Central Site Research Articles

Hexagonal Halide Perovskite Cs2LiInCl6: Cation Ordering, Face-Shared Octahedral Trimers and Mn2+ Luminescence.

The In-based double perovskite halides have been widely studied for promising optical-electric applications. The halide hexagonal perovskite Cs2LiInCl6 was isolated using solid-state reactions and investigated using X-ray diffraction and solid-state NMR spectra. The material adopts a 12-layered hexagonal structure (12R) consisting of layered cationic orders driven by the cationic charge difference and has Li+ cations in the terminal site and In3+ in the central site of face-shared octahedron trimers. Such a cationic ordering pattern is stabilized by electrostatic repulsions between the next-nearest neighboring cations in the trimers. The LiCl6 octahedron displays large distortion and is confirmed by 7Li SSNMR in the Cs2LiInCl6. The Cs2LiInCl6 material has a direct bandgap of ~4.98 eV. The Cs2LiInCl6: Mn2+ displays redshift luminescence (centered at ~610-622 nm) from the substituted Mn2+ emission in octahedron with larger PLQY (17.8 %-48 %) compared with that of Cs2NaInCl6: Mn2+. The Mn-doped materials show luminescent concentration quenching and thermal quenching. The composition Cs2Li0.99In0.99Mn0.02Cl6 exhibits the highest PL intensity, a maximum PLQY of 48 %, and high luminescent retention rate of ~86 % below 400 K and is suitable for application for pc-LED. These findings contribute to our understanding of the chloride perovskites and hold potential for widespread optical applications.

Two- and Three-Spin Hybrid Inorganic-Organic [2]Rotaxanes Containing Metallated Salen Groups.

Mono- and bis-salen functionalised [2]rotaxanes have been synthesised from the esterification of [2]rotaxanes containing phenol-terminated threads (salen=N,N'-bis(salicylidene)ethylenediamine). The [2]rotaxanes have general formula [RH][Cr7NiF8(O2CtBu)16], where [RH]+ is a thread with a central secondary ammonium site that templates a [Cr7NiF8(O2CtBu)16]- ring. The threads are terminated at one or both ends by carboxylic acid functionalised salen groups. The {M(salen)} groups can be free-base [M=(H+)2] or metallated [M=Cu2+, Ni2+, (VO)2+]. The [2]rotaxanes have been characterised by single crystal XRD and solid- and solution-state EPR spectroscopy. Where two paramagnetic M ions are involved [M=Cu2+ and/or (VO)2+] the [2]rotaxanes contain three electron spin S= centres, since the {Cr7Ni} ring has an S= ground state which is well isolated at low temperatures. These three-spin [2]rotaxanes have been characterised in solution by pulsed dipolar EPR spectroscopies (DEER, also known as PELDOR, and RIDME). The M⋅⋅⋅M and M⋅⋅⋅{Cr7Ni} interactions measured are consistent with dipolar interactions and also with the distances from single crystal XRD. The authors declare no competing financial interest.

Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants.

Epilepsy is a common neurological disorder characterized by abnormal activity of neuronal networks, leading to seizures. The racetam class of anti-seizure medications bind specifically to a membrane protein found in the synaptic vesicles of neurons called synaptic vesicle protein 2 (SV2) A (SV2A). SV2A belongs to an orphan subfamily of the solute carrier 22 organic ion transporter family that also includes SV2B and SV2C. The molecular basis for how anti-seizure medications act on SV2s remains unknown. Here we report cryo-electron microscopy structures of SV2A and SV2B captured in a luminal-occluded conformation complexed with anticonvulsant ligands. The conformation bound by anticonvulsants resembles an inhibited transporter with closed luminal and intracellular gates. Anticonvulsants bind to a highly conserved central site in SV2s. These structures provide blueprints for future drug design and will facilitate future investigations into the biological function of SV2s.

