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Background: Invasive management strategies range from preventing new invasive species incursions to eliminating established populations, with all requiring effective monitoring to guide action. The use of DNA sampled from the environment (eDNA) is one such tool that provides the ability to surveille and monitor target invasive species through passive sampling. Technology being developed to eliminate invasive species includes genetic biocontrol in the form of gene drive. This approach would drive a trait through a population and could be used to eliminate or modify a target population. Once a gene drive organism is released into a population then monitoring changes in density of the target species and the spread of the drive in the population would be critical. Results: In this paper, we use invasive Mus musculus as a model for development of an eDNA assay that detects wild-type M. musculus and gene drive M. musculus. We demonstrate successful development of an assay where environmental samples could be used to detect wild-type invasive M. musculus and the relative density of wild-type to gene drive M. musculus. Conclusions: The development of a method that detects both wild-type M. musculus and a gene drive M. musculus (tCRISPR) from environmental samples expands the utility of environmental DNA. This method provides a tool that can immediately be deployed for invasive wild M. musculus management across the world. This is a proof-of-concept that a genetic biocontrol construct could be monitored using environmental samples. [ABSTRACT FROM AUTHOR]

Timely and accurate detection and estimation of animal abundance is an important part of wildlife management. This is particularly true for invasive species where cost-effective tools are needed to enable landscape-scale surveillance and management responses, especially when targeting low-density populations residing in dense vegetation and under canopies. This research focused on investigating the feasibility and practicality of using uncrewed aerial systems (UAS) and hyperspectral imagery (HSI) to classify animals in the wild on a spectral—rather than spatial—basis, in the hopes of developing methods to accurately classify animal targets even when their form may be significantly obscured. We collected HSI of four species of large mammals reported as invasive species on islands: cow (Bos taurus), horse (Equus caballus), deer (Odocoileus virginianus), and goat (Capra hircus) from a small UAS. Our objectives of this study were to (a) create a hyperspectral library of the four mammal species, (b) study the efficacy of HSI for animal classification by only using the spectral information via statistical separation, (c) study the efficacy of sequential and deep learning neural networks to classify the HSI pixels, (d) simulate five-band multispectral data from HSI and study its effectiveness for automated supervised classification, and (e) assess the ability of using HSI for invasive wildlife detection. Image classification models using sequential neural networks and one-dimensional convolutional neural networks were developed and tested. The results showed that the information from HSI derived using dimensionality reduction techniques were sufficient to classify the four species with class F1 scores all above 0.85. The performances of some classifiers were capable of reaching an overall accuracy over 98%and class F1 scores above 0.75, thus using only spectra to classify animals to species from existing sensors is feasible. This study discovered various challenges associated with the use of HSI for animal detection, particularly intra-class and seasonal variations in spectral reflectance and the practicalities of collecting and analyzing HSI data over large meaningful areas within an operational context. To make the use of spectral data a practical tool for wildlife and invasive animal management, further research into spectral profiles under a variety of real-world conditions, optimization of sensor spectra selection, and the development of on-board real-time analytics are needed. [ABSTRACT FROM AUTHOR]

Use of rodenticides is a common method for eradication of invasive rodents from islands, with eradication projects increasingly being undertaken on inhabited islands or islands used by people for harvesting food. The expansion of eradication projects to inhabited islands will require that all real and perceived human health risks from the projects are socially acceptable, or effectively mitigated. When broad-scale use of rodenticide for eradication is proposed on inhabited islands, it is usual for concerns to be raised about the risks of rodenticide exposure to people, livestock, pets, game animals, and marine food sources. Although risks to humans have been assessed prior to some individual island eradications, there are currently no established frameworks for consistent and formal approaches to such assessments. To inform the focus of future assessments, we synthesized current understanding of the potential pathways of human exposure to rodenticides and risk mitigation measures associated with island rodent eradication projects. We sought to develop this through a literature and database review that identified 153 inhabited islands where rodent eradication projects had been undertaken, of which 95 documented a priori assessments of human risks and mitigation measures. We found no reports of adverse effects from human exposure resulting from any source during discrete rodent eradication programs on inhabited islands, including direct rodenticide bait consumption, inhalation, dermal absorption, secondary or tertiary exposure. To continue advancing eradications on inhabited islands of increasing scale and proactively manage risks and perceptions, we recommend engagement processes that integrate island communities into a priori risk assessments and mitigation measure selection. [ABSTRACT FROM AUTHOR]

