These antioxidants also help to protect the structural integrity of ischaemic or hypoxic tissues, and might have useful anti-thrombotic actions as well. Prevention, treatment, or palliation of cancer, cardiovascular disease, infection, inflammatory disorders, and some

complications arising out of diabetes could probably be better managed by supplementating with high doses of nutritional antioxidants.15 RAD001 mw Antioxidants play a vital role in both food systems as well as in the human body to reduce oxidative processes. In food systems, retarding lipid peroxidation and formation of secondary lipid peroxidation product can be prevented by the use of nutritional antioxidants thereby helping to maintain flavour, texture, and the colour of the food product during storage. Also learn more antioxidants are helpful in reducing protein oxidation as well as the interaction of lipid-derived carbonyls with proteins that leads to an alteration of protein function.26 Natural antioxidants such as vitamin C, tocopherols along with herbal extracts like rosemary, sage and tea have already been commercialized to be used as alternatives to synthetic antioxidants in food systems.27 Proteins and protein hydrolysates derived from sources like milk, soya, egg, and fish also exhibit antioxidant activity in various muscle foods.28, 29 and 30 In the human body, oxidative damage caused by reactive oxygen and

reactive nitrogen species such as hydroxyl radicals (OH−), peroxyl radicals (OOR−), superoxide anion (O2−), and peroxynitrite (ONOO−) is protected ADAMTS5 with the help of endogenous antioxidants. The endogenous antioxidative systems include enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, along with various non-enzymatic compounds such as selenium, α-tocopherol, and vitamin C.31 Apart from these, contribution of amino

acids, peptides, and proteins also helps in overall antioxidative capacity of cells and towards maintaining the health of biological tissues. For example, blood proteins are estimated to scavenge 10–50% of the peroxyl radicals formed in the plasma.32 and 33 Peptides like carnosine, anserine, and glutathione are well-known for their endogenous antioxidative activity.34 However, with progression of age the antioxidant-prooxidant balance in human body changes along with other factors such as environmental pollutants, fatigue, excessive alcohol intake, and high fat diets. The plasma and cellular antioxidant potential as well as the absorption of nutrients, including antioxidants, gradually diminish with progressing age.35 and 36 Researches have also indicated an accumulation of protein carbonyls with the ageing process in humans as a result of the action of free radicals on the proteins.37 and 38 Use of dietary antioxidants has been recognized as potentially effective to promote human health by increasing the body’s antioxidant load.

The H1 recombinant fusion protein of Ag85B and ESAT-6, is developed and manufactured by Statens Serum Institut (SSI, Copenhagen, Denmark). H1 sterile solution and CAF01 sterile suspension were manufactured by SSI, in an accredited

GMP facility and supplied to the LUMC pharmacy in separate vials of relevant strengths. The vaccine was reconstituted by addition of the specified volume of adjuvant to the antigen concentrate, and injected into the deltoid muscle with a 25 mm 22–25 Gauge needle in a volume of 0.5 ml. The trial was an open label, single-center, non-randomized phase I exploratory trial in mycobacteria-naïve individuals defined by a negative TST (<10 mm, 2 units RT-23 PPD (SSI, Denmark)) and a negative Quantiferon®-TB Gold In-Tube test (QFT; Qiagen, Venlo, The Netherlands). All individuals were HIV negative. The trial comprised four vaccination groups. Subjects in group 1 received 50 μg H1 with no adjuvant, whereas groups CT99021 chemical structure 2–4 received the same amount of antigen with 125/25 μg, 313/63 μg and 625/125 μg

CAF01, respectively. In all vaccination groups, the subjects were vaccinated on trial days 0 and 56. After Saracatinib the original trial was completed, a protocol amendment was approved (CCMO 12.1306/MA/26270, NL26270.000.09) and all trial participants were invited to attend a long-term visit 150 weeks after initial enrolment. Long-term visits were successfully conducted for 31 out of the original 34 volunteers that received

