Guidelines for Manufacturing and Application of Organoids: Liver.

Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable of accurately replicating liver functions for drug efficacy and toxicity predictions. Liver organoids, derived from human cell sources, offer promise as a reliable platform for drug evaluation. However, there is a lack of standardized quality evaluation methods, which hinders their regulatory acceptance. This paper proposes comprehensive quality standards tailored for liver organoids, addressing cell source validation, organoid generation, and functional assessment. These guidelines aim to enhance reproducibility and accuracy in toxicity testing, thereby accelerating the adoption of organoids as a reliable alternative or complementary tool to animal testing in drug development. The quality standards include criteria for size, cellular composition, gene expression, and functional assays, thus ensuring a robust hepatotoxicity testing platform.

Scoping review of the recommendations and guidance for improving the quality of rare disease registries.

BACKGROUND: Rare disease registries (RDRs) are valuable tools for improving clinical care and advancing research. However, they often vary qualitatively, structurally, and operationally in ways that can determine their potential utility as a source of evidence to support decision-making regarding the approval and funding of new treatments for rare diseases. OBJECTIVES: The goal of this research project was to review the literature on rare disease registries and identify best practices to improve the quality of RDRs. METHODS: In this scoping review, we searched MEDLINE and EMBASE as well as the websites of regulatory bodies and health technology assessment agencies from 2010 to April 2023 for literature offering guidance or recommendations to ensure, improve, or maintain quality RDRs. RESULTS: The search yielded 1,175 unique references, of which 64 met the inclusion criteria. The characteristics of RDRs deemed to be relevant to their quality align with three main domains and several sub-domains considered to be best practices for quality RDRs: (1) governance (registry purpose and description; governance structure; stakeholder engagement; sustainability; ethics/legal/privacy; data governance; documentation; and training and support); (2) data (standardized disease classification; common data elements; data dictionary; data collection; data quality and assurance; and data analysis and reporting); and (3) information technology (IT) infrastructure (physical and virtual infrastructure; and software infrastructure guided by FAIR principles (Findability; Accessibility; Interoperability; and Reusability). CONCLUSIONS: Although RDRs face numerous challenges due to their small and dispersed populations, RDRs can generate quality data to support healthcare decision-making through the use of standards and principles on strong governance, quality data practices, and IT infrastructure.

Physiologically Based Biopharmaceutics Modeling (PBBM): Best Practices for Drug Product Quality, Regulatory and Industry Perspectives: 2023 Workshop Summary Report.

Physiologically based biopharmaceutics modeling (PBBM) is used to elevate drug product quality by providing a more accurate and holistic understanding of how drugs interact with the human body. These models are based on the integration of physiological, pharmacological, and pharmaceutical data to simulate and predict drug behavior in vivo. Effective utilization of PBBM requires a consistent approach to model development, verification, validation, and application. Currently, only one country has a draft guidance document for PBBM, whereas other major regulatory authorities have had limited experience with the review of PBBM. To address this gap, industry submitted confidential PBBM case studies to be reviewed by the regulatory agencies; software companies committed to training. PBBM cases were independently and collaboratively discussed by regulators, and academic colleagues participated in some of the discussions. Successful bioequivalence "safe space" industry case examples are also presented. Overall, six regulatory agencies were involved in the case study exercises, including ANVISA, FDA, Health Canada, MHRA, PMDA, and EMA (experts from Belgium, Germany, Norway, Portugal, Spain, and Sweden), and we believe this is the first time such a collaboration has taken place. The outcomes were presented at this workshop, together with a participant survey on the utility and experience with PBBM submissions, to discuss the best scientific practices for developing, validating, and applying PBBMs. The PBBM case studies enabled industry to receive constructive feedback from global regulators and highlighted clear direction for future PBBM submissions for regulatory consideration.

Impact of Quality Standards on Stroke Management and Outcome Requires Appropriately Designed Studies.

How to cite this article: Mehri S, Finsterer J. Impact of Quality Standards on Stroke Management and Outcome Requires Appropriately Designed Studies. Indian J Crit Care Med 2024;28(4):406-407.

