Implementing constructed wetlands for nutrient reduction at watershed scale: Opportunity to link models and real-world execution.

The negative effects of nutrient pollution in streams, rivers, and downstream waterbodies remain widespread global problems. Understanding the cost-effectiveness of different strategies for mitigating nutrient pollution is critical to making informed decisions and defining expectations that best utilize limited resources, which is a research priority for the US Environmental Protection Agency. To this end, we modeled nutrient management practices including residue management, cover crops, filter strips, grassed waterways, constructed wetlands, and reducing fertilizer in the upper East Fork of the Little Miami River, an 892 km2 watershed in southwestern Ohio, United States. The watershed is 64% agriculture with 422 km2 of row crops contributing an estimated 71% of the system's nutrient load. The six practices were modeled to treat row crop area, and among them, constructed wetlands ranked highest for their low costs per kilogram of nutrient removed. To meet a 42% phosphorus (P) reduction target for row crops, the model results suggested that the runoff from 85.5% of the row crop area would need to be treated by the equivalent of 3.61 km2 of constructed wetlands at an estimated cost of US$2.4 million annually (or US$48.5 million over a 20-year life cycle). This prompted a series of projects designed to understand the feasibility (defined in terms of build, treatment, and cost potential) of retrofitting the system with the necessary extent of constructed wetlands. The practicalities of building this wetland coverage into the system, while leading to innovation in unit-level design, has highlighted the difficulty of achieving the nutrient reduction target with wetlands alone. Approximately US$1.2 million have been spent on constructing 0.032 km2 of wetlands thus far and a feasibility analysis suggests a cost of US$38 million for an additional 0.409 km2. However, the combined expenditures would only achieve an estimated 13% of the required treatment. The results highlight the potential effectiveness of innovative design strategies for nutrient reduction and the importance of considering realistic field-scale build opportunities, which include accounting for acceptance among landowners, in watershed-scale nutrient reduction simulations using constructed wetlands.

PDCA cycle helps the continuous improvement of laboratory diagnostics teaching / 中华医学教育探索杂志

In the context of "New Era" and "New Medicine", the teaching team of laboratory diagnostics proposed a new teaching method of PDCA (Plan, Do, Check, Action) cycle to innovate the instructional design and implementation of laboratory diagnosis on the base of traditional teaching model. Through optimizing the curriculum system, integrating superior resources, taking full advantage of information technology, mobilizing the virtual simulation laboratory, implementing moral education and multiple comprehensive evaluation results, the self-learning enthusiasm, innovation and development ability of students were improved significantly, accompanied with high humanistic care spirit. Moreover, the enthusiasm of participating in scientific research activities and professional competitions was enhanced obviously. Therefore, we believe that the PDCA cycle, with notable successes, deserves high promotion value and wide application.

Short Video Addiction on the Interaction of Creative Self-Efficacy and Career Interest to Innovative Design Profession Students.

In recent years, a variety of emerging online media, such as TikTok, Kuaishou, YouTube and other short video application platforms, have appeared. The problem of short video addiction has become an issue to education experts and the general public, as students' excessive use of short video has become increasingly serious with many hidden concerns to the students' learning effectiveness. In addition, to meet the growing demand for innovative design talents worldwide, the Taiwan government has been committed to promoting policies related to the cultivation of innovative and creative talents nowadays, particularly for innovative design profession students who often use the Internet and short videos for learning. Therefore, the study aims to use questionnaires to understand the habits and addiction of the innovative design profession students in using short videos, and to further investigate the relation of short video addiction to the students' creative self-efficacy (CSE) and career interests. A total of 561 valid questionnaires were collected after eliminating invalid questionnaires and reliability analysis. Structural equation modeling and model validation were conducted afterwards. The results showed that short video addiction had a negative effect on CSE; CSE had a positive effect on career interests; and CSE had an indirect effect between short video addiction and career interests.

Developing a predictive signature for two trial endpoints using the cross-validated risk scores method.

