History of NHTSA's upgrade of FMVSS 208 addressing airbag induced fatalities and serious injuries.

OBJECTIVE: The objective of this paper is to provide a history of the National Highway Traffic Safety Administration's (NHTSA's) extensive efforts of incorporating advanced airbag technology capability beyond that available in first-generation airbag systems into FMVSS No. 208. METHODS: In the paper, NHTSA's actions and their collaborative efforts with automakers, automaker suppliers, insurance industry, academia, and other Federal agencies were reviewed, and the key efforts have been highlighted. Through their efforts, NHTSA developed its strategy by first undertaking near term actions and then undertaking the strategy for longer term actions. Rulemaking was undertaken in three steps. Then, as sufficient data became available, NHTSA documented the effectiveness of the rulemakings. RESULTS: The approach taken by NHTSA with the goal of preserving the safety benefits of the first-generation of frontal airbags while minimizing their danger to children and at-risk adults paved the way for the advanced airbags final rule and an interim final rule issued on May 12, 2000 (see Federal Register Notice 65 FR 30680). A follow-up final rule was issued on August 31, 2006, to change the test speed of the belted 5th percentile female dummy from 48 km/h to 56 km/h (30 mph to 35 mph). The final rule was updated on November 2, 2007, to permit manufacturers to earn advance credits for vehicles that are certified in compliance with the new higher speed requirement one year in advance of the regulatory requirements. CONCLUSION: NHTSA engagement in efforts with multiple partners toward identifying the safety issues, was an integral part of NHTSA's strategy in addressing the problem, arriving at immediate actions that NHTSA took, and detailing a comprehensive look at the longer-term approach required to resolve the safety issues. The approach taken by NHTSA paved the way for the advanced airbags final rule and an interim final rule issued on May 12, 2000 (Federal Register Notice 65 FR 30680). NHTSA had undertaken a successful collaboration of the Federal Government, the automobile industry, equipment suppliers, insurance companies, traffic safety advocates, law enforcement agencies from across the country, and the media to solve the airbag related safety issue.

Cryo-EM structure of TMEM63C suggests it functions as a monomer.

The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various physiological functions. Deficiency of these channels would cause many diseases including hearing loss. However, their structures and physiological roles are not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure of the mouse TMEM63C at 3.56 Å, and revealed structural differences compared to TMEM63A, TMEM63B, and the plant orthologues OSCAs. Further structural guided mutagenesis and calcium imaging demonstrated the important roles of the coupling of TM0 and TM6 in channel activity. Additionally, we confirm that TMEM63C exists primarily as a monomer under physiological conditions, in contrast, TMEM63B is a mix of monomer and dimer in cells, suggesting that oligomerization is a regulatory mechanism for TMEM63 proteins.

A manifold neural population code for space in hippocampal coactivity dynamics independent of place fields.

Hippocampus place cell discharge is temporally unreliable across seconds and days, and place fields are multimodal, suggesting an "ensemble cofiring" spatial coding hypothesis with manifold dynamics that does not require reliable spatial tuning, in contrast to hypotheses based on place field (spatial tuning) stability. We imaged mouse CA1 (cornu ammonis 1) ensembles in two environments across three weeks to evaluate these coding hypotheses. While place fields "remap," being more distinct between than within environments, coactivity relationships generally change less. Decoding location and environment from 1-s ensemble location-specific activity is effective and improves with experience. Decoding environment from cell-pair coactivity relationships is also effective and improves with experience, even after removing place tuning. Discriminating environments from 1-s ensemble coactivity relies crucially on the cells with the most anti-coactive cell-pair relationships because activity is internally organized on a low-dimensional manifold of non-linear coactivity relationships that intermittently reregisters to environments according to the anti-cofiring subpopulation activity.

Rapid gastric emptying during pregnancy in a rat model.

