.0%), including ISRs in 1 (1.0%), 3 (2.9%), and 3 (2.8%) participants in the V–S, APFS, and AI groups. Median visual analog scale pain score (0–100 mm scale) was 2 mm immediately after injection and was 0 mm at 30 min for all groups. Implications Tezepelumab PK parameters after a single 210-mg SC dose were comparable when administered via V–S, APFS, or AI. In all groups, immunogenicity rate and injection site pain were low, and ISRs were uncommon. These findings support administration of tezepelumab via APFS or AI, in addition to V–S, providing patients and physicians with greater choice and the potential convenience of at-home use. ClinicalTrials.gov identifier: NCT03989544.

Background Endogenous Klebsiella pneumoniae endophthalmitis (EKPE) is a well-known entity in South-East Asia. We demonstrate a range of differing clinical features and outcomes of EKPE, and highlight the increasing incidence of EKPE in major centres in Sydney and Melbourne, Australia. Design Retrospective observational case study and case series in the hospital setting. Participants Four cases of EKPE. Methods EKPE cases from 2005 to 2015 were identified through established endophthalmitis databases as well as hospital-based microbiological searches. Main Outcome Measures EKPE cases were confirmed with positive K. pneumoniae intraocular samples. Results Rising trends of EKPE were noted in major centres in Australia. Six eyes of four patients with EKPE from January 2011 to December 2015 are reported. The mean age was 49 years (range 43–58 years). Two patients had bilateral involvement. There were systemic symptoms up to 10 days prior to ocular symptoms. The source of sepsis in all cases was a hepatic abscess. Two patients had diabetes mellitus. Five eyes had hypopyon panuveitis on presentation. All eyes underwent vitrectomy. The patient with the most delayed presentation underwent enucleation following globe perforation. Final best corrected visual acuity (BCVA) in one patient with bilateral EKPE was light perception (LP) only. The other three eyes had BCVA in at least one eye of 6/24 or better. Conclusions EKPE is an emerging condition in Australia. Although rare, EKPE is a sight-threatening and potentially life-threatening emergency that can initially present to ophthalmologists. One should suspect EKPE in septic patients with a B-scan showing a vitreous or retinal abscess.

Purpose To describe the anatomic and visual outcomes of eyes undergoing reoperation after failed primary surgery for idiopathic macular hole. Design Prospective registry study. Participants One hundred three patients who had undergone failed macular hole surgery. Methods Unclosed idiopathic macular holes were identified from a large national prospective registry run by the Australian and New Zealand Society of Retinal Specialists. Unclosed idiopathic macular holes were defined as idiopathic macular holes that underwent vitrectomy surgery for the first time, but were never observed to close in the postoperative period. Surgeons were contacted to submit retrospectively details of subsequent management and long-term outcome of these eyes. Main Outcome Measures Macular hole closure; visual acuity (VA) change relative to baseline at 3, 12, and 24 months; and hole size at all time points. Results One hundred three patients with failed macular hole surgery were identified, among whom 53 underwent reoperation, 49 did not, and 1 was lost to follow-up. Macular hole closure was achieved in 45 of 53 patients (85%) undergoing revision surgery. Mean change in VA from baseline in eyes undergoing revision surgery versus eyes that did not was +2.8 letters versus −1.9 letters at 3 months ( P = 0.278), +8.2 letters versus −1.9 letters at 12 months ( P = 0.167), and +18.3 letters versus −3.4 letters at 24 months ( P = 0.022). Thirty-six percent of eyes with reoperated holes showed improved VA of 15 letters or more at 3 months after operation, increasing to 48% at 12 months and 65% at 2 years. Before revision surgery, mean macular hole size was observed to increase from 483 μm to 562 μm after failed primary surgery ( P = 0.046). Conclusions In eyes undergoing revision surgery, reoperation for unclosed macular holes was significantly better than observation, although these visual gains took some time to occur. The surgical success rate was lower than that for primary idiopathic macular hole. The selection criteria for revision surgery need to be defined.

Summary Introduction Tiotropium, a once-daily long-acting anticholinergic agent, has been shown to be an efficacious and safe add-on treatment for adults with symptomatic asthma, despite treatment with inhaled corticosteroids (ICS). A large proportion of asthmatic adolescents have symptomatic disease despite a wide range of therapeutic options. We investigated the efficacy and safety of three doses of tiotropium, administered in the evening (via Respimat ® SoftMist™ inhaler), versus placebo in asthmatic adolescents symptomatic despite ICS treatment. Methods This randomised, double-blind, placebo-controlled, incomplete crossover study evaluated once-daily tiotropium 5 μg, 2.5 μg and 1.25 μg versus placebo in three 4-week treatment periods. Primary efficacy end point was change in peak forced expiratory volume in 1 s within 3 h post-dose from baseline (peak FEV 1(0–3h) ). Results From 139 enrolled patients, 105 were randomised to receive one of four treatment sequences. Peak FEV 1(0–3h) response for tiotropium 5 μg was significantly greater versus placebo ( p = 0.0043). Trough FEV 1 responses were significantly greater for tiotropium 5 μg ( p p = 0.0134) versus placebo, but not for 2.5 μg ( p = 0.0975), while FEV 1 area under the curve (0–3h) responses were significant for all doses ( p = 0.00001–0.0398). Overall incidence of adverse events was balanced across treatment groups, with no dose-dependent observations. The majority of adverse events were mild to moderate in intensity. Conclusion This first study of tiotropium in adolescents with symptomatic asthma demonstrates that tiotropium is well tolerated and efficacious as add-on to maintenance treatment with ICS. ClinicalTrials.gov identifier ; NCT01122680.

