Assessing population-level target product profiles of universal human influenza A vaccines.

Influenza A has two hemagglutinin groups, with stronger cross-immunity to reinfection within than between groups. Here, we explore the implications of this heterogeneity for proposed cross-protective influenza vaccines that may offer broad, but not universal, protection. While the development goal for the breadth of human influenza A vaccine is to provide cross-group protection, vaccines in current development stages may provide better protection against target groups than non-target groups. To evaluate vaccine formulation and strategies, we propose a novel perspective: a vaccine population-level target product profile (PTPP). Under this perspective, we use dynamical models to quantify the epidemiological impacts of future influenza A vaccines as a function of their properties. Our results show that the interplay of natural and vaccine-induced immunity could strongly affect seasonal subtype dynamics. A broadly protective bivalent vaccine could lower the incidence of both groups and achieve elimination with sufficient vaccination coverage. However, a univalent vaccine at low vaccination rates could permit a resurgence of the non-target group when the vaccine provides weaker immunity than natural infection. Moreover, as a proxy for pandemic simulation, we analyze the invasion of a variant that evades natural immunity. We find that a future vaccine providing sufficiently broad and long-lived cross-group protection at a sufficiently high vaccination rate, could prevent pandemic emergence and lower the pandemic burden. This study highlights that as well as effectiveness, breadth and duration should be considered in epidemiologically informed TPPs for future human influenza A vaccines.

Differential impact of COVID-19 non-pharmaceutical interventions on the epidemiological dynamics of respiratory syncytial virus subtypes A and B.

Nonpharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic have disrupted the dynamics of respiratory syncytial virus (RSV) on a global scale; however, the cycling of RSV subtypes in the pre- and post-pandemic period remains poorly understood. Here, we used a two subtype RSV model supplemented with epidemiological data to study the impact of NPIs on the two circulating subtypes, RSV-A and RSV-B. The model is calibrated to historic RSV subtype data from the United Kingdom and Finland and predicts a tendency for RSV-A dominance over RSV-B immediately following the implementation of NPIs. Using a global genetic dataset, we confirm that RSV-A has prevailed over RSV-B in the post-pandemic period, consistent with a higher R0 for RSV-A. With new RSV infant monoclonals and maternal and elderly vaccines becoming widely available, these results may have important implications for understanding intervention effectiveness in the context of disrupted subtype dynamics.

Safety and Effectiveness of Passeo-18 Lux Drug-Coated Balloon Catheter in Infrainguinal Endovascular Revascularization in the Korean Population: A Multicenter Post-Market Surveillance Study.

OBJECTIVE: To evaluate the safety and clinical outcomes of the Passeo-18 Lux drug-coated balloon (DCB) in endovascular revascularization procedures under real-world conditions in a Korean population with atherosclerotic disease of the infrainguinal arteries, including below-the-knee (BTK) arteries. MATERIALS AND METHODS: Eight institutions in the Republic of Korea participated in this prospective, multicenter, single-arm, post-market surveillance study. Two hundred patients with Rutherford class 2-5 peripheral arterial disease and infrainguinal lesions suitable for endovascular treatment were competitively enrolled. Data were collected at baseline, the time of intervention, discharge, and 1-, 6-, 12-, and 24-month follow-up visits. The primary safety endpoint was freedom from major adverse events (MAE) within 6 months (except when limiting the time frame for procedure- or device-related mortality to within 30 days), and the primary effectiveness endpoint was freedom from clinically driven target lesion revascularization (CD-TLR) within 12 months after the procedure. RESULTS: A total of 197 patients with 332 target lesions were analyzed. Two-thirds of the patients had diabetes mellitus, and 41.6% had chronic limb-threatening ischemia. The median target lesion length was 100 mm (interquartile range: 56-133 mm). Of the target lesions, 35.2% were occlusions, and 14.8% were located in the BTK arteries. Rate of freedom from MAE was 97.9% at 6 months, and the rate of freedom from CD-TLR was 95.0% and 92.2% at 12 and 24 months, respectively. Subgroup analysis of 43 patients and 49 target lesions involving the BTK arteries showed rate of freedom from MAE of 92.8% at 6 months and rates of freedom from CD-TLR of 88.8% and 84.4% at 12 and 24 months, respectively. CONCLUSION: The results of the present study, including the BTK subgroup analysis, showed outcomes comparable to those of other DCB studies, confirming the safety and effectiveness of Passeo-18 Lux DCB in the Korean population.

