Author Correction: Mapping the world's free-flowing rivers.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mapping the world's free-flowing rivers.

Free-flowing rivers (FFRs) support diverse, complex and dynamic ecosystems globally, providing important societal and economic services. Infrastructure development threatens the ecosystem processes, biodiversity and services that these rivers support. Here we assess the connectivity status of 12 million kilometres of rivers globally and identify those that remain free-flowing in their entire length. Only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length and 23 per cent flow uninterrupted to the ocean. Very long FFRs are largely restricted to remote regions of the Arctic and of the Amazon and Congo basins. In densely populated areas only few very long rivers remain free-flowing, such as the Irrawaddy and Salween. Dams and reservoirs and their up- and downstream propagation of fragmentation and flow regulation are the leading contributors to the loss of river connectivity. By applying a new method to quantify riverine connectivity and map FFRs, we provide a foundation for concerted global and national strategies to maintain or restore them.

Abnormal Bifurcation of the Double Binding Energy Differences and Proton-Neutron Pairing: Nuclei Close to N=Z Line from Ni to Rb.

The recently observed abnormal bifurcation of the double binding energy differences δV_{pn} between the odd-odd and even-even nuclei along the N=Z line from Ni to Rb has challenged the nuclear theories. To solve this problem, a shell-model-like approach based on the relativistic density functional theory is established, by treating simultaneously the neutron-neutron, proton-neutron, and proton-proton pairing correlations both microscopically and self-consistently. Without any ad hoc parameters, the calculated results well reproduce the observations, and the mechanism for this abnormal bifurcation is found to be due to the enhanced proton-neutron pairing correlations in the odd-odd N=Z nuclei, compared with the even-even ones. The present results provide an excellent interpretation for the abnormal δV_{pn} bifurcation, and provide a clear signal for the existence of the proton-neutron pairing correlations for nuclei close to the N=Z line.

Evidence for Chiral Wobbler in Nuclei.

Three ΔI=1 bands with the πg_{9/2}⊗νg_{9/2} configuration have been identified in _{35}^{74}Br_{39}. Angular distribution, linear polarization, and lifetime measurements were performed to determine the multipolarity, type, mixing ratio, and absolute transition probability of the transitions. By comparing these experimental observations with the corresponding fingerprints and the quantum particle rotor model calculations, the second and third lowest bands are, respectively, suggested as the chiral partner and one-phonon wobbling excitation built on the yrast band. The evidence indicates the first chiral wobbler in nuclei.

Two-Stage Treatment Protocol of Fungal Periprosthetic Hip and Knee Joint Infections: the Clinical Experience from a Single Center Experience.

PURPOSE OF THE STUDY: To evaluate the clinical results and safety of fungal periprosthetic joint Infections (fPJIs) using two-stage treatment protocol. MATERIAL AND METHODS: 8 patients with fPJIs (3 hips and 5 knees) using two-stage revision were reviewed retrospectively and followed up at least 2 years. The preoperative demographic data, two-stage treatment protocol, results of microbiology and histologic workup and postoperative follow-up results (reimplantation success rate and infection free time) were recorded. RESULTS: 7 patients got successful reimplantation, with a 75% reimplantation success rate. Two patients got knee arthrodesis eventually. All patients were infection free with a median follow-up of 4.0 ± 2.0 years (range, 2-7 years). Of them, Candida species were found in 7 patients, while non-Candida specimen was only isolated in 1 patient with Aspergillus. Only 2 patients had coexisting bacterial infection (Methicillin-resistant coagulase-negative Staphylococci and Proteus mirabilis respectively). The average interval between the initial surgery and diagnosis of fPJIs was 21.50±34.79 months (range, 4-104 months). The mean time of spacer implantation was 7.75±2.77 months (range, 6-14 months). None serious complication or above knee amputation was found. DISCUSSION: fPJIs are very rare and considerable challenge after total hip or knee arthroplasty. The goal of therapy is to eradicate local infection and maintain function. Candida species were the most common pathogen. The duration between spacer placement and staged reimplantation was highly variable, and generally dependent upon the results of joint aspirates and infl ammatory markers. The current study shows that the two-stage treatment protocol is recommended for fungal periprosthetic hip and knee joint infections. CONCLUSIONS: The two-stage treatment protocol is recommended for fungal periprosthetic hip and knee joint infections. The safety and effi cacy of biantibiotical impregnated (antifungal + antibiotics) cement spacer is confi rmed. Further evidence-based work is needed to determine the optimal drug dose and reimplantation time. KEY WORDS: two-stage treatment protocol, fungal periprosthetic infections, hip spacer, knee spacer.

