Risk Curves Research Articles

Economic Growth, Income Inequality and Food Safety Risk.

Food safety risk, as an implicit cost of social and economic development, endangers the health of global residents, including China. To systematically understand the impact of socioeconomic development on food safety risk and to establish a sound modern governance system of food safety in China, this paper uses provincial panel data from 2011 to 2020 to explore the relationship between food safety risk and socio-economic development factors such as economic growth and income inequality by employing a two-way fixed effect model and moderating effect model. The results show that the food safety risk is a Kuznets curve, and the turning point is about RMB 58,104.59 per capita GDP (based on prices in 2011). However, under the moderating effect of income inequality, the turning point of the Kuznets curve of food safety risk will shift to the right, and the curve will be flattened. In other words, income inequality has a negative moderating effect on the "inverted U-shaped" relationship between economic growth and food safety risk. When dealing with food safety problems, the goal of stable and sustained economic growth and common prosperity should be incorporated into policy formulation to enhance the governance effectiveness of food safety risk.

Impact of minimally invasive total mesoesophageal excision and minimally invasive esophagectomy on failure patterns of locally advanced esophageal squamous cell carcinoma: a matched cohort study with long-term follow-up.

The effects of minimally invasive total mesoesophageal excision (MITME) on the long-term prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remain unknown. The objective of this study was to compare the static and dynamic failure patterns of MITME and minimally invasive esophagectomy (MIE) for locally advanced ESCC. We use propensity score matching (PSM) method to analyze the postoperative failure patterns of the two groups. Cumulative event curves were analyzed for cumulative incidence of failure between different groups, and independent prognostic factors were assessed using time-dependent multivariate analyses. The risk of dynamic failure calculated at 12-month intervals was compared between the two groups using the lifetime table. A total of 366 ESCC patients were studied by 1:1 PSM for T stage and TNM stage (MITME group, n = 183; MIE group, n = 183). In the matched cohort, there was significant differences between the MITME and MIE groups in the failure pattern of regional lymph node recurrence (0.5 vs 3.8%, P = 0.032) and non-tumor death (10.9 vs 31.7%, P < 0.001). The cumulative event curve found that the 5-year cumulative failure rate was lower in the MITME group than in the MIE group (3.3 vs 17.1%, P = 0.026) after 5years of survival. In addition, multivariate Cox regression analysis showed that MIE was an independent poor prognostic factor for a high cumulative failure rate in locally advanced ESCC patients at 5years after surgery (HR:4.110; 95% CI 1.047-16.135; P = 0.043). The dynamic risk curve showed that the MITME group had a lower risk of failure within 5years after surgery than the MIE group. Considering that MITME can significantly improve the postoperative failure pattern and the benefit lasts for at least 5years, it is feasible to use MITME as a treatment for locally advanced ESCC.

Development and Validation of a Prediction Tool for Reoffending Risk in Domestic Violence.

Current risk assessment tools for domestic violence against family members were developed with small and selected samples, have low accuracy with few external validations, and do not report key performance measures. To develop new tools to assess risk of reoffending among individuals who have perpetrated domestic violence. This prognostic study investigated a national cohort of all individuals arrested for domestic violence between 1998 and 2013 in Sweden using information from multiple national registers, including National Crime Register, National Patient Register, Longitudinal Integrated Database for Health Insurance and Labour Market Studies Register, and Multi-Generation Register. Data were analyzed from August 2022 to June 2023. Arrest for domestic violence. Prediction models were developed for 3 reoffending outcomes after arrest for domestic violence: conviction of a new violent crime (including domestic violence), conviction of any new crime, and rearrest for domestic violence at 1 year, 3 years, and 5 years. The prediction models were created using sociodemographic factors, criminological factors, and mental health status-related factors, linking data from multiple population-based longitudinal registers. Cox proportional hazard multivariable regression was used to develop prediction models and validate them in external samples. Key performance measures, including discrimination at prespecified cutoffs and calibration statistics, were investigated. The cohort included 27 456 individuals (mean [SD] age, 39.4 [11.6] years; 24 804 men [90.3%]) arrested for domestic violence, of whom 4222 (15.4%) reoffended and were convicted for a new violent crime during a mean (SD) follow-up of 26.5 (27.0) months, 9010 (32.8%) reoffended and were convicted for a new crime (mean [SD] follow-up, 22.4 [25.1] months), and 2080 (7.6%) were rearrested for domestic violence (mean [SD] follow-up, 25.7 [30.6] months). Prediction models were developed with sociodemographic, criminological, and mental health factors and showed good measures of discrimination and calibration for violent reoffending and any reoffending. The area under the receiver operating characteristic curve (AUC) for risk of violent reoffending was 0.75 (95% CI, 0.74-0.76) at 1 year, 0.76 (95% CI, 0.75-0.77) at 3 years, and 0.76 (95% CI, 0.75-0.77) 5 years. The AUC for risk of any reoffending was 0.76 (95% CI, 0.75-0.77) at 1 year and at 3 years and 0.76 (95% CI, 0.75-0.76) at 5 years. The model for domestic violence reoffending showed modest discrimination (C index, 0.63; 95% CI, 0.61-0.65) and good calibration. The validation models showed discrimination and calibration performance similar to those of derivation models for all 3 reoffending outcomes. The prediction models have been translated into 3 simple online risk calculators that are freely available to use. This prognostic study developed scalable, evidence-based prediction tools that could support decision-making in criminal justice systems, particularly at the arrest stage when identifying those at higher risk of reoffending and screening out individuals at low risk of reoffending. Furthermore, these tools can enhance treatment allocation by enabling criminal justice services to focus on modifiable risk factors identified in the tools for individuals at high risk of reoffending.

