A Survey to Assess the Current Status of Structured Benefit-Risk Assessment in the Global Drug and Medical Device Industry.

BACKGROUND: This industry survey was conducted to gain insight into the ways structured Benefit-Risk assessment (sBRA) of medical products is approached across drug or medical device developing companies, including frameworks and methods that are currently used and areas where future work is being planned. METHODS: A survey containing 28 questions covering five key areas of sBRA was set-up and shared with representatives from the participating companies. Each company was asked to complete a single survey response including inputs across the company's multidisciplinary key representatives involved in benefit-risk assessment. RESULTS: Of the 26 participating companies, 21 (81%) are conducting sBRA. Considering these 21 qualitative frameworks were used by almost every company (19, 90%), while only 12 (57%) have used a quantitative method. Many companies have sBRA training (17, 81%), document templates (16,76%), Standard Operating Procedures (SOPs)/checklists (13, 62%), and /or best practice manuals/examples (12,57%) available. Considering all 26 companies Software tools (15, 58%) and BR planning documents (11,42%) were identified as areas into which many companies intend to put effort. CONCLUSIONS: The industry survey confirmed a wide usage of sBRA by many companies involved in research and development. Nevertheless, sBRA is evolving and several future opportunities like the implementation of visualization tools were identified by the representatives of the pharmaceutical companies. Finally, challenges like the cross-functional comprehension of the added value of sBRA are still seen.

Inequality characteristics and influencing factors of CO2 emissions per capita in Jiangsu Province, China.

Analyzing the inequality characteristics and influencing factors of CO2 emissions per capita (CEPC) is conducive to balancing regional development and CO2 emissions reduction. This study applied the Gini coefficient and Theil index to investigate the CEPC inequalities during 2005-2017 at the county level in Jiangsu Province, China. Considering the spatial spillover and interaction effects, the factors influencing CEPC were analyzed by a hierarchical spatial autoregressive model. The results showed that the inequalities in CEPC first increased and then decreased at the inter-regional, and inter-county levels. The spatial pattern of CEPC was stable, and there was a significantly positive spatial autocorrelation of CEPC at the county level. The High-High type counties were mainly located in Sunan (southern Jiangsu). The spatial interaction effects of the CEPC between the prefecture and county levels indicated that governments at the prefecture level should integrate their county governments to reduce the CEPC. Moreover, carbon intensity, GDP per capita, land urbanization, and industrial structure play an important role in reducing CEPC. Our findings provide a scientific basis for formulating reasonable and effective carbon emission reduction policies.

An Assessment of Trends in HIV-1 Prevalence and Incidence and Spatio-Temporal Analyses of HIV-1 Recent Infection Among MSM During the Surveillance Period Between 2018 and 2022 in Sichuan, China.

Background: Men who have sex with men (MSM) is one main type of high-risk activities facilitating HIV-1 transmission in Sichuan province. Previous works on HIV-1 incidence and prevalence among MSM only concentrated before 2018, the situation after that is unknown. In addition, the distribution of hot-spots related to current HIV-1 epidemic is also rarely known among MSM in Sichuan. Objective: To update trends of HIV-1 prevalence and incidence and to visualize hot-spots of ongoing transmission in Sichuan province during surveillance period among MSM between 2018 and 2022. Methods: Limiting Antigen Avidity assay was performed to detect recent infection within new HIV-1 diagnoses founded during surveillance period among MSM. The HIV-1 prevalence and incidence were calculated according to an extrapolation method proposed by publications and guidelines. Trend tests were performed using χ2 tests with linear-by-linear association. The spatial analysis was conducted with ArcGIS 10.7 to figure hot-spots of HIV-1 recent infections among MSM. Results: Between 2018 and 2022, 16,697 individuals participated in HIV-1 MSM sentinel surveillance program, of which 449 samples (98.25%) were tested with LAg-Avidity EIA, and 230 samples were classified as recent infection. Respectively, the overall prevalence and incidence were 2.74% and 3.69% (95% CI: 3.21, 4.16) and both had significant declining trends (p < 0.001). Luzhou city had a highest HIV-1 incidence (10.74%, 95% CI: 8.39, 13.10) over the study period and was recognized as a hot-spot for recent HIV-1 infection among MSM. Conclusion: During the surveillance period, both HIV-1 prevalence and incidence were declining. However, Luzhou city had an unusually high HIV-1 incidence and became an emerging hot-spot of recent HIV-1 infection among MSM. This finding suggested focused attention, cross-regional intervention strategies, and prevention programs are urgently required to curb the spread of ongoing transmission.