The existing cross-validated risk scores (CVRS) design has been proposed for developing and testing the efficacy of a treatment in a high-efficacy patient group (the sensitive group) using high-dimensional data (such as genetic data). The design is based on computing a risk score for each patient and dividing them into clusters using a nonparametric clustering procedure. In some settings, it is desirable to consider the tradeoff between two outcomes, such as efficacy and toxicity, or cost and effectiveness. With this motivation, we extend the CVRS design (CVRS2) to consider two outcomes. The design employs bivariate risk scores that are divided into clusters. We assess the properties of the CVRS2 using simulated data and illustrate its application on a randomized psychiatry trial. We show that CVRS2 is able to reliably identify the sensitive group (the group for which the new treatment provides benefit on both outcomes) in the simulated data. We apply the CVRS2 design to a psychology clinical trial that had offender status and substance use status as two outcomes and collected a large number of baseline covariates. The CVRS2 design yields a significant treatment effect for both outcomes, while the CVRS approach identified a significant effect for the offender status only after prefiltering the covariates.

A Bayesian model with application for adaptive platform trials having temporal changes.

Temporal changes exist in clinical trials. Over time, shifts in patients' characteristics, trial conduct, and other features of a clinical trial may occur. In typical randomized clinical trials, temporal effects, that is, the impact of temporal changes on clinical outcomes and study analysis, are largely mitigated by randomization and usually need not be explicitly addressed. However, temporal effects can be a serious obstacle for conducting clinical trials with complex designs, including the adaptive platform trials that are gaining popularity in recent medical product development. In this paper, we introduce a Bayesian robust prior for mitigating temporal effects based on a hidden Markov model, and propose a particle filtering algorithm for computation. We conduct simulation studies to evaluate the performance of the proposed method and provide illustration examples based on trials of Ebola virus disease therapeutics and hemostat in vascular surgery.

Bayesian Complex Innovative Trial Designs (CIDs) and Their Use in Drug Development for Rare Disease.

As the temporal, financial, and ethical cost of randomized clinical trials (RCTs) continues to rise, researchers and regulators in drug discovery and development face increasing pressure to make better use of existing data sources. This pressure is especially high in rare disease, where traditionally designed RCTs are often infeasible due to the inability to recruit enough patients or the unwillingness of patients or trial leaders to randomly assign anyone to placebo. Bayesian statistical methods have recently been recommended in such settings for their ability to combine disparate data sources, increasing overall study power. The use of these methods has received a boost in the United States thanks to a new willingness by regulators at the Food and Drug Administration to consider complex innovative trial designs. These designs allow trialists to change the nature of the trial (eg, stop early for success or futility, drop an underperforming trial arm, incorporate data on historical controls, etc) while it is still running. In this article, we review a broad collection of Bayesian techniques useful in rare disease research, indicating the benefits and risks associated with each. We begin with relatively innocuous methods for combining information from RCTs and proceed on through increasingly innovative approaches that borrow strength from increasingly heterogeneous and less carefully curated data sources. We also offer 2 examples from the very recent literature illustrating how clinical pharmacology principles can make important contributions to such designs, confirming the interdisciplinary nature of this work.

Design theory to better target public health priorities: An application to Lyme disease in France.

In the context of complex public health challenges led by interdependent changes such as climate change, biodiversity loss, and resistance to treatment, it is important to mobilize methods that guide us to generate innovative interventions in a context of uncertainty and unknown. Here, we mobilized the concept-knowledge (CK) design theory to identify innovative, cross-sectoral, and cross-disciplinary research and design programs that address the challenges posed by tick-borne Lyme disease in France, which is of growing importance in the French public health and healthcare systems. Within the CK methodological framework, we developed an iterative approach based on literature analysis, expert interviews, analysis of active French research projects, and work with CK experts to contribute to design "an action plan against Lyme disease." We produced a CK diagram that highlights innovative concepts that could be addressed in research projects. The outcome is discussed within four areas: (i) effectiveness; (ii) environmental sustainability in prevention actions; (iii) the promotion of constructive involvement of citizens in Lyme challenges; and (iv) the development of care protocols for chronic conditions with an unknown diagnosis. Altogether, our analysis questioned the health targets ranging from population to ecosystem, the citizen involvement, and the patient consideration. This means integrating social and ecological science, as well as the multidisciplinary medical patient journey, from the start. CK theory is a promising framework to assist public health professionals in designing programs for complex yet urgent contexts, where research and data collection are still not sufficient to provide clear guidance.