[Experimental study on the inhibition of the NLRP3 signaling pathway with Shengsan Jiedu Huayu decoction to alleviate inflammatory injury in rats with acute-on-chronic liver failure].

Objective: To observe the therapeutic effect of Shengsan Jiedu Huayu decoction in alleviating inflammatory liver injury in rats with acute-on-chronic liver failure (ACLF) and its effect on the activation intensity for the NLRP3 signaling pathway. Methods: 63 SD rats were randomly divided into a blank group, a model group, and low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction (7.29 g/kg/d, 14.58 g/kg/d, and 29.16 g/kg/d). The ACLF rat model was replicated using carbon tetrachloride combined with d-galactosamine and lipopolysaccharide. Different dose gradients of the Shengsan Jiedu Huayu decoction were used for a five-day intervention treatment, and then rat serum and tissue samples were collected. A biochemical analyzer was used to detect the serum levels of ALT, AST, and TBIL in rats. ELISA was used to detect serum IL-18 and IL-1ß content. HE staining was used to observe histomorphological changes in liver tissue. Immunohistochemistry was used to detect GSDMD expression in liver tissue. Western blot and PCR were used to detect NLRP3, Caspase1, ASC, TLR4, IL-1ß, IL-18 protein, and mRNA expression levels.The groups were compared using analysis of variance and the rank-sum test. Results: Compared with the blank group, the model group's rat liver tissue was severely injured. Serum levels of ALT, AST, and TBIL, inflammatory factors IL-1ß and IL-18, and the GSDMD protein expression level, NLRP3 expression level, TLR4, caspase 1, ASC, IL-1ß, IL-18 protein, and mRNA (P<0.01) were all significantly increased in the model than the blank group (P<0.01). Additionally, compared with the model group, the low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction had improved liver tissue injury in ACLF rats, while the serum levels of ALT, AST, TBIL, IL-1ß, IL-18, liver tissue GSDMD protein, NLRP3, TLR4, caspase 1, and ASC expressions were all lower in the different dose gradients of the Shengsan Jiedu Huayu decoction than the model group, with the most evident reduction in the high-dose group (P<0.01). Conclusion: Shengsan Jiedu Huayu decoction can weaken the activation intensity of the NLRP3 signaling pathway, alleviate liver tissue pathological injury, reduce inflammatory factor release, and alleviate inflammatory liver injury in ACLF rats.

[Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial].

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

[Airborne fungi monitoring].

Airborne fungi are an important class of aeroallergens that can lead to the development of allergic rhinitis and asthma, and reducing the exposure of fungi is an important strategy to prevent the exacerbation of symptoms in individuals with fungal allergy. Therefore, monitoring airborne fungi and understanding their dispersion patterns are important for clinical diagnosis, treatment and prevention. The purpose of this article is to review the methods of airborne fungi monitoring and factors influencing the distribution and dispersal of airborne fungi.

[Tajectories of the self-efficacy of HIV testing among MSM based on latent class growth model].

