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Abstract Introduction XTEND (NCT03939767) is a multicenter, observational, prospective study of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in routine clinical practice. The study aims to examine treatment outcomes of proactive intravitreal aflibercept (IVT-AFL) treatment regimens (fixed dosing or treat-and-extend) according to local marketing labels. Methods Study eyes received IVT-AFL injections as per the local label. The mean changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month (M) 12 and M24 were measured and stratified by baseline factors. Treatment exposure and safety data were evaluated. Statistical analysis was descriptive. Results Overall, 1466 patients from 17 countries were treated. For the overall population, the mean ± standard deviation (SD) age was 78.7 ± 8.5 (range 50–100) years, and 891 patients (60.8%) were female. The mean ± SD baseline BCVA was 54.3 ± 20.3 letters and CST was 374 ± 126 µm. At M12 and M24, mean (95% confidence interval [CI]) BCVA change was + 4.3 (3.4, 5.3) and + 2.3 (1.3, 3.3) letters, respectively. Mean (95% CI) CST was − 106 (− 114, − 99) μm and − 109 (− 117, − 102) μm at M12 and M24, respectively. At M24, 41.5% of patients had a BCVA ≥ 70 letters. Patients received a mean ± SD of 7.7 ± 2.7 injections by M12 and 10.8 ± 5.0 injections by M24 (3.1 injections between M12 and M24). Adverse events were consistent with the known safety profile of IVT-AFL. Conclusion The 24-month results indicate that, in routine clinical practice, a proactive IVT-AFL regimen achieves functional improvements in patients with treatment-naïve nAMD. The proportion of patients achieving ≥ 70 letters at M24 increased, and patients with baseline BCVA ≥ 70 letters maintained vision regardless of the followed IVT-AFL label. Trial registration ClinicalTrials.gov identifier: NCT03939767. Video abstract A video abstract is available for this article. Supplementary file2 (MP4 364624 KB)

Objectives To explore people’s views of recovery from total knee replacement (TKR) and which recovery domains they felt were important.Design Semi-structured interviews exploring the views of individuals about to undergo or who have undergone TKR. A constant-comparative approach with thematic analysis was used to identify themes. The process of sampling, collecting data and analysis were continuous and iterative throughout the study, with interviews ceasing once thematic saturation was achieved.Setting Tertiary care centre.Participants A purposive sample was used to account for variables including pre, early or late postoperative status.Results 12 participants were interviewed, 4 who were preoperative, 4 early postoperative and 4 late postoperative. Themes of pain, function, fear of complications, awareness of the artificial knee joint and return to work were identified. Subthemes of balancing acute and chronic pain were identified.Conclusions The results of this interview-based study identify pain and function, in particular mobility, that were universally important to those undergoing TKR. Surgeons should consider exploring these domains when taking informed consent to enhance shared decision-making. Researchers should consider these recovery domains when designing interventional studies.

Background: Tinnitus is the phantom perception of sound in the ears or head which may result from inflammation of the auditory pathway. A healthy diet consisting of a range of vitamins and minerals may be protective against tinnitus. This study aims to determine the association between intakes of dietary vitamins and minerals and the prevalence and incidence of tinnitus over 10 years. Methods: In this longitudinal cohort study of 2947 participants (aged ≥ 50 years), 935 (32%) cases of tinnitus were identified and included in prevalence analyses. The remaining 2012 participants were followed to establish 10-year incidence of tinnitus. A validated semi-quantitative food frequency questionnaire was used to determine intakes of dietary vitamins and minerals. Results: No significant associations with tinnitus prevalence were found. However, iron and zinc were significantly associated with incident tinnitus. There was a 44% (multivariate-adjusted HR: 1.44, 95% CI: 1.07–1.93) increased risk of developing incident tinnitus over 10 years with lower zinc intakes and a 35% increased risk with lower iron intakes (multivariate-adjusted HR: 1.35, 95% CI: 1.00–1.80). Conclusion: Higher intakes of zinc and iron were significantly associated with lower tinnitus risk. Due to a lack of comparable high-quality data, future research studies should include robust study designs.

In this essay, I analyse two episodes from the recent television series, Philip K. Dick’s Electric Dreams. I contend that, by adapting Philip K. Dick’s short stories from the 1950s for the screen, the creators of “Impossible Planet” and “The Commuter” offer an important new perspective from which to appreciate the value of his early fiction, which is too often dismissed by critics as juvenilia. Moreover, by re-visioning Dick’s work as posthuman Gothic narratives, the episodes refract long-standing Gothic anxieties about alterity and (post)human existence through a lens that is more often associated with science fiction. This hybridization is instrumental to Philip K. Dick’s Electric Dreams’ interrogation of the paradigmatic binaries between life/death, interiority/exteriority and reality/virtuality. In my analysis, I use Rosi Braidotti’s theory of posthuman death, as well as Roger Luckhurst’s concept of Weird zones, to illuminate how Electric Dreams explores some of the existential issues that arise from human-technological imbrication.

Abstract A plethora of classification models for the detection of glaucoma from fundus images have been proposed in recent years. Often trained with data from a single glaucoma clinic, they report impressive performance on internal test sets, but tend to struggle in generalizing to external sets. This performance drop can be attributed to data shifts in glaucoma prevalence, fundus camera, and the definition of glaucoma ground truth. In this study, we confirm that a previously described regression network for glaucoma referral (G-RISK) obtains excellent results in a variety of challenging settings. Thirteen different data sources of labeled fundus images were utilized. The data sources include two large population cohorts (Australian Blue Mountains Eye Study, BMES and German Gutenberg Health Study, GHS) and 11 publicly available datasets (AIROGS, ORIGA, REFUGE1, LAG, ODIR, REFUGE2, GAMMA, RIM-ONEr3, RIM-ONE DL, ACRIMA, PAPILA). To minimize data shifts in input data, a standardized image processing strategy was developed to obtain 30° disc-centered images from the original data. A total of 149,455 images were included for model testing. Area under the receiver operating characteristic curve (AUC) for BMES and GHS population cohorts were at 0.976 [95% CI: 0.967–0.986] and 0.984 [95% CI: 0.980–0.991] on participant level, respectively. At a fixed specificity of 95%, sensitivities were at 87.3% and 90.3%, respectively, surpassing the minimum criteria of 85% sensitivity recommended by Prevent Blindness America. AUC values on the eleven publicly available data sets ranged from 0.854 to 0.988. These results confirm the excellent generalizability of a glaucoma risk regression model trained with homogeneous data from a single tertiary referral center. Further validation using prospective cohort studies is warranted.

IntroductionVision and hearing impairments are highly prevalent and have a significant impact on physical, psychological and social wellbeing. There is a need for accurate, contemporary national data on the prevalence, risk factors and impacts of vision and hearing loss in Australian adults.ObjectivesThe Australian Eye and Ear Health Survey (AEEHS) aims to determine the prevalence, risk factors and impacts of vision and hearing loss in both Aboriginal and Torres Strait Islander and non-Indigenous older adults.Methods and analysisThe AEEHS is a population-based cross-sectional survey which will include 5,000 participants (3250 non-Indigenous aged 50 years or older and 1750 Aboriginal and Torres Strait Islander people aged 40 years or older) from 30 sites covering urban and rural/regional geographic areas, selected using a multi-stage, random cluster sampling strategy. Questionnaires will be administered to collect data on socio-demographic, medical, ocular and ontological history. The testing battery includes assessment of blood pressure, blood sugar, anthropometry, visual acuity (presenting, unaided, pinhole and best-corrected), refraction, tonometry, slit lamp and dilated eye examination, ocular imaging including optical coherence tomography (OCT), OCT-angiography and retinal photography, and automated visual fields. Audiometry, tympanometry and video otoscopy will also be performed. The primary outcomes are age-standardised prevalence of cause-specific vision and hearing impairment. Secondary outcomes are prevalence of non-blinding eye diseases (including dry eye disease), patterns in health service utilisation, universal health coverage metrics, risk factors for vision and hearing impairment, and impact on quality of life.

