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Aortic stenosis (AS) is a serious and complex condition, for which optimal management continues to evolve rapidly. An understanding of current clinical practice guidelines is critical to effective patient care and shared decision-making. This state of the art review of the 2021 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines and 2020 American College of Cardiology/American Heart Association Guidelines compares their recommendations for AS based on the evidence to date. The European and American guidelines were generally congruent with the exception of three key distinctions. First, the European guidelines recommend intervening at a left ventricular ejection fraction of 55%, compared with 60% over serial imaging by the American guidelines for asymptomatic patients. Second, the European guidelines recommend a threshold of ≥65 years for surgical bioprosthesis, whereas the American guidelines employ multiple age categories, providing latitude for patient factors and preferences. Third, the guidelines endorse different age cut-offs for transcatheter vs. surgical aortic valve replacement, despite limited evidence. This review also discusses trends indicating a decreasing proportion of mechanical valve replacements. Finally, the review identifies gaps in the literature for areas including transcatheter aortic valve implantation in asymptomatic patients, the appropriateness of Ross procedures, concomitant coronary revascularization with aortic valve replacement, and bicuspid AS. To summarize, this state of the art review compares the latest European and American guidelines on the management of AS to highlight three areas of divergence: timing of intervention, valve selection, and surgical vs. transcatheter aortic valve replacement criteria.

Life cycle cost analysis (LCCA) plays an essential role in the economic sustainability assessment of buildings, and building information modeling (BIM) offers a potentially valuable approach to fulfilling its requirement. However, the state of LCCA based on BIM is unclear despite previously published works. Therefore, this paper aims to address this gap by reviewing 45 relevant peer-reviewed articles through a systematic literature search, selection, and assessment. The results show that three data exchange methods integrate BIM and LCCA through data input, calculation, and output. Precision management, optimization measures, and parameter analysis through BIM significantly improve the value of buildings. Also, a methodological framework is summarized that combines LCC with other indicators based on BIM to consider economic, environmental, and social impacts, which can be monetized to assess life cycle sustainability costs. These findings provide insights for scholars and practitioners.

Randomized trials have compared percutaneous coronary intervention and coronary artery bypass grafting (CABG) in patients with left main coronary artery disease undergoing nonemergent revascularization. However, there is a paucity of real-world contemporary observational studies comparing percutaneous coronary intervention (PCI) and CABG.To compare the long-term clinical outcomes of CABG versus PCI in patients with left main coronary disease.Clinical and administrative databases for Ontario, Canada, were linked to obtain records of all patients with angiographic evidence of left main coronary artery disease (≥50% stenosis) treated with either isolated CABG or PCI from 2008 to 2020. Emergent, cardiogenic shock, and ST-segment elevation myocardial infarction patients were excluded. Baseline characteristics of patients were compared and 1:1 propensity score matching was performed. Late mortality and major adverse cardiac and cerebrovascular events were compared between the matched groups using a Cox proportional hazard model.After exclusions, 1,299 and 21,287 patients underwent PCI and CABG, respectively. Prior to matching, PCI patients were older (75.2 vs 68.0 years) and more likely to be women (34.6% vs 20.1%), although they had less CAD burden. Propensity score matching on 25 baseline covariates yielded 1,128 well-matched pairs. There was no difference in early mortality between PCI and CABG (5.5% vs 3.9%; P = 0.075). Over 7-year follow-up, all-cause mortality (53.6% vs 35.2%; HR: 1.63; 95% CI: 1.42-1.87; P 0.001) and major adverse cardiac and cerebrovascular events (66.8% vs 48.6%; HR: 1.77; 95% CI: 1.57-2.00) were significantly higher with PCI than CABG.CABG was the most common revascularization strategy in this real-world registry. Patients undergoing PCI were much older and of higher risk at baseline. After matching, there was no difference in early mortality but improved late survival and freedom from major adverse cardiac and cerebrovascular events with CABG.