HAS SECONDARY MORTGAGE MARKET PROMOTE HOUSE AFFORDABILITY? EVIDENCE FROM INDONESIA

The advantage of secondary mortgage market establishment to decrease housing cost, theoretically, had been mentioned frequently in domestic and international research. However, research on this matter in Indonesia is still limited to narrative descriptive. This research engages sequential explanatory design by utilizing empirical evidence from financial perspective to analyse the impact of securitization to the yield spread premium from monthly data ranging from June 2017-April 2021. In quantitative phase, this research found that either securitization volume or the launch of new series of asset backed securities (ABS) significantly affects mortgage rate, contrary to aggregate mortgage volume, prepayment risk, and yield curve risk. In the qualitative phase, it is explored that the reason of securitization’s stagnation is market unreadiness.

Prescriptive Building Regulations, Safety Objectives, and Residual Risk in Germany

AbstractIn Germany, building codes relating to fire safety are mainly prescriptive nature. Therefore, fire safety engineering is based on a combination of expert judgment and reverse engineering of prescriptive rules. This necessitates to connect the given objectives with the detailed prescriptive rules—if not already described within the law or bylaw. This paper proposes a table relating the fire safety objectives of European building regulations and their German counterpart with the prescriptive model building code in Germany. In addition, a risk curve for prenormative work is also given. This represents the prescriptive regulations concerning in terms of fatalities of a level acceptable to society and emphasizes the lower degree of acceptance of multiple fatalities occurring in a single incident. This residual risk limit represents the opinion of German firefighting associations. Data taken from the London area supports the suggested slope rate, as the level of safety in Britain is similar to that in Germany. The table of prescriptive building regulations and their corresponding objectives aids everyday planning decisions in the context of determining adequate compensation without missing out any essential aspects, such as firefighting and firefighter safety. The proposed table forms the basis of the current discussion of a European model performance-based model building code (PBC) within the European Committee for Standardization CEN. Moreover, the risk curve is the first to be discussed in Germany that takes into consideration the societal aspect. It forms an appropriate basis for performing fire safety risk calculations based on fault tree analysis or Bayes nets. The CEN working group for fire safety engineering discusses both aspects of the current development of a European, performance-based fire safety code. It is presented here for the first time.

Three Gorges Dam: Potential differential drivers and trend in the spatio-temporal evolution of the change in snail density based on a Bayesian spatial–temporal model and 5-year longitudinal study

BackgroundSnail abundance varies spatially and temporally. Few studies have elucidated the different effects of the determinants affecting snail density between upstream and downstream areas of the Three Gorges Dam (TGD). We therefore investigated the differential drivers of changes in snail density in these areas, as well as the spatial–temporal effects of these changes.MethodsA snail survey was conducted at 200 sites over a 5-year period to monitor dynamic changes in snail abundance within the Yangtze River basin. Data on corresponding variables that might affect snail abundance, such as meteorology, vegetation, terrain and economy, were collected from multiple data sources. A Bayesian spatial–temporal modeling framework was constructed to explore the differential determinants driving the change in snail density and the spatial–temporal effects of the change.ResultsVolatility in snail density was unambiguously detected in the downstream area of the TGD, while a small increment in volatility was detected in the upstream area. Regarding the downstream area of the TGD, snail density was positively associated with the average minimum temperature in January of the same year, the annual Normalized Difference Vegetation Index (NDVI) of the previous year and the second, third and fourth quartile, respectively, of average annual relative humidity of the previous year. Snail density was negatively associated with the average maximum temperature in July of the previous year and annual nighttime light of the previous year. An approximately inverted “U” curve of relative risk was detected among sites with a greater average annual ground surface temperature in the previous year. Regarding the upstream area, snail density was positively associated with NDVI and with the second, third and fourth quartile, respectively, of total precipitation of the previous year. Snail density was negatively associated with slope.ConclusionsThis study demonstrated a rebound in snail density between 2015 and 2019. In particular, temperature, humidity, vegetation and human activity were the main drivers affecting snail abundance in the downstream area of the TGD, while precipitation, slope and vegetation were the main drivers affecting snail abundance in the upstream area. These findings can assist authorities to develop and perform more precise strategies for surveys and control of snail populations.Graphical

