Climate change, social vulnerability and child nutrition in South Asia.

Despite recent advancements in global population well-being and food security, climate change threatens to undermine child nutritional health, particularly for marginalized populations in tropical low- and middle-income countries. South Asia is at particular risk for climate-driven undernutrition due to a combination of historical weather exposures, existing nutritional deficits, and a lack of sanitation access. Previous studies have established that precipitation extremes increase rates of undernutrition in this region, but the existing literature lacks adequate consideration of temperature anomalies, mediating social factors, and the developmentally-relevant timing of exposure. We combine high-resolution temperature and precipitation data with large-sample survey data on household demographics and child anthropometry, using an approach that incorporates three key developmental periods and a rigorous fixed effects design. We find that precipitation extremes in the first year of life significantly decrease children's height-for-age (HAZ) in South Asia. The detrimental effects of extreme precipitation are especially concentrated in under-resourced households, such as those lacking access to proper sanitation and education for women, while anomalous heat is particularly harmful for children in Pakistan, though it tends to benefit children in some demographic groups. These results indicate that nutritional status in South Asia is highly responsive to climate exposures, and that addressing sanitation infrastructure and other development priorities is a pathway towards reducing this vulnerability.

Identification and validation of DOCK4 as a potential biomarker for risk of bone metastasis development in patients with early breast cancer.

Skeletal metastasis occurs in around 75% of advanced breast cancers, with the disease incurable once cancer cells disseminate to bone, but there remains an unmet need for biomarkers to identify patients at high risk of bone recurrence. This study aimed to identify such a biomarker and to assess its utility in predicting response to adjuvant zoledronic acid (zoledronate). We used quantitative proteomics (stable isotope labelling by amino acids in cell culture-mass spectrometry; SILAC-MS) to compare protein expression in a bone-homing variant (BM1) of the human breast cancer cell line MDA-MB-231 with parental non-bone-homing cells to identify novel biomarkers for risk of subsequent bone metastasis in early breast cancer. SILAC-MS showed that dedicator of cytokinesis protein 4 (DOCK4) was upregulated in bone-homing BM1 cells, confirmed by western blotting. BM1 cells also had enhanced invasive ability compared with parental cells, which could be reduced by DOCK4-shRNA. In a training tissue microarray (TMA) comprising 345 patients with early breast cancer, immunohistochemistry followed by Cox regression revealed that high DOCK4 expression correlated with histological grade (p = 0.004) but not oestrogen receptor status (p = 0.19) or lymph node involvement (p = 0.15). A clinical validation TMA used tissue samples and the clinical database from the large AZURE adjuvant study (n = 689). Adjusted Cox regression analyses showed that high DOCK4 expression in the control arm (no zoledronate) was significantly prognostic for first recurrence in bone (HR 2.13, 95%CI 1.06-4.30, p = 0.034). No corresponding association was found in patients who received zoledronate (HR 0.812, 95%CI 0.176-3.76, p = 0.790), suggesting that treatment with zoledronate may counteract the higher risk for bone relapse from high DOCK4-expressing tumours. High DOCK4 expression was not associated with metastasis to non-skeletal sites when these were assessed collectively. In conclusion, high DOCK4 in early breast cancer is significantly associated with aggressive disease and with future bone metastasis and is a potentially useful biomarker for subsequent bone metastasis risk. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Aeromedical retrievals for gastrointestinal disorders in rural and remote Australia: the need for improved access to specialist advice.

The Royal Flying Doctor Service (RFDS) provides medical care to populations without access to traditional health-care services. From 2014 to 2018 the RFDS conducted 6007 (≈1201/year) aeromedical retrievals for gastrointestinal (GI) disorders. More detailed research is needed to determine specific GI disorders that contributed to this caseload, and in particular inform whether the establishment of a GI specialist service is justified.

Future warming and acidification result in multiple ecological impacts to a temperate coralline alga.