BackgroundAntibiotics are prescribed for over 50% of respiratory tract infections in primary care, despite good evidence of there being no benefit to the patient, and evidence of over prescribing driving microbial resistance. The high treatment rates are attributed to uncertainty regarding microbiological cause and clinical prognosis. Point-of-care-tests have been proposed as potential antibiotic stewardship tools, with some providing microbiological results in 15 minutes. However, there is little research on their impact on antibiotic use and clinical outcomes in primary care.MethodsThis is a multi-centre, individually randomised controlled trial with mixed-methods investigation of microbial, behavioural and antibiotic mechanisms on outcomes in patients aged 12 months and over presenting to primary care in the UK with a suspected respiratory tract infection, where the clinician and/or patient thinks antibiotic treatment may be, or is, necessary. Once consented, all participants are asked to provide a combined nose and throat swab sample and randomised to have a rapid microbiological point-of-care-test or no point-of-care-test. For intervention patients, clinicians review the result of the test, before contacting the patient to finalise treatment. Treatment decisions are made as per usual care in control group patients. The primary outcome is whether an antibiotic is prescribed at this point. All swab samples are sent to the central laboratory for further testing. Patients are asked to complete a diary to record the severity and duration of symptoms until resolution or day 28, and questionnaires at 2 months about their beliefs and intention to consult for similar future illnesses. Primary care medical records are also reviewed at 6-months to collect further infection consultations, antibiotic prescribing and hospital admissions. The trial aims to recruit 514 patients to achieve 90% power with 5% significance to detect a 15% absolute reduction in antibiotic prescribing. Qualitative interviews are being conducted with approximately 20 clinicians and 30 participants to understand any changes in beliefs and behaviour resulting from the point-of-care-test and generate attributes for clinician and patient discrete choice experiments.DiscussionThis trial will provide evidence of efficacy, acceptability and mechanisms of action of a rapid microbiological point-of-care test on antibiotic prescribing and patient symptoms in primary care.Trial registrationISRCTN16039192, prospectively registered on 08/11/2022.

Purpose: To elucidate a potential association between the apolipoprotein E (APOE) E4 allele and glaucoma prevalence in large cohorts. Design: A cross-sectional analysis of baseline and prospectively collected cohort data. Participants: UK Biobank (UKBB) participants of genetically determined European ancestry (n = 438 711). Replication analyses were performed using clinical and genotyping data collected from European participants recruited to the Canadian Longitudinal Study of Aging (CLSA; n = 18 199), the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG; n = 1970), and the Blue Mountains Eye Study (BMES; n = 2440). Methods: Apolipoprotein E alleles and genotypes were determined, and their distributions were compared on the basis of glaucoma status. Similar analyses were performed using positive control outcomes associated with the APOE E4 allele (death, dementia, age-related macular degeneration) and negative control outcomes not associated with the APOE E4 allele (cataract, diabetic eye disease). Outcome phenotypes were also correlated with Alzheimer’s dementia (AD), a clinical outcome highly associated with the APOE E4 allele. Main Outcome Measures: Results of APOE E4 genotype-phenotype comparisons were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Replication analyses investigated APOE E4 associations in 2 replication cohorts (CLSA and ANZRAG/BMES). Results: The APOE E4 allele was inversely associated with glaucoma (OR, 0.96; 95% CI, 0.93–0.99; P = 0.016) and both negative controls (cataract: OR, 0.98; 95% CI, 0.96–0.99; P = 0.015; diabetic eye disease: OR, 0.92; 95% CI, 0.87–0.97; P = 0.003) in the UKBB cohort. A paradoxical positive association was observed between AD and both glaucoma (OR, 1.30; 95% CI, 1.08–1.54; P < 0.01) and cataract (OR, 1.15; 1.04–1.28; P = 0.018). No association between the APOE E4 allele and glaucoma was observed in either replication cohort (CLSA: OR, 1.03; 95% CI, 0.89–1.19; P = 0.66; ANZRAG/BMES: OR, 0.97; 95% CI, 0.84–1.12; P = 0.65). Conclusions: A small negative association observed between APOE E4 and glaucoma within the UKBB was not evident in either replication cohort and may represent an artifact of glaucoma underdiagnosis in APOE E4 carriers. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Abstract Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. Anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab, bevacizumab, aflibercept, brolucizumab and faricimab have revolutionized the clinical management of nAMD. However, there remains an unmet clinical need for new and improved therapies for nAMD, since many patients do not respond optimally, may lose response over time or exhibit sub-optimal durability, impacting on real world effectiveness. Evidence is emerging that targeting VEGF-A alone, as most agents have done until recently, may be insufficient and agents that target multiple pathways (e.g., aflibercept, faricimab and others in development) may be more efficacious. This article reviews issues and limitations that have arisen from the use of existing anti-VEGF agents, and argues that the future may lie in multi-targeted therapies including alternative agents and modalities that target both the VEGF ligand/receptor system as well as other pathways.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Introduction: There are no clinically validated prognostic biomarkers in the management of extensive-stage SCLC (ES-SCLC). We explored the association between clinical characteristics and survival outcomes in patients with ES-SCLC treated with chemoimmunotherapy. Methods: In this retrospective cohort study, patients with ES-SCLC treated with first-line platinum-etoposide chemotherapy and atezolizumab were identified from medical records. Pretreatment clinical characteristics, biochemical parameters, and tumor and treatment characteristics were collected. Univariate and multivariate Cox regression were used to evaluate treatment effect on progression-free survival (PFS) and overall survival (OS). Results: We evaluated 75 patients in total. The median PFS and OS were 6.1 months and 9.2 months, respectively. Statistically significant associations were found with lower lactate dehydrogenase and improved OS (hazard ratio [HR] = 1.0, 95% confidence interval [CI]: 1.0–1.01, p = 0.006), whereas higher age (HR = 0.94, 95% CI: 0.90–0.98, p = 0.006) and lower neutrophil-to-lymphocyte ratio (HR = 1.08, 95% CI: 1.02–1.14, p = 0.005) were associated with improved PFS. The number of chemotherapy cycles received were associated with both an improved PFS (HR = 0.57, 95% CI: 0.37–0.89, p = 0.011) and OS (HR = 0.5, 95% CI: 0.30–0.84, p = 0.008). Conclusions: This study highlights the important effect of chemotherapy on survival. Furthermore, the association between lactate dehydrogenase and neutrophil-to-lymphocyte ratio on survival further suggests that baseline tumor burden and optimizing sarcopenia are important factors for clinicians to consider as we seek to develop personalized treatment for this disease.