Design and analysis of umbrella trials: Where do we stand?

Background: The efficiencies that master protocol designs can bring to modern drug development have seen their increased utilization in oncology. Growing interest has also resulted in their consideration in non-oncology settings. Umbrella trials are one class of master protocol design that evaluates multiple targeted therapies in a single disease setting. Despite the existence of several reviews of master protocols, the statistical considerations of umbrella trials have received more limited attention. Methods: We conduct a systematic review of the literature on umbrella trials, examining both the statistical methods that are available for their design and analysis, and also their use in practice. We pay particular attention to considerations for umbrella designs applied outside of oncology. Findings: We identified 38 umbrella trials. To date, most umbrella trials have been conducted in early phase settings (73.7%, 28/38) and in oncology (92.1%, 35/38). The quality of statistical information available about conducted umbrella trials to date is poor; for example, it was impossible to ascertain how sample size was determined in the majority of trials (55.3%, 21/38). The literature on statistical methods for umbrella trials is currently sparse. Conclusions: Umbrella trials have potentially great utility to expedite drug development, including outside of oncology. However, to enable lessons to be effectively learned from early use of such designs, there is a need for higher-quality reporting of umbrella trials. Furthermore, if the potential of umbrella trials is to be realized, further methodological research is required.

Amazing Fungi for Eco-Friendly Composite Materials: A Comprehensive Review.

The continually expanding use of plastic throughout our world, along with the considerable increase in agricultural productivity, has resulted in a worrying increase in global waste and related environmental problems. The reuse and replacement of plastic with biomaterials, as well as the recycling of agricultural waste, are key components of a strategy to reduce plastic waste. Agricultural waste is characterized as lignocellulosic materials that mainly consist of cellulose, hemicellulose, and lignin. Saprobe fungi are able to convert agricultural waste into nutrients for their own growth and to facilitate the creation of mycelium-based composites (MBC) through bio-fabrication processes. Remarkably, different fungal species, substrates, and pressing and drying methods have resulted in varying chemical, mechanical, physical, and biological properties of the resulting composites that ultimately vary the functional aspects of the finished MBC. Over the last two decades, several innovative designs have produced a variety of MBC that can be applied across a range of industrial uses including in packaging and in the manufacturing of household items, furniture, and building materials that can replace foams, plastics, and wood products. Materials developed from MBC can be considered highly functional materials that offer renewable and biodegradable benefits as promising alternatives. Therefore, a better understanding of the beneficial properties of MBC is crucial for their potential applications in a variety of fields. Here, we have conducted a brief review of the current findings of relevant studies through an overview of recently published literature on MBC production and the physical, mechanical, chemical, and biological properties of these composites for use in innovative architecture, construction, and product designs. The advantages and disadvantages of various applications of mycelium-based materials (MBM) in various fields have been summarized. Finally, patent trends involving the use of MBM as a new and sustainable biomaterial have also been reviewed. The resulting knowledge can be used by researchers to develop and apply MBC in the form of eco-friendly materials in the future.

Integrating design and ecological theory to achieve adaptive diverse pastures.

