Publications by authors named "Peter Simmons"

56 Publications

Safety and Efficacy of a Preservative-Free Artificial Tear Containing Carboxymethylcellulose and Hyaluronic Acid for Dry Eye Disease: A Randomized, Controlled, Multicenter 3-Month Study.

Clin Ophthalmol 2020 1;14:2951-2963. Epub 2020 Oct 1.

Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia.

Purpose: To compare the efficacy and safety of an artificial tear combining the polymers carboxymethylcellulose (CMC) and hyaluronic acid (HA), to a formulation of CMC alone in subjects with dry eye.

Methods: A preservative-free artificial tear (CMC-HA) was compared with an existing artificial tear (CMC). Subjects with mild-to-severe signs and symptoms of dry eye were enrolled in this double-masked, randomized, multicenter trial, and dosed at least twice daily for 90 days, with follow-up visits at Days 7, 30, 60, and 90. Ocular Surface Disease Index (OSDI) was the primary outcome measure. Secondary outcome measures were tear break-up time (TBUT), ocular surface staining, Schirmer test with anesthesia, and visual analog scale (VAS) scores of dry eye symptom severity and formulation acceptability. Safety measures included adverse events, biomicroscopy, and visual acuity.

Results: A total of 460 subjects were enrolled across 45 sites (38 in Europe; 7 in Australia), of whom 454 were randomized to receive treatment. The per-protocol (PP) population consisted of 394 subjects, 364 (92.4%) of whom completed the study. In the PP population, the mean ± SD change from baseline in OSDI score at the primary timepoint, Day 90, was -16.9±17.5 for CMC-HA and -16.0±16.1 for CMC. CMC-HA was non-inferior to CMC based upon a confidence interval method. Both treatments significantly improved (<0.001) OSDI, symptom VAS scores, TBUT, and ocular surface staining from baseline at all follow-up visits, with minimal differences between groups. Greater reduction of overall ocular pain/discomfort was reported in subjects using CMC-HA versus CMC (=0.048). Approximately 10% of subjects in each group reported treatment-related adverse events of generally mild to moderate severity.

Conclusion: The new CMC-HA formulation was effective and well tolerated, and demonstrates a greater potential for symptom relief compared with CMC. These data support implementation of this formula for the management of dry eye patients.
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http://dx.doi.org/10.2147/OPTH.S256480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534849PMC
October 2020

Multivariate Analysis: A Cautionary Tale of Mediators and Confounders.

J Cardiothorac Vasc Anesth 2020 05 8;34(5):1235-1237. Epub 2020 Jan 8.

Department of Anaesthesia, Waikato Hospital, Hamilton, New Zealand.

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http://dx.doi.org/10.1053/j.jvca.2019.12.033DOI Listing
May 2020

An artificial tear containing flaxseed oil for treating dry eye disease: A randomized controlled trial.

Ocul Surf 2020 01 14;18(1):148-157. Epub 2019 Nov 14.

Allergan Plc, Irvine, CA, USA.

Purpose: To evaluate the efficacy and safety of a nano-emulsion artificial tear (OM3) containing carboxymethylcellulose (CMC) and glycerin, flaxseed oil and castor oil, and three osmoprotectants (levocarnitine, erythritol, and trehalose) compared with an artificial tear (Refresh Optive Advanced [ROA]) containing the same ingredients with the exception of trehalose and flaxseed oil.

Methods: In this multicenter, double-masked, randomized, two-arm, parallel-group, 6-visit study (screening, baseline, and days 7, 30, 60, and 90), subjects with dry eye disease underwent an open-label, 7-day run-in with CMC 0.5% (Refresh Plus), before 1:1 randomization to OM3 or ROA for 90 days (both instilled ≥2 daily). Ocular Surface Disease Index (OSDI; primary endpoint change from baseline at day 90), tear film breakup time (TBUT), and ocular staining (combined/corneal/conjunctival) were assessed; change from baseline in these parameters was calculated at each timepoint. Treatment-related adverse events (AEs) were assessed at each visit.

Results: Overall, 242 subjects were randomized (OM3, n = 120; ROA, n = 122). At day 90, significant improvements in OSDI, ocular staining and TBUT were evident in both treatment groups. Significant (P < 0.05) between-group differences in favor of OM3 were observed for combined ocular staining (all timepoints), corneal staining (day 90), and conjunctival staining (day 30). Treatment-related AEs were higher in the ROA (9.8%) versus OM3 (6.7%) group; blurred vision was among the most commonly reported AE (OM3 0% vs ROA 4.1%).

Conclusion: These findings support the application of OM3, a novel preservative-free, nano-emulsion tear formulation with trehalose and flaxseed oil, for the treatment of dry eye disease.
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http://dx.doi.org/10.1016/j.jtos.2019.11.004DOI Listing
January 2020

Physicochemical Properties of Hyaluronic Acid-Based Lubricant Eye Drops.

Transl Vis Sci Technol 2019 Nov 1;8(6). Epub 2019 Nov 1.

Allergan plc, Irvine, CA, USA.

Purpose: To assess the physicochemical properties of hyaluronic acid (HA)-based artificial tears.

Methods: The average molecular weight (MW) and polydispersion index (PDI) of HA in 18 commercially available artificial tears were determined by light scattering/high-performance liquid chromatography. Osmolality, pH, viscosity, and sodium concentration were determined using an osmometer, pH meter, rheometer, and inductively coupled plasma mass spectrometer, respectively.

Results: The MW of HA varied considerably between formulations. The PDI was >2.0 in two formulations (2.28 and 4.94), suggesting the presence of a copolymer and/or HA size variability. Three formulations exhibited viscosity exceeding the blur threshold at different shear rates. Viscosity at low shear rates was generally highest in formulations containing high-MW HA. Correlations were found between observed viscosity and a predictive/calculated value, except for four copolymer-containing formulations, and osmolality (range, 154-335 mOsm/kg) and sodium concentration (range, 22-183 mM), with two exceptions. Compared with organic osmolytes, adding sodium decreased viscosity, particularly at lower shear rates.

Conclusions: In the context of the literature, our findings suggest that for most patients with dry eye disease, the ideal HA-based artificial tear should include high-MW HA with a low PDI and exhibit enhanced viscosity at low shear rate (without exceeding the blur threshold). The inclusion of synergistic copolymers and a low sodium concentration may increase viscosity, but whether any of these physicochemical properties or correlations can predict clinical efficacy will require further investigation.

Translational Relevance: Understanding the properties of HA-based artificial tears will support the development of unique formulations that target specific ocular surface conditions.
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http://dx.doi.org/10.1167/tvst.8.6.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827422PMC
November 2019

Evaluation of an enhanced viscosity artificial tear for moderate to severe dry eye disease: A multicenter, double-masked, randomized 30-day study.

