A GAN-based genetic algorithm for solving the 3D bin packing problem.

The 3D bin packing problem is a challenging combinatorial optimization problem with numerous real-world applications. In this paper, we present a novel approach for solving this problem by integrating a generative adversarial network (GAN) with a genetic algorithm (GA). Our proposed GAN-based GA utilizes the GAN to generate high-quality solutions and improve the exploration and exploitation capabilities of the GA. We evaluate the performance of the proposed algorithm on a set of benchmark instances and compare it with two existing algorithms. The simulation studies demonstrate that our proposed algorithm outperforms both existing algorithms in terms of the number of used bins while achieving comparable computation times. Our proposed algorithm also performs well in terms of solution quality and runtime on instances of different sizes and shapes. We conduct sensitivity analysis and parameter tuning simulations to determine the optimal values for the key parameters of the proposed algorithm. Our results indicate that the proposed algorithm is robust and effective in solving the 3D bin packing problem. The proposed GAN-based GA algorithm and its modifications can be applied to other optimization problems. Our research contributes to the development of efficient and effective algorithms for solving complex optimization problems, particularly in the context of logistics and manufacturing. In summary, the proposed algorithm represents a promising solution to the challenging 3D bin packing problem and has the potential to advance the state-of-the-art in combinatorial optimization.

[Study on revision of standard limits for nitrogen dioxide in "Standards for indoor air quality（GB/T 18883-2022）" in China].

Nitrogen dioxide (NO2) is an important indoor air pollutant, with both outdoor and indoor sources contributing to indoor NO2 exposure levels. Considering the association of high NO2 exposure with adverse health effects, the Standards for indoor air quality (GB/T 18883-2022) have been revised to further restrict indoor NO2 limit values. The 1-h average concentration limit value for NO2 has been reduced from 0.24 mg/m3 to 200 µg/m3.This study analyzed the technical contents related to the determination of the limits of indoor NO2 in Standards for Indoor Air Quality (GB/T 18883-2022), including source, exposure level, health effects, and the process and evidence basis for determining the limit value. It also proposed prospects for the direction for the implementation of the indoor NO2 standard.

[Association between gestational diabetes mellitus and preterm birth subtypes].

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.

[Progress and future perspective of epidemiological research of air pollution and climate change in the context of achieving carbon peaking and carbon neutrality goals].

Climate change is the great health challenge for human beings in the 21st century. Air pollution is also an important public health problem worldwide. China announced the climate commitment to achieve carbon peaking by 2030 and carbon neutrality by 2060. Achieving these goals would not only have far-reaching effects on air pollution control and climate change, but also improve the population health in China. Air pollution and climate change epidemiology are important aspects of environmental epidemiology. In this paper, we discuss the current status and future development of epidemiological research of air pollution and climate change in the context of achieving carbon peaking and carbon neutrality goals to provide ideas and suggestions for environmental and health studies in the future.

Genetic influences of the effect of circulating inflammatory cytokines on osteoarthritis in humans.

OBJECTIVE: The causal relationship between inflammatory cytokines and Osteoarthritis (OA) has not been well investigated. This study investigated the causal role of inflammatory cytokines in the risk of OA and total joint arthroplasty using the Mendelian randomization (MR) method. METHOD: Single nucleotide polymorphisms (SNPs) robustly associated with inflammatory cytokines were used as instrumental variables. The inverse-variance weighted (IVW) method with false discovery rate (FDR) adjusted P-value (q-value) for multiple comparisons were used as the main MR method to estimate causal effects based on the summary-level data for OA (knee and hip OA, respectively) and total joint arthroplasty (TJA). Sensitivity analyses validated the robustness of the results and ensured the absence of heterogeneity and horizontal pleiotropy. RESULTS: After FDR adjustment, macrophage colony-stimulating factor (MCSF) and vascular endothelial growth factor (VEGF) were identified as causally associated with knee OA (MCSF, odds ratio [OR]: 1.16, 95% confidence interval [CI]: 1.09-1.23, q = 5.05 × 10-5; VEGF, OR: 1.09, 95% CI: 1.04-1.15, q = 0.011). We also observed that genetically predicted MCSF and VEGF were positively associated with the risk of TJA, and MCP3 was negatively associated with for the risk of TJA, although the effects seem fairly modest. Sensitivity analysis further excluded the influence of heterogeneity and horizontal pleiotropy. CONCLUSIONS: Inflammatory cytokines, namely MCSF and VEGF, were causally associated with knee OA, which could enhance our understanding of inflammation in OA pathology.