Islands are global hotspots for biodiversity and extinction, representing ~ 5% of Earth's land area alongside 40% of globally threatened vertebrates and 61% of global extinctions since the 1500s. Invasive species are the primary driver of native biodiversity loss on islands, though eradication of invasive species from islands has been effective at halting or reversing these trends. A global compendium of this conservation tool is essential for scaling best-practices and enabling innovations to maximize biodiversity outcomes. Here, we synthesize over 100 years of invasive vertebrate eradications from islands, comprising 1550 eradication attempts on 998 islands, with an 88% success rate. We show a significant growth in eradication activity since the 1980s, primarily driven by rodent eradications. The annual number of eradications on islands peaked in the mid-2000s, but the annual area treated continues to rise dramatically. This trend reflects increases in removal efficacy and project complexity, generating increased conservation gains. Our synthesis demonstrates the collective contribution of national interventions towards global biodiversity outcomes. Further investment in invasive vertebrate eradications from islands will expand biodiversity conservation while strengthening biodiversity resilience to climate change and creating co-benefits for human societies. [ABSTRACT FROM AUTHOR]

DNA replication initiation requires the loading of MCM2-7 complexes at the origins of replication during G1. Replication licensing renders chromatin competent for DNA replication and its tight regulation is essential to prevent aberrant DNA replication and genomic instability. CDT1 is a critical factor of licensing and its activity is controlled by redundant mechanisms, including Geminin, a protein inhibitor of CDT1. Aberrant CDT1 and Geminin expression have been shown to promote tumorigenesis in vivo and are also evident in multiple human tumors. In this study, we developed an in vitro AlphaScreen™ high-throughput screening (HTS) assay for the identification of small-molecule inhibitors targeting the CDT1/Geminin protein complex. Biochemical characterization of the most potent compound, AF615, provided evidence of specific, dose-dependent inhibition of Geminin binding to CDT1 both in-vitro and in cells. Moreover, compound AF615 induces DNA damage, inhibits DNA synthesis and reduces viability selectively in cancer cell lines, and this effect is CDT1-dependent. Taken together, our data suggest that AF615 may serve as a useful compound to elucidate the role of CDT1/Geminin protein complex in replication licensing and origin firing as well as a scaffold for further medicinal chemistry optimisation. [ABSTRACT FROM AUTHOR]

Island rodent eradications are increasingly conducted to eliminate the negative impacts of invasive rodents. The success rate in the tropics has been lower than in temperate regions, triggering research and reviews. Environmental factors unique to the tropics (e.g., land crabs and year‐round rodent breeding) have been associated with eradication failure. Operational factors have also been important, but these have not been comprehensively assessed. The environmental and operational factors using global cases where rodent eradication initially failed and subsequent attempts occurred were compared. It was determined whether operational factors explained the initial failures, whether operational improvements explained subsequent successes, and whether re‐attempting eradication after failure was worthwhile. About 35 eradication attempts on 17 islands, each with 1–2 species from a total of 5 species (Mus musculus and 4 Rattus spp.) were identified. On 14 islands (82%), eradication was achieved on the second (86%) or third attempt (14%). On the remaining 3 islands, eradication was not achieved. Evidence of operational faults for all failed attempts was found (e.g., poor planning, low quality bait, and gaps during bait application). In some cases, operational faults were unequivocally the cause of failure, but in others, it was impossible to discriminate from confounding, environmental factors. Nonetheless, failures appeared to be mainly the result of not exposing all rodents to a lethal dose of toxin, violating a crucial eradication principle. This can cause operational failure on any temperate or tropical island. However, there may be less tolerance for errors such as gaps in bait coverage on tropical islands, mainly due to bait consumption by land crabs. The findings on factors leading to eradication success (e.g., expert reviewed plans, realistic funding and permits, high standard baiting operations) reflect current best practice recommendations. Strict adherence to best practice is expected to increase overall rates of eradication success. [ABSTRACT FROM AUTHOR]

