Beta spending function based on conditional power in group sequential design.

Conditional power (CP) serves as a widely utilized approach for futility monitoring in group sequential designs. However, adopting the CP methods may lead to inadequate control of the type II error rate at the desired level. In this study, we introduce a flexible beta spending function tailored to regulate the type II error rate while employing CP based on a predetermined standardized effect size for futility monitoring (a so-called CP-beta spending function). This function delineates the expenditure of type II error rate across the entirety of the trial. Unlike other existing beta spending functions, the CP-beta spending function seamlessly incorporates beta spending concept into the CP framework, facilitating precise stagewise control of the type II error rate during futility monitoring. In addition, the stopping boundaries derived from the CP-beta spending function can be calculated via integration akin to other traditional beta spending function methods. Furthermore, the proposed CP-beta spending function accommodates various thresholds on the CP-scale at different stages of the trial, ensuring its adaptability across different information time scenarios. These attributes render the CP-beta spending function competitive among other forms of beta spending functions, making it applicable to any trials in group sequential designs with straightforward implementation. Both simulation study and example from an acute ischemic stroke trial demonstrate that the proposed method accurately captures expected power, even when the initially determined sample size does not consider futility stopping, and exhibits a good performance in maintaining overall type I error rates for evident futility.

Evaluating the Effects of Food Deserts and Food Swamps in an Urban Burn Patient Population.

Poverty is a known risk factor for burn injury and is associated with residency in food deserts and food swamps. Our aim was to determine the prevalence of residency in food deserts and food swamps and to investigate the relationship between food environment, comorbidities, and wound healing in burn patients. We performed a retrospective chart review of all burn patients age ≥ 18 seen in the emergency department or admitted to the burn service at an ABA-verified urban academic center between January 2016 and January 2022. Patient GeoIDs were used to classify residency in food deserts and food swamps and comorbidities and demographics were recorded. A subset of patients with less than 20% total body surface area burns who underwent single-operation split-thickness skin grafting was identified for wound healing analysis. A total of 3,063 patients were included, with 206 in the heal-time analysis. 2,490 (81.3%) lived in food swamps and 96 (3.1%) lived in food deserts. Diabetes, hypertension, and tobacco smoking were more prevalent in food swamps than food deserts or good access areas. While there was no significant effect of food environment on wound healing, diabetes was associated with longer heal times. Most burn patients reside in food swamps, which are associated with a higher prevalence of hypertension, diabetes, and smoking. Food environment was not significantly associated with wound healing. Not having diabetes was associated with a shorter time to wound healing.

Psychopathology, disordered eating, and impulsivity as predictors of weight loss 24 months after metabolic and bariatric surgery.

BACKGROUND: The relationship between theoretically relevant psychosocial and behavioral variables and outcomes of metabolic and bariatric surgery remains unclear. Some studies have found that the presence of psychopathology, disordered eating, and impulsivity, either before surgery or during the early postoperative period, is associated with suboptimal postoperative weight loss. Other studies have not found these relationships. OBJECTIVE: Examine the relationship between psychopathology, disordered eating, impulsivity, and weight loss 24 months postoperatively. SETTING: Two large, urban university health systems. METHODS: Participant characteristics were collected using validated interviews, patient-reported outcome measures, and computerized assessment methods. Linear mixed effect models were used to test the association of the variables of interest on percent weight loss (%WL). RESULTS: Three hundred participants were enrolled at baseline; weight data at 24 months were available for 227 participants; between 181 and 53 individuals completed other outcome measures. The mean %WL was 23.3 ± 9.9% at 24 months. Patients who underwent Roux-en-Y gastric bypass lost more weight than those who underwent sleeve gastrectomy. The presence of subjective binge episodes at baseline was related to a greater %WL at 24 months; there were no other baseline predictors. The presence of eating disorder diagnoses and disordered eating symptoms after surgery were associated with smaller weight losses over 24 months. Current and lifetime psychopathology and impulsivity were unrelated to %WL at 24 months. CONCLUSION: Disordered eating after bariatric surgery was associated with a smaller %WL at postoperative year 2. Additional monitoring of these symptoms in the early postoperative period is recommended. Psychotherapeutic and/or dietary interventions may promote more optimal weight loss outcomes.

