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Michael Weekes

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Nick K. Jones1,2*, Lucy Rivett1,2*, Chris Workman3, Mark Ferris3, Ashley Shaw1, Cambridge COVID-19 Collaboration1,4, Paul J. Lehner1,4, Rob Howes5, Giles Wright3, Nicholas J. Matheson1,4,6¶, Michael P. Weekes1,7¶1 Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK2 Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, UK3 Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, UK4 Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK5 Cambridge COVID-19 Testing Centre and AstraZeneca, Anne Mclaren Building, Cambridge, UK6 NHS Blood and Transplant, Cambridge, UK7 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK*Joint first authorship¶Joint last authorshipCorrespondence: mpw1001@cam.ac.ukThe UK has initiated mass COVID-19 immunisation, with healthcare workers (HCWs) given early priority because of the potential for workplace exposure and risk of onward transmission to patients. The UK’s Joint Committee on Vaccination and Immunisation has recommended maximising the number of people vaccinated with first doses at the expense of early booster vaccinations, based on single dose efficacy against symptomatic COVID-19 disease.1-3At the time of writing, three COVID-19 vaccines have been granted emergency use authorisation in the UK, including the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). A vital outstanding question is whether this vaccine prevents or promotes asymptomatic SARS-CoV-2 infection, rather than symptomatic COVID-19 disease, because sub-clinical infection following vaccination could continue to drive transmission. This is especially important because many UK HCWs have received this vaccine, and nosocomial COVID-19 infection has been a persistent problem.Through the implementation of a 24 h-turnaround PCR-based comprehensive HCW screening programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT), we previously demonstrated the frequent presence of pauci- and asymptomatic infection amongst HCWs during the UK’s first wave of the COVID-19 pandemic.4 Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and cycle threshold (Ct) values in the asymptomatic arm of our programme, which now offers weekly screening to all staff.Vaccination of HCWs at CUHNFT began on 8th December 2020, with mass vaccination from 8th January 2021. Here, we analyse data from the two weeks spanning 18thto 31st January 2021, during which: (a) the prevalence of COVID-19 amongst HCWs remained approximately constant; and (b) we screened comparable numbers of vaccinated and unvaccinated HCWs. Over this period, 4,408 (week 1) and 4,411 (week 2) PCR tests were performed from individuals reporting well to work. We stratified HCWs <12 days or > 12 days post-vaccination because this was the point at which protection against symptomatic infection began to appear in phase III clinical trial.226/3,252 (0·80%) tests from unvaccinated HCWs were positive (Ct<36), compared to 13/3,535 (0·37%) from HCWs <12 days post-vaccination and 4/1,989 (0·20%) tests from HCWs ≥12 days post-vaccination (p=0·023 and p=0·004, respectively; Fisher’s exact test, Figure). This suggests a four-fold decrease in the risk of asymptomatic SARS-CoV-2 infection amongst HCWs ≥12 days post-vaccination, compared to unvaccinated HCWs, with an intermediate effect amongst HCWs <12 days post-vaccination.A marked reduction in infections was also seen when analyses were repeated with: (a) inclusion of HCWs testing positive through both the symptomatic and asymptomatic arms of the programme (56/3,282 (1·71%) unvaccinated vs 8/1,997 (0·40%) ≥12 days post-vaccination, 4·3-fold reduction, p=0·00001); (b) inclusion of PCR tests which were positive at the limit of detection (Ct>36, 42/3,268 (1·29%) vs 15/2,000 (0·75%), 1·7-fold reduction, p=0·075); and (c) extension of the period of analysis to include six weeks from December 28th to February 7th 2021 (113/14,083 (0·80%) vs 5/4,872 (0·10%), 7·8-fold reduction, p=1x10-9). In addition, the median Ct value of positive tests showed a non-significant trend towards increase between unvaccinated HCWs and HCWs > 12 days post-vaccination (23·3 to 30·3, Figure), suggesting that samples from vaccinated individuals had lower viral loads.We therefore provide real-world evidence for a high level of protection against asymptomatic SARS-CoV-2 infection after a single dose of BNT162b2 vaccine, at a time of predominant transmission of the UK COVID-19 variant of concern 202012/01 (lineage B.1.1.7), and amongst a population with a relatively low frequency of prior infection (7.2% antibody positive).5This work was funded by a Wellcome Senior Clinical Research Fellowship to MPW (108070/Z/15/Z), a Wellcome Principal Research Fellowship to PJL (210688/Z/18/Z), and an MRC Clinician Scientist Fellowship (MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM. Funding was also received from Addenbrooke’s Charitable Trust and the Cambridge Biomedical Research Centre. We also acknowledge contributions from all staff at CUHNFT Occupational Health and Wellbeing and the Cambridge COVID-19 Testing Centre.