[A panel study on the acute respiratory effects of ambient particles of different sizes on children in Shanghai].

Objective: To explore the association between size-fractionated particle number concentrations (PNC) and respiratory health in children. Methods: From November 2018 to June 2019, there were 65 children aged 6-9 years from an elementary school in shanghai recruited in this panel study with three rounds of follow-up. The forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and exhaled nitric oxide (FeNO) levels were measured and buccal mucosa samples of children were collected at each follow-up visit. The level of PNC, temperature and humidity of the elementary school was monitored from 3 days before each physical examination to the end of the physical examination. The linear mixed effects model was used to analyze the association between PNC and indicators of respiratory health in children. Results: Linear mixed effects model analysis revealed that, at lag 2 day, an interquartile range increase in PNC for particles measuring 0.25-0.40 µm was associated with the absolute changes in FVC, FEV1 and abundance-based coverage estimator (ACE) about -60.15 ml (95%CI:-88.97 ml, -31.32 ml), -34.26 ml (95%CI:-63.22 ml, -5.31 ml), -6.00 (95%CI:-9.15, -2.84) and percentage change in FeNO about 12.10% (95%CI: 3.05%, 21.95%), respectively. These adverse health effects increased with the decrease of particle size. Conclusion: The short-term exposure to particulate matter is associated with reduced lung function, buccal microbe diversity and higher airway inflammation level among children. These adverse health effects may increase with the decrease of particle size.

[Formation of study population for causal inference].

Epidemiological analysis describes and compares the characteristics of a certain number of people to make causal inferences. The formation of the study population is always the first step. In this paper, we first define the concepts of cross-sections at both individual level and population level and introduce the three assumptions needed in the measurements in observational studies, i. e. the true values of the attributes are stable with time, the attribute variables are independent and the individuals are independent during the measuring process. We also determine that the causal inference research should be unified based on the time of the occurrence or beginning of a postulated cause, or exposure, should be in. Then, based on the dual roles of the population cross-section with causal thinking, we propose that research designs can be classified into two types with different characteristics: history reconstruction research and future exploration research. Finally, we briefly analyze the research design framework and the relationship between estimated effects and different designs. The discussion of the formation of a study population from the perspective of causal thinking can make a foundation for the classification of causal inference research design with appropriate effect parameters, which needs to be further studied.

Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis: a retrospective analysis with propensity score matching.

BACKGROUND: Continuous infusion of conventional amphotericin B (CCAB) is used in ICUs for pre-emptive treatment of invasive fungal infections. Amphotericin B has previously been associated with nephrotoxicity. OBJECTIVES: To investigate if CCAB with therapeutic drug monitoring (TDM) results in renal impairment over time in critically ill patients with abdominal sepsis. PATIENTS AND METHODS: The study was conducted at mixed medical-surgical ICUs of two large teaching hospitals in the Netherlands. Consecutive patients who were treated on the ICUs between 2006 and 2019 for abdominal sepsis, with or without CCAB, were included. CCAB dosing was guided by TDM. Serum creatinine concentrations and renal failure scores of patients with CCAB treatment were compared with those without CCAB treatment. Excluded were: (i) patients treated with CCAB for less than 72 h; and (ii) patients with renal replacement therapy. RESULTS: A total of 319 patients were included (185 treated with CCAB and 134 controls). A multiple linear regression model showed that the serum creatinine concentration was independent of CCAB treatment (ß = -0.023; 95% CI = -12.2 to 7.2; P = 0.615). Propensity score matching resulted in 134 pairs of CCAB-treated and non-treated patients. Again, the analysis of these pairs showed that the cumulative CCAB dose was not associated with serum creatinine concentration during intensive care treatment (ß = 0.299; 95% CI = -0.38 to 0.98; P = 0.388). CONCLUSIONS: CCAB with TDM did not result in renal impairment over time in critically ill patients with abdominal sepsis.

The burden of heat-related mortality attributable to recent human-induced climate change.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study.

PURPOSE: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. MATERIALS & METHODS: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. RESULTS: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. CONCLUSIONS: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

Protective effects of dietary fish-oil supplementation on skin inflammatory and oxidative stress biomarkers induced by fine particulate air pollution: a pilot randomized, double-blind, placebo-controlled trial.