Developmental timing of child maltreatment in relation to obesity and substance use disorder in late adolescence.

Objective: Obesity and substance use are leading preventable causes of mortality, yet their origins in violence remain poorly understood. This study examined child maltreatment in relation to obesity and symptoms consistent with substance use disorder (SUD) in late adolescence, determining the roles of the child maltreatment type and timing, and gender. Methods: The sample (N = 1,161) was drawn from the Longitudinal Studies of Child Abuse and Neglect. Obesity and SUD were measured at 18-years. Lifetime child protective services records and youth self-reports indicated physical abuse, sexual abuse, supervisory neglect, failure-to-provide neglect, and emotional maltreatment during early childhood, middle childhood, and adolescence. Results: In the overall sample, emotional maltreatment during adolescence was associated with obesity (OR = 2.03, 95% CI: 1.25, 3.30) and SUD (OR = 2.00, 95% CI: 1.20, 3.35), and adolescent physical abuse with obesity (OR = 2.20, 95% CI: 1.36, 3.58). In girls, early childhood physical abuse was associated with SUD (OR = 2.35, 95% CI: 1.08, 5.12), and emotional maltreatment during adolescence with obesity (OR = 2.16, 95% CI: 1.10, 4.23) and SUD (OR = 3.21, 95% CI: 1.37, 7.3 5). Adolescent physical abuse and obesity were associated in boys (OR = 3.18, 95% CI: 1.45, 6.98). Gender moderation was identified for an inverse relationship between supervisory neglect and obesity in girls (OR = .26, 95% CI: .07, .99). Conclusions: Type and timing contribute to the effects of child maltreatment, contingent upon gender. Intervention focused on adolescent emotional maltreatment may reduce both SUD and obesity.

Sample size estimation for stratified cluster randomization trial with survival endpoint.

Cluster randomization trials with survival endpoint are predominantly used in drug development and clinical care research when drug treatments or interventions are delivered at a group level. Unlike conventional cluster randomization design, stratified cluster randomization design is generally considered more effective in reducing the impacts of imbalanced baseline prognostic factors and varying cluster sizes between groups when these stratification factors are adopted in the design. Failure to account for stratification and cluster size variability may lead to underpowered analysis and inaccurate sample size estimation. Apart from the sample size estimation in unstratified cluster randomization trials, there are no development of an explicit sample size formula for survival endpoint when a stratified cluster randomization design is employed. In this article, we present a closed-form sample size formula based on the stratified cluster log-rank statistics for stratified cluster randomization trials with survival endpoint. It provides an integrated solution for sample size estimation that account for cluster size variation, baseline hazard heterogeneity, and the estimated intracluster correlation coefficient based on the preliminary data. Simulation studies show that the proposed formula provides the appropriate sample size for achieving the desired statistical power under various parameter configurations. A real example of a stratified cluster randomization trial in the population with stable coronary heart disease is presented to illustrate our method.

Heat-Killed Saccharomyces boulardii Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Restoring the Intestinal Barrier, Reducing Inflammation, and Modulating the Gut Microbiota.

Ulcerative colitis (UC) is a global intestinal disease, and conventional therapeutic drugs often fail to meet the needs of patients. There is an urgent need to find efficient and affordable novel biological therapies. Saccharomyces boulardii has been widely used in food and pharmaceutical research due to its anti-inflammatory properties and gut health benefits. However, there is still a relatively limited comparison and evaluation of different forms of S. boulardii treatment for UC. This study aimed to compare the therapeutic effects of S. boulardii, heat-killed S. boulardii, and S. boulardii ß-glucan on UC, to explore the potential of heat-killed S. boulardii as a new biological therapy. The results demonstrate that all three treatments were able to restore body weight, reduce the disease activity index (DAI), inhibit splenomegaly, shorten colon length, and alleviate histopathological damage to colonic epithelial tissues in DSS-induced colitis mice. The oral administration of S. boulardii, heat-killed S. boulardii, and S. boulardii ß-glucan also increased the levels of tight junction proteins (Occludin and ZO-1), decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in the serum, and suppressed the expressions of TNF-α, IL-1ß, and IL-6 mRNA in the colon. In particular, in terms of gut microbiota, S. boulardii, heat-killed S. boulardii, and S. boulardii ß-glucan exhibited varying degrees of modulation on DSS-induced dysbiosis. Among them, heat-killed S. boulardii maximally restored the composition, structure, and functionality of the intestinal microbiota to normal levels. In conclusion, heat-killed S. boulardii showed greater advantages over S. boulardii and S. boulardii ß-glucan in the treatment of intestinal diseases, and it holds promise as an effective novel biological therapy for UC. This study is of great importance in improving the quality of life for UC patients and reducing the burden of the disease.

