Creating correct aberrations: why blur isn’t always bad in the eye

In optics in general, a sharp aberration-free image is normally the desired goal, and the whole field of adaptive optics has developed with the aim of producing blur-free images. Likewise, in ophthalmic optics we normally aim for a sharp image on the retina. But even with an emmetropic, or well-corrected eye, chromatic and high order aberrations affect the image. We describe two different areas where it is important to take these effects into account and why creating blur correctly via rendering can be advantageous. Firstly we show how rendering chromatic aberration correctly can drive accommodation in the eye and secondly report on matching defocus-l generated using rendering with conventional optical defocus

Ocular accommodation and wavelength: The effect of longitudinal chromatic aberration on the stimulus-response curve.

The longitudinal chromatic aberration (LCA) of the eye creates a chromatic blur on the retina that is an important cue for accommodation. Although this mechanism can work optimally in broadband illuminants such as daylight, it is not clear how the system responds to the narrowband illuminants used by many modern displays. Here, we measured pupil and accommodative responses as well as visual acuity under narrowband light-emitting diode (LED) illuminants of different peak wavelengths. Observers were able to accommodate under narrowband light and compensate for the LCA of the eye, with no difference in the variability of the steady-state accommodation response between narrowband and broadband illuminants. Intriguingly, our subjects compensated more fully for LCA at nearer distances. That is, the difference in accommodation to different wavelengths became larger when the object was placed nearer the observer, causing the slope of the accommodation response curve to become shallower for shorter wavelengths and steeper for longer ones. Within the accommodative range of observers, accommodative errors were small and visual acuity normal. When comparing between illuminants, when accommodation was accurate, visual acuity was worst for blue narrowband light. This cannot be due to the sparser spacing for S-cones, as our stimuli had equal luminance and thus activated LM-cones roughly equally. It is likely because ocular LCA changes more rapidly at shorter wavelength and so the finite spectral bandwidth of LEDs corresponds to a greater dioptric range at shorter wavelengths. This effect disappears for larger accommodative errors, due to the increased depth of focus of the eye

Illinois Waterfowl Surveys and Investigations W-43-R-63 Annual Progress Report FY2016 Period: 1 July 2015 – 30 June 2016

Objectives 1) Inventory abundance and distribution of waterfowl and other waterbirds (a minimum of 10 species and guilds) during autumn migration at a minimum of 30 sites along the Illinois and central Mississippi rivers of Illinois, 2) Estimate waterfowl and other waterbird population sizes (a minimum of 10 species and guilds) during autumn migration using an aerial quadrat survey along the central Illinois River for comparison with aerial inventories (Objective 1), 3) Investigate the ecology of up to 50 gadwall and 50 American green-winged teal during spring migration in and near the central Illinois River valley of Illinois, 4) Determine breeding bird use of and nest density in a minimum of 10 moist-soil wetlands managed for waterfowl during summer in central Illinois, 5) Investigate the breeding ecology of a minimum of 50 sandhill cranes during spring and summer in northeastern Illinois consistent with an ongoing research project, 6) Investigate movements and home range size of a minimum of 10 Canada geese during winter in and near the Greater Chicago Metropolitan Area of Illinois, and 7) Determine habitat quality of a minimum of 100 wetlands and deepwater habitats during spring, summer, and early autumn for migrating dabbling ducks, breeding wetland birds, and migrating shorebirds in Illinois.Illinois Department of Natural Resources, Division of Wildlife & U.S. Fish and Wildlife Service Contract Number: RC09-13FWUIUCunpublishednot peer reviewedOpe

The implementation of medical revalidation: an assessment using normalisation process theory

Abstract Background Medical revalidation is the process by which all licensed doctors are legally required to demonstrate that they are up to date and fit to practise in order to maintain their licence. Revalidation was introduced in the United Kingdom (UK) in 2012, constituting significant change in the regulation of doctors. The governing body, the General Medical Council (GMC), envisages that revalidation will improve patient care and safety. This potential however is, in part, dependent upon how successfully revalidation is embedded into routine practice. The aim of this study was to use Normalisation Process Theory (NPT) to explore issues contributing to or impeding the implementation of revalidation in practice. Methods We conducted seventy-one interviews with sixty UK policymakers and senior leaders at different points during the development and implementation of revalidation: in 2011 (n = 31), 2013 (n = 26) and 2015 (n = 14). We selected interviewees using purposeful sampling. NPT was used as a framework to enable systematic analysis across the interview sets. Results Initial lack of consensus over revalidation’s purpose, and scepticism about its value, decreased over time as participants recognised the benefits it brought to their practice (coherence category of NPT). Though acceptance increased across time, revalidation was not seen as a legitimate part of their role by all doctors. Key individuals, notably the Responsible Officer (RO), were vital for the successful implementation of revalidation in organisations (cognitive participation category). The ease with which revalidation could be integrated into working practices varied greatly depending on the type of role a doctor held and the organisation they work for and the provision of resources was a significant variable in this (collective action category). Formal evaluation of revalidation in organisations was lacking but informal evaluation was taking place. Revalidation had not yet reached the stage where feedback was being used for improvement (reflexive monitoring category). Conclusions Requiring all organisations to use the same revalidation model made revalidation easy to integrate into existing work for some but problematic for others. In order for revalidation to be fully embedded and successful, impeding factors, such as a lack of resources, need to be addressed

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Creating correct aberrations: why blur isn’t always bad in the eye

In optics in general, a sharp aberration-free image is normally the desired goal, and the whole field of adaptive optics has developed with the aim of producing blur-free images. Likewise, in ophthalmic optics we normally aim for a sharp image on the retina. But even with an emmetropic, or well-corrected eye, chromatic and high order aberrations affect the image. We describe two different areas where it is important to take these effects into account and why creating blur correctly via rendering can be advantageous. Firstly we show how rendering chromatic aberration correctly can drive accommodation in the eye and secondly report on matching defocus-l generated using rendering with conventional optical defocus