BAY 11-7082: An Anti-inflammatory Drug for COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus named by the International Committee on Taxonomy of Viruses. COVID-19 patients have high mortality due to respiratory failure from acute respiratory distress syndrome (ARDS) induced by SARS-CoV-2. The abnormal activation of P21-activated kinase (PAK1, RAC/CDC42-activated kinase 1) is reported in COVID-19. The PAK1 induces nuclear factor kappa B (NF-?B) activation as well as inflammatory pathways through its stimulation. BAY 11-7082 {(E) 3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile is one of the therapies that inhibit inflammation via mentioned signaling pathway, therefore, we suggest that this drug can potentially be effective in treating COVID-19.

Hydroxychloroquine and azithromycin alter the contractility of living porcine heart slices.

The cardiotoxicity risk of hydroxychloroquine (HCQ) and azithromycin (AZM) has been the subject of intensive research triggered by safety concerns in COVID-19 patients. HCQ and AZM have been associated with QT interval prolongation and drug-induced arrhythmias, however other cardiotoxicity mechanisms remain largely unexplored. Our group has pioneered the living heart slice preparation, an ex-vivo platform that maintains native cardiac tissue architecture and physiological electrical and contractile properties. Here, we evaluated the cardiotoxic effect of HCQ and AZM applied alone or in combination on cardiac contractility by measuring contractile force and contraction kinetics in heart slices prepared from porcine hearts. Our results show that clinically relevant concentrations of HCQ monotherapy (1-10 µM) reduced contractile force and contraction kinetics in porcine slices in a dose-dependent manner. However, AZM monotherapy decreased contractile force and contraction kinetics only at higher concentrations (30 µM). Combination of HCQ and AZM induced a dose-dependent effect similar to HCQ alone. Furthermore, pre-treating porcine heart slices with the L-type calcium channel agonist Bay K8644 prevented the effect of both drugs, while administration of Bay K8644 after drugs interventions largely reversed the effects, suggesting a mechanism involving inhibition of L-type calcium channels. These findings indicate that HCQ and AZM alter cardiac function beyond QT prolongation with significant contractile dysfunction in intact cardiac tissue. Our porcine heart slices provide a powerful platform to investigate mechanisms of drug cardiotoxicity.

Personal protective equipment-derived pollution during Covid-19 era: A critical review of ecotoxicology impacts, intervention strategies, and future challenges.

During the COVID-19 pandemic, people used personal protective equipment (PPE) to lessen the spread of the virus. The release of microplastics (MPs) from discarded PPE is a new threat to the long-term health of the environment and poses challenges that are not yet clear. PPE-derived MPs have been found in multi-environmental compartments, e.g., water, sediments, air, and soil across the Bay of Bengal (BoB). As COVID-19 spreads, healthcare facilities use more plastic PPE, polluting aquatic ecosystems. Excessive PPE use releases MPs into the ecosystem, which aquatic organisms ingest, distressing the food chain and possibly causing ongoing health problems in humans. Thus, post-COVID-19 sustainability depends on proper intervention strategies for PPE waste, which have received scholarly interest. Although many studies have investigated PPE-induced MPs pollution in the BoB countries (e.g., India, Bangladesh, Sri Lanka, and Myanmar), the ecotoxicity impacts, intervention strategies, and future challenges of PPE-derived waste have largely gone unnoticed. Our study presents a critical literature review covering the ecotoxicity impacts, intervention strategies, and future challenges across the BoB countries (e.g., India (162,034.45 tons), Bangladesh (67,996 tons), Sri Lanka (35,707.95 tons), and Myanmar (22,593.5 tons). The ecotoxicity impacts of PPE-derived MPs on human health and other environmental compartments are critically addressed. The review's findings infer a gap in the 5R (Reduce, Reuse, Recycle, Redesign, and Restructure) Strategy's implementation in the BoB coastal regions, hindering the achievement of UN SDG-12. Despite widespread research advancements in the BoB, many questions about PPE-derived MPs pollution from the perspective of the COVID-19 era still need to be answered. In response to the post-COVID-19 environmental remediation concerns, this study highlights the present research gaps and suggests new research directions considering the current MPs' research advancements on COVID-related PPE waste. Finally, the review suggests a framework for proper intervention strategies for reducing and monitoring PPE-derived MPs pollution in the BoB countries.