Guangming Wang

and 4 more

Tam Hunt

and 1 more

Tam Hunt [1], Jonathan SchoolerUniversity of California Santa Barbara Synchronization, harmonization, vibrations, or simply resonance in its most general sense seems to have an integral relationship with consciousness itself. One of the possible “neural correlates of consciousness” in mammalian brains is a combination of gamma, beta and theta synchrony. More broadly, we see similar kinds of resonance patterns in living and non-living structures of many types. What clues can resonance provide about the nature of consciousness more generally? This paper provides an overview of resonating structures in the fields of neuroscience, biology and physics and attempts to coalesce these data into a solution to what we see as the “easy part” of the Hard Problem, which is generally known as the “combination problem” or the “binding problem.” The combination problem asks: how do micro-conscious entities combine into a higher-level macro-consciousness? The proposed solution in the context of mammalian consciousness suggests that a shared resonance is what allows different parts of the brain to achieve a phase transition in the speed and bandwidth of information flows between the constituent parts. This phase transition allows for richer varieties of consciousness to arise, with the character and content of that consciousness in each moment determined by the particular set of constituent neurons. We also offer more general insights into the ontology of consciousness and suggest that consciousness manifests as a relatively smooth continuum of increasing richness in all physical processes, distinguishing our view from emergentist materialism. We refer to this approach as a (general) resonance theory of consciousness and offer some responses to Chalmers’ questions about the different kinds of “combination problem.”  At the heart of the universe is a steady, insistent beat: the sound of cycles in sync…. [T]hese feats of synchrony occur spontaneously, almost as if nature has an eerie yearning for order. Steven Strogatz, Sync: How Order Emerges From Chaos in the Universe, Nature and Daily Life (2003) If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.Nikola Tesla (1942) I.               Introduction Is there an “easy part” and a “hard part” to the Hard Problem of consciousness? In this paper, we suggest that there is. The harder part is arriving at a philosophical position with respect to the relationship of matter and mind. This paper is about the “easy part” of the Hard Problem but we address the “hard part” briefly in this introduction.  We have both arrived, after much deliberation, at the position of panpsychism or panexperientialism (all matter has at least some associated mind/experience and vice versa). This is the view that all things and processes have both mental and physical aspects. Matter and mind are two sides of the same coin.  Panpsychism is one of many possible approaches that addresses the “hard part” of the Hard Problem. We adopt this position for all the reasons various authors have listed (Chalmers 1996, Griffin 1997, Hunt 2011, Goff 2017). This first step is particularly powerful if we adopt the Whiteheadian version of panpsychism (Whitehead 1929).  Reaching a position on this fundamental question of how mind relates to matter must be based on a “weight of plausibility” approach, rather than on definitive evidence, because establishing definitive evidence with respect to the presence of mind/experience is difficult. We must generally rely on examining various “behavioral correlates of consciousness” in judging whether entities other than ourselves are conscious – even with respect to other humans—since the only consciousness we can know with certainty is our own. Positing that matter and mind are two sides of the same coin explains the problem of consciousness insofar as it avoids the problems of emergence because under this approach consciousness doesn’t emerge. Consciousness is, rather, always present, at some level, even in the simplest of processes, but it “complexifies” as matter complexifies, and vice versa. Consciousness starts very simple and becomes more complex and rich under the right conditions, which in our proposed framework rely on resonance mechanisms. Matter and mind are two sides of the coin. Neither is primary; they are coequal.  We acknowledge the challenges of adopting this perspective, but encourage readers to consider the many compelling reasons to consider it that are reviewed elsewhere (Chalmers 1996, Griffin 1998, Hunt 2011, Goff 2017, Schooler, Schooler, & Hunt, 2011; Schooler, 2015).  Taking a position on the overarching ontology is the first step in addressing the Hard Problem. But this leads to the related questions: at what level of organization does consciousness reside in any particular process? Is a rock conscious? A chair? An ant? A bacterium? Or are only the smaller constituents, such as atoms or molecules, of these entities conscious? And if there is some degree of consciousness even in atoms and molecules, as panpsychism suggests (albeit of a very rudimentary nature, an important point to remember), how do these micro-conscious entities combine into the higher-level and obvious consciousness we witness in entities like humans and other mammals?  This set of questions is known as the “combination problem,” another now-classic problem in the philosophy of mind, and is what we describe here as the “easy part” of the Hard Problem. Our characterization of this part of the problem as “easy”[2] is, of course, more than a little tongue in cheek. The authors have discussed frequently with each other what part of the Hard Problem should be labeled the easier part and which the harder part. Regardless of the labels we choose, however, this paper focuses on our suggested solution to the combination problem.  Various solutions to the combination problem have been proposed but none have gained widespread acceptance. This paper further elaborates a proposed solution to the combination problem that we first described in Hunt 2011 and Schooler, Hunt, and Schooler 2011. The proposed solution rests on the idea of resonance, a shared vibratory frequency, which can also be called synchrony or field coherence. We will generally use resonance and “sync,” short for synchrony, interchangeably in this paper. We describe the approach as a general resonance theory of consciousness or just “general resonance theory” (GRT). GRT is a field theory of consciousness wherein the various specific fields associated with matter and energy are the seat of conscious awareness.  A summary of our approach appears in Appendix 1.  All things in our universe are constantly in motion, in process. Even objects that appear to be stationary are in fact vibrating, oscillating, resonating, at specific frequencies. So all things are actually processes. Resonance is a specific type of motion, characterized by synchronized oscillation between two states.  An interesting phenomenon occurs when different vibrating processes come into proximity: they will often start vibrating together at the same frequency. They “sync up,” sometimes in ways that can seem mysterious, and allow for richer and faster information and energy flows (Figure 1 offers a schematic). Examining this phenomenon leads to potentially deep insights about the nature of consciousness in both the human/mammalian context but also at a deeper ontological level.

