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Intrinsically safe designs and a staged transparent development process will be essential.

Over the past two decades, research on bat-associated microbes such as viruses, bacteria and fungi has dramatically increased. Here, we synthesize themes from a conference symposium focused on advances in the research of bats and their microbes, including physiological, immunological, ecological and epidemiological research that has improved our understanding of bat infection dynamics at multiple biological scales. We first present metrics for measuring individual bat responses to infection and challenges associated with using these metrics. We next discuss infection dynamics within bat populations of the same species, before introducing complexities that arise in multi-species communities of bats, humans and/or livestock. Finally, we outline critical gaps and opportunities for future interdisciplinary work on topics involving bats and their microbes.

Introduction: Transmissible vaccines offer a novel approach to suppressing viruses in wildlife populations, with possible applications against viruses that infect humans as zoonoses - Lassa, Ebola, rabies. To ensure safety, current designs propose a recombinant vector platform in which the vector is isolated from the target wildlife population. Because using an endemic vector creates the potential for preexisting immunity to block vaccine transmission, these designs focus on vector viruses capable of superinfection, spreading throughout the host population following vaccination of few individuals., Areas Covered: We present original theoretical arguments that, regardless of its R 0 value, a recombinant vaccine using a superinfecting vector is not expected to expand its active infection coverage when released into a wildlife population that already carries the vector. However, if superinfection occurs at a high rate such that individuals are repeatedly infected throughout their lives, the immunity footprint in the population can be high despite a low incidence of active vaccine infections. Yet we provide reasons that the above expectation is optimistic., Expert Opinion: High vaccine coverage will typically require repeated releases or release into a population lacking the vector, but careful attention to vector choice and vaccine engineering should also help improve transmissible vaccine utility.

Aims and Objectives: The critical care nursing workforce is in crisis, with one-third of critical care nurses worldwide intending to leave their roles. This paper aimed to examine the problem from a wellbeing perspective, offering implications for research, and potential solutions for organisations., Design: Discursive/Position paper., Method: The discussion is based on the nursing and wellbeing literature. It is guided by the authors' collaborative expertise as both clinicians and researchers. Data were drawn from nursing and wellbeing peer-reviewed literature, such as reviews and empirical studies, national surveys and government and thinktank publications/reports., Results: Critical care nurses have been disproportionately affected by the COVID-19 pandemic with studies consistently showing critical care nurses to have the worst psychological outcomes on wellbeing measures, including depression, burnout and post-traumatic stress disorder (PTSD). These findings are not only concerning for the mental wellbeing of critical care nurses, they also raise significant issues for healthcare systems/organisations: poor wellbeing, increased burnout and PTSD are directly linked with critical care nurses intending to leave the profession. Thus, the wellbeing of critical care nurses must urgently be supported. Resilience has been identified as a protective mechanism against the development of PTSD and burnout, thus offering evidence-based interventions that address resilience and turnover have much to offer in tackling the workforce crisis. However, turnover data must be collected by studies evaluating resilience interventions, to further support their evidence base. Organisations cannot solely rely on the efficacy of these interventions to address their workforce crisis but must concomitantly engage in organisational change., Conclusions: We conclude that critical care nurses are in urgent need of preventative, evidence-based wellbeing interventions, and make suggestions for research and practice., (© 2023 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Objective: To evaluate the risk of low gestational weight gain (GWG) in women who use electronic cigarettes (e-cigarettes), combustible cigarettes, or both e-cigarettes and combustible cigarettes (dual use) during pregnancy., Methods: We conducted a secondary analysis of the data from 176 882 singleton pregnancies in the 2016-2020 US Pregnancy Risk Assessment Monitoring System (PRAMS). Postpartum women self-reported their use of e-cigarettes and/or cigarettes during the last 3 months of pregnancy. Low GWG was defined as the total GWG less than 12.7 kg, less than 11.3 kg, less than 6.8 kg, and less than 5.0 kg (<28, <25, <15, and < 11 lb) for women with underweight, normal weight, overweight, and obesity, respectively. We used multivariable logistic regression to estimate the odds ratios (ORs) of low GWG, adjusting for confounders., Results: In this national sample, 921 (weighted percentage, 0.5%) of women were e-cigarette users and 1308 (0.7%) were dual users during late pregnancy. Compared with non-users during late pregnancy (40 090, 22.1%), cigarette users (4499, 28.0%) and dual users (427, 26.0%) had a higher risk of low GWG, but e-cigarette users had a similar risk (237, 22.1%). Adjustment for sociodemographic and pregnancy confounders moderately attenuated these associations: confounder-adjusted ORs 1.26 (95% confidence interval [CI] 1.18-1.35) for cigarette users, 1.18 (95% CI 0.96-1.44) for dual users, and 0.99 (95% CI 0.78-1.27) for e-cigarette users., Conclusions: Unlike combustible cigarette use, e-cigarette use during late pregnancy does not appear to be a risk factor for low GWG., (© 2023 International Federation of Gynecology and Obstetrics.)

