A water probe for direct pH measurement of individual particles via micro-Raman spectroscopy.

The acidity of atmospheric aerosols influences fundamental physicochemical processes that affect climate and human health. We recently developed a novel and facile water-probe-based method for directly measuring of the pH for micrometer-size droplets, providing a promising technique to better understand aerosol acidity in the atmosphere. The complex chemical composition of fine particles in the ambient air, however, poses certain challenges to using a water-probe for pH measurement, including interference from interactions between compositions and the influence of similar compositions on water structure. To explore the universality of our method, it was employed to measure the pH of ammonium, nitrate, carbonate, sulfate, and chloride particles. The pH of particles covering a broad range (0-14) were accurately determined, thereby demonstrating that our method can be generally applied, even to alkaline particles. Furthermore, a standard spectral library was developed by integrating the standard spectra of common hydrated ions extracted through the water-probe. The library can be employed to identify particle composition and overcome the spectral overlap problem resulting from similar effects. Using the spectral library, all ions were identified and their concentrations were determined, in turn allowing successful pH measurement of multicomponent (ammonium-sulfate-nitrate-chloride) particles. Insights into the synergistic effect of Cl-, NO3-, and NH4+ depletion obtained with our approach revealed the interplay between pH and volatile partitioning. Given the ubiquity of component partitioning and pH variation in particles, the water probe may provide a new perspective on the underlying mechanisms of aerosol aging and aerosol-cloud interaction.

Readiness in implementing green industry standard for SMEs: Case of Indonesia's batik industry.

Green Industry Standard (GIS) acts as a guideline for industries, including the Small and Medium Enterprises (SMEs) to preserve the environment and economy in their production process. This study aims to assess the industry's readiness in the case of Indonesia's batik industry, to adopt the GIS and optimize its implementation. The method used in this study is survey and interviews. The survey and interviews involved 25 respondents, comprising owners or managers of the batik industry engaged in handcrafted, stamped, or combined batik production, from pattern-making to finishing stages. The analysis has been done using the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) instrument to evaluate the industry's readiness and employing TOWS (Threats, Opportunities, Weaknesses, Strengths) analytical tool to formulate optimization strategies. The results of this study show that an assessment of the batik industries' compliance with Green Industry Standards revealed that they have not yet adopted sustainable practices in their production processes concerning materials, energy, water, products, and waste. The SOCRATES analysis also indicates that the batik industry's readiness to meet the technical requirements of the GIS is currently low. In conclusion, the primary approach in applying green industry principles should focus on rectifying existing weaknesses concerning craftsmen's awareness and understanding of green industry practices. After the industry's awareness emerges, utilizing GIS can boost production, improve raw material efficiency, and provide customers with greater "green" value.

Reducing Chronic Spine Pain in an Adult Male by Decreasing Lumbar Scoliosis and Increasing Cervical Lordosis Using Chiropractic BioPhysics® Protocols: A 26-Month Follow-Up Case Report.