Fe3O4/biochar modified with molecularly imprinted polymer as efficient persulfate activator for salicylic acid removal from wastewater: Performance and specific recognition mechanism.

In this study, a novel Fe3O4-based biochar coupled surface-imprinted polymer was constructed via simple hydrothermal route for salicylic acid recognition and degradation in advanced oxidation processes. The material exhibited excellent adsorption capability, up to 118.23 mg g-1, and efficient degradation performance, 87.44% removal rate within 240 min, based on integrating the advantages of both huge specific surface area as well as abundant functional groups from biochars and specific recognition sites from imprinted cavities. Moreover, high selectivity coefficient (11.67) showed stable recognition in single and binary systems. SO4•- and •OH were confirmed as reactive oxygen species in catalytic reaction according to quenching experiments and EPR analysis. The degradation mechanism and pathway were unraveled by DFT calculations and LC-MS. Furthermore, the results of toxicity evaluation, stability and reusability demonstrated application potential in the field of water environment restoration. This study confirmed that molecular imprinting provided a promising solution to targeted removal of emerging environmental pollutants by degrading after the enrichment of pollutants to the composites surface.

The heterogeneity effect of surveillance intervals on progression free survival.

Progression-free survival (PFS) is an increasingly important surrogate endpoint in cancer clinical trials. However, the true time of progression is typically unknown if the evaluation of progression status is only scheduled at given surveillance intervals. In addition, comparison between treatment arms under different surveillance schema is not uncommon. Our aim is to explore whether the heterogeneity of the surveillance intervals may interfere with the validity of the conclusion of efficacy based on PFS, and the extent to which the variation would bias the results. We conduct comprehensive simulation studies to explore the aforementioned goals in a two-arm randomized control trial. We introduce three steps to simulate survival data with predefined surveillance intervals under different censoring rate considerations. We report the estimated hazard ratios and examine false positive rate, power and bias under different surveillance intervals, given different baseline median PFS, hazard ratio and censoring rate settings. Results show that larger heterogeneous lengths of surveillance intervals lead to higher false positive rate and overestimate the power, and the effect of the heterogeneous surveillance intervals may depend upon both the life expectancy of the tumor prognoses and the censoring proportion of the survival data. We also demonstrate such heterogeneity effect of surveillance intervals on PFS in a phase III metastatic colorectal cancer trial. In our opinions, adherence to consistent surveillance intervals should be favored in designing the comparative trials. Otherwise, it needs to be appropriately taken into account when analyzing data.

Changes of physicochemical and functional properties of processed cheese made with natural cheddar and mozzarella cheeses during refrigerated storage.

The present study aimed to investigate changes of physicochemical and functional properties of the processed cheeses (PCs) made with Cheddar (PC1), Mozzarella (PC2) and both of them at a ratio of 1:1 (PC3) during storage at 4 °C for 4 months. The results showed that the type of natural cheese used affected the composition of PCs with lower fat content in PC2 due to the lower fat content of Mozzarella cheese used. PC2 with lower fat content showed decreased meltability and oil leakage compared with PC1 and PC3. The stretchability of all the samples significantly (P < 0.05) decreased during storage, and PC1 showed lower stretchability. This was confirmed by increased protein hydrolysis of all the samples during the storage with a higher level of proteolysis in PC1, leading to decreased stretchability of PCs. Further low-field nuclear magnetic resonance analysis indicated more entrapped water in cheese due to moisture migration into the cheese matrix that might squeeze the fat globules to aggregate, causing more fat leakage during later stages of storage. This was evidenced by microstructural analysis showing different extents of increase in fat particle sizes and decrease in free serum in all the PC samples over the storage time. Therefore, the present study provides further understanding of the mechanism of quality change of PC during refrigerated storage as affected by proteolytic properties and composition of natural cheese used.