BACKGROUND: Exposure to fine particulate matter (with an aerodynamic diameter ≤ 2·5 µm, PM2·5 ) air pollution has been associated with skin-related diseases or disorders. OBJECTIVES: To evaluate the potential skin-protective effects of fish-oil supplementation against PM2·5 exposure. MATERIALS AND METHODS: This is an exploratory analysis based on a pilot randomized, double-blind, placebo-controlled trial among 65 healthy young adults between September 2017 and January 2018 in Shanghai, China. We randomly assigned participants to take either fish oil or placebo 2·5 g daily for four consecutive months. Four rounds of skin D-Squame® tape samples were collected in the last 2 months, and five secondary biomarkers of skin inflammation and oxidative stress were measured. Fixed-site PM2·5 concentrations on campus were measured in real time. We used linear mixed-effect models to analyse the associations between short-term PM2·5 exposure and biomarkers in each group. RESULTS: The 24-h average PM2·5 concentration was 34·68 ± 15·83 µg m-3 . There were generally weaker associations between PM2·5 and biomarkers in the fish-oil group than in the placebo group, but the associations and the between-group differences varied by biomarkers and lag periods. Compared with the placebo group, for a 10-µg m-3 increase in PM2·5 concentration, the increments of interleukin-1α and carbonyl protein in the fish-oil group were 41·55% smaller [95% confidence interval (CI) 4·61-78·48%] at lag 0-48 h and 22·01% smaller (95% CI 11·25-32·77%) at lag 0-24 h, respectively. No significant between-group differences were observed for other biomarkers. CONCLUSIONS: This study suggested that dietary fish-oil supplementation may improve biomarkers of skin inflammation and oxidative-stress response to short-term PM2·5 exposure.

[A new classification of measured temporalities: based on the time axis in nature].

In causal inference, the concept of temporality (or directionality) has not been fully clarified. Starting from causal thinking, this paper divides the time axis in nature into three time domains and two time points by the occurrence timings of both a real cause and a real effect. This has anchored that causal inference can only be realized in the third domain. The measured temporalities can be divided into five types: cross-first-to-third-domain longitudinal (or experimental temporalities), cross-second-to-third-domain longitudinal, within-domain longitudinal, within-domain reversely longitudinal, and within-domain transversal (or observational temporalities). This new classification encompasses all measurement strategies, either for first or multiple measurements, or timely and delayed measurements. Except that the actual measurement for the cause occurs either before its occurrence (only in experiment) or within the second domain, all other measurements are similar to the act of historical reconstruction or "archaeology" , where the importance of measured temporalities may be inferior to the accuracy of the measurements. From the point of view that research design should integrate bias design, this new classification for measured temporalities based on the time axis in Nature, which has a clear meaning and helps to judge the possible biases in the observation methods, provides a basis for correct causal inferences.

[May cross-sectional studies provide causal inferences?]

Due to the flaws inherited in synchronicity, statistical association and survivor bias on variables under measurement, a common 'consensus' has been reached on "cross-sectiional studies (CSS) can lead to failure on causal inference". In this paper, under both causal thinking and diagram, the real and measured cross-sections are clearly defined that these two concepts only exist theoretically. In real CSS research, the temporal orders of measured variables are all non-synchronic, equivalent to the assumption that measurement variables are independent to each other, or there is no differentiated classification bias. Similar to cumulative case-control or historical cohort studies, both exposure and outcome that exist or occur before their measurements in cross-sectional studies, are actions of historical reconstruction or doing 'Archaeology'. One of the common preconditions for causal inference in such studies is that: there must be a causal relation between the measured variables and their historical counterparts. The measured variables are all agents of their corresponding real counterparts, and the temporal orders are not that important in causal inference. It is necessary to better understand the analytic role of the CSS.

[On 'Negative control methods': related principles, methods and applications].

Negative control methods (NCM) are developed based on the idea that negative controls should be tested with negative results. It also extends to the multiple comparison groups and used for specificity of association in population studies. Negative controls do not take part in studying the causal hypothesis but sharing the same potential bias structures. Under different purposes, NCM can be divided into methods on negative exposure, negative period or negative outcome controls. They are mainly used to detect and control bias, such as: selection bias, confounding bias and measurement bias, but leaving the sample size at secondary importance. Rational application of NCM can help improving the accuracy of causal inference in both experimental and observational processes.

