Attitudes and understanding of premium intraocular lenses in cataract surgery: a public health sector patient survey.

OBJECTIVES: To investigate patient understanding of, and attitudes to, premium (toric, extended depth of focus/multifocal) intraocular lenses (premIOLs) in public health sector patients undergoing cataract surgery (CS) in the UK. METHODS: A 12 question survey with Likert scale questions was designed, to assess patient attitudes to post-operative spectacle dependence, refractive target and desirability of spectacle independence whilst considering possible complications of dysphotopsias and need for premIOL exchange/adjustment. RESULTS: 360 surveys were collected. CS had not been performed in 66.5%. Separate spectacles were worn for reading and distance in 28.8%, 19.2% had varifocals, 11.2% bifocals, 22.9% reading glasses only and 1.6% computer glasses only. Contact lenses were not worn in 95.7%. Only 41.6% were drivers. Most patients (85.8%) did not mind wearing glasses after CS, with 78.9% preferring reading glasses, compared with 29.7% preferring distance glasses. Most patients (75.3%) were not familiar with premIOLs, with 58.9% not willing to consider them in the context of a 2% risk of debilitating dysphotopsia and 54.2% rejecting a 5% risk of second surgery. CONCLUSIONS: There is a lack of awareness of premIOLs in public health sector (NHS) patients in the UK, suggesting limitations in the "fully informed" consent process for CS. Most NHS CS patients are currently willing to wear spectacles after CS, especially reading glasses. There is reluctance in such patients to consider premIOLs on a background of small risks of debilitating dysphotopsias and increased risks of a second operation.

Exact New Mobility Edges between Critical and Localized States.

The disorder systems host three types of fundamental quantum states, known as the extended, localized, and critical states, of which the critical states remain being much less explored. Here we propose a class of exactly solvable models which host a novel type of exact mobility edges (MEs) separating localized states from robust critical states, and propose experimental realization. Here the robustness refers to the stability against both single-particle perturbation and interactions in the few-body regime. The exactly solvable one-dimensional models are featured by a quasiperiodic mosaic type of both hopping terms and on-site potentials. The analytic results enable us to unambiguously obtain the critical states which otherwise require arduous numerical verification including the careful finite size scalings. The critical states and new MEs are shown to be robust, illustrating a generic mechanism unveiled here that the critical states are protected by zeros of quasiperiodic hopping terms in the thermodynamic limit. Further, we propose a novel experimental scheme to realize the exactly solvable model and the new MEs in an incommensurate Rydberg Raman superarray. This Letter may pave a way to precisely explore the critical states and new ME physics with experimental feasibility.

Time and Motion Studies to assess surgical productivity in cataract theatre lists within the National Health Service: Immediate Sequential Bilateral Cataract Surgery versus Delayed Sequential Bilateral Cataract Surgery.

BACKGROUND: To compare productivity of National Health Service cataract lists performing unilateral cataract (UC) surgery vs Immediate Sequential Bilateral Cataract Surgery (ISBCS). METHODS: Five 4-hour lists with ISBCS cases and five with UC were observed using time and motion studies (TMS). Individual tasks and timings of each staff member in theatre was recorded by two observers. All operations were performed by consultant surgeons under local anaesthesia (LA). RESULTS: Median number of eyes operated per 4-hour list was 8 (range 6-8) in the ISBCS group and 5 (5-7) in the UC group (p = 0.028). Mean total theatre time (defined as time between the entry of the first patient and the exit of the last patient from theatre) was 177.12 (SD 73.62) minutes in the ISBCS group and 139.16 (SD 47.73) minutes in the UC group (p = 0.36). Mean time to complete two consecutive unilateral cataract surgery operations was 48.71 minutes compared to 42.23 minutes for a single ISBCS case (13.30% time saved). Based on our collected TMS data, a possible 5 consecutive ISBCS cases and 1 UC (total 11 cataract surgeries) could be performed during a four-hour theatre session, with a theatre utilisation quotient of 97.20%, contrasting to nine consecutive UC, with a theatre utilisation quotient of 90.40%. DISCUSSION: Performing consecutive ISBCS cases under LA on routine cataract surgery lists can increase surgical efficiency. TMS are a useful way to investigate surgical productivity and test theoretical models for efficiency improvements.