BACKGROUND/AIMS: The effect of pregnancy on gastric emptying has not been established, although the predominant clinical assumption is that gastric emptying is delayed during pregnancy. We hypothesized that the rate of emptying of nutrients during pregnancy is not delayed, but is actually more rapid when compared to the non-pregnant state. The rate of gastric emptying is a major determinant of postprandial glucose elevations. MATERIALS AND METHODS: 24 female and 4 male Spague-Dawley rats were used. Female rats were randomly divided into two groups: eight rats for the control group and sixteen rats for the pregnant group. Using physiologic, non-traumatic nuclear medicine scintigraphy imaging methodology, the authors studied gastric emptying of a liquid mixed meal in pregnant rats and non-pregnant controls. Body weights, daily food ingestion, and the rate of nutrient gastric emptying were recorded in both groups at pre-pregnancy, early pregnancy, and late pregnancy. RESULTS: The authors found that pregnancy in this rat model is associated with a 37-43% increased rate of nutrient gastric emptying from the stomach in late pregnancy as compared to non-pregnant control rats and pre-pregnancy rats. CONCLUSION: These findings contradict the current clinical assumption that gastric emptying is delayed in pregnancy. If further studies confirm a more rapid gastric emptying rate during human pregnancy, new therapies aimed at slowing the rate of nutrient absorption should be considered for the prevention and treatment of pregnancy-associated nausea, gestational diabetes, and other insulin-resistant pregnancy-associated states such as pre-eclampsia.

Improved delivery of rate-adaptive pacing using an impedance-derived contractility sensor in high-intensity exercise: A case report.

Effective rate-adaptive pacing may be difficult in the presence of atrial fibrillation (AF), and is important during high-intensity exercise. This case presents a 74-year-old elite cyclist with AF and a biventricular pacemaker after atrioventricular (AV) node ablation. He reported sudden breathlessness due to heart rate drops, caused by breaching the artefact threshold on the minute-ventilation sensor. He was exchanged to a generator with an impedance-derived contractility sensor (closed-loop stimulation), resulting in resolution of symptoms, and no further rate drops. This is the first description of the utility of closed-loop stimulation in high-intensity exercise.

Linking specific biological signatures to different childhood adversities: findings from the HERO project.

BACKGROUND: Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited. METHODS: Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1ß, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145). RESULTS: Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1ß (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample. CONCLUSIONS: Our results indicate that these biological response systems may react differently to different forms of early-life adversity. IMPACT: Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking. Children with higher socioeconomic disadvantage had higher TNF-α, IL-1ß, and DHEA. Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage. Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.

Decreased Cerebral Oxygenation in Premature Infants with Progressive Posthemorrhagic Ventricular Dilatation May Help with Timing of Intervention.

OBJECTIVE: The objective of this study was to determine the degree of progressive posthemorrhagic ventricular dilatation (PHVD) that is associated with a significant decrease in regional cerebral oxygen saturation (rScO2) in premature infants at risk for periventricular-intraventricular hemorrhage (PIVH). STUDY DESIGN: Cranial ultrasound (US) and near-infrared spectroscopy (NIRS) measurements of rScO2 were performed on inborn infants with birth weights less than 1,250 g on admission and at 1, 4, and 8 weeks of age. Infants with severe PIVH were studied weekly. A 1-hour average of rScO2 was compared with the frontal-occipital horn ratio (FOHR) measured the same day. Generalized linear models were used to analyze the relationship between FOHR and rScO2, by severity of PIVH, and adjusted for gestational age. Cut-off points of 0.55 for FOHR and 45% for rScO2 were used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The study cohort included 63 infants with normal US, 15 with grade-1 or -2 PIVH (mild group), and 21 with grade-3 or -4 PIVH (severe group). Increases in FOHR in the severe group were associated with decreases in rScO2 at 1 week (p = 0.036), 4 weeks (p = 0.013), and 8 weeks of life (p = 0.001) compared with the normal and mild groups. Infants with FOHR greater than 0.55 were 92% more likely to have rScO2 less than 45% when compared with infants with FOHR less than 0.55 (OR = 0.08, 95% CI: [0.04, 0.13], p < 0.001). CONCLUSION: Progressive PHVD (FOHR > 0.55) is a strong predictor of compromised cerebral oxygenation. A combination of rScO2 and FOHR measurements may aid in identifying infants with PHVD that would benefit from early intervention. KEY POINTS: · Earlier intervention in PHVD may improve outcomes.. · PHVD is diagnosed with US measurements of ventricular size.. · FOHR > 0.55 is associated with decreased cerebral perfusion..