Assessing carrying capacity using demographics, visitor experience and field studies: the case of Hanauma Bay Nature Preserve

The Hanauma Bay Nature Preserve (HBNP) was designated the first Marine Life Conservation District in Hawai'i in 1967. It is the most popular visitor snorkelling experience on the island of O'ahu. A social carrying capacity study was conducted upon reopening, following a nine-month COVID-19 closure due to travel restrictions. Surveys were compared to three prior surveys conducted between 1990 and 2002 to provide a larger historical context of social dynamics and perceived human impacts over time. Demographics, recreational activities, crowding perceptions, and educational availability were assessed. Visitor activity photos and counts were evaluated in context with survey responses. Perceived visitor contact on the reef was compared to in situ snorkelling impact. These quantitative observations reported an average of one reef disturbance for every two individuals. Photographic analysis of breakage of selected baseline corals prior to closure were compared to corals following reopening of the preserve in 2021. Partial mortality occurred in 60% of coral colonies. Successful management policies that include social carrying capacities should align with biological carrying capacities to balance the health of the ecosystem with a positive experience for visitors. These management strategies provide a holistic approach to advance conservation and meet visitor satisfaction goals. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

Impact of COVID-19 Prevention and Control Measures on Expressway Transportation in Guangdong-Hong Kong-Macao Greater Bay Area

Under the background of normalized COVID-19 prevention and control, regional epidemics occur frequently in China. How to quantify the impact of COVID-19 prevention and control measures on economic operation and passenger and freight transportation has become an urgent problem. To this end, we design a calculation method for expressway transportation indicators, propose the level and stage division process of COVID-19 prevention and control measures, and then establish a difference-in-difference model to further analyze their impact on expressway transportation indicators. Taking major cities in the Guangdong-Hong Kong-Macao Greater Bay Area as an example, case studies are conducted based on the expressway toll data and COVID-19 prevention and control information from May 2020 to April 2022. The results show that in the level I (strengthened) stage, the passenger vehicle flow has dropped significantly, the drop in each case is between 8% and 27%, and the freight indicators have not changed significantly. In Shenzhen and Dongguan, both passenger and freight indicators dropped sharply in the level II (strict) stage. Passenger vehicle flow in the two cities dropped by 46.3% and 33.7%, and truck flow by 42.7% and 27.6%, respectively, and cargo and turnover decreased as much as truck flow. The average inter- city distance of expressway passenger cars has a downward trend under the level I stage, but under the level II stage, the average inter-city distance of passenger cars and trucks has increased significantly. This study can provide a certain reference value for the formulation and implementation of COVID-19 prevention and control measures in cities and urban agglomerations. © 2022 Science Press. All rights reserved.

A shock to the system: entrepreneurial ecosystem resilience and adaptation in a global pandemic