Corn is an example of an agricultural grain with a specific combustibility level and can promote smoldering fires during storage. This paper conducts an experimental design to numerically evaluate how three parameters, namely particle size, moisture, and air ventilation, influence the smoldering velocity. The work methodology is based on Minitab’s experimental design, which defined the number of experiments. First, a pile of corn is heated by a hot plate and a set of thermocouples registers all temperature variations. Then, a full-factorial experiment is implemented in Minitab to analyze the smoldering, which provides a mathematical equation to represent the smoldering velocity. The results indicate that particle size is the most influential factor in the reaction, with 35% and 45% variation between the dried and wet samples. Moreover, comparing the influence of moisture between corn flour and corn powder samples, a variation of 19% and 31% is observed; additionally, analyzing the ventilation as the only variant, we noticed variations of 15% and 17% for dried and wet corn flour, and 27% and 10% for dried and wet corn powder. Future studies may use the experimental design of this work to standardize the evaluation methodology and more effectively evaluate the relevant influencing factors.

Introduction Gastrointestinal mucositis (GIM) is a side effect of high-dose irinotecan (CPT-11), causing debilitating symptoms that are often poorly managed. The role of TLR4 in the development of GIM has been clearly demonstrated. We, therefore, aimed to investigate the potential of the TLR4 antagonist, IAXO-102, to attenuate gastrointestinal inflammation as well as supress tumour activity in a colorectal-tumour-bearing mouse model of GIM induced by CPT-11. Methods 24 C57BL/6 mice received a vehicle, daily i.p. IAXO-102 (3 mg/kg), i.p. CPT-11 (270 mg/kg) or a combination of CPT-11 and IAXO-102. GIM was assessed using validated toxicity markers. At 72 h, colon and tumour tissue were collected and examined for histopathological changes and RT-PCR for genes of interest; TLR4, MD-2, CD-14, MyD88, IL-6, IL-6R, CXCL2, CXCR1, and CXCR2. Results IAXO-102 prevented diarrhoea in mice treated with CPT-11. Tumour volume in IAXO-102-treated mice was lower compared to vehicle at 48 h (P P P > 0.05). In the colon, there was a difference in transcript expression in vehicle vs. IAXO-102 (P P Conclusion IAXO-102 was able to attenuate symptomatic parameters of GIM induced by CPT-11 as well as reduce tissue injury in the colon. However, there was no effect on cell proliferation and apoptosis. As such, TLR4 activation plays a partial role in GIM development but further research is required to understand the specific inflammatory signals underpinning tissue-level changes.

Activation of toll-like receptor 4 (TLR4) has been shown to be a major influence on the inflammatory signalling pathways in intestinal mucositis (IM), as demonstrated by TLR4 knock-out mice. Pharmacological TLR4 inhibition has thus been postulated as a potential new therapeutic approach for the treatment of IM but specific TLR4 inhibitors have yet to be investigated. As such, we aimed to determine whether direct TLR4 antagonism prevents inflammation in pre-clinical experimental models of IM. The non-competitive and competitive TLR4 inhibitors, TAK-242 (10 µM) and IAXO-102 (10 µM), respectively, or vehicle were added to human T84, HT-29, and U937 cell lines and mouse colonic explants 1 h before the addition of lipopolysaccharide (LPS) (in vitro: 100 µg/mL; ex vivo: 10 µg/mL), SN-38 (in vitro: 1 µM or 1 nM; ex vivo: 2 µM), and/or tumour necrosis factor-alpha (TNF-α) (5 µg/mL). Supernatant was collected for human IL-8 and mouse IL-6 enzyme-linked immunosorbent assays (ELISAs), as a measure of inflammatory signalling. Cell viability was measured using XTT assays. Explant tissue was used in histopathological and RT-PCR analysis for genes of interest: TLR4, MD2, CD14, MyD88, IL-6, IL-6R, CXCL2, CXCR1, CXCR2. SN-38 increased cytostasis compared to vehicle (P P > 0.05) in any of the 3 cell lines. Quantitative histological assessment scores showed no differences between vehicle and treatment groups (P > 0.05). There were no differences in in vitro IL-8 (P > 0.05, in all 3 cells lines) and ex vivo IL-6 (P > 0.05) concentrations between vehicle and treatment groups. Transcript expression of all genes was similar across vehicle and treatment groups (P > 0.05). TLR4 antagonism using specific inhibitors TAK-242 and IAXO-102 was not effective at blocking IM in these pre-clinical models of mucositis. This work indicates that specific epithelial inhibition of TLR4 with these compounds is insufficient to manage mucositis-related inflammation. Rather, TLR4 signalling through immune cells may be a more important target to prevent IM.