Bioorthogonal reactions are ideally suited to selectively modify proteins in complex environments, even in vivo. Kinetics and product stability of these reactions are crucial parameters to evaluate their usefulness for specific applications. Strain promoted inverse electron demand Diels–Alder cycloadditions (SPIEDAC) between tetrazines and strained alkenes or alkynes are particularly popular, as they allow ultrafast labeling inside cells. In combination with genetic code expansion (GCE)‐a method that allows to incorporate noncanonical amino acids (ncAAs) site‐specifically into proteins in vivo. These reactions enable residue‐specific fluorophore attachment to proteins in living mammalian cells. Several SPIEDAC capable ncAAs have been presented and studied under diverse conditions, revealing different instabilities ranging from educt decomposition to product loss due to β‐elimination. To identify which compounds yield the best labeling inside living mammalian cells has frequently been difficult. In this study we present a) the synthesis of four new SPIEDAC reactive ncAAs that cannot undergo β‐elimination and b) a fluorescence flow cytometry based FRET‐assay to measure reaction kinetics inside living cells. Our results, which at first sight can be seen conflicting with some other studies, capture GCE‐specific experimental conditions, such as long‐term exposure of the ring‐strained ncAA to living cells, that are not taken into account in other assays. [ABSTRACT FROM AUTHOR]

Summary: The United Nations 2030 Agenda for Sustainable Development sets a framework of universal Sustainable Development Goals (SDGs) to address challenges to society and the planet. Island invasive species eradications have well-documented benefits that clearly align with biodiversity conservation-related SDGs, yet the value of this conservation action for socioeconomic benefits is less clear. We examine the potential for island invasive vertebrate eradications to have ecological and socioeconomic benefits. Specifically, we examine: (1) how SDGs may have been achieved through past eradications; and (2) how planned future eradications align with SDGs and associated targets. We found invasive vertebrate eradication to align with 13 SDGs and 42 associated targets encompassing marine and terrestrial biodiversity conservation, promotion of local and global partnerships, economic development, climate change mitigation, human health and sanitation and sustainable production and consumption. Past eradications on 794 islands aligned with a median of 17 targets (range 13–38) by island. Potential future eradications on 292 highly biodiverse islands could align with a median of 25 SDG targets (range 15–39) by island. This analysis enables the global community to explicitly describe the contributions that invasive vertebrate management on islands can make towards implementing the global sustainable development agenda. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 2 (FGF2) is a cell survival factor with crucial functions in tumor‐induced angiogenesis. Here, we describe a novel time‐resolved FGF2 signaling assay based upon live cell imaging of neuroblastoma cells. To validate this system, we tested 8960 small molecules for inhibition of FGF2 signaling with kinetic resolution. Hit compounds were validated in dose‐response experiments for FGF2 signaling, FGF receptor antagonism, downstream ERK phosphorylation and FGF2‐dependent chemoresistance in a cellular leukemia model system. The new screening system for FGF2 signaling inhibitors has unique features, deselecting compounds with pleiotropic effects on cell proliferation and, along with the experimental pipeline reported, great potential for the discovery of new classes of FGF2 signaling inhibitors that block FGF2 dependent tumor cell survival. [ABSTRACT FROM AUTHOR]

Invasive alien species are a major threat to native insular species. Eradicating invasive mammals from islands is a feasible and proven approach to prevent biodiversity loss. We developed a conceptual framework to identify globally important islands for invasive mammal eradications to prevent imminent extinctions of highly threatened species using biogeographic and technical factors, plus a novel approach to consider socio-political feasibility. We applied this framework using a comprehensive dataset describing the distribution of 1,184 highly threatened native vertebrate species (i.e. those listed as Critically Endangered or Endangered on the IUCN Red List) and 184 non-native mammals on 1,279 islands worldwide. Based on extinction risk, irreplaceability, severity of impact from invasive species, and technical feasibility of eradication, we identified and ranked 292 of the most important islands where eradicating invasive mammals would benefit highly threatened vertebrates. When socio-political feasibility was considered, we identified 169 of these islands where eradication planning or operation could be initiated by 2020 or 2030 and would improve the survival prospects of 9.4% of the Earth’s most highly threatened terrestrial insular vertebrates (111 of 1,184 species). Of these, 107 islands were in 34 countries and territories and could have eradication projects initiated by 2020. Concentrating efforts to eradicate invasive mammals on these 107 islands would benefit 151 populations of 80 highly threatened vertebrates and make a major contribution towards achieving global conservation targets adopted by the world’s nations. [ABSTRACT FROM AUTHOR]