2 vaccinations within the appropriate time window. Timing of the long-term visit was on average 150.7 weeks (median 152.1 weeks; range 123–167 weeks) post primary vaccination and is referred to as ‘150 weeks’ throughout the manuscript. The trial population consisted of 38 volunteers, healthy adult females or males between 18 and 55 years of age who had not been BCG vaccinated and who did not have active, chronic or past TB disease, and who had no MTB infection as confirmed by a negative QFT and a negative TST at screening. The general health of all participants was assessed by reviewing their recorded medical history, and performing a physical examination, and standard blood (including hepatitis B, hepatitis C and HIV testing) and urine tests. The volunteers were financially compensated as approved by the Institutional Review Board for the Non-specific serine/threonine protein kinase number and amount of blood and urine samples, inconvenience with respect to the intramuscular administration and for the time spent on trial visits and transportation to the trial site. The subjects remained under medical observation for 3 h after each intramuscular vaccination, for possible immediate adverse reactions. During the first week after each vaccination, symptoms and evening armpit temperature were recorded on a daily basis, thereafter on a weekly basis. A medical examination of local adverse reactions and temperature was performed on days 0, 1, 7 and 42 after both vaccinations.

Immunoreactive bands were visualized using the enhanced chemiluminescence (ECL) plus or ECL prime systems and were quantified using densitometry. In addition, a portion of the RASMCs were further incubated for 24 h to detect cell viability using a 3-[4, 5-dimethylthiazol-2-phenyl]-2, 5-diphenyl-tetrazolium bromide (MTT) assay and cell death according to the Ponatinib concentration release of lactate dehydrogenase (LDH) into the medium. In some studies, RASMCs were pre-incubated with olmesartan, a JNK inhibitor (SP600125), and a p38 inhibitor

(SB203580) for 10 min, 20 min, and 4 h, respectively, before stimulation with cyclic mechanical stretch. Band intensities were quantified using the densitometry of the immunoblot with NIH Image J software. Olmesartan

(RNH-6270) was kindly provided by Daiichi-Sankyo Screening Library Co., Ltd. (Tokyo). All other materials were purchased from Wako (Kyoto) or Nakalai Tesque (Kyoto) unless stated otherwise. The antibodies used for western blot analysis, anti-pan- or phospho-SAPK/JNK (Thr183/Tyr185) antibody and anti-pan- or phospho-p38 MAP kinase (Thr180/Tyr182) antibody, were purchased from Cell Signaling Technology. The ECL plus and ECL prime systems were purchased from GE Healthcare. Collagen I was purchased from Nippon Meat Packers, Inc. (Osaka). All chemical compounds were dissolved in dimethyl sulfoxide (DMSO) to a final concentration of less than 1%, except where specifically noted. Data are reported as the mean ± standard deviation (S.D.). We used a Student’s t-test with Fisher’s post-hoc test for intergroup comparison. A P-value of <0.05 was considered to indicate statistical significance. The effect of cyclic mechanical stretch on RASMC death was examined by measuring the MTT reduction and LDH release from the cells. Fig. 1A and B show the viability and

death rate of RASMCs subject to cyclic mechanical stretch by 20% elongation for 0–4 h, respectively. It was observed that the cell viability was decreased by stretch in a time-dependent manner and 35% of cells were dead at 4 h, evaluated based on the MTT reduction (Fig. 1A). In accordance with these results, the LDH release from RASMCs was increased by stretch in a time-dependent manner up to 4 h (Fig. 1B). These results suggest that Dipeptidyl peptidase cyclic mechanical stretch-induced death in the RASMCs. Next, we examined the effect of olmesartan on cyclic mechanical stretch-induced death in RASMCs. As shown in Fig. 2, it was obvious that cell viability was significantly recovered with olmesartan treatment in a concentration-dependent manner. The effects of cyclic mechanical stretch on the activation of JNK and p38 were assessed using western blot analysis with phospho-specific antibodies. RASMCs were exposed to cyclic mechanical stretch with a 20% elongation for different periods of time and the phosphorylation of JNK and p38 was measured. As shown in Fig.

HPLC data acquisition and processing this website was performed by Shimadzu LC Solutions Ver 1.23 SP 1 software. PZA belongs to the basic class of drugs due to its amide functional group. Therefore adjusting the pH of mobile phase to the acidic side ionizes the PZA present in plasma thereby leading to poor recovery. In order to extract the un-ionized form of the drug, it is imperative to adjust the pH to the alkaline side, however, alkaline mobile phase characteristics causes deterioration of the bonded phase in the column due to alkaline hydrolysis of end-capped silica. Compared to acid catalyzed hydrolysis, the hydrolysis of end-capped

silica in alkaline conditions is usually very rapid. Therefore experiments were performed using potassium dihydrogen phosphate in a limited range of pH 7.0–8.0. The response was checked at the detector using a connector (without the column). A pH value of 7.4 ± 0.1 gave maximum VE822 response for the analyte at 268 nm. The run time of analysis was higher when a longer reverse phase column (250 × 4.6 mm i.d,) was used. The resolution

