Multifunctional targeting micelle nanocarriers with both imaging and therapeutic potential for bladder cancer.

BackgroundWe previously developed a bladder cancer-specific ligand (PLZ4) that can specifically bind to both human and dog bladder cancer cells in vitro and in vivo. We have also developed a micelle nanocarrier drug-delivery system. Here, we assessed whether the targeting micelles decorated with PLZ4 on the surface could specifically target dog bladder cancer cells.Materials and methodsMicelle-building monomers (ie, telodendrimers) were synthesized through conjugation of polyethylene glycol with a cholic acid cluster at one end and PLZ4 at the other, which then self-assembled in an aqueous solution to form micelles. Dog bladder cancer cell lines were used for in vitro and in vivo drug delivery studies.ResultsCompared to nontargeting micelles, targeting PLZ4 micelles (23.2 ± 8.1 nm in diameter) loaded with the imaging agent DiD and the chemotherapeutic drug paclitaxel or daunorubicin were more efficient in targeted drug delivery and more effective in cell killing in vitro. PLZ4 facilitated the uptake of micelles together with the cargo load into the target cells. We also developed an orthotopic invasive dog bladder cancer xenograft model in mice. In vivo studies with this model showed the targeting micelles were more efficient in targeted drug delivery than the free dye (14.3×; P < 0.01) and nontargeting micelles (1.5×; P < 0.05).ConclusionTargeting micelles decorated with PLZ4 can selectively target dog bladder cancer cells and potentially be developed as imaging and therapeutic agents in a clinical setting. Preclinical studies of targeting micelles can be performed in dogs with spontaneous bladder cancer before proceeding with studies using human patients

Apomixis and hybridization drives reticulate evolution and phyletic differentiation in sorbus l.: Implications for conservation

This is the final version. Available from Frontiers Media via the DOI in this record. Hybridization and polyploidy are major forces in the evolution of plant diversity and the study of these processes is of particular interest to understand how novel taxa are formed and how they maintain genetic integrity. Sorbus is an example of a genus where active diversification and speciation are ongoing and, as such, represents an ideal model to investigate the roles of hybridization, polyploidy and apomixis in a reticulate evolutionary process. To elucidate breeding systems and evolutionary origins of a complex of closely related Sorbus taxa, we assessed genotypic diversity and population structure within and among taxa, combining data from nuclear DNA microsatellite markers and flow cytometry. Clonal analysis and low genotypic diversity within the polyploid taxa suggest apomixis is obligate. However, genetic variation has led to groups of ‘clone-mates’ within apomictic taxa that strongly suggest mutation is responsible for the genotypic diversity of these apomictic lineages. In addition, microsatellite profiles and site demographics suggest hybridization events among apomictic polyploid Sorbus may have contributed to the extant diversity of recognized taxa in this region. This research demonstrates that both macro- and micro-evolutionary processes are active within this reticulate Sorbus complex. Conservation measures should be aimed at maintaining this process and should therefore be prioritized for those areas of Sorbus species richness where the potential for interspecific gene flow is greatest.Whitley Wildlife Conservation TrustNational Botanic Garden of Wale

Survival of branching random walks in random environment

We study survival of nearest-neighbour branching random walks in random environment (BRWRE) on ${\mathbb Z}$. A priori there are three different regimes of survival: global survival, local survival, and strong local survival. We show that local and strong local survival regimes coincide for BRWRE and that they can be characterized with the spectral radius of the first moment matrix of the process. These results are generalizations of the classification of BRWRE in recurrent and transient regimes. Our main result is a characterization of global survival that is given in terms of Lyapunov exponents of an infinite product of i.i.d. $2\times 2$ random matrices.Comment: 17 pages; to appear in Journal of Theoretical Probabilit

A taxonomic, genetic and ecological data resource for the vascular plants of Britain and Ireland

The vascular flora of Britain and Ireland is among the most extensively studied in the world, but the current knowledge base is fragmentary, with taxonomic, ecological and genetic information scattered across different resources. Here we present the first comprehensive data repository of native and alien species optimized for fast and easy online access for ecological, evolutionary and conservation analyses. The inventory is based on the most recent reference flora of Britain and Ireland, with taxon names linked to unique Kew taxon identifiers and DNA barcode data. Our data resource for 3,227 species and 26 traits includes existing and unpublished genome sizes, chromosome numbers and life strategy and life-form assessments, along with existing data on functional traits, species distribution metrics, hybrid propensity, associated biomes, realized niche description, native status and geographic origin of alien species. This resource will facilitate both fundamental and applied research and enhance our understanding of the flora’s composition and temporal changes to inform conservation efforts in the face of ongoing climate change and biodiversity loss