Cont Lens Anterior Eye 2019 08 17;42(4):443-449. Epub 2018 Dec 17.

Allergan International Medical Affairs, Marlow, Buckinghamshire, UK. Electronic address:

Purpose: In a randomized, controlled clinical trial, two lubricant artificial tear formulations with enhanced viscosity were compared: an investigational product at the time, containing carboxymethylcellulose 1.0% and glycerin 0.9% (CMC-GLY) with osmoprotectants, and a standard formula containing carboxymethylcellulose 1.0% alone (CMC).

Methods: This double-masked study recruited patients with moderate to severe dry eye at 10 US centers. After a 7-day run-in with CMC 0.5% (Refresh Tears) patients were randomized to use either CMC-GLY or CMC as needed, but at least 2 times daily for 30 days. Patients were stratified by Ocular Surface Disease Index (OSDI) score into moderate (23-32) and severe (> 32-65) subgroups. Assessments included OSDI (primary efficacy variable), corneal and conjunctival staining, tear break-up time (TBUT), symptom surveys, and safety variables. Study visits were days 1 (baseline/randomization), 7, and 30.

Results: A total of 188 patients (94 CMC-GLY, 94 CMC) were enrolled. The severe subgroup had 67 CMC-GLY and 65 CMC patients. OSDI scores progressively improved and were similar at day 30 between treatment groups. At day 7, only the CMC-GLY group demonstrated significant improvements from baseline in OSDI score (all patients p < 0.001, severe p < 0.001), corneal staining (p = 0.004), and TBUT (p < 0.001). Between-group dose frequency for CMC-GLY was lower at day 7 (p = 0.031). Other efficacy results were similar between groups. The most commonly reported adverse event in both groups was blurred vision.

Conclusions: Overall, the CMC-GLY artificial tear formulation was as effective as the CMC formulation. CMC-GLY demonstrated improvements at an earlier stage (day 7). Both artificial tear formulations were safe and well tolerated, with no treatment-related serious adverse events. These results support the use of the CMC-GLY artificial tear formulation as an effective treatment to reduce the symptoms and signs of dry eye disease.
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http://dx.doi.org/10.1016/j.clae.2018.12.003DOI Listing
August 2019

Management of post-LASIK dry eye: a multicenter randomized comparison of a new multi-ingredient artificial tear to carboxymethylcellulose.

Clin Ophthalmol 2018 7;12:839-848. Epub 2018 May 7.

Allergan Clinical Research, Allergan plc, Irvine, CA, USA.

Purpose: To compare the efficacy and safety of a preservative-free, multi-ingredient formulation of carboxymethylcellulose 0.5%, hyaluronic acid 0.1%, and organic osmolytes (CMC-HA), to preservative-free carboxymethylcellulose 0.5% (CMC) in the management of postoperative signs and symptoms of dry eye following laser-assisted in situ keratomileusis (LASIK).

Methods: This was a double-masked, randomized, parallel-group study conducted in 14 clinical centers in Canada and Australia. Subjects with no more than mild dry eye instilled CMC-HA or CMC for 90 days post-LASIK. Ocular Surface Disease Index (OSDI; primary efficacy measure), corneal staining, tear break-up time (TBUT), Schirmer's test, acceptability/tolerability surveys, and visual acuity were assessed at screening and days 2, 10, 30, 60, and 90 post-surgery. Safety analyses included all enrolled.

Results: A total of 148 subjects (CMC-HA, n=75; CMC, n=73) were enrolled and assigned to receive treatment, and 126 subjects completed the study without any protocol violations. Post-LASIK, dry eye signs/symptoms peaked at 10 days. OSDI scores for both groups returned to normal with no differences between treatment groups at day 90 (=0.775). Corneal staining, Schirmer's test, TBUT, and survey results were comparable. Higher mean improvements in uncorrected visual acuity were observed in the CMC-HA group at all study visits, reaching statistical significance at day 30 (=0.013). Both treatments were well tolerated.

Conclusion: CMC-HA-containing artificial tears relieved post-LASIK ocular dryness as well as CMC alone, and demonstrated incremental benefit in uncorrected vision, with a favorable safety profile. Results support use of CMC-HA eye drops to reduce signs and symptoms of ocular dryness post-LASIK.
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http://dx.doi.org/10.2147/OPTH.S163744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944453PMC
May 2018

Effect of tear supplements on signs, symptoms and inflammatory markers in dry eye.

Cytokine 2018 05 14;105:37-44. Epub 2018 Feb 14.

Vision Sciences, Glasgow Caledonian University, Glasgow, Scotland, United Kingdom.

Purpose: Three tear supplements were compared for their effects on the signs, symptoms and inflammatory status of subjects with dry eye disease. Assessments were made before and after both 2 and 4 weeks of treatment.

Methods: In this masked, randomized, 3-way crossover trial, eighteen dry eye subjects were recruited. At each visit, symptoms, tear evaporation rate, stability and osmolarity were measured and tear samples were analyzed for 7 inflammatory markers, using multiplex immunoassays. The 3 treatments included carboxymethylcellulose-glycerine-castor oil (CGC), carboxymethylcellulose (CMC) and hydroxypropyl guar (HPG). The CGC and HPG drops are emulsified lipids; CGC also contains osmoprotectants. The CMC drop is a standard aqueous polymeric supplement.

Results: Significant improvements were seen in symptoms (OSDI) and tear stability (NITBUT) with all 3 treatments at 4 weeks. At 4 weeks post-CGC, 6 out of 7 biomarkers demonstrated a >25% reduction (in 40% of subjects). The same reduction (>25%) was seen in 10% of the subjects for CMC and in none of the subjects for HPG. No significantly different change to either evaporation rate or tear osmolarity was found following any of the three treatments.

Conclusions: In this study, the CGC treatment resulted in the greatest reduction in ocular biomarkers of inflammation, while all 3 treatments reduced symptoms and improved tear stability. These results indicate that subject-perceived symptomatic improvements are not necessarily associated with a reduction in objective measures of inflammation.
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http://dx.doi.org/10.1016/j.cyto.2018.02.009DOI Listing
May 2018

Investigating the potential benefits of a new artificial tear formulation combining two polymers.

Clin Ophthalmol 2017 12;11:1637-1642. Epub 2017 Sep 12.

Allergan plc, Irvine, CA, USA.

Purpose: Artificial tear formulations typically contain a water-soluble polymer to enhance residence time, moisture retention, and binding to the mucin coat of the ocular surface, which facilitate corneal healing. This study investigated the potential advantages of combining carboxymethylcellulose (CMC) and hyaluronic acid (HA) polymers in a single formulation.

Materials And Methods: Individual CMC and HA solutions were prepared and tested for bulk viscosity in comparison to a solution that combined CMC and HA. Rheometry determined the differences between solutions at increasing shear rates, simulating eye movement and blinking.

Results: The bulk viscosity of the individual 0.5% CMC and 0.1% HA solutions was 2.5 and 5.7 cP, respectively. The viscosity of the combined solution (13.1 cP) was 60% higher than predicted by additive effects. Rheometry revealed shear rates between 10/second (open eye) and 10,000/second (blinking eye). At these rates, viscosity ranged from 2.7 to 3.5 cP for 0.5% CMC, 2.8 to 6.8 cP for 0.1% HA, and 5.2 to 15.3 cP for the 0.5% CMC-0.1% HA combination. Low-shear viscosity of the CMC-HA combination increased 48% over the sum of the individual solutions, but high-shear viscosity remained virtually unchanged. Data from CMC and HA solutions at higher concentrations were consistent with these results.

Conclusion: Combining CMC and HA polymers produced a synergistic increase in low-shear viscosity (which cannot be fully explained by simple molecular entanglement), while the high-shear viscoelasticity of the combined solution remained unaffected. These data suggest that CMC-HA combinations have properties that may be used to formulate artificial tears that optimize ocular retention (through higher low-shear viscosity), while minimizing blur and stickiness during blinking (through lower high-shear viscosity).
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http://dx.doi.org/10.2147/OPTH.S135550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602465PMC
September 2017

Dual-Polymer Drops, Contact Lens Comfort, and Lid Wiper Epitheliopathy.

Optom Vis Sci 2016 08;93(8):979-86

*OD, PhD, FAAO †OD, MS, FAAO ‡OD, FAAO §PhD ∥OD School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama (JJN); Southern College of Optometry, Memphis, Tennessee (CWL); Schwartz Laser Eye Center, Scottsdale, Arizona (MRB); and Allergan Clinical Research, Irvine, California (HL, PS, JV).

Purpose: This study compared a new contact lens rewetting drop containing both carboxymethylcellulose and hyaluronic acid (CMC-HA) with a standard drop containing carboxymethylcellulose only (CMC). Symptoms of discomfort typical in lens wear and lid wiper epitheliopathy (LWE) were assessed over a 3-month period in a diverse sample of contact lens wearers.

Methods: Adapted daily-wear contact lens subjects using hydrogel, silicone hydrogel, or rigid gas permeable lenses were enrolled in this prospective, randomized, double-masked, parallel-group, 90-day study conducted at 15 clinical sites. Subjects were randomized 2:1 to CMC-HA (n = 244) or CMC alone (n = 121) with dosage at least four times per day, along with their habitual lens care system. At baseline and at days 7, 30, 60, and 90, subject-completed questionnaires, bulbar conjunctival staining, LWE, contact lens distance visual acuity (CLDVA), and standard safety measures were assessed.

Results: At day 90, CMC-HA performed significantly better than CMC in ocular symptoms including dryness throughout the day (p = 0.006), and burning/stinging throughout the day (p = 0.02) and at the end of the day (p < 0.001). CMC-HA also performed numerically better for dryness at the end of day (p = 0.06). LWE staining was improved in the CMC-HA group at day 90 whereas it increased slightly in the CMC alone group, with a significant between-group difference (p = 0.009). CMC-HA also demonstrated greater reduction in conjunctival staining compared with CMC alone at day 90 (p = 0.08). No differences in CLDVA, contact lens wear time, acceptability, and product use were observed, and safety outcomes were similar between groups.

Conclusions: The addition of HA to a standard CMC rewetting drop improves clinical performance. In this comparison of rewetting drop efficacy in contact lens wearers, LWE was a useful clinical sign for differentiating clinical performance.
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http://dx.doi.org/10.1097/OPX.0000000000000878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972480PMC
August 2016

Community pharmacy automatic refill program improves adherence to maintenance therapy and reduces wasted medication.

Am J Manag Care 2015 Nov;21(11):785-91

CVS/caremark, 2211 Sanders Rd, NBT 326, Northbrook, IL 60062. E-mail:

Objectives: Automatic prescription refill programs are a popular means of improving medication adherence. A concern is the potential for prescription drug wastage and unnecessary healthcare spending. We evaluated the impact of an automatic refill program on patterns of medication use.

Study Design: Retrospective propensity score matched cohort study with multivariable generalized linear modeling.

Methods: The setting of the study was a pharmacy benefit manager administering benefits for patients of retail pharmacies. Participants included patients on medication for chronic conditions; those receiving a 30-day supply (n = 153,964) and a 90-day supply (n = 100,394) were analyzed separately. The intervention was the automatic prescription refill program. Measures included medication possession ratio (MPR) and average days excess at the time of refill. The results are reported across 11 therapeutic classes.

Results: Overall, patients receiving 30-day supplies of medication in the automatic refill program had an MPR that was 3 points higher than those not in the refill program; among those receiving 90-day fills and in the refill program, the MPR was 1.4 points higher (P < .001 for both 30- and 90-day fills). The MPR was higher for members in the refill program across all therapeutic classes. Limiting our analysis to members receiving more than 365 days of medication, we found that patients who received 30-day fills and enrolled in the automatic refill program had 2.5 fewer days' oversupply than those in the control group, whereas automatic refill patients receiving 90-day supplies had 2.18 fewer days' oversupply than the controls (P < .001 for both 30- and 90-day fills).

Conclusions: For this pharmacy provider, automatic refill programs result in improved adherence without adding to medication oversupply.
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November 2015

Evaluation of a Novel Artificial Tear in the Prevention and Treatment of Dry Eye in an Animal Model.

J Ocul Pharmacol Ther 2015 Nov 31;31(9):525-30. Epub 2015 Aug 31.

1 School of Ophthalmology and Optometry, Wenzhou Medical University , Wenzhou, Zhejiang, China .

Purpose: To evaluate effects of a novel multi-ingredient artificial tear formulation containing carboxymethylcellulose (CMC) and hyaluronic acid (HA) in a murine dry eye model.

Methods: Dry eye was induced in mice (C57BL/6) using an intelligently controlled environmental system (ICES). CMC+HA (Optive Fusion™), CMC-only (Refresh Tears(®)), and HA-only (Hycosan(®)) artificial tears and control phosphate-buffered saline (PBS) were administered 4 times daily and compared with no treatment (n = 64 eyes per group). During regimen 1 (prevention regimen), mice were administered artificial tears or PBS for 14 days (starting day 0) while they were exposed to ICES, and assessed on days 0 and 14. During regimen 2 (treatment regimen), mice exposed to ICES for 14 days with no intervention were administered artificial tears or PBS for 14 days (starting day 14) while continuing exposure to ICES, and assessed on days 0, 14, and 28. Corneal fluorescein staining and conjunctival goblet cell density were measured.