Impact of cessation of regular cataract surgery during the COVID pandemic on the rates of posterior capsular rupture and post-operative cystoid macular oedema.

BACKGROUND/OBJECTIVES: During the COVID-19, elective cataract surgery (CS) was significantly curtailed. We investigated whether consequent reduction of micro-surgical skills practice might lead to higher operative complications. METHODS: Single-centre, electronic note review of consecutive patients undergoing CS during three periods: 1st February 2019 to 13th January 2020 (P1) prior to pandemic; 3rd June 2020 to 11th January 2021 after 1st lockdown (P2); and 25th January to 30th July 2021 (P3) after/during second lockdown. RESULTS: 2276 operations occurred during P1, 999 during P2, 846 during P3. During P1, posterior capsular rupture (PCR) rate was 1.67%, similar to P2 (1.30%, p = 0.54), but lower than P3 (3.55%, p = 0.002). There was no difference in PCR risk percentage scores between routine and PCR cases during P1 (1.90% vs 2.03%, p = 0.83), P2 (2% vs 2.18%, p = 0.18), or P3 (1.87% vs. 2.71%, p = 0.08). During P2 and P3, there was a higher rate of cystoid macular oedema (CMO) compared with P1 (4.9% and 6.86% vs. 1.93%, p = 0.0001), with no differences in proportion of diabetics or cases with CMO in combination with PCR. There was no difference in surgeons grade experiencing PCR. CONCLUSIONS: In P3 following 9 months of curtailed elective CS, PCR rates were increased across all surgeon grades, occurring in cases with similar risk percentage scores. CMO rates were increased during COVID and not related to proportion of diabetics or increased PCR rates. The reduction in elective CS during the pandemic was associated with more complications, perhaps due to attenuation of microsurgical skills.

IL-15/IL-15Rα/CD80-expressing AML cell vaccines eradicate minimal residual disease in leukemic mice.

Engineered autologous acute myeloid leukemia (AML) cells present multiple leukemia-associated and patient-specific antigens and as such hold promise as immunotherapeutic vaccines. However, prior vaccines have not reliably induced effective antileukemic immunity, in part because AML blasts have immune inhibitory effects and lack expression of the critical costimulatory molecule CD80. To enhance induction of leukemia-specific cytolytic activity, 32Dp210 murine AML cells were engineered to express either CD80 alone, or the immunostimulatory cytokine interleukin-15 (IL-15) with its receptor α (IL-15Rα), or heterodimeric IL-15/IL-15Rα together with CD80 and tested as irradiated cell vaccines. IL-15 is a γc-chain cytokine, with unique properties suited to stimulating antitumor immunity, including stimulation of both natural killer and CD8+ memory T cells. Coexpression of IL-15 and IL-15Rα markedly increases IL-15 stability and secretion. Non-tumor-bearing mice vaccinated with irradiated 32Dp210-IL-15/IL-15Rα/CD80 and challenged with 32Dp210 leukemia had greater survival than did mice treated with 32Dp210-CD80 or 32Dp210-IL-15/IL-15Rα vaccines, whereas no unvaccinated mice inoculated with leukemia survived. In mice with established leukemia, treatment with 32Dp210-IL-15/IL-15Rα/CD80 vaccination stimulated unprecedented antileukemic immunity enabling 80% survival, an effect that was abrogated by anti-CD8 antibody-mediated depletion in vivo. Because, clinically, AML vaccines are administered as postremission therapy, we established a novel model in which mice with high leukemic burdens were treated with cytotoxic therapy to induce remission (<5% marrow blasts). Postremission vaccination with 32Dp210-IL-15/IL-15Rα/CD80 achieved 50% overall survival in these mice, whereas all unvaccinated mice achieving remission subsequently relapsed. These studies demonstrate that combined expression of IL-15/IL-15Rα and CD80 by syngeneic AML vaccines stimulates effective and long-lasting antileukemic immunity.

