Studying interactions among anthropogenic stressors in freshwater ecosystems: A systematic review of 2396 multiple-stressor experiments.

Understanding the interactions among anthropogenic stressors is critical for effective conservation and management of ecosystems. Freshwater scientists have invested considerable resources in conducting factorial experiments to disentangle stressor interactions by testing their individual and combined effects. However, the diversity of stressors and systems studied has hindered previous syntheses of this body of research. To overcome this challenge, we used a novel machine learning framework to identify relevant studies from over 235,000 publications. Our synthesis resulted in a new dataset of 2396 multiple-stressor experiments in freshwater systems. By summarizing the methods used in these studies, quantifying trends in the popularity of the investigated stressors, and performing co-occurrence analysis, we produce the most comprehensive overview of this diverse field of research to date. We provide both a taxonomy grouping the 909 investigated stressors into 31 classes and an open-source and interactive version of the dataset (https://jamesaorr.shinyapps.io/freshwater-multiple-stressors/). Inspired by our results, we provide a framework to help clarify whether statistical interactions detected by factorial experiments align with stressor interactions of interest, and we outline general guidelines for the design of multiple-stressor experiments relevant to any system. We conclude by highlighting the research directions required to better understand freshwater ecosystems facing multiple stressors.

Heatwaves and carbon dioxide enrichment impact invertebrate drift and insect emergence patterns across time in experimental streams.

Climate change and human land use are considered key threats to freshwater invertebrates. Heatwaves can impact the phenology of insects and population dynamics, yet have been largely ignored in experiments compared to mean temperature changes. Another major anthropogenic stressor driving invertebrate community changes is deposited fine sediment; therefore, effects of key climate-change drivers on invertebrate drift and insect emergence rates may differ between sediment-impacted and non-impacted streams. However, this has never been tested in a realistic outdoor experiment. We investigated the individual and combined effects of two 7-day heatwaves, CO2 enrichment, flow velocity variability (periods of fast and slow) and fine sediment on stream drift and emergence responses, sampled four times during a 7-week experiment in 128 flow-through stream mesocosms. We examined invertebrate drift and insect emergence responses to the four stressors, and used these responses to help explain the benthic invertebrate community responses already assessed (sampled at the end of the experiment). Heatwave 1 strongly increased emergence (dominated by Chironomidae), causing an earlier emergence peak, an effect not repeated during heatwave 2, seven days later. During heatwave 1, emerged chironomids were larger in heated channels, but smaller in heated channels afterwards, suggesting a different effect on body size of short-term heatwaves to previous constant warming experiments. CO2 enrichment reduced drifting EPT and total and Chironomidae emergence on three sampling occasions each. After heatwave 1, total drift and total emergence were strongly reduced by heating in ambient-CO2 channels, whereas no reduction occurred in CO2-enriched channels. During heatwave 2, total drift increased in channels without sediment but not in channels with added sediment. Overall, our findings suggest heatwaves can shift the timing of stream insect emergence, regardless of longer-term mean temperatures. They also show that heatwaves, raised CO2, and fine sediment can modulate each others' effects on drift and emergence dynamics.

Factors of global change affecting plants act at different levels of the ecological hierarchy.

Plants and ecosystems worldwide are exposed to a wide range of chemical, physical, and biological factors of global change, many of which act concurrently. As bringing order to the array of factors is required in order to generate an enhanced understanding of simultaneous impacts, classification schemes have been developed. One such classification scheme is dedicated to capturing the different targets of global change factors along the ecological hierarchy. We build on this pioneering work, and refine the conceptual framework in several ways, focusing on plants and terrestrial systems: (i) we more strictly define the target level of the hierarchy, such that every factor typically has just one target level, and not many; (ii) we include effects above the level of the community, that is, there are effects also at the ecosystem scale that cannot be reduced to any level below this; (iii) we introduce the level of the landscape to capture certain land use change effects while abandoning the level below the individual. We discuss how effects can propagate along the levels of the ecological hierarchy, upwards and downwards, presenting opportunities for explaining non-additivity of effects of multiple factors. We hope that this updated conceptual framework will help inform the next generation of plant-focused global change experiments, specifically aimed at non-additivity of effects at the confluence of many factors.

