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Scleractinian corals are colonial animals with a range of life history strategies, making up diverse species assemblages that define coral reefs. We tagged and tracked approximately 30 colonies from each of 11 species during seven trips spanning six years (2009-2015) in order to measure their vital rates and competitive interactions on the reef crest at Trimodal Reef, Lizard Island, Australia. Pairs of species were chosen from five growth forms where one species of the pair was locally rare (R) and the other common (C). The sampled growth forms were massive [Goniastrea pectinata (R) and G. retiformis (C)], digitate [Acropora humilis (R) and A. cf. digitifera (C)], corymbose [A. millepora (R) and A. nasuta (C)], tabular [A. cytherea (R) and A. hyacinthus (C)] and arborescent [A. robusta (R) and A. intermedia (C)]. An extra corymbose species with intermediate abundance, A. spathulata was included when it became apparent that A. millepora was too rare on the reef crest, making the 11 species in total. The tagged colonies were visited each year in the weeks prior to spawning. During visits, two or more observers each took 2-3 photographs of each tagged colony from directly above and on the horizontal plane with a scale plate to track planar area. Dead or missing colonies were recorded and new colonies tagged in order to maintain approximately 30 colonies per species throughout the six years of the study. In addition to tracking tagged corals, 30 fragments were collected from neighboring untagged colonies of each species for counting numbers of eggs per polyp (fecundity); and fragments of untagged colonies were brought into the laboratory where spawned eggs were collected for biomass and energy measurements. We also conducted surveys at the study site to generate size structure data for each species in several of the years. Each tagged colony photograph was digitized by at least two people. Therefore, we could examine sources of error in planar area for both photographers and outliners. Competitive interactions were recorded for a subset of species by measuring the margins of tagged colony outlines interacting with neighboring corals. The study was abruptly ended by Tropical Cyclone Nathan (Category 4) that killed all but nine of the over 300 tagged colonies in early 2015. Nonetheless, these data will be of use to other researchers interested in coral demography and coexistence, functional ecology, and parametrizing population, community and ecosystem models. The data set is not copyright restricted, and users should cite this paper when using the data. Publisher PDF

Galactosyl transferase knock-out pig lungs fail rapidly in baboons. Based on previously identified lung xenograft injury mechanisms, additional expression of human complement and coagulation pathway regulatory proteins, anti-inflammatory enzymes and self-recognition receptors, and knock-down of the β4Gal xenoantigen were tested in various combinations. Transient life-supporting GalTKO.hCD46 lung function was consistently observed in association with either hEPCR (n = 15), hTBM (n = 4), or hEPCR. hTFPI (n = 11), but the loss of vascular barrier function in the xenograft and systemic inflammation in the recipient typically occurred within 24 h. Co-expression of hEPCR and hTBM (n = 11) and additionally blocking multiple pro-inflammatory innate and adaptive immune mechanisms was more consistently associated with survival >1 day, with one recipient surviving for 31 days. Combining targeted genetic modifications to the lung xenograft with selective innate and adaptive immune suppression enables prolonged initial life-supporting lung function and extends lung xenograft recipient survival, and illustrates residual barriers and candidate treatment strategies that may enable the clinical application of other organ xenografts.

Global warming is killing corals; however, the effects of warming on population connectivity, a process fundamental to reef recovery, are largely unexplored. Using a high-resolution (as high as 200 m), empirically calibrated biophysical model of coral larval dispersal for the southern Great Barrier Reef, we show that the increased larval mortality and reduced competency duration under a 2 °C warming alter dispersal patterns, whereas projected changes in large-scale currents have limited effects. Overall, there was on average a 7% decrease in the distance larvae disperse (among-reef interquartile range (IQR), −10% to −4%), an 8% decrease in the number of connections into each reef (IQR, −11% to −3%) and a 20% increase in local retention (IQR, 0% to +49%). Collectively, these shifts imply that 2 °C of warming will reduce inter-reef connectivity, hampering recovery after disturbances and reducing the spread of warm-adapted genes. Such changes make protections more effective locally, but may require reducing spacing between protected areas.

Topological insulator (TI) nanoribbons with proximity-induced superconductivity are a promising platform for Majorana bound states (MBSs). In this work, we consider a detailed modeling approach for a TI nanoribbon in contact with a superconductor via its top surface, which induces a superconducting gap in its surface-state spectrum. The system displays a rich phase diagram with different numbers of end-localized MBSs as a function of chemical potential and magnetic flux piercing the cross section of the ribbon. These MBSs can be robust or fragile upon consideration of electrostatic disorder. We simulate a tunneling spectroscopy setup to probe the different topological phases of top-proximitized TI nanoribbons. Our simulation results indicate that a top-proximitized TI nanoribbon is ideally suited for realizing fully gapped topological superconductivity, in particular when the Fermi level is pinned near the Dirac point. In this regime, the setup yields a single pair of MBSs, well separated at opposite ends of the proximitized ribbon, which gives rise to a robust quantized zero-bias conductance peak., 12 pages, 5 figures