Concentrated disadvantage and functional disability: a longitudinal neighbourhood analysis in 100 US cities

BackgroundSocioeconomic disadvantage related to poverty, unemployment and social disinvestment contributes to significant disparities in community health in the USA. Yet, there remains limited ecological research on the relationship between neighbourhood...

Construction and validation of a cuproptosis-related five-lncRNA signature for predicting prognosis, immune response and drug sensitivity in breast cancer

BackgroundDespite advances in treatment, recurrence and mortality rates from breast cancer (BrCa) continue to rise, clinical effectiveness is limited, and prognosis remains disappointing, especially for patients with HER2-positive, triple-negative, or advanced breast cancer. Based on cuproptosis-related long noncoding RNAs (CRLs), this study aims to create a predictive signature to assess the prognosis in patients with BrCa.MethodsThe related CRLs RNA-seq data clinicopathological data were collected from The Cancer Genome Atlas (TCGA) database, and the predictive model was constructed after correlation analysis. Subsequently, we examined and validated connections and changes in the CRLs model with prognostic features (including risk curves, ROC curves and nomograms), pathway and functional enrichment, tumor mutation (TMB), tumor immune dysfunction and exclusion (TIDE) and treatment sensitivity.ResultsA prediction model formula composed of 5 CRLs was obtained, and divided breast cancer patients into high and low risk subgroups according to the obtained risk scores. The results showed that the overall survival (OS) of patients in the high-risk group was lower than that in the low-risk group, and the AUC of all samples at 1, 3 and 5 years were 0.704, 0.668 and 0.647, respectively. It was indicated that CRLs prognostic model could independently predict prognostic indicators of BrCa patients. In addition, analysis of gene set enrichment, immune function, TMB, and TIDE showed that these differentially expressed CRLs had a wealth of related pathways and functions, and might be closely related to immune response and immune microenvironment. Additionally, TP53 was found to have the highest mutation frequency in high-risk group (40%), while PIK3CA was found to have the highest mutation frequency in low-risk group (42%), which might become new targets for targeted therapy. Finally, we compared susceptibility to anticancer agents to identify potential treatment options for breast cancer. Lapatinib, Sunitinib, Phenformin, Idelalisib, Ruxolitinib, Cabozantinib were more sensitive to patients in the low-risk group, while Sorafenib, Vinorelbine, Pyrimethamine were more sensitive to patients in high-risk group, namely, these drugs could potentially be used in the future to treat breast cancer patients grouped according to the risk model.ConclusionThis study identified CRLs associated with breast cancer and provided a tailored tool for predicting prognosis, immune response, and drug sensitivity in patients with BrCa.

Study on the recurrence pattern of rectal cancer patients undergoing radical surgery after neoadjuvant chemoradiotherapy

Objective: To analyze the recurrence pattern of rectal cancer patients with radical surgery after neoadjuvant chemoradiotherapy. Methods: The clinicopathological characteristics and follow-up information of rectal cancer patients with radical surgery after neoadjuvant chemoradiotherapy in the Cancer Hospital of the Chinese Academy of Medical Sciences from June 2004 to December 2017 were retrospectively collected. The recurrence pattern including the time and site was investigated. Results: The age of 537 patients was (55.5±11.7) years, of whom 361 were male (67.2%). The median follow-up time [M(Q1,Q3)] was 77.9 (64.5, 95.6) months. Moreover, 30.7% (165/537) of patients had distant metastasis or local recurrence; 26.8% (144/537) of patients had distant metastasis; 5.6% (30/537) of patients had local recurrence; 1.7% (9/537) of patients had both distant metastasis and local recurrence. In all the recurrent patients, 23.6% (39/165) were in the first year after surgery, followed by 27.3% (45/165) in the second year, 17.0% (28/165) in the third year, and 15.8% (26/165) after five years. According to the risk curve drawn by the life table, the highest metastasis risk of patients occurred in the second year after surgery, and the metastasis risk peak occurred again after more than five years. The lung was the most common metastatic organ, accounting for 47.9% (69/144), followed by the liver (18.8%, 27/144). The ratios of the recurrent patients in each ypTNM stage were 9.5% (8/84), 12.0% (12/100), 26.5% (41/155), 52.5% (104/198), respectively. The proportion of recurrent patients in tumor regression grade (TRG) 1-2 and TRG 3-5 patients were 19.2% (38/198) and 37.5% (127/339), respectively. Conclusions: The recurrence pattern of patients undergoing radical surgery after neoadjuvant chemoradiotherapy is mainly distant metastasis. The lung is the primary metastatic organ. The risk of distant metastasis and local recurrence is high in the first three years after surgery, and there is still high risk of recurrence after five years. For patients with ypTNM stage 2, 3 and TRG3-5, the postoperative adjuvant chemotherapy and long-term follow-up should be strengthened.

