Quantifying Fluid and Function in Suboptimal Responders Switched From an Anti-vascular Endothelial Growth Factor (VEGF) to Faricimab.

Background Anti-vascular endothelial growth factor (VEGF) injections have been successful in reducing vision loss from neovascular age-related macular degeneration, a leading cause of blindness. Due to the high treatment burden and suboptimal responses, switching to bi-specific faricimab treatment may lead to improved outcomes. Methods This retrospective chart review evaluated if suboptimal responders to anti-VEGF injections had better outcomes when switched to faricimab. Suboptimal responders were defined as patients with a history of >3 months of injections and the presence of fluid after ≥3 injections. The primary endpoints were best-corrected visual acuity, treatment interval, and fluid levels. Visual acuity measurements and optical coherence tomography were performed before each injection. The total fluid area (TFA) was measured using MATLAB 2023a (MathWorks, Natick, MA, USA). Results Nineteen eyes were included in the analysis. After three faricimab injections, average letters increased from 54.5 to 59.0 (SD: 15.3; p<0.05), and the injection interval was extended from 7.6 to 9.3 weeks (SD: 3.9; p<0.01) after four injections. Patients also experienced anatomical retinal changes, with a reduction in the TFA to 47.3% (p<0.005) after the second injection and a reduction in pigment epithelial detachment height to 82.3% (p<0.005) after one injection. The central subfield thickness was significantly reduced after the second injection (90.6% (SD: 17.6%) p<0.05). Conclusion Switching to faricimab after a suboptimal anti-VEGF response results in improvements in visual acuity, reduced treatment burden, and reduced fluid levels.

Error Mitigation for Universal Gates on Encoded Qubits.

The Eastin-Knill theorem states that no quantum error-correcting code can have a universal set of transversal gates. For Calderbank-Shor-Steane codes that can implement Clifford gates transversally, it suffices to provide one additional non-Clifford gate, such as the T gate, to achieve universality. Common methods to implement fault-tolerant T gates, e.g., magic state distillation, generate a significant hardware overhead that will likely prevent their practical usage in the near-term future. Recently, methods have been developed to mitigate the effect of noise in shallow quantum circuits that are not protected by error correction. Error mitigation methods require no additional hardware resources but suffer from a bad asymptotic scaling and apply only to a restricted class of quantum algorithms. In this Letter, we combine both approaches and show how to implement encoded Clifford+T circuits where Clifford gates are protected from noise by error correction while errors introduced by noisy encoded T gates are mitigated using the quasiprobability method. As a result, Clifford+T circuits with a number of T gates inversely proportional to the physical noise rate can be implemented on small error-corrected devices without magic state distillation. We argue that such circuits can be out of reach for state-of-the-art classical simulation algorithms.

Prognostic value of left atrial size in hypertensive African Americans undergoing stress echocardiography.

BACKGROUND: Left atrial (LA) enlargement is a marker of increased risk in the general population undergoing stress echocardiography. African American (AA) patients with hypertension are known to have less atrial remodeling than whites with hypertension. The prognostic impact of LA enlargement in AA with hypertension undergoing stress echocardiography is uncertain. AIM: To investigate the prognostic value of LA size in hypertensive AA patients undergoing stress echocardiography. METHODS: This retrospective outcomes study enrolled 583 consecutive hypertensive AA patients who underwent stress echocardiography over a 2.5-year period. Clinical characteristics including cardiovascular risk factors, stress and echocardiographic data were collected from the electronic health record of a large community hospital. Treadmill exercise and Dobutamine protocols were conducted based on standard practices. Patients were followed for all-cause mortality. The optimal cutoff value of antero-posterior LA diameter for mortality was assessed by receiver operating characteristic analysis. Cox regression was used to determine variables associated with outcome. RESULTS: The mean age was 57 ± 12 years. LA dilatation was present in 9% (54) of patients (LA anteroposterior ≥ 2.4 cm/m2). There were 85 deaths (15%) during 4.5 ± 1.7 years of follow-up. LA diameter indexed for body surface area had an area under the curve of 0.72 ± 0.03 (optimal cut-point of 2.05 cm/m2). Variables independently associated with mortality included age [P = 0.004, hazard ratio (HR) 1.34 (1.10-1.64)], tobacco use [P = 0.001, HR 2.59 (1.51-4.44)], left ventricular hypertrophy [P = 0.001 , HR 2.14 (1.35-3.39)], Dobutamine stress [P = 0.003, HR 2.12 (1.29-3.47)], heart failure history [P = 0.031, HR 1.76 (1.05-2.94)], LA diameter ≥ 2.05 cm/m2 [P = 0.027, HR 1.73 (1.06-2.82)], and an abnormal stress echocardiogram [P = 0.033, HR 1.67 (1.04-2.68)]. LA diameter as a continuous variable was also independently associated with mortality but LA size ≥ 2.40 cm/m2 was not. CONCLUSION: LA enlargement is infrequent in hypertensive AA patients when traditional reference values are used. LA enlargement is independently associated with mortality when a lower than "normal" threshold (≥ 2.05 cm/m2) is used.