Transmissible vaccines are an emerging biotechnology that hold prospects to eliminate pathogens from wildlife populations. Such vaccines would genetically modify naturally occurring, nonpathogenic viruses ("viral vectors") to express pathogen antigens while retaining their capacity to transmit. The epidemiology of candidate viral vectors within the target wildlife population has been notoriously challenging to resolve but underpins the selection of effective vectors prior to major investments in vaccine development. Here, we used spatiotemporally replicated deep sequencing to parameterize competing epidemiological mechanistic models of Desmodus rotundus betaherpesvirus (DrBHV), a proposed vector for a transmissible vaccine targeting vampire bat-transmitted rabies. Using 36 strain- and location-specific time series of prevalence collected over 6 y, we found that lifelong infections with cycles of latency and reactivation, combined with a high R 0 (6.9; CI: 4.39 to 7.85), are necessary to explain patterns of DrBHV infection observed in wild bats. These epidemiological properties suggest that DrBHV may be suited to vector a lifelong, self-boosting, and transmissible vaccine. Simulations showed that inoculating a single bat with a DrBHV-vectored rabies vaccine could immunize >80% of a bat population, reducing the size, frequency, and duration of rabies outbreaks by 50 to 95%. Gradual loss of infectious vaccine from vaccinated individuals is expected but can be countered by inoculating larger but practically achievable proportions of bat populations. Parameterizing epidemiological models using accessible genomic data brings transmissible vaccines one step closer to implementation.

Vaccination is a powerful tool in combating infectious diseases of humans and companion animals. In most wildlife, including reservoirs of emerging human diseases, achieving sufficient vaccine coverage to mitigate disease burdens remains logistically unattainable. Virally vectored "transmissible" vaccines that deliberately spread among hosts are a potentially transformative, but still theoretical, solution to the challenge of immunising inaccessible wildlife. Progress towards real-world application is frustrated by the absence of frameworks to guide vector selection and vaccine deployment prior to major in vitro and in vivo investments in vaccine engineering and testing. Here, we performed deep sequencing on field-collected samples of Desmodus rotundus betaherpesvirus (DrBHV), a candidate vector for a transmissible vaccine targeting vampire bat-transmitted rabies. We discovered 11 strains of DrBHV that varied in prevalence and geographic distribution across Peru. The phylogeographic structure of DrBHV strains was predictable from both host genetics and landscape topology, informing long-term DrBHV-vectored vaccine deployment strategies and identifying geographic areas for field trials where vaccine spread would be naturally contained. Multistrain infections were observed in 79% of infected bats. Resampling of marked individuals over 4 years showed within-host persistence kinetics characteristic of latency and reactivation, properties that might boost individual immunity and lead to sporadic vaccine transmission over the lifetime of the host. Further, strain acquisitions by already infected individuals implied that preexisting immunity and strain competition are unlikely to inhibit vaccine spread. Our results support the development of a transmissible vaccine targeting a major source of human and animal rabies in Latin America and show how genomics can enlighten vector selection and deployment strategies for transmissible vaccines., Competing Interests: The authors have declared that no competing interests exist.