Do national culture and economic freedom affect bank risk-taking behavior? Evidence from GCC countries

PurposeThe global financial crisis of 2008 has put greater doubt on the bank risk-management effectiveness around the world. As a part of the response to such doubt, the Gulf Cooperation Council (GCC) region is formulating some feasible approaches to manage bank risk. In this regard, an understanding of the role of the region’s culture and economic freedom will provide immense input into this risk management approach. This study examines the impact of national culture and economic freedom on bank risk-taking behavior.Design/methodology/approachData on bank risk measures, culture and economic freedom are obtained from the FitchConnect, World Bank database, Hofstede’s insights and Heritage Foundation. Generalized least squares and two step-system generalized method of moments are then used to examine the risk-taking behavior of the region.FindingsBanks of the GCC region operating in the low power distance, high collectivism, masculine and low uncertainty avoidance cultures are susceptible to assuming more operational and insolvency risks. Furthermore, banks’ overall risk-taking inclination is positively increased once the region has considerable business and monetary freedom.Practical implicationsThe governments and bank regulatory bodies may benefit from the study findings by developing the best economic freedom index and national culture that enriches risk management practices and curves excessive risk-taking inclination.Originality/valueTo the best of the authors’ knowledge, this study is the first attempt to address the interplay among culture, economic freedom and bank risk to ensure constructive risk-taking behavior for the GCC banking industry.

Probability Assessment of the Seismic Risk of Highway Bridges with Various Structural Systems (Case Study: Tehran City)

Considering the development of urban transportation systems and the importance of highway bridges in a city’s resilience against earthquakes, it is critical to pay special attention to the seismic risk evaluation of highway bridges. The most significant issue to consider is the assessment of possible direct and indirect damages imposed on bridges before an earthquake. After this, the best practices for bridge rehabilitation can be adopted to minimize the induced damage. In this paper, we assessed the seismic risks associated with all 713 highway bridges in Tehran province (the capital of Iran). These bridges were initially divided into six categories according to their structural system and construction year and were also classified by whether or not seismic design was included. Among the 84,000 earthquakes recommended by the researchers’ ten-thousand-year catalog, a set of 50 ground motion records was selected in the course of a probabilistic approach via the Optimization-based Probabilistic Scenarios (OPS) algorithm in an attempt to obtain the least amount of error compared to the original catalog in the final hazard curve in different regions of Tehran province. Afterward, the seismic fragility curves were plotted in four damage states of slight, moderate, extensive, and complete for the six bridge structural systems of simple, steel, concrete slab box, concrete slab–steel box, concrete slab, and steel girder–concrete slab. The results of the fragility curves extracted from the decision tree analysis were validated with those developed from incremental dynamic analysis (IDA) for a bridge case study modeled in the OpenSEES software V2.5.0. Later, using logical relationships, seismic risk curves were drawn for each structural system. The results show that, in general, the average seismic damage of bridges over ten years old is 0.88 times the average damage of bridges less than ten years old. The highest level of vulnerability is associated with the simple bridge system with a median vulnerability of 0.44. Moreover, the lowest level of vulnerability is related to the steel girder–concrete slab bridge system with a median vulnerability of 0.98, showing an increase of approximately 2.2 times in the median vulnerability. In addition, based on the sensitivity analysis results, the indirect and total risk levels increase almost exponentially with increasing the reconstruction index.