Coralline algae are a crucial component of reef systems, stabilising reef substrate, providing habitat and contributing to accretion. Coralline algae and their surface microbial biofilms are also important as settlement cues for marine invertebrates, yet few studies address the impact of future environmental conditions on interactions between coralline algae, reef microbes and settlement by larvae of marine invertebrates. We exposed the temperate coralline algal species Amphiroa gracilis to warming and/or acidification scenarios for 21 days. Algae became bleached but photosystem II function was not measurably impacted. Settlement by larvae of the sea urchin Heliocidaris erythrogramma was reduced and the structure of the prokaryotic community associated with A. gracilis was altered. Coralline algae in ambient conditions were dominated by Alphaproteobacteria from the Rhodobacteraceae including Loktonella; those under warming were dominated by Bacteroidetes and Verrucomicrobia; acidification resulted in less Loktonella and more Planctomycetes and a combination of warming and acidification caused increases in Bacteroidetes, Verrucomicrobia and the Alphaproteobacteria family Hyphomonadaceae. These experiments indicate that predicted future environmental change may reduce the ability of some temperate reef coralline algae and associated reef microbes to facilitate settlement of invertebrate larvae as well as having a direct impact to algae via bleaching.

A gene trap transposon eliminates haematopoietic expression of zebrafish Gfi1aa, but does not interfere with haematopoiesis.

A transposon-mediated gene trap screen identified the zebrafish line qmc551 that expresses a GFP reporter in primitive erythrocytes and also in haemogenic endothelial cells, which give rise to haematopoietic stem and progenitor cells (HSPCs) that seed sites of larval and adult haematopoiesis. The transposon that mediates this GFP expression is located in intron 1 of the gfi1aa gene, one of three zebrafish paralogs that encode transcriptional repressors homologous to mammalian Gfi1 and Gfi1b proteins. In qmc551 transgenics, GFP expression is under the control of the endogenous gfi1aa promoter, recapitulates early gfi1aa expression and allows live observation of gfi1aa promoter activity. While the transposon integration interferes with the expression of gfi1aa mRNA in haematopoietic cells, homozygous qmc551 fish are viable and fertile, and display normal primitive and definitive haematopoiesis. Retained expression of Gfi1b in primitive erythrocytes and up-regulation of Gfi1ab at the onset of definitive haematopoiesis in homozygous qmc551 carriers, are sufficient to allow normal haematopoiesis. This finding contradicts previously published morpholino data that suggested an essential role for zebrafish Gfi1aa in primitive erythropoiesis.

Historical processes and contemporary ocean currents drive genetic structure in the seagrass Thalassia hemprichii in the Indo-Australian Archipelago.

Understanding spatial patterns of gene flow and genetic structure is essential for the conservation of marine ecosystems. Contemporary ocean currents and historical isolation due to Pleistocene sea level fluctuations have been predicted to influence the genetic structure in marine populations. In the Indo-Australian Archipelago (IAA), the world's hotspot of marine biodiversity, seagrasses are a vital component but population genetic information is very limited. Here, we reconstructed the phylogeography of the seagrass Thalassia hemprichii in the IAA based on single nucleotide polymorphisms (SNPs) and then characterized the genetic structure based on a panel of 16 microsatellite markers. We further examined the relative importance of historical isolation and contemporary ocean currents in driving the patterns of genetic structure. Results from SNPs revealed three population groups: eastern Indonesia, western Indonesia (Sunda Shelf) and Indian Ocean; while the microsatellites supported five population groups (eastern Indonesia, Sunda Shelf, Lesser Sunda, Western Australia and Indian Ocean). Both SNPs and microsatellites showed asymmetrical gene flow among population groups with a trend of southwestward migration from eastern Indonesia. Genetic diversity was generally higher in eastern Indonesia and decreased southwestward. The pattern of genetic structure and connectivity is attributed partly to the Pleistocene sea level fluctuations modified to a smaller level by contemporary ocean currents.

Accelerating Tropicalization and the Transformation of Temperate Seagrass Meadows.