Rabies is a viral zoonosis transmitted by vampire bats across Latin America. Substantial public health and agricultural burdens remain, despite decades of bats culls and livestock vaccinations. Virally vectored vaccines that spread autonomously through bat populations are a theoretically appealing solution to managing rabies in its reservoir host. We investigate the biological and epidemiological suitability of a vampire bat betaherpesvirus (DrBHV) to act as a vaccine vector. In 25 sites across Peru with serological and/or molecular evidence of rabies circulation, DrBHV infects 80-100% of bats, suggesting potential for high population-level vaccine coverage. Phylogenetic analysis reveals host specificity within neotropical bats, limiting risks to non-target species. Finally, deep sequencing illustrates DrBHV super-infections in individual bats, implying that DrBHV-vectored vaccines might invade despite the highly prevalent wild-type virus. These results indicate DrBHV as a promising candidate vector for a transmissible rabies vaccine, and provide a framework to discover and evaluate candidate viral vectors for vaccines against bat-borne zoonoses.

Background High sensitivity cardiac troponin T (hs-cTnT) is a validated marker of myocardial damage and may reflect the degree of silent myocardial ischaemia (SMI) and ventricular strain. Our aim was to compare hs-cTnT levels in black and white South Africans taking SMI into consideration. We further explored the capability of hs-cTnT to predict the presence of compensatory systolic hypertension in this South African cohort. Methods A bi-ethnic sex cohort ( n = 404) with similar socioeconomic status (198 black participants and 206 white participants, aged 20-65 years) participated in this target population study where 24 h ambulatory blood pressure, electrocardiogram and overnight fasting cardiometabolic variables were measured. Results Hypertension, higher glycated haemoglobin levels and more frequent and longer SMI events were observed more often in the black participants. Multivariate linear regression analysis showed positive associations between SMI events [Adj. R 2  = 0.19; β 0.35 (0.08-0.62); p < 0.01], SMI event maximum duration [Adj. R 2  = 0.17, β 0.43 (0.16-0.70), p < 0.01], SMI total duration [Adj. R 2  = 0.12; β 0.37 (0.10; 0.65), p = 0.05] and hs-cTnT in black males only.] A lower hs-cTnT cut-point ≥4.2 pg/ml for 24 h systolic hypertension was predicted in the black participants compared with ≥5.6 pg/ml in the white participants (area under the curve 0.66-67 (95% CI: 0.57-0.75), p < 0.001) with a respective sensitivity/specificity of 64/68% and 61/71%. Conclusions hs-cTnT may be a potential marker of SMI in the prediction of systolic blood pressure increases, as well as clusters of risk factors for cardiovascular disease. Ethnic- and possibly sex-specific references values for hs-cTnT should be considered for risk stratification.

Host specificity has been investigated for centuries in mistletoes, viruses, insects, parasitoids, lice and flukes, yet it is poorly understood. Reviewing the numerous studies on mistletoe host specificity may contribute to our understanding of these plants and put into context the dynamics at work in root parasitic plants and animal parasites. The mechanisms that determine host specificity in mistletoes are not as well documented and understood as those in other groups of parasites. To rectify this, we synthesized the available literature and analyzed data compiled from herbaria, published monographs and our own field studies in South Africa. As for other groups of parasites, multiple factors influence mistletoe host specificity. Initially, pollination affects gene flow. Subsequently, seed dispersal vectors (birds and marsupials), host abundance and compatibility (genetic, morphological, physiological and chemical), history and environmental conditions affect the interaction of mistletoes and their hosts and determine host specificity. Mistletoe-host network analyses and a geographic mosaic approach combined with long-term monitoring of reciprocal transplant experiments, genetic analyses of confined mistletoe populations and comparative phylogenetic studies could provide further insights to our understanding of host specificity. Some of these approaches have been used to study animal-plant interactions and could be adopted to test and evaluate host specificity in mistletoes at local and larger geographic scales., (© The Authors 2016. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Background: Urocortin 2 and urocortin 3 are endogenous peptides with an emerging role in cardiovascular pathophysiology. We assessed their pharmacodynamic profile and examined the role of the endothelium in mediating their vasomotor effects in vivo in man., Methods and Results: Eighteen healthy male volunteers (23±4 years) were recruited into a series of double-blind, randomized crossover studies using bilateral forearm venous occlusion plethysmography during intra-arterial urocortin 2 (3.6 to 120 pmol/min), urocortin 3 (1.2 to 36 nmol/min), and substance P (2 to 8 pmol/min) in the presence or absence of inhibitors of cyclooxygenase (aspirin), cytochrome P450 metabolites of arachidonic acid (fluconazole), and nitric oxide synthase (L-NMMA). Urocortins 2 and 3 evoked arterial vasodilatation (P<0.0001) without tachyphylaxis but with a slow onset and offset of action. Inhibition of nitric oxide synthase with L-NMMA reduced vasodilatation to substance P and urocortin 2 (P≤0.001 for both) but had little effect on urocortin 3 (P>0.05). Neither aspirin nor fluconazole affected vasodilatation induced by any of the infusions (P>0.05 for all). In the presence of all 3 inhibitors, urocortin 2- and urocortin 3-induced vasodilatation was attenuated (P<0.001 for all) to a greater extent than with L-NMMA alone (P≤0.005)., Conclusions: Urocortins 2 and 3 cause potent and prolonged arterial vasodilatation without tachyphylaxis. These vasomotor responses are at least partly mediated by endothelial nitric oxide and cytochrome P450 metabolites of arachidonic acid. The role of urocortins 2 and 3 remains to be explored in the setting of human heart failure, but they have the potential to have major therapeutic benefits., Clinical Trial Registration: http://www.clinicaltrials.gov//. Unique identifier: NCT01096706 and NCT01296607.