Emergency logistics siting-path question for engineering construction projects based on quantum particle swarm algorithm

Emergency material security is the key to post-disaster emergency relief in complex environment engineering construction projects. Aiming at the emergency logistics center site path planning problem, the uncertain parameters of congestion time and maximum rescue time are described using trapezoidal fuzzy numbers, and the emergency logistics site path model of the two-phase engineering construction project is established. A quantum particle swarm optimization model is designed to avoid premature population convergence and maintain population diversity. The particle swarm algorithm uses the quantum spin gate’s rotation angle update to represent the particle velocity update. Taking the engineering construction project in the western mountainous area as an example, the validity and applicability of the model are verified through model comparison and sensitivity analysis. The results of the example show that in the complex environment, the quantum particle swarm algorithm takes 29.35 s in convergence time, and the particle swarm algorithm takes 40.12 s, which is 36.69% higher than the efficiency of PSO. In total cost, the quantum particle swarm algorithm has a total cost of 46,632.40 RMB, and the particle swarm algorithm has a total cost of 48,319.51 RMB, which is 3.62% lower than the cost of PSO. The quantum particle swarm algorithm’s total distance is 550.57 km, and the particle swarm algorithm’s total distance is 579.35 km, 5.23% lower than the total distance of PSO. The model established in this study can scientifically select the location of emergency facilities and formulate the emergency rescue path, reduce the response time of emergency rescue and storage costs, and provide decision support for the scheduling of emergency supplies for engineering construction projects in complex and dangerous areas.

Response of hyporheic biofilms to temperature changes and dissolved organic carbon enrichment: a mesocosm study

PurposeHyporheic biofilms are the central site for biogeochemical cycling in streams and rivers. In view of global warming and increasing human pressures, this study aimed to compare the response of hyporheic biofilm biomass and activities from an unpolluted reference stream reach surrounded by forest with those from a stream reach exposed to agricultural and urban land use using a mesocosm experiment in which the water temperature and dissolved organic carbon (DOC) contents were manipulated.MethodsHyporheic sediments collected in the field from the two study reaches (i.e. reference and impacted) were incubated in the laboratory at two different temperatures (10 °C, 14 °C) and wetted with three types of synthetic water (control [C] – 0 mg L−1; low DOC – 5 mg L−1; high DOC – 30 mg L−1) for four weeks. The responses of the hyporheic biofilms were measured weekly using structural (total protein content [TPC] as a proxy for biofilm biomass) and functional measures (electron transport system activity [ETSA] and community-level physiological profiling [CLPP]).ResultsThe response of hyporheic biofilms to temperature changes and DOC enrichment was site-specific for all studied measures (TPC, ETSA and CLPP, including measured average well colour development [AWCD]). The addition of DOC to biofilms from the pristine stream reach significantly heightened the responses at 10 °C, a temperature within the normal environmental temperature ranges of the reference location, but not at 14 °C, which was here, a temperature outside normal environmental range. On the other hand, biofilms from the impacted stream reach exhibited increased responses following DOC enrichment under both temperature regimes, with a particularly pronounced response at 14 ºC, in this case, both experimental temperatures were within the normal environmental temperature ranges of the study locations.ConclusionHyporheic biofilms were shown to be, like benthic biofilms, sensitive to temperature changes and organic enrichment, but their response to temperature changes and enrichment caused by climate change and/or other anthropogenic pressures (i.e. point and non-point pollution, removal of the riparian zone, hydromorphological modifications, etc.) was not simply linear but site-specific. The intensity of the response, characterized by increased activity and biomass production, appears to be constrained within the temperature ranges prevalent in the environment from which the biofilms originate. These findings emphasize the importance of site-specific considerations in predicting the impacts of climate change and anthropogenic pressures on these critical components of river and stream ecosystems.

Drivers of autochthonous malaria cases over time: could the Central European present the African future?

BackgroundResults of spatial and temporal comparison of malaria hotspots and coldspots could improve the health measures of malaria control and eradication strategies. The study aimed to reveal the spatially and temporally independent correlations between the potentially most effective background variables and the number of autochthonous malaria cases.MethodsRelationships between malaria cases and background variables were studied in 2 km × 2 km sized quadrates (10 Central European and 10 African). In addition to the current habitat structure of the African sites, annual precipitation, and annual mean temperature, data of the above parameters detected in the nineteenth and twentieth centuries and currently in the Central European sites were included in the analyses (n = 40). Mann–Whitney tests, Principal Component Analysis, and Generalized Linear Models were used for the examinations.ResultsIn addition to the apparent significant positive correlation of malaria cases with annual rainfall and mean temperature, several correlations were found for habitat parameters. The cover of marshlands in the 19th-century habitat structure of Central European quadrates was considerably the same as in the recent African ones. The extent of rural residential areas was significantly smaller in the 19th-century habitat structure of Central European quadrats than in present-day African ones. According to the revealed correlations, the surface cover of rural residential areas is the main driver of the number of autochthonous malaria cases that we can directly impact.ConclusionsThe study confirmed with historical comparison that not only the annual rainfall and mean temperature, the cover of marshlands and other habitats with breeding sites, but also the elements of the rural human environment play a significant role in the high number of autochthonous malaria cases, probably through the concentration and enhancing sites for vector mosquitoes. The latter confirms that a rapid urbanization process could reduce malaria cases in the most infected areas of Africa. Until the latter happens, extensive biological control of Anopheles larvae and chemical control (both outdoor and indoor) of their imagoes, further mosquito nets, repellents, and carbon dioxide traps will need to be applied more widely in the most heavily infested areas.