#2906 INTEGRATED KIDNEY MARKERS AND CARDIOVASCULAR MORTALITY: A SURVIVAL ANALYSIS IN UK BIOBANK

Abstract Background and Aims The estimated glomerular filtration rate (eGFR) and other kidney function markers are associated with cardiovascular disease (CVD) mortality [1]. It remains unclear whether integrating multiple kidney markers together can improve CVD mortality risk prediction and what would be an appropriate method of integration. In a small general population sample, we recently showed that confirmatory factor analysis (CFA) may predict CVD risk better than single markers, but it did not outperform cystatin C-based eGFR (eGFRcys) [2]. To assess whether our findings were context-dependent and to which extent they may extend to mortality risk assessment, we applied CFA and exploratory factor analysis (EFA), integrating five kidney function markers in the UK Biobank (UKBB) study, comparing risk discrimination for CVD mortality and renal failure mortality versus established eGFR formulas. Method We analyzed data from 366,758 UKBB participants (mean age 56.6 years; females 53.7%) without clinical history of kidney failure at baseline. Information on participants’ mortality was collected from the National Health System registry, using ICD-10 codes I00-I99 and N17-N19 to identify CVD mortality and renal failure mortality. We applied CFA and EFA to creatinine-based estimated glomerular filtration rate (eGFRcre), eGFRcys, blood urea nitrogen (BUN), uric acid (UA), and serum albumin (Alb). EFA was fitted using maximum likelihood. Promax rotation was then applied. We fitted Cox regression models to examine the associations of mortality with kidney markers: CFA-based kidney index [CFA]; 1st EFA-based kidney index [EFA1]; 2nd EFA-based kidney index [EFA2]; eGFRcre; eGFRcys; and creatinine- and cystatin C-based eGFR (eGFRcrecys). Models were adjusted for sex, age, body mass index, education, self-reported ancestry, hypertension, diabetes, and tobacco smoking. The receiver operating characteristics (ROC) curve and the DeLong test were used to compare discriminatory ability of each index. Results CFA standardized factor loadings (λ) of eGFRcre, eGFRcys, BUN, UA and Alb were 0.81, 0.73, -0.55, -0.39, and 0.12, respectively. EFA identified two factors: EFA1, largely dependent on eGFRcys (λ = 0.85), and EFA2, reflecting BUN (λ = 0.88), eGFRcre (λ = -0.55) and UA (λ = 0.36). Over a median follow-up of 12.5 years, we observed 26,327mortality cases, of which 5,376 and 45 were related to CVD and renal failure. The hazard ratios (HR) and 95% confidence intervals (CI) for CVD mortality and renal failure mortality per each standard deviation change were of 1.22 (1.19–1.25) and 3.53 (2.98–4.18) for eGFRcre, 1.62 (1.57–1.67) and 7.34 (5.82–9.27) for eGFRcys, 1.47 (1.43–1.51) and 4.82 (4.04–5.76) for eGFRcrecys, 1.38 (1.34–1.41) and 2.94 (2.63–3.29) for CFA, 1.61 (1.56–1.66) and 7.54 (5.90–9.64) for EFA1, and 1.33 (1.30–1.35) and 1.98 (1.85–2.12) for EFA2. The area under the curve (AUC) for CVD mortality risk was higher for EFA1 (0.706, 0.699–0.713) than for any other kidney marker, except for eGFRcys (0.709, 0.702–0.716). The kidney failure mortality AUC of EFA1 (0.936, 0.901–0.972) was similar to that of eGFRcys (0.939, 0.905–0.972). Conclusion To assess the contribution of kidney function to CVD-related mortality in general population studies of mainly healthy individuals, EFA is a better way than using single markers. However, EFA does not outperform eGFRcys, which, being based on a simpler calculation, remains a better choice for CVD and renal failure mortality risk prediction.

Assessing the applicability of impact speed injury risk curves based on US data to defining safe speeds in the US and Sweden

Vision Zero is an approach to road safety that aims to eliminate all traffic-induced fatalities and lifelong injuries. To reach this goal, a multi-faceted safe system approach must be implemented to anticipate and minimize the risk associated with human mistakes. One aspect of a safe system is choosing speed limits that keep occupants within human biomechanical limits in a crash scenario. The objective of this study was to relate impact speed and maximum delta-v to risk of passenger vehicle (passenger cars and light trucks and vans) occupants sustaining a moderate to fatal injury (MAIS2+F) in three crash modes: head-on vehicle-vehicle, frontal vehicle–barrier, and front-to-side vehicle-vehicle crashes. Data was extracted from the Crash Investigation Sampling System, and logistic regression was used to construct the injury prediction models. Impact speed was a statistically significant predictor in head-on crashes, but was not a statistically significant predictor in vehicle-barrier or front–to–side crashes. Maximum delta-v was a statistically significant predictor in all three crash modes. A head-on impact speed of 62 km/h yielded 50% (±27%) risk of moderate to fatal injury for occupants at least 65 years old. A head-on impact speed of 82 km/h yielded 50% (±31%) risk of moderate to fatal injury for occupants younger than 65 years. Compared to the impact speeds, the maximum delta-v values yielding the same level of risk were lower within the head-on crash population. A head-on delta-v of 40 km/h yielded 50% (±21%) risk of moderate to fatal injury for occupants at least 65 years old. A head-on delta-v of 65 km/h yielded 50% (±33%) risk of moderate to fatal injury for occupants younger than 65 years. A maximum delta–v value of approximately 30 km/h yielded 50% (±42%) risk of MAIS2+F injury for passenger car occupants in vehicle-vehicle front-to-side crashes. A maximum delta–v value of approximately 44 km/h yielded 50% (±24%) risk of MAIS2+F injury for light truck and van occupants, respectively, in vehicle-vehicle front-to-side crashes.