Silent myocardial ischemia is a predictor of subclinical atherosclerosis driven by increased cardiovascular risk markers, although still unknown in Africans. The aim of this study was to assess if cardiovascular risk markers will be associated with subclinical atherosclerosis. African men were stratified into (i) 24-hour silent ischemia (SI, n = 38) and (ii) without (nSI, n = 40) groups. Ambulatory blood pressure (BP), SI, 12-lead resting electrocardiogram, ultrasound carotid intima-media thickness (CIMT) measurements, and fasting blood samples were obtained. Above-normal cardiovascular risk markers, that is, glucose level, heart rate, BP, and CIMT, were evident in men with SI. Hypertension prevalence was 89% in the African SI men as opposed to 64% in the nSI men. Regression analyses revealed that only SI events in SI men explained 35% (95% confidence interval [CI]: 0.22;0.52) of the variance in CIMT, while in all African men it explained 29% (95% CI: 0.19;0.39). In conclusion, SI was associated with structural vascular disease in African men. This could imply that SI is not necessarily driven by hypertension in African men but through other possible mechanisms such as increased sympathetic nervous system activity.

Background and Aims: Cross-pollination and satiation of seed predators are often invoked to explain synchronous mast reproduction in long-lived plants. However, explanations for the synchronous death of parent plants are elusive. The roles of synchronous seeding and post-reproductive mortality were investigated in a perennial monocarpic herb (Isoglossa woodii) in coastal dune forest in South Africa., Methods: Pre-dispersal seed predation and seed production were assessed by measuring fruit and seed set of inflorescences sprayed with insecticide or water and with no spray treatments. Seed predation was measured at different densities of I. woodii plants by monitoring removal rates of seed from the forest floor. The influence of adult plants on establishment of I. woodii seedlings was assessed by monitoring growth and survivorship of seedlings in caged and uncaged 1 × 1 m plots in understorey gaps and thickets., Key Results: Fruit and seed set were similar between spray treatments. An I. woodii stem produced 767·8 ± 160·8 seeds (mean ± s.e.) on dune crests and 1359·0 ± 234·4 seeds on the foredune. Seed rain was greater on the foredune than in other topographic locations. Seed predation rates were 32 and 54 % on dune crests and in dune slacks, respectively, and decreased with seed abundance, number of inflorescences per stem and plant height. Seedling recruitment was greater beneath synchronously dying adult plants than in natural understorey gaps (no I. woodii). However, seedling growth rate beneath I. woodii mid-way through its life-cycle was less than in gaps, although survivorship was similar., Conclusions: The selective advantage of masting in I. woodii derives from satiation of both pre- and post-dispersal seed predators. In addition, post-seeding mortality of adult plants facilitates seedling establishment. Satiation of seed predators and the benefits of seedling establishment are strong drivers of the evolution of synchronous monocarpy in I. woodii.