Increasing ratio of opportunistic infections associated with sunshine exposure and economic level burdening Chinese inflammatory bowel disease hospitalized patients: the first nationwide survey from 2014 to 2019.

BACKGROUND: The rising prevalence of opportunistic infections (OIs) in inflammatory bowel disease (IBD) in conjunction with the use of biologics/immunosuppressive agents has garnered attention. However, there is a dearth of research on OIs in Mainland China. This study seeks to evaluate the national ratio trend of OIs in IBD and elucidate the influence of economic and climate factors on IBD patients with OIs and their outcomes. METHODS: The nationwide data was obtained from the Inpatient medical record home page via the Health Statistics and Information Reporting System (HSRS). Patients diagnosed with IBD were enlisted for participation, and their demographic and clinical information, encompassing infection type, surgical procedures, and expenses, were gathered. The National Bureau of Statistics provided data on monthly sunshine exposure hours and yearly Gross Domestic Product (GDP). RESULTS: Findings indicate that between 2014 and 2019, a total of 381,752 patients with IBD were admitted to hospitals, with 364,249 patients lacking OIs and 17,503 patients presenting with OIs. The annual proportion of OIs exhibited an upward trend, rising from 3.54% in 2014 to 4.81% in 2019. There was a significant correlation observed between individuals who identified as male, those who visited hospitals in southern regions, or those originating from areas with lower GDP or shorter sunshine exposure hours, and a higher incidence of OIs. Among patients diagnosed with either Crohn's disease (CD) or ulcerative colitis (UC), Clostridium difficile was found to be the most prevalent infection, followed by Epstein-Barr virus and cytomegalovirus. Furthermore, the occurrence of OIs was found to be associated with an increased rate of surgical interventions in UC patients. CONCLUSIONS: The rising prevalence of OIs among hospitalized patients with IBD necessitates heightened attention towards mitigating associated risk factors, particularly among IBD patients residing in less developed regions or experiencing limited exposure to sunlight. This approach aims to minimize hospital stays and associated costs.

Differences in the incidence and mortality of digestive cancer between Global Cancer Observatory 2020 and Global Burden of Disease 2019.

The burden of digestive cancers is increasing worldwide. The Global Cancer Observatory (GLOBOCAN) 2020 and the Global Burden of Disease (GBD) 2019 are two primary cancer databases, which have a significant impact on policy formulation and resource allocation. We aim to compare the incidence and mortality of digestive cancers between them. Digestive cancer (esophageal, stomach, colorectal, liver, gallbladder and pancreatic cancer) incidence was obtained from the Cancer Today and GBD 2019 result tool. The top five countries with the most or minor difference between GLOBOCAN 2020 and GBD 2019 in age-standardized incidence rates (ASIRs) of digestive cancers were identified. A systematic search on the incidence of specific digestive cancer in selected countries from PubMed and Embase was conducted, and 20 of 281 publications were included. The most significant differences in digestive cancers incidence were commonly found in Asian countries (70%), particularly Indonesia, Vietnam and Myanmar, located in Southeast Asia. The ASIRs for most digestive cancers, except liver cancer, in GLOBOCAN 2020 were higher than those in GBD 2019. Gallbladder cancer had the highest average ratio, followed by liver cancer. The most commonly used standard population was Segi's standard population, followed by the World Health Organization standard population. The data sources nor the processing methods of GLOBOCAN 2020 and GBD 2019 were not similar. Low- and middle-income countries without population-based cancer registries were more likely to have selection bias in data collection and amplify regional variations of etiological factors. Better judgments on the quality of cancer data can be made.