Predicting hepatic encephalopathy in patients with cirrhosis: A UK population-based study and validation of risk scores.

BACKGROUND: HE is a common neurologic complication in cirrhosis associated with substantial disease and economic burden. HE symptoms are nonspecific and there are limited ways of identifying patients with cirrhosis at high risk of later developing HE. A risk score was previously developed to identify patients at risk of developing HE in a predominately male US cohort. Here, we evaluated the performance of the HE risk scores in a UK cohort study. METHODS: Health care records from Clinical Practice Research Datalink and linked Hospital Episode Statistics were used to select patients with cirrhosis who were diagnosed with HE, confirmed by a diagnosis code for HE or a rifaximin-α prescription. The index date was the date of incident cirrhosis. The study period was from January 2003 to June 2019. RESULTS: A total of 40,809 patients with cirrhosis were selected in the UK cohort, of whom 59% were male. A total of 1561 patients were diagnosed with HE. Applying the UK cohort to the baseline sensitivity risk cutoff (≥-11) from the US cohort provided a sensitivity of 92% and a negative predictive value of 99%. Within a longitudinal model, applying a sensitivity cutoff of ≥-3 to this cohort gave a sensitivity of 89% and a negative predictive value of 99%. CONCLUSIONS: Using data from the UK, the previously developed HE risk scores were found to be reliable for selecting those most likely to progress to HE in patients with liver cirrhosis. Despite the HE risk scores originally being estimated using the data from a predominately male US cohort, the scores were validated and found to be generalizable to female patients.

Winter is coming: Interactions of multiple stressors in winter and implications for the natural world.

Winter is a key driver of ecological processes in freshwater, marine and terrestrial ecosystems, particularly in higher latitudes. Species have evolved various adaptive strategies to cope with food limitations and the cold and dark wintertime. However, human-induced climate change and other anthropogenic stressors are impacting organisms in winter in unpredictable ways. In this paper, we show that global change experiments investigating multiple stressors have predominantly been conducted during summer months. However, effects of anthropogenic stressors sometimes differ between winter and other seasons, necessitating comprehensive investigations. Here, we outline a framework for understanding the different effects of anthropogenic stressors in winter compared to other seasons and discuss the primary mechanisms that will alter ecological responses of organisms (microbes, animals and plants). For instance, while the magnitude of some anthropogenic stressors can be greater in winter than in other seasons (e.g. some pollutants), others may alleviate natural winter stress (e.g. warmer temperatures). These changes can have immediate, delayed or carry-over effects on organisms during winter or later seasons. Interactions between stressors may also vary with season. We call for a renewed research direction focusing on multiple stressor effects on winter ecology and evolution to fully understand, and predict, how ecosystems will fare under changing winters. We also argue the importance of incorporating the interactions of anthropogenic stressors with winter into ecological risk assessments, management and conservation efforts.

Impact of COVID-19 on 1-Year Survival Outcomes in Hepatocellular Carcinoma: A Multicenter Cohort Study.

INTRODUCTION: The COVID-19 pandemic has caused severe disruption of healthcare services worldwide and interrupted patients' access to essential services. During the first lockdown, many healthcare services were shut to all but emergencies. In this study, we aimed to determine the immediate and long-term indirect impact of COVID-19 health services utilisation on hepatocellular cancer (HCC) outcomes. METHODS: A prospective cohort study was conducted from 1 March 2020 until 30 June 2020, correlating to the first wave of the COVID-19 pandemic. Patients were enrolled from tertiary hospitals in the UK and Germany with dedicated HCC management services. All patients with current or past HCC who were discussed at a multidisciplinary meeting (MDM) were identified. Any delay to treatment (DTT) and the effect on survival at one year were reported. RESULTS: The median time to receipt of therapy following MDM discussion was 49 days. Patients with Barcelona Clinic Liver Cancer (BCLC) stages-A/B disease were more likely to experience DTT. Significant delays across all treatments for HCC were observed, but delay was most marked for those undergoing curative therapies. Even though severe delays were observed in curative HCC treatments, this did not translate into reduced survival in patients. CONCLUSION: Interruption of routine healthcare services because of the COVID-19 pandemic caused severe delays in HCC treatment. However, DTT did not translate to reduced survival. Longer follow is important given the delay in therapy in those receiving curative therapy.