PurposeThis exploratory study uses a punctuated equilibrium paradigm (PEP) framework to examine the impact and adaptation of an entrepreneurial ecosystem (EE) to the COVID-19 pandemic at the organizational and ecosystem level. The aim is to provide guidance to EEs on ways to adapt to future external shocks.Design/methodology/approachAs this study is exploratory in nature, the authors use a sequential mixed method whereby a qualitative method is used first to identify emergent themes from in-depth interviews with EE members, followed by a quantitative method (survey) based on those themes across a broader cross section of EE members.FindingsEntrepreneurial ecosystem's geographical advantages have declined during the pandemic as EE firms adapted to this external shock by developing more digitally distributed organizations.Research limitations/implicationsBased on the findings, the authors propose an emerging model of EEs that extends the traditional clustering model focused on geography to account for more digitally distributed entrepreneurial clusters. However, the results, based on an in-depth study of one ecosystem, may not be fully generalizable to all EEs.Practical implicationsGiven the widespread pandemic impact, the findings may be instructive to EEs and organizations in EEs that aim to become more resilient in the face of potential future external shocks.Social implicationsAs part of the qualitative interview process the interviewees were asked what they would change in San Francisco Bay Area if they had a magic wand right now. They discussed a variety of inspiring ideas, but the most frequently mentioned was their wish to change the focus of business to solve societal problems with a global citizen mindset (e.g. recycling energy, climate change, income inequality, access to education and funding, inequity, wealth gaps, housing crisis and homelessness) to make the world a better place. Additionally, the pandemic exposed some inequality in work conditions across demographics. As firms reorganize to increase resiliency, attention to these issues should be addressed.Originality/valueThis study is unique in applying the PEP to EEs to deepen our understanding about how an EE evolves during periods of sudden external shocks.

A STUDY ON USAGE AND EVALUATION OF COURTYARDS IN MAKUHARI BAY TOWN DURING THE PERIOD OF SELF-QUARANTINE UNDER THE STATE OF EMERGENCY DECLARATION

By the infection spread of COVID-19, people were required to refrain from leaving their homes unnecessarily and lived with their families. And they spent time while having the uneasiness to going out of the residence ridge. The purpose of this paper is to clarify the activity status of usage and evaluation of courtyards in Makuhari Bay Town during the period of Self-Quarantine under the state of emergency declaration. This report analyzed the association with the resident attribute about the use actual situation and the evaluation of the courtyard. © 2023 Architectural Institute of Japan. All rights reserved.

Toxic Exposures Among Young Children One Year into the COVID-19 Pandemic: A Retrospective Review of Three San Francisco Bay Area Emergency Departments.

BACKGROUND: Daycare and school closures prompted by shelter-in-place orders may have increased opportunities for unintentional ingestions among young children. OBJECTIVES: We examined emergency department (ED) presentations for toxic exposures among young children during the COVID-19 pandemic in the San Francisco Bay Area, which had some of the strictest and most prolonged shelter-in-place policies in the United States. METHODS: We performed a retrospective cross-sectional study of children 0 to 5 years of age who presented with an ED International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis code of toxic exposure within a tertiary care hospital system between March 16, 2016 and March 15, 2021. We considered the period after March 16, 2020 to represent the pandemic. RESULTS: During the pandemic, the absolute number of poisonings among young children remained stable. Overall, ED encounters within this cohort decreased by 55%, which doubled the relative toxic exposure rate per 1000 ED encounters from 4.99 (95% confidence interval [CI] 3.19-5.90) to 9.79 (95% CI 8.09-11.49). Rates of admission, severe medical complications, operating room case requests, and length of stay were not significantly different. Shelter-in-place was associated with significantly higher odds of cannabis ingestion (odds ratio = 2.70, 95% CI 1.60-4.49). CONCLUSION: Despite dramatic decreases in overall ED patient volumes, the absolute number and severity of toxic exposures were similar during the pandemic compared with previous years. © 2022 Elsevier Inc.

Interaction of Laurusides 1 and 2 with the 3C-like Protease (Mpro) from Wild-Type and Omicron Variant of SARS-CoV-2: A Molecular Dynamics Study.