Aim To evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) agents.Methods This prospective, open-label, observational, real-world study included pseudophakic and phakic (scheduled for cataract surgery) eyes that did not achieve a ≥5-letter best corrected visual acuity (BCVA) gain and/or clinically significant central subfield retinal thickness (CRT) improvement after 3–6 anti-VEGF injections for DME (N=143 eyes), regardless of baseline BCVA and CRT. After an initial DEX injection (baseline visit), reinjection was permitted at ≥16-week intervals. Primary endpoints: changes in mean BCVA and CRT from baseline to week 52. Safety assessments included adverse events.Results Of 143 eyes, 53 (37.1%) and 89 (62.2%) switched to DEX after 3–6 (early) and >6 (late) anti-VEGF injections, respectively; 1 (0.7%) had missing information. With 2.3 injections (mean) over 52 weeks, the change in mean BCVA from a baseline of 57.8 letters was not significant at week 52. Mean CRT improved significantly from a baseline of 417.8 μm at week 52 (mean change –60.9 μm; p

Background: The cardiovascular risk associated with different levels of hypertensive retinopathy, including mild, remains unclear. We performed an individual participant meta-analysis from 6 population-based cohort studies to determine the relationship of hypertensive retinopathy with incident cardiovascular outcomes. Methods: We identified cohort studies that objectively assessed hypertensive retinopathy from photographs, documented incident cardiovascular outcomes, and were population-based. Six studies contributed data from 11,013 individuals at baseline with 5–13 years follow-up. Participants were recruited if they had hypertension and did not have confounding conditions such as diabetic retinopathy. Main outcome measures were incident coronary heart disease (CHD), stroke and a composite endpoint of cardiovascular disease (CHD or stroke). Pooled estimates of incident risk ratios (IRR) were obtained after adjusting for age, gender, systolic blood pressure, serum total cholesterol, high density lipoprotein and smoking. Results: Among eligible participants with hypertension and without diabetes, there were 1018/9662 (10.5%) incident CHD events, 708/11,013 (6.4%) incident stroke events and 1317/9378 (14.0%) incident CVD events. Mild hypertensive retinopathy was associated with increased risk of CVD (IRR 1.13, 95% CI 1.00 to 1.27) and CHD (IRR 1.17, 95% CI 1.02 to 1.34) but not stroke; moderate hypertensive retinopathy was associated with increased risk of CVD (IRR 1.25 95% CI 1.02 to 1.53) but not stroke or CHD individually. Conclusions: In persons with hypertension, both mild and moderate hypertensive retinopathy were associated with higher CVD risk.

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IntroductionObstructive sleep apnea (OSA) may increase stroke risk; retinal arteriolar (central retinal arteriolar equivalent, CRAE) diameter narrowing and/or retinal venular (central retinal venule equivalent, CRVE) widening may predict stroke. We examined relationships between sleep disordered breathing (SDB) and CRAE and CRVE and in a diabetes-free sleep clinic cohort.MethodsPatients for SDB assessment were recruited (Main Group, n = 264, age: 58.5 ± 8.9 yrs [mean ± SD]; males: 141) for in-laboratory polysomnography (standard metrics, eg apnea hypopnea index, AHI) and retinal photographs (evening and morning). A more severe SDB sub-group (n = 85) entered a 12-month cardiovascular risk factor minimisation (hypertension/hypercholesterolemia control; RFM) and continuous positive airway pressure (CPAP) intervention (RFM/CPAP Sub-Group); successfully completed by n = 66 (AHI = 32.4 [22.1-45.3] events/hour, median[IQR]). Univariate (Spearman's correlation, t-test) and multiple linear regression models examined non-SDB and SDB associations with CRAE and CRVE measures.ResultsMain Group: Evening CRAE predictors were: systolic blood pressure (0.18μm decrease per mmHg, p = 0.001), age (2.47μm decrease per decade, p = 0.012), Caucasian ethnicity (4.45 μm versus non-Caucasian, p = 0.011), height (0.24 μm decrease per cm increase, p = 0.005) and smoking history (3.08 μm increase, p = 0.052). Evening CRVE predictors were: Caucasian ethnicity (11.52 μm decrease versus non-Caucasian, p>0.001), diastolic blood pressure (0.34 μm increase in CRVE per mmHg, p = 0.001), hypertension history (6.5 μm decrease, p = 0.005), and smoking history (4.6 μm increase, p = 0.034). No SDB metric (all p>0.08) predicted CRAE or CRVE measures. RFM/CPAP Sub-Group: A one-unit increase in ln(AHI+1) was associated with a 0.046μm increase in CRAE (n = 85; p = 0.029). Mean evening CRAE and CRVE values did not change across the intervention (n = 66), but evening CRVE decreased ~6.0 μm for individuals with AHI >30 events/hr.ConclusionNo major SDB associations with CRAE or CRVE were identified, although the RFM/CPAP intervention reduced evening CRVE for severe OSA patients. Implications for cerebro-vascular disease risk remain uncertain.Trial registrationThe protocol was registered with the Australian New Zealand Clinical Trials Registry (Trial Id: ACTRN12620000694910).

Purpose: To investigate the association between the apolipoprotein E (APOE) E4 dementia-risk allele and prospective longitudinal retinal thinning in a cohort study of suspect and early manifest glaucoma. Design: Retrospective analysis of prospective cohort data. Participants: This study included all available eyes from participants recruited to the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study with genotyping data from which APOE genotypes could be determined. Methods: Apolipoprotein E alleles and genotypes were determined in PROGRESSA, and their distributions were compared with an age-matched and ancestrally matched normative cohort, the Blue Mountains Eye Study. Structural parameters of neuroretinal atrophy measured using spectral-domain OCT were compared within the PROGRESSA cohort on the basis of APOE E4 allele status. Main Outcome Measures: Longitudinal rates of thinning in the macular ganglion cell–inner plexiform layer (mGCIPL) complex and the peripapillary retinal nerve fiber layer (pRNFL). Results: Rates of mGCIPL complex thinning were faster in participants harboring ≥1 copies of the APOE E4 allele (β = –0.13 μm/year; P ≤0.001). This finding was strongest in eyes affected by normal-tension glaucoma (NTG; β = –0.20 μm/year; P = 0.003). Apolipoprotein E E4 allele carriers were also more likely to be lost to follow-up (P = 0.01) and to demonstrate a thinner average mGCIPL complex (70.9 μm vs. 71.9 μm; P = 0.011) and pRNFL (77.6 μm vs. 79.2 μm; P = 0.045) after a minimum of 3 years of monitoring. Conclusions: The APOE E4 allele was associated with faster rates of mCGIPL complex thinning, particularly in eyes with NTG. These results suggest that the APOE E4 allele may be a risk factor for retinal ganglion cell degeneration in glaucoma.

Abstract This article presents an experimental demonstration of a high-capacity millimeter-wave 5G NR signal transmission with analog radio-over-fiber (ARoF) fronthaul over multi-core fiber and full real-time processing. The demonstration validates the core of the blueSPACE fronthaul architecture which combines ARoF fronthaul with space division multiplexing in the optical distribution network to alleviate the fronthaul capacity bottleneck and maintain a centralized radio access network with fully centralized signal processing. The introduction of optical beamforming in the blueSPACE architecture brings true multi-beam transmission and enables full spatial control over the RF signal. The proposed ARoF architecture features a transmitter that generates the ARoF signal and an optical signal carrying a reference local oscillator employed for downconversion at the remote unit from a single RF reference at the central office. A space division multiplexing based radio access network with multi-core fibre allows parallel transport of the uplink ARoF signal and reference local oscillator at the same wavelength over separate cores. A complete description of the real-time signal processing and experimental setup is provided and system performance is evaluated. Transmission of an 800 MHz wide extended 5G NR fronthaul signal over a 7-core fibre is shown with full real-time signal processing, achieving 1.4 Gbit/s with a bit error rate $$

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Here, the authors report a multi-ethnic genome wide association meta-analysis of 12 studies from the International Cataract Genetics Consortium. They find six new loci associated with age-related nuclear cataract, in addition to replicating the association at CRYAA, and suggest a strong genetic link between age-related nuclear and congenital cataracts.