Recognition of Speech With Dynamic Pitch Manipulation in Noise: Effects of Manipulation Methods.

PURPOSE: Dynamic pitch, which is defined as the variation in fundamental frequency in speech, is one of the acoustic cues that affect speech recognition in noise. Built on the evidence that a symmetrical manipulation of dynamic pitch led to poorer speech recognition, the present study examined the effect of an asymmetrical manipulation method on speech recognition in noise by younger and older adults. METHOD: Speech recognition accuracy in noise was measured from younger adults with normal hearing in Experiment 1, and speech reception threshold (in dB SNR) from older adults with normal hearing to mild-moderate hearing loss in Experiment 2. The dynamic pitch contours of the speech stimuli were manipulated using both symmetrical and asymmetrical methods. RESULTS: Younger adults recognized speech better in noise with asymmetrical than symmetrical manipulation, and with weakened than strengthened dynamic pitch. A substantial amount of variability was observed in a group of older listeners. This variability was predominately predicted by the listeners' age but not hearing thresholds or their ability to perceive dynamic pitch in fluctuating noise. CONCLUSIONS: The asymmetrical manipulation of dynamic pitch had a less negative effect than the symmetrical manipulation. This effect also interacted with pitch-change direction. These findings suggest the influence of perceptual naturalness on speech recognition with signal modification. Directions for future research are also discussed.

Competitive adsorption behaviors and mechanisms of Cd, Ni, and Cu by biochar when coexisting with microplastics under single, binary, and ternary systems.

In this study, the effects of coexistence with microplastics and co-ageing with the soil on adsorption behaviors and mechanisms of biochar for heavy metals were investigated. Adsorption experiments of Cd, Ni, and Cu by microplastics, biochar, and their combination were conducted in single, binary, and ternary systems. The results indicated that the heavy metal adsorption by microplastics was ranked as Ni > Cd > Cu, which increased with decreasing particle size, and the adsorption capacity of microplastics was enhanced after dry-wet and freeze-thaw ageing. Biochar preferentially adsorbed Cd in the single system, while the maximum adsorption of Cu was observed in the binary and ternary systems due to the minimizing impact of competition on the Cu adsorption by biochar. The heavy metal adsorption by the combination of microplastics and biochar was less than that by single biochar, and the smaller the particle size of microplastics, the greater the negative effects on heavy metal adsorption. Coexistence with microplastics reduced Cd adsorption of biochar by 0.72 %-50.35 %, Ni adsorption by 1.17 %-30.43 %, and Cu adsorption by 5.78 %-47.88 %, respectively. Moreover, coexistence with microplastics exacerbated the adverse impacts of competition on biochar adsorption for heavy metals. The contribution percentages of biochar mineral mechanisms for heavy metal adsorption were ranked as Cu > Cd > Ni. When coexisting with microplastics or after ageing, the mineral mechanisms of heavy metal adsorption by biochar significantly decreased. This study investigated the competitive adsorption behaviors and mechanisms of heavy metals by biochar when coexisting with microplastics, which highlighted that the application of biochar for the remediation of heavy metal pollution should be concerned with the impacts of microplastics.

Thromboelastography (TEG) parameters as potential predictors of malignancy and tumor progression in colorectal cancer.