Climate-driven changes are altering production and functioning of biotic assemblages in terrestrial and aquatic environments. In temperate coastal waters, rising sea temperatures, warm water anomalies and poleward shifts in the distribution of tropical herbivores have had a detrimental effect on algal forests. We develop generalized scenarios of this form of tropicalization and its potential effects on the structure and functioning of globally significant and threatened seagrass ecosystems, through poleward shifts in tropical seagrasses and herbivores. Initially, we expect tropical herbivorous fishes to establish in temperate seagrass meadows, followed later by megafauna. Tropical seagrasses are likely to establish later, delayed by more limited dispersal abilities. Ultimately, food webs are likely to shift from primarily seagrass-detritus to more direct-consumption-based systems, thereby affecting a range of important ecosystem services that seagrasses provide, including their nursery habitat role for fishery species, carbon sequestration, and the provision of organic matter to other ecosystems in temperate regions.

The movement ecology of seagrasses.

A movement ecology framework is applied to enhance our understanding of the causes, mechanisms and consequences of movement in seagrasses: marine, clonal, flowering plants. Four life-history stages of seagrasses can move: pollen, sexual propagules, vegetative fragments and the spread of individuals through clonal growth. Movement occurs on the water surface, in the water column, on or in the sediment, via animal vectors and through spreading clones. A capacity for long-distance dispersal and demographic connectivity over multiple timeframes is the novel feature of the movement ecology of seagrasses with significant evolutionary and ecological consequences. The space-time movement footprint of different life-history stages varies. For example, the distance moved by reproductive propagules and vegetative expansion via clonal growth is similar, but the timescales range exponentially, from hours to months or centuries to millennia, respectively. Consequently, environmental factors and key traits that interact to influence movement also operate on vastly different spatial and temporal scales. Six key future research areas have been identified.

Loss of function of parathyroid hormone receptor 1 induces Notch-dependent aortic defects during zebrafish vascular development.

OBJECTIVE: Coarctation of the aorta is rarely associated with known gene defects. Blomstrand chondrodysplasia, caused by mutations in the parathyroid hormone receptor 1 (PTHR1) is associated with coarctation of the aorta in some cases, although it is unclear whether PTHR1 deficiency causes coarctation of the aorta directly. The zebrafish allows the study of vascular development using approaches not possible in other models. We therefore examined the effect of loss of function of PTHR1 or its ligand parathyroid hormone-related peptide (PTHrP) on aortic formation in zebrafish. APPROACH AND RESULTS: Morpholino antisense oligonucleotide knockdown of either PTHR1 or PTHrP led to a localized occlusion of the mid-aorta in developing zebrafish. Confocal imaging of transgenic embryos showed that these defects were caused by loss of endothelium, rather than failure to lumenize. Using a Notch reporter transgenic ([CSL:Venus]qmc61), we found both PTHR1 and PTHrP knockdown-induced defective Notch signaling in the hypochord at the site of the aortic defect before onset of circulation, and the aortic occlusion was rescued by inducible Notch upregulation. CONCLUSIONS: Loss of function of either PTHR1 or PTHrP leads to a localized aortic defect that is Notch dependent. These findings may underlie the aortic defect seen in Blomstrand chondrodysplasia, and reveal a link between parathyroid hormone and Notch signaling during aortic development.

Accuracy of transcutaneous bilirubinometry in term infants after phototherapy: a prospective observational study.

OBJECTIVE: To test the accuracy of transcutaneous bilirubinometry (TcB) in neonates 12 h after discontinuing phototherapy. STUDY DESIGN: In a prospective study of 91 neonates at ≥35 weeks of gestation, paired measurements of total serum bilirubin (TSB) and TcB were obtained 12 h after discontinuation of phototherapy. TcB measurements were obtained on the uncovered skin of the sternum and the covered skin of the lower abdomen. Bland-Altman plots were used to evaluate agreement between TSB and TcB. RESULTS: TcB was found to systematically underestimate TSB on both covered and uncovered skin. The smallest but statistically significant difference between TSB and TcB was found on the covered lower abdomen (-1.03, p < .0001) compared with the uncovered skin of the sternum (-1.44, p < .0001). The correlation between TSB and TcB was excellent on both covered (r = 0.86, p < .001) and uncovered skin (r = 0.90, p < .001). Bland and Altman plots showed poor agreement between TcB and TSB. CONCLUSIONS: This study demonstrated excellent correlation between TcB and TSB 12 h after phototherapy but poor TcB-TSB agreement. TcB cannot be reliably used in neonates exposed to phototherapy.