We present a case report of a patient suffering from chronic low back pain (CLBP) and chronic non-specific neck pain (CNSNP), both of which were caused and complicated by a physically demanding occupation, a history of mixed martial arts, and lumbar scoliosis. Improvements in patient-reported outcomes (PROs) and radiographic findings were observed following conservative spine rehabilitation. The patient, a 34-year-old male, had experienced chronic spine pain, particularly CLBP and CNSNP, for several years. He reported severe pain and increasing disability after a recent neck injury sustained while practicing jiu-jitsu. Radicular pain, along with numbness and tingling, was noted in the right upper extremity, extending to the first three digits, and there were also altered sensations and temperature changes in both feet. He described sharp, pinching mid-back pain and worsening disability due to the persistent pain, which led him to seek manual manipulative chiropractic spine therapy, though he reported little benefit from it. The patient had relied on over-the-counter pain medications for many years without achieving long-term pain and disability relief, and these medications were no longer used following treatment. Chiropractic BioPhysics® (CBP®) spinal structural rehabilitation protocols were used to improve coronal and sagittal balance, as well as paraspinal muscular strength, addressing posture, mobility, and related aspects. These protocols include postural exercises, postural Mirror Image® traction, and postural spinal manipulative therapy. All PROs improved, with a near resolution of all initial symptoms of chronic spine pain. Outcomes measured included disability indices and health-related quality of life (HRQoL) indicators. Radiographic parameter improvements were significant, demonstrating improved coronal and sagittal balance as a result of the treatment. Following 30 in-office treatments, administered three times per week for 10 weeks, initial outcomes were reassessed. The patient then received 13 in-office treatments periodically over one year, and all initial outcomes were repeated. The improvements remained stable over time. A 26-month follow-up found that the improvements were sustained over a very long period without additional treatment after the 13-month examination. Chronic spine pain, specifically CLBP and CNSNP, is a significant source of suffering and contributes substantially to the global burden of disease. Improvement in HRQoLs, PROs, and objective spine parameters are desirable clinical outcomes. Our case report documents objective improvement in lumbar scoliosis and spine pain, which is rare in conservative studies. This successful treatment of chronic pain with long-term follow-up contributes to the growing evidence supporting conservative, non-surgical treatments for CNSNP and CLBP. Successful management of chronic spine pain was observed in a patient undergoing CBP® treatment. The treatment was designed to address abnormal sagittal and coronal postural balance and radiographic abnormalities indicating spinal misalignment and reassess progress in PROs, as well as objective and subjective HRQoL measures, both following treatment and 13 months later. However, larger studies are needed to draw firm conclusions regarding the efficacy of this treatment for chronic pain.

Evaluation of Lyme serologic quantitative test indexes: High first-tier test index values predict positive second-tier result in standard and modified 2-tier Lyme testing algorithms.

OBJECTIVES: In this study, we evaluated the potential utility of reporting a quantitative Lyme serologic test index to improve the utility of results from first-tier Lyme assays. METHODS: Serum from consecutive samples sent to our laboratory for Lyme testing were tested on 2 commercial first-tier Lyme assays and evaluated to determine the probability of second-tier confirmation based on the serologic index value. RESULTS: For both assays, we identified an index value above which 100% of samples confirmed on second-tier testing using both standard and modified 2-tier testing algorithms. Lower rates of confirmation were observed for positive or equivocal samples with lower index values. CONCLUSION: The use of a Lyme test index value may eliminate the need for confirmatory testing on many positive first-tier samples, providing more rapid turnaround time to a definitive result. This practice would also increase efficiency in the clinical laboratory.

Deep integration of low-cost liquid handling robots in an industrial pharmaceutical development environment.

The pharmaceutical industry is increasingly embracing laboratory automation to enhance experimental efficiency and operational resilience, particularly through the integration of automated liquid handlers (ALHs). This paper explores the integration of the low-cost Opentrons OT-2 liquid handling robot with F. Hoffmann-La Roche AG's in-house workflow orchestration software, AutoLab, to overcome barriers to lab automation. By leveraging the OT-2's development-oriented interfaces and AutoLab's modular architecture, we achieved a user-friendly, cost-efficient, and flexible automation solution that aligns with FAIR (findable, accessible, interoperable, reusable) data principles. We demonstrate an advanced workflow development methodology, utilizing the software architecture, that facilitates the creation of two flexible pipetting protocols and medium complexity assays. This deep integration approach diminishes the learning curve for novice users while simultaneously enhancing the overall efficiency and reliability of the experimental workflow. Our findings suggest that such integrations can significantly mitigate the challenges associated with lab automation, including cost, complexity, and adaptability, paving the way for more accessible and robust automated systems in pharmaceutical research.

Socioeconomic determinants of small and medium-sized dairy farms in the Ecuador-Colombia border area.

The socioeconomic factors influencing small-scale dairy producers in the border area between Ecuador and Colombia were meticulously identified. Employing a non-experimental design, the study leveraged multivariate statistical analysis to discern key determinants. Data processing was executed using the statistical software SPSS v27, facilitating comprehensive analysis. A random survey was administered to 532 small and medium-scale dairy producers in the Carchi province of Ecuador, employing a structured questionnaire supplemented with a Likert scale for nuanced insights. Based on 35 original variables, seven determining factors were identified in dairy farms: political representation, adequate housing, equipment, innovation, empathy, profitability, social welfare, which combined explain 60.95% of the system's variability. Such factors affect production, the level of household income, as well as their effect on the standard of living of households. Three groups were formed, the first with a low perception of economic development (Traditionalists 33.3%); the second with a better expectation of economic development (Modernizers 27.6%); and the third, identified with greater economic development (Innovators 10.3%). Each group presents cases with a low to high standard of living perspective. The groups have peculiarities in terms of their performance that can be applied to the entire population. A significant relation was established between socioeconomic factors and standard of living.