Abstract Background Systematically review the evidence describing the impact of anti–vascular endothelial growth factor (anti-VEGF) therapy on neovascular age-related macular degeneration (nAMD) patient outcomes and healthcare resource utilization. Methods A systematic literature review was completed using Medline and EMBASE for publications prior to July 2018, and proceedings from major ophthalmology conferences (January 2016 to July 2018). The search strategy combined terms for nAMD with terms for anti-VEGF and study design. The review focused on publications describing the impact of anti-VEGF on blindness, visual impairment, vision-related quality of life (VRQoL), mortality, and costs. The search targeted data collected in epidemiological or observational studies to reflect real-world outcomes but also considered modeling-based approaches. Results The use of anti-VEGF in clinical practice was associated with significant reduction in the incidence of blindness by nAMD. Population-based analyses reported reduction in incidence among the general population of 47% (9.1 cases/100,000 in 2006 to 4.8 cases/100,000 in 2011). Among patients aged ≥50 years, a reduction of 50% was observed (52.2 cases/100,000 in 2000 to 25.7 cases/100,000 in 2010). In some cases, the odds of decreased vision (defined as decline from normal to moderate, moderate to severe, or severe to blindness) fell by 41% following introduction of anti-VEGF. Patients’ VRQoL improved with treatment, with patients reporting a positive impact shortly after treatment was initiated. Change on National Eye Institute 25-Item Visual Function Questionnaire score from baseline to month 12 ranged from 0.7 to 4.4. Although nAMD patients report signs of depression and anxiety, the evidence suggests that there is no association between the use of anti-VEGF and the prevalence or diagnosis of depression. The introduction of anti-VEGF led to increased overall treatment costs due to replacement of existing less frequently administered treatments (e.g. photodynamic therapy) and increased number of patients treated (prior to anti-VEGF, only ~ 20% of patients were eligible for treatment). Conclusions The introduction of anti-VEGF agents has been associated with a positive impact on patient-relevant outcomes, including a significant reduction in incidence of blindness and visual impairment by nAMD. Anti-VEGF agents replaced less-effective treatments, improving patient outcomes and broadening the patient population eligible for treatment.

The present study aimed to assess the longitudinal associations of coffee and tea consumption with metabolic syndrome and its component conditions in a group of Australian older adults who participated in the Blue Mountains Eye Study (n 2554, mean age: 64 years, 43 % female). Participants’ coffee and tea intake were measured using a validated food frequency questionnaire. Hazard ratios (HRs) over a 10-year period were estimated using Cox hazard regression models adjusting for lifestyle factors. Results showed that coffee consumption was not associated with the incidence of metabolic syndrome, high fasting glucose, high triglycerides, central obesity, high blood pressure and low HDL-cholesterol (HDL-C). Tea consumption was not associated with incidence of metabolic syndrome and the component conditions except for the risk of having low HDL-C, in which a nominally inverse association was observed (multivariate-adjusted HR at 2–3 cups/d: 0⋅48, 95 % CI 0⋅26, 0⋅87, P = 0⋅016; 4 cups/d or more: 0⋅50, 95 % CI 0⋅27, 0⋅93, P = 0⋅029). After stratifying for fruit consumption (Pinteraction between tea and fruit = 0⋅007), consuming four cups of tea per day was nominally associated with lower incidence of metabolic syndrome among those with high fruit consumption (multivariable-adjusted HR: 0⋅44, 95 % CI 0⋅20, 0⋅93, P = 0⋅033). Our results did not support a significant association between tea and coffee consumption and metabolic syndrome. Tea consumption may be associated with a lower risk of having low HDL-C, while high tea and fruit consumption together may be associated with a lower risk of developing metabolic syndrome.

This article responds to the critical debate around Jennifer Kent’s horror movie, The Babadook (2014), by offering an analysis that moves beyond its use of generic codes and its sociopolitical representation of maternity. It contends that reading the film as a trauma narrative allows us to better understand the horrifying experience suffered by Amelia Vanek (Essie Davis): her husband’s premature death in a car accident. Taking Dominick LaCapra’s concepts of acting out and working through as key interpretive tools, the analysis demonstrates how Kent conveys posttraumatic stress disorder as both a visceral and a material experience, inscribing absence and loss onto the cinematic texture of the film. The article offers the conclusion that, as The Babadook enacts Amelia’s process of recuperation, figured as a psychosomatic struggle against her monstrous Other, she becomes able to express her trauma and, in doing so, is finally able to accept her husband’s death.

Hearing loss and cognitive impairments are both highly prevalent neurological complications for older adults. While there is growing evidence to suggest that these two conditions are interrelated, little research has been conducted that directly examines the progression and developmental trajectories of these complications contemporaneously. The aim of the study is to identify the distinct trajectory profiles for hearing loss and cognitive function in an older population over a 10-year period. Through dual trajectory modeling, the interrelationship, co-occurring movements, and overlaps between these two complications were examined. We also investigated the influence of hearing aid ownership on cognitive function trajectories. We utilized longitudinal data from 1,445 participants in the Blue Mountains Hearing Study (aged 55+ years) involving repeated measures from a population-based survey with audiometric hearing assessments. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). The group-based trajectory modeling (GBTM) identified three trajectory profiles for both hearing loss and cognitive function in two older age groups (55–69 years and 70+ years). The outputs from the dual trajectories models showed the conditional probability for “no hearing loss” trajectories to be around 90% more likely to have “high-normal” cognitive function, demonstrating co-occurring overlap. In contrast, for “moderate to severe hearing loss” trajectories, the conditional probability drops to 65% and 79% for the 55–69 age group and 70+ age group respectively. There was also an increasing probability for “cognitive decline” conditional on the severity of hearing loss with 6.7%, 7.5%, and 8.7% for no hearing loss, mild hearing loss, and moderate to severe hearing loss trajectory groups. While we did not find any statistically significant difference in the influence of hearing aid use in the cognitive function trajectories, there was a consistent greater representation of non-hearing aid users in the trajectories with poorer cognitive function. This study found GBTM to identify trajectories that were in agreement with our current understanding of hearing loss and cognitive impairment in older adults. This study also adds to the existing evidence-base as dual trajectories demonstrated co-occurrence in developmental changes in these two common neurological complications for the older population.

