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The U.S. Geological Survey—National Wildlife Health Center (NWHC) provides diagnostic services, technical assistance, applied research, and training to federal, state, territorial, and local government agencies and Native American tribes on wildlife diseases and wildlife health issues throughout the United States and its territories, commonwealth, and freely associated states. Since 1975, >16,000 carcasses and specimens from vertebrate species listed under the Endangered Species Act have been submitted to NWHC for determination of causes of morbidity or mortality or assessment of health/disease status. Results from diagnostic investigations, analyses of the diagnostic database, technical assistance and consultation, field investigation of epizootics, and wildlife disease research by NWHC wildlife disease specialists have contributed importantly to the management and recovery of listed species.

AimsTo compare the effectiveness of continuous aflibercept versus pro re nata (PRN) ranibizumab therapy for neovascular age-related macular degeneration (nAMD).MethodsMulticentre, national electronic medical record (EMR) study on treatment naive nAMD eyes undergoing PRN ranibizumab or continuous (fixed or treat and extend (F/TE)) aflibercept from 21 UK hospitals. Anonymised data were extracted, and eyes were matched on age, gender, starting visual acuity (VA) and year of starting treatment. Primary outcome was change in vision at 1 year.Results1884 eyes (942 eyes in each group) were included. At year 1, patients on PRN ranibizumab gained 1.6 ETDRS (Early Treatment Diabetic Retinopathy Study) letters (95% CI 0.5 to 2.7, p=0.004), while patients on F/TE aflibercept gained 6.1 letters (95% CI 5.1 to 7.1, p=2.2e-16). Change in vision at 1 year of the F/TE aflibercept group was 4.1 letters higher (95% CI 2.5 to 5.8, p=1.3e-06) compared with the PRN ranibizumab group after adjusting for age, starting VA, gender and year of starting therapy. The F/TE aflibercept group had significantly more injections compared with the PRN ranibizumab group (7.0 vs 5.8, p<2.2e-16), but required less clinic visits than the PRN ranibizumab group (10.8 vs 9.0, p<2.2e-16). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 58 047.14 GBP/quality-adjusted life year for continuous aflibercept over PRN ranibizumab.ConclusionAflibercept achieved greater VA gains at 1 year than ranibizumab. The observed VA differences are small and likely to be related to more frequent treatment with aflibercept, suggesting that ranibizumab should also be delivered by F/TE posology.

ObjectivesTo determine the safety and efficacy at 12 months of follow-up after stereotactic radiotherapy in combination therapy with intravitreal ranibizumab injections in treatment naïve patients with neovascular age-related macular degeneration.MethodsRetrospective data analysis in patients who received stereotactic radiotherapy (IRay Therapy) during the induction phase of intravitreal ranibizumab injections and a monotherapy control group.ResultsThe baseline VA in the IRay and control group was 59.87 and 59.12 letters respectively. The real world visual acuity outcomes for the IRay group showed a mean gain of +3.0 letters at 12 months. The historical control group had a mean change of – 0.3 letters. The average number of injections for the IRay group and control group over 12 months was 4.45 and 5.64, respectively with three loading injections. Excluding the loading phase, the difference over 12 months was a 45.2% reduction in injections (P < 0.001). The number of subjects in the IRay group that didn’t require further injections following the loading phase was 45.5 vs. 24.0% control group (P = 0.005). The difference in mean change in central macular thickness from baseline is significant at 6 (P = 0.010) and 12 months (P < 0.01). There were no safety concerns with the IRay therapy group.ConclusionsStereotactic radiotherapy in the induction phase of intravitreal injections of ranibizumab for treatment naïve patients with neovascular age-related macular degeneration, resulted in improved visual outcome, statistically fewer injections and statistically drier macular at 12 months, compared to historical controls treated with monotherapy intravitreal ranibizumab injections.

Several species of wild raptors have been found in Eurasia infected with highly pathogenic avian influenza virus (HPAIV) subtype H5N1. Should HPAIV (H5N1) reach North America in migratory birds, species of raptors are at risk not only from environmental exposure, but also from consuming infected birds and carcasses. In this study we used American kestrels as a representative species of a North American raptor to examine the effects of HPAIV (H5N1) infection in terms of dose response, viral shedding, pathology, and survival. Our data showed that kestrels are highly susceptible to HPAIV (H5N1). All birds typically died or were euthanized due to severe neurologic disease within 4-5 days of inoculation and shed significant amounts of virus both orally and cloacally, regardless of dose administered. The most consistent microscopic lesions were necrosis in the brain and pancreas. This is the first experimental study of HPAIV infection in a North American raptor and highlights the potential risks to birds of prey if HPAIV (H5N1) is introduced into North America.