The effect and safety assessment of monitoring ethanol concentration in exhaled breath combined with intelligent control of renal pelvic pressure on the absorption of perfusion fluid during flexible ureteroscopic lithotripsy.

PURPOSE: Previously, we designed a ureteral access sheath with the capability of renal pelvic pressure (RPP) measurement and a medical perfusion and aspiration platform, allowing for the intelligent control of RPP. However, the effect of different RPP levels on perfusion fluid absorption remains unclear. This randomized controlled trial aimed to investigate the effects of exhaled ethanol concentration monitoring and intelligent pressure control on perfusion fluid absorption during flexible ureteroscopic lithotripsy. METHODS: Eighty patients scheduled for flexible ureteroscopic lithotripsy were randomly divided into four groups. In groups A, B, and C, the RPPs were set at 0, - 5, and - 10 mmHg, respectively. Group D was regarded as the controls with unfixed RPP. Isotonic saline containing 1% ethanol was used as the irrigation fluid, with an average irrigation flow rate of 100 mL/min. The primary outcome of this study was the absorption of perfusion fluid that was calculated based on the exhaled ethanol concentration. The secondary outcomes included duration of operation and amounts of perfusion fluid used. Postoperative complications, pre- and postoperative renal function, infection markers, and blood gas analysis were also recorded for safety assessment. RESULTS: In all, 76 patients were involved in this study, whose demographic characteristics and preoperative conditions were comparable among groups. Under the same perfusion flow rate, the groups with fixed RPP exhibited reduced absorption of perfusion fluid, duration of operation, and perfusion volume. In particular, the lowest values were observed in group C (RPP = - 10 mmHg). In contrast to the unfixed RPP group, no considerable difference were observed in levels of BUN, Scr, WBC, CRP, and blood gas values among the fixed RPP groups. Moreover, postoperative complications showed no significant difference among groups. CONCLUSION: In flexible ureteroscopic lithotripsy, the groups with fixed RPP had less absorption of perfusion fluid and perfusion volume, shorter duration of surgery, and higher safety than the unfixed group.

An optimized postsurgery follow-up strategy for patients with esophageal cancer: a cohort study.

BACKGROUND: After radical surgery, patients with esophageal cancer should undergo long-term surveillance of disease relapse. However, the optimal follow-up strategy remains to be explored. METHOD: A total of 4688 patients were recruited. Recursive partition analysis was applied to develop recurrence risk stratification for patients. The follow-up strategies of each stratification were developed based on monthly recurrence probability and validated by bootstrap validation and an external dataset. A Markov decision-analytic model was constructed to evaluate the cost-effectiveness of the follow-up strategies. RESULTS: Patients were stratified into four groups according to four pathological features. The authors applied a random survival forest to calculate the monthly recurrence probability of each group. Based on the temporal distribution of recurrences, the authors further established surveillance strategies for four groups. The strategies were validated as optimal protocols by bootstrap resampling and another dataset. Markov cost-effective analysis indicated that our recommended strategies outperformed the mainstream protocols from guidelines. Using less than 12 visits across the first 5 years on average, our follow-up strategies were more efficient than the NCCN recommended strategies (14 visits average). Our results also supported the computerized tomography from the neck to the upper abdomen as a routine examination and PETCT of distant metastasis for some groups with high risks. CONCLUSION: Our study provided data-driven evidence of personalized and economic follow-up strategies for esophageal cancer patients and shed light on follow-up optimization for other cancer types.

Benefit-risk assessment of Covid-19 vaccine, MRNA (MRNA-1273) for males age 18-64 years.