Sore throat, fever, and pancytopenia during winter.

Care must be taken to mitigate the effect of cognitive bias in times of frequent common presentations. The etiology of bicytopenias and pancytopenias must always be carefully investigated. Blast cells in low count B ALL may not be seen on a peripheral smear and diagnosis often requires confirmational bone marrow aspirate with flow cytometry and molecular typing.

Ocean connectivity and habitat characteristics predict population genetic structure of seagrass in an extreme tropical setting.

Understanding patterns of gene flow and processes driving genetic differentiation is important for a broad range of conservation practices. In marine organisms, genetic differentiation among populations is influenced by a range of spatial, oceanographic, and environmental factors that are attributed to the seascape. The relative influences of these factors may vary in different locations and can be measured using seascape genetic approaches. Here, we applied a seascape genetic approach to populations of the seagrass, Thalassia hemprichii, at a fine spatial scale (~80 km) in the Kimberley coast, western Australia, a complex seascape with strong, multidirectional currents greatly influenced by extreme tidal ranges (up to 11 m, the world's largest tropical tides). We incorporated genetic data from a panel of 16 microsatellite markers, overwater distance, oceanographic data derived from predicted passive dispersal on a 2 km-resolution hydrodynamic model, and habitat characteristics from each meadow sampled. We detected significant spatial genetic structure and asymmetric gene flow, in which meadows 12-14 km apart were less connected than ones 30-50 km apart. This pattern was explained by oceanographic connectivity and differences in habitat characteristics, suggesting a combined scenario of dispersal limitation and facilitation by ocean current with local adaptation. Our findings add to the growing evidence for the key role of seascape attributes in driving spatial patterns of gene flow. Despite the potential for long-distance dispersal, there was significant genetic structuring over small spatial scales implicating dispersal and recruitment bottlenecks and highlighting the importance of implementing local-scale conservation and management measures.

Guidelines for model adaptation: A study of the transferability of a general seagrass ecosystem Dynamic Bayesian Networks model.

In general, it is not feasible to collect enough empirical data to capture the entire range of processes that define a complex system, either intrinsically or when viewing the system from a different geographical or temporal perspective. In this context, an alternative approach is to consider model transferability, which is the act of translating a model built for one environment to another less well-known situation. Model transferability and adaptability may be extremely beneficial-approaches that aid in the reuse and adaption of models, particularly for sites with limited data, would benefit from widespread model uptake. Besides the reduced effort required to develop a model, data collection can be simplified when transferring a model to a different application context. The research presented in this paper focused on a case study to identify and implement guidelines for model adaptation. Our study adapted a general Dynamic Bayesian Networks (DBN) of a seagrass ecosystem to a new location where nodes were similar, but the conditional probability tables varied. We focused on two species of seagrass (Zostera noltei and Zostera marina) located in Arcachon Bay, France. Expert knowledge was used to complement peer-reviewed literature to identify which components needed adjustment including parameterization and quantification of the model and desired outcomes. We adopted both linguistic labels and scenario-based elicitation to elicit from experts the conditional probabilities used to quantify the DBN. Following the proposed guidelines, the model structure of the general DBN was retained, but the conditional probability tables were adapted for nodes that characterized the growth dynamics in Zostera spp. population located in Arcachon Bay, as well as the seasonal variation on their reproduction. Particular attention was paid to the light variable as it is a crucial driver of growth and physiology for seagrasses. Our guidelines provide a way to adapt a general DBN to specific ecosystems to maximize model reuse and minimize re-development effort. Especially important from a transferability perspective are guidelines for ecosystems with limited data, and how simulation and prior predictive approaches can be used in these contexts.

Increased extent of waterfowl grazing lengthens the recovery time of a colonizing seagrass (Halophila ovalis) with implications for seagrass resilience.