Observation of symmetry-protected topological band with ultracold fermions.

Symmetry plays a fundamental role in understanding complex quantum matter, particularly in classifying topological quantum phases, which have attracted great interests in the recent decade. An outstanding example is the time-reversal invariant topological insulator, a symmetry-protected topological (SPT) phase in the symplectic class of the Altland-Zirnbauer classification. We report the observation for ultracold atoms of a noninteracting SPT band in a one-dimensional optical lattice and study quench dynamics between topologically distinct regimes. The observed SPT band can be protected by a magnetic group and a nonlocal chiral symmetry, with the band topology being measured via Bloch states at symmetric momenta. The topology also resides in far-from-equilibrium spin dynamics, which are predicted and observed in experiment to exhibit qualitatively distinct behaviors in quenching to trivial and nontrivial regimes, revealing two fundamental types of spin-relaxation dynamics related to bulk topology. This work opens the way to expanding the scope of SPT physics with ultracold atoms and studying nonequilibrium quantum dynamics in these exotic systems.

Generic Theory for Majorana Zero Modes in 2D Superconductors.

It is well known that non-Abelian Majorana zero modes (MZM) are located at vortex cores in a p_{x}+𝒾p_{y} topological superconductor, which can be realized in a 2D spin-orbit coupled system with a single Fermi surface and by proximity coupling to an s-wave superconductor. Here we show that the existence of non-Abelian MZMs is unrelated to the bulk topology of a 2D superconductor, and propose that such exotic modes can result in a much broader range of superconductors, being topological or trivial. For a generic 2D system with multiple Fermi surfaces that is gapped out by superconducting pairings, we show that at least a single MZM survives if there are only an odd number of Fermi surfaces of which the corresponding superconducting orders have vortices; such a MZM is protected by an emergent Chern-Simons invariant, irrespective of the bulk topology of the superconductor. This result enriches new experimental schemes for realizing non-Abelian MZMs. In particular, we propose a minimal scheme to realize the MZMs in a 2D superconducting Dirac semimetal with trivial bulk topology, which can be well achieved based on recent cold-atom experiments.

Real-World Assessment of Acute Left Ventricular Lead Implant Success and Complication Rates: Results from the Attain Success Clinical Trial.

BACKGROUND: Left ventricular lead (LVL) implant success rates have historically ranged between 70.5% and 95.5%. To date, there are few large studies that evaluate LVL implant success utilizing a single family of delivery catheters and leads. The Attain Success study was a prospective nonrandomized multicenter global study with the main objectives of assessing single-system LVL implant success and complication rates. METHODS: Patients undergoing cardiac resynchronization therapy implantation were eligible for enrollment. There was no prespecified level of experience for investigator participation. LVL implant success and complication rates were assessed though 3 months of follow-up. RESULTS: A total of 2,014 patients (69.1 ± 12.0 years, 71% male and 38% atrial fibrillation) were enrolled from 114 centers with a follow-up of 3.5 ± 2.1 months. Coronary sinus cannulation success rate was 96.4% with Attain Family delivery catheters. Implant success rate for Attain Family leads using Attain Family catheters was 94.0%; overall LVL implant success rate was 97.1%. Median procedure time was 4 minutes for cannulation and 9 minutes for LVL placement. Median fluoroscopy time was 17 minutes and median contrast used was 25 cc. There were 55 catheter or LVL-related complications in 53 subjects; the majority were LVL dislodgements (34, 1.7%) and extracardiac stimulation (11, 0.5%). The Kaplan-Meier estimate of the 3-month complication probability was 2.6%. CONCLUSION: This study represents the largest prospective evaluation of LVL implantation to date, revealing a high LVL implant success rate and low complication rate using a single family of leads and delivery catheters.