Susanne Schilling*^

and 9 more

Jessica mead

and 6 more

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues including increasing burden of chronic disease, widening inequality, concerns over environmental degradation and anthropogenic climate change. While these criticisms overlook recent developments, there remains a need for biopsychosocial models that extend theoretical grounding beyond individual wellbeing, incorporating overlapping contextual issues relating to community and environment. Our first GENIAL model \cite{Kemp_2017} provided a more expansive view of pathways to longevity in the context of individual health and wellbeing, emphasising bidirectional links to positive social ties and the impact of sociocultural factors. In this paper, we build on these ideas and propose GENIAL 2.0, focusing on intersecting individual-community-environmental contributions to health and wellbeing, and laying an evidence-based, theoretical framework on which future research and innovative therapeutic innovations could be based. We suggest that our transdisciplinary model of wellbeing - focusing on individual, community and environmental contributions to personal wellbeing - will help to move the research field forward. In reconceptualising wellbeing, GENIAL 2.0 bridges the gap between psychological science and population health health systems, and presents opportunities for enhancing the health and wellbeing of people living with chronic conditions. Implications for future generations including the very survival of our species are discussed.  

Mark Ferris

and 14 more

IntroductionConsistent with World Health Organization (WHO) advice [1], UK Infection Protection Control guidance recommends that healthcare workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment (RPE), unless aerosol generating procedures (AGPs) are being undertaken or are likely, when a filtering face piece 3 (FFP3) respirator should be used [2]. In a recent update, an FFP3 respirator is recommended if “an unacceptable risk of transmission remains following rigorous application of the hierarchy of control” [3]. Conversely, guidance from the Centers for Disease Control and Prevention (CDC) recommends that HCWs caring for patients with COVID-19 should use an N95 or higher level respirator [4]. WHO guidance suggests that a respirator, such as FFP3, may be used for HCWs in the absence of AGPs if availability or cost is not an issue [1].A recent systematic review undertaken for PHE concluded that: “patients with SARS-CoV-2 infection who are breathing, talking or coughing generate both respiratory droplets and aerosols, but FRSM (and where required, eye protection) are considered to provide adequate staff protection” [5]. Nevertheless, FFP3 respirators are more effective in preventing aerosol transmission than FRSMs, and observational data suggests that they may improve protection for HCWs [6]. It has therefore been suggested that respirators should be considered as a means of affording the best available protection [7], and some organisations have decided to provide FFP3 (or equivalent) respirators to HCWs caring for COVID-19 patients, despite a lack of mandate from local or national guidelines [8].Data from the HCW testing programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT) during the first wave of the UK severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic indicated a higher incidence of infection amongst HCWs caring for patients with COVID-19, compared with those who did not [9]. Subsequent studies have confirmed this observation [10, 11]. This disparity persisted at CUHNFT in December 2020, despite control measures consistent with PHE guidance and audits indicating good compliance. The CUHNFT infection control committee therefore implemented a change of RPE for staff on “red” (COVID-19) wards from FRSMs to FFP3 respirators. In this study, we analyse the incidence of SARS-CoV-2 infection in HCWs before and after this transition.