Selenium-mercury interactions and relationship to aquatic toxicity: A review.

A review of the literature pertaining to selenium-mercury (Se/Hg) interactions in aquatic species was performed to provide insight into the mechanisms allowing for the reported changes in bioaccumulation and toxicity that have been observed when the two elements occur at elevated concentrations. Selenium (Se) has been shown to protect against mercury (Hg) toxicity in all animal models evaluated (fish, birds, mammals, and plants). To explore the interaction between the two elements, data are presented on concentrations of both elements in wild-caught fish at numerous locations. The data show that most fish have Se/Hg ratios >1.0. The importance of this ratio has been reported, with suggestions that the protective interaction is due in large part to the formation of HgSe. Data show that when the Se/Hg molar ratio is <1.0 in the diet of fish and animals, Hg toxicity will be expressed, provided that the Hg concentration is sufficiently high. This toxicity is likely the result of Se deficiency leading to an excess of reactive oxygen species. Laboratory fish toxicity studies reviewed show that Se toxicity can be reduced or eliminated when Hg is added to the diet in moderate amounts. Field studies have shown reduced accumulation of Hg when Se concentrations are increased. When Hg in the diet is significantly elevated (usually >10 µg/g), toxicity is expressed regardless of the Se present. Likewise, amelioration of Se toxicity by Hg occurs over a limited range. Tissue thresholds for Se toxicity have been derived primarily from studies where fish eggs were extracted from wild fish and embryo deformities were observed; however, the amount of Hg in the fish or ovaries was not considered, which could lead to uncertainty in the toxicity threshold. It is recommended that both elements be measured and evaluated when performing risk assessments and setting water quality criteria. Integr Environ Assess Manag 2024;00:1-11. © 2024 SETAC.

[Establishment and Optimization of Quality Standards for the Traditional Tibetan Medicine Preparation of Liuwei Nengxiao Pills]. / è—è¯å ­å‘³èƒ½æ¶ˆä¸¸è´¨é‡æ ‡å‡†çš„å»ºç«‹ä¸Žä¼˜åŒ–.

Objective: To establish quality standards for Liuwei Nengxiao pills, to optimize the quality control method, and to provide references for the quality control of Liuwei Nengxiao pills. Methods: Chebula, dried ginger, and Tibetan liqueur root in Liuwei Nengxiao pills of different batch numbers were analyzed by thin layer chromatography (TLC). Then, the content of chrysophanol in the preparation was determined by high performance liquid chromatography (HPLC). Furthermore, a series of methodological validation, including the investigation of the linear relationship, precision, stability, and reproducibility and sample recovery test, were performed to verify the reliability of the results. Results: The TLC identification method was easy to perform and demonstrated high specificity, clear spots, and good separation effect. In addition, the negative controls showed no interference. The HPLC method showed high accuracy. The results of methodological validation showed that the peak area of chrysophanol had a good linear relationship (r2=1.0) in the range of 0.06-0.80 µg, presenting good precision (with the relative standard deviation being lower than 2.0%), good stability and reproducibility (with the relative standard deviation being lower than 1.0%), and an average recovery rate of 100.8%. Conclusion: TLC and HPLC are easy to perform, showing high accuracy and reproducibility. The quality standards established are scientific, reasonable, stable, and feasible, providing references for the quality control of Liuwei Nengxiao pills.

Quality control and evaluation of Black chokeberry (Aronia melanocarpa) by three-wavelength fusion fingerprinting and electrochemical fingerprinting combined with antioxidant activity analysis.

In this study, Black chokeberry (Aronia melanocarpa) was used as an example to provide reference for improving the safety, efficacy and quality consistency of homologous foods. In this study, two quality markers (Q-markers) of 27 batches of Black chokeberry were determined using high performance liquid chromatography (HPLC), and there were some differences among the 27 samples. Origin B samples had the highest levels of Q-markers for S15, and origin C had lower than average levels overall. Samples were analyzed qualitatively and quantitatively by Systematic Quantitative Fingerprinting (SQFM). Subsequently, a three-wavelength fusion analysis (TWFP) was established on the chromatographic data to compensate for the lack of a single wavelength. Fourteen batches of TWFP samples were rated at Level 5 or above in the SQFM assessment, indicating that there is some variation in the content of samples from different origins. Principal component analysis (PCA) was used to observe the differences in chemical composition and content of TWFP samples. Subsequently, electrochemical fingerprinting (ECFP) was established and nine characteristic parameters were recorded, showing that the samples were suppressed for all electrochemical Belousov-Zhabotinsky oscillation systems (B-Z oscillation systems). Finally, antioxidant tests were performed using DPPH. The antioxidant capacity was predicted using Partial Least Squares (PLS) analysis with R2Y = 0.84, Q2 = 0.77, a good model fit and accurate prediction. The fingerprint-potency relationship between IC50-peak area showed that 17 of the 19 shared peaks were negatively correlated, indicating that 17 peaks contributed significantly to the antioxidant. The methods established in this study for the determination of TWFP and ECFP, as well as the spectral relationships with peak area and IC50, can be used for the quality inspection and antioxidant capacity test of Black chokeberry, which provides a new research direction for improving the quality standard of medicinal and foodstuffs.

Quality Standards in Upper Gastrointestinal Endoscopy: Can Deep Sedation Influence It?

Introduction: According to the guideline published by ESGE/UEG, a high-quality esophagogastroduodenoscopy (EGD) implies the application of some criteria that enable better healthcare outcomes. Although intra-procedural performance measures are dependent on patient factors, there is no reference to sedation practices in the guideline mentioned above. Objective: This study aimed to evaluate whether deep sedation influences EGD performance measures established by ESGE/UEG. Methods: This was a cross-sectional study, with a prospective enrollment, that considered for inclusion consecutive patients referred for EGD. Two questionnaires were used to assess performance measures and patient satisfaction after EGD. Results: Sedation had a statistically significant impact on most quality indicators, including complete examination (77.2% without sedation vs. 97.8% with sedation), inspection time (6.17 ± 3.45 vs. 8.39 ± 2.67 min), photodocumentation (78% vs. 97.8%), biopsies (39.3% vs. 60.7%), and patient satisfaction (5.42 ± 2.93 vs. 9.1 ± 1.19). The main reason for an incomplete procedure was patient intolerance (82.6%). Discussion: Deep sedation of patients submitted to EGD proved to be a determinant in the applicability of the ESGE/UEG quality indicators. Patient intolerance was eliminated in the group with sedation, enhancing procedure completeness, adequate pathology identification, management, and consequently, the effectiveness of the exam. Conclusion: Sedation administration should be considered in patients undergoing EGD since it ensures a high-quality procedure.

Introdução: Uma endoscopia digestiva alta (EDA) de qualidade proporciona melhores resultados em termos de saúde e implica a aplicação dos critérios descritos pelas recomendações da ESGE/UEG. Embora os critérios perprocedimento sejam dependentes da colaboração e tolerância do doente, não está explicito o papel da anestesia. Objetivos: Este estudo pretende avaliar se o recurso a anestesia influencia o cumprimento dos critérios de qualidade para a EDA publicados pela ESGE/UEG. Materiais e métodos: Estudo transversal, com recrutamento prospetivo, que incluiu pacientes consecutivamente encaminhados para realização de EDA. Foram utilizados 2 questionários para avaliar medidas de desempenho e satisfação dos pacientes após realização de EDA. Resultados: A anestesia teve um impacto estatisticamente significativo na maioria dos indicadores de qualidade: exame completo (77,2% sem anestesia vs. 97,8% com anestesia); tempo de inspeção (6,17 ± 3,45 vs. 8,39 ± 2,67 minutos); fotodocumentação (78% vs. 97,8%); biópsias (39,3% vs. 60,7%); satisfação do paciente (5,42 ± 2,93 vs. 9,1 ± 1,19). O principal motivo para um procedimento incompleto foi a intolerância do paciente (82,6%). Discussão: A sedação profunda dos doentes submetidos a EDA provou ser determinante na aplicabilidade dos critérios de qualidade da ESGE/UEG. Eliminando por completo a intolerância por parte do doente, proporcionou a realização de exames completos, com correta identificação e gestão de patologias, potenciando assim a efetividade do exame. Conclusão: A administração de anestesia deve ser ponderada, sempre que possível, nos doentes submetidos a EDA, visto que permite garantir a alta qualidade do procedimento.