Effect of motion discontinuities on discrimination of periodic trajectories.

Many biologically important motions are described by periodic trajectories. Radial frequency (RF) trajectories are one example, in which the motion of a difference of Gaussians (DOG) target moves along a path described by a sinusoidal deviation of the radius from a perfect circle (Or, Thabet, Wilkinson, & Wilson, 2011). Here we explore the hypothesis that visual processing of RF trajectories involves global spatio-temporal processes that are disrupted by motion discontinuity. To test this hypothesis, RF trajectories were used that interspersed smooth, continuous motion with three or four discontinuous jumps to other portions of the trajectory. These jumps were arranged so that the entire trajectory was traversed in the same amount of time as in the continuous motion control condition. The motion discontinuities increased thresholds by a factor of approximately 2.1 relative to continuous motion. This result provides support for global spatio-temporal processing of RF motion trajectories. Comparison with previous results suggests that motion discontinuities erase memory for earlier parts of the trajectory, thereby causing thresholds to be based on only the final segment viewed. Finally, it is shown that RF trajectories obey the 1/3 power law characteristic of biological motion.

Left ventricular three-dimensional quadripolar lead acute clinical study: the LILAC study.

AIMS: This multicenter acute clinical study was designed to verify novel three-dimensional (3D) quadripolar lead designs that can achieve ≤2.5 V average pacing capture threshold (PCT) not only at the apex, but also at the base of the left ventricle with phrenic nerve stimulation (PNS) avoidance for cardiac resynchronization. METHODS: During the implant procedure, up to two different left ventricular investigational leads were introduced and tested in the same target coronary vein based on the coronary sinus venogram in a wedged and unwedged position. Adverse events were collected in 30 days following the procedure. RESULTS: Eighty-seven leads were tested in 50 patients. When the best performing spiral electrode was chosen from each lead testing, the average of the best PCT on spiral in a wedged position was similar to the unwedged position (1.7 ± 1.5 V vs 1.9 ± 1.5 V, P = ns) and was similar to the wedged tip electrode average PCT (1.7 ± 1.5 V vs 1.6 ± 1.6 V, P = ns). In the majority of patients (89-96%), pacing was achievable in a mid-basal ventricular location without PNS. CONCLUSIONS: This acute study demonstrated that a 3D quadripolar spiral lead design can achieve acceptable PCTs and avoid PNS without repositioning the lead at implant in the vast majority of patients. It also demonstrated that this lead design can achieve mid-basal ventricular stimulation with low PCT and good acute stability.

Clinical relevance and therapeutic potential of angiopoietin-like protein 4 in hepatocellular carcinoma.

BACKGROUND: Development of novel adjuvant therapy to eradicate tumor angiogenesis and metastasis is a pressing need for patients with advanced hepatocellular carcinoma (HCC). We aimed to investigate the clinical relevance and therapeutic potential of angiopoietin-like 4 (ANGPTL4) in HCC. METHODS: ANGPTL4 mRNA levels in tumor and non-tumor liver tissues of HCC patients were analyzed to investigate its clinical relevance. The mechanisms of deregulation of ANGPTL4 in HCC were studied by copy number variation (CNV) and CpG methylation analyses. The orthotopic liver tumor nude mice model was applied using a human metastatic cell line. ANGPTL4-overexpressing adenovirus (Ad-ANGPTL4) was injected via portal vein to investigate its anti-tumorigenic and anti-metastatic potentials. RESULTS: HCC tissues expressed significantly lower levels of ANGPTL4 mRNA than non-tumor tissues. The copy number of ANGPTL4 gene in tumor tissues was significantly lower than in non-tumor tissues of HCC patients. Higher frequency of methylation of CpG sites of ANGPTL4 promoter was detected in tumor tissues compared to non-tumor tissues. Downregulation of ANGPTL4 mRNA in HCC was significantly associated with advanced tumor stage, presence of venous infiltration, poor differentiation, higher AFP level, appearance of tumor recurrence, and poor postoperative overall and disease-free survivals of HCC patients. Treatment with Ad-ANGPTL4 significantly inhibited the in vivo tumor growth, invasiveness and metastasis by promoting tumoral apoptosis, inhibiting tumoral angiogenesis and motility, and suppressing tumor-favorable microenvironment. Moreover, administration of recombinant ANGPTL4 protein suppressed the motility of HCC cells and altered the secretion profile of cytokines from macrophages. CONCLUSION: ANGPTL4 is a diagnostic and prognostic biomarker for HCC patients and a potential therapeutic agent to suppress HCC growth, angiogenesis and metastasis.