Geomagnetic storms are the main component of space weather. Enhancement of the ring current is a typical feature of the geomagnetic storm and a global decrease in the H component of the geomagnetic field is observed during the main phase of the geomagnetic storm. The ring current represents a diamagnetic current driven by the plasma pressure in the inner magnetosphere. The plasma pressure is mainly dominated by protons in an energy range of a few to a few hundred keVs during quiet times. The O+ contribution is also important, and sometimes dominates more than H+ during intense geomagnetic storms. However, electron contribution to the ring current is not studied well. Recently, we showed that the electron pressure also contributes to the depression of ground magnetic field during the November 2017 CIR-driven storm by comparing Ring current Atmosphere interactions Model with Self Consistent magnetic field (RAM-SCB) simulation, Arase in-situ plasma/particle data, and ground-based magnetometer data [Kumar et al., 2021]. Arase satellite observed 26 geomagnetic storms driven by Corotating Interaction Regions (CIR) during 2017-2021. In this study, we examine statistically the spatial and temporal distribution of ions (H+, He+, O+) and electrons pressure as a function of magnetic local time, L shell and wide range of energies during prestorm, main phase, early recovery and late recovery phase for 26 CIR storms using in situ plasma/particle data obtained by Arase. The results indicate that the electrons (20-50 keV) contribution to the ring current pressure is non-negligible.

The purpose of this paper is to develop gather data on the rheological and mechanical properties of self-compacting concrete (SCC) containing varying percentages of waste glass aggregate (WGA). In this current experiment, the coarse aggregate was substituted by adding WGA, with replacement percentages of 0%, 10%, 20%, and 30% by weight being investigated. The rheological properties of SCC were performed to explore the consequence of WGA using various methods, including the J-ring, slump flow, L-box, and V-funnel. In contrast, the compressive, flexural, modulus of elasticity, and stress-strain responses of hardened concrete were assessed in this study. The results of the fresh concrete tests revealed that the substitution of an optimal level of waste glass in SCC provides adequate implementation in flowability, passing ability, and viscosity behaviors. Besides, hardened characteristics were shown to have a steady decrease in strength with increasing WGA content in the concrete mixtures.

This file provides supplementary data pertaining to TSC2 mutation and protein expression analysis in human fibroblast cell lines (Figure S1); as well as Karyotypes (Figure S2), in vitro and in vivo pluripotency and differentiation potential (Figure S3), and genotyping mutation analysis (Figure S4) of human iPSC lines used in this study. Supplementary data regarding human-derived SMC lines, with and without TSC2 mRNA knock-down, specifically cell size analysis (Figure S5), gp100 and ER- expression (Figure S6) and cell death analysis (Figure S7), is also shown.

Lymphangioleiomyomatosis (LAM) is a progressive destructive neoplasm of the lung associated with inactivating mutations in the TSC1 or TSC2 tumor suppressor genes. Cell or animal models that accurately reflect the pathology of LAM have been challenging to develop. Here, we generated a robust human cell model of LAM by reprogramming TSC2 mutation–bearing fibroblasts from a patient with both tuberous sclerosis complex (TSC) and LAM (TSC-LAM) into induced pluripotent stem cells (iPSC), followed by selection of cells that resemble those found in LAM tumors by unbiased in vivo differentiation. We established expandable cell lines under smooth muscle cell (SMC) growth conditions that retained a patient-specific genomic TSC2+/− mutation and recapitulated the molecular and functional characteristics of pulmonary LAM cells. These include multiple indicators of hyperactive mTORC1 signaling, presence of specific neural crest and SMC markers, expression of VEGF-D and female sex hormone receptors, reduced autophagy, and metabolic reprogramming. Intriguingly, the LAM-like features of these cells suggest that haploinsufficiency at the TSC2 locus contributes to LAM pathology, and demonstrated that iPSC reprogramming and SMC lineage differentiation of somatic patient cells with germline mutations was a viable approach to generate LAM-like cells. The patient-derived SMC lines we have developed thus represent a novel cellular model of LAM that can advance our understanding of disease pathogenesis and develop therapeutic strategies against LAM. Cancer Res; 77(20); 5491–502. ©2017 AACR.

This file contains the full descriptive legends for Supplementary Figures S1-S7.

This file contains descriptions of materials and methods used in this study pertaining to cell and tissue staining, Western blot and mRNA analysis, and cell size and genotyping analyses. Corresponding references are also included.