Objectives We aimed to analyse the degree of carer burden and depressive symptoms in family carers of persons with age-related macular degeneration (AMD) and explore the factors independently associated with carer burden and depressive symptoms.Methods Cross-sectional study using self-administered and interviewer-administered surveys, involving 96 family carer–care recipient pairs. Participants were identified from tertiary ophthalmology clinics in Sydney, Australia, as well as the Macular Disease Foundation of Australia database. Logistic regression, Pearson and Spearman correlation analyses were used to investigate associations of explanatory factors (family caregiving experience, carer fatigue, carer quality of life and care-recipient level of dependency) with study outcomes—carer burden and depressive symptoms.Results Over one in two family carers reported experiencing mild or moderate-severe burden. More than one in five and more than one in three family carers experienced depressive symptoms and substantial fatigue, respectively. High level of care-recipient dependency was associated with greater odds of moderate-severe and mild carer burden, multivariable-adjusted OR 8.42 (95% CI 1.88 to 37.60) and OR 4.26 (95% CI 1.35 to 13.43), respectively. High levels of fatigue were associated with threefold greater odds of the carer experiencing depressive symptoms, multivariable-adjusted OR 3.47 (95% CI 1.00 to 12.05).Conclusions A substantial degree of morbidity is observed in family carers during the caregiving experience for patients with AMD. Level of dependency on the family carer and fatigue were independently associated with family carer burden and depressive symptoms.Trial registration number The trial registration number is ACTRN12616001461482. The results presented in this paper are Pre-results stage.

Purpose: To describe the prevalence, risk factors, and associations of vitreoretinal interface (VRI) abnormalities in a population-based study of older adults. Design: Cross-sectional analysis of cohort study participants. Participants: Of the 1149 participants (mean age, 76.1 ± 6.9 years) in the 15-year Blue Mountains Eye Study follow-up examination from 2007 through 2009, 905 (1791 eyes) had gradable time-domain or spectral-domain OCT scans of the macula from at least 1 eye. Methods: OCT scans were graded according to the International Vitreomacular Traction Study Group classification system of VRI abnormalities. Best-corrected visual acuity (BCVA) was recorded. Main Outcome Measures: Prevalence of VRIs. Results: Overall, 451 participants showed any VRI abnormality (49.8%). Prevalence of VRI abnormality by person was: vitreomacular adhesion (VMA), 33.6%; vitreomacular traction (VMT), 1.6%; epiretinal membrane (ERM), 21.4%; full-thickness macular hole (FTMH), 0.7%; and lamellar macular hole (LMH), 0.7%. Twenty-two percent of VMAs were focal, and 78% were broad based; 76% of VMTs were focal, and 24% were broad based. All FTMHs observed were large (>400 μm), with mean aperture size of 573 μm (range, 459–771 μm). Increased age was associated with higher ERM and lower VMA prevalence (P < 0.001 for both). Pseudophakia and myopia were associated with ERM (age- and sex-adjusted odds ratios [ORs], 1.48 [95% confidence interval (CI), 1.01–2.17] and 1.72 [95% CI, 1.05–2.81], respectively). Moderate or severe ERM and FTMH were associated with worse BCVA of 9.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (95% CI, 3.4–15.0 ETDRS letters; P = 0.008) and 26.0 ETDRS letters (95% CI, 10.9–41.1 ETDRS letters; P = 0.001), respectively. Conclusions: The prevalence of VRI abnormalities is high in older individuals. Epiretinal membrane was associated with increasing age, pseudophakia, and myopia. Epiretinal membrane and FTMH may account for significant visual loss in the affected eye. This study provided useful population-based data on the prevalence of VRI abnormalities in older individuals.

Abstract Background Real-world data (RWD) has been a valuable addition to the scientific literature regarding treatment pathways, clinical outcomes and characteristics of patients with retinal diseases in recent years. Registries, observational studies and patient databases are often used for real-world research. However, there is limited information for each data source on the design, consistency, data captured, limitations and usability for assessing research questions. Using a systematic approach, we identified RWD sources for patients with retinal diseases and assessed them for completeness of data relating to different outcomes. Methods A systematic literature review was carried out to identify RWD sources for patients with retinal disease. Potentially relevant articles published between 2006 and 2016 were screened following electronic searches in Embase and MEDLINE. Congress and supplementary searches were undertaken to identify RWD sources that may not be referenced in full publications. For each data source, availability and quantity of data on baseline status, clinical outcomes, treatment and management, safety, and patient-reported and economic burden were assessed using a bespoke completeness assessment tool based on International Consortium for Health Outcomes Measurement guidelines for macular degeneration. Completeness of data for each area of interest in each data source was assessed and rated using a ‘good–moderate–poor’ rating system based on availability and quantity of available data. Each data source was then given an overall score based on its score for each of the 7 areas of interest. Results A total of 128 RWD sources from 32 countries were identified. Of the identified sources, 64 sources from 16 countries of interest were analyzed. Most of these sources provided information on baseline status and clinical outcomes and treatment, but few collected data on economic and patient-reported burden. Of the RWD sources analyzed, 10 scored highly in the overall completeness assessment, collecting data on most or all of the areas of interest; these sources are considered to be robust data sources for performing ophthalmology real-world studies. Conclusions The study provides a comprehensive list of RWD sources for patients with retinal disease, many of which will be useful for conducting real-world studies in the field of ophthalmology.

Treatment of elderly patients with lung cancer is significantly hindered by concerns about treatment tolerability, toxicity and limited clinical trial data in the elderly; potentially giving rise to treatment nihilism amongst clinicians. This study aims to describe survival in elderly patients with lung cancer and explore potential causes for excess mortality. Patients diagnosed with lung cancer in the Victorian Lung Cancer Registry between 2011–2018 were analysed (n=3481). Patients were age-categorised and compared using Cox-regression modelling to determine mortality risk, after adjusting for confounding. Probability of being offered cancer treatments was also determined, further stratified by disease stage. The eldest patients (≥80 years old) had significantly shorter median survival compared with younger age groups (

Background: The evidence regarding the association between added sugar (AS) intake and obesity remains inconsistent. The aim of this study was to investigate the association between changes in the percentage of energy intake from AS (EAS%) and changes in body weight in a cohort study of older Australians during 15 years of follow-up. In addition, associations were assessed according to whether EAS% intake was provided from beverage or non-beverage sources.Methods: Data were analyzed from the participants of the Blue Mountains Eye Study Cohort. Dietary data were collected at baseline (1992–94) and three five-yearly intervals using a 145-item food frequency questionnaire. Participants' body weight was measured at each time point. Five-yearly changes in EAS% intake and body weight were calculated (n = 1,713 at baseline). A generalized estimating equation (GEE) model was used to examine the relationship between the overall five-yearly changes in EAS% intake and body weight, adjusted for dietary and lifestyle variables.Results: In each time interval, the EAS% intake decreased by ~5% in the lowest quartile (Q1) and increased by ~5% in the highest quartile (Q4). The mean (SD) body weight change in Q1 and Q4 were 1.24 (8.10) kg and 1.57 (7.50) kg (first time interval), 0.08 (6.86) kg and −0.19 (5.63) kg (second time interval), and −1.22 (5.16) kg and −0.37 (5.47) kg (third time interval), respectively. In GEE analyses, the overall five-yearly change in EAS% intake was not significantly associated with body weight change (Ptrend = 0.837). Furthermore, no significant associations were observed between changes in EAS% intake from either beverage or non-beverage sources and changes in body weight (Ptrend for beverage sources = 0.621 and Ptrend for non-beverage sources = 0.626).Conclusion: The findings of this older Australian cohort do not support the association between changes in EAS% intake and body weight, regardless of AS food sources (beverage or non-beverage).

