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Excess mortality studies provide crucial information regarding the health burden of pandemics and other large-scale events. Here, we use time series approaches to separate the direct contribution of SARS-CoV-2 infection on mortality from the indirect consequences of the pandemic in the United States. We estimate excess deaths occurring above a seasonal baseline from March 1, 2020 to January 1, 2022, stratified by week, state, age, and underlying mortality condition (including COVID-19 and respiratory diseases; Alzheimer’s disease; cancer; cerebrovascular diseases; diabetes; heart diseases; and external causes, which include suicides, opioid overdoses, and accidents). Over the study period, we estimate an excess of 1,065,200 (95% Confidence Interval (CI) 909,800–1,218,000) all-cause deaths, of which 80% are reflected in official COVID-19 statistics. State-specific excess death estimates are highly correlated with SARS-CoV-2 serology, lending support to our approach. Mortality from 7 of the 8 studied conditions rose during the pandemic, with the exception of cancer. To separate the direct mortality consequences of SARS-CoV-2 infection from the indirect effects of the pandemic, we fit generalized additive models (GAM) to age- state- and cause-specific weekly excess mortality, using covariates representing direct (COVID-19 intensity) and indirect pandemic effects (hospital intensive care unit (ICU) occupancy and measures of interventions stringency). We find that 84% (95% CI 65–94%) of all-cause excess mortality can be statistically attributed to the direct impact of SARS-CoV-2 infection. We also estimate a large direct contribution of SARS-CoV-2 infection (≥67%) on mortality from diabetes, Alzheimer’s, heart diseases, and in all-cause mortality among individuals over 65 years. In contrast, indirect effects predominate in mortality from external causes and all-cause mortality among individuals under 44 years, with periods of stricter interventions associated with greater rises in mortality. Overall, on a national scale, the largest consequences of the COVID-19 pandemic are attributable to the direct impact of SARS-CoV-2 infections; yet, the secondary impacts dominate among younger age groups and in mortality from external causes. Further research on the drivers of indirect mortality is warranted as more detailed mortality data from this pandemic becomes available.

As the risk of accidental explosions at ammunition storage or hydrogen charging station increases in populated area, it is needed to design the facilities against blast loading, particularly subjected to partially confined explosion. However, the partially confined explosion lacks experimental test data to efficiently design the facilities subjected to the potential threat, when compared to unconfined or confined explosion cases. As a fundamental study on partially confined explosion, two partially buried tunnel-type structures with normal- and high-strength concretes were tested under a weight charge of 5.9 kg TNT explosion. The major parameters were concrete compressive strength and reinforcement ratio. The test result showed that the damage of the concrete structure with normal-strength concrete was extremely severe, whereas that of the specimen with high-strength was relatively mild. Further, finite element (FE) analyses were performed to investigate the confinement effect of blast load. The FE analysis result showed that under partially confined explosion, the reduction of the maximum displacement by using higher concrete strength was significant, while preventing the failure of the structure. This study provides fundamental data for designing the facilities with explosives subjected to the partially confined explosion.

We investigated the association between retinal changes measured using optical coherence tomography (OCT) and diverse clinical grading scales in patients with Parkinson’s disease (PD). Seventy-four eyes of 74 patients with de novo PD and 53 eyes of age-matched control subjects were included. The thickness of the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) were measured. We analyzed the correlations between the clinical PD grading scales and OCT parameters, and between the OCT parameters and volumetric data in the cerebral cortical and subcortical structures. The area under the receiver operating characteristic curve (AUC) was calculated for diagnosing cognitive impairment in patients with PD. Statistically significant reductions in the thickness of average, temporal, and inferior pRNFL and overall mGCIPL were observed in patients with PD. The Montreal Cognitive Assessment score was significantly associated with mGCIPL thinning. The AUC of the mGCIPL parameters for diagnosing cognitive impairment in patients with PD ranged from 0.651 to 0.760. Moreover, thinning of the mGCIPL was significantly associated with the volumetric parameters of associated brain structures. Our findings highlight the clinical implications of OCT measurements as a potential biomarker for early detection of cognitive impairment in patients with PD.

We investigated the relationship between microstructure of β-parapapillary atrophy (β-PPA) and morphologic features of optic nerve head (ONH) and posterior pole in highly myopic eyes. Eighty-nine highly myopic eyes were included in this study. Bruch’s membrane opening (BMO) area, lamina cribrosa (LC) thickness, anterior laminar depth, peripapillary and subfoveal choroidal thickness (CT), macular Bruch’s membrane (BM) length, and width of β-PPA with and without Bruch’s membrane (PPA +BM and PPA −BM ) were evaluated. The mean age and axial length of the included subjects were 26.88 ± 2.44 years and 27.03 ± 0.88 mm, respectively. The width of PPA −BM was larger with increasing BMO area ( P  = 0.001), whereas the BMO area was not associated with the width of PPA +BM . The large PPA +BM was significantly related to a thinner LC ( P  = 0.003), deeper anterior lamina surface ( P  < 0.001), longer macular BM length ( P  = 0.008), and thinner temporal peripapillary CT ( P  = 0.034). We found that the morphologic features of the ONH and posterior pole in highly myopic eyes were different based on the microstructure of β-PPA. Whether these features are linked to the development of glaucoma in myopic eyes should be investigated in future studies.