Results: Artificial tear-treated mice had significantly better outcomes than control groups on corneal staining and goblet cell density (P < 0.01). Mice administered CMC+HA also showed significantly lower corneal fluorescein staining and higher goblet cell density, compared with CMC (P < 0.01) and HA (P < 0.05) in both regimens 1 and 2.

Conclusions: The artificial tear formulation containing CMC and HA was effective in preventing and treating environmentally induced dry eye. Improvements observed for corneal fluorescein staining and conjunctival goblet cell retention suggest that this combination may be a viable treatment option for dry eye disease.
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http://dx.doi.org/10.1089/jop.2015.0042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675178PMC
November 2015

Chronic institutional failure and enhanced vulnerability to flash-floods in the Cuenca Altadel Río Lerma, Mexico.

Disasters 2016 Jan 13;40(1):112-33. Epub 2015 Aug 13.

Researcher at the Centro de Investigaciones en Geografía Ambiental, Universidad Nacional Autónoma de México, Mexico.

The dominant paradigm in disaster risk reduction (DRR) policies has been seriously contested because of its reliance on interventions based on technocratic expertise. In the Mexican context, the influence of informal practices such as clientelism and cartelisation of the political system produces environmental degradation and vulnerability to disasters within the communities in the study site. This paper contributes to understanding of failed institutional processes and parallel practices that intensify vulnerability to disasters by contrasting the discourses of agents within a peri-urban community in central Mexico. Employing the Situational Analysis Approach as a methodological framework, the study identifies divergent views and practices within the community, leading to different responses to disasters and to different perceptions regarding institutional performance. In addition, it finds that institutional decision-making, based only on scientific and technical expertise, has resulted in unintended consequences that influence ongoing vulnerability to floods in the site under review.
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http://dx.doi.org/10.1111/disa.12134DOI Listing
January 2016

Efficacy and safety of two new formulations of artificial tears in subjects with dry eye disease: a 3-month, multicenter, active-controlled, randomized trial.

Clin Ophthalmol 2015 15;9:665-75. Epub 2015 Apr 15.

Allergan Clinical Research, Allergan, Inc., Irvine, CA, USA.

Purpose: To evaluate and compare the efficacy and safety of two investigational artificial tear formulations (CHO-1 and CHO-2) containing carmellose sodium, hyaluronic acid at different concentrations, and osmoprotectants, with a standard carmellose sodium-containing formulation (Refresh Tears [RT]) in the treatment of dry eye disease.

Subjects And Methods: In this 3-month, double-masked, multicenter study, subjects (n=305) were randomized 1:1:1 to receive CHO-1, CHO-2, or RT, used as needed but at least twice daily. The primary endpoint was change in ocular surface disease index (OSDI) score from baseline to day 90. Other key outcomes included symptoms evaluated on a visual analog scale, corneal and conjunctival staining, and adverse events.

Results: OSDI scores and dry eye symptoms showed a rapid and sustained reduction from baseline in each group. Both CHO-1 and CHO-2 met the primary efficacy endpoint of noninferiority to RT in day 90 OSDI score change from baseline. OSDI ocular symptoms subscale improved more with CHO-1 than CHO-2 (P=0.048). In subjects with clinically relevant baseline ocular surface staining (>14 total score of a maximum of 55), day 90 improvements were greater with CHO-1 and CHO-2 than RT (P≤0.044). Day 90 improvements in OSDI ocular symptoms subscale scores were also greater with CHO-1 than RT (P<0.007) in subjects with clinically relevant ocular staining. All treatments were well tolerated.

Conclusion: Both combination artificial tear formulations were efficacious and well tolerated in subjects with dry eye. CHO-1 demonstrated the best performance in improving ocular symptoms and reducing ocular staining in this heterogeneous study population.
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http://dx.doi.org/10.2147/OPTH.S78184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404880PMC
May 2015

Comparison of novel lipid-based eye drops with aqueous eye drops for dry eye: a multicenter, randomized controlled trial.

Clin Ophthalmol 2015 15;9:657-64. Epub 2015 Apr 15.

Ophthalmology Research and Development, Allergan, Inc., Irvine, CA, USA.

Background: Dry eye may be caused or exacerbated by deficient lipid secretion. Recently, lipid-containing artificial tears have been developed to alleviate this deficiency. Our study compared the efficacy, safety, and acceptability of lipid-containing eye drops with that of aqueous eye drops.

Methods: A non-inferiority, randomized, parallel-group, investigator-masked multicenter trial was conducted. Subjects with signs and symptoms of dry eye were randomized to use one of two lipid-containing artificial tears, or one of two aqueous artificial tears. Subjects instilled assigned drops in each eye at least twice daily for 30 days. The primary efficacy analysis tested non-inferiority of a preservative-free lipid tear formulation (LT UD) to a preservative-free aqueous tear formulation (AqT UD) for change in Ocular Surface Disease Index (OSDI) score from baseline at day 30. Secondary measures included OSDI at day 7, tear break-up time (TBUT), corneal and conjunctival staining, Schirmer's test, acceptability and usage questionnaires, and safety assessments.

Results: A total of 315 subjects were randomized and included in the analyses. Subjects reported instilling a median of three doses of study eye drops per day in all groups. At days 7 and 30, all groups showed statistically significant improvements from baseline in OSDI (P<0.001) and TBUT (P≤0.005). LT UD was non-inferior to AqT UD for mean change from baseline in OSDI score at day 30. No consistent or clinically relevant differences for the other efficacy variables were observed. Acceptability was generally similar across the groups and there was a low incidence of adverse events.

Conclusion: In this heterogeneous population of dry eye subjects, there were no clinically significant differences in safety, effectiveness, and acceptability between lipid-containing artificial tears and aqueous eye drops. The results suggest that lipid-containing artificial tears can be used to counteract lipid deficiency that is common in dry eye, without compromising overall acceptability.
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http://dx.doi.org/10.2147/OPTH.S74849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404875PMC
May 2015

Efficacy, safety, and acceptability of a lipid-based artificial tear formulation: a randomized, controlled, multicenter clinical trial.

Clin Ther 2015 Apr 4;37(4):858-68. Epub 2015 Feb 4.

Allergan Clinical Research, Allergan, Inc, Irvine, California.

