OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective To investigate clinical effect and safety of eccentric reamer technique foraminoplasty during percutaneous endoscopic lumbar discectomy for the treatment of lumbar lateral recess stenosis.Methods All of 45 cases diagnosed of lumbar lateral recess stenosis between Apr 2010 to Jun 2012 were analyzed in our study.Among these cases,28 cases were male and 17 were female.The age of enrolled cases was 39-62 years old and the average age was 49.23±23.96 years old.All the cases were one-level,25 cases in L4,5 and 20 cases in L5S1.All the patients underwent percutaneous endoscopic lumbar discectomy.During surgery,eccentric reamer technique was applied for foraminoplasty.Perioperative data included surgical segment,surgical duration and blood loss during surgery.Oswestry Disability Index (ODI) and Visual analogue scale (VAS) for lower back and leg pain were recorded for the evaluation of surgical effect.All the data were recorded before surgery,1 day,1 month after surgery and final follow-up.Recurrent lumbar disc herniation,spinal canal hematoma,intervertebral disc infection,nerve root injury and post-operative dysthesia (POD) were recorded for complications.Results All the cases finished surgery and none of the cases was changed to other surgery method and no other electronic drill were used in these patients.Surgical duration was 45-76 min and average time was 61.23± 13.89 min.Blood loss during surgery was 10-25 ml and average blood loss was 15.02±4.33 ml.Post-operative hospitalization days were 1-3 days and 2.80±1.57 days.The follow-up time was 60-84 months and the average time was 73.23±8.47 months.ODI in one-day after surgery was 9.34±6.54％,significantly lower than 68.06±24.14％ before surgery and no statistically change had been observed in one-month after surgery and final follow-up.The VAS for lower back was 1.54±0.97 in one-day after surgery,significantly lower than 3.57±3.12 before surgery.The VAS for leg pain was 1.14±0.79 in one-day after surgery,significantly lower than 6.24±2.35 before surgery.During follow-up,1 case suffered from recurrent lumbar disc herniation (2.22％) and no intervertebral disc infection,spinal canal hematoma and POD was observed.Conclusion Eccentric reamer technique foraminoplasty in percutaneous endoscopic lumbar discectomy is an effective and safe surgical method for the treatment of lumbar lateral recess stenosis.