PURPOSE: The purpose of this study was to investigate the use of thromboelastography (TEG) in patients with colorectal cancer and to examine whether the TEG parameters can be used as potential markers for disease screening and prediction of disease severity. METHODS: One-hundred fifteen healthy controls (HC), 43 patients with benign adenoma (BA), and 387 patients with colorectal cancers (CRC) were included in the study. TEG parameters (reaction time, R; clot kinetics, K; alpha angle, α-angle; maximum amplitude, MA), conventional laboratory parameters, and clinical information were collected and analyzed among the HC, BA, and CRC groups. Receiver operating characteristics (ROC) were used for differential analysis. The correlation between TEG parameters and pathological information of CRC (differentiation degree, vaso-nerve infiltration, TNM stage) was analyzed. The differences in TEG parameters at different stages of disease and pre-/post operation were compared. RESULTS: Shorter K and higher α-angle/MA were found in patients with CRC compared with HC and BA (P < 0.001). TEG parameters demonstrated moderate diagnostic value (distinguish CRC from HC + BA: K-AUC = 0.693, α-angle-AUC = 0.687, MA-AUC = 0.700) in CRC but did not outperform traditional laboratory parameters. TEG hypercoagulability was closely associated with tumor markers (carcinoma embryonic antigen and carbohydrate antigen 19-9) and pathological information (differentiation degree, vaso-nerve infiltration, and TNM stage) (P < 0.05). Trend analysis showed that K decreased, but α-angle/MA increased gradually as the tumor progressed (P < 0.001). K- and α-angle showed slightly better sensitivity in predicting advanced tumors compared to traditional laboratory parameters. In CRC patients, 3-6 months after tumor resection, K [from 1.8 (1.5, 2.3) to 1.9 (1.6, 2.6)], α-angle [from 65.3 (59.0, 68.6) to 63.7 (56.6, 68.5)], and MA [from 61.0 (58.2, 66.0) to 58.9 (55.8, 61.3)] exhibited modest improvements compared to their preoperative values (P < 0.05). CONCLUSION: TEG parameters possess moderate diagnostic value in CRC diagnosis and predicting advanced tumors, and they are closely linked to surgical interventions. Although TEG parameters do not significantly outperform traditional laboratory parameters, they still hold promise as potential alternative indicators in CRC patients.

Effects of Microplastic (MP) Exposure at Environmentally Relevant Doses on the Structure, Function, and Transcriptome of the Kidney in Mice.

As a common emerging environmental pollutant, microplastics (MPs) have been detected in a variety of environmental media and human bodies. The potential toxic effects and mechanisms of MPs need to be revealed urgently. MPs can be deposited in the kidney, and exposure to high doses of MPs can cause nephrotoxicity in experimental animals. In this study, we investigated the effects of exposure to polystyrene microplastics (PS-MPs) at environmentally relevant doses (0.1 and 1 mg/L) on kidney structure, function, and transcriptome in mice. We found that mice exposed to PS-MPs in drinking water for eight weeks had no change in body weight or kidney coefficient. PS-MPs administration decreased the levels of blood urea nitrogen (BUN) in mice, while serum creatinine (CRE) and uric acid (UA) concentrations were unaffected. Through using periodic acid-Schiff (PAS) and Masson staining, we discovered that the glomerular tuft area increased in the PS-MP-treated mice, while the degree of renal fibrosis remained unchanged. Furthermore, renal cortex transcriptomic analysis identified 388 and 303 differentially expressed genes (DEGs) in the 0.1 and 1 mg/L dose groups, respectively. The DEGs were highly enriched in mitochondrial-related terms and pathways of thermogenesis and oxidative phosphorylation. Moreover, protein-protein interaction (PPI) network analysis revealed that cytochrome b-c1 complex subunit 10 (UQCR11) and cytochrome c oxidase subunit 3 (MT-CO3) were important node proteins. These findings suggest that environmental exposure to MPs can cause abnormalities in renal structure and filtration function and that long-term exposure to MPs may be a risk factor for renal disease.

Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients.

BACKGROUND: Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. METHODS: We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates. RESULTS: In all, 290 OI patients met the inclusion criteria, where 221 had genetic records. Of these 221, about 2/3 had mutations in COL1A1 or COL1A2, followed by mutations in WNT1 (9.0%), IFITM5 (9.0%) and other OI risk genes. With an average age of 12.0 years (interquartile range [IQR] 6.9-16.1), 70.7% of the cohort had scoliosis (Cobb angle > 10°), including 106 (36.5%) mild (10°-25°), 40 (13.8%) moderate (25°-50°), and 59 (20.3%) severe (> 50°) scoliosis patients. Patients with either COL1A1 and COL1A2 were strongly biased toward having mild or no scoliosis, whereas patients with mutations in IFITM5, WNT1 and other recessive genes were more evenly distributed among the four outcome grades. Lower-limb discrepancy, bone mineral density (BMD) and age of first drug used were all significantly correlated with severity outcomes. Using multivariate logistic regression, we estimated that each year older adds an odds ratio of 1.13 (95% confidence interval [CI] 1.07-1.2) in progression into advanced stages of scoliosis. We estimated a cohort-wide progression rate of 2.7 degrees per year (95% CI 2.4-3.0). Early-onset patients experienced fast progressions during both infantile and adolescent stages. Twenty-five of the 59 (42.8%) patients with severe scoliosis underwent spinal surgeries, enjoying an average Cobb angle reduction of 33° (IQR 23-40) postoperatively. CONCLUSION: The severity and progression of scoliosis in osteogenesis imperfecta were affected by genetic factors including genotypes and mutation types, and non-genetic factors including age and BMD. As compared with COL1A1, mutations in COL1A2 were less damaging while those on IFITM5 and other recessive genes conferred damaging effects. Progression rates were the fastest in the adolescent adult age-group.