As the dominant producers of industrial greenhouse gas (GHG) emissions, companies have a vital role to play in efforts to mitigate global warming. Focussing on scope 1 and 2 emissions alone can distort a firm’s GHG estimates as scope 3 emissions often constitute a significant part of its overall GHG footprint, up to seventy-five percent in many firms. Lack of knowledge of scope 3 emissions inhibits a firm’s ability to pursue the most cost-effective carbon mitigation strategies. This paper investigates the methods and data currently used by Australian organizations to assess their scope 3 emissions. The exploratory study found a wide discrepancy in the number of emission sources reported. In addition there was a general lack of rigour in determining which emission sources to include. This suggests that more comprehensive guidance on relevant emission sources by industry or sector would likely improve the completeness and relevance of inventories in accordance with The Greenhouse Gas Protocol.

Endogenous Klebsiella pneumoniae endophthalmitis (EKPE) is a well-known entity in South-East Asia. We demonstrate a range of differing clinical features and outcomes of EKPE, and highlight the increasing incidence of EKPE in major centres in Sydney and Melbourne, Australia.Retrospective observational case study and case series in the hospital setting.Four cases of EKPE.EKPE cases from 2005 to 2015 were identified through established endophthalmitis databases as well as hospital-based microbiological searches.EKPE cases were confirmed with positive K. pneumoniae intraocular samples.Rising trends of EKPE were noted in major centres in Australia. Six eyes of four patients with EKPE from January 2011 to December 2015 are reported. The mean age was 49 years (range 43-58 years). Two patients had bilateral involvement. There were systemic symptoms up to 10 days prior to ocular symptoms. The source of sepsis in all cases was a hepatic abscess. Two patients had diabetes mellitus. Five eyes had hypopyon panuveitis on presentation. All eyes underwent vitrectomy. The patient with the most delayed presentation underwent enucleation following globe perforation. Final best corrected visual acuity (BCVA) in one patient with bilateral EKPE was light perception (LP) only. The other three eyes had BCVA in at least one eye of 6/24 or better.EKPE is an emerging condition in Australia. Although rare, EKPE is a sight-threatening and potentially life-threatening emergency that can initially present to ophthalmologists. One should suspect EKPE in septic patients with a B-scan showing a vitreous or retinal abscess.

Scholars and practitioners acknowledge the benefits of organizations understanding their contribution to global warming and implementing carbon management strategies to address climate change concerns. A key element of a carbon management strategy is to reduce emissions, which requires an assessment of a firm's greenhouse gas emissions. For most organizations the indirect (scope 3) emissions represent the largest portion of their total carbon footprint. When facility-specific data are not available, firms are encouraged to use standard emission factors to calculate scope 3 emissions. This paper investigates how sampled Australian organizations assess their scope 3 emissions with respect to the emission factors they are using to convert activity data into units of carbon dioxide equivalent emission (CO2-e), and the implications for producing an accurate emission assessment. The research study found that, where conversion information was not available in a recognized government publication, the use of varying conversion value sources resulted in wide discrepancies in reported emissions for like activities. This undermines the assessment quality, makes comparison of results across organizations difficult and can lead to inappropriate carbon management strategy choices and misallocation of resources. Copyright © 2012 John Wiley & Sons, Ltd and ERP Environment

1. The EC Water Framework Directive (WFD) came into force across the EU on 22 December 2000. It will significantly influence Scottish water policy development and implementation, and set aquatic and wetland natural heritage targets, for many years to come. 2. The new WFD will replace or integrate a range of previous water directives, including the aquatic and wetland aspects of the Natura Directives. The WFD offers a significant opportunity to establish a co-ordinated approach to aquatic monitoring. The development of effective monitoring regimes to facilitate holistic assessments of ecological status will be essential to its successful implementation. 3. Existing Scottish legislation does not fulfil the WFD's regulatory requirements, and so new statutory controls will be required over a range of activities that currently have little or no regulation in Scotland but which can damage the natural heritage. The Scottish Environment Protection Agency (SEPA) will be the lead Competent Authority in Scotland for implementing the WFD. As such, SEPA must prepare a monitoring strategy and take a lead role in carrying out the monitoring work to determine the status of the water environment and relevant territorial waters of Scotland. 4. The Scottish Monitoring Strategy proposal has been suggested for adoption by the other devolved UK administrations to ensure all relevant UK agencies contribute to the development of co-ordinated monitoring programmes for the WFD. A Scottish Monitoring Forum is proposed that would work to identify and fill any information gaps that might exist. However, much of the work on implementing the technical aspects of the WFD awaits the outcome of the various working groups of the European Common Implementation Strategy. 5. The products arising from the Scottish Monitoring Forum will feed into the Department for Environment, Food & Rural Affairs co-ordinated UK national marine monitoring strategy and advise the Scottish components of future UK ‘State of the Seas’ reporting. Copyright © 2004 John Wiley & Sons, Ltd.