Purpose: Dry eye disease is highly prevalent worldwide, causing discomfort and visual disturbances that can limit basic activities such as reading and driving. Although artificial tears represent first-line therapy, there is a paucity of published controlled clinical trials. The present study compared the efficacy, clinical safety, and acceptability of 2 multicomponent, lipid-based tear formulations (ADV1 and ADV2) to those of an existing lipid-based tear formulation (DET) in patients with signs and symptoms of dry eye disease.

Methods: This 3-month, multicenter, double-masked study was conducted in patients with dry eye symptoms, reduced tear break-up time (TBUT), and ocular surface damage. Patients were randomized to receive 1 of 2 lipid-based tear formulations containing carboxymethylcellulose, glycerin, polysorbate 80, and emulsified lipid (ADV1 or ADV2) or DET, and instilled 1 to 2 drops per eye at least twice daily. The primary end point was the mean change from baseline in Subjective Evaluation of Symptom of Dryness score at day 90 to determine noninferiority of the 2 ADV formulations versus DET. Secondary end points included Ocular Surface Disease Index (OSDI) score, TBUT, ocular surface staining, and tolerability.

Findings: Of 288 randomized patients, 256 completed the study. All 3 groups showed improvement in symptoms, and the 2 lipid-based formulations were noninferior to DET in reducing the severity of symptoms of dryness at 90 days. Of the 3 treatment groups, the ADV2 group had the greatest improvements in TBUT and OSDI. Significant improvements in mean tolerability scores for comfort, soothing, burning/stinging, and discomfort were observed in the ADV2 group versus the DET group at 90 days. Treatment-related adverse events were reported in 13 patients (13.4%) receiving ADV1, 8 (8.4%) receiving ADV2, and 21 (21.9%) receiving DET. Four patients (4.1%) in the ADV1 group and 2 (2.1%) in the ADV2 group discontinued owing to an adverse event compared with 14 (14.6%) receiving DET.

Implications: In these patients with dry eye symptoms, ADV2 was an effective and relatively well-tolerated artificial tear for first-line therapy and should be considered as a treatment option for dry eye, especially in those patients who would benefit from a lipid-based formulation in addition to lubrication. https://clinicaltrials.gov/ct2/show/NCT01010282.
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http://dx.doi.org/10.1016/j.clinthera.2015.01.001DOI Listing
April 2015

Decrease in hyperosmotic stress-induced corneal epithelial cell apoptosis by L-carnitine.

Mol Vis 2013 19;19:1945-56. Epub 2013 Sep 19.

Brien Holden Vision Institute, Sydney, Australia.

Purpose: To characterize the osmoprotective properties of L-carnitine on human corneal epithelial cell volume and apoptosis during hyperosmotic stress.

Methods: Human corneal limbal epithelial (HCLE) cells were exposed to culture medium at 300 mOsm (isotonic) or 500 mOsm (hyperosmotic) with or without L-carnitine (10 mM). Induction of apoptosis was detected by quantifying the proteolytic activity of caspase-8, caspase-9, and caspase-3/7 using caspase activity assays, the expression of tumor necrosis factor (TNF)-α with enzyme-linked immunosorbent assay, and annexin V/propidium iodide staining of HCLE cells evaluated with confocal microscopy and flow cytometry. Cell volume changes in response to hyperosmotic stress were analyzed using flow cytometry.

Results: After the HCLE cells were exposed to hyperosmotic medium (500 mOsm), the percentage of shrunken cells and damaged/dead cells (stained positively for annexin V and/or propidium iodide) was six- and three-fold, respectively, higher than that under isotonic conditions (300 mOsm). This was paralleled by an increase in TNF-α concentration in media and caspase-8, -9, and -3/7 activities (six-, four-, ten-, and twelve-fold, respectively; all showing p < 0.001). Addition of L-carnitine during hyperosmotic stress partly restored cell volume and significantly reduced the concentration of TNF-α released (p = 0.005) and caspase-9 activity (p = 0.0125). Addition of L-carnitine reduced the percentage of hyperosmolarity-induced damaged/dead cells to levels observed under isotonic conditions.

Conclusions: L-carnitine can regulate human corneal epithelial cell volume under hyperosmotic stress and ameliorate hyperosmotic stress-induced apoptosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782369PMC
March 2014

Looming detection by identified visual interneurons during larval development of the locust Locusta migratoria.

J Exp Biol 2013 Jun 26;216(Pt 12):2266-75. Epub 2013 Mar 26.

Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.

Insect larvae clearly react to visual stimuli, but the ability of any visual neuron in a newly hatched insect to respond selectively to particular stimuli has not been directly tested. We characterised a pair of neurons in locust larvae that have been extensively studied in adults, where they are known to respond selectively to objects approaching on a collision course: the lobula giant motion detector (LGMD) and its postsynaptic partner, the descending contralateral motion detector (DCMD). Our physiological recordings of DCMD axon spikes reveal that at the time of hatching, the neurons already respond selectively to objects approaching the locust and they discriminate between stimulus approach speeds with differences in spike frequency. For a particular approaching stimulus, both the number and peak frequency of spikes increase with instar. In contrast, the number of spikes in responses to receding stimuli decreases with instar, so performance in discriminating approaching from receding stimuli improves as the locust goes through successive moults. In all instars, visual movement over one part of the visual field suppresses a response to movement over another part. Electron microscopy demonstrates that the anatomical substrate for the selective response to approaching stimuli is present in all larval instars: small neuronal processes carrying information from the eye make synapses both onto LGMD dendrites and with each other, providing pathways for lateral inhibition that shape selectivity for approaching objects.
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http://dx.doi.org/10.1242/jeb.083360DOI Listing
June 2013

Effect of humidity variations in a controlled environment chamber on tear evaporation after dry eye therapy.

Eye Contact Lens 2013 Mar;39(2):169-74

Vision Sciences, Glasgow Caledonian University, Glasgow G4 OBA, United Kingdom.

Purpose: Many dry eye (DE) patients are sensitive to adverse environments where tear evaporation rate (TER) increases. Pilot study-A controlled environment chamber was used to determine the time of exposure required for TER to reach steady state equilibrium at 40% relative humidity (RH). Study 1-To assess the difference between normal and DE subjects in their tear physiology response. Study 2-To determine, under varying environmental conditions, the efficacy of an emulsion eye drop on tear physiology.

Methods: Pilot study-TER adaptation time was determined by exposing 3 normal and 3 DE subjects to RH of 40% at 72°F for 0, 5, 10, 15, 20, and 25 minutes. Study 1-The difference in noninvasive tear breakup time (NITBUT) and TER responses between DE and normal subjects were determined at various RH from 5% to 70% (at 72°F) for 20 subjects (10 normal subjects; 10 DE subjects). Study 2-To assess the efficacy of an emulsion eye drop, the same 20 subjects were dosed four times per day for 7 days with a drop containing emulsified castor oil and reassessed.