Temporal variations in micropollutant inlet concentrations matter when planning the design and compliance assessment of stormwater control measures.

Stormwater Control Measures (SCMs) contribute to reducing micropollutant emissions from separate sewer systems. SCM planning and design are often performed by looking at the hydrological performance. Assessment of pollutant removal and the ability to comply with discharge concentration limits is often simplified due to a lack of data and limited monitoring resources. This study analyses the impact of using different time resolutions of input stormwater concentrations when assessing the compliance of SCMs against water quality standards. The behaviour of three indicator micropollutants (MP - Copper, Diuron, Benzo[a]pyrene) was assessed in four SCM archetypes, which were defined to represent typical SCM removal processes. High resolution MP data were extrapolated by using high resolution (2 min) measurements of TSS over a long period (343 events). The compliance assessment showed that high resolution input concentrations can result in a different level of compliance with water quality standards, especially when discharged concentrations are close to the limit values. This study underlines the importance of considering the high temporal variability of stormwater micropollutants when planning and designing SCMs to identify the most effective solutions for stormwater pollution management and to ensure a thorough consideration of all the environmental implications.

Statistical analysis of air quality dataset of Kathmandu, Nepal, with a New Extended Kumaraswamy Exponential Distribution.

This paper aims to create a new probability distribution and conducts statistical analysis on air quality dataset from Kathmandu. Using this innovative distribution, we have studied the ground reality of air quality conditions of Kathmandu, Nepal. In our research, we have developed a new probability distribution known as the New Extended Kumaraswamy Exponential Distribution by introducing an additional shape parameter to the Extended Kumaraswamy Exponential (EKwE) Distribution. Statistical characteristics such as cumulative distribution function, probability density function, hazard function, reversed hazard function, skewness, kurtosis, survival function, and hazard rate function are studied. The suggested model is non-normal and positively skewed with increasing and inverted bathtub-shaped hazard rate curves. To assess the model's suitability, we utilized a real dataset comprising air quality data from Kathmandu, Nepal, during the year 2021. Study shows that the air quality data exhibit an increasing failure rate, but the P2.5, P10, and total suspended particle concentrations exhibited its lowest levels during the monsoon season and its highest levels during the winter season. Parameters of the model are estimated by using the least square estimation (LSE), maximum likelihood estimation (MLE), and Cramér-von Mises (CVM) approach for P10 at Ratnapark Station, Kathmandu. To assess the model's validity, P-P plots and Q-Q plots are employed. Model comparisons are carried out using Akaike Information Criterion (AIC), Corrected Akaike Information Criterion (CAIC), Bayesian Information Criterion (BIC), and Hannan-Quinn Information Criterion (HQIC). Furthermore, the goodness of fit of the proposed model is evaluated using test statistics such as Anderson-Darling (A2) test, Cramér-von Mises (CVM) test, and the Kolmogorov-Smirnov (KS) test along with their respective p-values. From the findings, we have found that the air quality status of Kathmandu, Nepal, was found to be poor. Proposed distribution provides a better fit with greater flexibility for forecasting air quality data and conducting reliability data analyses. Dataset is analyzed and visualized using R programming.

Fate and effects of a new generation fluorosurfactant (cC6O4) in freshwater mesocosms.