Biventricular pacing is superior to right ventricular pacing in bradycardia patients with preserved systolic function: 2-year results of the PACE trial.

AIMS: The Pacing to Avoid Cardiac Enlargement (PACE) trial is a prospective, double-blinded, randomized, multicentre study that reported the superiority of biventricular (BiV) pacing to right ventricular apical (RVA) pacing in the prevention of left ventricular (LV) adverse remodelling and deterioration of systolic function at 1 year. In the current analysis, we report the results at extended 2-year follow-up for changes in LV function and remodelling. METHODS AND RESULTS: Patients (n = 177) with bradycardia and preserved LV ejection fraction (EF ≥45%) were randomized to receive RVA or BiV pacing. The co-primary endpoints were LVEF and LV end-systolic volume (LVESV). Eighty-one (92%) of 88 in the RVA pacing group and 82 (92%) of 89 patients in the BiV pacing group completed 2-year follow-up with a valid echocardiography. In the RVA pacing group, LVEF further decreased from the first to the second year, but it remained unchanged in the BiV pacing group, leading to a significant difference of 9.9 percentage points between groups at 2-year follow-up (P < 0.001). Similarly, LVESV continues to enlarge from the first to the second year in the RVA pacing group, leading to a difference of 13.0 mL (P < 0.001) between groups. Predefined subgroup analysis showed consistent results with the whole study population for both co-primary endpoints, which included patients with pre-existing LV diastolic dysfunction. Eighteen patients in the BiV pacing group (20.2%) and 55 in the RVA pacing group (62.5%) had a significant reduction of LVEF (of ≥5%, P < 0.001). CONCLUSION: Left ventricular adverse remodelling and deterioration of systolic function continues at the second year after RVA pacing. This deterioration is prevented by BiV pacing.

Deleterious effect of right ventricular apical pacing on left ventricular diastolic function and the impact of pre-existing diastolic disease.

AIMS: Right ventricular apex (RVA) pacing may have deleterious effects on left ventricular (LV) systolic function, but its impact on LV diastolic function has not been explored. METHODS AND RESULTS: Ninety-seven patients with sinus node dysfunction and ejection fraction (EF) ≥ 50% with permanent RVA pacing were randomly programmed to V-sense and V-pace modes and examined by echocardiography. Tissue Doppler imaging was employed to assess myocardial systolic velocity (S') and early diastolic velocity (E') at the mitral annulus. Systolic dyssynchrony was assessed using 12 LV segmental model (Ts-SD). Switching from V-sense to V-pace resulted in the worsening of both diastolic and systolic functions as shown by the decreased EF, reduced mean E' and S' velocities, as well as increase in LV volume and Ts-SD (all P< 0.001). Reduction of mean E' and S' of ≥ 1 cm/s occurred in 35 (36%) and 45 (46%) patients, respectively. In pre-defined subgroup analysis, only patients with pre-existing LV diastolic dysfunction had a significant reduction of mean E' and S' (both P< 0.001) even after age adjustment. Multivariate logistic regression analysis showed that independent factors for the reduction of mean E' ≥ 1 cm/s or mean S' ≥ 1 cm/s at V-pace were pre-existing LV diastolic dysfunction [odds ratio (OR): 4.735, P= 0.007 for E'; OR: 3.307, P= 0.022 for S'] and systolic dyssynchrony at V-pace (OR: 5.459, P= 0.007 for E'; OR: 2.725, P= 0.035 for S'). CONCLUSION: In patients with preserved EF, RVA pacing is associated with the deterioration of both LV diastolic and systolic functions, which is particularly obvious in those with pre-existing LV diastolic dysfunction and V-pace-induced systolic dyssynchrony.