Long-Term Comparison of Esthetic Outcomes Between Hatchet and Transposition Flaps in Facial-Defect Reconstruction.

BACKGROUND: Transposition flaps are commonly used for facial-defect repair after wide excision of skin cancers. However, such repair often causes excessive tension at the donor site that can result in distortion of the adjacent area. The hatchet flap, a rotation-advancement flap, can prevent distortion by redistributing the donor site tension evenly to the recipient site. This study aims to compare the esthetic outcomes of the hatchet flap and transposition flap in facial-defect reconstruction. METHODS: We retrospectively included 50 patients who underwent facial reconstruction with the hatchet flap or transposition flap after excision of skin cancer. They were followed up for more than 6 months. At the last follow-up visit, the esthetic outcome was evaluated by subjective and objective assessments using the patients and observer scar assessment scale and Manchester scar scale. RESULTS: Thirty patients and 20 patients underwent reconstruction using the hatchet flap and the transposition flap, respectively. The total score from the patient and observer scar assessment scale was significantly lower in the hatchet flap group compared with the transposition flap group (p = 0.009). The Manchester scar scale showed a total score of 7.67 ± 2.2 for the hatchet flap and 9.95 ± 1.99 for the transposition flap: in the color (p < 0.001), distortion (p < 0.001), and texture (p < 0.02) categories, the hatchet flap yielded significantly better outcomes than the transposition flap. CONCLUSIONS: The hatchet flap had good esthetic outcome for facial reconstruction and could be a valuable option for reconstructing facial defects. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

Radiofrequency ablation for the treatment of great saphenous venous insufficiency using a newly developed VENISTAR catheter: A preliminary study.

OBJECTIVES: This study was aimed to assess the preliminary outcomes of radiofrequency ablation (RFA) using a newly developed catheter (VENISTAR) for the treatment of incompetent great saphenous veins (GSVs). METHODS: In this prospective observational study, endovenous RFA using a VENISTAR catheter was performed on 16 saphenous veins in 12 patients between August and November 2019. Patients' pre- and post-procedural data were recorded. Doppler ultrasound imaging and clinical evaluation were performed at 1 week and 1, 3, and 6 months to determine the efficacy and safety of the treatment. RESULTS: Technical success and complete closure of the targeted GSVs immediately after the procedure were observed in all 16 limbs (100%). However, one patient (one limb) was found to have partial occlusion without significant reflux after 1 week of follow-up. Kaplan-Meier analysis yielded a complete occlusion rate of 93% at 6 months of follow-up. The Venous Clinical Severity Scores at the time of all follow-up were significantly lower than those at baseline (3.3 ± 1.1 at baseline to 0.6 ± 0.6, 0.3 ± 0.6, 0.1 ± 0.4, and 0.2 ± 0.4 at 1 week and 1, 3, and 6 months, respectively) (p < .001). Mild post-procedural pain was noted in 7 and 4 limbs at 1 week and 1 month, respectively. Grade 1 ecchymosis over the ablated segment was noted in 5 (35.7%) of 14 limbs at 1-week follow-up. CONCLUSIONS: Endovenous treatment of GSV insufficiency using a new VENISTAR radiofrequency catheter has been shown to be feasible, effective, and safe throughout the 6-month follow-up.

Facile Approach for Metallic Precursor Engineering for Efficient Kesterite Thin-Film Solar Cells.