Since the authorization of the Moderna mRNA COVID-19 vaccine, real-world evidence has indicated its effectiveness in preventing COVID-19 cases. However, increased cases of mRNA vaccine-associated myocarditis/pericarditis have been reported, predominantly in young adults and adolescents. The Food and Drug Administration conducted a benefit-risk assessment to inform the review of the Biologics License Application for use of the Moderna vaccine among individuals ages 18 and older. We modeled the benefit-risk per million individuals who receive two complete doses of the vaccine. Benefit endpoints were vaccine-preventable COVID-19 cases, hospitalizations, intensive care unit (ICU) admissions, and deaths. The risk endpoints were vaccine-related myocarditis/pericarditis cases, hospitalizations, ICU admissions, and deaths. The analysis was conducted on the age-stratified male population due to data signals and previous work showing males to be the main risk group. We constructed six scenarios to evaluate the impact of uncertainty associated with pandemic dynamics, vaccine effectiveness (VE) against novel variants, and rates of vaccine-associated myocarditis/pericarditis cases on the model results. For our most likely scenario, we assumed the US COVID-19 incidence was for the week of December 25, 2021, with a VE of 30% against cases and 72% against hospitalization with the Omicron-dominant strain. Our source for estimating vaccine-attributable myocarditis/pericarditis rates was FDA's CBER Biologics Effectiveness and Safety (BEST) System databases. Overall, our results supported the conclusion that the benefits of the vaccine outweigh its risks. Remarkably, we predicted vaccinating one million 18-25 year-old males would prevent 82,484 cases, 4,766 hospitalizations, 1,144 ICU admissions, and 51 deaths due to COVID-19, comparing to 128 vaccine-attributable myocarditis/pericarditis cases, 110 hospitalizations, zero ICU admissions, and zero deaths. Uncertainties in the pandemic trajectory, effectiveness of vaccine against novel variants, and vaccine-attributable myocarditis/pericarditis rate are important limitations of our analysis. Also, the model does not evaluate potential long-term adverse effects due to either COVID-19 or vaccine-attributable myocarditis/pericarditis.

Target-Responsive Metal-Organic Framework Nanosystem with Synergetic Sensitive Detection and Controllable Degradation against the Pesticide Triazophos in Contaminated Samples for Environment Assessment and Food Safety.

Developing sensitive practical sensors for monitoring pesticide residues in edible foods and environmental samples is vital for food safety and environmental protection. Enzyme-inhibited biosensors offer effective alternative sensing strategies by using the inherent characteristics of pesticides. To further improve the degradation function of pesticide sensors, here, a target-triggered porphyrin metal-organic framework (MOF)-based nanosystem was designed with the synergetic bifunction of sensitive detection and controllable degradation of the triazophos pesticide. As a result of triazophos-inhibited glutathione consumption, the MOF collapsed and released the ligand porphyrin, leading to the recovery of fluorescence and photosensitization of the free porphyrin. The fluorescence recovery resulted in a sensitive detection limit of 0.6 ng mL-1 for triazophos, which was also applied for the determination of contaminated samples and bioaccumulation in rice. Furthermore, the target-activated photocatalytic ability of porphyrin endowed the system with the ability to effectively generate reactive oxygen species for degrading triazophos with a removal rate of ∼85%, achieving eco-friendly synergetic detection and photodegradation in a controllable way. Therefore, the intelligent multifunctional MOF system demonstrated the potential of programmable systems for jointly controllable tracking and elimination of pesticide residues in the environment and opened a new avenue for designing a precise mechanism for stimulus-triggered degradation of pesticide residues accompanied by sensitive detection for environmental friendliness and food safety.

Recovery of bio­sulfur and metal resources from mine wastewater by sulfide biological oxidation-alkali flocculation: A pilot-scale study.