Results: Pilot study-Evaporation at 40% RH showed a peak (around 5 minutes) followed by a decline to steady state level at 10 minutes. Dry eye subjects showed greater evaporation than normal subjects at 40% and 5% RH but not at 70%, where TER declined to zero in both groups. No significant change in NITBUT was found in either group for the various exposure times of the test period (P>0.05). Study 1-TER was higher in DE compared with normal subjects at 5% or 40% RH, however reduced to almost zero in both groups at 70% RH. A significant difference in NITBUT was found between the DE and normal groups at each humidity (P<0.05). Study 2-An emulsion-based drop effectively lowered the TER, especially in DE patients. For NITBUT, a significant improvement in both normal and DE subjects was found at 5% and 40% but not at 70% RH levels.

Conclusions: Pilot study-TER measurements required at least 10 minutes in the chamber to obtain a steady-state TER with no significant change to NITBUT. Study 1-TER has a reverse correlation with environmental humidity in the range of 5% to 70%, with TER reduced to zero at 70% RH. Dry eye subjects had a higher TER at all RH levels below 70%, and NITBUT is significantly different between DE and normal subjects at all humidities. Study 2-Emulsion-based drops reduced TER in DE patients by an amount equivalent to that obtained by raising environmental humidity by 30%. Noninvasive tear breakup time was improved in both normal and DE subjects at lower RH levels.
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http://dx.doi.org/10.1097/ICL.0b013e318283dfc6DOI Listing
March 2013

Effectiveness of dry eye therapy under conditions of environmental stress.

Curr Eye Res 2013 Feb 7;38(2):229-36. Epub 2013 Jan 7.

Vision Sciences, Glasgow Caledonian University, Glasgow, UK.

Purpose: Dry eye is often characterized by increased tear evaporation due to poor tear film quality, especially of the lipid component of the tear film. Using an environmental chamber to induce environmental stress, this study compared the effect of three lubricant eye drops on various aspects of tear physiology in a crossover design (evaporation was the principal outcome measure).

Methods: Three eye drop formulas were tested: 0.5% carmellose sodium (Drop C), 0.5% carmellose sodium with added lipid (Drop C-L) and 1.0% glycerine with added lipid (Drop G-L). Nineteen control and 18 dry eye subjects used each product for 2 weeks, three times per day, in a random order, with a minimum 1-week washout between treatment periods. Tear evaporation, break up time, osmolarity, tear structure (by interferometry) and patient symptoms were assessed with the subjects adapted for 10 min in an environmental chamber controlled at 20% relative humidity and 22 °C. The treatment effects were analyzed using general linear model repeated measures analyses of variance.

Results: In dry eye subjects, evaporation, break up time, osmolarity and symptoms improved for all formulas (p < 0.05). Normal subjects showed some improvements: evaporation with C-L, osmolarity with C and symptoms with C-L and G-L. Change in evaporation was greater for both C-L and G-L versus C (p < 0.05), and there was a trend for C-L to reduce evaporation more than G-L (p < 0.11). There were no significant treatment effects on tear film structure.

Conclusion: Overall, the eye drop formula containing both carmellose sodium and lipid (C-L) produced a greater treatment effect on tear evaporation than the other formulations containing only one of these ingredients. This study also demonstrates the utility of a controlled environmental chamber in showing the difference in performance between dry eye treatments.
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http://dx.doi.org/10.3109/02713683.2012.757323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585441PMC
February 2013

Betaine stabilizes cell volume and protects against apoptosis in human corneal epithelial cells under hyperosmotic stress.

Exp Eye Res 2013 Mar 12;108:33-41. Epub 2012 Dec 12.

Brien Holden Vision Institute, Sydney, Australia.

Elevated tear osmolarity is one of the key pathological factors in dry eye leading to ocular discomfort associated with damage to the ocular surface and inflammation. The aim of this study was to determine the capacity of the organic osmolyte, betaine, to act as an osmoprotectant against hypertonic stress-induced human corneal epithelial cell shrinkage and apoptosis using in vitro cell culture models. Human corneal limbal epithelial (HCLE) cells exposed to culture medium for 16 h at 300 mOsm (isotonic) or 500 mOsm (hyperosmotic) in the presence or absence of betaine (5 or 10 mM) were evaluated for cell volume changes; cell viability; and apoptosis. Betaine (10 mM) ameliorated hyperosmotically induced reduction of cell volume (from 27% reduction to 11%) and resulted in increased mitochondrial activity (by 17%) and an increase in viable cell numbers (by 12%) compared to controls (exposure to hyperosmotic medium without betaine). Hyperosmotically shocked HCLE cells in the presence of betaine (10 mM) halved the number of damaged cells (apoptotic/necrotic) compared to cells in the absence of betaine. The presence of betaine (at 5 or 10 mM) significantly reduced the activity of caspase-8, -9 and -3/7 and release of TNF-α was also reduced by 34% or 55% after exposure of HCLE to 500 mOsm in the presence of 5 or 10 mM betaine, respectively. Using polyclonal antibody against Betaine/GABA transporter 1 (BGT-1), we detected the presence of BGT-1 in HCLE. We demonstrated that the transport of betaine was facilitated by increased osmolarity. In conclusion, betaine stabilized corneal epithelial cell volume under hyperosmotic stress and limited hyperosmotic stress-induced HCLE apoptosis.
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http://dx.doi.org/10.1016/j.exer.2012.12.001DOI Listing
March 2013

Predator versus prey: locust looming-detector neuron and behavioural responses to stimuli representing attacking bird predators.

PLoS One 2012 27;7(11):e50146. Epub 2012 Nov 27.

Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth, United Kingdom.

