Overcoming the cardiac toxicities of cancer therapy immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have led recent advances in the field of cancer immunotherapy improving overall survival in multiple malignancies with abysmal prognoses prior to their introduction. The remarkable efficacy of ICIs is however limited by their potential for systemic and organ specific immune-related adverse events (irAEs), most of which present with mild to moderate symptoms that can resolve spontaneously, with discontinuation of therapy or glucocorticoid therapy. Cardiac irAEs however are potentially fatal. The understanding of autoimmune cardiotoxicity remains limited due to its rareness. In this paper, we provide an updated review of the literature on the pathologic mechanisms, diagnosis, and management of autoimmune cardiotoxicity resulting from ICIs and their combinations and provide perspective on potential strategies and ongoing research developments to prevent and mitigate their occurrence.

Compassionate Conservation and the Challenge of Sustainable Wildlife Management: A Survey of the Urban Public of China.

Sustainable wildlife management (SWM) is based on a synergy of traditional/local knowledge, advances in scientific knowledge, and fast-evolving economic and social circumstances. A widely accepted cornerstone of SWM globally is that conservation and utilization need to be effectively integrated, emphasizing the benefits humans can derive from biodiversity, thereby further encouraging people to protect and value wildlife though its management. However, with demand from biological resources growing at an unprecedented rate and the emergence of social media, conservationists must respond quickly to new challenges and conflicts associated with species management and public policy. For example, the rise of the "Compassionate Conservation" (CC) movement, fueled by social marketing and media, which promotes the welfare of individual animals, has introduced a set of challenges for conventional conservation management as it opposes most or all forms of wildlife utilization and hunting. CC advocates are increasingly influential at global and national policy levels; hence, it is imperative that conservationists are informed and aware of the future challenges from a rapidly changing global society. In this paper, we report the findings of a large semi-structured questionnaire in China which investigated the attitude of the urban public toward sustainable wildlife management (SWM) and wildlife conservation across a range of issues and identified the key socio-economic and demographic factor drivers for those attitudes. The survey was conducted from November 2018 to October 2020, across 15 cities randomly selected among China's seven administrative geographic regions. The survey was initially conducted through face-to-face interviews, but later, due to COVID-19 restrictions, was completed via online questionnaires. A Likert seven-point scale method was used to score the public's degree of agreement or disagreement for each question; a multivariate stepwise linear regression method was used to analyze whether the overall attitude of the respondents toward SWM and wildlife conservation was affected by their demographic characteristics; and a classification and regression tree (CART) was used to conduct an in-depth analysis of the issues with negative scores in the questionnaire, so as to understand how the respondents' demographic characteristics affected the public's attitude about such issues, which could supplement results obtained from the multivariate stepwise linear regression analysis. The results show that the public are broadly supportive of SWM, but only moderately so. On issues of "Animal Welfare and Rights," "Wildlife Utilization and Captive Breeding," and "Trophy Hunting", the core concerns of the "Compassionate Conservation" movement and the overall public view are more antagonistic to conventional SWM. We also find specific demographic characteristics significantly influence attitudes about SWM, with vegetarians, those with religious beliefs, and with lower educational standards demonstrating weaker support for SWM. For younger people, "Animal Welfare and Rights" is a special concern, hence, we identify this as a key issue to be addressed for SWM and conservation in the future. Our research suggests that conservation organisations may need to adapt their management aims and practices to avoid direct conflict with the rising tide of animal rights sentiment, especially among the young. Furthermore, significant investment will be required to promote science-based conservation in social marketing on all social media platforms to help educate and engage the public with the science behind conservation management.

Habitat complexity and lifetime predation risk influence mesopredator survival in a multi-predator system.