Objective: To analyze the trajectories of HIV testing self-efficacy among men who have sex with men (MSM) based on latent class growth model. Methods: From August 2019 to May 2021, 404 MSM were recruited in Shandong Province and subjected to a 1-year follow-up study with individual intervention (pushing intervention pictures and videos in WeChat and follow-up questionnaires) and community intervention (forwarding to friends and sharing and discussing HIV testing-related information in WeChat groups). The level of HIV testing self-efficacy among MSM was measured. The long-term trend of HIV testing self-efficacy was analyzed using the latent class growth model (LCGM), and the influencing factors of the trend were analyzed. Results: A total of 404 MSM were (28.25±8.95) years old, with the oldest being 58 and the youngest being 18. The scores of HIV testing self-efficacy M(Q1, Q3) at baseline and 4 follow-ups were 18.00 (17.00, 21.00), 19.00 (18.00, 22.00), 19.00 (18.00, 22.00), 19.00 (18.00, 22.00) and 19.00 (18.00, 22.00). The results of the freely estimated two-category LCGM model showed that the trend of HIV testing self-efficacy among MSM could be divided into two classes, "intervention response group" [255(63.1%)] and "intervention non-response group" [149(36.9%)]. The former had a higher level of HIV testing self-efficacy which tended to increase at first and then decrease over time, while the latter had a lower and more stable level. The results of the multifactorial logistic regression analysis showed that the OR values of MSM in business or service and jobless or unemployed were 0.261 (95%CI: 0.108-0.633) and 0.186 (95%CI: 0.057-0.610), respectively, using the students as the reference group. Conclusion: There is a group heterogeneity in the trend of HIV testing self-efficacy in the intervention conditions among MSM, and occupation may be an influencing factor.

[Standardized diagnosis results of suspected local anesthetics allergy].

To review and investigate the diagnosis results of local anesthetics (LA) allergy and improve the understanding of LA allergy in clinician. From March 2017 to February 2022, a total of 24 patients were investigated in Allergy Center of West China Hospital,Sichuan University on suspicion of LA allergy. Clinical data and results of skin tests and drug provocation tests (DPT) with the suspected drugs were retrospectively evaluated. The value of standardized diagnostic protocol in the LA allergy were analyzed. The results showed that 24 patients (3 men/21 women) were included with age range from 20 to 74 years. Three cases (12.5%) were positive in previous LA skin tests and proved to be tolerated through standardized tests. Twenty-one patients were initially diagnosed as "LA allergy" because of adverse reactions after previous use of LA, including 20 cases of immediate-type reaction and 1 case of delayed-type reaction. Three cases were considered LA allergy through standardized diagnosis approaches, including skin tests and DPT. One patient was diagnosed with anaphylaxis caused by chlorhexidine. Of the remaining 17 patients, 7 were considered as psychosomatic reactions (29.1%), 3 of sympathetic nervous system conditions (12.5%), 1 of spontaneous urticaria (4.2%), 2 of vasovagal syncope (8.3%), drug side effects (8.3%), skin irritation (8.3%), respectively. In conclusion, true allergic reactions to LA are rare. Through standardized skin tests and DPT, allergy can be ruled out in the vast majority of patients who complain of "LA allergy". For patients who are highly suspected of LA inducing anaphylaxis, other local anesthetics that can be used as safe alternatives should be determined by diagnostic tests according to future needs.

[Predictive value of left ventricular ejection fraction reserve assessed by SPECT G-MPI for major adverse cardiovascular event in patients with coronary artery disease].

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.

[Predictive value of the proportion of hibernating myocardium in total perfusion defect on reverse remodeling in patients with HFrEF underwent coronary artery bypass graft].

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with 18F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with 18F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and 18F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and 18F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.

[Three cases of occupational acute trimethyltin chloride poisoning].

Trimethyltin chloride is a highly toxic substance, which is absorbed through respiratory tract, skin and digestive tract, with central nervous system injury as the main clinical manifestations, and can be accompanied by damage to various organs. In this paper, the treatment process of 3 patients with acute trimethyltin chloride poisoning was reviewed, and their clinical manifestations, auxiliary examination, diagnosis and treatment were analyzed. Three patients were misdiagnosed as mental abnormality, encephalitis, and hepatic encephalopathy in different hospitals in the early stage of medical treatment, suggesting that clinicians should pay attention to the occupational contact history of poisoned patients and conduct toxicant detection in time to avoid misdiagnosis and mistreatment.

Genomic Epidemiology of Salmonella enterica Circulating in Surface Waters Used in Agriculture and Aquaculture in Central Mexico.

