Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the US

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multi-model ensemble forecast that combined predictions from dozens of different research groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naive baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-week horizon 3-5 times larger than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks. Significance StatementThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the US. Results show high variation in accuracy between and within stand-alone models, and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public health action.

COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.

Epidemic Model Guided Machine Learning for COVID-19 Forecasts in the United States

We propose a new epidemic model (SuEIR) for forecasting the spread of COVID-19, including numbers of confirmed and fatality cases at national and state levels in the United States. Specifically, the SuEIR model is a variant of the SEIR model by taking into account the untested/unreported cases of COVID-19, and trained by machine learning algorithms based on the reported historical data. Besides providing basic projections for confirmed and fatality cases, the proposed SuEIR model is also able to predict the peak date of active cases, and estimate the basic reproduction number ([Formula]). In particular, the forecasts based on our model suggest that the peak date of the US, New York state, and California state are 06/01/2020, 05/10/2020, and 07/01/2020 respectively. In addition, the estimated [Formula] of the US, New York state, and California state are 2.5, 3.6 and 2.2 respectively. The prediction results for all states in the US can be found on our project website: https://covid19.uclaml.org, which are updated on a weekly basis, and have been adopted by the Centers for Disease Control and Prevention (CDC) for COVID-19 death forecasts (https://www.cdc.gov/coronavirus/2019-ncov/covid-data/forecasting-us.html).

Prediction of left ventricular systolic function after repair or replacement of mitral regurgitation by two‐dimensional speckle tracking imaging / 中华超声影像学杂志

To investigate the predictive value of left ventricular longitudinal strain parameters in patients with severe mitral regurgitation before surgery on the reduction of transthoracic automatic left ventricular three －dimensional ejection fraction ( Heart Model EF ) aftersurgery . Methods Clinical data ,two‐dimensional and three‐dimensional dynamic images of 33 patients preparing for mitral regurgitation surgery and 39 healthy adults were obtained . T wo‐dimensional strain parameters of left ventricular ,and Heart Model EF of left ventricular were obtained by software analysis . Healthy adults were set as control group ,and patients with mitral regurgitation were divided into M R 1 group ( Heart M odel EF did not reduce or decrease ≤ 10% ) and M R2 group ( Heart M odel EF reduced ＞ 10% ) according to the degree of Heart M odel EF reduction 6 months after surgery . Logistic regression analysis was used to evaluate the parameters related to the decrease of Heart Model EF 6 months after operation in the longitudinal strain parameters of left ventricular myocardium before operation ,and the critical values of sensitive predictive parameters were obtained by drawing receiver operating characteristic ( ROC ) curve . Results ①T he absolute values of left ventricular strain parameters in M R 2 group were significantly lower than those in control group and M R1 group ( P ＜ 0 .05 ) . T he results of univariate Logistic regression analysis and ROC curve analysis showed that the left ventricular systolic global peak longitudinal strain ( GLS) ,left ventricular systolic basal peak longitudinal strain ( BLS) and left ventricular systolic inferior wall peak longitudinal strain ( I‐LS) can be used as predictors of post‐operative Heart Model EF reduction ( P ＜0 .05) . T he OR ( 95% CI ) value ,cut‐off value ,sensitivity and specificity were 0 .752 ( 0 .753 ,0 .987 ) ,－19 .35 ,67% ,92% ( GLS) ,0 .757 ( 0 .590 ,0 .970 ) ,－19 .01 ,78% ,77% ( BLS ) and 0 .821 ( 0 .675 ,0 .998 ) ,－18 .43 ,67% ,92% ( I‐LS ) ,respectively . ② T he multivariate logistic regression analysis of left ventricular strain parameters showed that only BLS can be used as predictors of post‐operative EF reduction . T he OR ( 95% CI ) value and P value were 0 .757 ( 0 .590 ,0 .970 ) and 0 .028 , respectively . Conclusions Two‐dimensional speckle tracking imaging has the ability to detect preoperative subclinical left ventricular dysfunction ,and is a reliable reference for selecting surgical timing for patients with severe mitral regurgitation . In addition to left ventricular GLS ,left ventricular BLS and left ventricular I‐LS can also predict postoperative left ventricular dysfunction ,among w hich left ventricular BLS is more significant .

Involvement of Orai1 in tunicamycin-induced endothelial dysfunction

Endoplasmic reticulum (ER) stress is mediated by disturbance of Ca²⁺ homeostasis. The store-operated calcium (SOC) channel is the primary Ca²⁺ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on Ca²⁺ influx in human umbilical vein endothelial cells (HUVECs) were observed with the fluorescent probe Fluo-4 AM. The effect of tunicamycin on the expression of the unfolded protein response (UPR)-related proteins BiP and CHOP was assayed by western blotting with or without inhibition of Orai1. Tunicamycin induced endothelial dysfunction by activating ER stress. Orai1 expression and the influx of extracellular Ca²⁺ in HUVECs were both upregulated during ER stress. The SOC channel inhibitor SKF96365 reversed tunicamycin-induced endothelial cell dysfunction by inhibiting ER stress. Regulation of tunicamycin-induced ER stress by Orai1 indicates that modification of Orai1 activity may have therapeutic value for conditions with ER stress-induced endothelial dysfunction.

Assessment of left ventricular hemodynamics and systolic function in patients with apical aneurysm after percutaneous ventricular restoration by echocardiography / 中华超声影像学杂志

Objective To evaluate the changes of left ventricular hemodynamics and systolic function in patients with apical aneurysm after percutaneous ventricular restoration ( PVR) by echocardiography . Methods Fifty patients with apical aneurysm were divided into PVR group ( 25 cases) and conservative treatment group ( control group ,25 cases ) . Two-dimensional transthoracic echocardiography ( 2D-TTE ) combined with real-time three-dimensional transesophageal echocardiography( RT-3DTEE) were applied for all the subjects in PVR group on preoperative ,one week after operaction ,three months after operaction and in control group on initial stage of prevent ventricular remodeling therapy ,one week after therapy ,three months after therapy to obtain left ventricular end-diastolic diameter( LVEDD) ,left ventricular end-systolic diameter( LVSDD) ,left ventricular end-diastolic volume( EDV ) ,end-systolic volume( ESV ) ,left ventricular ejection fraction( LVEF) ,left ventricular fractional shortening ( LVFS ) ,body surface area ( BSA ) ,stroke volume( SV) ,stroke volume index ( SVI) ,cardiac output ( CO ) ,cardiac output index ( CI) . Results There were significant differences in all parameters( P < 0 .05) especially in LVEF and SVI( P < 0 .01) between PVR group and control group in the following three months after operaction ,while there was no significant difference of the following one week after operaction( P > 0 .05) .Compared with preoperative ,there was no difference in all parameters in the following one week after operaction ( P > 0 .05) ,there was significant increase in SV and significant reduce in LVEDD and EDV ( P < 0 .01) between preoperative and in the following three months after operaction ,while there was no significant difference between preoperative and in the following one week after operaction ( P > 0 .05 ) .For the control group there was no significant difference between initial stage of prevevt ventricular remodeling therapy and in the following one week or three months after operaction .Conclusions PVR has a definite effect on left ventricular hemodynamics and systolic function in patients with apical aneurysm in the short term ,while 2D-TTE and RT-3DTEE provides a reliable basis for clinical to evaluate the effect of the PVR .

Occupational Stress and Mental Health in Staffs of Disabled Care Agencies / 中国康复理论与实践

@#Objective To investigate the occupational stress and mental health of the staffs of disabled care agency, and the main factors related. Methods The staffs were investigated with Work Stress Scale, Coping Style Questionnaire, and Symptom Checklist (SCL-90). Results The work stress was hard in the subjects with poor mental health condition. Their cope style was mainly positive and mature. Gender,levels of education, jobs, and coping styles related with the work stress, while the work stress and coping style related with the mental health. Conclusion The staffs in disabled care agency experience work stress and erious mental problems, which need to be solved.

Effects of therapy with small volume of different fluids on renal blood flow in endotoxemia rats / 中华麻醉学杂志

Objective To evaluate the effects of therapy with small volume of different fluids on renal blood flow in endotoxemia rats.Methods Thirty parthogen-free SD rats weighing 180-250 g were randomly divided into 5 groups (n = 6 each):group Ⅰ control; group Ⅱ LPS; group Ⅲ LPS + 7.5 % hypertonic saline (HS);group Ⅳ LPS + hydrozyethly starch (HES) 130/0.4 and groupⅤ LPS + hypertonic saline plus hydroxyethly starch (HS-HES) 40. The animals were anesthetized with intraperitoneal 3% pentobarbital 40 mg/kg. Left carotid artery was cannulated for BP and HR monitoring and fluid administration. In groupⅡ-Ⅴ LPS 1 mg/kg was administered via arterial cannula. In group Ⅲ, Ⅳ and V 4 ml/kg of 7.5% HS, HES 130/0.4 AND HS-HES 40 were administered via arterial cannula respectively at 30 min after LPS administration.In groupⅠ and Ⅱ normal saline 4 ml/kg was given insteadt. Renal blood flow was measured with Doppler ultrasound before LPS (T1 ,baseline), at 30 min after LPS (T2), 10, 30 and 60 min after fluid therapy (T3, T4, T5). The animals were then sacrificed and both kidneys were removed for microscopic examination with light microscope. Results Renal blood flow was significantly decreased and was significantly recovered to some extent by therapy with different fluids especially with HS-HES 40 in group Ⅴ. Conclusion Therapy with small volume of HS,HES or HS-HES could increase renal blood flow and inprove renal microcirculation especially HS-HES.

Effects of Endotoxin on Growth Activity and Gap Junction of NRK52E Cells / 中山大学学报(医学科学版)

[Objective]This study was designed to observe the effects of endotoxin(LPS)on the growth activity and gap junction(GJ)of NRK52E cells.[Methods]The NRK52E cells were divided into control group and LPS groups,and the NRK52E cells in LPS groups were treated with LPS 10 ng/mL,50 ng/mL,100 ng/mL,500 ng/mL,and 1 000 ng/mL for 24 h respectively.The NRK52E cells growth activity was measured through MTT method,and the function of gap junction of NRK52E cells was measured through the method of fluoroimmunoassay.The protein expression of connexin 43(Cx43)in control group,LPS 10 ng/mL group,and LPS 100 ng/mL group were also determined by Western blotting.[Results]①Compared with control group and LPS 10 ng/mL group,The NRK52E cells growth activity decreased significantly in LPS 50 ng/mL,100 ng/mL,500 ng/mL,and 1 000 ng/mL groups(P＜0.01).②Compared with control group,the function of GJ decreased significantly in LPS 100 ng/mL,500 ng/mL,and 1 000 ng/mL groups(P＜0.01).③There were negative correlations among the concentration of LPS and NRK52E cells growth activity and GJ function respectively(r=-0.941,-0.872,P＜0.01).④Compared with control group,the protein expression of Cx43 were decreased significantly in LPS 10 ng/mL and 100 ng/mL groups(P＜0.01).[Conclusions]LPS can inhibit the NRK52E cells growth activity in a dose-depend manner.GJ function is one of the mechanisms.

Effects of Small Volume Resuscitation with Different Fluids on Lung of Rats Undergoing Endotoxic Shock / 中山大学学报(医学科学版)

[Objective]This study was designed to investigate the effects of small volume resuscitation with different fluids on the lung of endotoxie rats.[Methods]Thirty SD rats weighting 180-250 g were divided randomly into 5 groups(n=6):Group C[lipopolysaccharide(LPS)negative control group],Group E(LPS+4 mL/kg physiologic saline),Group HSS(LPS+4 mL/kg 75 g/L hypertonic saline solution),Group HES(LPS+4 mL/kg hydroxyethyl starch 130/0.4),Group HSH(LPS+4 mL/kg 75 g/L hypertonic sodium chloride hydroxyethyl starch 40).Resuscitation was administrated 30 min after LPS injected.Pathological examination and score were made under optical microscope.Dry/wet ratios were observed.Levels of total protein of bronchoalveolar lavage fluid(BALF)were measured.Thibabituric acid(TBA)was used to measure tissue malonaldehyde(MDA)levels.Xanthine oxidase(XO)was employed to measure the tissue activity of superoxide dismutase(SOD).[Results]Compared with group C,in the other 4 groups,pathological changes were server.Levels of total protein of BALF were higher(P＜0.05).Pathological score of group E was significantly higher(P＜0.01).Dry/wet ratio of group E was lower(P＜0.05).Tissue activity of SOD of group E was lower(P＜0.01).Levels of tissue MDA in group E and HSS were significantly higher.Compared with group E,in group HSS,HES and HSH,pathological changes were slighter(P＜0.01).Pathological scores and tissue MDA levels were lower(P＜0.01).Dry/wet ratios were higher(P＜0.05).Tissue activity of SOD were higher(P＜0.01),levels of total protein of BALF were lower(P＜0.05,P＜0.01).[Conclusion]Small volume resuscitation with HSS,HES,and HSH had protective effects on the lung of endotoxie rats.HES and HSH had better effect on decreasing the capillary permeability of the lung of endotoxic rats lung compared with HSS.

Approaches of Speech Rehabilitation in Children with Autism / 中国康复理论与实践

@#One of the hallmark features of children with autism is language barrier,which mainly manifested with lack of visual contact and attention,imitation speech,broad pronunciation problems,poor understanding abilities to speech and abstract questions,deficiency of logicality,spoken language disorder,confusion about the usage of pronouns such as you,I and she or he,etc.According to the basic principles of language training,visual perception tracing,vision contact,cultivation of communication desire,auditory and understanding training can all be used to make children with autism to understand the relationship between pronunciation and words,try to pronounce syllables,make good preparation for valid pronunciation in the early stage of language training.Respiration training,point massage of oral surface and valid usage of pronunciation organs' practice can help them to say phrase and simple sentences gradually.They can say a sentence correctly and achieve the destination of grasping language through learning decorative words and enhancement of understanding and logic abilities.Very efficient result could be approached through correct evaluation,found existing problems and using correct training methods during language training of children with autism.