Variability in habitat selection can lead to differences in fitness; however limited research exists on how habitat selection of mid-ranking predators can influence population-level processes in multi-predator systems. For mid-ranking, or mesopredators, differences in habitat use might have strong demographic effects because mesopredators need to simultaneously avoid apex predators and acquire prey. We studied spatially-explicit survival of cheetahs (Acinonyx jubatus) in the Mun-Ya-Wana Conservancy, South Africa, to test hypotheses related to spatial influences of predation risk, prey availability, and vegetation complexity, on mesopredator survival. For each monitored cheetah, we estimated lion encounter risk, prey density, and vegetation complexity within their home range, on short-term (seasonal) and long-term (lifetime) scales and estimated survival based on these covariates. Survival was lowest for adult cheetahs and cubs in areas with high vegetation complexity on both seasonal and lifetime scales. Additionally, cub survival was negatively related to the long-term risk of encountering a lion. We suggest that complex habitats are only beneficial to mesopredators when they are able to effectively find and hunt prey, and show that spatial drivers of survival for mesopredators can vary temporally. Collectively, our research illustrates that individual variation in mesopredator habitat use can scale-up and have population-level effects.

Cardiac Syncope with Anoxic Seizure Activity.

This is a case report, which explores the presentation to the emergency department of a fit and well female with a known ventricular bigeminy. She presented with convulsive episodes. The working differential diagnosis was of possible cardiac syncope with anoxic seizure activity or neurogenically mediated arrhythmia secondary to subarachnoid haemorrhage. On further collateral history, the patient was on citalopram. The ECGs demonstrated PVCs of multiple morphologies that were transiently bidirectional, raising the possibility of catecholaminergic polymorphic ventricular tachycardia. The presentation of a young fit patient with syncope and seizure-like episodes should always raise concern for the admitting emergency medicine clinician of an underlying cardiac pathology.

Context dependency of top-down, bottom-up and density-dependent influences on cheetah demography.

Research on drivers of demographic rates has mostly focused on top predators and their prey, and comparatively less research has considered the drivers of mesopredator demography. Of those limited studies, most focused on top-down effects of apex predators on mesopredator population dynamics, whereas studies investigating alternative mechanisms are less common. In this study, we tested hypotheses related to top-down, bottom-up and density-dependent regulation of demographic rates in an imperilled mesopredator, the cheetah (Acinonyx jubatus). We used a 25-year dataset of lion density, cheetah density and prey density from the Mun-Ya-Wana Conservancy in South Africa and assessed the effects of top-down, bottom-up and density-dependent drivers on cheetah survival and reproduction. In contrast to the top-down and bottom-up predictions, both adult and juvenile cheetahs experienced the lowest survival during months with high prey densities and low lion densities. We observed support only for a density-dependent response in juvenile cheetahs, where they had a higher probability of reaching independence during times with low cheetah density and low prey density. We did not identify any strong drivers of litter size. Collectively, our results indicate that high apex predator abundance might not always have negative effects on mesopredator populations, and suggest that context dependency in top-down, bottom-up and density-dependent factors may regulate demographic rates of cheetahs and other mesopredators. Our results highlight the complexities of population-level drivers of cheetah demographic rates and the importance of considering multiple hypotheses of mesopredator population regulation.

Combining bacteriophage engineering and linear dichroism spectroscopy to produce a DNA hybridisation assay.

Nucleic acid detection is an important part of our bio-detection arsenal, with the COVID-19 pandemic clearly demonstrating the importance to healthcare of rapid and efficient detection of specific pathogenic sequences. As part of the drive to establish new DNA detection methodologies and signal read-outs, here we show how linear dichroism (LD) spectroscopy can be used to produce a rapid and modular detection system for detecting quantities of DNA from both bacterial and viral pathogens. The LD sensing method exploits changes in fluid alignment of bionanoparticles (bacteriophage M13) engineered with DNA stands covalently attached to their surfaces, with the read-out signal induced by the formation of complementary duplexes between DNA targets and two M13 bionanoparticles. This new sandwich assay can detect pathogenic material down to picomolar levels in under 1 minute without amplification, as demonstrated by the successful sensing of DNA sequences from a plant virus (Potato virus Y) and an ampicillin resistance gene, ampR.

Conservation businesses and conservation planning in a biological diversity hotspot.