Kesterite-based Cu2ZnSn(S,Se)4 (CZTSSe) thin-film solar cells (TFSCs) are a promising candidate for low-cost, clean energy production owing to their environmental friendliness and the earth-abundant nature of their constituents. However, the advancement of kesterite TFSCs has been impeded by abundant defects and poor microstructure, limiting their performance potential. In this study, we present efficient Ag-alloyed CZTSSe TFSCs enabled by a facile metallic precursor engineering approach. The positioning of the Ag nanolayer in the metallic stacked precursor proves crucial in expediting the formation of Cu-Sn metal alloys during the alloying process. Specifically, Ag-included metallic precursors promote the growth of larger grains and a denser microstructure in CZTSSe thin films compared to those without Ag. Moreover, the improved uniformity of Ag, facilitated by the evaporation deposition technique, significantly suppresses the formation of detrimental defects and related defect clusters. This suppression effectively reduces nonradiative recombination, resulting in enhanced performance in kesterite TFSCs. This study not only introduces a metallic precursor engineering strategy for efficient kesterite-based TFSCs but also accelerates the development of microstructure evolution from metallic stacked precursors to metal chalcogenide compounds.

Unraveling diffusion behavior in Cu-to-Cu direct bonding with metal passivation layers.

Cu/SiO2 hybrid bonding presents a promising avenue for achieving high-density interconnects by obviating the need for microbumps and underfills. Traditional copper bonding methods often demand temperatures exceeding 400 °C, prompting recent endeavors to mitigate bonding temperatures through investigations into metal passivation bonding. In this study, we scrutinized the diffusion behavior associated with various metal passivation layers (Platinum, Titanium, Tantalum, and Chromium) in the context of low-temperature direct copper bonding and delved into the essential bonding mechanisms. We observed a deviation from conventional metal-metal bonding factors, such as surface roughness and grain size, in the diffusion behavior. Remarkably, our analysis revealed a pronounced correlation between the crystallinity of the metal passivation layers and diffusion behavior, surpassing the influence of other experimental factors. Subsequent post-bonding examinations corroborated consistent diffusion behavior in Pt and Cr passivation samples with disparate crystallinities, reinforcing the significance of crystallinity in the bonding process. Our findings underscore crystallinity as a pivotal factor governing diffusion behavior, even under varied bonding conditions. These insights are instrumental in achieving exceptional bonding characteristics at lower temperatures in Cu/SiO2 hybrid bonding. Implications of this study extend to the prospect of advancing highly integrated systems through die-to-wafer bonding, marking a substantial stride toward future applications.

Synchrony of Bird Migration with Global Dispersal of Avian Influenza Reveals Exposed Bird Orders.

Highly pathogenic avian influenza virus (HPAIV) A H5, particularly clade 2.3.4.4, has caused worldwide outbreaks in domestic poultry, occasional spillover to humans, and increasing deaths of diverse species of wild birds since 2014. Wild bird migration is currently acknowledged as an important ecological process contributing to the global dispersal of HPAIV H5. However, this mechanism has not been quantified using bird movement data from different species, and the timing and location of exposure of different species is unclear. We sought to explore these questions through phylodynamic analyses based on empirical data of bird movement tracking and virus genome sequences of clade 2.3.4.4 and 2.3.2.1. First, we demonstrate that seasonal bird migration can explain salient features of the global dispersal of clade 2.3.4.4. Second, we detect synchrony between the seasonality of bird annual cycle phases and virus lineage movements. We reveal the differing exposed bird orders at geographical origins and destinations of HPAIV H5 clade 2.3.4.4 lineage movements, including relatively under-discussed orders. Our study provides a phylodynamic framework that links the bird movement ecology and genomic epidemiology of avian influenza; it highlights the importance of integrating bird behavior and life history in avian influenza studies.

Complete Preservation of Orbital Fat by Restoration of Attenuated Orbital Septa Using an Acellular Dermal Matrix in Lower Blepharoplasty.