Laurus nobilis (bay laurel) is a natural source of biological compounds, and some of its extracts and phytocompounds are also endowed with antiviral activity toward the family of the severe acute respiratory syndrome (SARS)-associated ß-coronaviruses. Some glycosidic laurel compounds such as laurusides were proposed as inhibitors of important protein targets of SARS-CoV-2, which clearly recalls their potential as anti-COVID-19 drugs. Due to the frequent genomic variations of the ß-coronaviruses and the consequent importance of evaluating a new drug candidate with respect to the variants of the target ß-coronavirus, we decided to investigate at an atomistic level the molecular interactions of the potential laurel-derived drugs laurusides 1 and 2 (L01 and L02, respectively) toward a well-conserved and crucial target, the 3C-like protease (Mpro), using the enzymes of both the wild-type of SARS-CoV-2 and of the more recent Omicron variant. Thus, we performed molecular dynamic (MD) simulations of laurusides-SARS-CoV-2 protease complexes to deepen the knowledge on the stability of the interaction and compare the effects of the targeting among the two genomic variants. We found that the Omicron mutation does not significantly impact the lauruside binding and that L02 connects more stably with respect to L01 in the complexes from both variants, even though both compounds prevalently interact within the same binding pocket. Although purely in silico, the current study highlights the potential role of bay laurel phytocompounds in the antiviral and specifically anti-coronavirus research and shows their potential binding toward Mpro, corroborating the important commitment of bay laurel as functional food and disclosing novel scenarios of lauruside-based antiviral therapies.

Seasonal variation and ecological risk assessment of Pharmaceuticals and Personal Care Products (PPCPs) in a typical semi-enclosed bay — The Bohai Bay in northern China

The Bohai Bay as a typical semi-enclosed bay in northern China with poor water exchange capacity and significant coastal urbanization, is greatly influenced by land-based inputs and human activities. As a class of pseudo-persistent organic pollutants, the spatial and temporal distribution of Pharmaceuticals and Personal Care Products (PPCPs) is particularly important to the ecological environment, and it will be imperfect to assess the ecological risk of PPCPs for the lack of systematic investigation of their distribution in different season. 14 typical PPCPs were selected to analyze the spatial and temporal distribution in the Bohai Bay by combining online solid-phase extraction (SPE) and HPLC-MS/MS techniques in this study, and their ecological risks to aquatic organisms were assessed by risk quotients (RQs) and concentration addition (CA) model. It was found that PPCPs widely presented in the Bohai Bay with significant differences of spatial and seasonal distribution. The concentrations of ∑PPCPs were higher in autumn than in summer. The distribution of individual pollutants also showed significant seasonal differences. The high values were mainly distributed in estuaries and near-shore outfalls. Mariculture activities in the northern part of the Bohai Bay made a greater contribution to the input of PPCPs. Caffeine, florfenicol, enrofloxacin and norfloxacin were the main pollutants in the Bohai Bay, with detection frequencies exceeding 80 %. The ecological risk of PPCPs to algae was significantly higher than that to invertebrates and fish. CA model indicated that the potential mixture risk of total PPCPs was not negligible, with 34 % and 88 % of stations having mixture risk in summer and autumn, respectively. The temporary stagnation of productive life caused by Covid-19 weakened the input of PPCPs to the Bohai Bay, reducing the cumulative effects of the pollutants. This study was the first full-coverage investigation of PPCPs in the Bohai Bay for different seasons, providing an important basis for the ecological risk assessment and pollution prevention of PPCPs in the bay. © 2022 Elsevier B.V.

‘Dying … to Connect': Postdigital Co-presence in Dead Centre's To Be a Machine (Version 1.0) (2020)

This article proposes to address the tension between digital co-presence and embodied spectatorship inaugurated by the pivot to online and hybrid forms of (post-)pandemic performance through the lens of the postdigital. The term is developed as a way of accounting for the complex mediatized co-presence between performer and audience in a representative example of this genre, Dead Centre's To Be a Machine (Version 1.0). As its theoretical framework, the article brings together the concept of ‘postdigital performance' (Causey) with co-presence as a central element of liveness and spectatorship. It puts forth the hypothesis that To Be a Machine (Version 1.0) constructs a postdigital sense of co-presence that is characterized by a blurring of the lines between embodied and virtual spectatorship, temporal co-presence and real-time interaction with the remote audience, and an increased sense of emotional alignment with the remote audience in lieu of physical proximity.

Transboundary microplastic pollution in Xiamen Bay and adjacent Jiulong River estuary after the outbreak of COVID-19.