Herbivore distributions and abundance are shifting because of climate change, leading to intensified grazing pressure on foundation species such as seagrasses. This, combined with rapidly increasing magnitudes of change in estuarine ecosystems, may affect seagrass resilience. While the overall resilience of seagrasses is generally well-studied, the timeframes of recovery has received comparatively little attention, particularly in temperate estuaries. We investigated how the recovery time (RT) of seagrass is affected by simulated grazing in a southwestern Australian estuary. Whilst excluding swans, we simulated different grazing intensities (25, 50, 75, and 100% removal from 1 m2 plots) at four locations in the Swan-Canning Estuary, Western Australia during summer and tracked the recovery of seagrass over 3 months, using seagrass cover as the main measure of recovery. We found that seagrass recovered within 4-6 weeks from the lower grazing intensities (25 and 50%) and 7-19 weeks from the higher grazing intensities (75 and 100%) across the estuary. Increased grazing intensity led to not only longer recovery times (RTs), but also greater variability in the RT among experimental locations. The RT from the higher grazing intensities at one location in particular was more than double other locations. Seagrass recovery was through vegetative mechanisms and not through sexual reproduction. There was a significant grazing treatment effect on seagrass meadow characteristics, particularly belowground biomass which had not recovered 3 months following grazing. As the pressure of climate change on estuarine environments increases, these quantified RTs for seagrass provide a baseline for understanding grazing pressure as a singular disturbance. Future work can now examine how grazing and other potentially interacting pressures in our changing climate could impact seagrass recovery even further.

Clinical trial recruiters' experiences working with trial eligibility criteria: results of an exploratory, cross-sectional, online survey in the UK.

BACKGROUND: Eligibility criteria are a fundamental element of clinical trial design, defining who can and who should not participate in a trial. Problems with the design or application of criteria are known to occur and pose risks to participants' safety and trial integrity, sometimes also negatively impacting on trial recruitment and generalisability. We conducted a short, exploratory survey to gather evidence on UK recruiters' experiences interpreting and applying eligibility criteria and their views on how criteria are communicated and developed. METHODS: Our survey included topics informed by a wider programme of work at the Clinical Trials Research Unit, University of Leeds, on assuring eligibility criteria quality. Respondents were asked to answer based on all their trial experience, not only on experiences with our trials. The survey was disseminated to recruiters collaborating on trials run at our trials unit, and via other mailing lists and social media. The quantitative responses were descriptively analysed, with inductive analysis of free-text responses to identify themes. RESULTS: A total of 823 eligible respondents participated. In total, 79% of respondents reported finding problems with eligibility criteria in some trials, and 9% in most trials. The main themes in the types of problems experienced were criteria clarity (67% of comments), feasibility (34%), and suitability (14%). In total, 27% of those reporting some level of problem said these problems had led to patients being incorrectly included in trials; 40% said they had led to incorrect exclusions. Most respondents (56%) reported accessing eligibility criteria mainly in the trial protocol. Most respondents (74%) supported the idea of recruiter review of eligibility criteria earlier in the protocol development process. CONCLUSIONS: Our survey corroborates other evidence about the existence of suboptimal trial eligibility criteria. Problems with clarity were the most often reported, but the number of comments on feasibility and suitability suggest some recruiters feel eligibility criteria and associated assessments can hinder recruitment to trials. Our proposal for more recruiter involvement in protocol development has strong support and some potential benefits, but questions remain about how best to implement this. We invite other trialists to consider our other suggestions for how to assure quality in trial eligibility criteria.

The surface bacterial community of an Australian kelp shows cross-continental variation and relative stability within regions.

Epiphytic microbial communities often have a close relationship with their eukaryotic host, assisting with defence, health, disease prevention and nutrient transfer. Shifts in the structure of microbial communities could therefore have negative effects on the individual host and indirectly impact the surrounding ecosystem, particularly for major habitat-forming hosts, such as kelps in temperate rocky shores. Thus, an understanding of the structure and dynamics of host-associated microbial communities is essential for monitoring and assessing ecosystem changes. Here, samples were taken from the ecologically important kelp, Ecklonia radiata, over a 17-month period, from six different sites in two distinct geographic regions (East and West coasts of Australia), separated by ∼3,300 kms, to understand variation in the kelp bacterial community and its potential environmental drivers. Differences were observed between kelp bacterial communities between the largely disconnected geographical regions. In contrast, within each region and over time the bacterial communities were considerably more stable, despite substantial seasonal changes in environmental conditions.