Non-generalizability of biomarkers for mortality in SARS-CoV-2: a meta-analyses series

ObjectivesSophisticated scores have been proposed for prognostication of mortality due to SARS-CoV-2 but perform inconsistently. We conducted these meta-analyses to uncover why and to pragmatically seek a single dependable biomarker for mortality. DesignWe searched the PubMed database for the keywords SARS-CoV-2 with biomarker name and mortality. All studies published from 01st December 2019 to 30th June 2021 were surveyed. To aggregate the data, the meta library in R was used to report overall mean values and 95% confidence intervals. We fitted a random effects model to obtain pooled AUCs and associated 95% confidence intervals for the European/North American, Asian, and overall datasets. Setting and ParticipantsData was collected from 131 studies on SARS-CoV-2 PCR-positive general hospital adult admissions (n=76,169 patients in total). Main Outcome MeasuresWe planned a comparison of pooled area under curves (AUCs) from Receiver Operator Characteristic curves plotted for admission D-dimer, CRP, urea, troponin and interleukin-6 levels. Main ResultsBiomarker effectiveness varies significantly in different regions of the world. Admission CRP levels are a good prognostic marker for mortality due to SARS-CoV-2 in Asian countries, with a pooled area under curve (AUC) of 0.83 (95% CI 0.80-0.85), but only an average predictor of mortality in Europe/North America, with a pooled AUC of 0.67 (95% CI 0.63-0.71, P<0.0001). We observed the same pattern for D-dimer and IL-6. This variability explains why the proposed prognostic scores did not perform evenly. Notably, urea and troponin had pooled AUCs [≥] 0.78 regardless of location, implying that end-organ damage at presentation is a key prognostic factor. These differences might be due to age, genetic backgrounds, or different modes of death (younger patients in Asia dying of cytokine storm while older patients die of multi-organ failure). ConclusionsBiomarker effectiveness for prognosticating SARS-CoV-2 mortality varies significantly by geographical location. We propose that biomarkers and by extension prognostic scores need to be tailored for specific populations. This also implies that validation of commonly used prognostic scores for other conditions should occur before they are used in different populations. Summary boxO_ST_ABSSection 1: What is already known on this topicC_ST_ABSBiomarkers such as CRP, D-dimer, and interleukin-6 have been proven to have prognostic value in SARS-CoV-2. However prognostic scores using these as building blocks perform unevenly in different locations. Section 2: What this study addsCommonly used biomarkers for SARS-CoV-2 have different efficacy in different parts of the world. For example, admission CRP and interleukin-6 levels are good prognostic markers for mortality in Asian countries but only average in Europe and North America. Prognostic markers and scores cannot be transplanted from one region to another. This has implications not just for SARS-CoV-2 but also for scores in other conditions.

Persistence of SARS-CoV-2 Antibodies in Vaccinated Health Care Workers Analyzed by Coronavirus Antigen Microarray.

Recent studies provide conflicting evidence on the persistence of SARS-CoV-2 immunity induced by mRNA vaccines. Here, we aim to quantify the persistence of humoral immunity following vaccination using a coronavirus antigen microarray that includes 10 SARS-CoV-2 antigens. In a prospective longitudinal cohort of 240 healthcare workers, composite SARS-CoV-2 IgG antibody levels did not wane significantly over a 6-month study period. In the subset of the study population previously exposed to SARS-CoV-2 based on seropositivity for nucleocapsid antibodies, higher composite anti-spike IgG levels were measured before the vaccine but no significant difference from unexposed individuals was observed at 6 months. Age, vaccine type, or worker role did not significantly impact composite IgG levels, although non-significant trends towards lower antibody levels in older participants and higher antibody levels with Moderna vaccine were observed at 6 months. A small subset of our cohort were classified as having waning antibody titers at 6 months, and these individuals were less likely to work in patient care roles and more likely to have prior exposure to SARS-CoV-2.

CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment.

PURPOSE: Glioblastoma (GBM) patients suffer from a dismal prognosis, with standard of care therapy inevitably leading to therapy-resistant recurrent tumors. The presence of cancer stem cells (CSCs) drives the extensive heterogeneity seen in GBM, prompting the need for novel therapies specifically targeting this subset of tumor-driving cells. Here, we identify CD70 as a potential therapeutic target for recurrent GBM CSCs. EXPERIMENTAL DESIGN: In the current study, we identified the relevance and functional influence of CD70 on primary and recurrent GBM cells, and further define its function using established stem cell assays. We use CD70 knockdown studies, subsequent RNAseq pathway analysis, and in vivo xenotransplantation to validate CD70's role in GBM. Next, we developed and tested an anti-CD70 chimeric antigen receptor (CAR)-T therapy, which we validated in vitro and in vivo using our established preclinical model of human GBM. Lastly, we explored the importance of CD70 in the tumor immune microenvironment (TIME) by assessing the presence of its receptor, CD27, in immune infiltrates derived from freshly resected GBM tumor samples. RESULTS: CD70 expression is elevated in recurrent GBM and CD70 knockdown reduces tumorigenicity in vitro and in vivo. CD70 CAR-T therapy significantly improves prognosis in vivo. We also found CD27 to be present on the cell surface of multiple relevant GBM TIME cell populations, notably putative M1 macrophages and CD4 T cells. CONCLUSION: CD70 plays a key role in recurrent GBM cell aggressiveness and maintenance. Immunotherapeutic targeting of CD70 significantly improves survival in animal models and the CD70/CD27 axis may be a viable polytherapeutic avenue to co-target both GBM and its TIME.

Primary repair of multiligament knee injury with InternalBrace ligament augmentation.

Multiligament injury of the knee usually occurs as a result of high-energy trauma causing tibiofemoral dislocation. These are rare but potentially limb-threatening injuries, frequently involving nerve or arterial damage and often leading to severe complex instability. Management generally favours surgical reconstruction of the affected ligaments, with controversy regarding optimal treatment. We present a severe multiligament knee injury (Schenk classification KD-IV involving both cruciate and both collateral ligaments) in a competitive showjumper. A combined arthroscopic/open technique of single-stage surgical repair and suture augmentation was used, repairing all affected ligaments. The patient made an excellent recovery, returning to work after 12 weeks and riding after 22 weeks. After 5-year follow-up, she has regained her previous level of competition without subsequent injury. Multiligament repair with suture augmentation is a viable approach to the management of knee dislocation injuries. We propose that this could provide superior outcomes to traditional reconstruction techniques using autograft or synthetic reconstruction.

Therapeutic Hypothermia Inhibits the Classical Complement Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: Complement activation is instrumental in the pathogenesis of Hypoxic-ischemic encephalopathy (HIE), a significant cause of neonatal mortality and disability worldwide. Therapeutic hypothermia (HT), the only available treatment for HIE, only modestly improves outcomes. Complement modulation as a therapeutic adjunct to HT has been considered, but is challenging due to the wide-ranging role of the complement system in neuroinflammation, homeostasis and neurogenesis in the developing brain. We sought to identify potential therapeutic targets by measuring the impact of treatment with HT on complement effector expression in neurons and glia in neonatal HIE, with particular emphasis on the interactions between microglia and C1q. METHODS: The Vannucci model was used to induce HIE in term-equivalent rat pups. At P10-12, pups were randomly assigned to three different treatment groups: Sham (control), normothermia (NT), and hypothermia (HT) treatment. Local and systemic complement expression and neuronal apoptosis were measured by ELISA, TUNEL and immunofluorescence labeling, and differences compared between groups. RESULTS: Treatment with HT is associated with decreased systemic and microglial expression of C1q, decreased systemic C5a levels, and decreased microglial and neuronal deposition of C3 and C9. The effect of HT on cytokines was variable with decreased expression of pro and anti-inflammatory effectors. HT treatment was associated with decreased C1q binding on cells undergoing apoptosis. CONCLUSION: Our data demonstrate the extreme complexity of the immune response in neonatal HIE. We propose modulation of downstream effectors C3a and C5a as a therapeutic adjunct to HT to enhance neuroprotection in the developing brain.

Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids.

Current approaches for the production of high-value compounds in microorganisms mostly use the cytosol as a general reaction vessel. However, competing pathways and metabolic cross-talk frequently prevent efficient synthesis of target compounds in the cytosol. Eukaryotic cells control the complexity of their metabolism by harnessing organelles to insulate biochemical pathways. Inspired by this concept, herein we transform yeast peroxisomes into microfactories for geranyl diphosphate-derived compounds, focusing on monoterpenoids, monoterpene indole alkaloids, and cannabinoids. We introduce a complete mevalonate pathway in the peroxisome to convert acetyl-CoA to several commercially important monoterpenes and achieve up to 125-fold increase over cytosolic production. Furthermore, peroxisomal production improves subsequent decoration by cytochrome P450s, supporting efficient conversion of (S)-(-)-limonene to the menthol precursor trans-isopiperitenol. We also establish synthesis of 8-hydroxygeraniol, the precursor of monoterpene indole alkaloids, and cannabigerolic acid, the cannabinoid precursor. Our findings establish peroxisomal engineering as an efficient strategy for the production of isoprenoids.

Artificial intelligence-based radiotherapy machine parameter optimization using reinforcement learning.

PURPOSE: To develop and evaluate a volumetric modulated arc therapy (VMAT) machine parameter optimization (MPO) approach based on deep-Q reinforcement learning (RL) capable of finding an optimal machine control policy using previous prostate cancer patient CT scans and contours, and applying the policy to new cases to rapidly produce deliverable VMAT plans in a simplified beam model. METHODS: A convolutional deep-Q network was employed to control the dose rate and multileaf collimator of a C-arm linear accelerator model using the current dose distribution and machine parameter state as input. A Q-value was defined as the discounted cumulative cost based on dose objectives, and experience-replay RL was performed to determine a policy to minimize the Q-value. A two-dimensional network design was employed which optimized each opposing leaf pair independently while monitoring the corresponding dose plane blocked by those leaves. This RL approach was applied to CT and contours from 40 retrospective prostate cancer patients. The dataset was split into training (15 patients) and validation (5 patients) groups to optimize the network, and its performance was tested in an independent cohort of 20 patients by comparing RL-based dose distributions to conformal arcs and clinical intensity modulated radiotherapy (IMRT) delivering a prescription dose of 78 Gy in 40 fractions. RESULTS: Mean ± SD execution time of the RL VMAT optimization was 1.5 ± 0.2 s per slice. In the test cohort, mean ± SD (P-value) planning target volume (PTV), bladder, and rectum dose were 80.5 ± 2.0 Gy (P < 0.001), 44.2 ± 14.6 Gy (P < 0.001), and 43.7 ± 11.1 Gy (P < 0.001) for RL VMAT compared to 81.6 ± 1.1 Gy, 51.6 ± 12.9 Gy, and 36.0 ± 12.3 Gy for clinical IMRT. CONCLUSIONS: RL was applied to VMAT MPO using clinical patient contours without independently optimized treatment plans for training and achieved comparable target and normal tissue dose to clinical plans despite the application of a relatively simple network design originally developed for video-game control. These results suggest that extending a RL approach to a full three-dimensional beam model could enable rapid artificial intelligence-based optimization of deliverable treatment plans, reducing the time required for radiotherapy planning without requiring previous plans for training.

A semiautomatic segmentation method for interstitial needles in intraoperative 3D transvaginal ultrasound images for high-dose-rate gynecologic brachytherapy of vaginal tumors.