between the peaks was decreased and peaks were not of acceptable peak shape when the experiment was performed using a shorter column (50 × 4.6 mm i.d,). However better resolution, less tailing and high theoretical plates were obtained with Phenomenex column C18 150 × 4.6 cm 5 μm column. The mobile consists of 15:85 v/v methanol and 10 mM potassium dihydrogen phosphate (pH 7.4). The flow rate of the method was 1.0 ml/min. The column temperature was maintained at 25 °C. At the reported flow rate peak shape was excellent,

however, increasing or decreasing the from flow rate increased the tailing factor and resulted in poor peak shape and in decreased resolution between the drug and internal standard. There was no interference in the drug and the internal standard, from the extracted blank. The peak shape and symmetry were found to be good when the mobile phase composition of 15:85 v/v was used with better resolution of the drug and internal standard. Increasing the organic portion of the mobile phase caused PZA to elute with high tailing and also merging of the peaks for PZA and MTZ. A mobile phase containing aqueous portion greater than 85% led to very late elution and very poor peak shape for MTZ. The peaks were also broad and had unacceptable asymmetry factor. Extraction methods were initially attempted using protein precipitation technique. Organic solvents such as acetonitrile and/or methanol were used as reagents for protein precipitation.13 Initial experiments of protein precipitation were done using 1:3 ratio of plasma:organic solvents. The recovery of the PZA was poor while that of the internal standard was relatively unchanged as compared with liquid–liquid extraction. Since the noise effects in solid phase extraction (SPE) method are similar to that of liquid–liquid extraction, the final analysis was carried out using liquid–liquid extraction (LLE).

The number of serotypes causing RVGE of any severity during Year 2 in the HRV_2D, HRV_3D and placebo groups were 3, 1, and 5, respectively for G1P [8]; 2, 2, and 4 respectively for G2/P [4] or P [6]; and 1 case of G12P [6] in a HRV_2D recipient. The ATP analysis for seroconversion consisted of 205 subjects from Cohort 1 (70 subjects in the HRV_2D group, 66 subjects in the HRV_3D group and 69 subjects in the placebo group) from whom blood had been obtained prior to the first dose and 1 month following the third dose of study vaccine. The seroconversion rate selleck products in the HRV_3D group was moderately higher (66.7%; 95% CI: 54.0–77.8%), although not significantly, than in the HRV_2D group (57.1%; 95% CI: 44.7–68.9%)

(Fig. 2). Similarly, a trend toward higher GMCs was observed in the HRV_3D group (94.3 U/mL; 95% CI: 56.5–157.4 U/mL) than the HRV_2D group (59.4 U/mL; 95% CI: 37.5–93.9 U/mL). This analysis confirmed protection against severe RVGE by Rotarix over 2 consecutive rotavirus seasons in South African children for the combined endpoint of infants who had received either a 2-dose or 3-dose HRV schedule during infancy. The 59% reduction of severe GSI-IX price RVGE

over 2 consecutive rotavirus seasons in the pooled cohort of HRV recipients was lower than the point-estimate observed during the first rotavirus season (77%; 95% CI: 56–88), which also included a combined analysis of Cohort 1 and Cohort 2 subjects enrolled in the study in South Africa. Interestingly, these results are similar to that observed in another vaccine study in 3 African countries with the pentavalent rotavirus vaccine [4]. In that study, efficacy against severe rotavirus diarrhea during the first two years of age in 3 African countries, was 39.3%; although vaccine efficacy against severe rotavirus diarrhea in the first year of life was 64.2%. This is distinct from the situation reported in Latin America, the US, Europe, or middle-income countries in Asia, where the level of clinical protection was maintained at very similar levels

over 2 years [7], [8], [9] and [10]. One of the Non-specific serine/threonine protein kinase possible explanations for this difference, besides the higher immunogenicity and higher point-estimate of efficacy in the European and pan-American studies, is the age at which children are infected with rotavirus. In Africa, rotavirus infections occur commonly in young infants between 3 and 12 months of age, where >75% of children with severe rotavirus gastroenteritis from hospital-based studies are observed [13], [21], [22] and [23] and only approximately 10% of rotavirus disease requiring a visit to hospital or the outpatient clinic was in the 12- to 18-month-old group in several African countries [24]. On the other hand, studies from Europe indicate that while rotavirus infection peaks in children 6–24 months of age [25], 40% of infection occurs in the group 12–23 months of age [26].