Salmonella enterica can survive in surface waters (SuWa), and the role of nonhost environments in its transmission has acquired increasing relevance. In this study, we conducted comparative genomic analyses of 172 S. enterica isolates collected from SuWa across 3 months in six states of central Mexico during 2019. S. enterica transmission dynamics were assessed using 87 experimental and 112 public isolates from Mexico collected during 2002 through 2019. We also studied genetic relatedness between SuWa isolates and human clinical strains collected in North America during 2005 through 2020. Among experimental isolates, we identified 41 S. enterica serovars and 56 multilocus sequence types (STs). Predominant serovars were Senftenberg (n = 13), Meleagridis, Agona, and Newport (n = 12 each), Give (n = 10), Anatum (n = 8), Adelaide (n = 7), and Infantis, Mbandaka, Ohio, and Typhimurium (n = 6 each). We observed a high genetic diversity in the sample under study, as well as clonal dissemination of strains across distant regions. Some of these strains are epidemiologically important (ST14, ST45, ST118, ST132, ST198, and ST213) and were genotypically close to those involved in clinical cases in North America. Transmission network analysis suggests that SuWa are a relevant source of S. enterica (0.7 source/hub ratio) and contribute to its dissemination as isolates from varied sources and clinical cases have SuWa isolates as common ancestors. Overall, the study shows that SuWa act as reservoirs of various S. enterica serovars of public health significance. Further research is needed to better understand the mechanisms involved in SuWa contamination by S. enterica, as well as to develop interventions to contain its dissemination in food production settings. IMPORTANCE Surface waters are heavily used in food production worldwide. Several human pathogens can survive in these waters for long periods and disseminate to food production environments, contaminating our food supply. One of these pathogens is Salmonella enterica, a leading cause of foodborne infections, hospitalizations, and deaths in many countries. This research demonstrates the role of surface waters as a vehicle for the transmission of Salmonella along food production chains. It also shows that some strains circulating in surface waters are very similar to those implicated in human infections and harbor genes that confer resistance to multiple antibiotics, posing a risk to public health. This study contributes to expand our current knowledge on the ecology and epidemiology of Salmonella in surface waters.

Roles of the protein disulphide isomerases AccPDIA1 and AccPDIA3 in response to oxidant stress in Apis cerana cerana.

Protein disulphide isomerase (PDI) plays an important role in a variety of physiological processes through its oxidoreductase activity and molecular chaperone activity. In this study, we cloned two PDI family members, AccPDIA1 and AccPDIA3, from Apis cerana cerana. AccPDIA1 and AccPDIA3 had typical sequence features of PDI family members and were constitutively expressed in A. cerana cerana. The expression levels of AccPDIA1 and AccPDIA3 were generally upregulated after treatment with a variety of environmental stress factors. Inhibition assays showed that E. coli expressing recombinant AccPDIA1 and AccPDIA3 proteins was more resistant to oxidative stress than control E. coli. In addition, silencing AccPDIA1 or AccPDIA3 in A. cerana cerana resulted in significant changes in the expression levels of several antioxidant-related genes as well as the enzymatic activities of peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) and reduced the survival rate of A. cerana cerana under oxidative stress caused by high temperature. In conclusion, our results suggest that AccPDIA1 and AccPDIA3 may play important roles in the antioxidant activities of A. cerana cerana.

Dynamical Synthesis of

In the exothermic process of fission decay, an atomic nucleus splits into two or more independent fragments. Several aspects of nuclear fission are not properly understood, in particular the formation of the neck between the nascent fragments, and the subsequent mechanism of scission into two or more independent fragments. Using an implementation of time-dependent density functional theory, based on a relativistic energy density functional and including pairing correlations, we analyze the final phase of the process of induced fission of ^{240}Pu, and show that the timescale of neck formation coincides with the assembly of two α-like clusters. Because of its much larger binding energy, the dynamical synthesis of ^{4}He in the neck predominates over other light clusters, e.g., ^{3}H and ^{6}He. At the instant of scission the neck ruptures exactly between the two α-like clusters, which separate because of the Coulomb repulsion and are eventually absorbed by the two emerging fragments. The mechanism of light charged clusters formation at scission could also be linked to ternary fission.

Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE): Phase 2.