There is paucity of population-based data on occupational noise exposure and risk of age-related hearing loss. Therefore, we assessed cross-sectional and longitudinal associations of past workplace noise exposure with hearing loss in older adults. At baseline, 1923 participants aged 50+ years with audiological and occupational noise exposure data included for analysis. The pure-tone average of frequencies 0.5, 1.0, 2.0 and 4.0 kHz (PTA0.5-4KHz) >25 dB HL in the better ear, established the presence of hearing loss. Participants reported exposure to workplace noise, and the severity and duration of this exposure. Prior occupational noise exposure was associated with a 2-fold increased odds of moderate-to-severe hearing loss: multivariable-adjusted OR 2.35 (95% CI 1.45-3.79). Exposure to workplace noise for >10 years increased the odds of having any hearing loss (OR 2.39, 95% CI 1.37-4.19) and moderate-to-severe hearing loss (OR 6.80, 95% CI 2.97-15.60). Among participants reporting past workplace noise exposure at baseline the 10-year incidence of hearing loss was 35.5% versus 29.1% in those who had no workplace noise exposure. Workplace noise exposure was associated with a greater risk of incident hearing loss during the 10-year follow-up: multivariable-adjusted OR 1.39 (95% CI 1.13-1.71). Prior occupational noise exposure was not associated with hearing loss progression. Workplace noise exposure increased the risk of incident hearing loss in older adults. Our findings underscore the importance of preventive measures which diminish noise exposure in the workplace, which could potentially contribute towards reducing the burden of hearing loss in later life.

PURPOSE:To assess the one-year effectiveness and safety of ranibizumab 0.5 mg in treatment- naïve patients with diabetic macular edema (DME) enrolled in the real-world LUMINOUS study. PATIENTS AND METHODS:A 5-year, prospective, observational, open-label, global study which recruited 30,138 patients across all approved indications. Consenting patients (≥18 years) who were treatment-naïve or previously treated with ranibizumab or other ocular treatments were treated as per the local ranibizumab label. Here, we present the change in visual acuity (VA) (Early Treatment Diabetic Retinopathy Study letter score; primary treated eye) at Year 1, as well as the change in VA based on injection frequencies (≤4 and ≥5), treatment exposure, and the overall adverse events (AEs) and serious AEs (SAEs) in treatment-naïve DME patients. RESULTS:Of the 4,710 DME patients enrolled in the study, 1,063 were treatment-naïve. At baseline, mean age was 64.5 years, 54.7% were male, and 69.2% were white. At 1 year, mean VA letter score improved by +3.5 (n = 502) from a baseline of 57.7 with a mean of 4.5 injections. Presented by injection frequencies ≤4 and ≥5, VA letter score gains were 0.5 (n = 264) and 6.9 (n = 238) from baseline letter scores of 56.6 and 59.0, respectively. Over 5 years, the incidence of ocular/non-ocular AEs and SAEs was 7.2%/10.1% and 0.3%/5.8%, respectively. No endophthalmitis cases were reported. CONCLUSIONS:The LUMINOUS study included patients with DME with more diverse baseline characteristics than those in randomized clinical trials. The 1-year data showed improvement in VA with low number of injections in treatment- naïve patients with DME. Greater VA gains were observed in patients who received ≥5 injections. No new safety findings were identified. LUMINOUS confirms the effectiveness and safety of ranibizumab for the treatment of patients with DME in a real-world clinical practice.

Background: People with advanced dementia who live and die in nursing homes experience variable quality of life, care and dying. There is a need to identify appropriate, cost-effective interventions that facilitate high-quality end-of-life care provision. Objectives: To establish the feasibility and acceptability to staff and family of conducting a cluster randomised controlled trial of the Namaste Care intervention for people with advanced dementia in nursing homes. Design: The study had three phases: (1) realist review and (2) intervention refinement to inform the design of (3) a feasibility cluster randomised controlled trial with a process evaluation and economic analysis. Clusters (nursing homes) were randomised in a 3 : 1 ratio to intervention or control (usual care). The nature of the intervention meant that blinding was not possible. Setting: Nursing homes in England providing care for people with dementia. Participants: Residents with advanced dementia (assessed as having a Functional Assessment Staging Test score of 6 or 7), their informal carers and nursing home staff. Intervention: Namaste Care is a complex group intervention that provides structured personalised care in a dedicated space, focusing on enhancements to the physical environment, comfort management and sensory engagement. Main outcome measures: The two contender primary outcome measures were Comfort Assessment in Dying – End of Life Care in Dementia for quality of dying (dementia) and Quality of Life in Late Stage Dementia for quality of life. The secondary outcomes were as follows: person with dementia, sleep/activity (actigraphy), neuropsychiatric symptoms, agitation and pain; informal carers, satisfaction with care at the end of life; staff members, person-centred care assessment, satisfaction with care at the end of life and readiness for change; and other data – health economic outcomes, medication/service use and intervention activity. Results: Phase 1 (realist review; 86 papers) identified that a key intervention component was the activities enabling the development of moments of connection. In phase 2, refinement of the intervention enabled the production of a user-friendly 16-page A4 booklet. In phase 3, eight nursing homes were recruited. Two homes withdrew before the intervention commenced; four intervention and two control homes completed the study. Residents with advanced dementia (n = 32) were recruited in intervention (n = 18) and control (n = 14) homes. Informal carers (total, n = 12: intervention, n = 5; control, n = 7) and 97 staff from eight sites (intervention, n = 75; control, n = 22) were recruited over a 6-month period. Recruitment is feasible. Completion rates of the primary outcome questionnaires were high at baseline (100%) and at 4 weeks (96.8%). The Quality of Life in Late Stage Dementia was more responsive to change over 24 weeks. Even where economic data were missing, these could be collected in a full trial. The intervention was acceptable; the dose varied depending on the staffing and physical environment of each care home. Staff and informal carers reported changes for the person with dementia in two ways: increased social engagement and greater calm. No adverse events related to the intervention were reported. Conclusions: A subsequent definitive trial is feasible if there are amendments to the recruitment process, outcome measure choice and intervention specification. Future work: In a full trial, consideration is needed of the appropriate outcome measure that is sensitive to different participant responses, and of clear implementation principles for this person-centred intervention in a nursing home context. Trial registration: Current Controlled Trials ISRCTN14948133. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 6. See the NIHR Journals Library website for further project information.

Abstract Background Lung cancer is the leading cause of cancer mortality worldwide. Early diagnosis and treatment is a key factor in reducing mortality and improving patient outcomes. To achieve this, it is important to understand the diagnostic pathways of cancer patients. Patients from Culturally and Linguistically Diverse (CALD) are a vulnerable group for lung cancer with higher mortality rates than Caucasian patients. The aim of this study is to explore differences in the lung cancer diagnostic pathways between CALD and Anglo-Australian patients and factors underlying these differences. Methods This is a prospective, observational cohort study using a mixed-method approach. Quantitative data regarding time intervals in the lung cancer diagnostic pathways will be gathered via patient surveys, General practitioner (GP) review of general practice records, and case-note analysis of hospital records. Qualitative data will be gathered via structured interviews with lung cancer patients, GPs, and hospital specialists. The study will be conducted in five study sites across three states in Australia. Anglo-Australian patients and patients from five CALD groups (i.e., Arabic, Chinese, Greek, Italian and Vietnamese communities) will mainly be identified through the list of new cases presented at lung multidisciplinary team meetings. For the quantitative component, it is anticipated that 724 patients (362 Anglo-Australian and 362 CALD patients) will be recruited to obtain a final sample of 290 (145 per group) assuming a 50% patient survey completion rate and a 80% GP record review completion rate. For the qualitative component, 60 interviews with lung cancer patients (10 Anglo-Australian and 10 patients per CALD group), 20 interviews with GPs, and 20 interviews with specialists will be conducted. Discussion This is the first Australian study to compare the time intervals along the lung cancer diagnostic pathway between CALD and Anglo-Australian patients. The study will also explore the underlying patient, healthcare provider, and health system factors that influence the time intervals in the two groups. This information will improve our understanding of the effect of ethnicity on health outcomes among lung cancer patients and will inform future interventions aimed at early diagnosis and treatment for lung cancer, particularly patients from CALD backgrounds. Trial registration The project was retrospectively registered with Australian New Zealand Clinical Trials Registry (registration number: ACTRN12617000957392, date registered: 4th July 2017).