A nonlinear relationship between the hemoglobin level and prognosis of elderly patients with sepsis: an analysis based on MIMIC-IV

To investigate the correlation of hemoglobin (Hb) level with prognosis of elderly patients diagnosed as sepsis. A retrospective cohort study was conducted. Information on the cases of elderly patients with sepsis in the Medical Information Mart for Intensive Care-IV (MIMIC-IV), including basic information, blood pressure, routine blood test results [the Hb level of a patient was defined as his/her maximum Hb level from 6 hours before admission to intensive care unit (ICU) and 24 hours after admission to ICU], blood biochemical indexes, coagulation function, vital signs, severity score and outcome indicators were extracted. The curves of Hb level vs. 28-day mortality risk were developed by using the restricted cubic spline model based on the Cox regression analysis. The patients were divided into four groups (Hb < 100 g/L, 100 g/L ≤ Hb < 130 g/L, 130 g/L ≤ Hb < 150 g/L, Hb ≥ 150 g/L groups) based on these curves. The outcome indicators of patients in each group were analyzed, and the 28-day Kaplan-Meier survival curve was drawn. Logistic regression model and Cox regression model were used to analyze the relationship between Hb level and 28-day mortality risk in different groups. A total of 7 473 elderly patients with sepsis were included. There was a "U" curve relationship between Hb levels within 24 hours after ICU admission and the risk of 28-day mortality in patients with sepsis. The patients with 100 g/L ≤ Hb < 130 g/L had a lower risk of 28-day mortality. When Hb level was less than 100 g/L, the risk of death decreased gradually with the increase of Hb level. When Hb level was ≥ 130 g/L, the risk of death gradually increased with the increase of Hb level. Multivariate Logistic regression analysis revealed that the mortality risks of patients with Hb < 100 g/L [odds ratio (OR) = 1.44, 95% confidence interval (95%CI) was 1.23-1.70, P < 0.001] and Hb ≥ 150 g/L (OR = 1.77, 95%CI was 1.26-2.49, P = 0.001) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (OR = 1.21, 95%CI was 0.99-1.48, P = 0.057). The multivariate Cox regression analysis suggested that the mortality risks of patients with Hb < 100 g/L [hazard ratio (HR) = 1.27, 95%CI was 1.12-1.44, P < 0.001] and Hb ≥ 150 g/L (HR = 1.49, 95%CI was 1.16-1.93, P = 0.002) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (HR = 1.17, 95%CI was 0.99-1.37, P = 0.053). Kaplan-Meier survival curve showed that the 28-day survival rate of elderly septic patients in 100 g/L ≤ Hb < 130 g/L group was significantly higher than that in Hb < 100 g/L, 130 g/L ≤ Hb < 150 g/L and Hb ≥ 150 g/L groups (85.26% vs. 77.33%, 79.81%, 74.33%; Log-Rank test: χ2 = 71.850, P < 0.001). Elderly patients with sepsis exhibited low mortality risk if their 100 g/L ≤ Hb < 130 g/L within 24 hours after admission to ICU, and both higher and lower Hb levels led to increased mortality risks.

Assessment of risk of overall and late distant recurrence by Breast Cancer Index in postmenopausal women with early-stage, HR+ breast cancer in the TEAM trial.