Multi-Agent Deep Reinforcement Learning for Multi-Robot Applications: A Survey.

Deep reinforcement learning has produced many success stories in recent years. Some example fields in which these successes have taken place include mathematics, games, health care, and robotics. In this paper, we are especially interested in multi-agent deep reinforcement learning, where multiple agents present in the environment not only learn from their own experiences but also from each other and its applications in multi-robot systems. In many real-world scenarios, one robot might not be enough to complete the given task on its own, and, therefore, we might need to deploy multiple robots who work together towards a common global objective of finishing the task. Although multi-agent deep reinforcement learning and its applications in multi-robot systems are of tremendous significance from theoretical and applied standpoints, the latest survey in this domain dates to 2004 albeit for traditional learning applications as deep reinforcement learning was not invented. We classify the reviewed papers in our survey primarily based on their multi-robot applications. Our survey also discusses a few challenges that the current research in this domain faces and provides a potential list of future applications involving multi-robot systems that can benefit from advances in multi-agent deep reinforcement learning.

Modified future diurnal variability of the global surface ocean CO2 system.

Our understanding of how increasing atmospheric CO2 and climate change influences the marine CO2 system and in turn ecosystems has increasingly focused on perturbations to carbonate chemistry variability. This variability can affect ocean-climate feedbacks and has been shown to influence marine ecosystems. The seasonal variability of the ocean CO2 system has already changed, with enhanced seasonal variations in the surface ocean pCO2 over recent decades and further amplification projected by models over the 21st century. Mesocosm studies and CO2 vent sites indicate that diurnal variability of the CO2 system, the amplitude of which in extreme events can exceed that of mean seasonal variability, is also likely to be altered by climate change. Here, we modified a global ocean biogeochemical model to resolve physically and biologically driven diurnal variability of the ocean CO2 system. Forcing the model with 3-h atmospheric outputs derived from an Earth system model, we explore how surface ocean diurnal variability responds to historical changes and project how it changes under two contrasting 21st-century emission scenarios. Compared to preindustrial values, the global mean diurnal amplitude of pCO2 increases by 4.8 µatm (+226%) in the high-emission scenario but only 1.2 µatm (+55%) in the high-mitigation scenario. The probability of extreme diurnal amplitudes of pCO2 and [H+ ] is also affected, with 30- to 60-fold increases relative to the preindustrial under high 21st-century emissions. The main driver of heightened pCO2 diurnal variability is the enhanced sensitivity of pCO2 to changes in temperature as the ocean absorbs atmospheric CO2 . Our projections suggest that organisms in the future ocean will be exposed to enhanced diurnal variability in pCO2 and [H+ ], with likely increases in the associated metabolic cost that such variability imposes.

Arctic Ocean annual high in [Formula: see text] could shift from winter to summer.

Long-term stress on marine organisms from ocean acidification will differ between seasons. As atmospheric carbon dioxide (CO2) increases, so do seasonal variations of ocean CO2 partial pressure ([Formula: see text]), causing summer and winter long-term trends to diverge1-5. Trends may be further influenced by an unexplored factor-changes in the seasonal timing of [Formula: see text]. In Arctic Ocean surface waters, the observed timing is typified by a winter high and summer low6 because biological effects dominate thermal effects. Here we show that 27 Earth system models simulate similar timing under historical forcing but generally project that the summer low, relative to the annual mean, eventually becomes a high across much of the Arctic Ocean under mid-to-high-level CO2 emissions scenarios. Often the greater increase in summer [Formula: see text], although gradual, abruptly inverses the chronological order of the annual high and low, a phenomenon not previously seen in climate-related variables. The main cause is the large summer sea surface warming7 from earlier retreat of seasonal sea ice8. Warming and changes in other drivers enhance this century's increase in extreme summer [Formula: see text] by 29 ± 9 per cent compared with no change in driver seasonalities. Thus the timing change worsens summer ocean acidification, which in turn may lower the tolerance of endemic marine organisms to increasing summer temperatures.