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Abby Good

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Introduction: Limited data exist on the gross motor abilities of children with cystic fibrosis (CF). The objective of this quality improvement project was to implement a systematic gross motor assessment in children with CF ages 4-12 years. Methods: Physical therapists aimed to evaluate at least 50% of eligible children at our CF Center over 1 year using the Bruininks-Oseretsky Test of motor Proficiency, second edition (BOT-2), a norm referenced assessment for gross motor skills, with delays defined by scores less than 18 th percentile. Demographic and clinical data including body mass index, hospitalizations, genotype, and comorbidities were collected. Basic descriptive statistics summarized patient information. Parametric and non-parametric methods compared groups of interest. Linear regression assessed associations between BOT-2 measures and clinical characteristics. Results: Of the 105 eligible children, 72 (69%) completed the BOT-2 over 1 year. Forty-five (62.5%) scored below average in at least one category. Impaired strength (22.2%) was most common, followed by impaired balance (16.7%), running speed and agility (15.3%), and bilateral coordination (8.3%). Eleven (15.5%) scored below average on their total motor composite score (TMC). Increased age, comorbidities and hospitalizations were associated with a lower TMC. Conclusions: The BOT-2 was successfully implemented as part of routine CF care to screen for gross motor delays. Results suggest that a high percentage of children with CF, especially older children with comorbid conditions or a history of hospitalization, have impaired gross motor function. These findings support the need for routine gross motor evaluations and physical therapy interventions within pediatric CF clinics.

Jasneek Chawla

and 1 more

Alyssa M. Medenblik

and 6 more

N Pavithra

and 3 more

Leather and leather products are the most traded commodities and play a significant role in the world’s economy. The traditional tanning methods and the high quality of Indian leathers receive global appreciation. The existing leather manufacturing methods made a significant loss in epidermal constituents which impact the commercial importance of the animal species. Embossing techniques could potentially contribute to an increase in fraudulent activities. Since the fate of genetic material in finished leather is questionable, which poses a challenge to the molecular approach for identification. In order to obviate the problem, the present study aims to recover amplifiable mtDNA from leather products and focus on developing probes and primers for RT-PCR, which significantly enhance cross-specificity. Data mining and phylogenetic analyses of mtDNA genes (12S rRNA, COI, and Cyt b) for Indian Ovis aries skins exhibit the taxonomic positions and the intraspecies relationships, thereby facilitating the probes desigining. The results indicate that the maximum intraspecies genetic divergence observed within 12S rRNA, followed by COI and Cyt b. Since the availability of genetic sequences with reference to Cyt b is comparatively large (602), primers and probes were designed for Cyt b. The RT-PCR analysis of finished Ovis aries leather mtDNA samples yield a ct value in the range of 22–23 cycles, even with a minimum quantity of template DNA as low as 0.3 ng. Results on the cross-specificity analysis are highly encouraging. Hence, it is feasible to identify genuine Ovis aries leather using mtDNA instilling confidence in the export of leather.