The ability of bacterial pathogens to adapt to host niches is driven by the carriage and regulation of genes that benefit pathogenic lifestyles. Genes that encode virulence or fitness-enhancing factors must be regulated in response to changing host environments to allow rapid response to challenges presented by the host. Furthermore, this process can be controlled by preexisting transcription factors (TFs) that acquire new roles in tailoring regulatory networks, specifically in pathogens. However, the mechanisms underlying this process are poorly understood. The highly conserved Escherichia coli TF YhaJ exhibits distinct genome-binding dynamics and transcriptome control in pathotypes that occupy different host niches, such as uropathogenic E. coli (UPEC). Here, we report that this important regulator is required for UPEC systemic survival during murine bloodstream infection (BSI). This advantage is gained through the coordinated regulation of a small regulon comprised of both virulence and metabolic genes. YhaJ coordinates activation of both Type 1 and F1C fimbriae, as well as biosynthesis of the amino acid tryptophan, by both direct and indirect mechanisms. Deletion of yhaJ or the individual genes under its control leads to attenuated survival during BSI. Furthermore, all three systems are up-regulated in response to signals derived from serum or systemic host tissue, but not urine, suggesting a niche-specific regulatory trigger that enhances UPEC fitness via pleiotropic mechanisms. Collectively, our results identify YhaJ as a pathotype-specific regulatory aide, enhancing the expression of key genes that are collectively required for UPEC bloodstream pathogenesis.

The ability of bacterial pathogens to adapt to host niches is driven by the carriage and regulation of genes that benefit pathogenic lifestyles. Genes that encode virulence or fitness-enhancing factors must be regulated in response to changing host environments to allow rapid response to challenges presented by the host. Furthermore, this process can be controlled by preexisting transcription factors (TFs) that acquire new roles in tailoring regulatory networks, specifically in pathogens. However, the mechanisms underlying this process are poorly understood. The highly conserved

Ecologically beneficial traits in bacteria are encoded by intrinsic and horizontally acquired genes. However, such traits are not universal, and the highly mosaic nature of bacterial genomes requires control at the transcriptional level to drive these processes. It has emerged that regulatory flexibility is widespread in the Escherichia coli species, whereby preexisting transcription factors can acquire new and unrelated roles in regulating beneficial traits. DsdC is the regulator of D-serine tolerance in E . coli , is essential for D-serine catabolism, and is often encoded by two copies in neonatal meningitis–associated E . coli (NMEC). Here, we reveal that DsdC is a global regulator of transcription in NMEC and does not require D-serine for the control of novel beneficial traits. We show that DsdC binds the chromosome in an unusual manner, with many binding sites arranged in clusters spanning entire operons and within gene coding sequences, such as neuO . Importantly, we identify neuO as the most significantly down-regulated gene in a strain deleted for both dsdC copies, in both the presence and absence of D-serine. NeuO is prophage encoded in several NMEC K1 isolates and mediates capsule O -acetylation but has no effect on attachment to or invasion of human brain endothelial cells. Instead, we demonstrate that NeuO provides resistance against K1 bacteriophage attack and that this critical function is regulated by DsdC. This work highlights how a horizontally acquired enzyme that functions in cell-surface modulation can be controlled by an intrinsic regulator to provide a key ecological benefit to an E . coli pathotype.

Ecosystems have always been shaped by disturbances, but many of these events are becoming larger, more severe and more frequent. The recovery capacity of depleted populations depends on the frequency of disturbances, the spatial distribution of mortality and the scale of dispersal. Here, we show that four mass coral bleaching events on the Great Barrier Reef (in 1998, 2002, 2016 and 2017) each had markedly larger disturbance footprints and were less patchy than a severe category 5 tropical cyclone (Cyclone Yasi, 2011). Severely bleached reefs in 2016 and 2017 were isolated from the nearest lightly affected reefs by up to 146 and 200 km, respectively. In contrast, reefs damaged by Cyclone Yasi were on average 20 km away from relatively undisturbed reefs, well within the estimated range of larval dispersal for most corals. Based on these results, we present a model of coral reef disturbance and recovery to examine (1) how the spatial clustering of disturbances modifies large-scale recovery rates; and (2) how recovery rates are shaped by species' dispersal abilities. Our findings illustrate that the spatial footprint of the recent mass bleaching events poses an unprecedented threat to the resilience of coral species in human history, a threat that is even larger than the amount of mortality suggests.

Antibody-mediated rejection has long been known to be one of the major organ failure mechanisms in xenotransplantation. In addition to the porcine α1,3-galactose (α1,3Gal) epitope, N-Glycolylneuraminic acid (Neu5Gc), a sialic acid, has been identified as an important porcine antigen against which most humans have pre-formed antibodies. Here we evaluate GalTKO.hCD46 lungs with an additional cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) gene knock-out (Neu5GcKO) in a xenogeneic ex vivo perfusion model METHODS: Eleven GalTKO.hCD46.Neu5GcKO pig lungs were perfused for up to 6 h with fresh heparinized human blood. Six of them were treated with histamine (H) blocker famotidine and 1-thromboxane synthase inhibitor Benzylimidazole (BIA) and five were left untreated. GalTKO.hCD46 lungs without Neu5GcKO (n = 18: eight untreated and 10 BIA+H treated) served as a reference. Functional parameters, blood, and tissue samples were collected at pre-defined time points throughout the perfusion RESULTS: All but one Neu5GcKO organs maintained adequate blood oxygenation and "survived" until elective termination at 6 h whereas two reference lungs failed before elective termination at 4 h. Human anti-Neu5Gc antibody serum levels decreased during the perfusion of GalTKO.hCD46 lungs by flow cytometry (∼40% IgM, 60% IgG), whereas antibody levels in Neu5GcKO lung perfusions did not fall (IgM p = .007; IgG p .001). Thromboxane elaboration, thrombin generation, and histamine levels were significantly reduced with Neu5GcKO lungs compared to reference in the untreated groups (p = .007, .005, and .037, respectively); treatment with BIA+H masked these changes. Activation of platelets, measured as CD62P expression on circulating platelets, was lower in Neu5GcKO experiments compared to reference lungs (p = .023), whereas complement activation (as C3a rise in plasma) was not altered. MCP-1 and lactotransferin level elevations were blunted in Neu5GcKO lung perfusions (p = .007 and .032, respectively). Pulmonary vascular resistance (PVR) rise was significantly attenuated and delayed in untreated GalTKO.hCD46.Neu5GcKO lungs in comparison to the untreated GalTKO.hCD46 lungs (p = .003) CONCLUSION: Additional Neu5GcKO in GalTKO.hCD46 lungs significantly reduces parameters associated with antibody-mediated inflammation and activation of the coagulation cascade. Knock-out of the Neu5Gc sialic acid should be beneficial to reduce innate immune antigenicity of porcine lungs in future human recipients.