Visualization of Nigrosome 1 from the Viewpoint of Anatomic Structure.

BACKGROUND AND PURPOSE: Parkinson disease is related to neurodegeneration and iron deposition in the substantia nigra pars compacta and nigrosome 1. However, visualization of nigrosome 1 via MR imaging is poor owing to the bilateral asymmetry, regardless of whether it is healthy. We focused on the magic angle and susceptibility effect and evaluated the anatomic slant structure of nigrosome 1 by tilting subjects' heads in the B0 direction. MATERIALS AND METHODS: To investigate the effectiveness of the magic angle, we tilted the volunteers' heads to the right and left in the B0 direction or not at all for evaluating correlations between the degree of head tilting and visualization of the right nigrosome 1 and left nigrosome 1 using 3D spoiled gradient-echo sequences with multiecho acquisitions. We evaluated the susceptibility of nigrosome 1 and the local field using quantitative susceptibility mapping to assess static magnetic field inhomogeneity. RESULTS: The heads tilted to the right and left showed significantly higher contrasts of nigrosome 1 and the substantia nigra pars compacta than the nontilted heads. No significant differences were observed in the visualization and susceptibility between the right nigrosome 1 and left nigrosome 1 for each head tilt. The effect of the magic angle was remarkable in the nontilted heads. This finding was supported by quantitative susceptibility mapping because the anatomic slant structure of nigrosome 1 was coherent between the axis of nigrosome 1 and the magic angle. CONCLUSIONS: The asymmetric visualization of nigrosome 1 is affected by the magic angle and susceptibility. The anatomic slant structure of nigrosome 1 causes these challenges in visualization.

An in vitro developmental neurotoxicity screening assay for retinoic acid-induced neuronal differentiation using the human NT2/D1 cell line.

Traditional approaches (e.g., neurobehavior, neuropathology) can detect alterations in apical endpoints indicative of developmental neurotoxicity (DNT). However, there is an increasing desire to understand mode-of-action (MOA) for DNT effects; thus, this short communication describes initial work on a neuronal differentiation assay. Basically, our laboratory used the human NT2/D1 cell line to develop an assay to evaluate toxicants for effects on all-trans retinoic acid (RA)-induced neuronal differentiation. Based on literature reports, we selected a neuronal protein, neuronal class III ß-tubulin (ß3-tubulin), as a marker of differentiation. For this assay, cultured RA-treated NT2 cells were trypsinized to individual cells, methanol fixed, and labeled with a ß3-tubulin specific monoclonal antibody (TUJ1). Characterization studies using 100,000 cells/sample showed that NT2 cells had appreciable expression of ß3-tubulin starting around day 7 of the differentiation process with a peak expression noted around day 12. Methylmercury, 22(R)-hydroxycholesterol, N-(4-hydroxyphenol)retinamide (4HPR), and 9-cis retinoic acid were selected as initial test compounds. Of these, only 9-cis RA, which is known to affect the RA pathway, was positive for specific impacts on differentiation. These results demonstrate the feasibility of using a flow cytometry method targeting specific cellular biomarkers for evaluating effects on neuronal differentiation. Additional assays are needed to detect compounds targeting other (non-RA) neuronal differentiation pathways. Ultimately, a battery of in vitro assays would be needed to evaluate the potential MOAs involved in altered neuronal differentiation.

Non-surgical treatment of knee osteoarthritis.

Knee osteoarthritis is one of the most common degenerative diseases causing disability in elderly patients. Osteoarthritis is an increasing problem for ageing populations, such as that in Hong Kong. It is important for guidelines to be kept up to date with the best evidence-based osteoarthritis management practices available. The aim of this study was to review the current literature and international guidelines on non-surgical treatments for knee osteoarthritis and compared these with the current guidelines in Hong Kong, which were proposed in 2005. Internationally, exercise programmes for non-surgical management of osteoarthritis have been proven effective, and a pilot programme in Hong Kong for comprehensive non-surgical knee osteoarthritis management has been successful. Long-term studies on the effectiveness of such exercise programmes are required, to inform future changes to guidelines on osteoarthritis management.

[Research progress of ambient air pollution and human health in China].

As one of the major environmental and health problems in China, ambient air pollution has attracted substantial public concerns. This paper reviews the current evidence on air pollution and population health in China, including acute health effect studies, chronic health effect studies, disease burden, and interventions studies. Future research directions are also discussed.