509 Background: Individual risk assessment of distant recurrence (DR) is particularly relevant for early-stage HR+ breast cancer patients, as they face a prolonged risk of recurrence even after adjuvant endocrine therapy. Previously, we have shown that the Breast Cancer Index (BCI) and BCIN+ risk groups are significantly prognostic for risk of overall (0-10y) and late (5-10y) distant recurrence in N0 and N1 breast cancer patients, respectively, enrolled in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial. Here, the prognostic performance of BCI and BCIN+ as a continuous risk score for overall and late distant recurrence was evaluated in the TEAM trial. Methods: BCI testing was performed blinded to clinical outcome with BCI/BCIN+ risk scores calculated as previously described. Cox proportional hazard models adjusted for age, tumor size, grade and treatments were used to estimate hazard ratios (HRs) and the associated 95% confidence intervals (CIs) for BCI/ BCIN+ continuous risk scores. The 10y risk of overall and late DR were estimated as a function of risk scores from the Cox models using Breslow estimates. Results: Continuous risk curves for overall and late DR were obtained in patients who did not receive adjuvant chemotherapy and those who remained DR-free at 5 years regardless of chemotherapy, respectively, to reflect the two key time points for breast cancer treatment decision-making. InN0 patients not treated with chemotherapy (N = 1197), BCI was significantly prognostic for overall DR with a HR of 1.39 (95% CI 1.25-1.54; p &lt; 0.001), while BCIN+ was significantly prognostic in N1 patients who did not receive chemotherapy (N = 1319) with a HR of 4.29 (95% CI 2.93-6.28; p &lt; 0.001). Among patients who remained DR-free at 5 years, in the N0 subset (N = 1285), BCI was significantly prognostic for late DR with a HR of 1.23 (95% CI 1.07-1.42; p &lt; 0.001), while BCIN+ remained to be significantly prognostic in the N1 subset (N = 1762) with a HR of 2.78 (95% CI 1.75-4.43; p &lt; 0.001). Similar results were observed in the HER2- subset for both overall and late DR. Continuous risk curves for BCI and BCIN+ for overall and late DR showed an increasing risk of DR with higher BCI/BCIN+ scores. Conclusions: Results from this largest BCI study to date further support the use of BCI to provide individualized risk estimates for both overall and late DR in women with HR+ breast cancer to aid in personalized decision-making for adjuvant therapy. [Table: see text]

One-step targeted maximum likelihood estimation for targeting cause-specific absolute risks and survival curves

Summary This paper considers the one-step targeted maximum likelihood estimation methodology for multi-dimensional causal parameters in general survival and competing risk settings where event times take place on the positive real line and are subject to right censoring. We focus on effects of baseline treatment decisions possibly confounded by pretreatment covariates, but remark that our work generalizes to settings with time-varying treatment regimes and time-dependent confounding. We point out two overall contributions of our work. First, our methods can be used to obtain simultaneous inference for treatment effects on multiple absolute risks in competing risk settings. Second, our methods can be used to achieve inference for the full survival curve, or a full absolute risk curve, across time. The one-step targeted maximum likelihood procedure is based on a one-dimensional universal least favourable submodel for each cause-specific hazard that we implement in recursive steps along a corresponding nonuniversal multivariate least favourable submodel. Our empirical study demonstrates the practical use of the methods.

Evaluating the application of the 2009 Institute of Medicine gestational weight gain guidelines on pregnant Chinese women

ABSTRACT Background The 2009 Institute of Medicine (IOM) gestational weight gain (GWG) guidelines were initially developed for pregnant women in the United States. Objective This study aimed to investigate whether the IOM guidelines were suitable for pregnant Chinese women. Methods A retrospective cohort study comprising 20,593 singleton pregnant women was conducted at the Beijing Obstetrics and Gynaecology Hospital (1 January 2018 to 31 December 2019). Applicability was evaluated by comparing the GWG corresponding to the lowest point of the predicted composite risk curve with the 2009 IOM GWG Guidelines. The IOM Guidelines serve as the standard for the GWG categories and the pre-pregnancy body mass index. An exponential function model was used to fit the weight gain during pregnancy and the probability of caesarean section, preterm birth, small for gestational age, and large for gestational age. A quadratic function model was used to fit the combined probability of the above-mentioned adverse pregnancy outcomes. The applicability of the IOM guidelines was evaluated by comparing the weights corresponding to the lowest predicted probability with the GWG range recommended by the IOM guidelines. Results According to the 2009 IOM GWG Guidelines, 43% of the women achieved adequate weight, almost 32% gained excessive weight, and 25% gained inadequate weight. The GWG range proposed by the IOM included the lowest predicted probability value for underweight women and exceeded the lowest predicted probability for normal weight, overweight, and obese women. Conclusions The 2009 IOM guidelines were suitable for Chinese women whose pre-pregnancy body mass index was classified as underweight. The guidelines were not suitable for normal, overweight, or obese pre-pregnancy body mass index classifications. Therefore, based on the above evidence, the 2009 IOM guidelines are not suitable for all Chinese women.

Effect of bridge design parameters on multi-hazard performance of river-crossing bridges

River-crossing bridges in seismically active regions are typically susceptible to two natural hazards – earthquakes and floods. For such bridges, design parameters related to piers may play major roles in bridge multi-hazard performance. In this study, the same was explored for key bridge design parameters – the aspect ratio and longitudinal reinforcement ratio of piers and the differential ground elevation between multiple bents. The multi-hazard condition in the southeast of Nepal was considered as the test-bed hazard condition. The regional seismic hazard was represented using a suite of earthquakes generated based on regional seismic design spectra. Due to the flood hazard in the region, expected pier scour of investigated bridges was estimated from 100-year flood discharge (including climate change projection) in the Koshi River, Nepal. Three-dimensional finite-element models of the chosen bridges, with and without scour and with ±10% variations in the stated design parameters, were developed. Fragility and risk curves of the bridges were developed and compared in order to assess the relative influence of the design parameters on bridge performance. It was found that the aspect ratio and longitudinal reinforcement ratio of piers can significantly influence the multi-hazard performance of riverine bridges. The findings also demonstrate how design parameters may be revised to perform risk-targeted multi-hazard design of bridges.