The effect of air pollution quality on lung cancer rates in middle-income and high-income countries: a panel data analysis approach.

Background: Air pollution is one of the biggest problems in societies today. The intensity of indoor and outdoor air pollutants and the urbanization rate can cause or trigger many different diseases, especially lung cancer. In this context, this study's aim is to reveal the effects of the indoor and outdoor air pollutants, and urbanization rate on the lung cancer cases. Methods: Panel data analysis method is applied in this study. The research includes the period between 1990 and 2019 as a time series and the data type of the variables is annual. The dependent variable in the research model is lung cancer cases per 100,000 people. The independent variables are the level of outdoor air pollution, air pollution level indoor environment and urbanization rate of countries. Results: In the modeling developed for the developed country group, it is seen that the variable with the highest level of effect on lung cancer is the outdoor air pollution level. Conclusions: In parallel with the development of countries, it has been determined that the increase in industrial production wastes, in other words, worsening the air quality, may potentially cause an increase in lung cancer cases. Indoor air quality is also essential for human health; negative changes in this variable may negatively impact individuals' health, especially lung cancer.

A hierarchical residual correction-based hyperspectral inversion method for soil heavy metals considering spatial heterogeneity.

Promising hyperspectral remote sensing exhibits substantial potential in monitoring soil heavy metal (SHM) contamination. Nevertheless, the local spatial perturbation effects induced by environmental factors introduce considerable variability in SHM distribution. This engenders non-stationary relationship between SHM concentrations and spectral reflectance, posing challenges for accurate inversion of SHM globally. Addressing this gap, a novel Hierarchical Residual Correction-based Hyperspectral Inversion Method (HRCHIM) is proposed for SHM, considering their spatial heterogeneity. Initially, a global model is constructed using ground hyperspectral data to predict SHM concentration, capturing overarching contamination trends. Subsequently, four hierarchical levels, segmented by residual standard deviation (SD) intervals, identify critical environmental factors via Geodetector. These factors inform local residual correction models, refining global model predictions. HRCHIM aims to synergize global trends and local stochasticity to enhance prediction accuracy and interpretation of SHM spatial heterogeneity. Validated through a case study of a Cadmium(Cd)-contaminated mine area, six critical environmental factors were identified, exhibiting significant differences across hierarchical levels. By incorporating hierarchical correction models, HRCHIM demonstrated superior inversion performance compared to other conventional methods, achieving optimal prediction accuracies (Rv2 = 0.94, RMSEv = 0.21, and RPDv = 4.11). This innovative method can facilitate more precise and targeted strategies for preventing and controlling SHM contamination.

Performance comparison of three commercial multiplex molecular panels for respiratory viruses at a South African academic hospital.

Background: Respiratory infections are a major contributor to hospital admissions. Identification of respiratory pathogens by means of conventional culture and serology methods remains challenging. Multiplex molecular assays are an appealing alternative that endeavours to be rapid, more accurate and less arduous. Objective: The study aimed to compare the clinical performance of three commercial multiplex molecular assays for respiratory viruses. Methods: Forty-eight respiratory specimens obtained from patients at Tygerberg Hospital in the Western Cape province of South Africa were studied. These specimens were collected between May 2020 and August 2020. The results of the Seegene Anyplex™ II RV16, FilmArray® Respiratory 2.1 plus Panel (FARP), and QIAstat-Dx® Respiratory SARS-CoV-2 Panel (QRP) were analysed based on the overlapping targets. A composite reference standard was applied to provide a standard reference for comparison. Results: The overall sensitivity of the Seegene Anyplex™ II RV16 was 96.6% (57/59), the FARP 98.2% (56/57) and the QRP 80.7% (46/57). The overall specificities were 99.8% (660/661), 99.0% (704/711) and 99.7% (709/711), respectively. The QRP failed to detect coronaviruses and parainfluenza viruses in 41.7% (5/12) and 28.6% (4/14) of positive specimens, respectively, while the FARP produced the lowest target specificity of 88.4% (38/43) for rhinovirus/enterovirus. Conclusion: The overall specificity of all three platforms was comparable; however, the sensitivity of the QRP was inferior to that of the ARV and FARP. What this study adds: This study adds to the body of performance characteristics described for respiratory multiplex panels, especially in the African context where molecular diagnostics for infectious diseases are gaining momentum.

Comparison of parasitological methods for the identification of soil-transmitted helminths, including Strongyloides stercoralis, in a regional reference laboratory in northwestern Argentina: An observational study.

Soil-transmitted helminths (STH) are a significant public health problem in impoverished communities of tropical and subtropical areas. Improved diagnostic methods are crucial for Neglected Tropical Diseases programs, particularly for S. stercoralis, as traditional methods are inadequate. Thus, it is important to identify the most accurate and efficient methods for the diagnosis of STH. We performed a retrospective study analyzing laboratory data at the Instituto de Investigaciones de Enfermedades Tropicales from 2010 to 2019. The study included data from outpatients referred for stool analysis and public health interventions from urban and rural communities in northern Salta province, Argentina. Samples were included in this analysis if processed through sedimentation/concentration, Baermann, Harada-Mori and McMaster's, with a subgroup that also included Agar plate culture method (APC). Sensitivity was calculated against a composite reference standard. Of the 5625 samples collected, 944 qualified for this analysis, with a prevalence of 11.14% for A. lumbricoides, 8.16% for hookworm, 1.38% for T. trichiura, and 6.36% for S. stercoralis. The sedimentation/concentration method was the most sensitive for A. lumbricoides (96%), compared to the McMaster method, with a sensitivity of 62%. Similarly, for hookworms, sedimentation/concentration was more sensitive than McMaster's, Harada-Mori, and Baermann with sensitivities of 87%, 70%, 43%, and 13%, respectively. Most of these infections were of light intensity. For S. stercoralis, Baermann and sedimentation/concentration methods were the most sensitive, with 70% and 62% respectively, while Harada-Mori was the least sensitive. In a subset of 389 samples also analyzed by the APC, Baermann was more sensitive than APC for detecting S. stercoralis, and both methods were superior to Harada-Mori. Parasitological methods, mostly when used combined, offer adequate opportunities for the diagnosis of STH in clinical and public health laboratories. The incorporation of S. stercoralis into the control strategies of the World Health Organization requires rethinking the current diagnostic approach used for surveys. With sedimentation/concentration and Baermann appearing as the most sensitive methods for this species. Further studies, including implementation assessments, should help in identifying the most adequate and feasible all-STH diagnostic approach.

Stapedotomy Utilizing a Fixed-Size Prosthesis in a Tertiary Care Center: A Retrospective Study.

Background Stapes surgery success depends on several factors, including the length of the prosthesis used. Whether to use a standard-size prosthesis or measure the length of the stapes prosthesis has been debated in the literature. This study aims to assess the surgical outcomes of a stapedotomy using the standard 4.5 mm prosthesis without custom measurements. Methodology This retrospective study involved patients with otosclerosis who underwent primary stapedotomy using a standardized 4.5 mm fixed-length prosthesis between January 2017 and February 2023 at a tertiary care center. Results Out of 111 charts reviewed, 99 ears (56 males and 43 females) were studied. The mean air-bone gap (ABG) significantly improved from 27.9 ± 9.12 dB preoperatively to 3.95 ± 3.54 dB post-operatively (p-value < 0.05). Hearing results showed that out of 99 ears, 96.96% had a postoperative ABG of ≤10 dB and 98.98% ≤20 dB. Only three patients showed postoperative mild transient dizziness that lasted a few days. None of the patients had persistent dizziness for more than one week. One patient developed postoperative reparative granuloma with tinnitus and sensory-neural hearing loss. None had a recurrence of the conductive hearing loss during the study period. Conclusion Our retrospective study on stapes surgery utilizing a standardized 4.5 mm prosthesis without custom measurements showed notable surgical success and safety. Using a standard-size prosthesis shortens the surgical time and eliminates the complexities associated with intraoperative measurements, potentially reducing the risk of complications.

The adult ADHD assessment quality assurance standard.

Background: Attention Deficit Hyperactivity Disorder (ADHD) frequently persists into adulthood. There are practice guidelines that outline the requirements for the assessment and treatment of adults. Nevertheless, guidelines specifying what constitutes a good quality diagnostic assessment and report and the competencies required to be a specialist assessor are lacking. This can lead to variation in the quality and reliability of adult ADHD assessments. Poor quality assessments may not be accepted as valid indicators of the presence of ADHD by other clinicians or services, resulting in wasteful re-assessments and delays in providing treatment. To address this issue the UK Adult ADHD Network (UKAAN) proposes a quality framework for adult ADHD assessments - the Adult ADHD Assessment Quality Assurance Standard (AQAS). Methods: The co-authors agreed on five questions or themes that then guided the development of a set of consensus statements. An initial draft was reviewed and amended in an iterative process to reach a final consensus. Results: What constitutes a high-quality diagnostic assessment and report was agreed by consensus of the co-authors. The resulting guideline emphasises the need to evaluate impairment, describes core competencies required by the assessor and highlights the importance of linking the diagnosis to an appropriate post-diagnostic discussion. Assessments should be completed in the context of a full psychiatric and neurodevelopmental review, and need good interview skills, using a semi-structured interview with open questioning and probing to elicit real life examples of symptoms and impairments. It is recommended that 2 hours or more is required for an adequate assessment including both the diagnostic assessment and initial post-assessment discussions. Conclusion: The AQAS has been developed as a practical resource to support reliable and valid diagnostic assessments of adult ADHD. It is intended to complement formal training. A secondary objective is to empower patients by providing them with evidence-based information on what to expect from an assessment and assessment report.

Clinical Audit of Assisting Renal Biopsy Procedure Performed in Nephrology Unit of a Tertiary Care Hospital with a View to Develop Standard Nursing Procedure Protocol.

Background: Renal biopsy is one of the most commonly performed diagnostic procedures in the nephrology unit. Nurses play a very important role in pre-biopsy preparation, assisting during procedure and post-biopsy care. Nursing care provided during or after renal biopsy is of utmost importance in reducing complications. The study aims to perform a clinical audit of nursing practices to find the gaps in existing practices for the procedure of assisting renal biopsy and to develop standard protocol. Materials and Methods: This descriptive observational study was conducted on 19 nurses who were working in the nephrology unit of the tertiary care center. They were enrolled through total enumerative sampling. Sociodemographic profile and clinical profile were collected. The observation checklist was formed based on standard nursing practices, which included three dimensions for the procedure of assisting renal biopsy. Based on the gaps identified, a standard protocol was developed. Nurses were observed during two shifts and each nurse was observed once. Scoring of items was done in each dimension and for acceptable practices, nurses have to score ≥80% in each dimension. Data were analyzed using descriptive statistics. Results: The majority of nurses (73.7%) have not undergone any special training in nephrology. None (100%) showed an acceptable level of nursing practices for all the dimensions of assisting renal biopsy procedure. Standard protocol was developed by the researcher following a rigorous process. Conclusion: The clinical audit found that there were gaps in the existing nursing practices for the procedure of assisting renal biopsy and these gaps have been addressed by the development of a standard protocol.

An Efficient Certificateless Anonymous Signcryption Scheme for WBAN.

A Wireless Body Area Network (WBAN), introduced into the healthcare sector to improve patient care and enhance the efficiency of medical services, also brings the risk of the leakage of patients' privacy. Therefore, maintaining the communication security of patients' data has never been more important. However, WBAN faces issues such as open medium channels, resource constraints, and lack of infrastructure, which makes the task of designing a secure and economical communication scheme suitable for WBAN particularly challenging. Signcryption has garnered attention as a solution suitable for resource-constrained devices, offering a combination of authentication and confidentiality with low computational demands. Although the advantages offered by existing certificateless signcryption schemes are notable, most of them only have proven security within the random oracle model (ROM), lack public ciphertext authenticity, and have high computational overheads. To overcome these issues, we propose a certificateless anonymous signcryption (CL-ASC) scheme suitable for WBAN, featuring anonymity of the signcrypter, public verifiability, and public ciphertext authenticity. We prove its security in the standard model, including indistinguishability, unforgeability, anonymity of the signcrypter, and identity identifiability, and demonstrate its superiority over relevant schemes in terms of security, computational overheads, and storage costs.

Research on the Application of Dynamic Process Correlation Based on Radar Data in Mine Slope Sliding Early Warning.

With the gradual expansion of mining scale in open-pit coal mines, slope safety problems are increasingly diversified and complicated. In order to reduce the potential loss caused by slope sliding and reduce the major threat to the safety of life and property of residents in the mining area, this study selected two mining areas in Xinjiang as cases and focused on the relationship between phase noise and deformation. The study predicts the specific time point of slope sliding by analyzing the dynamic history correlation tangent angle between the two. Firstly, the time series data of the micro-variation monitoring radar are used to obtain the small deformation of the study area by differential InSAR (D-InSAR), and the phase noise is extracted from the radar echo in the sequence data. Then, the volume of the deformation body is calculated by analyzing the small deformation at each time point, and the standard deviation of the phase noise is calculated accordingly. Finally, the sliding time of the deformation body is predicted by combining the tangent angle of the ratio of the volume of the deformation body to the standard deviation of the phase noise. The results show that the maximum deformation rates of the deformation bodies in the studied mining areas reach 10.1 mm/h and 6.65 mm/h, respectively, and the maximum deformation volumes are 2,619,521.74 mm3 and 2,503,794.206 mm3, respectively. The predicted landslide time is earlier than the actual landslide time, which verifies the effectiveness of the proposed method. This prediction method can effectively identify the upcoming sliding events and the characteristics of the slope, provide more accurate and reliable prediction results for the slope monitoring staff, and significantly improve the efficiency of slope monitoring and early warning.

Study on the Shear Strength and Erosion Resistance of Sand Solidified by Enzyme-Induced Calcium Carbonate Precipitation (EICP).

Sand solidification of earth-rock dams is the key to flood discharge capacity and collapse prevention of earth-rock dams. It is urgent to find an economical, environmentally friendly, and durable sand solidification technology. However, the traditional grouting reinforcement method has some problems, such as high costs, complex operations, and environmental pollution. Enzyme-induced calcium carbonate precipitation (EICP) is an anti-seepage reinforcement technology emerging in recent years with the characteristics of economy, environmental protection, and durability. The erosion resistance and shear strength of earth-rock dams solidified by EICP need further verification. In this paper, EICP-solidified standard sand is taken as the research object, and EICP-cemented standard sand is carried out by a consolidated undrained triaxial test. A two-stage pouring method is adopted to pour samples, and the effects of dry density, cementation times, standing time, and confining pressure on the shear strength of cemented standard sand are emphatically analyzed. The relationship between cohesion, internal friction angle, and CaCO3 formation was analyzed. After the optimal curing conditions are obtained through the triaxial shear strength test, the erosion resistance model test is carried out. The effects of erosion angle, erosion flow rate, and erosion time on the erosion resistance of EICP-solidified sand were analyzed through an erosion model test. The results of triaxial tests show that the standard sand solidified by EICP exhibits strain softening, and the peak strength increases with the increase in initial dry density, cementation times, standing time, and confining pressure. When the content of CaCO3 increases from 2.84 g to 12.61 g, the cohesive force and internal friction angle change to 23.13 times and 1.18 times, and the determination coefficients reach 0.93 and 0.94, respectively. Erosion model test results indicate that the EICP-solidified sand dam has good erosion resistance. As the increase in erosion angle, erosion flow rate, and erosion time, the breach of solidified samples gradually becomes larger. Due to the deep solidification of sand by EICP, the development of breaches is relatively slow. Under different erosion conditions, the solidified samples did not collapse and the dam broke. The research results have important reference value and scientific significance for the practice of sand consolidation engineering in earth-rock dams.

Individualized clinical decisions within standard-of-care pragmatic clinical trials: Implications for consent.

Pragmatic clinical trials of standard-of-care interventions compare the relative merits of medical treatments already in use. Traditional research informed consent processes pose significant obstacles to these trials, raising the question of whether they may be conducted with alteration or waiver of informed consent. However, to even be eligible, such a trial in the United States must have no more than minimal research risk. We argue that standard-of-care pragmatic clinical trials can be designed to ensure that they are minimal research risk if the random assignment of an intervention in a pragmatic clinical trial can accommodate individualized, clinically motivated decision-making for each participant. Such a design will ensure that the patient-participants are not exposed to any risks beyond the clinical risks of the interventions, and thus, the trial will have minimal research risk. We explain the logic of this view by comparing three scenarios of standard-of-care pragmatic clinical trials: one with informed consent, one without informed consent, and one recently proposed design called Decision Architecture Randomization Trial. We then conclude by briefly showing that our proposal suggests a natural way to determine when to use an alteration versus a waiver of informed consent.

Concurrent chemoradiotherapyof different radiation doses and different irradiation fields for locally advanced thoracic esophageal squamous cell carcinoma: A randomized, multicenter, phase III clinical trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. METHODS: This trial compared two aspects of radiation treatment, total dose and field, using a two-by-two factorial design. The high-dose (HD) group received 59.4 Gy radiation, and the standard-dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. RESULTS: The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80-1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82-1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72-1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. CONCLUSIONS: IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.

Conscience, Disobedience, and Standard of Care.

In the article "Principled Conscientious Provision: Referral Symmetry and Its Implications for Protecting Secular Conscience," Abram L. Brummett, Tanner Hafen, and Mark C. Navin reject what they call the "referral asymmetry" in U.S. conscientious objection law in medicine, which recognizes rights of conscientiously objecting physicians to withhold referrals for medical interventions but does not (yet) recognize rights of physicians to make referrals for medical interventions to which they are morally committed but to which their health care institutions are morally opposed. This commentary concentrates on a second asymmetry, namely, the relationship of a health care provider's referral or nonreferral to the medical standard of care. The commentary argues that this second asymmetry seems to require action more appropriately recognized as civil disobedience than conscientious provision of referral.

A novel approach for health state valuation: Multiple bounded dichotomous choice compared to the traditional standard gamble.

OBJECTIVE: to assess the feasibility of a new stated preference approach, the multiple bounded dichotomous choice (MBDC), designed to generate value sets for preference-based measurement of health-related quality of life. METHODS: MBDC and standard gamble (SG) tasks were completed to derive SF-6Dv2 value sets from a sample of the general population in Quebec, Canada. Participants were randomized between the two approaches: 6 health states were evaluated in SG and 11 health states in MBDC. Several models were used to estimate data in each approach, and the preferred models were chosen by using mean absolute error (MAE), logical consistency of parameters, and significance levels. Results of MBDC were compared with SG in terms of acceptability (self-reported difficulty and quality levels in answering, and completion time), consistency (monotonicity of model coefficients), accuracy (standard errors), dimensions coefficient magnitude, correlation between the value sets estimated, and the range of estimated values. The intra-class correlation coefficient (ICC) was computed to assess value sets' consistency. RESULTS: Out of 655 individuals who completed MBDC tasks and 828 who completed SG tasks, a total of 585 participants for MBDC and 714 for SG tasks were included for analysis. The preferred models for both approaches were GLS Tobit. No significant difference was observed in self-reported difficulties and qualities in answers among approaches, but MBDC had less excluded participants and was less prone to report difficulties in answering. Additionally, completion time in the MBDC group was significantly lower (99.80 vs 68.12 s). Most standard errors in the MBDC were lower than those in SG, and the number of non-significant parameters was also lower. The range of utility values generated by MBDC tended to be wider (-0.372 to 1) than those generated by the SG (-0.137 to 1) and the number of worse-than-dead states in MBDC (0.91%) was higher than for SG (0.08%). The Pain dimension was identified as the most significant, while the Vitality dimension showed the lowest significant decrement. Both approaches exhibited a tendency to overestimate severe health state values and underestimate better health state values. The correlation and ICC between the two value sets were 0.937 and 0.983, respectively. CONCLUSION: Based on empirical evidence, it can be inferred that the MBDC method is not only feasible but also holds the potential to generate meaningful and well-informed preference data from respondents. This approach can be used to derive a value set for preference-based instrument.