The power of quantum neural networks.

It is unknown whether near-term quantum computers are advantageous for machine learning tasks. In this work we address this question by trying to understand how powerful and trainable quantum machine learning models are in relation to popular classical neural networks. We propose the effective dimension-a measure that captures these qualities-and prove that it can be used to assess any statistical model's ability to generalize on new data. Crucially, the effective dimension is a data-dependent measure that depends on the Fisher information, which allows us to gauge the ability of a model to train. We demonstrate numerically that a class of quantum neural networks is able to achieve a considerably better effective dimension than comparable feedforward networks and train faster, suggesting an advantage for quantum machine learning, which we verify on real quantum hardware.

Chain Rule for the Quantum Relative Entropy.

The chain rule for the classical relative entropy ensures that the relative entropy between probability distributions on multipartite systems can be decomposed into a sum of relative entropies of suitably chosen conditional distributions on the individual systems. Here, we prove a chain rule inequality for the quantum relative entropy. The new chain rule allows us to solve an open problem in the context of asymptotic quantum channel discrimination: surprisingly, adaptive protocols cannot improve the error rate for asymmetric channel discrimination compared to nonadaptive strategies.

Extended Synaptotagmin Localizes to Presynaptic ER and Promotes Neurotransmission and Synaptic Growth in Drosophila.

The endoplasmic reticulum (ER) is an extensive organelle in neurons with important roles at synapses including the regulation of cytosolic Ca2+, neurotransmission, lipid metabolism, and membrane trafficking. Despite intriguing evidence for these crucial functions, how the presynaptic ER influences synaptic physiology remains enigmatic. To gain insight into this question, we have generated and characterized mutations in the single extended synaptotagmin (Esyt) ortholog in Drosophila melanogaster Esyts are evolutionarily conserved ER proteins with Ca2+-sensing domains that have recently been shown to orchestrate membrane tethering and lipid exchange between the ER and plasma membrane. We first demonstrate that Esyt localizes to presynaptic ER structures at the neuromuscular junction. Next, we show that synaptic growth, structure, and homeostatic plasticity are surprisingly unperturbed at synapses lacking Esyt expression. However, neurotransmission is reduced in Esyt mutants, consistent with a presynaptic role in promoting neurotransmitter release. Finally, neuronal overexpression of Esyt enhances synaptic growth and the sustainment of the vesicle pool during intense activity, suggesting that increased Esyt levels may modulate the membrane trafficking and/or resting Ca2+ pathways that control synapse extension. Thus, we identify Esyt as a presynaptic ER protein that can promote neurotransmission and synaptic growth, revealing the first in vivo neuronal functions of this conserved gene family.

Universal recovery map for approximate Markov chains.

A central question in quantum information theory is to determine how well lost information can be reconstructed. Crucially, the corresponding recovery operation should perform well without knowing the information to be reconstructed. In this work, we show that the quantum conditional mutual information measures the performance of such recovery operations. More precisely, we prove that the conditional mutual information I(A:C|B) of a tripartite quantum state ρABC can be bounded from below by its distance to the closest recovered state [Formula: see text], where the C-part is reconstructed from the B-part only and the recovery map [Formula: see text] merely depends on ρBC . One particular application of this result implies the equivalence between two different approaches to define topological order in quantum systems.