Improving Operating Room Efficiency: Relocating a Surgical Oncology Program Within a Health Care System.

Background: To meet increased community and regional needs for quality services, our hospital system concluded that its established surgical oncology program-consisting of gynecologic oncology (4 physicians), surgical oncology (2 physicians), and otolaryngologic oncology (2 physicians)-would be best served by the transition of the comprehensive surgical oncology program to a new oncology-naive hospital. We describe the overall strategy and approach involved with this move, its implementation, operating room efficiency results, and physician satisfaction associated with the relocation. Methods: The purpose of the systematic plan for relocation, which was developed and refined during the 2 years preceding the move, was to facilitate a collective awareness and understanding of important patient-centered concepts and essential workflow. All parties involved in direct patient cancer care participated in multiple workgroups to successfully transition the surgical oncology practice. Following the transition to the oncology-naive hospital, components of the operative cases and surgical data were prospectively collected for the initial 6 weeks and compared to retrospective data from the last 8 weeks at the established hospital. The surgical day for each surgeon was deconstructed, and measured variables included total surgical cases, total surgical hours, surgical minutes per case, total anesthesia hours, first case on-time surgical starts, surgical stretcher wheels out to surgical stretcher wheels in, surgical stretcher wheels out to next case start, case end to postanesthesia care unit (PACU), and case end to case start. Results: Five hundred twenty-nine surgical cases encompassing 1,076 anesthesia hours and 710 surgical hours were completed during the 14-week evaluation period. The gynecologic oncologists completed the majority of surgical procedures in both settings. The percentage of first case on-time surgical starts initially decreased during the 6-week interval at the oncology-naive hospital, but interval subset analysis suggested a return to the pre-move norm. Surgical stretcher wheels out to surgical stretcher wheels in had a wide range (9 minutes to 305 minutes) for all surgical sections, but no statistically significant difference was seen overall or for any surgical section. Case end to PACU significantly increased for gynecologic oncology but not for surgical oncology or otolaryngologic oncology. Overall case end to case start times decreased nonsignificantly (63.7 ± 3.1 mean minutes vs 60.3 ± 1.7 mean minutes) following the move. A physician survey found that physicians' expectations were met in terms of the move occurring smoothly without major issues, surgical scheduling and accommodation, anesthesia services, and surgical personnel. Physicians indicated less satisfaction with quality and availability of instrumentation. Conclusion: The transfer of established surgical oncology services to an oncology-naive hospital was associated with early surgeon and operating room staff support, as well as process and programmatic alignment among stakeholders. The success of this transition required transparency, open and honest communication, and problem solving at all levels. The move of a surgical oncology program to an oncology-naive hospital was deemed successful without deterioration of time-related variables associated with operating room efficiency and physician satisfaction. The breakdown and analysis of key components of the surgical day offered additional opportunities for quality improvement in operating room efficiency.

EASL clinical practice guidelines: non-invasive liver tests for evaluation of liver disease severity and prognosis.

The European Association for the Study of the Liver has recently published updated guidelines on the use of non-invasive tests to identify and stratify chronic liver disease. Here, we provide a summary of the key recommendations from the guideline.