Escape Rates and Physically Relevant Measures for Billiards with Small Holes

We study the billiard map corresponding to a periodic Lorentz gas in 2-dimensions in the presence of small holes in the table. We allow holes in the form of open sets away from the scatterers as well as segments on the boundaries of the scatterers. For a large class of smooth initial distributions, we establish the existence of a common escape rate and normalized limiting distribution. This limiting distribution is conditionally invariant and is the natural analogue of the SRB measure of a closed system. Finally, we prove that as the size of the hole tends to zero, the limiting distribution converges to the smooth invariant measure of the billiard map.Comment: 39 pages, 4 figure

Dragon-kings: mechanisms, statistical methods and empirical evidence

This introductory article presents the special Discussion and Debate volume "From black swans to dragon-kings, is there life beyond power laws?" published in Eur. Phys. J. Special Topics in May 2012. We summarize and put in perspective the contributions into three main themes: (i) mechanisms for dragon-kings, (ii) detection of dragon-kings and statistical tests and (iii) empirical evidence in a large variety of natural and social systems. Overall, we are pleased to witness significant advances both in the introduction and clarification of underlying mechanisms and in the development of novel efficient tests that demonstrate clear evidence for the presence of dragon-kings in many systems. However, this positive view should be balanced by the fact that this remains a very delicate and difficult field, if only due to the scarcity of data as well as the extraordinary important implications with respect to hazard assessment, risk control and predictability.Comment: 20 page

Environmental DNA reveals links between abundance and composition of airborne grass pollen and respiratory health

This is the final version. Available on open access from Elsevier via the DOI in this recordData and Code Availability Statement: Data collected using qPCR is archived and on NERC EIDC [https://doi.org/10.5285/28208be4-0163-45e6-912c-2db205126925]. Standard pollen monitoring ‘count’ data were sourced from the MEDMI database, with the exception of data from Bangor which were produced as part of the present study and are available on request. Prescribing datasets are publicly available, as are weather, air pollution, deprivation (IMD) and rural-urban category data. Hospital episode statistics (HES) datasets are sensitive, individual-level health data, which are subject to strict privacy regulations and are not publicly available. The study did not generate any unique codeGrass (Poaceae) pollen is the most important outdoor aeroallergen, exacerbating a range of respiratory conditions, including allergic asthma and rhinitis (‘hay fever’). Understanding the relationships between respiratory diseases and airborne grass pollen with view to improving forecasting has broad public health and socioeconomic relevance. It is estimated that there are over 400 million people with allergic rhinitis and over 300 million with asthma, globally, often comorbidly . In the UK, allergic asthma has an annual cost of around US$ 2.8 billion (2017). The relative contributions of the >11,000 (worldwide) grass species to respiratory health have been unresolved, as grass pollen cannot be readily discriminated using standard microscopy. Instead, here we used novel environmental DNA (eDNA) sampling and quantitative PCR (qPCR) , to measure the relative abundances of airborne pollen from common grass species, during two grass pollen seasons (2016 and 2017), across the UK. We quantitatively demonstrate discrete spatiotemporal patterns in airborne grass pollen assemblages. Using a series of generalised additive models (GAMs), we explore the relationship between the incidences of airborne pollen and severe asthma exacerbations (sub-weekly) and prescribing rates of drugs for respiratory allergies (monthly). Our results indicate that a subset of grass species may have disproportionate influence on these population-scale respiratory health responses during peak grass pollen concentrations. The work demonstrates the need for sensitive and detailed biomonitoring of harmful aeroallergens in order to investigate and mitigate their impacts on human health.Natural Environment Research Council (NERC)National Institute for Health Research (NIHR)Public Health EnglandUniversity of ExeterUniversity College LondonMet Offic

Linking Grass Pollen Biodiversity and Human Health: an Environmental Genomic Approach

In Europe and the UK, grass pollen is the single most important outdoor aeroallergen; 27% of the population are sensitised to grass pollen. Grass pollen allergy has been linked to increased risk of allergic asthma exacerbations, which can lead to hospitalisation and fatalities. Sensitivity towards grass pollen varies between species, of which there are over 150 in the UK. However, due to few unique morphological features, grass pollen from different species cannot be discriminated using traditional observational methods. Currently, there is no way of detecting, modelling or forecasting the aerial-dispersion of pollen from the biodiversity of UK grasses. Consequently, grasses are coalesced into a single group in the UK forecast. PollerGEN is an interdisciplinary NERC project with the aim of revolutionising the way that pollen dispersion is measured and forecast, with concomitant synergies for understanding the ecology of aerial dispersed pollen. In collaboration with the UK Met Office, a key goal is to build a more accurate forecast of individual grass pollen species. Using environmental genomics, we will identify which species of grass pollen are present during the summer months across 16 specific collection sites in the UK, and measure the abundance of the different allergenic species of grass. The information will be used to model the spatial and temporal deposition of different species of grass pollen and identify linkages to human health. The project therefore aims to provide a paradigm shift in our understanding of the ecology of windborne pollen in time and space and inform the public about the timing and environmental factors that put them at risk of exposure to pollen they are allergic to; a key strategy in the prevention of allergy and asthma attacks

Predicting the severity of the grass pollen season and the effect of climate change in Northwest Europe

Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season's severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season

2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates