Tumor microenvironment(TME) and single-source dual-energy CT(ssDECT) on assessment of inconformity between RECIST1.1 and pathological remission in neoadjuvant immunotherapy of NSCLC.

BACKGROUND: The inconformity (IC) between pathological and imaging remissions after neoadjuvant immunotherapy in patients with NSCLC can affect the evaluation of curative effect of neoadjuvant therapy and the decision regarding the chance of surgery. MATERIALS AND METHODS: Patients who achieved disease control(CR/PR/SD) after neoadjuvant chemoimmunotherapy from a clinical trial (NCT04326153) and after neoadjuvant chemotherapy during the same period were enrolled in this study. All patients underwent radical resection and systematic mediastinal lymphadenectomy after neoadjuvant treatments. The pathological remission, immunohistochemistry (CD4, CD8, CD20, CD56, FoxP3, CD68, CD163, CD11b tumor-infiltrating lymphocytes, or macrophages), and single-source dual-energy computed tomography (ssDECT) scans were assessed. The IC between imaging remission by CT and pathological remission was investigated. The underlying cause of IC, the correlation between IC and DFS, and prognostic biomarkers were explored. RESULTS: After neoadjuvant immunotherapy, enhanced immune killing and reduced immunosuppressive performance were observed. 70 % of neoadjuvant chemoimmunotherapy patients were in high/medium IC level. Massive necrosis and repair around and inside the cancer nest were the main pathological changes observed 30-45 days post-treatment with PD1/PD-L1 antibody and were the main causes of IC between the pathology and imaging responses after neoadjuvant immunotherapy. High IC and preoperative CD8 expression (H score ≥ 3) indicate a high pathological response rate and prolonged DFS. Iodine material density ssDECT images showed that the iodine content in the lesion causes hyperattenuation in post-neoadjuvant lesion in PCR patient. CONCLUSIONS: Compared to chemotherapy and targeted therapy, the efficacy of neoadjuvant immunotherapy was underestimated based on the RECIST criteria due to the unique antitumor therapeutic mechanism. Preoperative CD8+ expression and ssDECT predict this IC and evaluate the residual tumor cells. This is of great significance for screening immune beneficiaries and making more accurate judgments about the timing of surgery.

Assessment of the depositional characteristics of the Yellow River estuary from 1960s by 239+240Pu and 137Cs.

The spatial and vertical distribution of 239+240Pu and 137Cs in the sediments of the Yellow River Delta was studied to evaluate the deposition dynamics in the Yellow River estuary from 1960s. The activity of 239+240Pu and 137Cs in sediment core ranged from 0.001 to 0.212 Bq/kg and 0.52-2.53 Bq/kg, respectively. A maximum accumulation peak and two secondary accumulation peaks appeared in the sediment core YR2. The average deposition rate of 8.3 cm/y for the Yellow River estuary from 1964 to 1976 was obtained. The proportion of Pu from the Yellow River net input and direct deposition to the total inventory of Pu in the estuary was assessed, with a total inventory of Pu in the abandoned estuary of 7.4 × 1010 Bq and a net input of 2.2 × 1010 Bq from the Yellow River. Pu deposited in the estuary only accounts for 18 % of the total Pu transported by the Yellow River, and most of the Pu is injected into the Bohai Sea with the Yellow River.

Unleashing the nexus among urban land use, national physical health inputs and environment: an environmental sustainability paradigm.

Nowadays, the contemporary ecological environment has a significant impact on human survival and development. Consequently, an in-depth examination of the link between humans and nature has significant practical significance and aspirational appeal. This research analyzes provincial panel data from 2011 to 2019 using an empirical model to determine the relationship between urban land use, the ecological environment, and national physical health inputs in China. The results indicate that (1) urbanization and air pollution do not have an "inverted U-shaped" traditional environmental Kuznets curve relationship, but rather a significant "positive U" relationship; (2) urbanization and environmental management do have an inverted U-shaped classical environmental Kuznets curve relationship; (3) GDP per capita and infrastructure have a negative impact on air quality and environmental quality, and strict environmental rules can improve air quality and green amenities; (4) national physical health investment has a substantial moderating effect on the relationship between urban land use and the ecological environment.

Social determinants of health and premature death among adults in the USA from 1999 to 2018: a national cohort study.

BACKGROUND: Racial and ethnic disparities in mortality persist in the US population. We studied the contribution of social determinants of health (SDoH) to racial and ethnic disparities in premature death. METHODS: A nationally representative sample of individuals aged 20-74 years who participated in the US National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 were included. Self-reported SDoH (employment, family income, food security, education, access to health care, health insurance, housing instability, and being married or living with a partner) were collected in each survey cycle. Participants were categorised into four groups of race and ethnicity: Black, Hispanic, White, and other. Deaths were ascertained from linkage to the National Death Index with follow-up until 2019. Multiple mediation analysis was used to assess simultaneous contributions of each individual SDoH to racial disparities in premature all-cause mortality. FINDINGS: We included 48 170 NHANES participants in our analyses, consisting of 10 543 (21·9%) Black participants, 13 211 (27·4%) Hispanic participants, 19 629 (40·7%) White participants, and 4787 (9·9%) participants of other racial and ethnic groups. Mean survey-weighted age was 44·3 years (95% CI 44·0-44·6), 51·3% (50·9-51·8) of participants were women, and 48·7% (48·2-49·1) were men. 3194 deaths before age 75 years were recorded (930 Black participants, 662 Hispanic participants, 1453 White participants, and 149 other participants). Black adults had significantly higher premature mortality than other racial and ethnic groups (p<0·0001): premature death rates per 100 000 person-years were 852 (95% CI 727-1000) for Black adults, 445 (349-574) for Hispanic adults, 546 (474-630) for White adults, and 521 (336-821) for other adults. Unemployment, lower family income, food insecurity, less than high school education, no private health insurance, and not being married nor living with a partner were significantly and independently associated with premature death. Dose-response associations were observed between cumulative number of unfavourable SDoH and premature all-cause mortality: hazard ratios (HRs) were 1·93 (95% CI 1·61-2·31) for those with one unfavourable SDoH, 2·24 (1·87-2·68) for those with two, 3·98 (3·34-4·73) for those with three, 4·78 (3·98-5·74) for those with four, 6·08 (5·06-7·31) for those with five, and 7·82 (6·60-9·26) for those with six or more unfavourable SDoH (p<0·0001 for linear trend). After adjusting for SDoH, HRs for premature all-cause mortality for Black adults compared with White adults decreased from 1·59 (1·44-1·76) to 1·00 (0·91-1·10), suggesting complete mediation of this racial difference in mortality. INTERPRETATION: Unfavourable SDoH are associated with increased rates of premature death and contribute to differences between Black and White racial groups in premature all-cause mortality in the US population. Innovative public health policies and interventions targeting SDoH are needed to reduce premature deaths and health disparities in this population. FUNDING: US National Institutes of Health.

Pyrolysis temperature-switchable Fe-N sites in pharmaceutical sludge biochar toward peroxymonosulfate activation for efficient pollutants degradation.

Pyrolysis of pharmaceutical sludge (PS) is a promising way of safe disposal and to recover energy and resources from waste. The resulting PS biochar (PSBC) is often used as adsorbent, but has seldom been explored as catalyst. Herein we demonstrate that PSBC (0.4 g/L) could efficiently activate peroxymonosulfate (PMS) to 100% degrade 4-chlorophenol (4-CP) with rate constants of 0.42-1.70 min-1, outperforming other reported catalysts. Interestingly, the PMS activation pathway highly depended on PSBC pyrolysis temperature, which produced dominantly high-valent iron species (e.g., FeIVO2+) at low temperature but more sulfate radical (SO4·-) and hydroxyl radical (·OH) at higher temperature, e.g., 0.17, 0.23, 0.12 mmol/L of FeIVO2+ and 0.009, 0.038, 0.102 mmol/L of SO4·-/·OH were produced within 10 min by PSBC-600/PMS, PSBC-800/PMS, and PSBC-1000/PMS, respectively. Characterization, density functional theory (DFT) simulation and Pearson correlation analysis revealed that along with the increase of pyrolysis temperatures, the active sites of PSBC gradually shifted from atomically dispersed N-coordinated Fe moieties (FeNx) to iron nitrides (FexN), which activated PMS to produce FeIVO2+ and SO4·-/·OH, respectively. This study clarifies the structure-activity relationships of PSBC for PMS activation, and opens a new avenue for the treatment and utilization of PS as high value-added resources.

Occurrence and exposure risk assessment of pesticide residues in green tea samples cultivated in Hangzhou area, China.

The concentration of pesticide residues in 105 green tea samples grown in Hangzhou area were investigated. Of the 14 pesticides analysed using gas chromatography-tandem mass spectrometry and the 27 pesticides analysed using liquid chromatography-tandem mass spectrometry, only 18 were detected in the tea samples. The most frequently detected pesticide residues were imidacloprid (35.2%), acetamiprid (26.7%), carbendazim (21.0%), bifenthrin (21.0%), and cyhalothrin (19.1%). Carbofuran was the only pesticide which exceeded in one sample the maximum residue limit. The concentrations of the analytes in tea samples ranged from below the limit of detection (LOD) to 2.64 mg/kg. Their mean concentrations were all below the LOD, except for imidacloprid, acetamiprid, carbendazim, bifenthrin and cyhalothrin. Based on a preliminary long-term exposure assessment, the hazard quotient values of the detected pesticides varied in the range 0.47 × 10-3 - 1.1 × 10-3%, which indicates that these levels did not pose a risk to human health in Hangzhou area.

Monochloropropanediol in edible vegetable oils from Hangzhou market in China: occurrence and exposure risk assessment.

In this study, 241 vegetable-oil food samples were collected from the Hangzhou market in China and analysed for fatty acid esters of 3- and 2-monochloropropanediol (3-MCPD and 2-MCPD) using non-derivative gas chromatography tandem mass spectrometry (GC-MS/MS). Food consumption data were taken from a food consumption survey of urban and rural residents in Hangzhou city performed in 2010-2011. Levels of 3-MCPD esters in edible oil ranged from not detected to 7.98 mg/kg, and the highest mean levels were found in tea seed oil, with concentrations of 2.94 mg/kg. Esters of 2-MCPD levels ranged from not detected to 4.03 mg/kg, and the highest mean levels were also found in tea seed oil, containing 1.49 mg/kg. The range of mean dietary intake of 3-MCPD esters in different groups of edible oil was from 0.096 to 1.54 µg/kg body weight (bw) per day, which is lower than the tolerable daily intake (TDI) established by the European Food Safety Authority (EFSA) (2 µg/kg bw/day). For people aged above 6 years old, the dietary intake of 3-MCPD from edible oil was 0.42 µg/kg bw per day (mean) and 1.22 µg/kg bw per day (P97.5). The range of mean dietary intake of 2-MCPD esters in different groups of edible oil was from 0.025 to 0.79 µg/kg bw/day, and 2-MCPD esters intake was 0.20 µg/kg bw per day (mean) and 0.60 µg/kg bw per day (P97.5). In addition, the dietary intake exposure to 3-MCPD and 2-MCPD esters for urban residents was lower than that for rural residents. The findings indicate that the potential health risks caused by dietary 3-MCPD esters from edible oils were of low concern for most of the Hangzhou residents. However, the exposure risk for consumers with excessive consumption of certain kind of edible oil calls for attention.

Cost-effectiveness analysis of the integrated control strategy for schistosomiasis japonica in a lake region of China: a case study.

BACKGROUND: Schistosomiasis japonica remains an important public health concern due to its potential to cause severe outcomes and long-term sequelae. An integrated control strategy implemented in the Peoples' Republic of China has been shown to be effective to control or interrupt the transmission of schistosomiasis. The objective of this study is to estimate the disease burden of schistosomiasis and assess the cost-effectiveness of the integrated control strategy focused on different major interventions at three stages for schistosomiasis control in a lake setting, to provide reference for policy making or planning. METHODS: Annual cost data of schistosomiasis control during 2009-2019 were obtained from the control program implementers in Jiangling County, Hubei Province, China. Economic costs are provided in constant 2009 Chinese Yuan (CNY). Epidemiological data of schistosomiasis were collected from the Jiangling county station for schistosomiasis control. Disease burden of schistosomiasis was assessed by calculating years of life lost (YLLs) owing to premature death, years lived with disability (YLDs) and disability-adjusted life years (DALYs). DALYs were calculated as the sum of YLLs and YLDs. We then conducted a rudimentary cost-effectiveness analysis by determining the ratio by dividing the difference between the average cost of integrated control strategy at transmission control (2013-2016) or transmission interruption (2017-2019) and the average cost at stage of infection control (2009-2012) with the difference between the DALYs of schistosomiasis at different control stages. Descriptive statistics on the costs and DALYs were used in the analysis. RESULTS: The total economic costs for schistosomiasis control in Jiangling County from 2009 to 2019 were approximately CNY 606.88 million. The average annual economic costs for schistosomiasis prevention and control at stages of infection control (2009-2012), transmission control (2013-2016), and transmission interruption (2017-2019) were approximately CNY 41.98 million, CNY 90.19 million and CNY 26.06 million respectively. The overall disease burden caused by schistosomiasis presented a downward trend. Meanwhile, the disease burden of advanced cases showed an upward trend with the DALY increased from 943.72 to 1031.59 person-years. Most disease burden occurred in the age group over 45 years old (especially the elderly over 60 years old). Taking the infection control stage as the control, the incremental cost-effectiveness ratio of integrated control strategy was CNY 8505.5 per case averted, CNY 60 131.6 per DALY decreased at transmission control stage and CNY -2217.6 per case averted, CNY -18 116.0 per DALY decreased at transmission interruption stage. CONCLUSIONS: The disease burden of schistosomiasis decreased significantly with the implementation of the integrated prevention and control strategy. Surveillance and management on elder population should be strengthened to decrease diseases burden. There remains a need for well-conducted studies that examine the long-term cost-effectiveness of the integrated control strategy for schistosomiasis. GRAPHIC ABSTARCT.

Cost-effectiveness analysis of different sequences of osimertinib administration for epidermal growth factor receptor-mutated non-small-cell lung cancer.

Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is clinically effective in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, the use of this treatment is limited by its high cost. A cost-effectiveness analysis of different sequences of osimertinib administration in China and the United States was conducted in the present study. Markov models were established based on data from the FLAURA and AURA3 trials. First-line osimertinib was compared with both first-generation EGFR-TKIs and second-line osimertinib after the failure of first-generation EGFR-TKIs. The analysis also considered different payment modalities available in China. Additionally, one-way and probability sensitivity analyses, with a willingness-to-pay threshold (WTP) of three times the per capita gross domestic product [$27,783/quality-adjusted life year (QALY) for China and $100,000/QALY for the United States], were performed. The first-line osimertinib group displayed higher QALYs and costs than those of the first-generation EGFR-TKI group. The first generation EGFR-TKI group displayed an incremental cost-effectiveness ratio (ICER) of $212,252/QALY in China and $151,922/QALY in the United States. In addition, the ICERs were negative in the second-line osimertinib group, with higher QALYs and lower costs compared with those in the first-line osimertinib group. Furthermore, osimertinib company donation was of benefit in China, with an average cost-effectiveness of $836/QALY. The one-way sensitivity analysis highlighted the influence of utilities in different states. First-line osimertinib could be cost-effective either with higher WTP or a price reduction of 68% in China and 9% in the United States. Although first-line osimertinib therapy could have health benefits, it was not cost-effective compared with first-line first-generation EGFR-TKIs and second-line osimertinib therapy. However, paying via company donation may be a good choice in China.

Comparing quality of primary healthcare between public and private providers in China: study protocol of a cross-sectional study using unannounced standardised patients in seven provinces of China.

INTRODUCTION: The Chinese government has encouraged the development of private sector in delivering healthcare, including primary healthcare (PHC) in the new round of national health reform since 2009. However, the debate about the role of the private sector in achieving universal health coverage continues with poor support from theories and empirical evidence. This study intends to compare the quality of PHC services between the private and public providers in seven provinces in China, using unannounced standardised patients (USPs). METHODS: We are developing and validating 13 USP cases most commonly observed in the PHC setting. Six domains of quality will be assessed by the USP: effectiveness, safety, patient centredness, efficiency, timeliness and equity. The USP will make 2200 visits to 705 public and 521 private PHC institutions across seven provinces, following a multistage clustered sample design. Using each USP-provider encounter as the analytical unit, we will first descriptively compare the raw differences in quality between the private and public providers and then analyse the association of ownership types and quality, using propensity score weighting. ETHICS AND DISSEMINATION: The study was primarily funded by the National Natural Science Foundation of China (#71974211, #71874116 and # 72074163) and was also supported by the China Medical Board (#16-260, #18-300 and #18-301), and have received ethical approval from Sun Yat-sen University (#2019-024). The validated USP tool and the data collected in this study will be freely available for the public after the primary analysis of the study. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry: #ChiCTR2000032773.

Glycosaminoglycan / gold nanocluster hybrid nanoparticles as a new sensing platform: Metastatic potential assessment of cancer cells.

A novel fluorescent heparanase assay based on hybrid nano-assembly of gold nanocluster and glycosaminoglycan is developed. The nanoparticle probes are fabricated through the co-assembly of positively charged gold nanoclusters with negatively charged heparin molecules, which is accompanied by a dramatic size change and a 2.5-fold fluorescence enhancement. It is demonstrated that the fluorescence enhancement is due to denser aggregation of Au-thiolate complexes in the hybrid nanoparticle and the fluctuation of the fluorescence intensity is an indicator of the variation in assembly efficiency. Experiments in solution and in cell lysis media showed that the heparanase could turn-off the fluorescence with a high selectivity, which could be utilized for the assessment of heparanase activity and the metastatic potentials of different tumour cells. This assay technique is low cost, easy to prepare, and showing good performance. The co-assembly strategy has potential to be transferable to construct other functional nanomaterial.

Making a Genetic Diagnosis in a Level IV Neonatal Intensive Care Unit Population: Who, When, How, and at What Cost?

OBJECTIVE: To investigate the prevalence of genetic disease and its economic impact in a level IV neonatal intensive care unit (NICU) by identifying and describing diseases diagnosed, genetic testing methodologies used, timing of diagnosis, length of NICU stay, and charges for NICU care. STUDY DESIGN: A retrospective chart review of patients admitted to a level IV NICU from 2013 to 2014 (n = 1327) was undertaken and data collected up to 2 years of age from the electronic medical record. RESULTS: In total, 117 patients (9%) received 120 genetic diagnoses using a variety of methodologies. A significant minority of diagnoses, 36%, were made after NICU discharge and 41% were made after 28 days of age. Patients receiving a genetic diagnosis had significantly longer mean lengths of stay (46 days vs 29.1 days; P < .01) and costlier mean charges ($598 712 vs $352 102; P < .01) for their NICU care. The NICU stay charge difference to care for a newborn with a genetic condition was on average $246 610 in excess of that for a patient without a genetic diagnosis, resulting in more than $28 000 000 in excess charges to care for all patients with genetic conditions in a single NICU over a 2-year period. CONCLUSIONS: Given the high prevalence of genetic disease in this population and the documented higher cost of care, shortening the time to diagnosis and targeting therapeutic interventions for this population could make a significant impact on neonatal care in level IV NICUs.