Sustainably managing fisheries requires regular and reliable evaluation of stock status. However, most multispecies reef fisheries around the globe tend to be data-poor and lack research and monitoring capacity (e.g., long-term fishery data), preventing the estimation of sustainable reference points against which stocks can be assessed. Here, combining fish biomass data for more than 2000 coral reefs with catch estimates from 99 jurisdictions, we estimate site-specific sustainable reference points for coral reef fisheries and use these to assess the status of coral reef fish stocks. We reveal that more than half of jurisdictions with available information have stocks of conservation concern, having failed at least one fisheries sustainability benchmark. We quantify the trade-offs between biodiversity, mean fish length, and ecosystem functions relative to key benchmarks and highlight the ecological benefits of increasing sustainability. Our approach yields multispecies sustainable reference points for coral reef fisheries using environmental conditions, a promising means for enhancing the sustainability of the world’s coral reef fisheries.TeaserA global assessment of the sustainability of multispecies reef fisheries indicates that more than half of jurisdictions have failed at least one of two key sustainability benchmarks.

Estimating the angular separation between two incoherent thermal sources is a challenging task for direct imaging, especially when it is smaller than or comparable to the Rayleigh length. In addition, the task of discriminating whether there are one or two sources followed by detecting the faint emission of a secondary source in the proximity of a much brighter one is in itself a severe challenge for direct imaging. Here, we experimentally demonstrate two tasks for superresolution imaging based on quantum state discrimination and quantum imaging techniques. We show that one can significantly reduce the probability of error for detecting the presence of a weak secondary source, especially when the two sources have small angular separations. In this work, we reduce the experimental complexity down to a single two-mode interferometer: we show that (1) this simple set-up is sufficient for the state discrimination task, and (2) if the two sources are of equal brightness, then this measurement can super-resolve their angular separation, saturating the quantum Cram\'er-Rao bound. By using a collection baseline of 5.3~mm, we resolve the angular separation of two sources that are placed 15~$\mu$m apart at a distance of 1.0~m with an accuracy of $1.7\%$--this is between 2 to 3 orders of magnitudes more accurate than shot-noise limited direct imaging., Comment: 17 pages, 16 figures

The phenomenon of diminishing hematocrit after in vivo liver and lung xenotransplantation and during ex vivo liver xenoperfusion has largely been attributed to action by resident liver porcine macrophages, which bind and destroy human erythrocytes. Porcine sialoadhesin (siglec-1) was implicated previously in this interaction. This study examines the effect of porcine genetic modifications, including knockout of the CMAH gene responsible for expression of Neu5Gc sialic acid, on the adhesion of human red blood cells (RBCs) to porcine macrophages. Wild-type (WT) porcine macrophages and macrophages from several strains of genetically engineered pigs, including CMAH gene knockout and several human transgenes (TKO+hTg), were incubated with human RBCs and "rosettes" (≥3 erythrocytes bound to one macrophage) were quantified by microscopy. Our results show that TKO+hTg genetic modifications significantly reduced rosette formation. The monoclonal antibody 1F1, which blocks porcine sialoadhesin, significantly reduced rosette formation by WT and TKO+hTg macrophages compared with an isotype control antibody. Further, desialation of human RBCs with neuraminidase before addition to WT or TKO+hTg macrophages resulted in near-complete abrogation of rosette formation, to a level not significantly different from porcine RBC rosette formation on porcine macrophages. These observations are consistent with rosette formation being mediated by binding of sialic acid on human RBCs to sialoadhesin on porcine macrophages. In conclusion, the data predict that TKO+hTg genetic modifications, coupled with targeting of porcine sialoadhesin by the 1F1 mAb, will attenuate erythrocyte sequestration and anemia during ex vivo xenoperfusion and following in vivo liver, lung, and potentially other organ xenotransplantation.

JSM and MM were supported by the National Science Foundation (NSF)1948946. MD is supported by the Warman Foundation, the Leverhulme Centre for Anthropocene Biodiversity (RC-2018-021) and NSF-NERC grant NE/V009338/1. MM is supported by a Leverhulme Trust Early Career Fellowship (ECF-2021-512). Life-history traits are promising tools to predict species commonness and rarity because they influence a population's fitness in a given environment. Yet, species with similar traits can have vastly different abundances, challenging the prospect of robust trait-based predictions. Using long-term demographic monitoring, we show that coral populations with similar morphological and life-history traits show persistent (decade-long) differences in abundance. Morphological groups predicted species positions along two, well-known life-history axes (the fast-slow continuum and size-specific fecundity). However, integral projection models revealed that density-independent population growth (λ) was more variable within morphological groups, and was consistently higher in dominant species relative to rare species. Within-group λ differences projected large abundance differences among similar species in short timeframes, and were generated by small but compounding variation in growth, survival, and reproduction. Our study shows that easily-measured morphological traits predict demographic strategies, yet small life-history differences can accumulate into large differences in λ and abundance among similar species. Quantifying the net effects of multiple traits on population dynamics is therefore essential to anticipate species commonness and rarity. Publisher PDF