Increasing plant diversity is often suggested as a way of overcoming some of the challenges faced by managers of intensive pasture systems, but it is unclear how to design the most suitable plant mixtures. Using innovative design theory, we identify two conceptual shifts that foster potentially beneficial design approaches. Firstly, reframing the goal of mixture design to supporting ecological integrity, rather than delivering lists of desired outcomes, leads to flexible design approaches that support context-specific solutions that should operate within identifiable ecological limits. Secondly, embracing, rather than minimising uncertainty in performance leads to adaptive approaches that could enhance current and future benefits of diversifying pasture. These two fundamental shifts could therefore accelerate the successful redesign of intensive pastures.

Adaptive Designs: Benefits and Cautions for Neurosurgery Trials.

BACKGROUND: It is well accepted that randomized controlled trials provide the greatest quality of evidence about effectiveness and safety of new interventions. In neurosurgery, randomized controlled trials face challenges, with their use remaining relatively low compared with other clinical areas. Adaptive designs have emerged as a method for improving the efficiency and patient benefit of trials. They allow modifications to the trial design to be made as patient outcome data are collected. The benefit they provide is highly variable, predominantly governed by the time taken to observe the primary endpoint compared with the planned recruitment rate. They also face challenges in design, conduct, and reporting. METHODS: We provide an overview of the benefits and challenges of adaptive designs, with a focus on neurosurgery applications. To investigate how often an adaptive design may be advantageous in neurosurgery, we extracted data on recruitment rates and endpoint lengths for ongoing neurosurgery trials registered in ClinicalTrials.gov. RESULTS: We found that a majority of neurosurgery trials had a relatively short endpoint length compared with the planned recruitment period and therefore may benefit from an adaptive trial. However, we did not identify any ongoing ClinicalTrials.gov registered neurosurgery trials that mentioned using an adaptive design. CONCLUSIONS: Adaptive designs may provide benefits to neurosurgery trials and should be considered for use more widely. Use of some types of adaptive design, such as multiarm multistage, may further increase the number of interventions that can be tested with limited patient and financial resources.

Drive-Through Urgent Care Centers: Could They Be the Future of Healthcare Facilities?

OBJECTIVE: This study assessed the perception of people toward drive-through healthcare services, their willingness to use them, and the scope of services they would like to receive in a post-pandemic world. BACKGROUND: The abrupt spread of COVID-19 urged healthcare facilities to adopt new infection-control measures. Drive-through testing facilities were implemented as one of the measures to minimize physical contact between healthcare workers and test-takers. Many studies describe drive-through models' merits, but people's opinions about them as a permanent attachment to healthcare facilities are unclear. METHODS: An online survey was distributed through snowball sampling. The survey solicited feedback from adults who lived in the United States. The survey consisted of Likert-type and multiple-choice questions and was completed by176 eligible participants. RESULTS: The use of drive-through pharmacies increased after the spread of COVID-19. Most people agreed drive-through healthcare services could be more convenient and safer to use. People prefer to have their vitals checked, and vaccinations received in a drive-through because of the improved infection-control matters and increased comfort; however, they are neutral about the level of privacy they have and the hygiene of drive-through healthcare settings. CONCLUSIONS: This study shows permanent drive-throughs offering medical services benefit people in times of crisis for the perceived infection control purposes and the improved convenience. A drive-through model can redefine the waiting experience and serve as a new safe triage system in urgent care centers. Drive-through urgent care centers can be adopted as a hybrid of telemedicine and in-person visits.

Experiences of running a stratified medicine adaptive platform trial: Challenges and lessons learned from 10 years of the FOCUS4 trial in metastatic colorectal cancer.