Land-based transport from nearshore areas is a key pathway of microplastic (MP) pollution in the oceans. Therefore, transport, fate, and intervention on MPs necessitate an investigation of MP contamination in coastal regions. Here, MP pollution in the surface waters of Xiamen Bay and Jiulong River estuary was evaluated in 2021 after the outbreak of COVID-19. The abundance of MPs in Xiamen Bay ranged from 0.20 to 5.79 items m-3 with an average of 1.03 items m-3, whereas that in the Jiulong River estuary spanned from 0.55 to 2.11 items m-3 with a mean of 1.30 items m-3. A yearly decreasing trend in the abundance of MPs in surface waters in both regions was observed. The particle sizes of MPs were concentrated in the range of 2.50-5.00 mm, and the colors were mainly white, transparent, and green. The micro-Raman spectroscopic results showed that MP polymer types were predominantly polyethylene, polypropylene, and polystyrene. A lower abundance of MPs in Xiamen Bay with no obvious pattern was observed, while that in the Jiulong River estuary showed a wavelike distribution from upstream to downstream. Ecological risk assessment of MP pollution in surface waters of two regions was performed using the pollution load index (PLI), giving the risk level in descending order: wastewater discharge area > aquaculture area > sloughs > estuary mouth > estuarine rivers > shipping lane. The average risk level of Xiamen Bay (I) was lower than that in Jiulong River estuary (II). The MP pollution in the Jiulong River estuary appeared heavier than that in Xiamen Bay, which may be due to the combined effects of COVID-19 and marine governance. This study provided insights into the prevention and management of MP pollution in nearshore semi-enclosed bays.

Use of the Improvement Index to Evaluate Equitable COVID-19 Vaccine Allocation in the San Francisco Bay Area.

Introduction: A social determinants of health index score or Vaccine Equity Metric was used to prioritize resources and address geographic disparities in California's vaccination coverage. We calculated the improvement index or percentage of the vaccination disparity gap closed to evaluate the impacts of this vaccination strategy in the San Francisco Bay Area during the SARS-CoV-2 Delta variant surge. Methods: We conducted a cross-sectional study on San Francisco Bay Area ZIP codes during the Delta surge (July 6-October 5, 2021). Data came from the California Immunization Registry and the 2019 5-year American Community Survey. We used Spearman correlations to examine the relationships between Vaccine Equity Metric category and vaccine coverage and Kruskal-Wallis tests to compare vaccination improvement index across Vaccine Equity Metric categories. Results: We studied 248 ZIP codes in the San Francisco Bay Area. Those with the lowest resources (Vaccine Equity Metric Level 1) had the highest absolute increase in vaccination coverage (14.3 vs 5.4 percentage points in Vaccine Equity Metric Level 4), although a contribution was higher starting vaccination rates in Level 4 ZIP codes with the greatest resources. The ratio of vaccination coverage between the lowest- and highest-resourced ZIP codes increased from 0.79 to 0.9, suggesting reduced disparity. However, it is difficult to interpret given wide differences in n (Level 1 n=8 vs Level 4 n=151). In contrast, the vaccination improvement index accounts for each Vaccine Equity Metric category's baseline vaccination; all were statistically similar (grand mean=41.5%, p=0.367), implying comparable improvement across all ZIP codes. Conclusions: Using a Vaccine Equity Metric to identify and prioritize resources to vulnerable communities contributed to equitable vaccine allocation in the San Francisco Bay Area. Our study shows an example of the improvement index's advantages over conventional health equity metrics, such as absolute differences and relative effect measures, which can overestimate an intervention's impact.