Environmental fluctuations are becoming increasingly volatile in many ecosystems, highlighting the need to better understand how stochastic and deterministic processes shape patterns of commonness and rarity, particularly in high-diversity systems like coral reefs. Here, we analyze reef fish time-series across the Great Barrier Reef to show that approximately 75% of the variance in relative species abundance is attributable to deterministic, intrinsic species differences. Nevertheless, the relative importance of stochastic factors is markedly higher on reefs that have experienced stronger coral cover volatility. By contrast, α-diversity and species composition are independent of coral cover volatility but depend on environmental gradients. Our findings imply that increased environmental volatility on coral reefs erodes assemblage’s niche structure, an erosion that is not detectable from static measures of biodiversity.One-Sentence SummaryCoral cover volatility modulates how stochastic and deterministic processes shape commonness and rarity in coral reef fishes.

We use a superconducting microresonator as a cavity to sense absorption of microwaves by a superconducting quantum point contact defined by surface gates over a proximitized two-dimensional electron gas. Renormalization of the cavity frequency with phase difference across the point contact is consistent with coupling to Andreev bound states. Near pi phase difference, we observe random fluctuations in absorption with gate voltage, related to quantum interference-induced modulations in the electron transmission. Close to pinch-off, we identify features consistent with the presence of a single Andreev bound state and describe the Andreev-cavity interaction using a Jaynes-Cummings model. By fitting the weak Andreev-cavity coupling, we extract similar to GHz decoherence consistent with charge noise and the transmission dispersion associated with a localized state.

PURPOSE: Families play a key role in managing chronic illness. Among chronically ill children, we describe the Patient-Reported Outcomes Measurement Information System (PROMIS) Family Relationships measure over time and its associations with sociodemographics, environmental deprivation, and health. METHODS: Parents of children aged 8-18 years with asthma (n=171), type 1 diabetes (n=199), or sickle cell disease (n=135), recruited in pediatric clinics and emergency departments (ED), completed demographic surveys. Every six months for up to three years, children completed PROMIS Family Relationships, Anxiety, and Depressive Symptoms short forms (T-scores; mean 50, SD=10), and a 5-level health status item. Linear mixed models were fit to estimate associations. RESULTS: Older baseline age was associated with weaker family relationships. For example, for each 3-year higher baseline age, relationships were 3-points weaker for males (−3.0; 95%CI −5.7 to −.0.2) and females (−3.1; 95%CI −6.0 to −0.3) with asthma recruited in the ED. For each 1-unit higher mean overall health, relationships were 4.6 points (95%CI 3.2-6.1) stronger for children with diabetes and about 2 points stronger for children with asthma (2.3; 0.7-3.9) and sickle cell disease (2.1; 0.3-3.9). Family relationships were 0.3-0.5 points weaker for each 1-unit increment in mean anxiety or depressive symptoms across all three diseases. Relationships were not significantly associated with environmental deprivation and generally stable over time. CONCLUSIONS: Family relationships were weaker among older children and generally stable over time, yet fluctuated with physical and mental health. Monitoring PROMIS Family Relationships scores may facilitate referrals for chronically ill children who need support.

Since the first publication of the Essais in Bordeaux in 1580, readers of this work have recognized skepticism underlying the judgment of its author, Michel de Montaigne. Arguing that the Pyrrhonist school of skepticism relies upon cultural diversity, or that Montaigne was influenced by sixteenth-century proto-ethnographic accounts of European travellers to the New World, many scholars of the Essais have read “Des cannibales” (1, 31) as proto-anthropological. In my close reading of this chapter, however, I contend that Montaigne’s rhetorical use of equity, and not his debated practice of a proto-anthropological cultural relativism, shares a special reciprocity with his skeptical judgment in the Essais. Equity, a para-legal procedure that Montaigne used to judge while he was a magistrate in the Bordeaux parlement (1557–70), remains largely underdeveloped in scholarship on the Essais., Depuis la première parution des Essais à Bordeaux en 1580, les lecteurs ont reconnu dans les jugements de leur auteur, Michel de Montaigne, un fondement sceptique. De nombreux spécialistes des Essais ont soutenu que l’école pyrrhoniste du scepticisme reposait sur la diversité culturelle, ou que Montaigne était influencé par les rapports proto-ethnographiques fournis au XVIe siècle par les voyageurs européens au Nouveau Monde ; ils ont ainsi lu « Des cannibales » (1, 31) comme un texte proto-anthropologique. Cependant, dans ma lecture rapprochée de ce chapitre, je soutiens que Montaigne fait jouer dans les Essais une utilisation rhétorique de l’équité par Montaigne, et non pas une pratique, encore à débattre, de relativisme culturel proto-anthropologique, pour établir, en une relation de réciprocité particulière, un dialogue avec le jugement sceptique. L’équité est une procédure para-juridique que Montaigne a utilisée dans l’exercice de ses fonctions comme magistrat au parlement de Bordeaux (1557–70) : cette notion reste néanmoins très peu abordée dans les études sur les Essais.

Consistent survival of life-supporting pig heart xenograft recipients beyond 90 days was recently reported using genetically modified pigs and a clinically applicable drug treatment regimen. If this remarkable achievement proves reproducible, published benchmarks for clinical translation of cardiac xenografts appear to be within reach. Key mechanistic insights are summarized here that informed recent pig design and therapeutic choices, which together appear likely to enable early clinical translation.