Mine wastewater treatment using bio-sulfate reduction technology forms sulfur-containing wastewater that comprises sulfides (HS- and S2-) and metal ions. Bio­sulfur generated by sulfur-oxidizing bacteria in such wastewater is usually negatively charged hydrocolloidal particles. However, bio­sulfur and metal resource recovery are difficult using traditional methods. In this study, the sulfide biological oxidation-alkali flocculation (SBO-AF) method was investigated to recover the above resources, and to provide a technical reference for mine wastewater resource recovery and heavy metal pollution control. Specifically, the performance of SBO in forming bio­sulfur and the key parameters of SBO-AF were explored and then applied in a pilot-scale process to recover resources from wastewater. Results show that partial sulfide oxidation was achieved under a sulfide loading rate of 5.08 ± 0.39 kg/m3·d, dissolved oxygen of 2.9-3.5 mg/L and temperature of 27-30 °C. The average sulfide oxidation rate and sulfur selectivity ratio were 92.86 % and 90.22 %, respectively. At pH 10, metal hydroxide and bio­sulfur colloids co-precipitated through the precipitation catching and adsorption charge neutralization effect. The average manganese, magnesium and aluminum concentrations and turbidity in the wastewater were 53.93 mg/L, 522.97 mg/L, 34.20 mg/L and 505 NTU, respectively, and decreased to 0.49 mg/L, 80.65 mg/L, 1.00 mg/L and 23.33 NTU, respectively, after treatment. The recovered precipitate mainly contained sulfur, along with metal hydroxides. The average sulfur, manganese, magnesium and aluminum contents were 45.6 %, 29.5 %, 15.1 % and 6.5 %, respectively. Economic feasibility analysis and the above results show that SBO-AF has obvious technical and economic advantages in the recovery resources from mine wastewater.

A Retrospective Review of Center for Biologics Evaluation and Research Advisory Committee Meetings in the Context of the FDA's Benefit-Risk Framework.

The US FDA Center for Biologics Evaluation and Research (CBER) is responsible for the regulation of biologically derived products. FDA has established Advisory Committees (AC) as vehicles to seek external expert advice on scientific and technical matters related to the development and evaluation of products regulated by the agency. We aimed to identify and evaluate common topics discussed in CBER AC meetings during the regulatory decision-making process for biological products and medical devices. We analyzed the content of 119 CBER-led AC meetings between 2009 and 2021 listed on the FDA AC webpage. We reviewed publicly available meeting materials such as briefing documents, summaries, and transcripts. Using a structured review codebook based on FDA benefit-risk guidance, we identified important considerations within the benefit-risk dimensions discussed at the AC meetings: therapeutic context, benefit, risk and risk management, and benefit-risk trade-off, where evidence and uncertainty are critical parts of the FDA benefit-risk framework. Based on a detailed review of 24 topics discussed in 23 selected AC meetings conducted between 2016 and 2021, the two most frequently discussed considerations were "Uncertainty about assessment of the safety profile" and "Uncertainty about assessment of the benefit based on clinical trial data" (16/24 times each) as defined in our codebook. Most of the reviewed meetings discussed Investigational New Drug or Biologics License Applications of products. This review could help sponsors better plan and design studies by contextualizing how the benefit-risk dimensions were embedded in the AC discussions and the considerations that went into the final AC recommendations.

Trends in Health Care Access Disparities Among Asian and Pacific Islander Health Fair Participants in Los Angeles, 2011-2019.

OBJECTIVES: Given several efforts to improve health care access in California and nationally, we studied whether linguistic and socioeconomic disparities in health care access changed from 2011 to 2019 among Asian and Pacific Islander American (APIA) people in Los Angeles, California. METHODS: We analyzed survey responses from APIA health fair participants (n = 5032) in the Greater Los Angeles area from May 15, 2011, through October 20, 2019. To assess the effect of socioeconomic factors on and shifts in health care access (ie, health insurance status/regular doctor), we used a logistic regression model. Covariates included English proficiency, year, age, sex, ethnicity, income, employment, and education. We also ran an interaction analysis between English proficiency and year. RESULTS: Health insurance access increased and doctor access remained stable throughout the study period; however, disparities in health insurance status widened by a factor of 1.08 per year between participants with high English proficiency (HEP) and participants with low English proficiency (LEP) (P = .01). People with HEP were 2.02 times more likely to have a regular doctor than people with LEP (P < .001), and this disparity persisted from 2011 to 2019 (P = .58). Participants who were young (P < .001) and male (P = .005) were significantly less likely to have health insurance and a regular doctor (P < .001) than participants who were older and female. Chinese participants were significantly more likely than Thai (P = .002) and Korean (P < .001) participants to be insured but not more likely to have a regular doctor, when controlling for health insurance. CONCLUSIONS: Policy changes targeting language and cultural barriers to care for APIA people with LEP may address the disparities observed.