The allocation of land to biological diversity conservation competes with other land uses and the needs of society for development, food, and extraction of natural resources. Trade-offs between biological diversity conservation and alternative land uses are unavoidable, given the realities of limited conservation resources and the competing demands of society. We developed a conservation-planning assessment for the South African province of KwaZulu-Natal, which forms the central component of the Maputaland-Pondoland-Albany biological diversity hotspot. Our objective was to enhance biological diversity protection while promoting sustainable development and providing spatial guidance in the resolution of potential policy conflicts over priority areas for conservation at risk of transformation. The conservation-planning assessment combined spatial-distribution models for 646 conservation features, spatial economic-return models for 28 alternative land uses, and spatial maps for 4 threats. Nature-based tourism businesses were competitive with other land uses and could provide revenues of >US$60 million/year to local stakeholders and simultaneously help meeting conservation goals for almost half the conservation features in the planning region. Accounting for opportunity costs substantially decreased conflicts between biological diversity, agricultural use, commercial forestry, and mining. Accounting for economic benefits arising from conservation and reducing potential policy conflicts with alternative plans for development can provide opportunities for successful strategies that combine conservation and sustainable development and facilitate conservation action.

Nonsolvent annealing polymer films with ionic liquids.

Neutron reflectometry has been used to determine the interface structure and swelling of thin polymer films, when annealed in contact with a series of 1-alkyl-3-methylimidazolium ionic liquids (ILs). By choosing immiscible polymer/IL combinations, we have established that thin polymer films can be annealed for several hours in contact with ILs at temperatures well above the glass transition temperature and that this nonsolvent annealing environment can be exploited to direct self-assembly in polymer films. The ingress of IL into polymer films was quantified in terms of the swelling up to 10%. The polymer/IL interfacial width generally also increased from 0.9 nm up to ∼3 nm, but there was remarkably little correlation between interfacial width and swelling. For one combination of polymer and IL (deuterated PMMA and Bmim-BF(4)) the interfacial width decreased slightly with increasing temperature, consistent with LCST behavior for this system. All of the ILs tested had a profound influence the distribution of carboxy-end-functionalized deuterated polystyrene, "dPS-COOH", in blended films with polystyrene homopolymers. The ILs promoted dPS-COOH adsorption at the film/IL interface and the simultaneous rapid desorption at the film silicon-oxide interface. The rate of desorption was found to correlate with the swelling behavior of the polymer with respect to the IL anion species: PF(6)(-) < Br(-) < Cl(-) < BF(4)(-), suggesting that the polymer films are plasticized by the IL as it penetrates the film.

Molecular factor computing for predictive spectroscopy.

PURPOSE: The concept of molecular factor computing (MFC)-based predictive spectroscopy was demonstrated here with quantitative analysis of ethanol-in-water mixtures in a MFC-based prototype instrument. METHODS: Molecular computing of vectors for transformation matrices enabled spectra to be represented in a desired coordinate system. New coordinate systems were selected to reduce the dimensionality of the spectral hyperspace and simplify the mechanical/electrical/computational construction of a new MFC spectrometer employing transmission MFC filters. A library search algorithm was developed to calculate the chemical constituents of the MFC filters. The prototype instrument was used to collect data from 39 ethanol-in-water mixtures (range 0-14%). For each sample, four different voltage outputs from the detector (forming two factor scores) were measured by using four different MFC filters. Twenty samples were used to calibrate the instrument and build a multivariate linear regression prediction model, and the remaining samples were used to validate the predictive ability of the model. RESULTS: In engineering simulations, four MFC filters gave an adequate calibration model (r2 = 0.995, RMSEC = 0.229%, RMSECV = 0.339%, p = 0.05 by f test). This result is slightly better than a corresponding PCR calibration model based on corrected transmission spectra (r2 = 0.993, RMSEC = 0.359%, RMSECV = 0.551%, p = 0.05 by f test). The first actual MFC prototype gave an RMSECV = 0.735%. CONCLUSION: MFC was a viable alternative to conventional spectrometry with the potential to be more simply implemented and more rapid and accurate.