The "City-Suburb" Tourist Flow Network Structure Characteristics in the Guangdong-Hong Kong-Macao Greater Bay Area in the Post-Pandemic Era: Analysis Based on the Network Digital Footprint

To explore the movement of "city-suburb" tourism flow in the post-pandemic period, this study examines the tourist flow network of the Guangdong-Hong Kong-Macao Greater Bay Area from 2018 to 2021 based on online travel data. After screening and deduplication, 4882 valid travelogues were chosen and divided into pre-pandemic data (3, 967 articles) and post-pandemic data (915 articles) using November 2019 as the dividing line. A total of 4, 461 attractions on Ctrip. com were selected to build a scenic spot database of the Guangdong-Hong Kong-Macao Greater Bay Area, including the full names, aliases (common names), and city names of scenic spots. After matching the travelogues with the scenic spots in the attraction database, it was found that 1848 attractions appeared in the travel notes, and the top 300 attractions were chosen for the generation of tourism routes according to the number of matches. After converting travel routes to a directed connectivity matrix and the following dichotomization procedure, a social network analysis (SNA) was conducted to investigate the distribution of tourism flows and preferences in the Greater Bay Area. Using the SNA software Ucinet 6.0, the network density, centrality, and relevant metrics of the structural holes and cohesive subgroups were calculated. The node characteristics and network structure were analyzed, and the distribution characteristics of attractions and tourist intention trends in the Greater Bay Area were obtained. The study results indicate the following: 1) The tourism network density of the Greater Bay Area has decreased substantially since the COVID-19 outbreak. Megacities, especially overseas cities, were more affected by the pandemic. Tourism network connectivity and aggregation effects were severely weakened, and the network structure was more scattered and fragmented. 2) After the pandemic, the "core-periphery" structure of tourism networks weakened, and the boundaries between core and periphery areas blurred. Some suburban and rural scenic spots have become new core areas and their importance in the network has been significantly enhanced. 3) After the pandemic, the connectivity and control power of traditional core urban nodes, such as Hong Kong, Zhuhai, Macao, and Guangzhou, weakened. The cohesive subgroups of scenic points show a high cohesion of Guangzhou with cities on the west side of the Pearl River Estuary, such as Foshan, Zhuhai, and Macao, before the pandemic. After the pandemic, the cohesive subgroup of rural attractions was strengthened and tourism showed a development trend of multi-point and ruralization. 5) The tourism network has changed from the three-core development mode of Guangzhou-Hong Kong-Macao before the pandemic to the "four-wheel drive" mode of Guangzhou-Macao-Shenzhen-Foshan after the outbreak with the declined linkage of the Hong Kong-Zhuhai-Macao Bridge in the network. It is believed that travel mobility restrictions and tourism drivers are two-way driving forces for the structural change in tourism in the post-pandemic period. The Greater Bay Area's tourist flow network presents a two-loop structure with two-way dynamics owing to some pandemic factors, and may gradually show a decentralized and scattered development trend. Based on network analysis, it is proposed that more efforts be made to integrate city-suburb-countryside resources in the post-pandemic period. © 2022 Editorial Committee of Tropical Geography. All rights reserved.

Early Predication of Covid-19 by Machine Learning Algorithms

In COVID-19 is the most significant issue for the human community. The virus is easily converted into a new variant, which behaves differently from the previous one. Besides its changing behavior, its transmission and infection rate are very high which causes high death rate. It is a very challenging situation for the healthcare system to early diagnosis of diseases so that predict the transmission growth of virus the number of new, confirmed, recovered, and dead cases can be reduced. To deal with these issues, some prediction tools are required which can help to test and find the cause of existing cases so that it can help the effective and rapid arrangement to overcome the pandemic. To address this issue, we propose a symptom-base Recommendation System which are tested over the dataset by applying the concept of Machine Learning algorithms. In this work, we test our proposed system by suing various machine learning algorithm like LR, SVM, Navie Bays,KNN,Random Forest etc. The experimental results reveal that the proposed system is capable to diagnose the disease accurately approximate 99%. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

A study on the evolution of economic patterns and urban network system in Guangdong-Hong Kong-Macao greater bay area.