Psychometric evaluation of an Adverse Childhood Experiences (ACEs) measurement tool: an equitable assessment or reinforcing biases?

BACKGROUND: Utilizing Adverse Childhood Experiences (ACEs) measurement scales to assess youths' adversities has expanded exponentially in health and justice studies. However, most of the ACEs assessment scales have yet to meet critical psychometric standards, especially for key demographic and minority groups. It is critical that any assessment or screening tool is not reinforcing bias, warranting the need for validating ACEs tools that are equitable, reliable and accurate. The current study aimed to examine the structural validity of an ACEs scale. Using data from the 2019 Behavioral Risk Factor Surveillance System (BRFSS), which collected of 97,314 responses collected from adults across sixteen states. This study assessed the psychometric properties and measurement invariance of the ACEs tool under the structural equation modeling framework. RESULTS: We found the 11-item ACEs screening tool as a second-order factor with three subscales, all of which passed the measurement invariance tests at metric and scalar levels across age, race, sex, socioeconomic status, gender identity, and sexual orientation. We also found that minority groups experienced more childhood adversity with small effect size, with the exception of the gender identity. CONCLUSION: The ACEs measurement scale from the BRFSS is equitable and free from measurement bias regardless of one's age, race, sex, socioeconomic status, gender identity, and sexual orientation, and thus is valid to be used to compare group mean differences within these groups. The scale is a potentially valid, viable, and predictive risk assessment in health and justice and research settings to identify high-risk groups or individuals for treatments.

Pollution, sources, and human health risk assessment of heavy metals in urban areas around industrialization and urbanization-Northwest China.

Heavy metal pollution in urban soils and dust is mostly caused by extensive anthropogenic activity during urbanization and industrialization. In this research study, the pollution characteristics, sources, ecological and human health risks of heavy metals in urban soil, and dust have been thoroughly evaluated. The research findings demonstrate that dust has a higher level of contamination than urban soil, such as Pb, Cu, and Zn metals are more contaminated in both urban soil and dust throughout the city, and Hg and As are also found in locations with a high concentration of heavy industrial companies. This implies that traffic emissions are still a significant source of metals in urban areas, though industrial companies also contribute. The health risk assessment model used to calculate human exposure revealed that the non-carcinogenic and carcinogenic risks of selected metals in soil and dust were generally in the low range, except for the carcinogenic risk from Cr in children. Statistical analysis revealed that Cr and Ni concentrations were mainly of natural origin, Cu and Zn have been sourced from traffic, whereas Pb, Hg, and As have been sourced from industrial activities. The overall recommendation is that the road traffic environment and municipal construction facilities need to be improved to ensure the sustainable development of the city's environment, while pollution from industrial waste is strongly controlled.

Ongoing Clinical Trials in Aging-Related Tissue Fibrosis and New Findings Related to AhR Pathways.

Fibrosis is a pathological manifestation of wound healing that replaces dead/damaged tissue with collagen-rich scar tissue to maintain homeostasis, and complications from fibrosis contribute to nearly half of all deaths in the industrialized world. Ageing is closely associated with a progressive decline in organ function, and the prevalence of tissue fibrosis dramatically increases with age. Despite the heavy clinical and economic burden of organ fibrosis as the population ages, to date, there is a paucity of therapeutic strategies that are specifically designed to slow fibrosis. Aryl hydrocarbon receptor (AhR) is an environment-sensing transcription factor that exacerbates aging phenotypes in different tissues that has been brought back into the spotlight again with economic development since AhR could interact with persistent organic pollutants derived from incomplete waste combustion. In addition, gut microbiota dysbiosis plays a pivotal role in the pathogenesis of numerous diseases, and microbiota-associated tryptophan metabolites are dedicated contributors to fibrogenesis by acting as AhR ligands. Therefore, a better understanding of the effects of tryptophan metabolites on fibrosis modulation through AhR may facilitate the exploitation of new therapeutic avenues for patients with organ fibrosis. In this review, we primarily focus on how tryptophan-derived metabolites are involved in renal fibrosis, idiopathic pulmonary fibrosis, hepatic fibrosis and cardiac fibrosis. Moreover, a series of ongoing clinical trials are highlighted.