To compare the efficacy, patient-reported satisfaction, and safety of preservative-free (PF)-tafluprost, PF-dorzolamide/timolol and preservative-containing (P)-latanoprost in Korean glaucoma patients with ocular surface disease (OSD). In a multicenter, prospective, interventional, non-randomized, controlled 12-week trial, 107 eligible patients received PF-tafluprost (n = 37), PF-dorzolamide/timolol (n = 34), or P-latanoprost eye drops (n = 36). Outcomes included changes from baseline in OSD Index (OSDI) scores (primary endpoint), intraocular pressure (IOP), and patient-reported treatment satisfaction, and safety at 12 weeks. At 12 weeks, the mean total OSDI and subdomain (dry eye symptoms, visual-related function, environmental triggers) scores significantly improved from baseline with PF-tafluprost and PF-dorzolamide/timolol, but not with P-latanoprost. Significantly more PF-tafluprost than P-latanoprost recipients reported ‘highly improved/improved’ satisfaction (no significant difference between PF-dorzolamide/timolol and P-latanoprost). IOP changes were comparable among all three treatment groups. No new safety concerns were observed. PF-tafluprost and PF-dorzolamide/timolol showed statistically and clinically significant reductions in OSDI compared with P-latanoprost in Korean glaucoma patients with OSD.

To study the usefulness of virtual reality (VR)-based training for diagnosing strabismus. Fourteen residents in ophthalmology performed at least 30 VR training sessions to diagnose esotropia and exotropia. Examinations of real patients with esotropia or exotropia before and after the VR training were video-recorded and presented to a strabismus expert to assess accuracy and performance scores for measuring the deviation angle and diagnosing strabismus with anonymization. A feedback survey regarding the usefulness and ease of use of the VR application was conducted for participants. The mean age of the 14 ophthalmology residents (10 men and 4 women), was 29.7 years. Before VR training, participants showed a mean accuracy score of 14.50 ± 5.45 and a performance score of 9.64 ± 4.67 for measuring the deviation angle and diagnosing strabismus in real patients with strabismus. After VR training, they showed a significantly improved accuracy score of 22.14 ± 4.37 (p = 0.012) and a performance score of 15.50 ± 1.99 (p = 0.011). According to the survey, most participants agreed on the usefulness of VR applications. This study suggests that VR-based training improved ophthalmology residents’ clinical diagnostic skills for strabismus in a short period.

The COVID-19 pandemic has caused more than 1,000,000 reported deaths globally, of which more than 200,000 have been reported in the United States as of October 1, 2020. Public health interventions have had significant impacts in reducing transmission and in averting even more deaths. Nonetheless, in many jurisdictions, the decline of cases and fatalities after apparent epidemic peaks has not been rapid. Instead, the asymmetric decline in cases appears, in most cases, to be consistent with plateau- or shoulder-like phenomena—a qualitative observation reinforced by a symmetry analysis of US state-level fatality data. Here we explore a model of fatality-driven awareness in which individual protective measures increase with death rates. In this model, fast increases to the peak are often followed by plateaus, shoulders, and lag-driven oscillations. The asymmetric shape of model-predicted incidence and fatality curves is consistent with observations from many jurisdictions. Yet, in contrast to model predictions, we find that population-level mobility metrics usually increased from low levels before fatalities reached an initial peak. We show that incorporating fatigue and long-term behavior change can reconcile the apparent premature relaxation of mobility reductions and help understand when post-peak dynamics are likely to lead to a resurgence of cases.

An epidemic can be characterized by its strength (i.e., the reproductive number 𝓡) and speed (i.e., the exponential growth rate r). Disease modellers have historically placed much more emphasis on strength, in part because the effectiveness of an intervention strategy is typically evaluated on this scale. Here, we develop a mathematical framework for the classic, strength-based paradigm and show that there is a dual speed-based paradigm which can provide complementary insights. In particular, we note that r = 0 is a threshold for disease spread, just like 𝓡 = 1 [1], and show that we can measure the strength and speed of an intervention on the same scale as the strength and speed of an epidemic, respectively. We argue that, while the strength-based paradigm provides the clearest insight into certain questions, the speed-based paradigm provides the clearest view in other cases. As an example, we show that evaluating the prospects of ‘test-and-treat’ interventions against the human immunodeficiency virus (HIV) can be done more clearly on the speed than strength scale, given uncertainty in the proportion of HIV spread that happens early in the course of infection. We also discuss evaluating the effects of the importance of pre-symptomatic transmission of the SARS-CoV-2 virus. We suggest that disease modellers should avoid over-emphasizing the reproductive number at the expense of the exponential growth rate, but instead look at these as complementary measures.

Nonpharmaceutical interventions (NPIs) have been employed to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet these measures are already having similar effects on other directly transmitted, endemic diseases. Disruptions to the seasonal transmission patterns of these diseases may have consequences for the timing and severity of future outbreaks. Here we consider the implications of SARS-CoV-2 NPIs for two endemic infections circulating in the United States of America: respiratory syncytial virus (RSV) and seasonal influenza. Using laboratory surveillance data from 2020, we estimate that RSV transmission declined by at least 20% in the United States at the start of the NPI period. We simulate future trajectories of both RSV and influenza, using an epidemic model. As susceptibility increases over the NPI period, we find that substantial outbreaks of RSV may occur in future years, with peak outbreaks likely occurring in the winter of 2021–2022. Longer NPIs, in general, lead to larger future outbreaks although they may display complex interactions with baseline seasonality. Results for influenza broadly echo this picture, but are more uncertain; future outbreaks are likely dependent on the transmissibility and evolutionary dynamics of circulating strains.