Search

Disorders affecting the neurological and musculoskeletal systems represent international health priorities. A significant impediment to progress in trials of new therapies is the absence of responsive, objective, and valid outcome measures sensitive to early disease changes. A key finding in individuals with neuromuscular and musculoskeletal disorders is the compositional changes to muscles, evinced by the expression of fatty infiltrates. Quantification of skeletal muscle composition by MRI has emerged as a sensitive marker for the severity of these disorders; however, little is known about the composition of healthy muscles across the lifespan. Knowledge of what is ‘typical’ age-related muscle composition is essential to accurately identify and evaluate what is ‘atypical’. This innovative project, known as the MuscleMap, will achieve the first important steps towards establishing a world-first, normative reference MRI dataset of skeletal muscle composition with the potential to provide valuable insights into various diseases and disorders, ultimately improving patient care and advancing research in the field.

The common Deep Eutectic Solvent (DES) ‘ethaline’ (1:2 choline chloride:ethylene glycol) was examined here as a basis for the self-assembly of the surfactant dodecyltrimethylammonium bromide (C12TAB). A phase diagram was constructed, showing evidence for a L1 (micellar) phase, confirmed by tensiometry to have a room temperature critical micelle concentration (CMC) of 1.2 wt.%. Small angle neutron scattering (SANS) measurements indicate formation of interacting globular micelles with slightly smaller apparent radii than in water. The apparent mesophase/multiphase region was studied using SWAXS, demonstrating rich mesoscopic lyotropic liquid crystalline phase behaviour, with evidence for lamellar Lα peaks, alongside potential co-crystalline phases. We attempted to tailor the self-assembly by studying binary DES containing longer diols including 1,2-propanediol, 1,3-propanediol, 1,4-butanediol, and 1,5-pentanediol, and ternary DES where the HBD component was a 1:1 ethylene glycol:diol mixture. However, synchrotron SAXS showed that only ternary ‘propethaline’ mixtures displayed signs of self-assembly and micellization, perhaps due to the reduction in calculated Gordon parameter, which decreases linearly with increasing alkyl chain length. Systematic differences were thus observed in the ability of the solvents to modulate assembly, from globular micelles in ChCl:EG, to weaker assembly in long-tail DES, and complete solubilisation in butaline and pentaline.

Peptide-based hydrogels are of great interest in the biomedical field according to their biocompatibility, simple structure and tunable properties via sequence modification. In recent years, multicomponent assembly of peptides have expanded the possibilities to produce more versatile hydrogels, by blending gelating peptides with different type of peptides to add new features. In the present study, the assembly of gelating P5 peptide SFFSF blended with P21 peptide, SFFSFGVPGVGVPGVGSFFSF, an elastin-inspired peptides or, alternatively, with FF dipeptide, was investigated by oscillatory rheology and different microscopy techniques in order to shed light on the nanotopologies formed by the self-assembled peptide mixtures. Our data show that, depending on the added peptides, cooperative or disruptive assembly can be observed giving rise to distinct nanotopologies to which correspond different mechanical properties that could be exploited to fabricate materials with desired properties.

Managed plantations of saltbush have the potential to increase the productivity and climate resilience of the farming systems of the low rainfall areas of the world, where livestock are important. The objective was to dynamically simulate the behaviour of grazing saltbush plantations with a new modelling capacity in the APSIM framework to enable the dynamic grazing of forage systems. Scenarios simulated included: the choice of plant species growing in the interrow area between shrub-rows, density of saltbush spatial arrangement, locations with different climates and soils, and grazing strategy by sheep. Comparisons of scenarios across systems were insightful during rainfall years when the shrub systems are of high value (i.e., driest/lowest 20% rainfall years in the simulation period). Overall, the efficient grazing of shrubs by dry sheep with little supplementary feeding, required the availability of a large amount of low quality interrow. Shrub plantations with an interrow of standing oats required least supplementation. Summer grazing was the optimal time for grazing shrub plantations in low rainfall years. Plantations with more shrubs relative to interrow increased the need for supplementary feeding but reduced the variation between years. This is one of the first uses of systems modelling to explore forage shrub system designs that maximise the grazing value of shrub plus interrow.

Numerous cases of spontaneous humeral fracture in primiparous dairy cows from New Zealand have prompted the study of the condition to establish probable causes or risk factors associated with the condition. Previous studies identified inadequate protein-calorie malnutrition as an important contributory factor. Earlier case studies also reported that ~50% of cows have low liver and/or serum copper concentration at the time of humeral fracture. Because copper is so closely associated with the formation of collagen cross-links, the aim of this study was to compare collagen and collagen crosslink content in the humerus from primiparous cows with and without humeral fractures and to determine the role of copper in the occurrence of these fractures. Humeri were collected from cows with and without humeral fractures, ground, and the collagen and collagen cross-link content measured using high-performance liquid chromatography. Collagen content was significantly higher in the humeri of cows without humeral fractures, while total collagen crosslink content was significantly higher in the humerus of cows with humeral fractures. These results indicate other factor/s (e.g., protein-calorie undernutrition) might be more important than the copper status in the occurrence of humeral fractures in dairy cows in New Zealand.

This article describes the radiation facilities and associated sample preparation, management, and analysis equipment currently in place at the Dalton Cumbrian Facility, a facility which opened in 2011 to support the UK’s nuclear industry. Examples of measurements performed using these facilities are presented to illustrate their versatility and the breadth of research they make possible. Results are presented from research which furthers our understanding of radiation damage to polymeric materials, radiolytic yield of gaseous products in situations relevant to nuclear materials, radiation chemistry in light water reactor cooling systems, material chemistry relevant to immobilization of nuclear waste, and radiation-induced corrosion of fuel cladding elements. Applications of radiation chemistry relevant to health care are also described. Research concerning the mechanisms of radioprotection by dietary carotenoids is reported. An ongoing open-labware project to develop a suite of modular sample handling components suited to radiation research is described, as is the development of a new neutron source able to provide directional beams of neutrons.

Non-fungible tokens (NFTs) make it technically possible for digital assets to be owned and traded, introducing the concept of scarcity in the digital realm for the first time. Resulting from this technical development, this paper asks the question, do they provide an opportunity for fundraising for galleries, libraries, archives and museums (GLAM), by selling ownership of digital copies of their collections? Although NFTs in their current format were first invented in 2017 as a means for game players to trade virtual goods, they reached the mainstream in 2021, when the auction house Christie’s held their first-ever sale exclusively for an NFT of a digital image, that was eventually sold for a record 69 million USD. The potential of NFTs to generate significant revenue for artists and museums by selling effectively a cryptographically signed copy of a digital image (similar to real-world limited editions, which are signed and numbered copies of a given artwork), has sparked the interest of the financially deprived museum and heritage sector with world-renowned institutions such as the Uffizi Gallery and the Hermitage Museum, having already employed NFTs in order to raise funds. Concerns surrounding the environmental impact of blockchain technology and the rise of malicious projects, exploiting previously digitised heritage content made available through OpenGLAM licensing, have attracted criticism over the speculative use of the technology. In this paper, we present the current state of affairs in relation to NFTs and the cultural heritage sector, identifying challenges, whilst highlighting opportunities that they create for revenue generation, in order to help address the ever-increasing financial challenges of galleries and museums.

The isothiourea-catalyzed enantioselective 1,6-conjugate addition of para-nitrophenyl esters to 2,6-disubstituted para-quinone methides is reported. para-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the para-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of para-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides at up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er).

Insects harbor a variety of maternally inherited bacterial symbionts. As such, variation in symbiont presence/absence, in the combinations of harbored symbionts, and in the genotypes of harbored symbiont species provide heritable genetic variation of potential use in the insects’ adaptive repertoires. Understanding the natural importance of symbionts is challenging but studying their dynamics over time can help to elucidate the potential for such symbiont-driven insect adaptation. Toward this end, we studied the seasonal dynamics of six maternally transferred bacterial symbiont species in the multivoltine pea aphid (Acyrthosiphon pisum). Our sampling focused on six alfalfa fields in southeastern Pennsylvania, and spanned 14 timepoints within the 2012 growing season, in addition to two overwintering periods. To test and generate hypotheses on the natural relevance of these non-essential symbionts, we examined whether symbiont dynamics correlated with any of ten measured environmental variables from the 2012 growing season, including some of known importance in the lab. We found that five symbionts changed prevalence across one or both overwintering periods, and that the same five species underwent such frequency shifts across the 2012 growing season. Intriguingly, the frequencies of these dynamic symbionts showed robust correlations with a subset of our measured environmental variables. Several of these trends supported the natural relevance of lab-discovered symbiont roles, including anti-pathogen defense. For a seventh symbiont—Hamiltonella defensa—studied previously across the same study periods, we tested whether a reported correlation between prevalence and temperature stemmed not from thermally varying host-level fitness effects, but from selection on co-infecting symbionts or on aphid-encoded alleles associated with this bacterium. In general, such “hitchhiking” effects were not evident during times with strongly correlated Hamiltonella and temperature shifts. However, we did identify at least one time period in which Hamiltonella spread was likely driven by selection on a co-infecting symbiont—Rickettsiella viridis. Recognizing the broader potential for such hitchhiking, we explored selection on co-infecting symbionts as a possible driver behind the dynamics of the remaining six species. Out of twelve examined instances of symbiont dynamics unfolding across 2-week periods or overwintering spans, we found eight in which the focal symbiont underwent parallel frequency shifts under single infection and one or more co-infection contexts. This supported the idea that phenotypic variation created by the presence/absence of individual symbionts is a direct target for selection, and that symbiont effects can be robust under co-habitation with other symbionts. Contrastingly, in two cases, we found that selection may target phenotypes emerging from symbiont co-infections, with specific species combinations driving overall trends for the focal dynamic symbionts, without correlated change under single infection. Finally, in three cases—including the one described above for Hamiltonella—our data suggested that incidental co-infection with a (dis)favored symbiont could lead to large frequency shifts for “passenger” symbionts, conferring no apparent cost or benefit. Such hitchhiking has rarely been studied in heritable symbiont systems. We propose that it is more common than appreciated, given the widespread nature of maternally inherited bacteria, and the frequency of multi-species symbiotic communities across insects.

Solar-induced chlorophyll fluorescence (SIF) is increasingly known as an effective proxy for plant photosynthesis, and therefore, has great potential in monitoring gross primary production (GPP). However, the relationship between SIF and GPP remains highly uncertain across space and time. Here, we analyzed the SIF (reconstructed, SIFc)–GPP relationships and their spatiotemporal variability, using GPP estimates from FLUXNET2015 and two spatiotemporally contiguous SIFc datasets (CSIF and GOSIF). The results showed that SIFc had significant positive correlations with GPP at the spatiotemporal scales investigated (p < 0.001). The generally linear SIFc–GPP relationships were substantially affected by spatial and temporal scales and SIFc datasets. The GPP/SIFc slope of the evergreen needleleaf forest (ENF) biome was significantly higher than the slopes of several other biomes (p < 0.05), while the other 11 biomes showed no significant differences in the GPP/SIFc slope between each other (p > 0.05). Therefore, we propose a two-slope scheme to differentiate ENF from non-ENF biome and synopsize spatiotemporal variability of the GPP/SIFc slope. The relative biases were 7.14% and 11.06% in the estimated cumulative GPP across all EC towers, respectively, for GOSIF and CSIF using a two-slope scheme. The significantly higher GPP/SIFc slopes of the ENF biome in the two-slope scheme are intriguing and deserve further study. In addition, there was still considerable dispersion in the comparisons of CSIF/GOSIF and GPP at both site and biome levels, calling for discriminatory analysis backed by higher spatial resolution to systematically address issues related to landscape heterogeneity and mismatch between SIFc pixel and the footprints of flux towers and their impacts on the SIF–GPP relationship.

Paneth cell defects in Crohn’s disease (CD) patients (called the Type I phenotype) are associated with worse clinical outcomes. Recent studies have implicated mitochondrial dysfunction in Paneth cells as a mediator of ileitis in mice. We hypothesized that CD Paneth cells exhibit impaired mitochondrial health and that mitochondrial-targeted therapeutics may provide a novel strategy for ileal CD. Terminal ileal mucosal biopsies from adult CD and non-IBD patients were characterized for Paneth cell phenotyping and mitochondrial damage. To demonstrate the response of mitochondrial-targeted therapeutics in CD, biopsies were treated with vehicle or Mito-Tempo, a mitochondrial-targeted antioxidant, and RNA transcriptome was analyzed. During active CD inflammation, the epithelium exhibited mitochondrial damage evident in Paneth cells, goblet cells, and enterocytes. Independent of inflammation, Paneth cells in Type I CD patients exhibited mitochondrial damage. Mito-Tempo normalized the expression of interleukin (IL)-17/IL-23, lipid metabolism, and apoptotic gene signatures in CD patients to non-IBD levels. When stratified by Paneth cell phenotype, the global tissue response to Mito-Tempo in Type I patients was associated with innate immune, lipid metabolism, and G protein-coupled receptor (GPCR) gene signatures. Targeting impaired mitochondria as an underlying contributor to inflammation provides a novel treatment approach for CD.

This study investigated the expression of components of the renin-angiotensin system (RAS) by cancer stem cells (CSCs) we have recently demonstrated in renal clear cell carcinoma (RCCC). Fifteen RCCC tissue samples underwent immunohistochemical staining for components of the RAS: renin, pro-renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), and angiotensin II receptor 2 (AT2R). Immunofluorescence co-staining or double immunohistochemical staining of these components of the RAS with stemness-associated markers OCT4 or KLF4 was performed on two of the samples. Protein and transcript expression of these components of the RAS in six RCCC tissue samples was investigated using western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, angiotensin II receptor 1 (AT1R) was investigated using RT-qPCR only. Immunohistochemical staining demonstrated expression of renin, PRR, and ACE2 in 11, 13, and 13 out of 15 RCCC samples, respectively, while AT2R was expressed in all 15 samples. ACE was detected in the endothelium of normal vasculature only. Double immunohistochemical staining demonstrated localization of ACE2, but not renin, to the KLF4+ CSCs. Immunofluorescence staining showed localization of PRR and AT2R to the OCT4+ CSCs. Western blotting confirmed protein expression of all components of the RAS except renin. RT-qPCR demonstrated transcript expression of all components of the RAS including AT1R, but not AT2R, in all six RCCC tissue samples. This study demonstrated expression of PRR, ACE2, and AT2R by the CSCs within RCCC. Further studies may lead to novel therapeutic targeting of CSCs by manipulation of the RAS in the treatment of this aggressive cancer.

(1) Psychology must play an important role in the prevention and management of the COVID-19 pandemic. The aim of the present study was to examine associations between the perceptions of information overload and wellbeing in China during the initial phase of COVID-19. (2) Methods: The present research involved a cross-sectional online survey, which controlled for established predictors of wellbeing and the perception of general (not COVID-19-specific) information overload. The setting of the research was China, February 2020. A total of 1349 participants completed an online survey, and the results from 1240 members of the general public who stated that they were uninfected are reported here (55.6% female; 49.4% single; age distribution: 17–25 years: 26%; 26–30 years: 24.3%; 31–40 years: 23.9%; 41–50 years: 16.2%; 51 years+: 9.6%; the most frequent occupations were: 21.5% students; 19.5% teachers; 25.9% office workers; 10.8% managers, plus a few in a wide range of jobs). The outcomes were positive wellbeing (positive affect and life satisfaction) and negative wellbeing (stress, negative affect, anxiety and depression). (3) Results: Regressions were carried out, controlling for established predictors of wellbeing (psychological capital, general information overload, positive and negative coping). Spending time getting information about COVID-19 was associated with more positive wellbeing. In contrast, perceptions of COVID-19 information overload and feeling panic due to COVID-19 were associated with more negative wellbeing. (4) Conclusions: These results have implications for the communication of information about COVID-19 to the general public and form the basis for further research on the topic.

Odontarrhena serpyllifolia (Desf.) Jord. & Fourr. (=Alyssum serpyllifolium Desf.) occurs in the Iberian Peninsula and adjacent areas on a variety of soils including both limestone and serpentine (ultramafic) substrates. Populations endemic to serpentine are known to hyperaccumulate nickel, and on account of this remarkable phenotype have, at times, been proposed for recognition as taxonomically distinct subspecies or even species. It remains unclear, however, to what extent variation in nickel hyperaccumulation within this taxon merely reflects differences in the substrate, or whether the different populations show local adaptation to their particular habitats. To help clarify the physiological basis of variation in nickel hyperaccumulation among these populations, 3 serpentine accessions and 3 limestone accessions were cultivated hydroponically under common-garden conditions incorporating a range of Ni concentrations, along with 2 closely related non-accumulator species, Clypeola jonthlaspi L. and Alyssum montanum L. As a group, serpentine accessions of O. serpyllifolia were able to tolerate Ni concentrations approximately 10-fold higher than limestone accessions, but a continuous spectrum of Ni tolerance was observed among populations, with the least tolerant serpentine accession not being significantly different from the most tolerant limestone accession. Serpentine accessions maintained relatively constant tissue concentrations of Ca, Mg, K, and Fe across the whole range of Ni exposures, whereas in the limestone accessions, these elements fluctuated widely in response to Ni toxicity. Hyperaccumulation of Ni, defined here as foliar Ni concentrations exceeding 1g kg−1 of dry biomass in plants not showing significant growth reduction, occurred in all accessions of O. serpyllifolia, but the higher Ni tolerance of serpentine accessions allowed them to hyperaccumulate more strongly. Of the reference species, C. jonthlaspi responded similarly to the limestone accessions of O. serpyllifolia, whereas A. montanum displayed by far the lowest degree of Ni tolerance and exhibited low foliar Ni concentrations, which only exceeded 1 g kg−1 in plants showing severe Ni toxicity. The continuous spectrum of physiological responses among these accessions does not lend support to segregation of the serpentine populations of O. serpyllifolia as distinct species. However, the pronounced differences in degrees of Ni tolerance, hyperaccumulation, and elemental homeostasis observed among these accessions under common-garden conditions argues for the existence of population-level adaptation to their local substrates.

(1) Background: During the COVID-19 pandemic, strict lock-down and quarantine were widely imposed by most governments to minimize the spread of the virus. Previous studies have investigated the consequences of the quarantine and social isolation on mental health and the present study examines loneliness and problematic internet use. (2) Methods: The current research used a cross-sectional survey during a lock-down phase of the COVID-19 pandemic. A sample of 593 participants from the Middle East region (Kuwait, Saudi Arabia) were tested using the short form of the Revised UCLA Loneliness Scale and the Internet Addiction Test. (3) Results: Results from regression analyses showed an association between loneliness and Problematic Internet Use (PIU), and an association between loneliness and the number of hours spent online. Younger participants reported greater loneliness. The quality of the relationship with the person(s) with whom they were spending their lock-down was also correlated with loneliness. Those who reported greater loneliness also obtained frequent news about the pandemic from social media. Problematic internet use was associated with loneliness and the predictors of loneliness. ANOVA analyses showed a dose-response between the predictors and PIU. (4) Conclusions: This study highlights the influence of the social characteristics of the local culture during the COVID-19 lock-down on feelings of loneliness and on PIU.

As an important vegetation canopy parameter, the leaf area index (LAI) plays a critical role in forest growth modeling and vegetation health assessment. Estimating LAI is helpful for understanding vegetation growth and global ecological processes. Machine learning methods such as k-nearest neighbors (kNN) and random forest (RF) with remote sensing images have been widely used for mapping LAI. However, the accuracy of mapping LAI in arid and semi-arid areas using these methods is limited due to remote and large areas, the high cost of collecting field data, and the great spatial variability of the vegetation canopy. Here, a novel and modified kNN method was presented for mapping LAI in arid and semi-arid areas of China using Sentinel-2 and Landsat 8 images with field data collected in Ganzhou and Kangbao of China. The modified kNN was developed by integrating the traditional kNN estimation and RF classification. The results were compared with those from kNN and RF regression alone using three sets of input predictors: (i) spectral reflectance bands (input 1); (ii) vegetation indices (input 2); and (iii) a combination of spectral reflectance bands and vegetation indices (input 3). Our analysis showed that in Ganzhou, the red-edge bands of the Sentinel-2 image had a high correlation with LAI. Using the red-edge band-derived vegetation indices increased the accuracy of mapping LAI compared with using other spectral variables. Among the three sets of input predictors, input 3 resulted in the highest prediction accuracy. Based on the combination, the values of RMSE obtained by the traditional kNN, RF, and modified kNN were 0.526, 0.523, and 0.372, respectively, and the modified kNN significantly improved the accuracy of LAI prediction by 29.3% and 28.9% compared with the kNN and RF alone, respectively. A similar improvement was achieved for input 1 and input 2. In Kangbao, the improvement of the prediction accuracy obtained by the modified kNN was 31.4% compared with both the kNN and RF. Therefore, this study implied that the modified kNN provided the potential to improve the accuracy of mapping LAI in arid and semi-arid regions using the images.

The scope and limitations of a tandem N-allylation/[2,3]-rearrangement protocol are investigated through the incorporation of a variety of functional groups within an allylic phosphate precursor. This method uses readily accessible N,N-dimethylglycine aryl esters and functionalized allylic phosphates, forming quaternary ammonium salts in situ in the presence of a palladium catalyst. Subsequent enantioselective [2,3]-sigmatropic rearrangement, promoted by the chiral isothiourea tetramisole, generates α-amino acid derivatives with two contiguous stereocenters. The incorporation of electron-withdrawing ester and amide groups gave the best results, furnishing the desired products in moderate to good yields (29–70%), with low diastereocontrol (typically 60:40 dr) but high enantioselectivity (up to 90:10 er). These results indicate that substrate–catalyst interactions in the proposed transition state are sensitive to the substitution pattern of the substrates.

Background: The odontogenic keratocyst (OKC) is an odontogenic cyst that shows aggressive and intriguing biological behavior. It is suggested that a hypoxic environment occurs in OKC, which led us to investigate the immunoexpression and location of hypoxia-inducible factor 1-alpha (HIF-1α) and other hypoxia-related proteins. Methods: Twenty cases of OKC were evaluated for the expression of Notch homolog 1 (NOTCH1), HIF-1α, disintegrin and metalloproteinase domain-containing protein 12 (ADAM-12), and heparin-binding epidermal growth factor-like growth factor (HBEGF) by immunohistochemistry and compared to eight control cases of calcifying odontogenic cystic (COC), orthokeratinized odontogenic cyst (OOC), and normal oral mucosa (OM) in basal and parabasal layers. Results: In OKC, all the proteins tested were expressed significantly higher in both basal (except for NOTCH1 and HBEGF in OOC) and suprabasal epithelial layers compared to controls. Looking at the epithelial layers within OKC, we observed an increased NOTCH1 and HIF-1α expression in parabasal layers. Conclusions: These results suggest that hypoxia occurs more intensively in OKC compared to COC, OM, and OOC. Hypoxia appeared to be stronger in parabasal layers as observed by higher HIF-1α expression in upper cells. Overexpression of NOTCH1, ADAM-12, and HBEGF in OKC was observed, which suggests that microenvironmental hypoxia could potentially regulate the expression of hypoxia-related proteins, and consequently, its clinical and biological behavior.

Previous research has shown that both experimentally induced upper respiratory tract illnesses (URTIs) and naturally occurring URTIs influence mood and performance. The present study investigated possible cognitive mechanisms underlying the URTI-performance changes. Those who developed a cold (N = 47) had significantly faster, but less accurate, performance than those who remained healthy (N = 54). Illness had no effect on manipulations designed to influence encoding, response organisation (stimulus-response compatilibility) or response preparation. Similarly, there was no evidence that different components of working memory were impaired. Overall, the present research confirms that URTIs can have an effect on performance efficiency. Further research is required to identify the physiological and behavioral mechanisms underlying these effects.

CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Previously, we demonstrated the efficacy of CMX001 in protecting New Zealand White rabbits from mortality following intradermal infection with rabbitpox virus as a model for smallpox, monkeypox and for treatment of adverse reactions to smallpox vaccination. Here we extend these studies by exploring different dosing regimens and performing randomized, blinded, placebo-controlled studies. In addition, because rabbitpox virus can be transmitted via naturally generated aerosols (animal to animal transmission), we report on studies to test the efficacy of CMX001 in protecting rabbits from lethal rabbitpox virus disease when infection occurs by animal to animal transmission. In all cases, CMX001 treatment was initiated at the onset of observable lesions in the ears to model the use of CMX001 as a treatment for symptomatic smallpox. The results demonstrate that CMX001 is an effective treatment for symptomatic rabbitpox virus infection. The rabbitpox model has key similarities to human smallpox including an incubation period, generalized systemic disease, the occurrence of lesions which may be used as a trigger for initiating therapy, and natural animal to animal spread, making it an appropriate model.

Degenerative neurological disorders and traumatic brain injuries cause significant damage to quality of life and often impact survival. As a result, novel treatments are necessary that can allow for the regeneration of neural tissue. In this work, a new biomimetic scaffold was designed with potential for applications in neural tissue regeneration. To develop the scaffold, we first prepared a new bolaamphiphile that was capable of undergoing self-assembly into nanoribbons at pH 7. Those nanoribbons were then utilized as templates for conjugation with specific proteins known to play a critical role in neural tissue growth. The template (Ile-TMG-Ile) was prepared by conjugating tetramethyleneglutaric acid with isoleucine and the ability of the bolaamphiphile to self-assemble was probed at a pH range of 4 through 9. The nanoribbons formed under neutral conditions were then functionalized step-wise with the basement membrane protein laminin, the neurotropic factor artemin and Type IV collagen. The conductive polymer polyaniline (PANI) was then incorporated through electrostatic and π–π stacking interactions to the scaffold to impart electrical properties. Distinct morphology changes were observed upon conjugation with each layer, which was also accompanied by an increase in Young’s Modulus as well as surface roughness. The Young’s Modulus of the dried PANI-bound biocomposite scaffolds was found to be 5.5 GPa, indicating the mechanical strength of the scaffold. Thermal phase changes studied indicated broad endothermic peaks upon incorporation of the proteins which were diminished upon binding with PANI. The scaffolds also exhibited in vitro biodegradable behavior over a period of three weeks. Furthermore, we observed cell proliferation and short neurite outgrowths in the presence of rat neural cortical cells, confirming that the scaffolds may be applicable in neural tissue regeneration. The electrochemical properties of the scaffolds were also studied by generating I-V curves by conducting cyclic voltammetry. Thus, we have developed a new biomimetic composite scaffold that may have potential applications in neural tissue regeneration.

In 1995 technology analyst Gartner [1] developed a hype cycle model for the adoption of technology. The cycle comprises five stages from the initial technology trigger through to a final plateau of productivity along a with a peak of inflated expectations, a tough of disillusionment and the slope of enlightenment. The hype cycle is notable technique for plotting and identifying waves of innovation and hype in technology and digital communications. Yet, from where we stand, we can see the waves of innovation becoming increasingly shorter, the troughs less deep and the peaks of expectations higher. The read-write revolution, that is arguably known as Web 2.0, has transformed our experience of using the Internet from a source of information to a means of communication and participation. It has introduced mirror worlds, the cloud, wikitecture, social shaping, connected places, folksonomies and many other terms that I am sure many of us have used in recent grant applications and papers. This is the here and now, all of these technologies are past the technology trigger point and rising up the peak of inflated expectations with a few already heading towards the trough before becoming mainstream and approaching mass adoption. [...]

There is increasing use of digital technologies in urban planning, including in the generation of designs and the participative side of planning. We examine this digital planning by reporting on the application of an experimental online participatory platform in the regeneration of a London housing estate, enabling reflection on participation processes and outcomes. Drawing on lessons learned, the paper synthesises a conceptual representation of online participation and a relational framework for understanding the participatory platform and its context. We subsequently develop a ‘matrix of participative space’, building on Arnstein’s ‘ladder of participation’, to present a two-dimensional framework of online participation, identifying cases of ‘participative deficit’ and ‘democratic deficit’. We conclude with implications for future digital participation in urban planning and design.

The healthcare industry continues to experience high rates of burnout, turnover, and staffing shortages that erode quality care. Interventions that are feasible, engaging, and impactful are needed to improve cultures of support and mitigate harm from exposure to morally injurious events. This quality improvement project encompassed the methodical building, implementation, and testing of RECONN (Reflection and Connection), an organizational intervention designed by an interdisciplinary team to mitigate the impact of moral injury and to increase social support among nurses. This quality improvement project was conducted in a medical intensive care unit (MICU) in a rural, academic medical center. We employed an Evidence-Based Quality Improvement (EBQI) approach to design and implement the RECONN intervention while assessing the feasibility, acceptability, and preliminary effectiveness via surveys (n = 17). RECONN was found acceptable and appropriate by 70% of nurses who responded to surveys. Preliminary effectiveness data showed small to moderate effect sizes for improving social support, moral injury, loneliness, and emotional recovery. Further evaluation is warranted to establish the effectiveness and generalizability of RECONN to other healthcare settings.

Alpha emitters like plutonium pose severe health risks when ingested, damaging DNA and potentially causing cancer. Traditional detection methods require proximity within millimeters of the contamination source, presenting safety risks and operational inefficiencies. Long-range detection through alpha radioluminescence (RL) offers a promising alternative. However, most of the previous experiments have been carried out under controlled conditions that preclude the overwhelming effect of ambient light. This study demonstrates the successful detection of a 3 MBq alpha emitter in an open environment using a compact alpha camera. This camera incorporates a deep-cooled CCD and a low f-number lens system designed to minimize the blue shift effects of filters. Night-time imaging was achieved with a dual-filter system using a sandwich filter assembly centered at 337 nm and 343 nm for capturing alpha RL and subtracting background light, respectively. At night, the alpha source was detected from 1 m away within one minute, and the lowest detection limit can be calculated as 75 kBq. The system was also evaluated under simulated urban lighting conditions. For daytime imaging, a stack of tilted 276 nm short pass filters minimized sunlight interference, enabling the detection of the alpha source at 70 cm within 10 min under indirect sunlight. This research highlights the viability of long-range optical detection of alpha emitters for environmental monitoring in real-world settings.