Many arthropods possess escape-triggering neural mechanisms that help them evade predators. These mechanisms are important neuroethological models, but they are rarely investigated using predator-like stimuli because there is often insufficient information on real predator attacks. Locusts possess uniquely identifiable visual neurons (the descending contralateral movement detectors, DCMDs) that are well-studied looming motion detectors. The DCMDs trigger 'glides' in flying locusts, which are hypothesised to be appropriate last-ditch responses to the looms of avian predators. To date it has not been possible to study glides in response to stimuli simulating bird attacks because such attacks have not been characterised. We analyse video of wild black kites attacking flying locusts, and estimate kite attack speeds of 10.8±1.4 m/s. We estimate that the loom of a kite's thorax towards a locust at these speeds should be characterised by a relatively low ratio of half size to speed (l/|v|) in the range 4-17 ms. Peak DCMD spike rate and gliding response occurrence are known to increase as l/|v| decreases for simple looming shapes. Using simulated looming discs, we investigate these trends and show that both DCMD and behavioural responses are strong to stimuli with kite-like l/|v| ratios. Adding wings to looming discs to produce a more realistic stimulus shape did not disrupt the overall relationships of DCMD and gliding occurrence to stimulus l/|v|. However, adding wings to looming discs did slightly reduce high frequency DCMD spike rates in the final stages of object approach, and slightly delay glide initiation. Looming discs with or without wings triggered glides closer to the time of collision as l/|v| declined, and relatively infrequently before collision at very low l/|v|. However, the performance of this system is in line with expectations for a last-ditch escape response.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0050146PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507823PMC
June 2013

The effects of temperature on signalling in ocellar neurons of the desert locust, Schistocerca gregaria.

Authors:
Peter J Simmons

J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2011 Nov 10;197(11):1083-96. Epub 2011 Aug 10.

Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.

In Schistocerca gregaria ocellar pathways, large second-order L-neurons use graded potentials to communicate signals from the ocellar retina to third-order neurons in the protocerebrum. A third-order neuron, DNI, converts graded potentials into axonal spikes that have been shown in experiments at room temperature to be sparse and precisely timed. I investigated effects of temperature changes that a locust normally experiences on these signals. With increased temperature, response latency decreases and frequency responses of the neurons increase. Both the graded potential responses in the two types of neuron and the spikes in DNI report greater detail about a fluctuating light stimulus. Over a rise from 22 to 35°C the power spectrum of the L-neuron response encompasses higher frequencies and its information capacity increases from about 600 to 1,700 bits/s. DNI generates spikes more often during a repeated stimulus but at all temperatures it reports rapid decreases in light rather than providing a continual measure of light intensity. Information rate carried by spike trains increases from about 50 to 185 bits/s. At warmer temperatures, increased performance by ocellar interneurons may contribute to improved aerobatic performance by delivering spikes earlier and in response to smaller, faster light stimuli.
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http://dx.doi.org/10.1007/s00359-011-0669-yDOI Listing
November 2011

Structural organization of the presynaptic density at identified synapses in the locust central nervous system.

J Comp Neurol 2012 Feb;520(2):384-400

Institute of Cell Biology, Histology and Embryology, Center for Molecular Medicine (ZMM), Medical University of Graz, Austria. [email protected]

In a synaptic active zone, vesicles aggregate around a densely staining structure called the presynaptic density. We focus on its three-dimensional architecture and a major molecular component in the locust. We used electron tomography to study the presynaptic density in synapses made in the brain by identified second-order neuron of the ocelli. Here, vesicles close to the active zone are organized in two rows on either side of the presynaptic density, a level of organization not previously reported in insect central synapses. The row of vesicles that is closest to the density's base includes vesicles docked with the presynaptic membrane and thus presumably ready for release, whereas the outer row of vesicles does not include any that are docked. We show that a locust ortholog of the Drosophila protein Bruchpilot is localized to the presynaptic density, both in the ocellar pathway and compound eye visual neurons. An antibody recognizing the C-terminus of the Bruchpilot ortholog selectively labels filamentous extensions of the presynaptic density that reach out toward vesicles. Previous studies on Bruchpilot have focused on its role in neuromuscular junctions in Drosophila, and our study shows it is also a major functional component of presynaptic densities in the central nervous system of an evolutionarily distant insect. Our study thus reveals Bruchpilot executes similar functions in synapses that can sustain transmission of small graded potentials as well as those relaying large, spike-evoked signals.
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http://dx.doi.org/10.1002/cne.22744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263340PMC
February 2012

Transport of L-carnitine in human corneal and conjunctival epithelial cells.

Mol Vis 2010 Sep 4;16:1823-31. Epub 2010 Sep 4.

Brien Holden Vision Institute, The University of New South Wales, Sydney, NSW, Australia.

Purpose: Previously we demonstrated expression and localization of carnitine/organic cation transporters, OCTN1 and OCTN2, in human corneal and conjunctival epithelia. The present study aimed to examine the characteristics of L-carnitine transporters in cultured human limbal corneal (HCLE) and conjunctival epithelial (HCjE) cells.

Methods: Time-course, Na(+)-dependence, kinetics, energy- and pH- dependence of L-carnitine transport were investigated by monitoring L-[(3)H]carnitine uptake into HCLE and HCjE cells. To determine the specificity of action, competition and inhibition studies were performed.

Results: The uptake of L-carnitine into HCLE and HCjE cells was saturable and time-dependent. An Eadie-Hofstee plot showed two distinct components: a high- and a low- affinity carnitine transport system in HCLE and/or HCjE cells. L-carnitine transport was significantly inhibited by the metabolic inhibitors (sodium azide, dinitrophenol, iodoacetic acid). The L-carnitine analogs (D-carnitine, acetyl-L-carnitine and γ-butyrobetaine), tetraethylammonium (TEA), 2-amino-2-norbornane carboxylic acid (BCH), strongly inhibited uptake of L-[(3)H]carnitine. Uptake of L-[(3)H]carnitine also required the presence of Na(+) in the external medium and the uptake activity was maximal at pH 5.5. The anti-OCTN2 antibody blocked L-carnitine uptake in both HCLE and HCjE cells whereas the anti-OCTN1 antibody did not significantly block L-carnitine uptake.

Conclusions: L-carnitine is transported into HCLE and HCjE cells by an active carrier mediated transport system that is time-, Na(+)-, energy- and pH- dependent. The carnitine/organic cation transporter OCTN2 appears to play a dominant role in this process.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956661PMC
September 2010

Sparse but specific temporal coding by spikes in an insect sensory-motor ocellar pathway.

J Exp Biol 2010 Aug;213(Pt 15):2629-39

Institute of Neuroscience and School of Biology, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

We investigate coding in a locust brain neuron, DNI, which transforms graded synaptic input from ocellar L-neurons into axonal spikes that travel to excite particular thoracic flight neurons. Ocellar neurons are naturally stimulated by fluctuations in light collected from a wide field of view, for example when the visual horizon moves up and down. We used two types of stimuli: fluctuating light from a light-emitting diode (LED), and a visual horizon displayed on an electrostatic monitor. In response to randomly fluctuating light stimuli delivered from the LED, individual spikes in DNI occur sparsely but are timed to sub-millisecond precision, carrying substantial information: 4.5-7 bits per spike in our experiments. In response to these light stimuli, the graded potential signal in DNI carries considerably less information than in presynaptic L-neurons. DNI is excited in phase with either sinusoidal light from an LED or a visual horizon oscillating up and down at 20 Hz, and changes in mean light level or mean horizon level alter the timing of excitation for each cycle. DNI is a multimodal interneuron, but its ability to time spikes precisely in response to ocellar stimulation is not degraded by additional excitation. We suggest that DNI is part of an optical proprioceptor system, responding to the optical signal induced in the ocelli by nodding movements of the locust head during each wing-beat.
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http://dx.doi.org/10.1242/jeb.043547DOI Listing
August 2010

Escapes with and without preparation: the neuroethology of visual startle in locusts.