Per- and polyfluorinated alkyl substances (PFAS) have raised international concerns due to their widespread use, environmental persistence and potential bioaccumulative and ecotoxicological effects. Therefore, the chemical industry has been dedicated to develop new generation fluorosurfactants which are aimed to replace the most concerning PFAS. Here we investigated the fate and effects of cyclic C6O4 (cC6O4), a compound used as alternative to long-chain perfluorocarboxylic acids, in freshwater mesocosms located in the Mediterranean region (Spain) over a period of 90 days. cC6O4 was applied as ammonium salt once at the following nominal concentrations: 0 µg/L (control), 1 µg/L, 20 µg/L, 400 µg/L, and 8,000 µg/L. The study shows that cC6O4 is relatively persistent in water (dissipation: 34-37 % after 90 days), has very low sorption capacity to sediments (sediment-water partition coefficient: 0.18-0.32 L/kg) and very limited bioconcentration (BCF: 0.09-0.94), bioaccumulation (BAF: 0.09-4.06) and biomagnification (BMF: 0.05-0.28) potential. cC6O4 did not result in significant adverse effects on aquatic populations and communities of phytoplankton and zooplankton at the tested concentrations. As for the macroinvertebrate community, the ephemeropteran Cloeon sp. showed a population decline at the highest test concentration on day 60 onwards, and a significant effect on the macroinvertebrate community was identified on the last sampling day at the same exposure level. Therefore, the calculated NOEC for cC6O4 in freshwater mesocosms exposed over a period of 90 days was 400 µg/L, which corresponded to a time weighted average concentration of 611 µg/L, given the water evaporation in the test systems. This concentration is about an order of magnitude higher than the highest exposure concentration monitored in freshwater ecosystems. Therefore, it can be concluded that cC6O4 poses insignificant ecological risks for freshwater plankton and macroinvertebrate communities given the current environmental exposure levels.

Patient-Centric Quality Standards.

To ensure the quality, safety and efficacy of medicinal products, it is necessary to develop and execute appropriate manufacturing process and product control strategies. Traditionally, product control strategies have focused on testing known quality attributes with limits derived from levels administered in preclinical and clinical studies with an associated statistical analysis to account for variability. However, not all quality attributes have impact to the patient and those with the potential to impact safety and efficacy may not be significant when dosed at patient-centric levels. Therefore, achieving patient-centricity is understanding patient relevance, which is defined as the level of impact that a quality attribute could have on safety and efficacy within the potential exposure range. A patient-centric quality standard (PCQS) is therefore a set of patient relevant attributes and their associated acceptance ranges to which a drug product should conform within the expected patient exposure range. This manuscript describes historical perspectives details the way to create and leverage a PCQS in a variety of pharmaceutical product modalities.

Historic distribution of Polycyclic Aromatic Compounds (PAC) in a Skagerrak fjord, Swedish west coast as reflected in a high-resolution sediment record and compared to the Environmental Quality Standards (EQS).

We present the historic distribution of Polycyclic Aromatic Compounds (PAC) in a Skagerrak fjord, a relatively unexploited area, on the Swedish west coast. PACs encompass various compounds, including PAHs, alkyl-PAHs, nitro-PAHs, and oxy-PAHs. These compounds, have environmental implications due to their harmful properties. Using a high-resolution sediment record, PAC variations including standard PAHs, nitro-PAHs and oxy-PAHs were investigated over the last approximately 170 years, comparing them with other European records. The sediment record reveals a significant increase in PAC levels during the 1940s-1950s, followed by peaks in the 1960s and 1970s, and a subsequent decrease in the 1980s. These trends align with industrial growth and evolving stronger environmental regulations in the region. The highest recorded concentration of PACs (1950-1970) reached levels comparable to present-day polluted urban environments. The study also compared PAH levels with EQS values. Results indicated that PAH levels exceeded EQS standards, potentially posing risks to sediment-dwelling organisms.

The upcoming European Soil Monitoring Law: An effective instrument for the protection of terrestrial ecosystems?