[Analysis on Spatial-temporal Characteristics and Driving Factors of PM2.5 in Henan Province from 2015 to 2019].

PM2.5 is the main component of haze, and Henan Province has become one of the key areas of PM2.5 pollution control. Based on the PM2.5 concentration data of Henan Province from 2015 to 2019, spatial autocorrelation, spatial hot spot detection, and other methods were used to analyze its temporal and spatial characteristics, and the geodetector method was introduced to analyze the interpretation strength of meteorological factors, air quality factors, and social factors on PM2.5 concentration. The results showed that:from 2015 to 2019, the concentration of PM2.5 in Henan Province showed an overall downward trend, the days of high pollution decreased, the days of low pollution increased, and the high pollution gradually transformed into medium pollution. The concentration of PM2.5 had obvious characteristics of spatial aggregation. The five-year global spatial autocorrelation index first dropped and then rose, and the spatial hot spots were concentrated in northern Henan (Anyang, Hebi, Xinxiang, and Jiaozuo); the spatial cold spots were concentrated in western Henan (Sanmenxia, Luoyang, and Nanyang). The shift in space center of gravity showed a trend of going north. Single-factor detection showed that among the nine influencing factors, land use type (0.511), precipitation (0.312), and NO2(0.277) were the most obvious factors affecting PM2.5 concentration, and the other factors were PM10(0.255), temperature (0.209), wind speed (0.183), O3(0.121), GDP(0.073), and population (0.046). Interaction detection showed that the combined effect of multiple factors was more significant than that of single factors. These results can provide theoretical support for the control of air pollution in Henan Province.

Copy number assessment of SMN1 based on real-time PCR with high-resolution melting: fast and highly reliable testing.

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease mainly caused by the absence of both copies of the survival motor neuron 1 (SMN1) gene. Multiple regions recommended population-wide SMA screening to quantify the copy number of SMN1. SMN1 diagnostic assays for the simplified procedure, high sensitivity, and throughput continue to be needed. METHODS: Real-time PCR with high-resolution melting for the quantifying of the SMN1 gene exon 7 copies and exon 8 copies were established and confirmed by multiplex ligation-dependent probe amplification (MLPA). The diagnosis of 2563 individuals, including SMA patients, suspected cases, and the general population, was tested by real-time PCR. The results were compared with the gold standard test MLPA. RESULTS: In this study, the homozygous and heterozygous deletions were detected by real-time PCR with a high-resolution melting method with an incidence of 10.18% and 2.26%, respectively. In addition, the R-value distribution (P > 0.05) among 8 replicates and the coefficient of variation (CV < 0.003) suggested that the real-time PCR screening test had high reproducibility. High concordance was obtained between real-time PCR with high-resolution melting and MLPA. CONCLUSIONS: The real-time PCR based on high-resolution melting provides a sensitive and high-throughput approach to large-scale SMA carrier screening with low cost and labor.

Benefit-risk assessment of COVID-19 vaccine, mRNA (Comirnaty) for age 16-29 years.