Evaluating future risk of NAFLD in adolescents: a prediction and decision curve analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the commonest liver condition in the western world and is directly linked to obesity and the metabolic syndrome. Elevated body mass index is regarded as a major risk factor of NAFL (steatosis) and NAFLD fibrosis. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we sought to investigate whether other variables from adolescence could improve prediction of future NAFL and NAFLD fibrosis risk at 24 years, above BMI and sex. METHODS: Aged 24 years, 4018 ALSPAC participants had transient elastography (TE) and controlled attenuation parameter (CAP) measurement using Echosens 502 Touch. 513 participants with harmful alcohol consumption were excluded. Logistic regression models examined which variables measured at 17 years were predictive of NAFL and NAFLD fibrosis in young adults. Predictors included sex, BMI, central adiposity, lipid profile, blood pressure, liver function tests, homeostatic model assessment for insulin resistance (HOMA-IR), and ultrasound defined NAFL at 17 years (when examining fibrosis outcomes). A model including all these variables was termed "routine clinical measures". Models were compared using area under the receiver operator curve (AUROC) and Bayesian Information Criterion (BIC), analysis, which penalises model complexity. Models were tested in all participants and those with overweight or obese standardised BMIs (BMI SDS) centiles at the 17-year time point. A decision curve analysis (DCA) was performed to evaluate the clinical utility of models in overweight and obese adolescents predicting NAFLD fibrosis at a threshold probability of 0.1. RESULTS: The "routine clinical measures" model had the highest AUROC for predicting NAFL in all adolescent participants (AUROC 0.79 [SD 0.00]) and those with an overweight/obese BMI SDS centile (AUROC 0.77 [SD 0.01]). According to BIC analysis, insulin resistance was the best predictor of NAFL in all adolescents, whilst central adiposity was the best predictor in those with an overweight/obese BMI SDS centile. The "routine clinical measures" model also had the highest AUROC for predicting NAFLD fibrosis in all adolescent participants (AUROC 0.78 [SD 0.02]) and participants with an overweight/obese BMI SDS centile (AUROC 0.84 [SD 0.03]). However, following BIC analysis, BMI was the best predictor of NAFLD fibrosis in all adolescents including those with an overweight/obese BMI SDS centile. A decision curve analysis examining overweight/obese adolescent participants showed the model that had the greatest net benefit for increased NAFLD fibrosis detection, above a treat all overweight and obese adolescents' assumption, was the "routine clinical measures" model. However, the net benefit was marginal (0.0054 [0.0034-0.0075]). CONCLUSION: In adolescents, routine clinical measures were not superior to central adiposity and BMI at predicting NAFL and NAFLD fibrosis respectively in young adulthood. Additional routine clinical measurements do provide incremental benefit in detecting true positive fibrosis cases, but the benefit is small. Thus, to reduce morbidity and mortality associated with NASH cirrhosis in adults, the ultimate end point of NAFLD, the focus must be on obesity management at a population level.

Documenting fishes in an inland sea with citizen scientist diver surveys: using taxonomic expertise to inform the observation potential of fish species.

Long-term monitoring enables scientists and managers to track changes in the temporal and spatial distributions of fishes. Given the anthropogenic stressors affecting marine ecosystem health, there is a critical need for robust, comprehensive fish monitoring programs. Citizen science can serve as a meaningful, cost-effective strategy to survey fish communities. We compared data from 13,000 surveys collected over 21 years (1998-2019) by Reef Environmental Education Foundation (REEF) volunteer divers to a published compilation of Salish Sea ichthyofauna collected using an assortment of methods. Volunteer divers observed 138 of 261 recognized species in the Salish Sea, expanded the range of 18 species into additional Salish Sea sub-basins, and identified one species novel to the Salish Sea (Gibbonsia metzi - Striped Kelpfish). To identify Salish Sea fish species that are most suitable to be monitored by underwater visual census and to evaluate confidence in in situ identification, we developed a categorization system based on the likelihood of recreational divers and snorkelers encountering a given species, and on whether identification required a specimen in hand or could be classified to species visually (with or without a high-quality photograph). REEF divers encountered 62% (138 of 223) of the visually detectable species occurring in the region and 85% (102 of 120) of species most likely to be observed by recreational divers. Our findings show that citizen scientists provide valuable monitoring data for over half of the 261 marine and anadromous fish species known to occupy the Salish Sea, many of which are not routinely monitored otherwise.

Rapid evolution generates synergism between multiple stressors: Linking theory and an evolution experiment.