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Context. Worldwide, invasive vertebrate eradication campaigns are increasing in scale and complexity, requiring improved decision making tools to achieve and validate success. For managers of these campaigns, gaining access to timely summaries of field data can increase cost-efficiency and the likelihood of success, particularly for successive control-event style eradications. Conventional data collection techniques can be time intensive and burdensome to process. Recent advances in digital tools can reduce the time required to collect and process field information. Through timely analysis, efficiently collected data can inform decision making for managers both tactically, such as where to prioritise search effort, and strategically, such as when to transition from the eradication phase to confirmation monitoring. Aims. We highlighted the advantages of using digital data collection tools, particularly the potential for reduced project costs through a decrease in effort and the ability to increase eradication efficiency by enabling explicit data-informed decision making. Methods. We designed and utilised digital data collection tools, relational databases and a suite of analyses during two different eradication campaigns to inform management decisions: a feral cat eradication utilising trapping, and a rodent eradication using bait stations. Key results. By using digital data collection during a 2-year long cat eradication, we experienced an 89% reduction in data collection effort and an estimated USD42 845 reduction in total costs compared with conventional paper methods. During a 2-month rodent bait station eradication, we experienced an 84% reduction in data collection effort and an estimated USD4525 increase in total costs. Conclusions. Despite high initial capital costs, digital data collection systems provide increasing economics as the duration and scale of the campaign increases. Initial investments can be recouped by reusing equipment and software on subsequent projects, making digital data collection more cost-effective for programs contemplating multiple eradications. Implications. With proper pre-planning, digital data collection systems can be integrated with quantitative models that generate timely forecasts of the effort required to remove all target animals and estimate the probability that eradication has been achieved to a desired level of confidence, thus improving decision making power and further reducing total project costs. [ABSTRACT FROM AUTHOR]

The functional role of inositol 1,4,5-trisphosphate (InsP3) signaling in cardiomyocytes is not entirely understood but it was linked to an increased propensity for triggered activity. The aim of this study was to determine how InsP3 receptors can translate Ca2+ release into a depolarization of the plasma membrane and consequently arrhythmic activity. We used embryonic stem cell-derived cardiomyocytes (ESdCs) as a model system since their spontaneous electrical activity depends on InsP3-mediated Ca2+ release. [InsP3]i was monitored with the FRET-based InsP3-biosensor FIRE-1 (Fluorescent InsP3 Responsive Element) and heterogeneity in sub-cellular [InsP3]i was achieved by targeted expression of FIRE-1 in the nucleus (FIRE-1nuc) or expression of InsP3 5-phosphatase (m43) localized to the plasma membrane. Spontaneous activity of ESdCs was monitored simultaneously as cytosolic Ca2+ transients (Fluo-4/AM) and action potentials (current clamp). During diastole, the diastolic depolarization was paralleled by an increase of [Ca2+]i and spontaneous activity was modulated by [InsP3]i. A 3.7% and 1.7% increase of FIRE-1 FRET ratio and 3.0 and 1.5 fold increase in beating frequency was recorded upon stimulation with endothelin-1 (ET-1, 100 nmol/L) or phenylephrine (PE, 10 µmol/L), respectively. Buffering of InsP3 by FIRE-1nuc had no effect on the basal frequency while attenuation of InsP3 signaling throughout the cell (FIRE-1), or at the plasma membrane (m43) resulted in a 53.7% and 54.0% decrease in beating frequency. In m43 expressing cells the response to ET-1 was completely suppressed. Ca2+ released from InsP3Rs is more effective than Ca2+ released from RyRs to enhance INCX. The results support the hypothesis that in ESdCs InsP3Rs form a functional signaling domain with NCX that translates Ca2+ release efficiently into a depolarization of the membrane potential. [ABSTRACT FROM AUTHOR]

Climate change represents a planetary emergency that is exacerbating the loss of native biodiversity. In response, efforts promoting climate change adaptation strategies that improve ecosystem resilience and/or mitigate climate impacts are paramount. Invasive Alien Species are a key threat to islands globally, where strategies such as preventing establishment (biosecurity), and eradication, especially invasive mammals, have proven effective for reducing native biodiversity loss and can also advance ecosystem resilience and create refugia for native species at risk from climate change. Furthermore, there is growing evidence that successful eradications may also contribute to mitigating climate change. Given the cross-sector potential for eradications to reduce climate impacts alongside native biodiversity conservation, we sought to understand when conservation managers and funders explicitly sought to use or fund the eradication of invasive mammals from islands to achieve positive climate outcomes. To provide context, we first summarized available literature of the synergistic relationship between invasive species and climate change, including case studies where invasive mammal eradications served to meet climate adaptation or mitigation solutions. Second, we conducted a systematic review of the literature and eradication-related conference proceedings to identify when these synergistic effects of climate and invasive species were explicitly addressed through eradication practices. Third, we reviewed projects from four large funding entities known to support climate change solutions and/or native biodiversity conservation efforts and identified when eradications were funded in a climate change context. The combined results of our case study summary paired with systematic reviews found that, although eradicating invasive mammals from islands is an effective climate adaptation strategy, island eradications are poorly represented within the climate change adaptation and mitigation funding framework. We believe this is a lost opportunity and encourage eradication practitioners and funders of climate change adaptation to leverage this extremely effective nature-based tool into positive conservation and climate resilience solutions. [ABSTRACT FROM AUTHOR]