Bacterial pathogens employ diverse fitness and virulence mechanisms to gain an advantage in competitive niches. These lifestyle-specific traits require integration into the regulatory network of the cell and are often controlled by pre-existing transcription factors. In this review, we highlight recent advances that have been made in characterizing this regulatory flexibility in prominent members of the Enterobacteriaceae. We focus on the direct global interactions between transcription factors and their target genes in pathogenic Escherichia coli and Salmonella revealed using chromatin immunoprecipitation coupled with next-generation sequencing. Furthermore, the implications and advantages of such regulatory adaptations in benefiting distinct pathogenic lifestyles are discussed.

Neural development requires the orchestration of dynamic changes in gene expression to regulate cell fate decisions. This regulation is heavily influenced by epigenetics, heritable changes in gene expression not directly explained by genomic information alone. An understanding of the complexity of epigenetic regulation is rapidly emerging through the development of novel technologies that can assay various features of epigenetics and gene regulation. Here, we provide a broad overview of several commonly investigated modes of epigenetic regulation, including DNA methylation, histone modifications, noncoding RNAs, as well as epitranscriptomics that describe modifications of RNA, in neurodevelopment and diseases. Rather than functioning in isolation, it is being increasingly appreciated that these various modes of gene regulation are dynamically interactive and coordinate the complex nature of neurodevelopment along multiple axes. Future work investigating these interactions will likely utilize 'multi-omic' strategies that assay cell fate dynamics in a high-dimensional and high-throughput fashion. Novel human neurodevelopmental models including iPSC and cerebral organoid systems may provide further insight into human-specific features of neurodevelopment and diseases.

The integration of semiconductor Josephson junctions (JJs) in superconducting quantum circuits provides a versatile platform for hybrid qubits and offers a powerful way to probe exotic quasiparticle excitations. Recent proposals for using circuit quantum electrodynamics (cQED) to detect topological superconductivity motivate the integration of novel topological materials in such circuits. Here, we report on the realization of superconducting transmon qubits implemented with $(Bi_{0.06}Sb_{0.94})_{2}Te_{3}$ topological insulator (TI) JJs using ultra-high vacuum fabrication techniques. Microwave losses on our substrates with monolithically integrated hardmask, used for selective area growth of TI nanostructures, imply microsecond limits to relaxation times and thus their compatibility with strong-coupling cQED. We use the cavity-qubit interaction to show that the Josephson energy of TI-based transmons scales with their JJ dimensions and demonstrate qubit control as well as temporal quantum coherence. Our results pave the way for advanced investigations of topological materials in both novel Josephson and topological qubits., Comment: A second experimental run allowed for time-domain measurements of a TI-based transmon qubit. In the updated manuscript additional data on qubit control and coherence are included. Taking account of these new results, the focus and the title of the manuscript have been reworked, 14 pages, 10 figures

In an era of increasing antimicrobial resistance, appropriate antimicrobials are essential to optimise patient outcomes. In 2017, antimicrobial use prevalence (AMU) on the two neurosurgical wards in our tertiary teaching hospital varied from 23% on ward A to 33% on ward B with 67% and 100% 'appropriate' prescriptions, respectively. In July 2018, a weekly antimicrobial stewardship multidisciplinary round led by a senior neurosurgery registrar commenced, attended by the antimicrobial stewardship team (AST).This report evaluates whether a multi-disciplinary approach on neurosurgical prescribing was beneficial, specifically in reducing AMU.The following data was collected on AST rounds for 30 weeks in total from August 2018 to July 2019: number of patients on antimicrobials, appropriateness and stewardship actions. A questionnaire was distributed to neurosurgical doctors on two occasions to canvass opinions and attitudes on antimicrobial prescribing.1716 prescriptions were reviewed (mean 57.2 per week). Of these 321 (18.7%) included antimicrobial prescriptions; 200 on ward A (19.8%), and 121 on ward B (17%), representing a decrease in AMU from 2017. The majority of antimicrobial prescriptions, 271 (84.4%) were deemed appropriate. Stewardship actions were taken in 215 (67%) prescriptions.Fifteen questionnaires were completed by neurosurgical doctors. The majority, 87%, stated the AST round was helpful overall. 93% indicated that informal training on the AST round was a source of education in antibiotic prescribing.The weekly AST round provided a timely opportunity for multidisciplinary discussion, implementation of antimicrobial stewardship actions and opportunistic antimicrobial stewardship education.

Petechial development as a result of venous compression has variously been described as acute dermal capillary rupture, mask phenomenon, and Rumpel-Leede Phenomenon. We describe the case of a patient who developed a facial petechial rash following a laparoscopic abdominal hysterectomy in steep Trendelenburg position. We review the physiological effects of laparoscopic surgical techniques and Trendelenburg positioning. These physiological effects lead to cephalad venous compression and are analogous to the venous compression caused by a tourniquet. The circumstances preceding its development and the characteristics of the facial rash lead us to conclude that the patient we present developed facial Rumple-Leede Phenomenon.

The transplantation of organs across species offers the potential to solve the shortage of human organs. While activation of human platelets by human von Willebrand factor (vWF) requires vWF activation by shear stress, contact between human platelets and porcine vWF (pvWF) leads to spontaneous platelet adhesion and activation. This non-physiologic interaction may contribute to the thrombocytopenia and coagulation pathway dysregulation often associated with xenotransplantation of pig organs in nonhuman primates. Pigs genetically modified to decrease antibody and complement-dependent rejection (GTKO.hCD46) were engineered to express humanized pvWF (h*pvWF) by replacing a pvWF gene region that encodes the glycoprotein Ib-binding site with human cDNA orthologs. This modification corrected for non-physiologic human platelet aggregation on exposure to pig plasma, while preserving in vitro platelet activation by collagen. Organs from pigs with h*pvWF demonstrated reduced platelet sequestration during lung (p ≤ .01) and liver (p ≤ .038 within 4 h) perfusion ex vivo with human blood and after pig-to-baboon lung transplantation (p ≤ .007). Residual platelet sequestration and activation were not prevented by the blockade of canonical platelet adhesion pathways. The h*pvWF modification prevents physiologically inappropriate activation of human or baboon platelets by porcine vWF, addressing one cause of the thrombocytopenia and platelet activation observed with xenotransplantation.