Cuproptosis-related lncRNAs forecast the prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a highly heterogeneous cluster of hematologic malignancies. Leukemic stem cells (LSCs) are one of the culprits for the persistence and relapse of AML. The discovery of copper-induced cell death, namely cuproptosis, gives bright insights into the treatment of AML. Analogous to copper ions, long non-coding RNAs (lncRNAs) are not bystanders for AML progression, especially for LSC physiology. Uncovering the involvement of cuproptosis-related lncRNAs in AML will benefit clinical management. Detection of prognostic relevant cuproptosis-related lncRNAs are carried out by Pearson correlation analysis and univariate Cox analysis with RNA sequencing data of The Cancer Genome Atlas-Acute Myeloid Leukemia (TCGA-LAML) cohort. After the least absolute shrinkage and selection operator (LASSO) regression and the subsequent multivariate Cox analysis, a cuproptosis-related risk score (CuRS) system was derived to weigh the risk of AML patients. Thereafter, AML patients were classified into two groups by their risk property which was validated with principal component analysis (PCA), risk curves, Kaplan-Meier survival analysis, the combined receiver operating characteristic (ROC) curves, and nomogram. Variations in biological pathways and divergences in immune infiltration and immune-related processes between groups were resolved by GSEA and CIBERSORT algorism, respectively. Response to chemotherapies were scrutinized as well. The expression profiles of the candidate lncRNAs were examined by real-time quantitative polymerase chain reaction (RT-qPCR) and the specific mechanisms of lncRNA FAM30A were determined by transcriptomic analysis. We fabricated an efficient prognostic signature named CuRS incorporating 4 lncRNAs (TRAF3IP2-AS1, NBR2, TP53TG1, and FAM30A) relevant to immune environment and chemotherapy responsiveness. The relevance of lncRNA FAM30A with proliferation, migration ability, Daunorubicin resistance and its reciprocal action with AUF1 were demonstrated in an LSC cell line. Transcriptomic analysis suggested correlations between FAM30A and T cell differentiation and signaling, intercellular junction genes. The prognostic signature CuRS can guide prognostic stratification and personalized AML therapy. Analysis of FAM30A offers a foundation for investigating LSC-targeted therapies.

Effects of a ground-glass opacity component on the recurrence and survival of pathological stage IA3 lung adenocarcinoma: a multi-institutional retrospective study.

This study aimed to evaluate the effect of the presence of a radiographically manifested ground-glass opacity (GGO) component on the prognosis of patients with pathological stage IA3 lung adenocarcinoma. Patients diagnosed with pathological stage IA3 lung adenocarcinoma who underwent radical surgery at two medical institutions in China between July 2012 and July 2020 were enrolled. The cumulative incidence of recurrence (CIR) and cumulative incidence of death (CID) in patients with and without a GGO component were compared. Risk curves for the recurrence and tumor-related death overtime were analyzed between the two groups according to life table. In order to validate the prognostic value of GGO components, the recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated. Decision curve analysis (DCA) was performed to evaluate the clinical benefit rate of different models. Among the 352 included patients, the presence of a GGO component was radiographically shown in 166 (47.2%) patients, while 186 (52.8%) displayed solid nodules. Patients exhibiting the absence of a GGO component had higher incidences of total recurrence (17.2% vs. 3.0%, P<0.001), local-regional recurrence (LRR) (5.4% vs. 0.6%, P=0.010), distant metastasis (DM) (8.1% vs. 1.8%, P=0.008), and multiple recurrences (4.3% vs. 0.6%, P=0.028) than the presence-GGO component group. The 5-year CIR and CID were 7.5% and 7.4% in the presence-GGO component group, and 24.5% and 17.0% in the absence-GGO component group, respectively, with statistically significant differences between the two groups (P<0.05). The risk of recurrence in patients with the presence of GGO components showed a single peak at 3 years postoperatively, while patients with the absence of GGO components showed a double peak at 1 and 5 years after surgery, respectively. However, the risk of tumor-related death peaked in both groups at 3 and 6 years postoperatively. Multivariate Cox analysis showed that the presence of a GGO component was a favorable independent risk factor for pathological stage IA3 lung adenocarcinoma patients (P<0.05). Pathological stage IA3 lung adenocarcinoma with or without GGO components are two types of tumors with different invasive abilities. In clinical practice, we should develop different treatment and follow-up strategies.