Participants were excluded if they had: an unstable cardiac status precluding them from participation in a treadmill training program (ie, permission not granted by their medical practitioner); or had severe

cognitive and/or language deficits (aphasia) precluding them from participation Cytoskeletal Signaling inhibitor in the training sessions (ie, unable to follow two-step commands). Participants were divided into two subgroups according to baseline comfortable walking speed (> 0.4 m/s and ≤ 0.4 m/s), measured during a 10-m walk test. This cut-off was decided prior to analysis.7 The experimental group received training based on a previous treadmill walking program.9 Thirty minutes of walking was carried out three times a week for 16 weeks. Given that participants could already walk, treadmill training was conducted without Selleckchem GPCR Compound Library any body-weight support. It was structured to increase step length, speed, workload, and automaticity. Overground walking was practised each session to reinforce the gains achieved during treadmill training. Overground walking initially comprised 20% of the intervention time and was progressively increased each week so that it comprised 50% of the 30-minute intervention time. Overground walking was defined as a whole-task practice involving propulsion forwards, backwards, sideways

or up and down stairs. Guidelines were used to outline the progression of treadmill

and overground walking training. Oxygenase The control group received no intervention. The primary outcome was walking, which was quantified by measuring the distance walked (in m) during a six-minute walk test. The instructions for the test were standardised according to Lipkin and colleagues.10 Participants were instructed to cover as much ground as possible in six minutes. They were told to walk as continuously as possible, but they could slow down or stop if necessary. No encouragement was given, but the investigator informed participants at the halfway point (three minutes) and when there was one minute remaining. Participants wore shoes and used aids if necessary. Walking was also quantified by measuring speed (in m/s) during a 10-m walk test. Participants were timed while walking independently at their comfortable and fast speeds over the middle 10-m of a 15-m track (to allow for acceleration and deceleration). Health status was measured using the EuroQol EQ-5D-3L, which is a standardised instrument providing a single value for health status. The EQ-5D-3L records self-rated health on a vertical, 100-mm visual analogue scale where the endpoints are labelled ‘best imaginable health state’ and ‘worst imaginable health state’. In the main AMBULATE Trial,6 all outcomes were analysed using an intention-to-treat analysis.

Three primary outcomes were measured: the Maximal Lean Test (also called the Maximal Balance Range), the Maximal

Sideward Reach Test, and the Performance Item of the Canadian Occupational Performance Measure (COPM). Five secondary outcomes were used: the Satisfaction Item of the COPM, the T-shirt Test, Participants’ Impressions of Change, Clinicians’ Impressions of Change, and Spinal Cord Injury Falls Concern Scale. These outcomes were selected on the basis of a study comparing the validity and reliability of each test (Boswell-Ruys et al 2010a, Boswell-Ruys et al 2009) and on the basis of the results of a similar clinical trial (Boswell-Ruys et al 2010b). buy PCI-32765 The Maximal Lean Test assessed participants’ ability to lean as far forwards and backwards as possible without falling and without using the hands for support. The Maximal Sideward Reach Test assessed participants’ ability to reach in a 45° direction to the right while seated unsupported on a physiotherapy bed (Boswell-Ruys et al 2009). The T-shirt Test measured the time taken for participants to don and doff a T-shirt (Boswell-Ruys et al 2009, Chen et al 2003).

The best attempt of two trials was analysed for each outcome. A mean between-group difference equivalent to 20% of mean baseline C59 wnt price data was deemed clinically important for the three outcomes prior to the commencement of the study. The COPM determines participants’ perceptions about treatment effectiveness in relation to self-nominated goals (Law et al 1990). The Performance and Satisfaction

ratings 17-DMAG (Alvespimycin) HCl of the COPM were averaged across the two activities identified as most important to the participant. A mean between-group difference of 2 points was deemed clinically important prior to the commencement of the study as recommended by others (Law et al 2010). Participants’ Impressions of Change were assessed at the end of the 6-week study period by asking both control and experimental participants to rate their global impressions of change in their ability to sit unsupported over the preceding six weeks on a 15-point Likert-style scale, in which –7 indicated ‘a very great deal worse’, 0 indicated ‘no change’, and +7 indicated ‘a very great deal better’ (Barrett et al 2005, Jaeschke et al 1989). Clinicians’ Impressions of Change were assessed with the use of video clips (Harvey et al 2011). Short video clips of participants sitting unsupported were taken at the beginning and end of the 6-week study period. The video clips were then shown to two blinded physiotherapists who were asked to rate their global impressions of change in performance of each participant after viewing the first video clip in relation to the second video clip. The therapists used the same 15-point rating scale used by participants.