Multilaboratory Assessment of a New Reference Material for Quality Assurance of Cell-Free Tumor DNA Measurements.

We conducted a multilaboratory assessment to determine the suitability of a new commercially available reference material with 40 cancer variants in a background of wild-type DNA at four different variant allele frequencies (VAFs): 2%, 0.50%, 0.125%, and 0%. The variants include single nucleotides, insertions, deletions, and two structural variations selected for their clinical importance and to challenge the performance of next-generation sequencing (NGS) methods. Fragmented DNA was formulated to simulate the size distribution of circulating wild-type and tumor DNA in a synthetic plasma matrix. DNA was extracted from these samples and characterized with different methods and multiple laboratories. The various extraction methods had differences in yield, perhaps because of differences in chemistry. Digital PCR assays were used to measure VAFs to compare results from different NGS methods. Comparable VAFs were observed across the different NGS methods. This multilaboratory assessment demonstrates that the new reference material is an appropriate tool to determine the analytical parameters of different measurement methods and to ensure their quality assurance.

Lay health supporters aided by mobile text messaging to improve adherence, symptoms, and functioning among people with schizophrenia in a resource-poor community in rural China (LEAN): A randomized controlled trial.

BACKGROUND: Schizophrenia is a leading cause of disability, and a shift from facility- to community-based care has been proposed to meet the resource challenges of mental healthcare in low- and middle-income countries. We hypothesized that the addition of mobile texting would improve schizophrenia care in a resource-poor community setting compared with a community-based free-medicine program alone. METHODS AND FINDINGS: In this 2-arm randomized controlled trial, 278 community-dwelling villagers (patient participants) were randomly selected from people with schizophrenia from 9 townships of Hunan, China, and were randomized 1:1 into 2 groups. The program participants were recruited between May 1, 2015, and August 31, 2015, and the intervention and follow-up took place between December 15, 2015, and July 1, 2016. Baseline characteristics of the 2 groups were similar. The patients were on average 46 years of age, had 7 years of education, had a duration of schizophrenia of 18 years with minimal to mild symptoms and nearly one-fifth loss of functioning, and were mostly living with family (95%) and had low incomes. Both the intervention and the control groups received a nationwide community-based mental health program that provided free antipsychotic medications. The patient participants in the intervention group also received LEAN (Lay health supporters, E-platform, Award, and iNtegration), a program that featured recruitment of a lay health supporter and text messages for medication reminders, health education, monitoring of early signs of relapses, and facilitated linkage to primary healthcare. The primary outcome was medication adherence (proportion of dosages taken) assessed by 2 unannounced home-based pill counts 30 days apart at the 6-month endpoint. The secondary and other outcomes included patient symptoms, functioning, relapses, re-hospitalizations, death for any reason, wandering away without notifying anyone, violence against others, damaging goods, and suicide. Intent-to-treat analysis was used. Missing data were handled with multiple imputations. In total, 271 out of 278 patient participants were successfully followed up for outcome assessment. Medication adherence was 0.48 in the control group and 0.61 in the intervention group (adjusted mean difference [AMD] 0.12 [95% CI 0.03 to 0.22]; p = 0.013; effect size 0.38). Among secondary and other outcomes we noted substantial reduction in the risk of relapse (26 [21.7%] of 120 interventional participants versus 40 [34.2%] of 117 controls; relative risk 0.63 [95% CI 0.42 to 0.97]; number needed to treat [NNT] 8.0) and re-hospitalization (9 [7.3%] of 123 interventional participants versus 25 [20.5%] of 122 controls; relative risk 0.36 [95% CI 0.17 to 0.73]; NNT 7.6). The program showed no statistical difference in all other outcomes. During the course of the program, 2 participants in the intervention group and 1 in the control group died. The limitations of the study include its lack of a full economic analysis, lack of individual tailoring of the text messages, the relatively short 6-month follow-up, and the generalizability constraint of the Chinese context. CONCLUSIONS: The addition of texting to patients and their lay health supporters in a resource-poor community setting was more effective than a free-medicine program alone in improving medication adherence and reducing relapses and re-hospitalizations. Future studies may test the effectiveness of customization of the texting to individual patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-ICR-15006053.