Since authorization of the Pfizer-BioNTech COVID-19 Vaccine, mRNA (Comirnaty), real-world evidence has indicated the vaccines are effective in preventing COVID-19 cases and related hospitalizations and deaths. However, increased cases of myocarditis/pericarditis have been reported in the United States associated with vaccination, particularly in adolescents and young adults. FDA conducted a benefit-risk assessment to determine whether the benefits of vaccination outweigh the risks among various age (16-17, 18-24, 25-29) and sex (M/F) subgroups being considered for approved use of the vaccine. We conducted a simulation study with sensitivity analysis of the benefits and risks of the vaccine across possible pandemic scenarios. The model results show benefits outweigh the risks for all scenarios including the high-risk subgroup, males 16-17 years old. Our worst-case scenario used sex and age subgroup-specific incidences for COVID-19 cases (47-98 per million per day) and hospitalizations (1-4 per million per day) which are the US COVID-19 incidences as of July 10, 2021, vaccine efficacy of 70% against COVID-19 cases and 80% against hospitalization, and unlikely, pessimistic, non-zero vaccine-attributable myocarditis death rate. For males 16-17 years old, the model predicts prevented COVID cases, hospitalizations, ICUs, and deaths of 13577, 127, 41, and 1, respectively; while the predicted ranges for excess myocarditis/pericarditis cases, hospitalizations, and deaths attributable to the vaccine are [98-196], [98-196], and 0, respectively, for the worst-case scenario. Considering the different clinical implications of hospitalization due to COVID-19 infection versus vaccine-attributable myocarditis/pericarditis cases, we determine the benefits still outweigh the risks even for this high-risk subgroup. Our results demonstrate that the benefits of the vaccine outweigh its risks for all age and sex subgroups we analyze in this study. Uncertainties exist in this assessment as both benefits and risks of vaccination may change with the continuing evolution of the pandemic.

Inter- and intra-observer reliability of the "Assessment of Motor Repertoire- 3 to 5 Months" based on video recordings of infants with Prader-Willi syndrome.

BACKGROUND: The "Assessment of Motor Repertoire-3 to 5 Months", which is a part of Prechtl's General Movements Assessment (GMA), has been gradually applied to infants with genetic metabolic disorders. However, there have been no studies on the application of the GMA for infants with Prader-Willi syndrome (PWS). AIMS: The purpose of this study was to determine the inter- and intra-observer reliability of the assessment tool in a population of infants with PWS. STUDY DESIGN: This was a reliability and agreement study. SUBJECTS: This was a cross-sectional study with15 infants with PWS born at an average gestational age of 38 weeks. OUTCOME MEASURES: Standardized video recordings of 15 infants with PWS (corrected ages of 3 to 5 months) were independently assessed by three observers. Kappa and ICC statistics were applied in inter- and intra- observer reliability analyses. RESULTS: The overall reliability ICC values of the "Motor Optimality Score" (MOS) ranged from 0.84 to 0.98, and the pairwise agreement ranged between 0.86 and 0.95 for inter- observe reliability. In addition, ICC values for the MOS ranged between 0.95 and 0.98 for tester agreement in intra-observer reliability. Complete agreement reliability (100%) was achieved in the subcategories of "Fidgety Movements" and "Movement Character" for the inter- and intra-observer reliability. Moderate to high inter- and intra-observer reliability were found in the subcategories of "Repertoire of Co-Existent Other Movements", "Quality of Other Movements" and "Posture", with kappa values ranging between 0.63 and 1.00. CONCLUSION: There were high levels of inter-and intra-observer agreement in the "Assessment of Motor Repertoire-3 to 5 Months" for infants with PWS. It is possible to carry out standardized quantitative assessments of the motor performance of infants with PWS.

Highly sensitive fluorescent quantification of acid phosphatase activity and its inhibitor pesticide Dufulin by a functional metal-organic framework nanosensor for environment assessment and food safety.

Developing a rapid and accurate strategy of sensing Dufulin is a vital challenge for risk assessment and food crops along with its spreading usage. Herein a dye-encapsulated azoterephthalate metal-organic framework (MOF)-based fluorescent sensing system was designed for Dufulin analysis by acid phosphatase (ACP) enzyme-controlled collapse of MOF framework and subsequent release of the encapsulated dye. The fluorescence intensity of the DMOF/AAP/ACP system was negatively related to the dosage of Dufulin (0-5 µg mL-1) with detection limit of 2.96 ng mL-1. The sensing system able to rapidly and sensitively sense the activity of ACP and Dufulin, and was also applicable for assessment of the real samples including paddy water and soil, polished rice and cucumber. Accordingly, this study illustrated the feasibility and the potential of MOF-derived nanosensors for improving pesticide analysis and opening up the design of the enzyme-based probes for pesticide sensing in environmental assessment and food safety.