Appropriate interpretation of environmental signals facilitates niche specificity in pathogenic bacteria. However, the responses of niche-specific pathogens to common host signals are poorly understood. d-Serine (d-ser) is a toxic metabolite present in highly variable concentrations at different colonization sites within the human host that we previously found is capable of inducing changes in gene expression. In this study, we made the striking observation that the global transcriptional response of three Escherichia coli pathotypes – enterohaemorrhagic E. coli (EHEC), uropathogenic E. coli (UPEC) and neonatal meningitis-associated E. coli (NMEC) – to d-ser was highly distinct. In fact, we identified no single differentially expressed gene common to all three strains. We observed the induction of ribosome-associated genes in extraintestinal pathogens UPEC and NMEC only, and the induction of purine metabolism genes in gut-restricted EHEC, and UPEC indicating distinct transcriptional responses to a common signal. UPEC and NMEC encode dsdCXA – a genetic locus required for detoxification and hence normal growth in the presence of d-ser. Specific transcriptional responses were induced in strains accumulating d-ser (WT EHEC and UPEC/NMEC mutants lacking the d-ser-responsive transcriptional activator DsdC), corroborating the notion that d-ser is an unfavourable metabolite if not metabolized. Importantly, many of the UPEC-associated transcriptome alterations correlate with published data on the urinary transcriptome, supporting the hypothesis that d-ser sensing forms a key part of urinary niche adaptation in this pathotype. Collectively, our results demonstrate distinct pleiotropic responses to a common metabolite in diverse E. coli pathotypes, with important implications for niche selectivity.

Appropriate interpretation of environmental signals facilitates niche specificity in pathogenic bacteria. However, the responses of niche-specific pathogens to common host signals are poorly understood. d-Serine (d-ser) is a toxic metabolite present in highly variable concentrations at different colonization sites within the human host that we previously found is capable of inducing changes in gene expression. In this study, we made the striking observation that the global transcriptional response of three

We report the presentation, operative management and follow-up of a 31-year-old nulliparous woman who experienced a cervical avulsion injury (CAI) during labour. The woman was induced with dinoprostone gel, followed by oxytocin infusion and had a prolonged active phase. During the second stage, fetal decelerations were noted and the consultant asked to make a plan for delivery. When assessing to perform a midpelvic instrumental delivery, a cord of tissue was felt below the fetal head. A caesarean delivery was recommended based on this finding. After delivery, injuries to the broad ligament, posterior lower uterine segment vagina and cervix were repaired. The cervix was retained with the intent that some tissue be salvaged. At 6-week follow-up, transvaginal ultrasound confirmed blood flow in the cervical tissue, though cervical insufficiency was suspected on clinical examination. Our findings reinforce the seriousness of CAI and support conservative surgical management as opposed to trachelectomy or hysterectomy.

The recent dramatic advances in preventing “initial xenograft dysfunction” in pig-to-non-human primate heart transplantation achieved by minimizing ischemia suggests that ischemia reperfusion injury (IRI) plays an important role in cardiac xenotransplantation. Here we review the molecular, cellular, and immune mechanisms that characterize IRI and associated “primary graft dysfunction” in allotransplantation and consider how they correspond with “xeno-associated” injury mechanisms. Based on this analysis, we describe potential genetic modifications as well as novel technical strategies that may minimize IRI for heart and other organ xenografts and which could facilitate safe and effective clinical xenotransplantation.

Coral reef fisheries support the livelihoods of millions of people in tropical countries, despite large-scale depletion of fish biomass. While human adaptability can help to explain the resistance of fisheries to biomass depletion, compensatory ecological mechanisms may also be involved. If this is the case, high productivity should coexist with low biomass under relatively high exploitation. Here we integrate large spatial scale empirical data analysis and a theory-driven modelling approach to unveil the effects of human exploitation on reef fish productivity-biomass relationships. We show that differences in how productivity and biomass respond to overexploitation can decouple their relationship. As size-selective exploitation depletes fish biomass, it triggers increased production per unit biomass, averting immediate productivity collapse in both the modelling and the empirical systems. This 'buffering productivity' exposes the danger of assuming resource production-biomass equivalence, but may help to explain why some biomass-depleted fish assemblages still provide ecosystem goods under continued global fishing exploitation.

Methyl-CpG binding protein 2 (MeCP2) plays fundamental roles in the nervous system, as both gain-of-function and loss-of-function of MECP2 are associated with severe neurological conditions. Understanding the molecular function of MeCP2 will not only provide insights into the pathogenesis of MeCP2-related disorders, but will also shed light on the epigenetic regulation of neuronal function. In the past few years, a number of studies have provided mechanistic evidence that MeCP2 recruits co-repressor complexes to particular sequences of methylated DNA. Additionally, innovative design and high-throughput sequencing technologies have provided opportunities to study the effects of MeCP2 on the neuronal transcriptome at an unprecedented level of detail, demonstrating that MeCP2 modulates gene expression in a context-specific manner. These findings have raised new questions and challenged current models of MeCP2 function. In this review, we describe several recent developments, highlight future challenges, and articulate a model by which MeCP2 functions as an organizer of chromatin architecture to modulate global gene expression in the nervous system.