Osteoarthritis in Older Adults: Is More Emphasis on Managing and Mitigating its Stressful Ramifications, and Enhancing Coping, and Self Efficacy Cognitions Indicated?

Efforts to mitigate or prevent painful disabling osteoarthritis have been pursued for more than a century with limited success. This current overview briefly summarizes how selected beliefs and behaviors, including coping and stress management approaches are potential mediators or moderators of osteoarthritis pain and its overall common adverse prognosis and outcome. Published data housed predominantly in PUBMED, PUBMED CENTRAL, SCIENCE DIRECT, and GOOGLE SCHOLAR sites and pertaining to selected aspects of the literature of current interest, cumulative results reported as of May 30, 2024, show a modest to strong rationale exists for considering the abovementioned factors in efforts to reduce pain and enable daily functions. Accordingly this line of research should be continued, and translated clinically without undue delay, especially in the face of increases in the aging population and osteoarthritis prevalence and undue suffering.

Relationship between indoor and outdoor temperature and humidity in a residential building in Central Europe

Relative humidity and temperature in indoor spaces are two important environmental factors that not only determine the behaviour and well-being of building occupants but also influence airborne transmission of respiratory diseases in closed spaces. While recent studies have examined how well indoor conditions relate to outdoor ambient weather, most studies on weather-related health effects still use a single central site monitor such as a weather station since outdoor values are more convenient to measure. However, the correlation between indoor and outdoor values is not always straightforward. Our case study explores the relationships between indoor and outdoor temperature and humidity in a residential building apartment in a temperate climate in Central Europe. Measurements performed over the period of one year allow for a detailed comparison and analysis of correlations between both daily averages as well as daily profiles of indoor and outdoor variables. The results of this case study add further evidence to the observations that day-to-day variation in indoor temperature and relative humidity are not well-represented by outdoor measurements. It further adds to the growing body of data on indoor environmental variables and should thus prove useful in studies aiming to determine the influence of relative humidity and temperature on indoor transmission of airborne diseases as well as in studies examining the influence of these two variables on the well-being of building occupants.

Rational design of disulfide bonds to improve the thermostability and γ-cyclodextrin production capacity of γ-cyclodextrin glycosyltransferase

The ability of γ-cyclodextrin(γ-CD)to form inclusion complexes with various guest compounds, together with its relatively high solubility, gives γ-CD advantages over both α-cyclodextrin(α-CD) and β-cyclodextrin(β-CD). The thermostability of γ-cyclodextrin glycosyltransferases (γ-CGTase) which can produce γ-CD discovered so far is poor, which is one of the problems limiting its industrial application. To enhance the thermostability of γ-CGTase from Bacillus clarkii 7364, potential disulfide bond mutants were predicted by Disulfide by Design. Five pairs of mutants were constructed by analyzing the predicted results. The t1/2 of S172C-R183C was 2.25 h, which was 3.17 times of WT. Molecular dynamics simulations confirmed that the increase of thermostability of S172C-R183C may be due to the formation of disulfide bond, which leads to the increase of structure rigidity of protein. Then the ability of S172C-R183C mutant to produce cyclodextrins(CDs) was tested. Compared with WT, the maximum CD yield, γ-CD yield and γ-CD specificity of S172C-R183C in the non-complexant catalysed reaction were increased by 6.9 %, 8.8 %, and 2.4 % respectively. In the complexant catalyzed reaction, the CDs yield of S172C-R183C increased by 17.0 %, in which the γ-CD yield increased by 21.7 %, and the γ-CD specificity increased by 3.9 %. Molecular docking results showed that S172C-R183C formed more hydrogen bonds with γ-CD, especially Y186, which was the key central site affecting product specificity. This work involving rational protein engineering provided a new method for adjusting γ-CGTase thermostability.

