Detecting deformation asymmetries on multiple meridians in an ex vivo keratoconic eye model

Purpose : Ocular biomechanical simulations show that air-puff induced corneal deformation imaging (APCDI) can reveal pathological asymmetric responses, as in eccentric keratoconus. Such asymmetries often go undetected when monitoring deformation on only one meridian (Birkenfeld et al., IOVS, 2019), as is the case with commercial instruments. We present a novel custom optical coherence tomography (OCT) system coupled with an air-puff module capable of detecting deformation asymmetries on multiple meridians in a keratoconic-mimicking ex vivo porcine eye model. Methods : Corneal deformation was induced by a piston-based air-puff module colinearly coupled to a custom OCT system. The puff module provided an air-puff FWHM duration of ~11 ms, reaching a maximum pressure on the corneal apex of ~13 kPa. Our OCT system used a 200 kHz 1300 nm VCSEL swept source, with an axial range of 26 mm. A freshly enucleated porcine eye globe was treated with a cross-linking (CXL) protocol with Rose Bengal (RB) photosensitizer and Green light irradiation (0.25 W/cm2, 2x200 s) of only the lower half of the cornea. We performed OCT APCDI measurements under controlled intraocular pressure (IOP, 15-30 mmHg) after application of RB (=baseline, BSL) and after partial CXL. We quantified the displaced area (DA) between the undeformed and deformed anterior cornea positions and asymmetry in displaced area (ADA), i.e. the difference between the nasal/temporal (or superior/inferior) DA referenced to the undeformed corneal apex. Results : We implemented a cross-meridian scan pattern over a lateral range of 15 mm sampled with 64 points at a repetition frequency of 1 kHz. For the BSL case, we validated the system by verifying the reduction of DA, from a maximum of ~4.3 to 1.8 mm2, with increasing IOP, from 15 to 30 mmHg. ADA was limited to below 0.2 mm2 in all cases for both meridians. For the partial CXL case and an IOP of 15 mm Hg, the ADA peaked at 0.5 mm2 for the vertical meridian, while it was below 0.2 mm2 at all times for the horizontal meridian. Conclusions : We acquired corneal deformation images with a cross-meridian scan pattern over a field of view of 15 mm at unprecedented scan rates. In keratoconus-mimicking cases, we detected deformation asymmetries up to 0.5 mm2, otherwise missed on a single meridian, that will substantially aid in corneal biomechanics diagnostics and pathology screening

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Deterministic Decoupling of Global Features and its Application to Data Analysis

We introduce a method for deterministic decoupling of global features and show its applicability to improve data analysis performance, as well as to open new venues for feature transfer. We propose a new formalism that is based on defining transformations on submanifolds, by following trajectories along the features gradients. Through these transformations we define a normalization that, we demonstrate, allows for decoupling differentiable features. By applying this to sampling moments, we obtain a quasi-analytic solution for the orthokurtosis, a normalized version of the kurtosis that is not just decoupled from mean and variance, but also from skewness. We apply this method in the original data domain and at the output of a filter bank to regression and classification problems based on global descriptors, obtaining a consistent and significant improvement in performance as compared to using classical (non-decoupled) descriptors.Comment: 29 pages, 12 figure