Soils are a precious resource consistently placed under several threats and urgently in need of protection within a regulatory framework at the European level. Soils are central to the provision of environmental services as well as human existence on earth. The need to protect soil has been identified by several recent European strategies and fortunately, a specific European regulation for soil protection is on the way-the European Soil Monitoring Law (formerly: Soil Health Law). However, efforts need to ensure that the upcoming Soil Monitoring Law closes gaps between existing regulations for chemicals and acknowledges current European strategies for environmental protection and sustainability. This brief communication started from a fruitful discussion among SETAC Global Soils Interest Group members on a recent public consultation on the newly proposed Soil Monitoring Law of the European Commission and highlights critical points focusing on the chemical pollution of soils. We emphasize urgent needs such as the essential definition of a "healthy state" of soils; the implementation of a suitable set of indicators and quality standards for the description of physical, chemical, and biological states of soils; the enforcement of the "polluter-pays" principle; and the establishment of a Europe-wide monitoring program. Results from monitoring need to be fed back into regulatory frameworks, including the regulation of chemicals. Guidance documents for the risk assessment of chemicals are outdated and need to be updated. Finally, actions need to be taken to foster healthy soils, stop biodiversity decline, and ensure the functioning of ecosystem services for future generations. Integr Environ Assess Manag 2024;20:316-321. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Optimizing the development of contaminated land in China: Exploring machine-learning to identify risk markers.

Often available for use, previously developed land, which includes residential and commercial/industrial areas, presents a significant challenge due to the risk to human health. China's 2018 release of health risk assessment standards for land reuse aimed to bridge this gap in soil quality standards. Despite this, the absence of representative indicators strains risk managers economically and operationally. We improved China's land redevelopment approach by leveraging a dataset of 297,275 soil samples from 352 contaminated sites, employing machine learning. Our method incorporating soil quality standards from seven countries to discern patterns for establishing a cost-effective evaluative framework. Our research findings demonstrated that detection costs could be curtailed by 60% while maintaining consistency with international soil standards (prediction accuracy = 90-98%). Our findings deepen insights into soil pollution, proposing a more efficient risk assessment system for land redevelopment, addressing the current dearth of expertise in evaluating land development in China.

Quality parameters for the medicinal plant Drosera rotundifolia L.: A new approach with established techniques.

Monographs of the European Pharmacopoeia (Ph. Eur.) are the basis for quality control of medicinal plants and therefore important to ensure the consistency, quality, safety, and efficacy of phytopharmaceuticals. The traditional medicinal plant sundew (Drosera sp.) has disappeared from therapy due to nature conservation, but can now be cultivated sustainably on rewetted peatland. However, currently there is no valid Ph. Eur. monograph for the quality control of Droserae herba. In this study, sundew material from different species and sources was investigated with the aim of developing quality control methods based on the Ph. Eur. and defining a uniform quality standard for Droserae herba. It was possible to distinguish between sundew species of different quality, using macroscopic, microscopic, and chromatographic methods. Special emphasis was laid on the content of flavonoids and naphthoquinones as important quality parameters as their content differed between the sundew species. The differences in content and toxicity result in the recommendation that only round-leaved sundew (Drosera rotundifolia L.) should be used as a medicinal plant for the production of phytopharmaceuticals in the future.

Meta-analysis of the efficacy of invisible orthodontic appliances for maxillary molar distalization in adult patients / 口腔疾病防治

Objective@#To evaluate the clinical efficacy of invisible orthodontic appliances without brackets for the distal movement of maxillary molars to improve the ability of orthodontists to predict treatment outcomes.@*Methods@#Web of Science, Cochrane Library, Embase, PubMed, Wanfang Database, CNKI Database, and VIP Database were searched for studies investigating the efficacy of invisible orthodontic appliances for distal movement of maxillary molars in adult patients and published from database inception to August 1, 2023. A total of three researchers screened the studies and evaluated their quality and conducted a meta-analysis of those that met quality standards.@*Results@#This study included 13 pre- and postcontrol trials with a total sample size of 281 patients. The meta-analysis revealed no significant differences in the sagittal or vertical parameters of the jawbone after treatment when compared with those before treatment (P>0.05). The displacement of the first molar was MD=-2.34, 95% CI (-2.83, -1.85); the displacement was MD=-0.95, 95% CI (-1.34, -0.56); and the inclination was MD=-2.51, 95% CI (-3.56, -1.46). There was a statistically significant difference in the change in sagittal, vertical, and axial tilt of the first molar before and after treatment. After treatment, the average adduction distance of the incisors was MD=-0.82, 95% CI (-1.54, -0.09), and the decrease in lip inclination was MD=-1.61, 95% CI (-2.86, -0.36); these values were significantly different from those before treatment (P<0.05).@*Conclusion@#Invisible orthodontic appliances can effectively move the upper molars in a distal direction and control the vertical position of the molars. When the molars move further away, there is some degree of compression and distal tilt movement, which is beneficial for patients with high angles. The sagittal movement of incisors is beneficial for improving the patient's profile.