J Insect Physiol 2010 Aug 5;56(8):876-83. Epub 2010 May 5.

Institute of Neuroscience and School of Biology, Ridley Building, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK.

Locusts respond to the images of approaching (looming) objects with responses that include gliding while in flight and jumping while standing. For both of these responses there is good evidence that the DCMD neuron (descending contralateral movement detector), which carries spike trains from the brain to the thoracic ganglia, is involved. Sudden glides during flight, which cause a rapid loss of height, are last-chance manoeuvres without prior preparation. Jumps from standing require preparation over several tens of milliseconds because of the need to store muscle-derived energy in a catapult-like mechanism. Locusts' DCMD neurons respond selectively to looming stimuli, and make connections with some motor neurons and interneurons known to be involved in flying and jumping. For glides, a burst of high-frequency DCMD spikes is a key trigger. For jumping, a similar burst can influence timing, but neither the DCMD nor any other single interneuron has been shown to be essential for triggering any stage in preparation or take-off. Responses by the DCMD to looming stimuli can alter in different behavioural contexts: in a flying locust, arousal ensures a high level of both DCMD responsiveness and glide occurrence; and there are significant differences in DCMD activity between locusts in the gregarious and the solitarious phase.
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http://dx.doi.org/10.1016/j.jinsphys.2010.04.015DOI Listing
August 2010

Role of carnitine in disease.

Nutr Metab (Lond) 2010 Apr 16;7:30. Epub 2010 Apr 16.

Institute for Eye Research, Sydney, New South Wales, Australia.

Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.
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http://dx.doi.org/10.1186/1743-7075-7-30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861661PMC
April 2010

Decision-makers' perspectives on the use of bioaccessibility for risk-based regulation of contaminated land.

Environ Int 2010 May 29;36(4):383-389. Epub 2010 Mar 29.

University of East Anglia, School of Environmental Sciences, NR4 7TJ, Norwich, Norfolk, UK. Electronic address:

Information on contaminant bioaccessibility has been recognized by researchers, legislators and regulators as a decision-support tool for contaminated land assessment and has been subject to interest and discussion at both national and international levels. A sustainable, proportionate and risk-based approach to contaminated land management has been adopted by contaminated land regimes throughout the world. While this approach guides national and international priorities, its practical implementation in many countries, including the United Kingdom, is reliant upon local authorities. Here, we present an investigation into the views of local authorities in England and Wales regarding the practical application of bioaccessibility and constraints associated with its implementation. The research involved an online survey followed by semi-structured interviews with selected respondents. A majority of survey respondents (70%) perceived bioaccessibility to be a useful tool that facilitates contaminated land management. However, 76% of participants indicated a need for more information regarding bioaccessibility as well as emphasising a need for more research into polycyclic aromatic hydrocarbons. Lack of statutory guidance was indicated by 78% of respondents as the main factor hampering the use of bioaccessibility data in regulatory decision-making. Divergence of policy-maker and local regulator perceptions of bioaccessibility was also indicated by the respondents. This research brings the voice of front-line regulators for contaminated land into the on-going discussion between policy-makers and scientists on the uses of bioaccessibility. This study concludes by proposing action priorities both for the research community and for policy-makers, which are transferable to risk-based regimes elsewhere.
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http://dx.doi.org/10.1016/j.envint.2010.02.007DOI Listing
May 2010

Effect of castor oil emulsion eyedrops on tear film composition and stability.

Cont Lens Anterior Eye 2010 Apr 6;33(2):76-82. Epub 2009 Dec 6.

OTG Research & Consultancy, London, UK.

Purpose: An emulsion eyedrop containing castor oil has been shown to modify the tear film lipid layer and increase tear film stability. The primary objectives of this investigation were to measure the prevalence of castor oil in the tear fluid over time and quantify the effects on the lipid layer. A secondary objective was to quantify the initial effects on ocular symptomatology.

Methods: The investigation was an open label pilot study on 5 normal and 10 dry eye subjects. A single eyedrop (Castor oil emulsion, Allergan) was instilled in each eye; the tear film appearance and composition were monitored for 4h via in vivo visualisation using the Tearscope and post in vivo tear samples analysis by HPLC.

Results: Combined results for both normal and dry eye subjects showed that castor oil was detected up to 4h after a single eyedrop instillation and associated with an increase in the level of tear film lipid. The relative amount of various lipid families was also changed. An increase in tear lipid layer thickness was significant up to one hour post-instillation for the symptomatic sub-population. The changes in tear film characteristics were associated with significantly lower symptoms up to four hours post-instillation for the symptomatic sub-population.

Conclusion: This pilot investigation showed that castor oil eyedrops achieved a residence time of at least four hours post-instillation, producing a more stable tear film and an associated significant decrease in ocular symptoms over the entire follow-up period for the symptomatic subjects.
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http://dx.doi.org/10.1016/j.clae.2009.10.005DOI Listing
April 2010

Absencing/presencing risk: Rethinking proximity and the experience of living with major technological hazards.

Geoforum 2009 Sep 11;40(5):864-872. Epub 2009 Sep 11.

School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom.

There is now a substantial body of sociocultural research that has investigated the ways in which specific communities living in physical proximity with a variety of polluting or hazardous technological installations experience and respond to their exposure to the associated risk. Much of this research has sought to understand the apparent acceptance or acquiescence displayed by local populations towards established hazards of the kind that are typically resisted when the subject of siting proposals. However, recent theoretical contributions, produced largely outside the field of risk research, have problematised the objective distinction between proximity and distance. In this paper we explore the potential of some of these ideas for furthering our understanding of the relationship between place and the constitution of risk subjectivities. To do this we re-examine a number of existing sociocultural studies that are predicated on a localised approach and conceptualise the relationship of physically proximate sources of risk to everyday experience in terms of practices of 'presencing' and 'absencing'. We conclude with some thoughts on the methodological and substantive implications of this reworking of proximity for future research into risk subjectivities.
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http://dx.doi.org/10.1016/j.geoforum.2009.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094491PMC
September 2009
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