Summary Recently collected data comparing the distribution and performance of the rare lagoonal charophyte Lamprothamnium papulosum across a number of UK coastal lagoon sites, including nine sites in the Western Isles, is presented. The surveys revealed that the species occurred over a wide range of salinities but was absent from sites with high phosphorus concentrations. The sites in the Western Isles held the most extensive populations and were least threatened by nutrient pollution. The discovery of two other endangered and vulnerable charophytes of brackish water, Tolypella nidifica and Chara baltica, at two of the Western Isles sites further highlights the importance of Scotland's saline lagoon resource. The use of the autoecological data on salinity and nutrient conditions for supporting Biodiversity Action Plan implementation for Lamprothamnium papulosum and for saline lagoon conservation in general is considered. Status summaries for all the charophyte species of brackish water recorded in Scotlan...

To determine the intraretinal and periretinal pathological changes in early anterior proliferative vitreoretinopathy (APVR). Observational case series. Eighteen patients undergoing retinectomy for APVR. Retinectomy specimens removed at vitrectomy surgery were analysed by (a) semithin light microscopy, (b) immunohistochemistry and (c) electron microscopy. The specimens showed consistent outer retinal degenerative changes, marked Muller cell hypertrophy and glial continuity to epiretinal membranes. Photoreceptor outer and inner segments were markedly disrupted and occasional photoreceptor nuclear had pyknosis and chromatin clumping consistent with apoptosis. Muller cells expressed upregulated levels of glial fibrillary acid protein (GFAP) and extended through glial bridges to complex epiretinal membranes which in some areas had a bilaminar structure with a glial-negative inner lamina. Retinal degeneration and photoreceptor apoptosis occur in retinal detachment complicated by proliferative vitreoretinopathy (PVR), although during the early stages of the process neural retinal cells remain present, suggesting potential for recovery. The intraretinal glial response appears to be centrally involved in the formation of contractile epiretinal membranes. The retina retains the capacity for a degree of functional recovery following surgery for PVR. Surgical separation of anterior epiretinal membranes in PVR may be difficult and incomplete and alternative surgical strategies may be necessary to prevent recurrence.

Methods This randomised, placebo-controlled, double-blind, incomplete crossover study (NCT01122680) evaluated the efficacy and safety of 5, 2.5 and 1.25 μg once-daily (evening) tiotropium (via Respimat Soft MistTM Inhaler) versus placebo in three 4-week treatment periods in adolescents (aged 12-17 years) with symptomatic asthma despite medium-dose ICS. The primary efficacy end point was change in peak forced expiratory volume in 1 second within 3 hours post-dose (peak FEV1(0-3h)) assessed as a response (difference from baseline). Secondary end points included trough FEV1, FEV1 area under the curve (AUC)(0-3h), peak expiratory flow (PEFam/pm) responses and Asthma Control Questionnaire (ACQ) score.

WYKO Corporation is currently designing and manufacturing specialized phase shifting interferometers to aid in the qualification of large optics for the U.S. NIF program. The interferometers will be used to qualify homogeneity of raw material and provide in-process inspection information and final inspection qualification data. The 24' systems will be the largest commercially available Fizeau phase shifting interferometers ever manufactured. Systems will be produced using traditional CCD cameras as well as megapixel CCD camera for applications requiring higher lateral resolution. Mechanical and optical design considerations include vibration and distortion control of critical optical elements, polarization control of the laser source, imaging system design, and optical transfer function optimization. We also address effects in the test cavity arising from measuring transmitted and reflected wavefronts of optics mounted at Brewster's angle.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Objective To describe adverse sequelae of retinal prophylaxis in fellow eyes of patients with rhegmatogenous retinal detachment. Design Records were reviewed for 17 patients who had retinal breaks or detachment subsequent to prophylactic retinopexy applied to the fellow eye (without posterior vitreous detachment) at the time of primary rhegmatogenous retinal detachment surgery. Subsequent treatment included cryotherapeutic and laser retinopexy, scleral buckling, and vitrectomy. Results Of the 17 patients, 12 were male (mean age, 49 years). Laser retinopexy alone was used in 6 cases. Sixteen (94%) developed retinal tears related to acute posterior vitreous detachment, of which 8 (47%) were at the edge of retinopexy and 8 (47%) were in the normal or untreated retina. Thirteen (76%) developed a retinal detachment, of which 11 (85%) did not involve the fovea. Median visual acuity following treatment was 0.18 logMAR (6/9 Snellen equivalent). Conclusions Prophylactic retinopexy in fellow eyes without posterior detachment is not completely successful and may cause breaks to develop at the edge of treated areas during subsequent acute posterior vitreous detachment. Patient education alone regarding the symptoms of retinal tear and detachment may be preferable to prophylactic retinopexy of the fellow eye in the absence of a posterior vitreous detachment.