The regeneration niche is commonly partitioned along a gradient from shade-tolerant to shade-intolerant species to explain plant community assembly in forests. We examined the shade tolerance of tree seedlings in a subtropical coastal forest to determine whether the ecological filtering effect of a dominant, synchronously monocarpic herb (Isoglossa woodii) selects for species at either end of the light response continuum during the herb's vegetative and reproductive phases. Photosynthetic characteristics of seedlings of 20 common tree species and the herb were measured. Seedlings were grown in the greenhouse at 12-14% irradiance, and their light compensation points measured using an open-flow gas exchange system. The light compensation points for the tree species were low, falling within a narrow range from 2.1 ± 0.8 μmol m(-2) s(-1) in Celtis africana to 6.4 ± 0.7 μmol m(-2) s(-1) in Allophylus natalensis, indicating general shade tolerance, consistent with a high and narrow range of apparent quantum yield among species (0.078 ± 0.002 mol CO(2) mol(-1) photon). Rates of dark respiration were significantly lower in a generalist pioneer species (Acacia karroo) than in a forest pioneer (C. africana), or in late successional phase forest species. We argue that the general shade tolerance, and phenotypic clustering of shade tolerance, in many tree species from several families in this system, is a result of ecological filtering by the prevailing low light levels beneath the I. woodii understorey, which excludes most light-demanding species from the seedling community.

Synchronous monocarpy in long-lived plants is often associated with pollination by wind, in part because infrequent mass flowering may satiate pollinators. Selfing in synchronous monocarps may provide reproductive assurance but conflict with the benefits of outcrossing, a key evolutionary driver of synchrony. We predicted that animal-pollinated species with synchronous flowering would have unspecialised flowers and attract abundant generalised pollinators, but predictions for selfing and outcrossing frequencies were not obvious. We examined the pollination biology of Isoglossa woodii (Acanthaceae), an insect-pollinated, monocarpic herb that flowers synchronously at 4-7-year intervals. The most frequent visitor to I. woodii flowers was the African honeybee, Apis mellifera adansonii. Hand-pollination failed to enhance seed production, indicating that the pollinators were not saturated. No seed was set in the absence of pollinators. Seed set was similar among selfed and outcrossed flowers, demonstrating a geitonogamous mixed-mating strategy with no direct evidence of preferential outcrossing. Flowers contained four ovules, but most fruits only developed one seed, raising the possibility that preferential outcrossing occurs by post-pollination processes. We argue that a number of the theoretical concerns about geitonogamous selfing as a form of reproductive assurance do not apply to a long-lived synchronous monocarp such as I. woodii.

The Putranjivaceae is an enigmatic family, notable for being the only lineage outside the Capparales to possess the glucosinolate biochemical pathway, which forms the basis of an induced chemical defense system against herbivores (the "mustard oil bomb"). We investigated the pollination biology and floral scent chemistry of Drypetes natalensis (Putranjivaceae), a dioecious subcanopy tree with flowers borne on the stem (cauliflory). Flowering male trees were more abundant than female ones and produced about 10-fold more flowers. Flowers of both sexes produce copious amounts of nectar on disc-like nectaries accessible to short-tongued insects. The main flower visitors observed were cetoniid beetles, bees, and vespid wasps. Pollen load analysis indicated that these insects exhibit a high degree of fidelity to D. natalensis flowers. Insects effectively transfer pollen from male to female plants resulting in about 31% of female flowers developing fruits with viable seeds. Cetoniid beetles showed significant orientation toward the scent of D. natalensis flowers in a Y-maze olfactometer. The scents of male and female flowers are similar in chemical composition and dominated by fatty acid derivatives and isothiocyanates from the glucosinolate pathway. The apparent constitutive emission of isothiocyanates raises interesting new questions about their functional role in flowers.

The land crab Gecarcinus quadratus is an engineering species that controls nutrient cycling in tropical forests. Factors regulating their coastal distribution are not fully understood. We quantified land crab distribution during the dry season at Sirena Field Station in Corcovado National Park, Costa Rica, and found that land crab burrow density decreases with increasing distance from the ocean. Leaf litter depth and tree seedling density are negatively correlated with land crab burrow density. Burrows are strongly associated with sand substrate and burrow density is comparatively low in clay substrate. Results suggest that G. quadratus is limited to a narrow coastal zone with sand substrate, and this distribution could have profound effects on plant community structure.

Coastal sandplain heathlands are a rare plant community in the northeastern United States. Salt spray and water availability are likely important factors determining heathland distribution. Field surveys and manipulative experiments were performed to examine heathland species' responses to salt spray and water availability. We surveyed field distributions of four typical heathland species: Solidago puberula, Solidago rugosa, Gaylussacia baccata, and Myrica pensylvanica. The distributions of two native tree species, Pinus rigida and Quercus ilicifolia, were also surveyed because they succeed into coastal heathlands with low disturbance frequency. We then manipulated salt spray and water in the field and measured species' water status, necrosis, and growth responses to the treatments. Predawn xylem pressure potential and necrosis were strongly affected by high salt spray and low water availability. Shoot elongation was also limited in S. puberula and S. rugosa grown in high salt, low water treatments. Gaylussacia baccata and Q. ilicifolia were particularly sensitive to high salt spray and low water, suggesting that they might excluded be from areas with those conditions. The interaction between salt spray and water availability could affect the landscape scale and should be incorporated into conservation management plans.

Sandplain heathlands are disturbance-dependent plant communities that occur infrequently in coastal areas of the northeastern United States. We hypothesize that salt spray plays a role in maintaining the composition of the heathland community by excluding salt-intolerant species close to the ocean. We examined the distributions of Solidago nemoralis, Myrica pensylvanica, Pinus rigida, and Quercus spp. in heathlands and conducted greenhouse studies to determine whether different levels of salt spray tolerance explain patterns found in the field. We found that common heathland forb and shrub species grow closer to the ocean than successional woody species. In greenhouse experiments, these species differ in their water status, necrosis, and growth responses to salt spray. The tree species P. rigida and Q. rubra are more susceptible to salt spray than the common heathland species M. pensylvanica. Our results suggest that salt spray may prevent tree species in heathlands from growing close to the ocean and therefore might be an important factor in maintaining the characteristic community composition of these dwarf shrublands in coastal habitats.

The performance of hybrids depends upon the inheritance and expression of resistance traits. Secondary chemicals are one such resistance trait. In this study, we measured the concentrations of phenolic glycosides and condensed tannins in parental and F1 hybrid willows to examine the sources of chemical variation among hybrids. S. sericea produces phenolic glycosides, salicortin and 2'-cinnamoylsalicortin, and low concentrations of condensed tannin in its leaves. In contrast, S. eriocephala produces no phenolic glycosides but high concentrations of condensed tannins in its leaves. These traits are inherited quantitatively in hybrids. On average, F1 hybrids are intermediate for condensed tannins, suggesting predominantly additive inheritance or balanced ambidirectional dominance of this defensive chemical from the parental species. In contrast, the concentration of phenolic glycosides is lower than the parental midpoint, indicating directional dominance. However, there is extensive variation among F1 hybrids. The concentration of tannin and phenolic glycosides in F1 hybrid families is either (1) lower than the midpoint, (2) higher than the midpoint, or (3) indistinguishable from the midpoint of the two parental taxa. It appears that the production of the phenolic glycosides, especially 2'-cinnamoylsalicortin, is controlled by one or more recessive alleles. We also observed a two-fold or greater difference in concentration between some hybrid families. We discuss how chemical variation may effect the relative susceptibility of hybrid willows to herbivores.

Insulin has been purified from kangaroo pancreas by acidic ethanol extraction, diethyl ether precipitation and gel filtration. The amino-acid sequence of this, the first marsupial insulin to be studied, is reported. It differs from human insulin by only four amino-acid substitutions, all in regions of the molecule previously known to be variable. However, it should be noted that one of these, asparagine for threonine at A8, has not been reported before. Computer comparisons of all 43 insulin sequences reported to date with kangaroo insulin show it to be most closely related to a group of mammalian insulins (dog, pig, cow, human) known to be of high biological potency. The measurement of blood glucose lowering in the rabbit by kangaroo insulin is consistent with this conclusion. Comparisons of amino-acid sequences of other proteins with their kangaroo counterparts show a greater difference, in line with the time of divergence of marsupials. The limited differences observed in insulin and cytochrome c suggest that their structures need to be closely conserved in order to maintain function.