Reducing greenhouse gas emissions: a duopoly market pricing competition and cooperation under the carbon emissions cap.

This article studies the price competition and cooperation in a duopoly that is subjected to carbon emissions cap. The study assumes that in a departure from the classical Bertrand game, there is still a market for both firms' goods regardless of the product price, even though production capacity is limited by carbon emissions regulation. Through the decentralized decision making of both firms under perfect information, the results are unstable. The firm with the lower maximum production capacity under carbon emissions regulation and the firm with the higher maximum production capacity both seek market price cooperation. By designing an internal carbon credits trading mechanism, we can ensure that the production capacity of the firm with the higher maximum production capacity under carbon emissions regulation reaches price equilibrium. Also, the negotiation power of the duopoly would affect the price equilibrium.

Assessment of Digital PCR as a Primary Reference Measurement Procedure to Support Advances in Precision Medicine.

BACKGROUND: Genetic testing of tumor tissue and circulating cell-free DNA for somatic variants guides patient treatment of many cancers. Such measurements will be fundamental in the future support of precision medicine. However, there are currently no primary reference measurement procedures available for nucleic acid quantification that would support translation of tests for circulating tumor DNA into routine use. METHODS: We assessed the accuracy of digital PCR (dPCR) for copy number quantification of a frequently occurring single-nucleotide variant in colorectal cancer (KRAS c.35G>A, p.Gly12Asp, from hereon termed G12D) by evaluating potential sources of uncertainty that influence dPCR measurement. RESULTS: Concentration values for samples of KRAS G12D and wild-type plasmid templates varied by <1.2-fold when measured using 5 different assays with varying detection chemistry (hydrolysis, scorpion probes, and intercalating dyes) and <1.3-fold with 4 commercial dPCR platforms. Measurement trueness of a selected dPCR assay and platform was validated by comparison with an orthogonal method (inductively coupled plasma mass spectrometry). The candidate dPCR reference measurement procedure showed linear quantification over a wide range of copies per reaction and high repeatability and interlaboratory reproducibility (CV, 2%-8% and 5%-10%, respectively). CONCLUSIONS: This work validates dPCR as an SI-traceable reference measurement procedure based on enumeration and demonstrates how it can be applied for assignment of copy number concentration and fractional abundance values to DNA reference materials in an aqueous solution. High-accuracy measurements using dPCR will support the implementation and traceable standardization of molecular diagnostic procedures needed for advancements in precision medicine.

Measuring the Effectiveness of a Genetic Counseling Supervision Training Conference.

Genetic counselors who receive formal training report increased confidence and competence in their supervisory roles. The effectiveness of specific formal supervision training has not been assessed previously. A day-long GC supervision conference was designed based on published supervision competencies and was attended by 37 genetic counselors. Linear Mixed Model and post-hoc paired t-test was used to compare Psychotherapy Supervisor Development Scale (PSDS) scores among/between individuals pre and post conference. Generalized Estimating Equation (GEE) model and post-hoc McNemar's test was used to determine if the conference had an effect on GC supervision competencies. PSDS scores were significantly increased 1 week (p < 0.001) and 6 months (p < 0.001) following the conference. For three supervision competencies, attendees were more likely to agree they were able to perform them after the conference than before. These effects remained significant 6 months later. For the three remaining competencies, the majority of supervisors agreed they could perform these before the conference; therefore, no change was found. This exploratory study showed this conference increased the perceived confidence and competence of the supervisors who attended and increased their self-reported ability to perform certain supervision competencies. While still preliminary, this supports the idea that a one day conference on supervision has the potential to impact supervisor development.

[Simultaneous determination of ten antibiotics in pharmaceutical wastewater using ultra-high performance liquid chromatography-tandem mass spectrometry].

A simultaneous analytical method was established for ten selected antibiotics from three categories in pharmaceutical wastewater with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The water samples were enriched and cleaned-up by solid phase extraction cartridges. The types of solid phase extraction cartridges and eluents were optimized by comparing the recoveries of the analytes in water samples under different conditions. The target compounds were separated on an Agilent C18 column (75 mmx 2.1 mm, 2.7 µm) with the mobile phases of acetonitrile and 0.2% (v/v) formic acid aqueous solution, and then determined by electrospray ionization mass spectrometry (ESI-MS). The results showed that the calibration curves were linear in the range of 0.1-1000 µg/L (r2>0.995). The limits of detection (LODs, S/N≥3) and the limits of quantification (LOQs, S/N≥10) of the ten compounds were 0.07-4.37 ng/L and 0.22-14.55 ng/L, respectively. The recovery experiments were performed with samples spiked in the range of 0.002-40 µg/L. The recoveries of the target compounds were in the range of 50.4%-114.1% (RSDs≤9.89%, n=3). Based on this analytical method, the raw and treated sewage samples from a pharmaceutical manufacturer wastewater treatment plant in Jiangsu Province were analyzed. Three compounds were detected in the samples from different sewage treatment units in the range of 0.46-1033.60 µg/L. It shows that the method is accurate, reliable, highly sensitive and can be used to analyze the water samples of pharmaceutical wastewater treatment plant containing aminoglycosides, spiramycin and fluoroquinolones antibiotics.

[Cost-effectiveness evaluation on comprehensive control measures carrying out in schistosomiasis endemic areas with regard to different layers of administrative villages stratified by infection situation of human and domestic animals. II Correlation analysis of costs and inputs with changes of schistosomiasis endemic situation in inner embankment of marshland and lake regions from 2006 to 2013].

OBJECTIVE: To investigate the correlations between inputs and costs and endemic situation of schistosomiasis in inner embankment, so as tb provide the references for the strategy optimization of schistosomiasis control. METHODS: Jiangling County was selected as the study field. The correlatibn and regression analyses were applied to analyze the endemic situation of schistosomiasis in Jiangling County from 2006 to 2013. The methods of two-stages least squares and path analysis were applied to analyze the impacts between costs and inputs and endemic situation of schistosomiasis. RESULTS: The adjusted infection rate of population, number of bovines and Oncomelania hupensis snail areas reduced by 77.42%, 76.34% and 19.43%, respectively in Jiangling County from 2006 to 2013. The correlations between the infection rate of snails and the population positive rates of blood and fecal exams, and the infection rate of bovines were significant (all P < 0.05); and there was a significant linear regression between the infection rates of snails and bovines (P < 0.05). There were statistically significant regressions between inputs at different levels and the population positive rates of blood and fecal exams, and the infection rates of bovines and snails, as well as between the costs and the population positive rate of fecal exams and the infection rates of bovines and snails (all P < 0.05), whereas there was no statistically significant regression between the costs and the population positive rate by blood exams (P > 0.05). The inputs at county level had an impact on the population positive rate of blood exams; the costs of comprehensive treatment had an impact on the population positive rate of fecal exams; the costs of human labor and measures for exams and treatments had an impact on the infeiction rate of bovines; the inputs at national level and the costs of measures for exams and treatments had an impact on the infection rate of snails (all P < 0.05). CONCLUSION: The inputs and costs of schistosomiasis control were related to the epidemic situation of schistosomiasis in Jiangling County from 2006 to 2013; therefore, it is necessary to develop a comprehensive surveillance system as substitute for the current indexes on schistosomiasis control.