Reduced central corneal thickness (CCT) is observed in common eye diseases as well as in rare Mendelian disorders. Here, in a cross-ancestry GWAS, the authors identify 19 novel genetic loci associated with CCT, a subset of which is involved in rare corneal or connective tissue disorders.

This paper investigates the application of underwater acoustic sensor networks for large scale monitoring of the ocean environment. The low propagation speed of acoustic signals presents a fundamental challenge in coordinating the access to the shared communication medium in such networks. In this paper, we propose two medium access control (MAC) protocols, namely, Transmit Delay Allocation MAC (TDA-MAC) and Accelerated TDA-MAC, that are capable of providing time division multiple access (TDMA) to sensor nodes without the need for centralized clock synchronization. A comprehensive simulation study of a network deployed on the sea bed shows that the proposed protocols are capable of closely matching the throughput and packet delay performance of ideal synchronized TDMA. The TDA-MAC protocols also significantly outperform T-Lohi, a classical contention-based MAC protocol for underwater acoustic networks, in terms of network throughput and, in many cases, end-to-end packet delay. Furthermore, the assumption of no clock synchronization among different devices in the network is a major advantage of TDA-MAC over other TDMA-based MAC protocols in the literature. Therefore, it is a feasible networking solution for real-world underwater sensor network deployments.

Abstract Background Within- and between-person variation in nutrient intake is well established, but little is known about variability in dietary flavonoid intake, including the effect of seasonality. Methods Within- and between-individual variability of flavonoid intake, and intake of flavonoid subclasses was examined in older adults (n = 79; mean age 70.1 y (range: 60y-80y)), using three separate 4-day weighed food records (WFR) collected approximately 4 months apart. The effects of seasonality were also examined. Mixed-effects linear regression models were used to estimate within- and between-individual variance components for flavonoids and subclasses. The number of days of dietary assessment required for a high level of hypothetical accuracy was calculated from variance ratios. Results Within- and between-individual variability was high for flavonoid intake, and intake of flavonoid subclasses, with variance ratios > 1. It was calculated that six days of WFR data are required for total flavonoid intake, and between 6 and 10 days was required for flavonoid subclasses. There was no effect of seasonality for total flavonoid intake or intake of flavonoid subclasses, with the exception that flavan-3-ol and flavanone intakes which were relatively low in summer, and in summer and winter, respectively. Conclusion While the effects of seasonality on total flavonoid intake may be small, within- and between-individual variation associated with flavonoid intake assessment appears to be substantial across 12 days of WFR data in older adults. It is recommended that a minimum of 6 days of weighed food records are collected to minimise the impact of within- and between-individual variability on total flavonoid intake assessments in this population.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article.

Tinnitus is the phantom perception of sound in the ears or head that increases in prevalence as age increases. With strong evidence supporting the benefits of dietary fibre for vascular health and hearing loss, intake of dietary fibre may also have a role in the prevention of tinnitus symptoms. This longitudinal study aims to determine the association between the intake of dietary fibre and other carbohydrate nutrition variables including glycaemic index (GI), glycaemic load (GL) and total carbohydrate intakes, and incident tinnitus over 10 years. Of the 1730 participants (aged ≥50 years) from the Blue Mountains Hearing Study with complete baseline data on tinnitus symptoms and carbohydrate intakes, 536 (31%) cases of tinnitus were identified and excluded from further incidence analysis. Dietary data were collected using a validated semi-quantitative food frequency questionnaire to determine intakes of total dietary fibre and fibre contributions from cereals, vegetables, and fruit. A purpose-built database based on Australian GI values was used to calculate mean GI. Lower versus higher intakes of fruit fibre (≤3.6 g/day vs. >3.6 g/day) and cereal fibre (≤4.2 g/day vs. >4.2 g/day) were significantly associated with a 65% (HR = 1.65; 95% CI: 1.15–2.36) and 54% (HR = 1.54; 95% CI: 1.07–2.22) increased risk of developing tinnitus over 10 years, respectively. Associations between intake of other carbohydrate nutrients and incident tinnitus were mostly non-significant. In summary, our study showed modest associations between intake of dietary fibre and incident tinnitus. The protective effects of fibre, particularly insoluble fibre, could underlie observed associations by reducing the risk of tinnitus via vascular risk factors such as cardiovascular disease. Further longitudinal studies evaluating different types and sources of fibre and tinnitus risk are needed to confirm our study findings.

Abstract We aimed to establish the collective influence of four lifestyle practices (physical activity, diet, smoking and alcohol consumption) on the prevalence and incidence of AMD. At baseline, 2428 participants aged 49+ with complete lifestyle and AMD data were examined, and of these, 1903 participants were re-examined 15 years later. AMD was assessed from retinal photographs. A health behaviour score was calculated, allocating 1 point for each poor behaviour: current smoking; fruits and vegetables consumed 2 alcoholic drinks per day. Cross-sectional analysis showed that participants who engaged in all 4 poor health behaviours (n = 29) versus those who did not engage in unhealthy behaviours (reference group; n = 677) had greater odds of any and late AMD: multivariable-adjusted OR, 5.14 (95% CI, 1.04–25.45) and OR 29.53 (95% CI 2.72–321.16), respectively. A marginally non-significant association was observed between increasing number of poor health behaviours and 15-year incidence of early AMD (multivariable-adjusted P-trend = 0.08). Our data suggests that motivating patients with AMD to eat better, exercise more, limit alcohol intake and avoid smoking seems advisable to decelerate the development or worsening of existing AMD.

Background: Little is known about the significance of severe coronary tortuosity (SCT) despite it being a relatively common finding on coronary angiography. We examined whether the presence of tortuosity was influenced by gender or cardiac risk factors. Methods and results: We examined 870 patients (Men = 589, Women = 281) who presented to Westmead Hospital, Sydney, Australia for invasive coronary angiography for the assessment of chest pain due to suspected CAD. Female gender and age were significantly associated with SCT (p

[This corrects the article DOI: 10.1371/journal.pone.0220143.].

PurposeTo evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM).MethodsA candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM).ResultsIn the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance.ConclusionsOf the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.

This report by the Consortium for Refractive Error and Myopia uses gene-environment-wide interaction study (GEWIS) to identify genetic loci that affect environmental influence in myopia development, and identifies ethnic specific genetic loci that attribute to eye refractive errors.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

This paper discusses requirements for autonomy and communications in maritime environments through two use cases which are sourced from military scenarios: Mine Counter Measures (MCM) and Anti-Submarine Warfare (ASW). To address these requirements, this work proposes a service-oriented architecture that breaks the typical boundaries between the autonomy and the communications stacks. An initial version of the architecture has been implemented and its deployment during a field trial done in January 2019 is reported. The paper discusses the achieved results in terms of system flexibility and ability to address the MCM and ASW requirements.