Comment on Rogers et al. The Combined Effects of Cannabis, Methamphetamine, and HIV on Neurocognition. Viruses 2023, 15, 674.

We read with great interest the article by Rogers et al. (2023), The Combined Effects of Cannabis, Methamphetamine, and HIV on Neurocognition, published in Viruses [...].

Both Saccharomyces boulardii and Its Postbiotics Alleviate Dextran Sulfate Sodium-Induced Colitis in Mice, Association with Modulating Inflammation and Intestinal Microbiota.

OBJECTIVE: To investigate the effect of Saccharomyces boulardii and its freeze-dried and spray-dried postbiotics on the intervention and potential mechanism of dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. [Methods] After the acclimation period of C67BL/6J mice, a colitis model was constructed by applying 2% DSS for 7 d, followed by 7 d of intervention. Subsequently, the disease activity index (DAI), organ index, colon length, colon HE staining of pathological sections, ELISA for blood inflammatory factors (Interleukin (IL)-1ß, IL-6, IL-10, Tumor necrosis factor (TNF)-α), Real time quantitative polymerase chain reaction (RT-qPCR) to determine the levels of colonic inflammatory factors (IL-1ß, IL-6, IL-10, TNF-α), Occludin gene expression, and intestinal flora were assessed to evaluate the protective effects of S. boulardii and its postbiotics on colitis in mice. RESULTS: Compared with the DSS group, S. boulardii and the postbiotics interventions effectively improved colonic shortening and tissue damage, increased the expression of intestinal tight junction protein, reduced the secretion of pro-inflammatory factors, increased the secretion of anti-inflammatory factors, and maintained the homeostasis of intestinal microorganisms. Postbiotics intervention is better than probiotics. CONCLUSIONS: S. boulardii and its postbiotics can effectively alleviate DSS-induced colitis in mice through modulating host immunity and maintaining intestinal homeostasis. Postbiotics are promising next-generation biotherapeutics for ulcerative colitis treatment.

Competitive adsorption and immobilization of Cd, Ni, and Cu by biochar in unsaturated soils under single-, binary-, and ternary-metal systems.

This study investigated the competitive adsorption and immobilization of cadmium (Cd), nickel (Ni), and copper (Cu) by biochar in unsaturated soils under single-, binary-, and ternary-metal systems. The results showed that the immobilization effects by the soil itself were in the order of Cu > Ni > Cd, and the adsorption capacities of freshly contaminated heavy metals by biochar were in the order of Cd > Ni > Cu in unsaturated soils. The adsorption and immobilization of Cd by biochars in soils was weakened by competition more in the ternary-metal system than that in the binary-metal system; the competition with Cu caused a more significant weakening effect than that with Ni. For Cd and Ni, nonmineral mechanisms preferentially adsorbed and immobilized Cd and Ni compared to mineral mechanisms, but the contributions of the mineral mechanisms to the adsorption gradually increased and became dominant with increasing concentrations (at average percentages of 62.59%-83.30% and 41.38%-74.29%, respectively). However, for Cu, the contributions of the nonmineral mechanisms to Cu adsorption were always dominant (average percentages of 60.92%-74.87%) and gradually increased with increasing concentrations. This study highlighted that the types of heavy metals and coexistence should be focused when remediating heavy metal contamination in soils.