Conflict of interest: None declared. “
“Rotavirus is the leading cause of fatal and severe diarrhea in children [1]. In India, it is responsible for almost 100,000 deaths annually [2]. The WHO has recommended inclusion of rotavirus vaccines in all national immunization programs. Currently there are two licensed rotavirus vaccines available; Rotarix®, GSK Biologicals and RotaTeq®, Merck & Co. Both vaccines have demonstrated high efficacy (>90%) against severe rotavirus diseases and rotavirus associated hospitalization

in clinical trials in high- and middle-income countries [3], [4] and [5]. However, trials of these two vaccines conducted in developing settings in Africa and Asia showed lower efficacy, of approximately 60% [6], [7], [8] and [9]. Most recently, the indigenously manufactured live,

oral 116E monovalent human–bovine vaccine has completed an efficacy trial and is expected to be licensed Compound C cost in India soon. The efficacy Selleckchem SB431542 of the 116E vaccine was 54% [10] which is similar to that of Rotateq® and Rotarix® in these settings. Other live oral vaccines have also performed poorly in low-income countries as compared to more affluent countries [11]. Current evidence indicates that decreased vaccine performance could be attributed to several factors including child or maternal malnutrition, environmental enteropathy, interference from maternal antibodies and presence of other intestinal infections [11]. Presence of rotavirus antibodies in breast milk and transplacental maternal antibodies is associated with impaired responses to rotavirus vaccines [12], [13] and [14]. Indian women seem to have higher concentrations of rotavirus neutralizing antibodies in breast milk than women in industrialized countries [15]. In vitro studies of the neutralizing effect of breast milk have suggested that withholding of breastfeeding around the time of rotavirus vaccine administration could improve the immune response to the vaccine [15]. Previous trials of rotavirus vaccines had not shown any difference

in the immune response to vaccine regardless of whether breast milk was given or not at the time of vaccine administration. In those trials information Dichloromethane dehalogenase on breastfeeding was available, however, breastfeeding was self-reported by mothers and the duration between breastfeeding and vaccination was not adequately assessed [16] and [17]. A recent study from South Africa reported that abstention from breastfeeding an hour before and after each vaccination had no substantial effect on the immune response to a rotavirus vaccine in HIV-uninfected infants [18]. Without clear evidence, it is difficult to determine whether rotavirus antibodies in breast milk interfere with immune response to oral rotavirus vaccines in infants. It is important to explore this association, as it may help improve the impact of the vaccines.

05 mol) and refluxed for over 20 h. The progress of the reaction was monitored by TLC analysis and after completion of the reaction, the reaction mixture was poured into ice cold water with constant stirring. Further, find more it was extracted with dichloromethane. The organic layer was collected and solvent was evaporated under reduced pressure. The crude product (3) was purified through silica gel column using petroleum ether: ethyl acetate as eluent. OXD-6: IR (cm−1) (KBr): C C (str) 1589.40, C N (str) 1558.54, Ar C–H (str) 3047.63, C–Br (str)

688.61; 1H-NMR (ppm) (CDCl3): δ 8.02 (s, 1H), 8.02–7.99 (dd, J = 6 Hz, 3 Hz, 1H), 7.86–7.82 (m, 2H), 7.75–7.72 (dd, J = 7.29, 1.32 Hz, 1H), 7.74–7.40 (m, 3H), 7.37–7.29 (m, 2H); MS (m/z): [M+]300. OXD-7: IR (cm−1) (KBr): C C (str) 1580.01, C N (str) 1548.89, Ar C–H (str) 3115.14, C–H (str) 2922.25; 1H-NMR (ppm) (CDCl3): δ 7.96–7.90