Dietary flavonoids are vasoactive phytochemicals with promising anti-inflammatory properties. We aimed to assess the associations between baseline intakes of six commonly consumed flavonoid subclasses and 10-year incidence of age-related hearing loss. At baseline, 1691 participants aged 50+ years had information on dietary intakes and hearing status. Hearing loss was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz > 25 dB hearing level (HL). Dietary data were collected through a semi-quantitative food frequency questionnaire. The flavonoid content of foods was estimated using US databases. During the 10-year follow-up, 260 (31.6%) new cases of hearing loss (incident) were observed. After multivariable adjustment, participants in the fourth versus first quartile (reference group) of intake of dietary isoflavone had 36% lower risk of incident hearing loss after 10 years: odds ratios (OR) 0.64 (95% confidence intervals, CI, 0.42–0.99); p-value for trend = 0.03. Nonsignificant associations were observed between the other five flavonoid subclasses and 10-year incidence of hearing loss. Our findings do not support the hypothesis that the intake of dietary flavonoids protect against long-term risk of hearing loss. The association with isoflavone intake needs to be confirmed by other population-based studies.

There is an evidence–practice gap between the dietary recommendations for age-related macular degeneration (AMD) presented in the literature and those practiced by patients. This study reports on the 3-month post-intervention results of a randomised controlled trial (RCT) evaluating telephone-delivered counselling to improve dietary behaviours among AMD patients. A total of 155 AMD patients (57% female, aged 78 ± 8 years; control: 78, intervention: 77), primarily residing in New South Wales, Australia, were recruited. Participants completed a baseline questionnaire and a short dietary questionnaire (SDQ-AMD). The intervention included an evidence-based nutrition resource and four monthly calls with a dietitian. Immediately post-intervention, intervention participants repeated the SDQ-AMD and completed a feedback form. At 3 months post-intervention, both study arms repeated the SDQ-AMD. Statistical analyses included t-tests and McNemar’s test. Intervention participants reported satisfaction with the tailored phone calls, nutrition resource and nutrition education provided. At 3 months post-intervention, there was no statistically significant difference between study arms in the proportion of participants meeting the dietary goals nor in intake (mean servings ± SE) of total vegetables (primary outcome) and other key food groups; however, there was a significantly higher intake of nuts (secondary outcome) (3.96 ± 0.51 vs. 2.71 ± 0.32; p = 0.04) among participants in the intervention versus control group. Within the intervention arm, there were also significant improvements in intakes of the following secondary outcomes: dark green leafy vegetables (0.99 ± 0.17 vs. 1.71 ± 0.22; p = 0.003) and legumes (0.69 ± 0.10 vs. 1.12 ± 0.16; p = 0.02) and intake of sweets and processed/prepared foods (8.31 ± 0.76 vs. 6.54 ± 0.58, p = 0.01). In summary, although there were few dietary differences between study arms at 3 months post-intervention, the intervention involving four monthly calls was acceptable and helpful to the participants. This type of intervention therefore has the potential to provide people with AMD the needed support for improving their nutrition knowledge and dietary practices, especially if continued over a longer period.

This article presents the findings of a national survey on Islam in Australia based on responses of 1034 Muslim Australian citizens and permanent residents. Knowing what Muslim Australians think about Islam in relation to Australian society is essential for a more informed understanding about Islam and Muslims needed to address misinformation, Islamophobia, and extremism. The findings presented in this article include typologies of Muslims; sources of influence concerning Islam; interpretations of the Qur’an; perspectives on ethical, social, and theological issues; issues of concern; social connections and sense of belonging; views on various Muslim-majority countries; and perspectives concerning political Islam, including jihad, caliphate, and shariah. While respondents’ understandings, interpretations, and expressions of Islam overall align with values and principles of equality, human rights, social cohesion, and social justice, a minority were found to understand and interpret Islam in ways that reflect the influence of late 20th and early 21st century ideas associated with Islamist political ideology, and a smaller sub-group were found to have views that could be considered extreme. This article discusses these findings in relation to the early 21st century time-period factors and the Australian social context.

Introduction The cancer burden preventable through modifications to risk factors can be quantified by calculating their population attributable fractions (PAFs). PAF estimates require large, prospective data to inform risk estimates and contemporary population-based prevalence data to inform the current exposure distributions, including among population subgroups. Objectives and Approach We provide estimates of the preventable future cancer burden in Australia using large linked datasets. We pooled data from seven Australian cohort studies (N=367,058) and linked them to national registries to identify cancers and deaths. We estimated the strength of the associations between behaviours and cancer risk using a proportional hazards model, adjusting for age, sex, study and other behaviours. Exposure prevalence was estimated from contemporary National Health Surveys. We harmonised risk factor data across the data sources, and calculated PAFs and their 95% confidence intervals using a novel method accounting for competing risk of death and risk factor interdependence. Results During the first 10-years follow-up, there were 3,471 incident colorectal cancers, 640 premenopausal and 2,632 postmenopausal breast cancers, 2,025 lung cancers and 22,078 deaths. The leading preventable causes were current smoking (53.7% of lung cancers), body fatness or BMI ≥ 25kg/m2 (11.1% of colorectal cancers, 10.9% of postmenopausal breast cancers), and regular alcohol consumption (12.2% of premenopausal breast cancers). Three in five lung cancers, but only one in four colorectal cancers and one in five breast cancers, were attributable to modifiable factors, when we also considered physical inactivity, dietary and hormonal factors. The burden attributable to modifiable factors was markedly higher in certain population subgroups, including men (colorectal, lung), people with risk factor clustering (colorectal, breast, lung), and individuals with low educational attainment (breast, lung). Conclusion/Implications Estimating PAFs for modifiable risk factors across cancers using contemporary exposure prevalence data can inform timely public health action to improve health and health equity. Testing PAF effect modification may identify population subgroups with the most to gain from programs that support behaviour change and early detection.

[This corrects the article DOI: 10.1371/journal.pone.0025598.].

The adverse long-term consequences following traumatic brain injury are poorly understood, particularly on the cerebral microvasculature. Retinal vessels are a surrogate marker of cerebral vascular changes. We therefore aimed to examine the cross-sectional association between serious head injury or being knocked unconscious, and/or concussion and retinal microvascular signs, specifically, mean retinal arteriolar and venular calibre, in older adults after accounting for potential confounders. This cohort study involved 2,624 adults with mean age of 66.9 (±9.1) years who self-reported head injury and concussion parameters, and had gradable retinal photographs. Face-to-face interviews with trained interviewers allowed participants to report prior serious head injury or being knocked unconscious, and/or a previous diagnosis of concussion by a medical professional. Fundus photographs were taken and retinal vascular calibre measured using computer-assisted techniques and summarized. There were 25.9%, 15.3% and 10.1% who reported a prior serious head injury or being "knocked unconscious", concussion, and both, respectively. Participants in the first group compared to non-injured participants had significantly wider (~2 μm) mean retinal venular calibre (p = 0.02), after adjusting for age, sex, smoking, body mass index, mean arterial blood pressure, type 2 diabetes and fellow vessel calibre. No significant associations were observed in people reporting medically diagnosed concussion or with mean retinal arteriolar calibre. Our exploratory study suggests that head injury is independently associated with wider retinal venular caliber. These findings warrant further investigation in longitudinal cohort studies.