Malamides (diamide derivatives of malic acid) are prevalent in nature and of significant biological interest, yet only limited synthetic methods to access functionalised enantiopure derivatives have been established to date. Herein, an effective synthetic method to generate this molecular class is developed through in situ formation of spirocyclic β-lactone-oxindoles (employing a known enantioselective isothiourea-catalysed formal [2+2] cycloaddition of C(1)-ammonium enolates and isatin derivatives) followed by a subsequent dual ring-opening protocol (of the β-lactone and oxindole) with amine nucleophiles. The application of this protocol is demonstrated across twelve examples to give densely functionalised malamide derivatives with high enantio- and diastereo-selectivity (up to >95:5 dr and >99:1 er).

Light-curing units (LCUs) are often subject to clinician-determined factors such as infection control barriers (ICBs) and different positionings of the light tip that may reduce their radiant exposure. The objective of this study was to investigate the individual and cumulative effects of ICBs and LCU positioning on light output. One LCU was used, in combination with five different ICBs and five different distances and angles. ICBs were also tested when placed correctly to manufacturers’ guidelines, and with creases or seams obstructing the light tip. All variables were tested in isolation and in combination with other variables. Measurements were taken from a laboratory-grade spectrometer, giving values of radiant exposure, irradiance and spectral emission. All ICBs, angles and distances showed significant reductions in light output compared to the control (p < 0.001). With increasing angle and distance, the light output was decreased further, with the greatest reduction of 80.6% from the control seen at 40° and 8 mm with an incorrectly placed ICB. When used with an ICB, an increasing angle also showed a protective relationship on the light output. When ICBs are used or when an increase in distance/angle is unavoidable, clinicians should consider compensating for the loss in radiant exposure by increasing curing times.

Heavy nuclides like uranium and their decay products are commonly found in nuclear industries and can pose a significant health risk to humans due to their alpha-emitting properties. Traditional alpha detectors require close contact with the contaminated surface, which can be time-consuming, labour-intensive, and put personnel at risk. Remote detection is urgently needed but very challenging. To this end, a candidate detection mechanism is alpha-induced radio-luminescence. This approach uses the emission of photons from radio-ionised excited nitrogen molecules to imply the presence of alpha emitters from a distance. Herein, the use of this phenomenon to remotely image various alpha emitters with unparalleled levels of sensitivity and spatial accuracy is demonstrated. Notably, the system detected a 29 kBq Am-241 source at a distance of 3 m within 10 min. Furthermore, it demonstrated the capability to discern a 29 kBq source positioned 7 cm away from a 3 MBq source at a 2 m distance. Additionally, a ‘sandwich’ filter structure is described that incorporates an absorptive filter between two interference filters to enhance the ambient light rejection. The testing of the system is described in different lighting environments, including room light and inside a glovebox. This method promises safer and more efficient alpha monitoring, with applications in nuclear forensics, waste management and decommissioning.

Complications such as peri-implantitis could ultimately affect the survival of a dental implant. The prevention and treatment of peri-implant diseases require managing bacterial biofilm and controlling environmental risks, including the presence of pro-inflammatory titanium (Ti) particles in the peri-implant niche. Objectives included the evaluation of the size and quantity of Ti particles released from moderately roughened Ti surfaces during common mechanical surface decontamination methods. One hundred and forty moderately roughened Ti discs were divided into seven groups (n = 20 per group); six groups received mechanical decontamination procedures (ultrasonic scaling (US) with a metal tip and poly-ether-ketone (PEEK) under low and medium power settings, air-polishing with erythritol powder, and Ti brush), and the control group underwent air–water spray using a dental triplex. The rinsing solution was collected for Ti mass analysis using inductively coupled plasma mass spectrometry (ICPMS), as well as for Ti particle size and count analysis under scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS). US metal tip instrumentation generated 34.00 ± 12.54 μg and 34.44 ± 6.08 μg of Ti under low and medium power settings, respectively. This amount of Ti generation was significantly higher than other instrumentation methods. The mean Ti particle size of the US groups ranged from 0.89 ± 0.27 μm to 1.25 ± 0.24 μm. No statistically significant difference was found in the particle size among US groups and Ti brush group (1.05 ± 0.11 μm), except for US with the PEEK tip, where a significantly smaller mean particle diameter was found at the low power setting (0.89 ± 0.27 μm). Mechanical instrumentation can produce Ti particulates and modify the implant surfaces. US using a metal tip generated the highest amount of Ti with smaller Ti size particles compared to all other commonly used mechanical surface instrumentations. The EDS analysis confirmed Ti in PEEK US tips. It can be suggested that deterioration from the PEEK US tip and Ti brush, as observed under SEM, is an additional source of Ti release during Ti surface decontamination.

While the use of antibiotics has been reported as extensive in the rearing of agricultural animals, insufficient information is available on the antibiotic residues in animal products and the adverse impact that consistent low-level exposure to antibiotics might have on the human body and its microbiome. The aim of this study was to estimate the antibiotic concentrations that humans are exposed to via their diet using the concentration of antibiotics in animal food products and water and an online survey on dietary intake. A total of 131 participants completed the dietary intake survey, with the majority belonging to the omnivorous diet group (76.3%). Distinct dietary trends were observed in the omnivorous and unknown groups eating animal products, with specific food types dominating each meal: pork (e.g., ham) and dairy products (e.g., milk, yoghurt) during breakfast, beef (e.g., burgers) and chicken (e.g., chicken breast) products during lunch, and fish (e.g., salmon fillet) during dinner. In total, 34 different animal-based food and drink products were tested for the presence of ten different antibiotics. Of all the products tested, over 35% exceeded the acceptable daily antibiotic intake for amoxicillin, ampicillin, and enrofloxacin.

Long time series land cover classification information is the basis for scientific research on urban sprawls, vegetation change, and the carbon cycle. The rapid development of cloud computing platforms such as the Google Earth Engine (GEE) and access to multi-source satellite imagery from Landsat and Sentinel-2 enables the application of machine learning algorithms for image classification. Here, we used the random forest algorithm to quickly achieve a time series land cover classification at different scales based on the fixed land classification sample points selected from images acquired in 2022, and the year-by-year spectral differences of the sample points. The classification accuracy was enhanced by using multi-source remote sensing data, such as synthetic aperture radar (SAR) and digital elevation model (DEM) data. The results showed that: (i) the maximum difference (threshold) of the sample points without land class change, determined by counting the sample points of each band of the Landsat time series from 1986 to 2022, was 0.25; (ii) the kappa coefficient and observed accuracy of the same sensor from Landsat 8 are higher than the results of the TM and ETM+ sensor data from 2013 to 2022; and (iii) the addition of a mining land cover type increases the kappa coefficient and overall accuracy mean values of the Sentinel 2 image classification for a complex mining and forest area. Among the land classifications via multi-source remote sensing, the combined variables of Spectral band + Index + Terrain + SAR result in the highest accuracy, but the overall improvement is limited. The method proposed is applicable to remotely sensed images at different scales and the use of sensors under complex terrain conditions. The use of the GEE cloud computing platform enabled the rapid analysis of remotely sensed data to produce land cover maps with high accuracy and a long time series.

Policing is considered a high-stress occupation due to the demanding nature of the job. Addressing police stress requires a detailed understanding of how psychosocial risk factors influence various aspects of their well-being. Moreover, an analysis of the direct effects of work conditions and the mediating effects of cognitive appraisals is also warranted. Using the Demands–Resources–Individual Effects (DRIVE) model of work-related stress this study investigated the direct effects of work conditions on well-being and also examined the intermediate role of perceived job stress and job satisfaction in the relationship between work conditions and well-being. Five hundred and seventy-eight police officers from the Jamaica Constabulary Force (J.C.F.) completed the questionnaire. Data were analyzed using hierarchical regressions and the Hayes Process tool for mediation analysis. Both perceived job stress and satisfaction mediated the relationship between work conditions and general physical health. Perceived job stress was an indirect pathway through which work conditions influenced psychological distress, whereas job satisfaction was not a significant mediator. In contrast, job satisfaction mediated the relationship between work conditions and positive well-being, but perceived job stress did not. These findings provide significant evidence for periodically monitoring and auditing perceptions of stress and job satisfaction, as they are likely precursors to subsequent health problems.

Work withdrawal behavior is a type of negative reaction when employees face obstacles at work. Its negative impact on individuals and organizations has caught the attention of academic circles and managers. In this study, data from 596 full-time employees were collected using two timepoint measurements one month apart. The internal mechanism of the link between obstructive stress and job withdrawal behavior was analyzed, and the combined effects of work control and cognitive flexibility on the negative effects of obstructive stress were analyzed in terms of the work demand–control–personal model. The results showed that negative work rumination played a complete mediating role between obstructive stress and work withdrawal behavior, and cognitive flexibility, obstructive stress, and work control had a significant three-way interaction. The results suggest that more attention should be paid to the role of employee cognition to avoid employees’ withdrawal behavior in the face of work obstacles. In addition, when providing work resources to employees, the organization should also consider ensuring that work resources can be fully utilized to play a positive role in buffering work obstacles.

Gravel pits are considered potentially hazardous in terms of groundwater quality protection as they represent an open part of the aquifer system, increasing the aquifer’s vulnerability to contamination from the surface. The aim of this research was to determine the biogeochemical processes in gravel pits that have a positive effect on the groundwater quality in the alluvial aquifer in NW Croatia. The aquifer is situated below developed agricultural land, with high groundwater nitrate concentrations having been recorded over the last decades. The differences between two gravel pits and the surrounding groundwater were studied using in situ, hydrochemical, and isotopic parameters (δ15N-NO3 and δ18O-NO3), together with existing microbial data. The analyses of nitrogen species indicated that nitrate attenuation processes take place in gravel pits. Bacterial denitrification and nitrate uptake by algae were responsible for significant decreases in nitrate concentration. These processes were more effective in the inactive gravel pit, which has a longer water residence time and during warm periods, when microbial biomass, abundance, and activity were high. The seasonally variable microbial activity also affected trace metals, removing them from groundwater, possibly through the biosorption of metal ions. The presented research shows that the observed biogeochemical processes are associated with seasonal changes that affect the types and number of microbial communities and the chemical composition of water, resulting in gravel pits being groundwater remediation points.