Changes in disturbance regimes due to climate change are increasingly challenging the capacity of ecosystems to absorb recurrent shocks and reassemble afterwards, escalating the risk of widespread ecological collapse of current ecosystems and the emergence of novel assemblages1–3. In marine systems, the production of larvae and recruitment of functionally important species are fundamental processes for rebuilding depleted adult populations, maintaining resilience and avoiding regime shifts in the face of rising environmental pressures4,5. Here we document a regional-scale shift in stock–recruitment relationships of corals along the Great Barrier Reef—the world’s largest coral reef system—following unprecedented back-to-back mass bleaching events caused by global warming. As a consequence of mass mortality of adult brood stock in 2016 and 2017 owing to heat stress6, the amount of larval recruitment declined in 2018 by 89% compared to historical levels. For the first time, brooding pocilloporids replaced spawning acroporids as the dominant taxon in the depleted recruitment pool. The collapse in stock–recruitment relationships indicates that the low resistance of adult brood stocks to repeated episodes of coral bleaching is inexorably tied to an impaired capacity for recovery, which highlights the multifaceted processes that underlie the global decline of coral reefs. The extent to which the Great Barrier Reef will be able to recover from the collapse in stock–recruitment relationships remains uncertain, given the projected increased frequency of extreme climate events over the next two decades7. A regional-scale shift in the relationships between adult stock and recruitment of corals occurred along the Great Barrier Reef, following mass bleaching events in 2016 and 2017 caused by global warming.

Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent pain in pediatric populations compared with adult populations; thus, data to support treatment efficacy in children are limited. This article evaluates the design features and reporting practices of RCTs for chronic and recurrent pain that are likely unique to, or particularly important in, a pediatric population to promote improvements in the evidence base for pediatric pain treatments. Areas covered include outcome measure selection and reporting and reporting of adverse events and challenges to recruitment and retention. A search of PubMed and EMBASE identified primary publications describing RCTs of treatments for select chronic and recurrent pain conditions in children or adolescents published between 2000 and 2017. Only 49% of articles identified a primary outcome measure. The primary outcome measure assessed pain intensity in 38% of the trials, specifically measure by verbal rating scale (13%), faces pain scale (11%), visual analogue scale (9%), or numeric rating scale (5%). All of the CONSORT harms reporting recommendations were fulfilled by 10%. The goal of this article is to promote comprehensive reporting of pediatric pain RCTs to improve the design of future trials, facilitate conduction of systematic reviews and meta-analyses, and better inform clinical practice. PERSPECTIVE: This review of chronic and recurrent pediatric pain trials demonstrates inadequacies in the reporting quality of key features specifically important to pediatric populations. It provides recommendations that address these shortcomings to promote continued efforts toward improving the quality of the design and publication of future pediatric clinical pain trials.

Anthropogenic climate change is a rapidly intensifying selection pressure on biodiversity across the globe and, particularly, on the world's coral reefs. The rate of adaptation to climate change is proportional to the amount of phenotypic variation that can be inherited by subsequent generations (i.e., narrow-sense heritability, h2 ). Thus, traits that have higher heritability (e.g., h2 > 0.5) are likely to adapt to future conditions faster than traits with lower heritability (e.g., h2

We present the first realisation of simultaneous multi-spectral fluorescence imaging using a single-photon avalanche diode (SPAD) array, where the spectral unmixing is facilitated by a plasmonic metasurface mosaic colour filter array (CFA). A 64 × 64 pixel format silicon SPAD array is used to record widefield fluorescence and brightfield data from four biological samples. A plasmonic metasurface composed of an arrangement of circular and elliptical nanoholes etched into an aluminium thin film deposited on a glass substrate provides the high transmission efficiency CFA, enabling a bespoke spectral unmixing algorithm to reconstruct high fidelity, full colour images from as few as ∼3 photons per pixel. This approach points the way toward real-time, single-photon sensitive multi-spectral fluorescence imaging. Furthermore, this is possible without additional bulky components such as a filter wheel, prism or diffraction grating, nor the need for multiple sample exposures or multiple detectors.

The discovery of multi-species synchronous spawning of scleractinian corals on the Great Barrier Reef in the 1980s stimulated an extraordinary effort to document spawning times in other parts of the globe. Unfortunately, most of these data remain unpublished which limits our understanding of regional and global reproductive patterns. The Coral Spawning Database (CSD) collates much of these disparate data into a single place. The CSD includes 6178 observations (3085 of which were unpublished) of the time or day of spawning for over 300 scleractinian species in 61 genera from 101 sites in the Indo-Pacific. The goal of the CSD is to provide open access to coral spawning data to accelerate our understanding of coral reproductive biology and to provide a baseline against which to evaluate any future changes in reproductive phenology., info:eu-repo/semantics/published

Marine multicellular organisms host a diverse collection of bacteria, archaea, microbial eukaryotes, and viruses that form their microbiome. Such host-associated microbes can significantly influence the host’s physiological capacities; however, the identity and functional role(s) of key members of the microbiome (“core microbiome”) in most marine hosts coexisting in natural settings remain obscure. Also unclear is how dynamic interactions between hosts and the immense standing pool of microbial genetic variation will affect marine ecosystems’ capacity to adjust to environmental changes. Here, we argue that significantly advancing our understanding of how host-associated microbes shape marine hosts’ plastic and adaptive responses to environmental change requires (i) recognizing that individual host–microbe systems do not exist in an ecological or evolutionary vacuum and (ii) expanding the field toward long-term, multidisciplinary research on entire communities of hosts and microbes. Natural experiments, such as time-calibrated geological events associated with well-characterized environmental gradients, provide unique ecological and evolutionary contexts to address this challenge. We focus here particularly on mutualistic interactions between hosts and microbes, but note that many of the same lessons and approaches would apply to other types of interactions., This Essay argues that in order to truly understand how marine hosts benefit from the immense diversity of microbes, we need to expand towards long-term, multi-disciplinary research focussing on few areas of the world’s ocean that we refer to as “natural experiments,” where processes can be studied at scales that far exceed those captured in laboratory experiments.