Applying water quality standards to pollution from diffuse sources.

Water quality standards are instrumental in evaluating the status of water bodies, and in providing protective and restorative endpoints. To date, much of the infrastructure used to implement water quality standards has been directed towards remediating and managing pollution from point source discharges. However, pollution from diffuse sources is the leading cause of water quality impairment, especially by nutrients. Although the effects of nutrient enrichment on streams is well studied, and ecological thresholds identified, those thresholds have not been widely adopted as standards primarily because they are not attainable by point sources. Clearly, a framework for adopting and applying standards to manage pollution from diffuse sources needs to be decoupled from those intended for point sources. This paper argues for a relatively unstructured distributional approach to predict how ecological responses might shift in response to management of diffuse sources. The approach calls for first developing a deterministic model of stressor and response variables, followed by a reformulation as a Bayesian model. In the case here, a structural equation model was developed that linked nutrient enrichment, habitat quality, and chloride and manganese concentrations to an index of macroinvertebrate quality. Results from the Bayesian representation suggest that in landscapes where the drainage network has been highly modified for agricultural production, reduction in total phosphorus alone is expected to have a modest (but non-trivial) effect on macroinvertebrate condition, shifting the distribution of scores up by 1 point. The addition of habitat restoration is likely to shift the distribution upwards by 4 points, an effect size observed in Ohio, USA from other large-scale restoration efforts.

Monitoring of ECFS quality standards for the clinical management of adults with cystic fibrosis.

BACKGROUND: Although cystic fibrosis (CF) standards of care have been produced and regularly updated, they are not specifically targeting at the adult population. The ECFS Standards of Care Project established an international task force of experts to identify quality standards for adults with CF and assess their adherence. METHODS: This study was composed of two phases. In the first one, a task force of international experts derived from published guidelines and graded ten quality standards for adult CF care using a modified Delphi methodology. In the second phase, an international audit was conducted among adult CF centers to retrospectively validate the quality statements and monitor adherence. RESULTS: The task force identified 10 quality standards specific to the care of adults with CF, mainly based on the 2018 ECFS standards of care. 14 adult CF centers participated in the audit, which showed that most quality standards for the management of CF in adults are met across Europe. Heterogeneity in adherence to standards was found across centers according to geographical setting and centers' characteristics. CONCLUSIONS: The identification of quality standards is a valuable resource for the standardization and monitoring of care delivery across centers taking care of adults with CF.

Delphi Plus: A novel methodology for identifying evidence-based data standards for health service decision-making.

The underlying tenet of evidence-based decision-making in health services is assessing all the relevant evidence. Using the traditional qualitative and quantitative approaches to identifying evidence may not capture the full spectrum of factors that need to be addressed. A selective mixed-method approach may provide a comprehensive assessment of the relevant knowledge. This paper adds to the methodological literature by outlining a novel sequential, mixed-method, exploratory process for identifying evidence-based data standards that may be used for health service decision-making. The three-phase process, entitled Delphi Plus, engages peer-nominated topic-specific experts to assess all publicly available and practice-based items and, through a series of reviews, reach an evidence-based consensus on standards for decision-making. Each process phase is outlined in-depth and supplemented by practical learnings gained through its implementation. The Delphi Plus methodology provides the first comprehensive process for combining the published and practised data to develop evidence-based data standards. The routine use of Delphi Plus would provide a framework for benchmarking in health services, enabling greater monitoring and evaluation of client outcomes and improving quality care. This manuscript describes the process of implementing Delphi Plus and provides an example of data standards generated from its use, which directly inform the Australian Government's Primary Health Care 10 Year Plan.