ABSTRACT: I give here a brief review of Bhaskar's transcendental realist view of science both to clarify my differences with my critics and to spell out some of the ideas presupposed in an earlier paper (Will 1984). I hope that this exposition might stimulate readers to explore Bhaska's own writings. [ABSTRACT FROM AUTHOR]

This paper describes a survey of the first 5 years' work of a specialist NHS child sexual abuse team (CSAT), which provides a post-disclosure treatment service to young people aged between 13 and 19. Information was obtained on the demographic characteristics of young people referred, the nature of their abuse and its perpetrators, and the type, length and outcome of the treatment provided. The survey was also used to ask four questions. Was the team providing a service to its target population, young people whose sexual abuse had been severe? Did the severity of abuse predict the intensity or length of therapy provided? Were there differences in the service provided to boys as opposed to girls? Finally, did experienced therapists achieve different results when compared with non-experienced therapists? It was found that the service was being used by its target group and that severity of abuse was associated with longer or more intensive therapy. The service did not appear to be adequately meeting the needs of boys. There was some indication that experienced therapists achieved the same treatment outcome as inexperienced therapists in a shorter period of time. [ABSTRACT FROM AUTHOR]

Group programs for adolescent perpetrators of sexually abusive behavior can take many forms. This paper describes the evolution of one such group program that arose from the experience involved with running four groups for adolescent perpetrators of sexual abuse. First, the basic principles underpinning the approach to this group method of treatment are described, and it is stated that the primary goal is to reduce the likelihood of perpetrators repeating sexually abusive acts. All groups contained a heterogeneous mix of perpetrators with a median age of 15 years. Groups are described in the context of the four phases: (1) developing control techniques; (2) working on cognitive distortions, victim awareness, and sex education; (3) acquiring social and dating skills, assertiveness training, and anger control; and (4) preventing relapse and reviewing the other phases. While all groups had a common core of client characteristics, each group was different, and the program evolved from group to group in the belief that flexibility is essential in designing group programs. This program is continuing to evolve.

Basic fibroblast growth factor (bFGF), a potent mitogen for arterial smooth muscle cells has been shown to play a fundamental role in the pathogenesis of arteriosclerosis and restenisos by stimulating the proliferation of vascular smooth muscle cells. We found that partially phosphorothioate-modified 15-redisue antisense oligodeoxynucleotides complementary to bFGF mRNA at 0.1-2.0 μM clock growth and division of cultured human and bovine coronary smooth muscle cells I a dose-dependent manner. The effect is sequence specific at low (0.1-0.5 μM) nontoxic concentrations. It is associated with inhibition of expression of pericellular and intracellular bFGF, with a decreased de novo synthesis of bFGF and is partly reversible by the addition of exogenous (recombinant) bFGF. The antisense effect lasts 48-72h and diminishes therafter. If the antisense oligodeoxynucleotide medium is replaced by an oligonucleotide-free medium after 24 h. the [³H]thymidine incorporation rate returns to control levels. Under the same conditions, the corresponding sense oligodeoxynucleotide exerts negligible nonspecific inhibitoty actions. The antiproliferative potency of the 15-residue antisense oligodeoxynucleotide is markedly enhanced by adding 3-4 nobase-pairing guanosine residues at the 5'- and 3'-termini of the 15-residue antisense oligonucleotide. [ABSTRACT FROM AUTHOR]

The article presents a study on an integrated approach to dysfunction in interprofessional systems. This study has focused on dysfunction in inter-professional systems and will argue that it is important to develop an integrated approach to understanding the dysfunction. It has reviewed psychoanalytic theories of counter-transference and of mirroring within interprofessional systems, describes one of the types of family which commonly engenders interprofessional discord, and then uses a case study of work with a school-phobic family

A letter to the editor is presented in response to the article "The Heterosexual Presumption," in the vol. 22, no. 1, 1981 issue.

The article announces that Howard Heinz and Vira I. Heinz Endowments received the 1997 Thomas deGaetani Award at the United States Institute for Theatre Technology (USIIT) Annual Meeting and Keynote Speech on March 19, 2007 in Pittsburgh, Pennsylvania.