BACKGROUND: Complex innovative design trials are becoming increasingly common and offer potential for improving patient outcomes in a faster time frame. FOCUS4 was the first molecularly stratified trial in metastatic colorectal cancer and it remains one of the first umbrella trial designs to be launched globally. Here, we aim to describe lessons learned from delivery of the trial over the last 10 years. METHODS: FOCUS4 was a Phase II/III molecularly stratified umbrella trial testing the safety and efficacy of targeted therapies in metastatic colorectal cancer. It used adaptive statistical methodology to decide which sub-trial should close early, and new therapies were added as protocol amendments. Patients with newly diagnosed metastatic colorectal cancer were registered, and central laboratory testing was used to stratify their tumour into molecular subtypes. Following 16 weeks of first-line therapy, patients with stable or responding disease were eligible for randomisation into either a molecularly stratified sub-trial (FOCUS4-B, C or D) or non-stratified FOCUS4-N. The primary outcome for all studies was progression-free survival comparing the intervention with active monitoring/placebo. At the close of the trial, feedback was elicited from all investigators through surveys and interviews and consolidated into a series of recommendations and lessons learned for the delivery of similar future trials. RESULTS: Between January 2014 and October 2020, 1434 patients were registered from 88 UK hospitals. Of the 20 drug combinations that were explored for inclusion in the platform trial, three molecularly targeted sub-trials were activated: FOCUS4-D (February 2014-March 2016) evaluated AZD8931 in the BRAF-PIK3CA-RAS wildtype subgroup; FOCUS4-B (February 2016-July 2018) evaluated aspirin in the PIK3CA mutant subgroup and FOCUS4-C (June 2017-October 2020) evaluated adavosertib in the RAS+TP53 double mutant subgroup. FOCUS4-N was active throughout and evaluated capecitabine monotherapy versus a treatment break. A total of 361 (25%) registered patients were randomised into a sub-trial. Feedback on the experiences of delivery of FOCUS4 could be grouped into three main areas of challenge: funding/infrastructure, biomarker testing procedures and trial design efficiencies within which 20 recommendations are summarised. CONCLUSION: Adaptive stratified medicine platform studies are feasible in common cancers but present challenges. Our stakeholder feedback has helped to inform how these trial designs can succeed and answer multiple questions efficiently, providing resource is adequate.

Working at Green Care Farms and Other Innovative Small-Scale Long-Term Dementia Care Facilities Requires Different Competencies of Care Staff.

The culture change movement within long-term care in which radical changes in the physical, social and organizational care environments are being implemented provides opportunities for the development of innovative long-term care facilities. The aim of this study was to investigate which competencies care staff working at green care farms and other innovative types of small-scale long-term dementia care facilities require, according to care staff themselves and managers, and how these competencies were different from those of care staff working in more traditional large-scale long-term dementia care facilities. A qualitative descriptive research design was used. Interviews were conducted with care staff (n = 19) and managers (n = 23) across a diverse range of long-term facilities. Thematic content analysis was used. Two competencies were mainly mentioned by participants working in green care farms: (1) being able to integrate activities for residents into daily practice, and (2) being able to undertake multiple responsibilities. Two other competencies for working in long-term dementia care in general were identified: (3) having good communication skills, and (4) being able to provide medical and direct care activities. This study found unique competencies at green care farms, showing that providing care in innovative long-term care facilities requires looking further than the physical environment and the design of a care facility; it is crucial to look at the role of care staff and the competencies they require.

Research on the process planning and multi-method integration strategy of product conceptual design with cognitive mechanisms.

Innovative product design is essentially an activity involving creative cognitive thinking. Therefore, research on the innovative design process and of methods, computer-aided innovation tools should be conducted based on systematic exploration based on the principles of innovative cognitive thinking. We aim to uncover some general principles that can serve as a systematic thinking framework for product designers, provide a feasible framework and method of innovative thinking for designers, and provide theoretical and methodological support for further development of computer-aided innovation platforms. This paper summarizes the sources and content of studies on the idea generation and design processes behind product innovation. Specifically, we break down the general innovative design process of products, outlining the cognitive mechanisms and propose an integrated application strategy that incorporates multiple methods. And taking "the solution program to the coking of oily sludge pyrolysis equipment" as an example, this paper demonstrated and verified the effectiveness and practicability of the method and strategy proposed. Based on the results on improvements in the equipment, the designers put forward some creative and implementable design schemes. The entire thinking process was relatively smooth and efficient. The example presented in this paper shows that the proposed method can effectively guide/assist/motivate designers to think creatively.