Travel-time barriers to specialized cancer care for adolescents and young adults with acute lymphoblastic leukemia.

Prior studies demonstrate that 20%-50% of adolescents and young adults (age 15-39 years) with acute lymphoblastic leukemia (ALL) receive care at specialty cancer centers, yet a survival benefit has been observed for patients at these sites. Our objective was to identify patients at risk of severe geographic barriers to specialty cancer center-level care. We used data from the North American Association of Central Cancer Registries Cancer in North America database to identify adolescent and young adult ALL patients diagnosed between 2004 and 2016 across 43 US states. We calculated driving distance and travel time from counties where participants lived to the closest specialty cancer center sites. We then used multivariable logistic regression models to examine the relationship between sociodemographic characteristics of counties where adolescent and young adult ALL patients resided and the need to travel more than 1 hour to obtain care at a specialty cancer center. Among 11 813 adolescent and young adult ALL patients, 43.4% were aged 25-39 years, 65.5% were male, 32.9% were Hispanic, and 28.7% had public insurance. We found 23.6% of adolescent and young adult ALL patients from 60.8% of included US counties would be required to travel more than 1 hour one way to access a specialty cancer center. Multivariable models demonstrate that patients living in counties that are nonmetropolitan, with lower levels of educational attainment, with higher income inequality, with lower internet access, located in primary care physician shortage areas, and with fewer hospitals providing chemotherapy services are more likely to travel more than 1 hour to access a specialty cancer center. Substantial travel-related barriers exist to accessing care at specialty cancer centers across the United States, particularly for patients living in areas with greater concentrations of historically marginalized communities.

CuCo2O4 Nanoflowers with Multiple Enzyme Activities for Treating Bacterium-Infected Wounds via Cuproptosis-like Death.

Nanozyme-driven catalytic therapy provides a promising treatment strategy for bacterial biofilm-infected wounds. However, the single functionality and limited catalytic efficiency of nanozyme-based materials often restrict the effectiveness of wound infection treatment. In this study, CuCo2O4 nanoflowers with multiple enzymatic activities were prepared for antibacterial/antibiofilm treatment by cuproptosis-like death. CuCo2O4 exhibited peroxidase-like (POD-like) and oxidase-like (OXD-like) dual enzyme activities that generated large amounts of •OH and O2•-. Moreover, the glutathione peroxidase-like (GSH-Px-like) activity of CuCo2O4 was able to reduce the overexpression of GSH in the wound microenvironment, enhancing the therapeutic effects of reactive oxygen species (ROS). The morphology of CuCo2O4 was modified using a hydrothermal method with PEG4000 as the solvent, resulting in the exposure of more active center sites and a significant improvement in enzyme catalytic activity. The in vitro results demonstrated the pronounced disruption effect of CuCo2O4 on biofilms formed by bacteria. In vivo, CuCo2O4 significantly promoted angiogenesis, collagen deposition, and cell proliferation. Transcriptome sequencing revealed that elevated ROS levels in bacteria led to cell membrane damage and metabolic disruption. In addition, Cu2+ overload in bacteria induces lipid peroxidation accumulation and disrupts the respiratory chain and tricarboxylic acid (TCA) cycle, ultimately leading to bacterial cuproptosis-like death. This therapeutic strategy, which combines the synergistic effects of multiple enzyme-like activities with cuproptosis-like death, provides an approach for treating biofilm infections.

Pilot study to evaluate automated laboratory data transfer into Medidata Rave for NCI-supported pediatric cooperative group trials in the Pediatric Early Phase Clinical Trials Network (PEP-CTN) and Pediatric Brain Tumor Consortium (PBTC).