In chronic central serous chorioretinopathy (CSCR), fluid accumulates in the subretinal space. CSCR is a common visually disabling condition that develops in individuals up to 60 years of age, and there is no definitive treatment. Previous research suggests the mineralocorticoid receptor antagonist, eplerenone, is effective for treating CSCR; however, this drug is not licensed for the treatment of patients with CSCR. We aimed to evaluate whether eplerenone was superior to placebo in terms of improving visual acuity in patients with chronic CSCR. This randomised, double-blind, parallel-group, multicentre placebo-controlled trial was done at 22 hospitals in the UK. Participants were eligible if they were aged 18–60 years and had had treatment-naive CSCR for 4 months or more. Patients were randomly assigned (1:1) to either the eplerenone or the placebo group by a trial statistician through a password-protected system online. Allocation was stratified by best-corrected visual acuity (BCVA) and hospital. Patients were given either oral eplerenone (25 mg/day for 1 week, increasing to 50 mg/day for up to 12 months) plus usual care or placebo plus usual care for up to 12 months. All participants, care teams, outcome assessors, pharmacists, and members of the trial management group were masked to the treatment allocation. The primary outcome was BCVA, measured as letters read, at 12 months. All outcomes apart from safety were analysed on a modified intention-to-treat basis (participants who withdrew consent without contributing a post-randomisation BCVA measurement were excluded from the primary analysis population and from most secondary analysis populations). The trial is registered with ISRCTN, ISRCTN92746680, and is completed. Between Jan 11, 2017, and Feb 22, 2018, we enrolled and randomly assigned 114 patients to receive either eplerenone (n=57) or placebo (n=57). Three participants in the placebo group withdrew consent without contributing a post-randomisation BCVA measurement and were excluded from the primary outcome analysis population. All patients from the eplerenone group and 54 patients from the placebo group were included in the primary outcome. Modelled mean BCVA at 12 months was 79·5 letters (SD 4·5) in the placebo group and 80·4 letters (4·6) in the eplerenone group, with an adjusted estimated mean difference of 1·73 letters (95% CI −1·12 to 4·57; p=0·24) at 12 months. Hyperkalaemia occurred in eight (14%) patients in each group. No serious adverse events were reported in the eplerenone group and three unrelated serious adverse events were reported in the placebo group (myocardial infarction [anticipated], diverticulitis [unanticipated], and metabolic surgery [unanticipated]). Eplerenone was not superior to placebo for improving BCVA in people with chronic CSCR after 12 months of treatment. Ophthalmologists who currently prescribe eplerenone for CSCR should discontinue this practice. Efficacy and Mechanism Evaluation Programme, and National Institute for Health Research and Social Care.

Most psychologists and educators assume that intelligence is a linear construct, meaning that smart people simply have more intelligence than their less gifted peers. Likewise, individuals with mental retardation are thought to have less intelligence. In contrast to this widely accepted belief, the authors posed an alternative hypothesis-that intelligence is qualitatively different in various populations. Using factor analysis of a standardization sample of the Woodcock-Johnson Test of Cognitive Ability (R. W. Woodcock & M. B. Johnson, 1989), the authors examined the nature of intellect across ability. Results indicated that the amount of variance attributable to Spearman's g declined as measured intellectual ability increased.

The neutron flux of three neutron beam experiments was measured using a novel neutron spectrometer system, referred to as a Scatter Time-of-Flight (STOF) spectrometer. The neutron beam was generated via the nuclear breakup of 14 and 23 MeV deuteron beams on a thick natural carbon target at the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory (LBNL). The system is shown to be capable of measuring the energy-dependent neutron flux on a per-experiment basis. Furthermore, the resulting neutron flux was unfolded using experimentally determined activation foil reaction rates and a maximum entropy spectral unfolding algorithm. The spectrum unfolding was needed to determine the STOF efficiency as a function of neutron energy. The modular nature of the system allows for it to work in low and high-intensity fluxes, broad energy ranges, and various experimental configurations. The STOF spectrometer, in conjunction with activation foils and spectral unfolding techniques, provides a powerful, high-efficiency capability to noninvasively monitor neutron spectra at experimental facilities like GENESIS where a high beam repetition rate makes traditional time-of-flight techniques not possible due to knowledge of the appropriate start time.