A platform trial in practice: adding a new experimental research arm to the ongoing confirmatory FLAIR trial in chronic lymphocytic leukaemia.

BACKGROUND: The FLAIR trial in chronic lymphocytic leukaemia has a randomised, controlled, open-label, confirmatory, platform design. FLAIR was successfully amended to include an emerging promising experimental therapy to expedite its assessment, greatly reducing the time to reach the primary outcome compared to running a separate trial and without compromising the validity of the research or the ability to recruit to the trial and report the outcomes. The methodological and practical issues are presented, describing how they were addressed to ensure the amendment was a success. METHODS: FLAIR was designed as a two-arm trial requiring 754 patients. In stage 2, two new arms were added: a new experimental arm and a second control arm to protect the trial in case of a change in practice. In stage 3, the original experimental arm was closed as its planned recruitment target was reached. In total, 1516 participants will be randomised to the trial. RESULTS: The changes to the protocol and randomisation to add and stop arms were made seamlessly without pausing recruitment. The statistical considerations to ensure the results for the original and new hypotheses are unbiased were approved following peer review by oversight committees, Cancer Research UK, ethical and regulatory committees and pharmaceutical partners. These included the use of concurrent comparators in case of any stage effect, appropriate control of the type I error rate and consideration of analysis methods across trial stages. The operational aspects of successfully implementing the amendments are described, including gaining approvals and additional funding, data management requirements and implementation at centres. CONCLUSIONS: FLAIR is an exemplar of how an emerging experimental therapy can be assessed within an existing trial structure without compromising the conduct, reporting or validity of the trial. This strategy offered considerable resource savings and allowed the new experimental therapy to be assessed within a confirmatory trial in the UK years earlier than would have otherwise been possible. Despite the clear efficiencies, treatment arms are rarely added to ongoing trials in practice. This paper demonstrates how this strategy is acceptable, feasible and beneficial to patients and the wider research community. TRIAL REGISTRATION: ISRCTN Registry ISRCTN01844152 . Registered on August 08, 2014.

Application Oriented is the Core of Traditional Chinese Medicine Research / 世界科学技术-中医药现代化

Traditional Chinese Medicine (TCM) has distinctive traditional features and unique therapeutic advantages.The characteristics of TCM including long history, rich theory, efficacy diversity, complex chemical composition, fuzzy mechanism, leading health care, compound-based, dose confidential, and dialectical pharmacy and so on, but TCM research findings with few practical applications now. We need a profound understanding of the characteristics of TCM and Chinese medicine research and application of full advantage of clear objectives that to accurate selection of TCM research focus and appropriate methods, creative design scheme of TCM. In this way, we may have satisfied the anticipated target about TCM and TCM academic truly promote the maintenance of health. In the medicine industry is bound to promote the great development of TCM to the world.

Eliciting thinking from the competition in basic medical design of experimentation for cultivating excellent doctors / 中华医学教育探索杂志

The purpose of the National Competition in Basic Medicine Innovation Forum & Ex-perimental Design in colleges is to boost Excellent-doctor Education Training Plan, cultivating students' scientific research ability and other comprehensive capacity. In practice, the originality and the scientific nature of the selected topic were emphasized through the provision of scientific research funding. The teachers changed their traditional instructional concept and teaching models. They guided the students to select the scientific subjects and took various measures to change students ' learning mode, resulting in gradually pro-moting the students' scientific research level and comprehensive ability. The results showed that these novel strategies are feasible and effective, which may provide a new way for improvement of the excellent doctor program.

Launching independent design in physiological experiments to promote innovative capability among students in medical school / 中华医学教育探索杂志

Thought and consciousness of experimental design were carried in the experimental teaching and the classical physiological experiments were merged. Innovational design and practice were penetrated through the whole experimental class. After consulting literature, designing experi-ments, observing the phenomenon, dealing with the data and summurizing the results, the designers experienced the basic research procedure, got the innovate results, gained the chance to further study and improved the innovative capability.