INTRODUCTION: Mortality is associated with long-term exposure to fine particulate matter (particulate matter ≤2.5 µm in aerodynamic diameter; PM2.5), although the magnitude and form of these associations remain poorly understood at lower concentrations. Knowledge gaps include the shape of concentration-response curves and the lowest levels of exposure at which increased risks are evident and the occurrence and extent of associations with specific causes of death. Here, we applied improved estimates of exposure to ambient PM2.5 to national population-based cohorts in Canada, including a stacked cohort of 7.1 million people who responded to census year 1991, 1996, or 2001. The characterization of the shape of the concentration-response relationship for nonaccidental mortality and several specific causes of death at low levels of exposure was the focus of the Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE) Phase 1 report. In the Phase 1 report we reported that associations between outdoor PM2.5 concentrations and nonaccidental mortality were attenuated with the addition of ozone (O3) or a measure of gaseous pollutant oxidant capacity (Ox), which was estimated from O3 and nitrogen dioxide (NO2) concentrations. This was motivated by our interests in understanding both the effects air pollutant mixtures may have on mortality and also the role of O3 as a copollutant that shares common sources and precursor emissions with those of PM2.5. In this Phase 2 report, we further explore the sensitivity of these associations with O3 and Ox, evaluate sensitivity to other factors, such as regional variation, and present ambient PM2.5 concentration-response relationships for specific causes of death. METHODS: PM2.5 concentrations were estimated at 1 km2 spatial resolution across North America using remote sensing of aerosol optical depth (AOD) combined with chemical transport model (GEOS-Chem) simulations of the AOD:surface PM2.5 mass concentration relationship, land use information, and ground monitoring. These estimates were informed and further refined with collocated measurements of PM2.5 and AOD, including targeted measurements in areas of low PM2.5 concentrations collected at five locations across Canada. Ground measurements of PM2.5 and total suspended particulate matter (TSP) mass concentrations from 1981 to 1999 were used to backcast remote-sensing-based estimates over that same time period, resulting in modeled annual surfaces from 1981 to 2016.Annual exposures to PM2.5 were then estimated for subjects in several national population-based Canadian cohorts using residential histories derived from annual postal code entries in income tax files. These cohorts included three census-based cohorts: the 1991 Canadian Census Health and Environment Cohort (CanCHEC; 2.5 million respondents), the 1996 CanCHEC (3 million respondents), the 2001 CanCHEC (3 million respondents), and a Stacked CanCHEC where duplicate records of respondents were excluded (Stacked CanCHEC; 7.1 million respondents). The Canadian Community Health Survey (CCHS) mortality cohort (mCCHS), derived from several pooled cycles of the CCHS (540,900 respondents), included additional individual information about health behaviors. Follow-up periods were completed to the end of 2016 for all cohorts. Cox proportional hazard ratios (HRs) were estimated for nonaccidental and other major causes of death using a 10-year moving average exposure and 1-year lag. All models were stratified by age, sex, immigrant status, and where appropriate, census year or survey cycle. Models were further adjusted for income adequacy quintile, visible minority status, Indigenous identity, educational attainment, labor-force status, marital status, occupation, and ecological covariates of community size, airshed, urban form, and four dimensions of the Canadian Marginalization Index (Can-Marg; instability, deprivation, dependency, and ethnic concentration). The mCCHS analyses were also adjusted for individual-level measures of smoking, alcohol consumption, fruit and vegetable consumption, body mass index (BMI), and exercise behavior.In addition to linear models, the shape of the concentration-response function was investigated using restricted cubic splines (RCS). The number of knots were selected by minimizing the Bayesian Information Criterion (BIC). Two additional models were used to examine the association between nonaccidental mortality and PM2.5. The first is the standard threshold model defined by a transformation of concentration equaling zero if the concentration was less than a specific threshold value and concentration minus the threshold value for concentrations above the threshold. The second additional model was an extension of the Shape Constrained Health Impact Function (SCHIF), the eSCHIF, which converts RCS predictions into functions potentially more suitable for use in health impact assessments. Given the RCS parameter estimates and their covariance matrix, 1,000 realizations of the RCS were simulated at concentrations from the minimum to the maximum concentration, by increments of 0.1 µg/m3. An eSCHIF was then fit to each of these RCS realizations. Thus, 1,000 eSCHIF predictions and uncertainty intervals were determined at each concentration within the total range.Sensitivity analyses were conducted to examine associations between PM2.5 and mortality