BACKGROUND: We hypothesized that application of acellular dermal matrix (ADM) over the orbital septum overlying the herniated orbital fat to tighten and strengthen the attenuated orbital septum in lower blepharoplasty would allow successful repositioning of the herniated orbital fat within the bony orbit. METHODS: The author prospectively compared the cosmetic outcomes of lower blepharoplasty using ADM with standard blepharoplasty. We evaluated recurrence of eyelid bulging and tear trough deformity, volume of the lower periorbital region, and enophthalmos and eyelid droop 1 year after surgery. RESULTS: Twenty-two of the 24 enrolled patients completed the study. There was no significant difference in recurrence of eyelid bulging and tear trough deformity between standard blepharoplasty and blepharoplasty with ADM graft groups. In the standard blepharoplasty group, the volume of the lower periorbital region decreased significantly after surgery. In the blepharoplasty with ADM graft group, there was no significant change in the volume of the lower periorbital region after surgery. In the standard blepharoplasty group, there was no significant change in eyelid droop on either side after surgery. In the blepharoplasty with ADM graft group, the eyelid droop decreased significantly after surgery on the right side but showed no significant change on the left side. There was no significant change in enophthalmos after surgery for either group. CONCLUSIONS: This study demonstrated that ADM graft provided effective support for maintaining the replaced orbital fat in lower blepharoplasty. In the long-term, blepharoplasty with ADM graft might be effective in slowing development of age-related enophthalmos. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Prospective Multicenter Randomized Controlled Trial for Comparing Drug-Coated and Conventional Balloon Angioplasty in Venous Anastomotic Stenosis of Hemodialysis Arteriovenous Grafts.

PURPOSE: To evaluate the efficacy and safety of drug-coated balloon angioplasty compared to conventional balloon angioplasty in the treatment of dysfunctional arteriovenous grafts. MATERIALS AND METHODS: This prospective, multicenter, randomized clinical trial enrolled 190 patients with venous anastomotic stenosis in arteriovenous grafts at five participating hospitals. During pre-dilation, 4 patients dropped out due to ruptures requiring further treatment (n = 2) and residual stenosis of > 30% (n = 2). On successful pre-dilation with a 7 mm conventional balloon, patients were randomized to undergo either a 7 mm drug-coated balloon (n = 94) or conventional balloon angioplasty (n = 92). The primary out-come measure was target lesion primary patency at 3 and 6 months. The secondary out-come measures included target lesion primary patency at 12 months and access circuit primary patency at 6 and 12 months, clinical and technical success rates, and 12-month mortality differences between the groups. RESULTS: The target lesion primary patency and access circuit patency rates at 3 and 6 months were significantly higher in drug-coated balloon angioplasty group as compared to conventional balloon angioplasty group. The technical and clinical success rates were 100% for both the groups. As a procedure-related complication, anastomotic site rupture occurred during pre-dilation in 4 cases. The number of deaths during the 12-month follow-up was one for each group. The number of early thrombotic events (at < 3 months) was significantly higher in the drug-coated balloon group (p = 0.002). CONCLUSION: Drug-coated balloon angioplasty was more effective and safer for the treatment of dysfunctional arteriovenous grafts compared to conventional balloon angioplasty.

Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US.

Recent outbreaks of enterovirus D68 (EV-D68) infections, and their causal linkage with acute flaccid myelitis (AFM), continue to pose a serious public health concern. During 2020 and 2021, the dynamics of EV-D68 and other pathogens have been significantly perturbed by non-pharmaceutical interventions against COVID-19; this perturbation presents a powerful natural experiment for exploring the dynamics of these endemic infections. In this study, we analyzed publicly available data on EV-D68 infections, originally collected through the New Vaccine Surveillance Network, to predict their short- and long-term dynamics following the COVID-19 interventions. Although long-term predictions are sensitive to our assumptions about underlying dynamics and changes in contact rates during the NPI periods, the likelihood of a large outbreak in 2023 appears to be low. Comprehensive surveillance data are needed to accurately characterize future dynamics of EV-D68. The limited incidence of AFM cases in 2022, despite large EV-D68 outbreaks, poses further questions for the timing of the next AFM outbreaks.