AimTo assess the rate of ‘treatment-requiring diabetic macular oedema (DMO)’ in eyes for the two  years before and after cataract surgery.MethodsMulticentre national diabetic retinopathy (DR) database study with anonymised data extraction across 19 centres from an electronic medical record system. Inclusion criteria: eyes undergoing cataract surgery in patients with diabetes with no history of DMO prior to study start. The minimum dataset included: age, visual acuity (all time-points), injection episodes, timing of cataract surgery and ETDRS grading of retinopathy and maculopathy. Main outcome measure: rate of developing first episode of treatment-requiring DMO in relation to timing of cataract surgery in the same eye.Results4850 eyes met the inclusion criteria. The rate of developing treatment-requiring DMO in this cohort was 2.9% in the year prior to surgery versus 5.3% in the year after surgery (p<0.01). The risk of ‘treatment-requiring DMO’ increased sharply after surgery, peaking in the 3–6 months' period (annualised rates of 5.2%, 6.8%, 5.6% and 4.0% for the 0–3, 3–6, 6–9 and 9–12 months' post-operative time periods respectively). Risk was associated with pre-operative grade of retinopathy: risk of DMO in the first year post-operatively being 1.0% (no DR pre-operatively), 5.4% (mild non-proliferative diabetic retinopathy; NPDR), 10.0% (moderate NPDR), 13.1% (severe NPDR) and 4.9% (PDR) (p<0.01).ConclusionsThis large real-world study demonstrates that the rate of developing treatment-requiring DMO increases sharply in the year after cataract surgery for all grades of retinopathy, peaking in the 3–6 months' postoperative period. Patients with moderate and severe NPDR are at particularly high risk.

Purpose Evaluation of 1-year safety profile of intravitreal ranibizumab 0.5 mg in neovascular age-related macular degeneration (NV-AMD) within routine clinical practice. Methods The LUMINOUS programme comprises a prospective observational study assessing ranibizumab ‘real-world’ safety and clinical effectiveness across licensed indications worldwide and an annual retrospective pooled safety analysis from completed NV-AMD ranibizumab registries. 1-year data from four European registries are available. This retrospective pooled safety analysis assessed 1-year incidence rates for safety events of particular interest (key ocular or systemic events possibly related to the injection procedure or vascular endothelial growth factor inhibition) together with treatment exposure. Patients were treated according to local protocols within the ranibizumab licence. Results Data of 4444 patients from registries in Germany (n=3470), the Netherlands (n=243), Belgium (n=260) and Sweden (n=471) were retrospectively pooled. Between 70.4% and 84.4% of enrolled patients completed 1 year of follow-up. Most frequent overall ocular events of particular interest were retinal pigment epithelial tears (27 patients; <1%) and intraocular pressure-related events (12 patients; <0.3%). Most frequent non-ocular event of particular interest was stroke (19 patients; 0.4%); annual incidence of stroke was low across all registries (0.0–0.5%). Conclusions Ranibizumab demonstrated favourable 1-year safety profile for NV-AMD in this routine clinical practice sample, consistent with previous reported trial data. Additional data from a larger patient population are needed to better describe the long-term safety profile of ranibizumab in routine clinical practice and further evaluate risk for infrequent but serious events in ‘real-life’ settings. The 5-year LUMINOUS prospective observational study will address this need.

Background/aimsClinical trials suggest anti-vascular endothelial growth factor is more effective than intravitreal dexamethasone as treatment for macular oedema secondary to branch retinal vein occlusion. This study asks if ‘real world’ data from a larger and more diverse population, followed for a longer period, also support this conclusion.MethodsData collected to support routine care at 27 NHS (National Health Service) Trusts between February 2002 and September 2017 contained 5661 treatment-naive patients with a single mode of treatment for macular oedema secondary to branch retinal vein occlusion and no history of cataract surgery either during or recently preceding the treatment. Number of treatment visits and change in visual acuity from baseline was plotted for three treatment groups (anti-vascular endothelial growth factor (anti-VEGF), intravitreal dexamethasone, macular laser) for up to 3 years.ResultsMean baseline visual acuity was 57.1/53.1/62.3 letters in the anti-VEGF/dexamethasone/macular laser groups, respectively. This changed to 66.72 (+9.6)/57.6 (+4.5)/63.2 (+0.9) at 12 months. Adequate numbers allowed analysis at 18 months for all groups (66.6 (+9.5)/56.1 (+3.0)/60.8 (-1.5)) and for anti-VEGF at 36 months (68.0, +10.9) Mean number of treatments were 5.1/1.5/1.2 at 12 months, 5.9/1.7/1.2 at 18 months for all three groups and 10.3 at 36 months for anti-VEGF.ConclusionsVisual acuity improvements were higher and more sustained with anti-VEGF. Higher treatment burden occurred with anti-VEGF but this reduced over 36 months. Patients with better vision at baseline than those in the clinical trials maintained high levels of vision with both anti-VEGF and dexamethasone.