Julia Dunker

and 2 more

Phenotypic covariation among suites of traits may constrain or promote diversification both within and between species, yet few studies have empirically investigated this relationship. In this study we investigate whether phenotypic covariation of craniofacial traits is associated with diversification in an adaptive radiation of pupfishes found only on San Salvador Island, Bahamas. The full radiation of pupfishes includes generalist, durophagous, and lepidophagous pupfish species. We compare phenotypic variation and covariation (i.e., P matrix) between 1) allopatric populations of generalist pupfish from neighboring islands and estuaries in the Caribbean, 2) San Salvador Island pupfish populations not containing the full radiation of fishes, and 3) San Salvador Island pupfish populations containing the full radiation in sympatry. Additionally, we explore whether phenotypic covariation varies between purebred and hybrid pupfish. We found that the P matrix of SSI generalist populations not found in sympatry with specialists exhibited higher levels of mean trait correlation, higher levels of constraints, and lower levels of flexibility compared to generalist populations on other Caribbean islands and sympatric populations of all three species found on SSI. We also documented significant differences between hybrid and purebred phenotypic covariation, where hybrids displayed lower correlations between traits and higher levels of flexibility, which may produce differential fitness in the wild. Ultimately, this study suggests that differences in phenotypic covariation significantly contribute to producing and maintaining organismal diversity.

Shijie Zhou

and 9 more

Soil fungi are involved in the decomposition of organic matter, and they alter soil structure and physicochemical properties and drive the material cycle and energy flow in terrestrial ecosystems. Grazing exclusion is one of the most common measures used to restore degraded grasslands worldwide. However, changes in soil fungal community characteristics during grazing exclusion in different types of grasslands are unknown. Here, we investigated the effects of a 9-year grazing exclusion on soil properties, fungal community composition and diversity in three grassland types (temperate desert, temperate steppe and mountain meadow). The results showed that in the 0-5 cm soil layer, grazing exclusion significantly affected the physicochemical parameters of all three studied grassland types. In the 5-10 cm soil layer, grazing exclusion significantly increased total phosphorus (TP) in temperate deserts by 34.1%, while significantly decreasing bulk density (BD) by 9.8% and the nitrogen: phosphorus ratio (N:P) by 47.1%. The soil fungal community composition differed among the grassland types, For example, significant differences were found among the three grassland types for the Glomeromycota and Mucoromycota, Grazing exclusion, grassland type, and the interaction between the two did not significantly affect soil fungal α-diversity or community composition(P > 0.05), but significantly altered fungal β-diversity (P < 0.05). Overall, our results highlight the importance of soil nutrient content, especially soil Kjeldahl nitrogen, total phosphorus and organic carbon on fungal diversity, and the results provide key insights into how soil fungi respond to grazing exclusion in different grassland types.

Yao Li

and 6 more

:The Qinghai−Tibet Plateau (QTP) is among the most sensitive regions to global environmental change worldwide. Although the climate change and engineering construction on the QTP have jointly modified the regional vegetation activity, little is known about how vegetation variation responds. Using Moderate Resolution Imaging Spectroradiometer (MODIS) enhanced vegetation index (EVI) data during 2000−2021, this study investigated the spatiotemporal variation of vegetation activity and the compound effects of climate change and construction along the G318 highway on the QTP (TG318) through the integration of trend, residual, and partial correlation analyses, as well as structural equation modeling. The results showed that the growing season EVI increased significantly at a rate of about 0.0020/year in the western QTP after reconstruction, but fluctuated in the east. Reconstruction generally had a significant effect on the growing season EVI, with contributions of 7.67%, 19.12%, 18.24%, and −4.15% in different sections of TG318, whereas climate change contributed −10.14% to 8.84% of the total variation. The growing season EVI negatively correlated with snow cover and minimum temperature in humid and sub-humid regions, whereas positively related to vapor pressure in semi-arid regions. Moreover, there existed an obvious lag effect of climate change on the growing season EVI, with lag time generally decreasing from west to east and apparent heterogeneity among different months and regions. These findings would help better understand the environmental impacts along the engineering corridors and provide a scientific basis for ecological conservation in the QTP region.