Aggregation is a key process for determining the environmental behavior and impact of a nanoparticle (NP). Since organophosphate esters (OPEs), which are recognized as emerging contaminants, are distributed widely in the natural aquatic environment, they may contribute to interacting with NPs and ultimately influence their transport and fate. Here, we investigated two typical organophosphate esters OPEs on aggregation the Fe2O3 NP in aquatic environments. The results showed that both tri-ethylhexyl phosphate (TEHP) and tris (chloroisopropyl) phosphate (TCPP) improved the colloidal stability of Fe2O3 NP in artificial water and environmental matrices. TEHP exhibited an obvious effect than TCPP on the Zeta potential and aggregation rates of Fe2O3 NP in artificial water. In the presence of electrolyte, 10 mg/L TCPP and TEHP increased the critical coagulation concentration (CCC) by 3.6 times and 17.4 times, respectively. Compared with pore-water, the aggregation rates of Fe2O3 NP in river water were slightly higher than those in pore-water, which can be attributed to the higher DOC in pore-water. We suggested that the high hydrophobicity and molecular weight of OPEs were considered important factors against the aggregation of Fe2O3 NP in water. Greater surface charge and steric hindrance originating from TCPP and TEHP dominated the colloidal stability of Fe2O3 NP.

Australia has ranked as one of the most vulnerable countries to the effects of climate change. The rising trend of temperature is intensifying the creation and extension of urban heat islands (UHI). This paper investigates different cooling street strategies in line with developing resilient Sydney to the effects of climate change. Two different approaches are investigated including, green canopy and cool pavement. A wide range of impacted parameters is examined including Air Temperature, Surface Temperature, Sensible Heat Flux, Sky View Factor, Human Thermal Comfort, and Mean Radiant Temperature. Also, different surface reactions to the sun and shadow were surveyed to investigate the various materials responses to the different levels of shadow. ENVImet software is adopted to simulate and quantify microclimate processes before and after introducing cooling street strategies. This study demonstrates that replacing asphalt pavement with light concrete pavement reduces surface temperature by up to 20°C. Planting short to medium height trees reduces air temperature by up to 3°C and surface temperature by up to 11°C. Also, human thermal comfort has a direct relationship with the Sky View Factor at daytime. Besides, the study proves that the Mean Radiant Temperature is reduced considerably by both green canopy and light pavement scenarios in the daytime; however, the night time radiant heat does not differ substantially in any of the scenarios. Overall, both proposed initiatives show the positive cooling effects on air, surface, and mean radiant temperature, human thermal comfort, and the heat fluxes in the daytime; however, the cool pavement scenario decreases both daytime and night-time air and surface temperature.

Building information Modeling (BIM) has been applied to the whole life cycle planning of construction projects, becoming the latest “engineering brain”. Currently, researches on BIM involve various stages, but most of the review fields are relatively single and lack of systematic review and analysis. In order to comprehensively analyze the research trend of BIM in the field of engineering management, this paper takes the holistic analysis method as the framework. In the first stage, 2066 research projects were quantitatively analyzed by bibliometrics to clarify their research environment. In the second stage, scientometric analysis method is adopted to identify scholars, countries, key words and journal sources that have achieved fruitful results and influence in BIM research, and to clarify the research environment. In the last stage, indepth qualitative discussion is carried out to achieve three objectives: (1) to divide the whole life cycle of the article and summarize the research hotspots in each stage; (2) identify BIM application problems; (3) determine the future research direction. This work is helpful for researchers and practitioners in this field to quickly find influential and fruitful research or journals, and to understand the current research hot spots and trends for the next research planning.

Candidate probability distributions for the Standardized Precipitation Evapotranspiration Index (SPEI) for Canada were examined using the Canadian Gridded (CANGRD) temperature and precipitation dataset and CMIP5 projections. The probability distribution is a core component to the calculation of standardized values. For SPEI, a continuous probability distribution is fitted to the water balance time series so that the resulting transformed index follows a standard normal distribution. Selection of an appropriate distribution is therefore important as an inappropriate distribution may lead to biased values and subsequently affect the interpretation of SPEI results. Candidate distributions considered for SPEI included the generalized logistic (GLO), generalized extreme value (GEV), Pearson Type III (PE3) and normal (NOR) distributions. A range of goodness of fit tests were used to assess how well the distributions fit SPEI. Differences in CANGRD SPEI time series between three pairs of distributions, GLO-GEV, GLO-PE3, and GEV-PE3, showed that there were larger differences in SPEI values between GLO and the other two distributions than the difference between GEV and PE3. SPEI results fitted with GLO resulted in lower threshold exceedances of extreme SPEI (-/+2) than GEV and GLO. A comparison between CMIP5 SPEI values fitted with GLO (SPEI-GLO) and PE3 (SPEI-PE3) showed that there were seasonal and spatial variations in results, although the use of multi-model ensembles reduced these differences. As was the case for CMIP5 SPEI-GLO projections, projected annual changes in CMIP5 SPEI-PE3 show an increase in drying at the surface in central/southern Canada. Overall, the study recommends using PE3 or GEV for SPEI analysis for Canada.