The COVID-19 pandemic has seriously affected China's macroeconomy, industrial transformation, and high-quality development. Research on economic patterns and urban network systems can provide a reference for healthy development of the regional economic system. The evolution of the economic pattern and urban network system of Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 2010 to 2020 is investigated using methods (e.g., the gravity center model, the gravitational force model, social network analysis, and geographic information system). (1) The gravity center of gross domestic product (GDP) of the GBA is located in Nansha district, Guangzhou, with a skewing direction northwest-east-northwest and a movement rate of "large-small-large." The center of import and export and the center of consumption show a "zigzagging migration" in which the center of investment shows an "irregular (random) migration". (2) The economic connection degree of cities in the GBA exhibits a high ascending velocity, and the whole area tends to be mature, with a significant effect of spatial proximity. With the steady increase in network density, there is significant polarization of network centrality in the region. The four major cohesive subgroups have been relatively stable and consistent with the degree of geographic proximity of the cities. The center-periphery structure is more significant, in which the core area is extended to the cities on the east coast of the Pearl River Estuary, thus forming the core cluster of "Hong Kong-Shenzhen-Guangzhou-Dongguan." In this study, the evolution of economic patterns and urban network systems in the GBA over the past decade is analyzed using multiple methods (i.e., gravity model, urban network system analysis, and geographic information system) based on urban socioeconomic data by starting from various spatial elements (e.g., "points, lines, and networks") to gain insights into and optimize research on regional economic development after the COVID-19 pandemic.

Seasonal variation and ecological risk assessment of Pharmaceuticals and Personal Care Products (PPCPs) in a typical semi-enclosed bay — The Bohai Bay in northern China

The Bohai Bay as a typical semi-enclosed bay in northern China with poor water exchange capacity and significant coastal urbanization, is greatly influenced by land-based inputs and human activities. As a class of pseudo-persistent organic pollutants, the spatial and temporal distribution of Pharmaceuticals and Personal Care Products (PPCPs) is particularly important to the ecological environment, and it will be imperfect to assess the ecological risk of PPCPs for the lack of systematic investigation of their distribution in different season. 14 typical PPCPs were selected to analyze the spatial and temporal distribution in the Bohai Bay by combining online solid-phase extraction (SPE) and HPLC-MS/MS techniques in this study, and their ecological risks to aquatic organisms were assessed by risk quotients (RQs) and concentration addition (CA) model. It was found that PPCPs widely presented in the Bohai Bay with significant differences of spatial and seasonal distribution. The concentrations of ∑PPCPs were higher in autumn than in summer. The distribution of individual pollutants also showed significant seasonal differences. The high values were mainly distributed in estuaries and near-shore outfalls. Mariculture activities in the northern part of the Bohai Bay made a greater contribution to the input of PPCPs. Caffeine, florfenicol, enrofloxacin and norfloxacin were the main pollutants in the Bohai Bay, with detection frequencies exceeding 80 %. The ecological risk of PPCPs to algae was significantly higher than that to invertebrates and fish. CA model indicated that the potential mixture risk of total PPCPs was not negligible, with 34 % and 88 % of stations having mixture risk in summer and autumn, respectively. The temporary stagnation of productive life caused by Covid-19 weakened the input of PPCPs to the Bohai Bay, reducing the cumulative effects of the pollutants. This study was the first full-coverage investigation of PPCPs in the Bohai Bay for different seasons, providing an important basis for the ecological risk assessment and pollution prevention of PPCPs in the bay.

Staff experiences of working on a new Critical Care Unit during the COVID 19 pandemic