e23017 Background: Electronic data capture (EDC) has the potential to improve data accuracy and efficiency. As an initial step toward improvement in the accuracy and completeness of data acquisition for clinical trials, PEP-CTN and PBTC conducted a pilot project to assess the feasibility of automated transfer of laboratory data from participating institutions’ electronic health records to the NCI Medidata Rave EDC that is housed within each consortium’s Uniform Resource Locator (URL). The pilot aimed to assess feasibility of automated laboratory data extraction and transfer and to evaluate discrepancies between laboratory data obtained retrospectively through automated extraction and data manually ascertained during the original conduct of the study. Methods: Data from patients treated on 7 completed PEP-CTN or PBTC trials at 7 sites were included. Each consortium created a Rave EDC study to receive data. Sites used the ExtractEHR R package or local methods to map and extract laboratory data for designated patients. Post-extraction data were uploaded via a file transfer protocol (FTP) periodically polled by the Rave Batch Uploader (BU) that uploaded data into Rave EDC. After successful upload, extracted data (EHR) were compared to laboratory data that had been manually reported when patients were enrolled on the trials (MANUAL) and discrepancies were identified. Discrepancy types were categorized and 2 sites reviewed discrepancies at their sites to identify reasons. Results: Preparation and support for automated extraction and upload required significant central operations and local site effort. All sites successfully extracted specified laboratory data and had at least one complete upload via BU to Rave EDC. There were more laboratory data in the EHR datasets than MANUAL datasets across most sites. These results were due to multiple EHR results on a given day or from additional days in the study window than specified in MANUAL. Sites verified that laboratory data in MANUAL and not EHR were stored in un-extractable formats (e.g. PDFs) or outside laboratories. Most discrepant results in both EHR and MANUAL were mismatched values or units. Conclusions: This pilot demonstrated the feasibility of implementing automated laboratory data extraction and transfer in the cooperative group setting. Automated data transfer requires significant central operational support as well as detailed protocols, data specifications, and case report forms and engagement of site technical teams to be successful, but also permits collection of more comprehensive data with reduced manual data entry. Clinical trial information: NCT05020951 .

Climate therapy: Developing a climate change charter for Cancer Trials Ireland (CTI).

e23214 Background: Climate change is a threat to human existence. Healthcare is the 5th leading cause of CO2 emissions globally, while clinical trials generate the equivalent of half the CO2 emissions of Denmark. Consequently, both enterprises represent significant, potentially modifiable, causes of climate change. In response to this climate toxicity (PMID 36773799), CTI launched the National Green Cancer Clinical Trials Initiative in 2022. A climate charter, which was to consist of a living document of actionable areas, was commissioned by the CTI board to implement them. Methods: Carbon footprint touch points of CTI’s activity on climate change were identified such as travel, procurement, energy use, financial management. An online scoping review of existing academic and non-academic sustainability initiatives, funding agency and national policy documents, peer reviewed and grey literature sources was conducted using the terms climate change and sustainability. Action points were categorised and collated. No exemplar climate charters for clinical trial organisations were identified in the search. Results: 5 pillars of interaction with sustainability initiatives were evident. These were education, engagement, empowerment, embedding, and emphasising. These pillars related to 8 themes for climate smart involvement by CTI staff and members. Personal commitment to sustainability at an individual level eg dietary choices, EU climate pact participation. Trial design and management eg sustainability assessment & integration into protocols Recycling and waste management at central office and sites. Energy and water use eg optimise computing infrastructure, prioritise low carbon sources. Procurement and contracts eg promote green purchasing, integrate environmental and social sustainability clauses in contracts, sustainability assessment of financial services including pensions Meetings and conferences eg prioritising virtual meetings, select conference venues and accommodation with environmental certs. Commuting and business travel. Outreach eg, to University partners, trainees, network with Green Trial groups. Conclusions: The climate charter provides a structure to facilitate sustainability integration at CTI. This living document registers existing activities, highlights areas for engagement, facilitates horizon scanning and outreach to emerging initiatives, empowers staff , and demonstrates an organisational commitment to climate smart, clinical trial conduct.

Optimisation of dose level and vaccination schedule for the VLA15 Lyme borreliosis vaccine candidate among healthy adults: two randomised, observer-blind, placebo-controlled, multicentre, phase 2 studies

Rising Lyme borreliosis incidence rates, potential for severe outcomes, and limitations in accurate and timely diagnosis for treatment initiation suggest the need for a preventive vaccine; however, no vaccine is currently available for human use. We performed two studies in adults to optimise the dose level and vaccination schedule for VLA15, an investigational Lyme borreliosis vaccine targeting outer surface protein A (OspA) serotypes 1-6, which are associated with the most common pathogenic Borrelia species in Europe and North America. Both randomised, observer-blind, placebo-controlled, multicentre phase 2 studies included participants aged 18-65 years without recent history of Lyme borreliosis or tick bites. Study one was conducted at nine clinical research and study centre sites in the USA (n=6), Germany (n=2), and Belgium (n=1); study two was conducted at five of the study one US sites. Based on a randomisation list created by an unmasked statistician for each study, participants were randomly assigned via an electronic case report form randomisation module to receive 90 μg (study one only), 135 μg, or 180 μg VLA15 or placebo by intramuscular injection at months 0, 1, and 2 (study one) or 0, 2, and 6 (study two). Study one began with a run-in phase to confirm safety, after which the Data Safety Monitoring Board recommended the removal of the 90 μg group and continuation of the study. In the study one run-in phase, randomisation was stratified by study site, whereas in the study one main phase and in study two, randomisation was stratified by study site, age group, and baseline B burgdorferi (sensu lato) serostatus. All individuals were masked, other than staff involved in randomisation, vaccine preparation or administration, or safety data monitoring. The primary endpoint for both studies was OspA-specific IgG geometric mean titres (GMTs) at 1 month after the third vaccination and was evaluated in the per-protocol population. Safety endpoints were evaluated in the safety population: all participants who received at least one vaccination. Both studies are registered at ClinicalTrials.gov (study one NCT03769194 and study two NCT03970733) and are completed. For study one, 573 participants were screened and randomly assigned to treatment groups between Dec 21, 2018, and Sept, 26, 2019. For study two, 248 participants were screened and randomly assigned between June 26 and Sept 3, 2019. In study one, 29 participants were assigned to receive 90 μg VLA15, 215 to 135 μg, 205 to 180 μg, and 124 to placebo. In study two, 97 participants were assigned to receive 135 μg VLA15, 100 to 180 μg, and 51 to placebo. At 1 month after the third vaccination (ie, month 3), OspA-specific IgG GMTs in study one ranged from 74·3 (serotype 1; 95% CI 46·4-119·0) to 267·4 units per mL (serotype 3; 194·8-367·1) for 90 μg VLA15, 101·9 (serotype 1; 87·1-119·4) to 283·2 units per mL (serotype 3; 248·2-323·1) for 135 μg, and 115·8 (serotype 1; 98·8-135·7) to 308·6 units per mL (serotype 3; 266·8-356·8) for 180 μg. In study two, ranges at 1 month after the third vaccination (ie, month 7) were 278·5 (serotype 1; 214·9-361·0) to 545·2 units per mL (serotype 2; 431·8-688·4) for 135 μg VLA15 and 274·7 (serotype 1; 209·4-360·4) to 596·8 units per mL (serotype 3; 471·9-754·8) for 180 μg. Relative to placebo, the VLA15 groups had more frequent reports of solicited local adverse events (study one: 94%, 95% CI 91-96 vs 26%, 19-34; study two: 96%, 93-98 vs 35%, 24-49 after any vaccination) and solicited systemic adverse events (study one: 69%, 65-73 vs 43%, 34-52; study two: 74%, 67-80 vs 51%, 38-64); most were mild or moderate. In study one, unsolicited adverse events were reported by 52% (48-57) of participants in the VLA15 groups and 52% (43-60) of those in the placebo groups; for study two these were 65% (58-71) and 69% (55-80), respectively. Percentages of participants reporting serious unsolicited adverse events (study one: 2%, 1-4; study two: 4%, 2-7) and adverse events of special interest (study one: 1%, 0-2; study two: 1%, 0-3) were low across all groups. A single severe, possibly related unsolicited adverse event was reported (worsening of pre-existing ventricular extrasystoles, which resolved after change of relevant concomitant medication); no related serious adverse events or deaths were reported. VLA15 was safe, well tolerated, and elicited robust antibody responses to all six OspA serotypes. These findings support further clinical development of VLA15 using the 180 μg dose and 0-2-6-month schedule, which was associated with the greatest immune responses. Valneva.

The University As Infrastructure of Becoming: Re-Activating Academic Freedom Through Humility in Times of Radical Uncertainty

ABSTRACT Traditionally, the field of science and technology studies (STS) considered the scientific laboratory as the central site of knowledge production and technological development. While providing rich analyses of the social construction of scientific knowledge and the role of non-human actors, STS scholars have often neglected the university – the very context in which laboratories themselves are embedded – as a relevant object of research. In this paper, we argue for re-introducing the university as a relevant category and object of analysis by using the notion of epistemic virtues to link epistemic culture – traditionally the focus of STS – and epistemic structure – traditionally the focus of higher education studies. Advancing this line of argumentation, we make three analytical moves. First, we explore academic freedom as a specific version of negative liberty that extends beyond disciplinary boundaries. We suggest that academics continuously negotiate academic freedom considering culturally and socially situated epistemic virtues such as objectivity and neutrality. Second, we introduce the notion of humility to revisit scientific knowledge production more generally and academic freedom in particular. Finally, we argue that practicing humility leads to enacting the university as an infrastructure of becoming otherwise, thereby enriching our understanding of universities as distinct and highly complex social spaces with a logic of their own.

Engineering multiform quantum state transfers and topological devices in a splicing Su–Schrieffer–Heeger chain

We propose to implement the various kinds of topological quantum state transfers (QSTs) in a splicing Su–Schrieffer–Heeger (SSH) chain, where the transfer forms vary with the introduction of the on-site potential and are distinguished by different output ports. The splicing SSH chain without the on-site potential shows an interface symmetry in chain configuration and supports a zero-energy gap state to realize a symmetric state transfer from the central site to the two ends with equal probabilities. After introducing the on-site potential on one end or two ends, we further obtain two asymmetric versions of the splicing SSH chain. The existence of the on-site potential leads to the transformation of the zero-energy gap state into a nonzero gap state, and the nonzero gap state exhibits different distribution characteristics in two asymmetric versions. Accordingly, three QST channels with different forms in a splicing SSH chain are designed, each of which possesses the robustness against the disorder of the couplings and the inaccuracy of the evolution time. In addition, we demonstrate the scalability of a multiform QST protocol with high fidelity. The protocol with different transfer forms is expected to realize diverse functional quantum devices, which effectively improves the utilization of a splicing SSH chain and economizes the physical resource.

Feasibility of Provision and Vaccine Hesitancy at a Central Hospital COVID-19 Vaccination Site in South Africa after Four Waves of the Pandemic.

As mortality declined significantly during the fourth and fifth waves compared to previous waves, the question of the future role of COVID-19 vaccination arose among both experts and the public in South Africa. Turning attention away from the general public, now considered to be at very low risk of severe COVID-19 disease, a commonly held view was that the vaccination campaign should focus only on those who remain highly vulnerable to severe disease and death from COVID-19. Primary amongst this group are patients with common chronic diseases attending hospital outpatient departments. We hypothesized that providing COVID-19 vaccinations on-site at a central hospital will increase uptake for the patients with co-morbid chronic conditions who need them most in the Omicron phase of the pandemic. Evaluate the acceptability, need, and uptake of a hospital-based vaccination site for patients attending the medical hospital outpatient departments. To assess vaccination uptake, coverage, and hesitancy in people attending a central hospital, to determine factors associated with and influencing vaccination uptake, and to document implementation and assess acceptability of the vaccination project among staff and persons attending the hospital. Mixed-methods study using quantitative and qualitative methods. Of the 317 participants enrolled in the study, 229 (72%) had already received at least one dose of the COVID-19 vaccine. A total of 296 participants were eligible for a first vaccination, additional vaccination, or booster vaccination according to the South African Department of Health guidelines. Of those previously vaccinated, 65% opted for an additional dose on the day it was offered (same day). Only 13 previously unvaccinated participants (15% of vaccine naïve participants) opted for vaccination, increasing vaccine coverage with at least one dose from 72% to 76%. Approximately 24% (n = 75) of all participants refused vaccination (vaccine hesitant). Variables tested for an association with vaccination status demonstrated that age reached statistical significance. Emerging themes in the qualitative analysis included perceptions of vulnerability, vaccine safety and efficacy concerns, information gaps regarding vaccinations, the value of convenience in the decision to vaccinate, and the role of health promoters. This study has shown that it is logistically acceptable to provide a vaccination site at a large hospital targeting patients attending outpatient services for chronic medical conditions. This service also benefits accompanying persons and hospital staff. Access and convenience of the vaccination site influence decision-making, increasing the opportunity to vaccinate. However, vaccine hesitancy is widespread with just under one-quarter of all those offered vaccinations remaining unvaccinated. Strengthening health education and patient-clinician engagement about the benefits of vaccination is essential to reach highly vulnerable populations routinely attending hospital outpatient departments with an appropriate vaccination program.

Histopathological and Biochemical Effects of Methanol and Aqueous Extracts of the Leaf of Irvingia Gabonensis (African wild mango) on the liver of Albino Wistar Rat

Background: The use of Irvingia gabonensis locally for different purposes from eating down to drinking its extracts and concoctions for treating various ailments has been a common practice over the ages. The liver is a very vital metabolic organ and the central site for food and drug metabolism and subsequent excretion. In that case, the understanding of the effects of these foods and drugs both orthodox and herbal is ever invaluable both to the clinicians and the patients. This research work aims to investigate the effects of its leaf extract on the liver using histological and biochemical parameters. Methods: The experimental rats (n=20) used were divided into five (5) groups of four (4) each. Group one served as control and received only water and standard pellets. Groups two and three were administered with the methanolic extract of 150 mg/ kg and 300 mg/kg respectively. Groups four and five were administered with the aqueous extract of 250 mg/kg and 500 mg/kg respectively. The liver samples were harvested, fixed and processed in an automated tissue processor. The blood sample obtained through retro-orbital puncture was made to clot. The serum was then used to analyze the ALT, AST, ALP and Bilirubin content of the liver. Results were obtained and analyzed statistically, showing a significant (p < 0.05) increase in the AST and ALP levels in groups three (3) and five (5). The Serum bilirubin and ALT levels showed insignificant (p > 0.05) increases in all the groups. The photomicrograph indicates mild fibrosis and sinusoidal dilations and cellular infiltrations in groups three and five with no visual changes in the rest of the groups. Conclusion: The findings suggest that at high doses of both methanolic and aqueous extracts (300 and 500mg/kg respectively), the leaf extract is mildly toxic to the liver.

Oxygen Doping Cooperated with Co-N-Fe Dual-Catalytic Sites: Synergistic Mechanism for Catalytic Water Purification within Nanoconfined Membrane.

Atom-site catalysts, especially for graphitic carbon nitride-based catalysts, represents one of the most promising candidates in catalysis membrane for water decontamination. However, unravelling the intricate relationships between synthesis-structure-properties remains a great challenge. This study addresses the impacts of coordination environment and structure units of metal central sites based on Mantel test, correlation analysis, and evolution of metal central sites. An optimized unconventional oxygen doping cooperated with Co-N-Fe dual-sites (OCN Co/Fe) exhibits synergistic mechanism for efficient peroxymonosulfate activation, which benefits from a significant increase in charge density at the active sites and the regulation in the natural population of orbitals, leading to selective generation of SO4 •-. Building upon these findings, the OCN-Co/Fe/PVDF composite membrane demonstrates a 33min-1 ciprofloxacin (CIP) rejection efficiency and maintains over 96% CIP removal efficiency (over 24h) with an average permeance of 130.95Lm-2h-1. This work offers a fundamental guide for elucidating the definitive origin of catalytic performance in advance oxidation process to facilitate the rational design of separation catalysis membrane with improved performance and enhanced stability.

Fish gill chemosensing: knowledge gaps and inconsistencies.

In this review, we explore the inconsistencies in the data and gaps in our knowledge that exist in what is currently known regarding gill chemosensors which drive the cardiorespiratory reflexes in fish. Although putative serotonergic neuroepithelial cells (NEC) dominate the literature, it is clear that other neurotransmitters are involved (adrenaline, noradrenaline, acetylcholine, purines, and dopamine). And although we assume that these agents act on neurons synapsing with the NECs or in the afferent or efferent limbs of the paths between chemosensors and central integration sites, this process remains elusive and may explain current discrepancies or species differences in the literature. To date it has been impossible to link the distribution of NECs to species sensitivity to different stimuli or fish lifestyles and while the gills have been shown to be the primary sensing site for respiratory gases, the location (gills, oro-branchial cavity or elsewhere) and orientation (external/water or internal/blood sensing) of the NECs are highly variable between species of water and air breathing fish. Much of what has been described so far comes from studies of hypoxic responses in fish, however, changes in CO2, ammonia and lactate have all been shown to elicit cardio-respiratory responses and all have been suggested to arise from stimulation of gill NECs. Our view of the role of NECs is broadening as we begin to understand the polymodal nature of these cells. We begin by presenting the fundamental picture of gill chemosensing that has developed, followed by some key unanswered questions about gill chemosensing in general.