when in the presence of, or stratified by tertile of, O3 or Ox. Additionally, associations between PM2.5 and mortality were assessed for sensitivity to lower concentration thresholds, where person-years below a threshold value were assigned the mean exposure within that group. We also examined the sensitivity of the shape of the nonaccidental mortality-PM2.5 association to removal of person-years at or above 12 µg/m3 (the current U.S. National Ambient Air Quality Standard) and 10 µg/m3 (the current Canadian and former [2005] World Health Organization [WHO] guideline, and current WHO Interim Target-4). Finally, differences in the shapes of PM2.5-mortality associations were assessed across broad geographic regions (airsheds) within Canada. RESULTS: The refined PM2.5 exposure estimates demonstrated improved performance relative to estimates applied previously and in the MAPLE Phase 1 report, with slightly reduced errors, including at lower ranges of concentrations (e.g., for PM2.5 <10 µg/m3).Positive associations between outdoor PM2.5 concentrations and nonaccidental mortality were consistently observed in all cohorts. In the Stacked CanCHEC analyses (1.3 million deaths), each 10-µg/m3 increase in outdoor PM2.5 concentration corresponded to an HR of 1.084 (95% confidence interval [CI]: 1.073 to 1.096) for nonaccidental mortality. For an interquartile range (IQR) increase in PM2.5 mass concentration of 4.16 µg/m3 and for a mean annual nonaccidental death rate of 92.8 per 10,000 persons (over the 1991-2016 period for cohort participants ages 25-90), this HR corresponds to an additional 31.62 deaths per 100,000 people, which is equivalent to an additional 7,848 deaths per year in Canada, based on the 2016 population. In RCS models, mean HR predictions increased from the minimum concentration of 2.5 µg/m3 to 4.5 µg/m3, flattened from 4.5 µg/m3 to 8.0 µg/m3, then increased for concentrations above 8.0 µg/m3. The threshold model results reflected this pattern with -2 log-likelihood values being equal at 2.5 µg/m3 and 8.0 µg/m3. However, mean threshold model predictions monotonically increased over the concentration range with the lower 95% CI equal to one from 2.5 µg/m3 to 8.0 µg/m3. The RCS model was a superior predictor compared with any of the threshold models, including the linear model.In the mCCHS cohort analyses inclusion of behavioral covariates did not substantially change the results for both linear and nonlinear models. We examined the sensitivity of the shape of the nonaccidental mortality-PM2.5 association to removal of person-years at or above the current U.S. and Canadian standards of 12 µg/m3 and 10 µg/m3, respectively. In the full cohort and in both restricted cohorts, a steep increase was observed from the minimum concentration of 2.5 µg/m3 to 5 µg/m3. For the full cohort and the <12 µg/m3 cohort the relationship flattened over the 5 to 9 µg/m3 range and then increased above 9 µg/m3. A similar increase was observed for the <10 µg/m3 cohort followed by a clear decline in the magnitude of predictions over the 5 to 9 µg/m3 range and an increase above 9 µg/m3. Together these results suggest that a positive association exists for concentrations >9 µg/m3 with indications of adverse effects on mortality at concentrations as low as 2.5 µg/m3.Among the other causes of death examined, PM2.5 exposures were consistently associated with an increased hazard of mortality due to ischemic heart disease, respiratory disease, cardiovascular disease, and diabetes across all cohorts. Associations were observed in the Stacked CanCHEC but not in all other cohorts for cerebrovascular disease, pneumonia, and chronic obstructive pulmonary disease (COPD) mortality. No significant associations were observed between mortality and exposure to PM2.5 for heart failure, lung cancer, and kidney failure.In sensitivity analyses, the addition of O3 and Ox attenuated associations between PM2.5 and mortality. When analyses were stratified by tertiles of copollutants, associations between PM2.5 and mortality were only observed in the highest tertile of O3 or Ox. Across broad regions of Canada, linear HR estimates and the shape of the eSCHIF varied substantially, possibly reflecting underlying differences in air pollutant mixtures not characterized by PM2.5 mass concentrations or the included gaseous pollutants. Sensitivity analyses to assess regional variation in population characteristics and access to healthcare indicated that the observed regional differences inconcentration-mortality relationships, specifically the flattening of the concentration-mortality relationship over the 5 to 9 µg/m3 range, was not likely related to variation in the makeup of the cohort or its access to healthcare, lending support to the potential role of spatially varying air pollutant mixtures not sufficiently characterized by PM2.5 mass concentrations. CONCLUSIONS: In several large, national Canadian cohorts, including a cohort of 7.1 million unique census respondents, associations were observed between exposure to PM2.5 with nonaccidental mortality and several specific causes of death. Associations with nonaccidental mortality were observed using the eSCHIF methodology at concentrations as low as 2.5 µg/m3, and there was no clear evidence in the observed data of a lower threshold, below which PM2.5 was not associated with nonaccidental mortality.