PURPOSE: The purpose of this study was to evaluate the use of a semiautomatic algorithm to simultaneously segment multiple high-dose-rate (HDR) gynecologic interstitial brachytherapy (ISBT) needles in three-dimensional (3D) transvaginal ultrasound (TVUS) images, with the aim of providing a clinically useful tool for intraoperative implant assessment. METHODS AND MATERIALS: A needle segmentation algorithm previously developed for HDR prostate brachytherapy was adapted and extended to 3D TVUS images from gynecologic ISBT patients with vaginal tumors. Two patients were used for refining/validating the modified algorithm and five patients (8-12 needles/patient) were reserved as an unseen test data set. The images were filtered to enhance needle edges, using intensity peaks to generate feature points, and leveraged the randomized 3D Hough transform to identify candidate needle trajectories. Algorithmic segmentations were compared against manual segmentations and calculated dwell positions were evaluated. RESULTS: All 50 test data set needles were successfully segmented with 96% of algorithmically segmented needles having angular differences <3° compared with manually segmented needles and the maximum Euclidean distance was <2.1 mm. The median distance between corresponding dwell positions was 0.77 mm with 86% of needles having maximum differences <3 mm. The mean segmentation time using the algorithm was <30 s/patient. CONCLUSIONS: We successfully segmented multiple needles simultaneously in intraoperative 3D TVUS images from gynecologic HDR-ISBT patients with vaginal tumors and demonstrated the robustness of the algorithmic approach to image artifacts. This method provided accurate segmentations within a clinically efficient timeframe, providing the potential to be translated into intraoperative clinical use for implant assessment.

An Australian Response to the COVID-19 Pandemic and Its Implications on the Practice of Neurosurgery.

OBJECTIVE: This study was designed to assess the impact of public health policy in Australia in response to the coronavirus disease identified in 2019 (COVID-19) pandemic on the delivery of neurosurgical services. Being essential services, we postulated that there would not be a decrease in elective and emergency neurosurgical presentations and surgeries. METHODS: This is a prospective, observational, epidemiologic study in strict adherence to the "STROBE" (Strengthening The Reporting of OBservational studies in Epidemiology) guidelines. It is a cross-sectional, multicentric study involving 5 tertiary neurosurgical centers to capture all public neurosurgical admissions in Queensland during the past 3 months (February-April, 2020) of significant public health policy changes to combat COVID-19. RESULTS: An analysis of the 1298 admissions for the Queensland population of 5.07 million Australians demonstrated a decrease in the number of elective and emergency admissions. The decline in elective admissions, particularly degenerative spine, benign neoplasms, and vascular pathologies, was a direct response of government strategy to curb activity to urgent surgical interventions only. Moreover, a trend toward fewer emergency admissions was also noted, partly explained by less trauma and also a decline in vascular pathologies including subarachnoid hemorrhage. CONCLUSIONS: In comparison with Europe and North America, this study demonstrates the impact of proactive public health measures in Australia that successfully flattened the COVID-19 curve while facilitating ongoing care of acutely unwell neurosurgical patients.

An international comparison of the second derivative of COVID-19 deaths after implementation of social distancing measures

This work compares deaths for confirmed COVID-19 cases in China to eight other countries, Italy, Spain, France, USA, UK, Germany, Netherlands and South Korea. After implementing varying intensities and timing of social distancing measures, several appear to be converging onto the decline in the daily growth rate of deaths, or relative second derivative of total deaths, seen in China after the implementation an aggressive social distancing policy. By calculating future trajectories in these countries based on the observed Chinese fatality statistics, an estimate of the total deaths and maximum daily death rates over a defined period of time is made. Our lower bound estimate for the United Kingdom based on the real data approximates the lower bound estimate of the recent modelling study of Ferguson et al. [1]. These results suggest there may be a threshold of effective public health intervention. Our method of viewing the data may be helpful in monitoring the course of the epidemic, judging the effectiveness of implementation, and monitoring the relaxation of social distancing.