PurposeThis study aims to map out contractors' thoughts on construction-related environmental recovery as an excuse for deliberately carrying on unsustainable construction.Design/methodology/approachA typical highway construction project in China was investigated. Textual materials were collected through semistructured interviews. Content analysis was conducted to derive qualitative data from the textual materials.FindingsThe research findings reveal a trend of environmental recovery associated with construction activities. It is found that contractors utilize this trend to maintain unsustainable construction. Furthermore, the effects of environmental recovery equip local governments with a tolerance for environmental degradation, and the environmental tolerance allows contractors to continue unsustainable construction without being discovered.Originality/valueThis paper presents an environmental recovery-based perspective on unsustainable construction and sheds some light on the promotion of sustainable construction.

Through a secondary data analysis of administrative data of the Ontario Disability Support Program (ODSP) between 2003 and 2013, we aim to understand the interlocking challenges encountered by newcomers with disabilities in Canada that contribute to this population’s financial hardship. Our findings show that newcomers with disabilities on ODSP were more likely to have post-secondary education, to be older adults, to be married, common-law, and to be female who were divorced, separated, or widowed as compared to Canadian-born recipients, who were more likely to be less educated, younger, single and male. The ratio of Canadian-born to newcomer recipients on the ODSP was high between 2003 and 2013, indicating that the latter were under-represented on the program. Implications for this under-representation support future research to examine the full integration and participation of newcomers with disabilities in Canada.

PURPOSE Irinotecan can cause high levels of diarrhea caused by toxic injury to the gastrointestinal microenvironment. Toll-like receptor 4 (TLR4) and the gut microbiome have previously been implicated in gastrointestinal toxicity and diarrhea; however, the link between these two factors has not been definitively determined. We used a tumor-bearing, intestinal epithelial cell (IEC) TLR4 knockout model (Tlr4ΔIEC) to assess microbiome changes following irinotecan treatment. We then determined if a fecal microbiota transplant (FMT) between Tlr4ΔIEC and wild-type (WT) mice altered irinotecan-induced gastrointestinal toxicity. METHODS MC-38 colorectal cancer cells were injected into WT and Tlr4ΔIEC mice. Fecal samples were collected prior to tumor inoculation, prior to irinotecan treatment and at cull. 16S rRNA gene sequencing was used to assess changes in the microbiome. Next, FMT was used to transfer the microbiome phenotype between Tlr4ΔIEC and WT mice prior to irinotecan treatment. Gastrointestinal toxicity symptoms were assessed. RESULTS In study 1, there were no compositional differences in the microbiome between Tlr4ΔIEC and WT mice at baseline. However, predicted functional capacity of the microbiome was different between WT and Tlr4ΔIEC at baseline and post-irinotecan. In study 2, Tlr4ΔIEC mice were protected from grade 3 diarrhea. Additionally, WT mice who did not receive FMT had more colonic damage in the colon compared to controls (P = 0.013). This was not seen in Tlr4ΔIEC mice or WT mice who received FMT (P > 0.05). CONCLUSION Tlr4ΔIEC and WT had no baseline compositional microbiome differences, but functional differences at baseline and following irinotecan. FMT altered some aspects of irinotecan-induced gastrointestinal toxicity.