Sintayehu Daba

and 5 more

Seeds are an important part of plants, ensuring the continuation of plants’ life and providing nutrient reserves for humans and animals. Seed development is controlled by the interplay of several physiological processes. We applied label-free proteomics to round and wrinkled peas using seeds sampled at five growth stages (4 days after anthesis (DAA), 7DAA, 12DAA, 15DAA, and maturity). Phenotypic results indicated that wrinkled peas had lower starch concentration compared to round peas (29.5% vs. 46.6-55.1%). A total of 4,126 high confident proteins were detected, with 22–26% shared across all sampling times within an entry. Early seed growth stages were characterized by more unique proteins compared to maturity. Two-way ANOVA revealed 1,685 proteins significantly different among samples, of which 722 proteins were characterized into 29 functional classes. The four major classes (comprising over 50 proteins) were protein biosynthesis, protein homeostasis, enzymes, and carbohydrate metabolism. Of the two types of comparisons (time-point and entry-wise), time-point comparisons yielded more differentially abundance proteins (596 proteins in total). Different protein classes exhibited different patterns of change during seed development. For example, cell division related proteins were abundant early in seed development, whereas storage proteins were abundant later in seed development (especially after 12DAA). Compared to the round pea entries, the wrinkled entry had significantly lower abundance of starch branching enzymes, a protein involved in the biosynthesis of amylopectin in starch. In conclusion, the results of this study provide valuable information to improve our understanding of seed development and form the basis for further studies.

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Gizem Koken

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Background: Food-induced immediate response of the esophagus (FIRE) is a new phenomenon that has been described in eosinophilic esophagitis (EoE) patients. It is suspected when unpleasant symptoms occur suddenly on contact of the triggering food with the esophageal surface and recur with repeated exposures. It can often be mistaken for pollen-food allergy syndrome (PFAS) and solid food dysphagia. Data on FIRE is limited to one survey study and case reports, and there are no screening studies conducted on either adults or children with EoE. In this study, we aimed to screen children aged ≥7 years old with EoE for FIRE. Methods: Demographic data were collected from medical records. A questionnaire about FIRE was applied to all participants. Skin prick tests (SPTs) were done on suspected patients to identify the triggering foods. FIRE is defined as suitable clinical symptoms with suspected food allergen exposure. Results: Seventy-eight patients (74.4% male, median age: 13.5 years) were included. Unpleasant and recurrent symptoms distinct from dysphagia with specific foods were reported in %16.7 of the patients, all of whom had concomitant allergic rhinitis (AR). The symptoms described by almost all patients were oropharyngeal itching and tingling (PFAS: 15.3%) excluding only one patient reporting retrosternal narrowing and pressure after specific food consumption (FIRE: 1.2%). Conclusions: Although definitive conclusions regarding the true prevalence of FIRE cannot be made, it does not seem to be common as PFAS. However, it deserves questioning particularly in the presence of concurrent AR and/or PFAS in children with EoE.

Shen Shen

and 3 more

Optimizing the spatial configuration of diverse best management practices (BMPs) can provide valuable decision-making support for comprehensive watershed management. Most existing methods focus on selecting BMP types and locations but neglect their implementation time or order in management scenarios, which are often investment-restricted. This study proposes a new simulation-optimization framework for determining the implementation plan of BMPs by using the net present value to calculate the economic costs of BMP scenarios and the time-varying effectiveness of BMPs to evaluate the environmental effectiveness of BMP scenarios. The proposed framework was implemented based on a Spatially Explicit Integrated Modeling System and demonstrated in an agricultural watershed case study. This case study optimized the implementation time of four erosion control BMPs in a specific spatial configuration scenario under a 5-year stepwise investment process. The proposed method could effectively provide more feasible BMP scenarios with a lower overall investment burden with only a slight loss of environmental effectiveness. Time-varying BMP effectiveness data should be gathered and incorporated into watershed modeling and scenario optimization to better depict the environmental improvement effects of BMPs over time. The proposed framework was sufficiently flexible to be applied to other technical implementations and extensible to more actual application cases with sufficient BMP data. Overall, this study demonstrated the basic idea of extending the spatial optimization of BMPs to a spatiotemporal level by considering stepwise investment, emphasizing the value of integrating physical geographic processes and anthropogenic influences.

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