Introduction: Intensive Care Unit (ICU) design impacts staff well-being1 with relocation to a different ICU layout causing staff stress.2,3 During the COVID-19 pandemic our new critical care centre was opened expediently allowing increased patient capacity and providing a purpose-built environment for ICU patients. The new single-bed room layout differed to other open plan multi-bed ICUs in the hospital. New design features included large floor-to-ceiling windows with park views, modernised equipment such as computer screens on movable pendants and noise reduction features. The pandemic accelerated the opening of the new unit and practice was adapted to address surge conditions (e.g., there were two patients in each 'single' room, and PPE could only be worn in specific areas of the unit, restricting movement). Objectives: We sought to understand the impact of the ICU design on staff experiences during pandemic conditions. Methods: Following ethical approval, staff who had worked on the new unit were invited to participate in a semi-structured interview. The interview guide was based on the Theoretical Domains Framework (TDF),4 a framework to identify the determinants of behaviour change. Interviews were audio recorded, anonymised and transcribed verbatim. We used line-by-line coding and analysed data informed by the TDF. Results: 21 participants captured experiences of a wide range of multi-disciplinary staff members. The most common domain identified within the data was 'Environmental context and resources', including data pertaining to barriers and facilitators of the new unit to effective working: Having large bed spaces is perfect for getting people out [of bed]. They are soundproofed as well, so patients were sleeping really well at night. Also, 'social/professional role and identity' (including group identity, leadership), 'skills' (including competence, skills development), and 'beliefs about consequences' (perception of the effects of the new units) were frequently identified in positive and negative ways: .because of where it [the patient's room] is located you do not get to see people often. I got forgotten for rolls.It was a constant struggle Medical staff and allied health professionals described advantages over the old unit design including improved team-working, oversight of patients, and mood from the design features. Participants perceived patient benefits from improved lighting and views and stimulation due to access to social media. Conversely, nurse participants perceived less support, less team-working and increased levels of anxiety due to the single rooms. Nurse experiences improved as patient numbers reduced. However, changes in how nurse teams worked was an ongoing challenge: staffing breaks and things is quite tricky. You need a permanent floater that is never allocated to patients, to try and help people, because they cannot leave their bays. Conclusions: Our findings support previous research2 demonstrating increased nurses stress when transitioning to a single-bed room ICU layout. Providing systems to alleviate nurse isolation, promote teamworking and reduce stress in future relocations may significantly improve staff well-being (e.g., video-calling and messaging between patient rooms). A multidisciplinary awareness of the impact on nurses is vital to support strategies to ameliorate the impact of changes during relocation.

21stRSC/SCI Medicinal Chemistry Symposium Cambridge/Virtual - September 13-15, 2021

The Royal Chemistry Society/Society of Chemistry Industry (RSC/SCI) Medicinal Chemistry Symposium is a key symposium in the field of medicinal chemistry that takes place every 2 years at the University of Cambridge, U.K., under the auspices of the RSC and the SCI. This year, in its 21st edition, it was run as a hybrid event, simultaneously attended by both in-person and virtual attendees. Its theme was 'Improving Success', and 25 orals and 30 posters were presented. The scientific program covered recent medicinal chemistry achievements in major therapeutic areas, with a few first-time structure disclosure presentations and particular emphasis on emerging early-stage drug discovery and lead optimization strategies, including reports of successful case studies illustrating fragment-based screening and phenotypic target engagement approaches. Applications of artificial intelligence (AI), mass spectrometry and photochemistry in drug design and discovery were also highlighted. This report will cover some of the medicinal chemistry presentations delivered at the meeting.

Evaluation and Influencing Factors of Network Resilience in Guangdong-Hong Kong-Macao Greater Bay Area: A Structural Perspective

Currently, urban crises are spreading, even tending to be magnified along the urban networks. Improving urban network resilience can effectively reduce the loss and cope with sudden disasters. Based on the dimensions of regional resilience and the framework of urban network, a new evaluation system of network resilience, including economic, social, and engineering networks, was established to assess the network resilience of the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from a structural perspective. We analyzed the spatial characteristics and influencing factors of network resilience using social network analysis and quadratic assignment procedure. The results were as follows: (1) regional difference was biggest in GBA's economic network strength while smallest in its transportation network strength, and the east bank of the Pearl River represented an extremely resilient connection axis;(2) the structures of network resilience and its subsystems were heterogeneous, and the connection paths of network resilience were more heterogeneous and diversified than those of the subsystems;(3) network resilience presented an obvious core-edge structure, and the spatial correlation and spillover effect between blocks were substantial;and (4) geographical proximity, as well as differences in economic development, urban agglomeration, and market development, had a significant impact on network resilience. This study provides a more systematic approach to evaluate the regional network resilience, and the results provide references for the construction of bay areas in developing countries.