The sixth Young Microbiologists Symposium on 'Microbe Signalling, Organisation and Pathogenesis' was scheduled to be held at the University of Southampton, UK, in late August 2020. However, due to the health and safety guidelines and travel restrictions as a response to the COVID-19 pandemic, the symposium was transitioned to a virtual format, a change embraced enthusiastically as the meeting attracted over 200 microbiologists from 40 countries. The event allowed junior scientists to present their work to a broad audience and was supported by the European Molecular Biology Organization, the Federation of European Microbiological Societies, the Society of Applied Microbiology, the Biochemical Society, the Microbiology Society and the National Biofilms Innovation Centre. Sessions covered recent advances in all areas of microbiology including: Secretion and transport across membranes, Gene regulation and signalling, Host–microbe interactions, and Microbial communities and biofilm formation. This report focuses on several of the highlights and exciting developments communicated during the talks and poster presentations.

While evolution proceeds through the generation of random variant alleles, the application of selective pressures can select for subsets of mutations that confer fitness-improving physiological benefits. This, in essence, defines the process of adaptive evolution. The rapid replication rate of bacteria has allowed for the design of experiments to study these processes over a reasonable timeframe within a laboratory setting. This has been greatly assisted by advances in tractability of diverse microorganisms, next generation sequencing technologies and bioinformatic analysis pipelines. Examining the processes by which organisms adapt their genetic code to cope with sub-optimal growth conditions has yielded a wealth of molecular insight into diverse biological processes. Here we discuss how the study of adaptive evolutionary trajectories in bacteria has allowed for improved understanding of stress responses, revealed important insight into microbial physiology, allowed for the production of highly optimised strains for use in biotechnology and increased our knowledge of the role of genomic plasticity in chronic infections.

The thoracic outlet is the space between the thorax and axilla through which the subclavian vein, subclavian artery, and brachial plexus travel from their central origins to their peripheral termini. Its bounds include the clavicle, first thoracic rib, insertion of the pectoralis minor muscle onto the coracoid process of the humerus, and the sternum. It contains three areas: the scalene triangle, the costoclavicular space, and the subcoracoid or pectoralis minor space. Aberrant anatomy is common in the thoracic outlet and may predispose patients to compression of the neurovascular bundle and development of clinical thoracic outlet syndrome (TOS). Much of this aberrancy is explained by the embryologic origins of the structures that comprise the thoracic outlet. A thorough understanding of this anatomy and embryology is therefore critical to the understanding of TOS.

The age or size structure of a population has a marked influence on its demography and reproductive capacity. While declines in coral cover are well documented, concomitant shifts in the size-frequency distribution of coral colonies are rarely measured at large spatial scales. Here, we document major shifts in the colony size structure of coral populations along the 2300 km length of the Great Barrier Reef relative to historical baselines (1995/1996). Coral colony abundances on reef crests and slopes have declined sharply across all colony size classes and in all coral taxa compared to historical baselines. Declines were particularly pronounced in the northern and central regions of the Great Barrier Reef, following mass coral bleaching in 2016 and 2017. The relative abundances of large colonies remained relatively stable, but this apparent stability masks steep declines in absolute abundance. The potential for recovery of older fecund corals is uncertain given the increasing frequency and intensity of disturbance events. The systematic decline in smaller colonies across regions, habitats and taxa, suggests that a decline in recruitment has further eroded the recovery potential and resilience of coral populations.

BackgroundThis study aimed to investigate the physiological profile of elite Bicycle Motocross (BMX) cyclists and assess the physiological and perceptual demands of a simulated BMX race. In addition, the neuromuscular fatigue induced by BMX race simulation was investigated.MethodsTwelve male elite BMX cyclists performed two testing sessions. On the first day, incremental submaximal and maximal cycling tests were performed, as well as baseline measurements of muscle contractile qualities, a vertical jump test, short sprint cycling test and Wingate test. Following a recovery period of 48 h, athletes race performance times, physiological intensity and fatigue were determined before and after each heat (4 in total) via muscular evaluations, blood samples and perceptual ratings.ResultsDuring testing, cyclists attained a V̇O2max of 55.7±4.8 ml min-1 kg-1; peak power output during a short cycling sprint of 1498±189 W and average during Wingate of 1344±158 W; counter movement jump peaks were 58.6±7.7 cm (height), 4625±768 W (power) and 64.3±7.5 N kg-1 (force). During the BMX race simulation performance times improved slightly and perceived exertion increased, blood lactate and hydrogen ions concentrations significantly increased across heats while bicarbonate concentrations decreased (PConclusionsElite BMX cyclists show high anaerobic characteristics (Wingate and sprint) and neuromuscular qualities (height and power jump), while the aerobic qualities are not comparable to those typical of road cyclists. BMX races appear to induce metabolic disturbance, peripheral fatigue and increase perceived exertion, however performance times across heats appears not to be affected.