Spontaneous resolution of long-standing choroidal effusion after glaucoma drainage implant surgery without significant visual deterioration : a case report.

BACKGROUND: Choroidal effusion is a common complication of glaucoma surgery. Although most cases of choroidal effusions resolve spontaneously with observation or medical management alone as intraocular pressure normalizes, surgical drainage might be needed in severe or persistent cases. Herein, we report a case of spontaneous resolution of long-standing severe choroidal effusion after Ahmed glaucoma valve implantation. CASE PRESENTATION: An 85-year-old man with uncontrolled primary open-angle glaucoma and medical history of chronic kidney disease underwent uneventful Ahmed glaucoma valve implantation. On postoperative day 8, transient hypotony occurred, and large 360° peripheral choroidal detachments developed. Although the intraocular pressure increased to normal levels on postoperative day 15, choroidal effusion did not resolve. Fundus examination over 8 months showed that the large choroidal effusion persisted despite a well-controlled intraocular pressure. Laboratory test performed at preoperatively and follow-up period revealed persistently elevated potassium and creatinine levels. On postoperative 9 months, the lesion resolved spontaneously without any surgical intervention. We found that the patient's creatinine level was normalized, pre-existing hyperkalemia was corrected, and accordingly his general condition was improved. CONCLUSIONS: Considering the underlying medical condition may be helpful in patients with persistent choroidal effusion of an unclear etiology following glaucoma filtering surgery.

Comparison of the Visual Outcomes of Enhanced and Standard Monofocal Intraocular Lens Implantations in Eyes with Early Glaucoma.

This study aimed to compare the efficacies and safety of enhanced and standard monofocal intraocular lenses (IOLs) in eyes with early glaucoma. Patients with concurrent cataracts and open-angle glaucoma (OAG) were enrolled. They underwent cataract surgery with IOL implantation. The comprehensive preoperative ophthalmic examination included the manifest refraction; monocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), and uncorrected near visual acuity (UNVA); visual field (VF); and contrast sensitivity (CS); defocus curves and questionnaires were assessed three months postoperatively. Totals of 34 and 38 patients had enhanced and standard monofocal IOLs, respectively. The enhanced monofocal IOL provided better UIVA than the standard monofocal IOL (p = 0.003) but similar UDVA, CDVA, and UNVA. The enhanced monofocal IOL had more consistent defocus curves than the standard monofocal IOL, especially at -1 (p = 0.042) and -1.5 (p = 0.026) diopters. The enhanced monofocal IOL provided better satisfaction (p = 0.019) and lower spectacle dependence (p = 0.004) than the standard monofocal IOL for intermediate vision, with similar VF and CS outcomes. In conclusion, enhanced monofocal IOLs are recommended for patients with OAG because they provide better intermediate vision, higher satisfaction, and lower dependence on spectacles than standard monofocal IOLs, without worsening other visual outcomes.

Evaluating the Safety and Effectiveness of Quick-Soluble Gelatin Sponge Particles for Genicular Artery Embolization for Chronic Knee Pain Associated with Osteoarthritis.

PURPOSE: To evaluate the effectiveness and safety of genicular artery embolization (GAE) using quick-soluble gelatin sponge particles (QS-GSPs) to alleviate chronic knee pain associated with osteoarthritis. MATERIALS AND METHODS: This retrospective study included 71 patients (97 procedures, including 26 patients for both knees) who underwent GAE to treat osteoarthritic knee pain between August 2019 and January 2022. QS-GSPs were used for all the procedures. Technical success was defined as the embolization of at least 1 feeding artery. Clinical outcomes were evaluated using a 10-point visual analog scale (VAS). Clinical success was defined as a decrease in the VAS score of >50%. RESULTS: The technical success rate was 100% (97 of 97). The mean VAS scores at baseline, immediately after TAE, and at 1 day, 1 week, 1 month, 3 months, and 6 months after TAE were 6.3, 4.3, 5.0, 3.0, 2.9, 2.9, and 2.8, respectively. The clinical success rate was 72% (70 of 97 patients) at 6 months. No major adverse events were reported, and temporary skin color change (50.5%, 49 of 97) and hematoma at the puncture site (10.3%, 10 of 97) were observed. CONCLUSIONS: GAE using QS-GSPs had a high technical success rate and was considered safe. Clinical outcomes using QS-GSPs were comparable with those of existing materials.

Relative role of community transmission and campus contagion in driving the spread of SARS-CoV-2: Lessons from Princeton University.

Mathematical models have played a crucial role in exploring and guiding pandemic responses. University campuses present a particularly well-documented case for institutional outbreaks, thereby providing a unique opportunity to understand detailed patterns of pathogen spread. Here, we present descriptive and modeling analyses of SARS-CoV-2 transmission on the Princeton University (PU) campus-this model was used throughout the pandemic to inform policy decisions and operational guidelines for the university campus. Epidemic patterns between the university campus and surrounding communities exhibit strong spatiotemporal correlations. Mathematical modeling analysis further suggests that the amount of on-campus transmission was likely limited during much of the wider pandemic until the end of 2021. Finally, we find that a superspreading event likely played a major role in driving the Omicron variant outbreak on the PU campus during the spring semester of the 2021-2022 academic year. Despite large numbers of cases on campus in this period, case levels in surrounding communities remained low, suggesting that there was little spillover transmission from campus to the local community.

High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner.

We aimed to investigate the effects of different concentrations of vascular endothelial growth factor (VEGF) on the extracellular matrix (ECM) and fibrotic proteins in human trabecular meshwork (TM) cells. We also explored how the Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway modulates VEGF-induced fibrosis. We determined cross-linked actin network (CLAN) formation using TM cells. Changes in fibrotic and ECM protein expression were determined. High VEGF concentrations (10 and 30 ng/mL) increased TAZ and decreased p-TAZ/TAZ expression in TM cells. Western blotting and real-time PCR revealed no YAP expression changes. Fibrotic and ECM protein expression decreased at low VEGF concentrations (1 and 10 ρg/mL) and significantly increased at high VEGF concentrations (10 and 30 ng/mL). CLAN formation increased in TM cells treated with high VEGF concentrations. Moreover, TAZ inhibition by verteporfin (1 µM) rescued TM cells from high-VEGF-concentration-induced fibrosis. Low VEGF concentrations reduced fibrotic changes, whereas high VEGF concentrations accelerated fibrosis and CLAN formations in TM cells in a TAZ-dependent manner. These findings reflect the dose-dependent influences of VEGF on TM cells. Moreover, TAZ inhibition might be a therapeutic target for VEGF-induced TM dysfunction.

Factors Associated with Visual Acuity in Advanced Glaucoma.

This study aimed to comprehensively analyze various parameters in advanced glaucoma patients to identify the factors that can affect best-corrected visual acuity (BCVA) in advanced glaucoma. This cross-sectional retrospective study included 113 patients (mean age, 61.66 ± 13.26 years; males, 67) who had advanced glaucomatous damage (113 eyes; mean BCVA, 0.18 ± 0.38 logMAR; mean deviation of 30-2 visual field [VF], -19.08 ± 6.23 dB). Peripapillary retinal nerve fiber layer (RNFL) and total and segmented macular thickness (RNFL, ganglion cell layer (GCL), and inner plexiform layer (GCL)) were measured using Spectralis optical coherence tomography (OCT). Correlations between BCVA and OCT parameters or 30-2 VF parameters were assessed using Pearson correlation analysis. Multivariate regression analysis was performed to determine the factors associated with BCVA in advanced glaucoma patients. Peripapillary RNFL thickness, subfoveal choroidal thickness, and global macular RNFL, GCL, IPL, and total thickness were found to be significantly correlated with BCVA and central visual function. Multivariate analysis showed a significant correlation between subfoveal choroidal thickness and BCVA. In addition, central VF mean sensitivity, especially inferior hemifield, showed a significant relationship with BCVA. In conclusion, subfoveal choroidal thickness and central VF sensitivity, especially the inferior hemifield area, are factors that affect BCVA in advanced glaucoma.

Inferring the differences in incubation-period and generation-interval distributions of the Delta and Omicron variants of SARS-CoV-2.

Estimating the differences in the incubation-period, serial-interval, and generation-interval distributions of SARS-CoV-2 variants is critical to understanding their transmission. However, the impact of epidemic dynamics is often neglected in estimating the timing of infection-for example, when an epidemic is growing exponentially, a cohort of infected individuals who developed symptoms at the same time are more likely to have been infected recently. Here, we reanalyze incubation-period and serial-interval data describing transmissions of the Delta and Omicron variants from the Netherlands at the end of December 2021. Previous analysis of the same dataset reported shorter mean observed incubation period (3.2 d vs. 4.4 d) and serial interval (3.5 d vs. 4.1 d) for the Omicron variant, but the number of infections caused by the Delta variant decreased during this period as the number of Omicron infections increased. When we account for growth-rate differences of two variants during the study period, we estimate similar mean incubation periods (3.8 to 4.5 d) for both variants but a shorter mean generation interval for the Omicron variant (3.0 d; 95% CI: 2.7 to 3.2 d) than for the Delta variant (3.8 d; 95% CI: 3.7 to 4.0 d). The differences in estimated generation intervals may be driven by the "network effect"-higher effective transmissibility of the Omicron variant can cause faster susceptible depletion among contact networks, which in turn prevents late transmission (therefore shortening realized generation intervals). Using up-to-date generation-interval distributions is critical to accurately estimating the reproduction advantage of the Omicron variant.

Intermediate levels of asymptomatic transmission can lead to the highest epidemic fatalities.

Asymptomatic infections have hampered the ability to characterize and prevent the transmission of SARS-CoV-2 throughout the pandemic. Although asymptomatic infections reduce severity at the individual level, they can make population-level outcomes worse if asymptomatic individuals-unaware they are infected-transmit more than symptomatic individuals. Using an epidemic model, we show that intermediate levels of asymptomatic infection lead to the highest levels of epidemic fatalities when the decrease in symptomatic transmission, due either to individual behavior or mitigation efforts, is strong. We generalize this result to include presymptomatic transmission, showing that intermediate levels of nonsymptomatic transmission lead to the highest levels of fatalities. Finally, we extend our framework to illustrate how the intersection of asymptomatic spread and immunity profiles determine epidemic trajectories, including population-level severity, of future variants. In particular, when immunity provides protection against symptoms, but not against infections or deaths, epidemic trajectories can have faster growth rates and higher peaks, leading to more total deaths. Conversely, even modest levels of protection against infection can mitigate the population-level effects of asymptomatic spread.

Effect of chemically modified lignin addition on the physicochemical properties of PCL nanofibers.

In this study, a chemically modified lignin additive was successfully prepared to improve the physicochemical properties of biodegradable polycaprolactone (PCL)-based nanofibers. The molecular weight and surface functional group characteristics of lignin were effectively controlled through a solvent fractionation process using ethanol. Then, PCL-g-lignin was successfully synthesized by using ethanol-fractionated lignin as a platform for the PCL grafting process. Finally, PCL/PCL-g-lignin composite nanofibers were simply prepared by adding PCL-g-lignin to the PCL doping solution and performing a solution blow spinning process. The addition of PCL-g-lignin could dramatically improve the physical and chemical properties of PCL nanofibers, and in particular, the tensile strength (0.28 MPa) increased by approximately 280 % compared to the conventional PCL. In addition, the lignin moiety present in PCL-g-lignin was able to impart UV blocking properties to PCL nanofibers, and as a result, it was possible to effectively suppress the photolysis phenomenon that occurred rapidly in existing PCL nanofibers. Therefore, PCL-g-lignin may be widely used not only as a reinforcing agent of existing biodegradable nanofibers but also as a functional additive for UV protection.