Assessment of Patient Satisfaction Among Cancer Patients Undergoing Radiotherapy.

The patient-provider relationship is a key driver of patient satisfaction as it relates to overall healthcare experience. We surveyed patients undergoing radiation therapy to determine what they consider to be the most valued qualities in their interactions with the healthcare team. An ethics-approved 35-item patient satisfaction survey was developed in-house to gain insights on patients' perception of their relationship with the healthcare team throughout their cancer journey. There were 199 completed survey, median age 68 years, 54% women and 45% men. Almost all (95%) "agreed" or "strongly agreed" that their physicians had been sensitive and compassionate. Over 90% felt that they received adequate explanations about their treatment, and had their questions answered. The vast majority (93%) felt included in the decision-making process. Patients reported the 5 most highly rated qualities among their healthcare providers (HCPs) as knowledge, kindness, honesty, good communication, and a cheerful attitude. Overall satisfaction was high but areas for improvement were identified including being offered future appointments for further discussion, more information about clinical trials, other treatments, and community resources. Patients noted their HCPs tended to focus on the physical and emotional needs of patients, but spiritual and cultural needs were rarely addressed. Patients receiving radiotherapy reported high rates of satisfaction across many aspects of their care. These findings also reinforce the different aspects of holistic care that can be improved, and serve as a reminder to clinicians that patients perceive their role as more than just that of a medical expert.

[The influence of residual astigmatism on the postoperative visual quality in patients with implantation of an extended depth of focus intraocular lens].

Objective: To investigate the influence of residual astigmatism on the postoperative visual acuity in cataract patients with implantation of an extended depth of focus intraocular lens (IOL). Methods: Retrospective cohort study. A total of 56 eyes of 56 cataract patients who underwent phacoemulsification combined with extended depth of focus IOL implantation from January 2019 to December 2020 at Eye & ENT Hospital of Fudan University were included. There were 29 males and 27 females in all patients, and the age was (65±9) years. Patients were divided into two groups according to their postoperative residual astigmatism: low astigmatism group (<0.75 D, 28 eyes) and high astigmatism group (0.75 to 1.50 D, 28 eyes). At 3 months after surgery, measurements were completed, including postoperative uncorrected distance (5 m) visual acuity, uncorrected intermediate (80 cm) visual acuity, uncorrected near (40 cm) visual acuity, best corrected visual acuity (all the visual acuity was converted to the logarithm of the minimum angle of resolution visual acuity), defocus curves, quick contrast sensitivity function, wavefront aberration, and VF-14 questionnaire scores. The independent samples t-test and Mann-Whitney U test were used for data analysis. Results: The low astigmatism group and high astigmatism group's uncorrected distance visual acuity [M (Q1, Q3)] were 0.05 (-0.06, 0.10), 0.08 (0.00, 0.22), their uncorrected intermediate visual acuity were 0.11 (0.00, 0.20), 0.14 (0.10, 0.21), their uncorrected near visual acuity were 0.28 (0.20, 0.32), 0.26 (0.20, 0.30), and their best corrected visual acuity were 0.17 (0.05, 0.30), 0.14 (0.04, 0.22), respectively. The differences were not statistically significant (all P>0.05). No significant difference was found in the defocus curves from +1.00 to -4.00 D, at intervals of +0.50 D, between the two groups (all P>0.05). No significant difference was found in the quick contrast sensitivity of low, middle and high frequency of dark vision between the low astigmatism group and high astigmatism group (all P>0.05), and the area under Log contrast sensitivity function of the two groups were 0.87±0.28 and 0.77±0.30 (P>0.05). The total whole-eye aberrations were 0.59±0.18 and 0.74±0.51, and the total higher-order aberrations were 0.30±0.13 and 0.37±0.25 in the two groups at 4.0-mm pupil diameter. The differences were not statistically significant when the total whole-eye aberration, total higher-order aberration, coma, cloverleaf aberration, and spherical aberration were compared (all P>0.05). The differences of the total VF-14 visual scores, near visual acuity scores and the distance visual acuity scores of the two groups were not statistically significant (all P>0.05). Conclusion: Cataract patients with residual postoperative astigmatism 0.75 to 1.50 D can obtain as good visual quality as those with postoperative residual astigmatism<0.75 D after implantation of an extended depth of focus IOL.