The health impacts of waste incineration: a systematic review.

INTRODUCTION: Waste incineration is increasingly used to reduce waste volume and produce electricity. Several incinerators have recently been proposed in Australia and community groups are concerned about health impacts. An overview of the evidence on health effects has been needed. METHOD: A systematic review of English language literature for waste incinerators and health using PRISMA methodology. RESULTS: A range of adverse health effects were identified, including significant associations with some neoplasia, congenital anomalies, infant deaths and miscarriage, but not for other diseases. Ingestion was the dominant exposure pathway for the public. Newer incinerator technologies may reduce exposure. DISCUSSION: Despite these findings, diverse chemicals, poor study methodologies and inconsistent reporting of incinerator technology specifications precludes firmer conclusions about safety. CONCLUSION: Older incinerator technology and infrequent maintenance schedules have been strongly linked with adverse health effects. More recent incinerators have fewer reported ill effects, perhaps because of inadequate time for adverse effects to emerge. A precautionary approach is required. Waste minimisation is essential. Implications for public health: Public health practitioners can offer clearer advice about adverse health effects from incinerators. We suggest improved research design and methods to make future studies more robust and comparable. We offer ideas for better policy and regulation.

Determining light stress responses for a tropical multi-species seagrass assemblage.

Existing mitigations to address deterioration in water clarity associated with human activities are based on responses from single seagrass species but may not be appropriate for diverse seagrass assemblages common to tropical waters. We present findings from a light experiment designed to determine the effects of magnitude and duration of low light on a mixed tropical seagrass assemblage. Mixed assemblages of three commonly co-occurring Indo-West Pacific seagrasses, Cymodocea serrulata, Halodule uninervis and Halophila ovalis were grown in climate-controlled tanks, where replicate pots were subjected to a gradient in light availability (0.9-21.6 mols PAR m-2 day-1) for 12 weeks. Increased shading resulted in declines in growth and changes in cellular and photosynthesis responses for all species, although time-scale and magnitude of response were species-specific. Applying management criteria (e.g. thresholds) relevant to one species may under- or over-estimate potential for impact on other species and the meadow as a whole.

Seagrass ecosystem trajectory depends on the relative timescales of resistance, recovery and disturbance.

Seagrass ecosystems are inherently dynamic, responding to environmental change across a range of scales. Habitat requirements of seagrass are well defined, but less is known about their ability to resist disturbance. Specific means of recovery after loss are particularly difficult to quantify. Here we assess the resistance and recovery capacity of 12 seagrass genera. We document four classic trajectories of degradation and recovery for seagrass ecosystems, illustrated with examples from around the world. Recovery can be rapid once conditions improve, but seagrass absence at landscape scales may persist for many decades, perpetuated by feedbacks and/or lack of seed or plant propagules to initiate recovery. It can be difficult to distinguish between slow recovery, recalcitrant degradation, and the need for a window of opportunity to trigger recovery. We propose a framework synthesizing how the spatial and temporal scales of both disturbance and seagrass response affect ecosystem trajectory and hence resilience.

Response of the seagrass Halophila ovalis to altered light quality in a simulated dredge plume.

Seagrass meadows are globally threatened, largely through activities that reduce light quantity (photosynthetic photon flux density) such as dredging. However, these activities can simultaneously alter the spectral quality of light. Previous studies showed that Halophila ovalis seagrass productivity is reduced under monochromatic yellow/green light, wavelengths associated with dredge plumes, but it is unclear how they respond to spectra produced by real dredging projects. We simultaneously subjected adult H. ovalis plants to altered light quality and quantity simulating a real commercial dredging operation (15mgL-1 TSS, 50 and 200µmol photonsm-2s-1). There was a significant effect of reduced light quantity on physiological and morphological variables and a significant effect of light quality on the pigment antheraxanthin. The lack of effect of light quality on growth indicates that while seagrass are sensitive to changes in light quality, natural- and anthropogenic-driven changes may not always be sufficient to produce strong effects on H. ovalis.