Study design and methods of the Wells and Enteric disease Transmission (WET) Trial: a randomised controlled trial.

INTRODUCTION: The burden of disease attributed to drinking water from private wells is not well characterised. The Wells and Enteric disease Transmission trial is the first randomised controlled trial to estimate the burden of disease that can be attributed to the consumption of untreated private well water. To estimate the attributable incidence of gastrointestinal illness (GI) associated with private well water, we will test if the household treatment of well water by ultraviolet light (active UV device) versus sham (inactive UV device) decreases the incidence of GI in children under 5 years of age. METHODS AND ANALYSIS: The trial will enrol (on a rolling basis) 908 families in Pennsylvania, USA, that rely on private wells and have a child 3 years old or younger. Participating families are randomised to either an active whole-house UV device or a sham device. During follow-up, families will respond to weekly text messages to report the presence of signs and symptoms of gastrointestinal or respiratory illness and will be directed to an illness questionnaire when signs/symptoms are present. These data will be used to compare the incidence of waterborne illness between the two study groups. A randomly selected subcohort submits untreated well water samples and biological specimens (stool and saliva) from the participating child in both the presence and absence of signs/symptoms. Samples are analysed for the presence of common waterborne pathogens (stool and water) or immunoconversion to these pathogens (saliva). ETHICS: Approval has been obtained from Temple University's Institutional Review Board (Protocol 25665). The results of the trial will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04826991.

Quantitative transport and immobilization of cadmium in saturated-unsaturated soils with the combined application of biochar and organic fertilizer.

In this study, cadmium (Cd) transport and immobilization on passivators (biochar, organic fertilizer) and soils under saturated-unsaturated conditions were independently analyzed. The results showed that the Cd adsorption capacities of biochar and organic fertilizer were comparable in acidic soils. But in alkaline soils, the Cd adsorption capacity of organic fertilizer was significantly larger than that of biochar. In acidic soils, passivators effectively immobilized Cd, and the total net effects were in the order: combination (44.05-58.13%) > 3% biochar (31.96-46.88%) > 3% organic fertilizer (28.78-41.82%). In alkaline soils, all treatments had negative effects on Cd immobilization. For acidic soils, the immobilization of Cd was mainly attributed to the passivators, and the positive contribution percentages of relatively stable Cd increase by passivators were 81.05-100%, while those by soils were 0-18.95%. For alkaline soils, after the treatments of passivators, although a considerable amount of Cd was immobilized inside the passivator, Cd was activated more inside the soil. Therefore, it is noteworthy that soil conditions must be fully considered when applying biochar and organic fertilizers for Cd remediation.

Glial fibrillary acidic protein astrocytopathy and tuberculous meningoencephalitis occurring in a patient with Legionella pneumonia: a case report.

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently identified recurrent meningoencephalomyelitis with GFAP immunoglobulin G presence in the serum or cerebrospinal fluid (CSF) as a specific biomarker. GFAP astrocytopathy is closely associated with the occurrence of some tumors and often coexists with other antibodies, such as the N-methyl-D-aspartate receptor and aquaporin-4 antibodies. However, GFAP astrocytopathy complicated by central nervous system infection is rare. CASE PRESENTATION: Here, we present the case of a patient admitted to a local hospital due to a prominent fever and cough. The patient had a 1-month history of headaches before admission that were not considered serious at the time. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid revealed a high sequence number of Legionella pneumophila and a few mycobacteria. His cough and fever improved significantly after antibiotic treatment. Still, a slight headache remained. Subsequently, his condition worsened, and he visited our hospital with a disturbance of consciousness. Mycobacterium tuberculosis was detected with mNGS of the CSF, while the CSF and serum were also positive for GFAP antibodies. Following anti-tuberculosis and steroid therapy, the patient's symptoms improved, and he tested negative for the GFAP antibody. CONCLUSION: This is the first reported case of GFAP astrocytopathy complicated by tuberculous meningoencephalitis. Due to overlaps in the clinical manifestations of the two diseases, GFAP astrocytopathy is sometimes misdiagnosed as tuberculous meningoencephalitis. Therefore, in addition to ensuring careful identification of the two diseases, clinicians need to be aware of their possible co-existence.