Background Transcatheter aortic valve replacement (TAVR)/intervention has become the standard of care for treatment of severe aortic stenosis across the spectrum of risk. There are socioeconomic disparities in access to TAVR. The impact of these disparities on postprocedural outcomes remains unknown. Our objective was to examine the association between neighborhood‐level social deprivation and post‐TAVR mortality and hospital readmission. Methods and Results We conducted a population‐based retrospective cohort study of all 4145 patients in Ontario, Canada, who received TAVR from April 1, 2017, to March 31, 2020. Our co‐primary outcomes were 1‐year postprocedure mortality and 1‐year postprocedure readmission. Using Cox proportional hazards models for mortality and cause‐specific competing risk hazard models for readmission, we evaluated the relationship between neighborhood‐level measures of residential instability, material deprivation, and concentration of racial and ethnic groups with post‐TAVR outcomes. After multivariable adjustment, we found a statistically significant relationship between residential instability and postprocedural 1‐year mortality, ranging from a hazard ratio of 1.64 to a hazard ratio of 2.05. There was a significant association between the highest degree of residential instability and 1‐year readmission (hazard ratio, 1.23 [95% CI, 1.01–1.49]). There was no association between material deprivation and concentration of racial and ethnic groups with post‐TAVR outcomes. Conclusions Residential instability was associated with increased risk for post‐TAVR mortality, and the highest quintile of residential instability was associated with increased post‐TAVR readmission. To reduce health disparities and promote an equitable health care system, further research and policy interventions will be required to identify and support economically and socially minoritized patients undergoing TAVR.

Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial decreased major adverse cardiovascular events with very low‐dose rivaroxaban and aspirin in patients with coronary artery disease and peripheral artery disease. We examined the eligibility and potential real‐world impact of this strategy on the COMPASS‐eligible population. Methods and Results COMPASS eligibility criteria were applied to the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) registry, a population‐based cohort of Ontario adults. We compared 5‐year major adverse cardiovascular events and major bleeding rates stratified by COMPASS eligibility and by clinical risk factors. We applied COMPASS trial rivaroxaban/aspirin arm hazard ratios to estimate the potential impact on the COMPASS‐eligible cohort. Among 362 797 patients with coronary artery disease or peripheral artery disease, 38% were deemed eligible, 47% ineligible, and 15% indeterminate. Among eligible patients, a greater number of risk factors was associated with higher rates of cardiovascular outcomes, whereas bleeding rates increased minimally. Over 5 years, applying COMPASS treatment effects to eligible patients resulted in a 2.4% absolute risk reduction of major adverse cardiovascular events and a number needed to treat of 42, and a 1.3% absolute risk increase of major bleeding and number needed to harm (NNH) of 77. Those with at least 2 risk factors had a 3.0% absolute risk reduction of major adverse cardiovascular events (number needed to treat =34) and a 1.6% absolute risk increase of major bleeding (number needed to harm =61). Conclusions Implementation of very‐low‐dose rivaroxaban therapy would potentially impact ≈ $$ \approx $$ 2 in 5 patients with atherosclerotic disease in Ontario. Eligible individuals with ≥ $$ \ge $$ 2 comorbidities represent a high‐risk subgroup that may derive the greatest benefit‐to‐risk ratio. Selection of patients with high‐risk predisposing factors appears appropriate in routine practice.

The reverse fragility index (RFI) describes the number of event conversions needed to convert a statistically non-significant dichotomous outcome to significant. The objective of this study was to assess the RFI of vascular surgery randomized controlled trials (RCTs) comparing endovascular vs. open surgery in the treatment of abdominal aortic aneurysms (AAA), carotid artery stenosis (CAS), and peripheral artery disease (PAD).MEDLINE and Embase were searched for RCTs investigating AAA, CAS, or PAD with statistically non-significant binary primary outcomes. The primary outcome of this study was the median RFI. Calculation of the RFI was done by creating two-by-two contingency tables and subtracting events from the group with fewer events while adding non-events to the same group until a two-tailed Fisher exact test produced a statistically significant result (p≤0.05).Of 4187 articles, 49 studies reporting 103 different primary endpoints were included. The overall median RFI was 7 (IQR 5, 13). The specific RFIs for AAA, CAS, and PAD were 10 (6-15.5), 6 (5-9.5), and 7 (5.5 -10) respectively. 42 (47%) endpoints had a loss to follow-up greater than RFI, of which 10 (24%) were AAA trials, 23 (55%) CAS trials, and 9 (21%) PAD trials. Pearson correlation demonstrated a significant positive relationship between a study's RFI to the impact factor of its publishing journal (r=0.38 [95% CI 0.20 to 0.54], p0.01), length of follow-up (r=0.43 [95% CI: 0.26 to 0.58], p0.01), and sample size (r = 0.28, 95% CI: 0.09 to 0.45, p0.01).A small number of events (median 7) were required to change the outcome of negative RCTs from statistically non-significant to significant with 47% of studies missing data that could have reversed the finding of its primary outcome. Reporting of the RFI relative to the loss-to-follow-up may be of benefit in future trials and provide confidence towards the robustness of P-value.