[Comparison of tolerance to decentration and tilt in the early postoperative period between the continuous range and bifocal intraocular lens implantation in myopic eyes].

Objective: To compare decentration and tilt tolerances between continuous range intraocular lens (IOL) and bifocal IOL in myopia during the early stages post intraocular implantation. Method: A retrospective cohort study was conducted using follow-up data of 145 patients (145 eyes) who underwent phacoemulsification combined with IOL implantation in the Eye & ENT Hospital of Fudan University from January 2018 to December 2020. According to whether the axial length was less than 24.5 mm, patients were divided into non-myopic and myopic groups. According to IOL type, patients were divided into extend depth of focus (EDOF) ZXR00 IOL group (myopic 38 eyes, non-myopic 41 eyes) and bifocal ZMB00 IOL group (myopic 23 eyes, non-myopic 43 eyes). The distance and near visual acuity (log of the minimum angle of resolution visual acuity), IOL tilt and decentration, intraocular high-order aberration (HOA), coma, trefoil, spherical aberrations, modulation transfer function (MTF), as well as VF-14 index and the incidence of dysphotopsia were compared between the 2 groups at 3 months after surgery. Statistics were performed using Student's t-test, χ2 test, Pearson correlation analysis and multiple linear regression analysis. Results: In either the myopic or non-myopic group, no significant differences were found in age, gender, eye laterality, axial length and IOL degree between eyes with the two different types of IOLs (all P>0.05). At 3 months after surgery, there was no significant difference in uncorrected and best-corrected distance visual acuity between the ZXR00 IOL group and the ZXR00 IOL group, while uncorrected near visual acuity was better in the ZMB00 IOL group than the ZXR00 IOL group (t=10.41, P<0.01). The total postoperative IOL decentration in the ZXR00 IOL group and ZMB00 IOL group in myopic eyes were (0.32±0.17) and (0.38±0.16) mm, respectively, which were greater than those in non-myopic eyes [(0.22±0.12), (0.28±0.12) mm; t=3.16, 2.57; both P<0.05]. However, there were no significant differences in IOL tilt between myopic and non-myopic eyes in the 2 groups (both P>0.05). There were no significant differences in postoperative IOL tilt and decentration between the 2 groups regardless of myopia or non-myopia (all P>0.05). In myopic eyes, HOA, coma aberration and spherical aberration in the ZXR00 IOL group were significantly lower than those in the ZMB00 IOL group, while the total ocular MTF (38.15±10.12) was significantly higher than that in the ZMB00 IOL group (30.46±10.53) (all P<0.05). Pearson correlation analysis and multiple linear regression analysis showed a positive correlation between postoperative HOA and both IOL tilt and decentration in the ZMB00 IOL group (r=0.627, 0.726; ß=0.446, 0.587; all P<0.01). However, no such relationship was found in the ZXR00 IOL group (all P>0.05). In myopic eyes, when the IOL tilt aberration and decentration were greater than the median, the HOAs in the ZXR00 IOL group [(0.33±0.14), (0.27±0.11) µm] were lower than those in the ZMB00 IOL group [(0.88±0.56), (0.96±0.45) µm], while the total ocular MTF (42.87±10.97, 40.22±9.30) were higher than those in the ZMB00 IOL group (25.02±8.99, 29.87±10.19) (all P<0.05). In myopic eyes, the proportion of patients with visual interference symptoms in the ZXR00 IOL group [42.11% (16/38)] was significantly lower than that in the ZMB00 IOL group [78.26%(18/23), χ²=7.59, P<0.05]. Conclusion: During the early stages after IOL implantation in myopic eyes, EDOF IOL is more tolerant to decentration and tilt than bifocal IOL.