(m, 3H), δ 7.85–7.81 (m, 2H), δ 7.46–7.27 (m, 5H), δ 7.44 (m, 3H); MS (m/z): M+235. OXD-9: IR (cm−1) (KBr): C C (str) 1620.26, C N (str) 1566.25, Ar C–H (str) 3110.27, C–O (str) 1263.42, N O 1518.03; 1H-NMR (ppm) (CDCl3): δ 8.85 (d, J = 3 Hz, 1H), 8.31–8.27 (dd, J = 9Hz, 3 Hz, 1H), 7.97 (s, 1H), 7.83–7.79 (m, 2H), δ 7.47–7.49 (m, 2H), 7.47–7.42 (m, 2H), 7.38–7.32 (m, 1H), 4.04 (s, 3H); MS (m/z): M+296. OXD-11: IR (cm−1) (KBr): C C (str) 1604.83, C N (str) 1581.68, Ar C–H (str) 3026.41; 1H-NMR (ppm) (CDCl3): δ 8.05–8.02 (dd, J = 6 Hz, 3 Hz, 1H), 7.73–7.70 (m, 3H), 7.56–7.27 (m,

11H); MS (m/z): [M+1]+ 297, 165 (100%). The assay was carried out in a 96 well microtitre buy C646 plate. 100 μL of DPPH solution was added to 100 μL of each of the test sample of concentrations 500, 250, 125, 62.5, 31.25, 15.62 and 7.81 μg/ml or the standard solution i.e., ascorbic acid, separately in each well of the microtitre plate. The plates were incubated at 37 °C for 20 min and the absorbance of each solution was measured at 540 nm, using Enzyme Linked Immuno Sorbent Assay (ELISA) else microtitre plate reader. The absorbance of solvent control containing the same amount of methanol and DPPH solution was measured as well. The experiment was performed in triplicate and % scavenging activity was calculated using the formula given below. IC50 (Inhibitory Concentration) is the concentration of the sample required to scavenge 50% of DPPH free radicals and it was calculated from the graph, % scavenging vs concentration.9 The Nitric oxide scavenging activity of the compounds was tested at 500, 250, 125, 62.5, 31.25, 15.62 and 7.81 μg/ml concentrations.

Furthermore, we showed that omega-3 supplementation specifically lowers vitreous levels of VEGF-A without influencing plasma levels of VEGF-A in patients with wet AMD who were receiving a bevacizumab pro re nata regimen. This is likely because AMD provokes a local rise in VEGF-A, and hence only vitreous, but not systemic, levels increase. The average time

from last injection in both groups being treated with bevacizumab was 8 weeks, without ABT-888 order any significant difference between groups 1 and 2 (Table). Although recent studies have demonstrated decreased systemic VEGF levels up to 4 weeks after intravitreal bevacizumab injection, our study did not show any significant difference between groups 1 and 2 (treated with bevacizumab) and group 3 (treatment naïve) at 8 weeks after their last anti-VEGF

injection.39 and 40 Therefore, our data suggest that omega-3 supplementation selectively lowers pathologic ocular VEGF-A in the retina, but not physiologic systemic VEGF-A. Long-term studies will be required to determine if the observed reduction in VEGF-A by omega-3- supplementation combined with anti-VEGF translates into lesser CNV progression or activity. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and the following GDC0199 were reported. Dr Rezende has received consultation fees from Novartis, Lachine, Quebec, Canada, Alcon Canada, Bausch & Lomb, Montreal, Quebec, Canada, Allergan, Markham, Ontario, Canada, and Bayer, Toronto, Ontario, Canada, none of which are related to the current study. Przemyslaw Sapieha holds a Canada Research Chair and has received

consultation fees from Gerson Lehman Group not related to the current research. Supported by the Department of Ophthalmology, University of Montreal; Department of Ophthalmology, Maisonneuve-Rosemont Hospital; MRIP Fond de Recherche en Ophtalmologie, University of Montreal; Foundation Fighting Blindness Canada; Grant 324573 from the Canadian Institutes of Health Research; Retina Foundation of Canada; Insight Instruments, Stuart, Florida, USA; Synergetics, Inc., O’Fallon, Missouri, USA; Novartis Canada, Montreal, Quebec, Canada; Grants EY022275, EY017017, and P01 HD18655 from the National Institutes of Health, Bethesda, Maryland; a Senior Investigator Award from Research to Prevent Blindness, New York, New York, USA; the Lowy Medical Foundation; and FP7 project 305485 of the European Commission (LEHS). The sponsors or funding organizations had no role in the design or conduct of this research. Involved in Design and conduct of study (F.A.R., P.S.); Collection of data (F.A.R., E.L., C.X.Q.); Management of data (F.A.R., E.L., P.S.); Analysis and interpretation of data (F.A.R., E.L., L.S., J.P.S., P.S.); Preparation of manuscript (F.A.R., E.L., P.S.); and Review and approval of manuscript (F.A.R., L.S., J.