Improving prediction of outcomes in African Americans with normal stress echocardiograms using a risk scoring system.

Cardiovascular mortality is high in African Americans, and those with normal results on stress echocardiography remain at increased risk. The aim of this study was to develop a risk scoring system to improve the prediction of cardiovascular events in African Americans with normal results on stress echocardiography. Clinical data and rest echocardiographic measurements were obtained in 548 consecutive African Americans with normal results on rest and stress echocardiography and ejection fractions ≥50%. Patients were followed for myocardial infarction and death for 3 years. Predictors of cardiovascular events were determined with Cox regression, and hazard ratios were used to determine the number of points in the risk score attributed to each independent predictor. During follow-up of 3 years, 47 patients (8.6%) had events. Five variables-age (≥45 years in men, ≥55 years in women), history of coronary disease, history of smoking, left ventricular hypertrophy, and exercise intolerance (<7 METs in men, <5 METs in women, or need for dobutamine stress)-were independent predictors of events. A risk score was derived for each patient (ranging from 0 to 8 risk points). The area under the curve for the risk score was 0.82 with the optimum cut-off risk score of 6. Among patients with risk scores ≥6, 30% had events, compared with 3% with risk score <6 (p <0.001). In conclusion, African Americans with normal results on stress echocardiography remain at significant risk for cardiovascular events. A risk score can be derived from clinical and echocardiographic variables, which can accurately distinguish high- and low-risk patients.

Recreational fishing selectively captures individuals with the highest fitness potential.

Fisheries-induced evolution and its impact on the productivity of exploited fish stocks remains a highly contested research topic in applied fish evolution and fisheries science. Although many quantitative models assume that larger, more fecund fish are preferentially removed by fishing, there is no empirical evidence describing the relationship between vulnerability to capture and individual reproductive fitness in the wild. Using males from two lines of largemouth bass (Micropterus salmoides) selectively bred over three generations for either high (HV) or low (LV) vulnerability to angling as a model system, we show that the trait "vulnerability to angling" positively correlates with aggression, intensity of parental care, and reproductive fitness. The difference in reproductive fitness between HV and LV fish was particularly evident among larger males, which are also the preferred mating partners of females. Our study constitutes experimental evidence that recreational angling selectively captures individuals with the highest potential for reproductive fitness. Our study further suggests that selective removal of the fittest individuals likely occurs in many fisheries that target species engaged in parental care. As a result, depending on the ecological context, angling-induced selection may have negative consequences for recruitment within wild populations of largemouth bass and possibly other exploited species in which behavioral patterns that determine fitness, such as aggression or parental care, also affect their vulnerability to fishing gear.

Identification of nicotinic acetylcholine receptor recycling and its role in maintaining receptor density at the neuromuscular junction in vivo.

In the CNS, receptor recycling is critical for synaptic plasticity; however, the recycling of receptors has never been observed at peripheral synapses. Using a novel imaging technique, we show here that nicotinic acetylcholine receptors (AChRs) recycle into the postsynaptic membrane of the neuromuscular junction. By sequentially labeling AChRs with biotin-bungarotoxin and streptavidin-fluorophore conjugates, we were able to distinguish recycled, preexisting, and new receptor pools at synapses in living mice. Time-lapse imaging revealed that recycled AChRs were incorporated into the synapse within hours of initial labeling, and their numbers increased with time. At fully functional synapses, AChR recycling was robust and comparable in magnitude with the insertion of newly synthesized receptors, whereas chronic synaptic activity blockade nearly abolished receptor recycling. Finally, using the same sequential labeling method, we found that acetylcholinesterase, another synaptic component, does not recycle. These results identify an activity-dependent AChR-recycling mechanism that enables the regulation of receptor density, which could lead to rapid alterations in synaptic efficacy.