Background Coronary artery bypass grafting (CABG) and surgical aortic valve replacement (AVR) are the 2 most common cardiac surgery procedures in North America. We derived and externally validated clinical models to estimate the likelihood of death within 30 days of CABG, AVR or combined CABG + AVR. Methods We obtained data from the CorHealth Ontario Cardiac Registry and several linked population health administrative databases from Ontario, Canada. We derived multiple logistic regression models from all adult patients who underwent CABG, AVR or combined CABG + AVR from April 2017 to March 2019, and validated them in 2 temporally distinct cohorts (April 2015 to March 2017 and April 2019 to March 2020). Results The derivation cohorts included 13 435 patients who underwent CABG (30-d mortality 1.73%), 1970 patients who underwent AVR (30-d mortality 1.68%) and 1510 patients who underwent combined CABG + AVR (30-d mortality 3.05%). The final models for predicting 30-day mortality included 15 variables for patients undergoing CABG, 5 variables for patients undergoing AVR and 5 variables for patients undergoing combined CABG + AVR. Model discrimination was excellent for the CABG (c-statistic 0.888, optimism-corrected 0.866) AVR (c-statistic 0.850, optimism-corrected 0.762) and CABG + AVR (c-statistic 0.844, optimism-corrected 0.776) models, with similar results in the validation cohorts. Interpretation Our models, leveraging readily available, multidimensional data sources, computed accurate risk-adjusted 30-day mortality rates for CABG, AVR and combined CABG + AVR, with discrimination comparable to more complex American and European models. The ability to accurately predict perioperative mortality rates for these procedures will be valuable for quality improvement initiatives across institutions.

Background The novel SARS-CoV-2 (COVID-19) pandemic has dramatically altered the delivery of healthcare services, resulting in significant referral pattern changes, delayed presentations, and procedural delays. Our objective was to determine the effect of the COVID-19 pandemic on all-cause mortality in patients awaiting commonly performed cardiac procedures. Methods Clinical and administrative data sets were linked to identify all adults referred for: (1) percutaneous coronary intervention; (2) coronary artery bypass grafting; (3) valve surgery; and (4) transcatheter aortic valve implantation, from January 2014 to September 2020 in Ontario, Canada. Piece-wise regression models were used to determine the effect of the COVID-19 pandemic on referrals and procedural volume. Multivariable Cox proportional hazards models were used to determine the effect of the pandemic on waitlist mortality for the 4 procedures. Results We included 584,341 patients who were first-time referrals for 1 of the 4 procedures, of whom 37,718 (6.4%) were referred during the pandemic. The pandemic period was associated with a significant decline in the number of referrals and procedures completed compared with the prepandemic period. Referral during the pandemic period was a significant predictor for increased all-cause mortality for the percutaneous coronary intervention (hazard ratio, 1.83; 95% confidence interval, 1.47-2.27) and coronary artery bypass grafting (hazard ratio, 1.96; 95% confidence interval, 1.28-3.01), but not for surgical valve or transcatheter aortic valve implantation referrals. Procedural wait times were shorter during the pandemic period compared with the prepandemic period. Conclusions There was a significant decrease in referrals and procedures completed for cardiac procedures during the pandemic period. Referral during the pandemic was associated with increased all-cause mortality while awaiting coronary revascularization.

This study analyzed the nature, mechanisms and drivers for hot-and-polluted episodes (HPEs) in the Pearl River Delta, China. Numerical model simulations were conducted for the summer and autumn of 2009–2011. A total of eight HPEs were identified, mainly occurring in August and September. K-means clustering was applied to group the HPEs into three clusters based on their characteristics and mechanisms. We found three HPEs were driven by weak subsidence and convection induced by approaching tropical cyclones (TC-HPE) and two HPEs were controlled by calm (stagnant) conditions (ST-HPE) with low wind speed in the lower atmosphere, whereas the remaining three HPEs were driven by the combination (hybrid) of both aforementioned systems (HY-HPE). A positive synergistic effect between the HPE and urban heat island (UHI; ∼ 1.1 ∘C increase) was observed in TC-HPE and ST-HPE, whereas no discernible synergistic effect was found in HY-HPE. Total aerosol radiative forcing (TARF) caused a reduction in temperature (0.5–1.0 ∘C) in TC-HPE and ST-HPE but an increase (0.5 ∘C) in HY-HPE.