A novel multi-layer approach of measuring myocardial strain and torsion by 2D speckle tracking imaging in normal subjects and patients with heart diseases.

BACKGROUND: This study adopted a new multi-layer approach of measuring myocardial deformation by two-dimensional (2D) speckle tracking imaging to examine whether a transmural gradient exists in normal subjects and cardiac diseases. METHODS: Eighty patients were included with 20 in each group: (1) normal control; (2) acute coronary syndrome (ACS) with ejection fraction (EF) >45%; (3) right ventricular apical (RVA) pacing with EF>45%; (4) systolic heart failure (SHF) with EF<45%. Circumferential strain (ε-circum), torsion (Tor) and systolic dyssynchrony defined as the maximal difference in the time to peak circumferential strain were measured in the subendocardial and subepicardial myocardium layers (QLab 6.0, Philips). RESULTS: In all the 4 groups, a subendocardial to subepicardial gradient was present in both ε-circum (-20.7 ± 7.6 vs. -14.9 ± 5.6%, p<0.001) and Tor (12.0 ± 6.0 vs. 9.3 ± 4.7°, p<0.05), with higher values in the subendocardial layer. However, it was significantly narrowed for ε-circum (2.7 ± 1.2%) and Tor (0.8 ± 0.9°) in SHF patients (all p ≤ 0.001 vs. other groups). On the contrary, systolic dyssynchrony measured in the 2 layers showed no difference (264 ± 107 vs. 273 ± 110 ms, p = NS) and a homogenous distribution in ε-circum was observed from basal to apical planes (-17.0 ± 6.8 vs. -18.1 ± 7.4 vs. -18.1 ± 7.8%, all p = NS). CONCLUSIONS: A transmural gradient exists in circumferential strain and torsion, with higher values in the subendocardial layer. It might be reduced when systolic function is impaired. Therefore, the multi-layer approach of 2D speckle tracking imaging provides further information on assessment of myocardial diseases.

Different determinants of improvement of early and late systolic mitral regurgitation contributed after cardiac resynchronization therapy.

BACKGROUND: Functional mitral regurgitation (MR) at different phases of the regurgitant period may respond differently to cardiac resynchronization therapy (CRT). The aims of this study were to examine the impact of CRT on the phasic changes of MR (early vs late systole) and to explore the mechanisms of such changes. METHODS: Instantaneous MR flow rate and total MR volume were evaluated in 60 patients who had more than mild functional MR before and 3 months after CRT. In addition, indices of global left ventricular (LV) remodeling, mitral deformation, and LV systolic dyssynchrony were assessed. RESULTS: CRT diminished MR volume (38 ± 18 vs 32 ± 20 mL) by reducing both the early (72 ± 47 vs 58 ± 48 mL/sec) and late (48 ± 42 vs 40 ± 42 mL/sec) systolic components (all p values < .01). In patients with ≥10% reductions in total MR volume but not in patients without this improvement, there were significant reductions in LV end-systolic volume, increases in LV +dP/dt, decreases in mitral valvular tenting, and improvements of systolic dyssynchrony at 3 months (all P values < .05). By multivariate regression, the reductions in LV end-systolic volume and tenting area were independent determinants of a reduction in total MR volume: the reductions in LV end-systolic volume and global dyssynchrony determined the reduction in early systolic MR, and the reductions in tenting area and global dyssynchrony determined reduction in late systolic MR. CONCLUSIONS: CRT decreases MR volume by reducing both early and late systolic MR. The determinants of the phasic improvement in functional MR are different.