Global change encompasses many co-occurring anthropogenic stressors. Understanding the interactions between these multiple stressors, whether they be additive, antagonistic or synergistic, is critical for ecosystem managers when prioritizing which stressors to mitigate in the face of global change. While such interactions between stressors appear prevalent, it remains unclear if and how these interactions change over time, as the majority of multiple-stressor studies rarely span multiple generations of study organisms. Although meta-analyses have reported some intriguing temporal trends in stressor interactions, for example that synergism may take time to emerge, the mechanistic basis for such observations is unknown. In this study, by analysing data from an evolution experiment with the rotifer Brachionus calyciflorus (~35 generations and 31,320 observations), we show that adaptation to multiple stressors shifts stressor interactions towards synergism. We show that trade-offs, where populations cannot optimally perform multiple tasks (i.e. adapting to multiple stressors), generate this bias towards synergism. We also show that removal of stressors from evolved populations does not necessarily increase fitness and that there is variation in the evolutionary trajectories of populations that experienced the same stressor regimes. Our results highlight outstanding questions at the interface between evolution and global change biology, and illustrate the importance of considering rapid adaptation when managing or restoring ecosystems subjected to multiple stressors under global change.

Origins and evolution of extreme life span in Pacific Ocean rockfishes.

Pacific Ocean rockfishes (genus Sebastes) exhibit extreme variation in life span, with some species being among the most long-lived extant vertebrates. We de novo assembled the genomes of 88 rockfish species and from these identified repeated signatures of positive selection in DNA repair pathways in long-lived taxa and 137 longevity-associated genes with direct effects on life span through insulin signaling and with pleiotropic effects through size and environmental adaptations. A genome-wide screen of structural variation reveals copy number expansions in the immune modulatory butyrophilin gene family in long-lived species. The evolution of different rockfish life histories is coupled to genetic diversity and reshapes the mutational spectrum driving segregating CpG→TpG variants in long-lived species. These analyses highlight the genetic innovations that underlie life history trait adaptations and, in turn, how they shape genomic diversity.

Association of maternal pre-pregnancy BMI and breastfeeding with NAFLD in young adults: a parental negative control study.

BACKGROUND: The importance of the maternal-infant dyad in the genesis of nonalcoholic fatty liver disease (NAFLD) is of increasing interest. The Avon Longitudinal Study of Parents and Children (ALSPAC) showed that at age 24, 1 in 5 had NAFLD measured by transient elastography and controlled attenuation parameter (CAP). Our aim was to investigate the association between breastfeeding duration and maternal pre-pregnancy BMI on offspring NAFLD in young adulthood. METHODS: 4021 participants attended clinic for FibroScan and CAP measurement using Echosens 502 Touch®. 440 participants with Alcohol Use Disorders were excluded. Offspring of 100 non-singleton pregnancies were excluded. 2961 valid CAP measurements for NAFLD were analysed. Exposures of interest were breastfeeding of any duration, ≥6months exclusive breastfeeding, and maternal pre-pregnancy BMI. Multivariable regression models estimated the odds of NAFLD at 24 years. We performed a paternal negative control test to explore residual confounding in the analyses of pre-pregnancy BMI. FINDINGS: There was a modest inverse association of exclusive and non-exclusive breastfeeding ≥6 months having a protective effect on NAFLD in offspring (OR 0·92 [95%CI 0·66-1·27] and OR 0·90 [0·67-1·21] respectively).The odds of offspring NAFLD in overweight pre-pregnancy maternal BMI and paternal BMI was OR 2·09 [1·62-2·68] and OR 1·33 [95%CI 1·07-1·65] respectively, with the ratio of effect sizes OR 1·57 [1·11-2·22]. Similarly, odds of offspring NAFLD with obese pre-pregnancy maternal BMI and paternal BMI was OR 2·66 [1·71-4·14] and OR 1·35 [0·91-2·00] respectively, with the ratio of effect sizes OR 1·98 [1·05-3·74]. INTERPRETATION: Higher maternal pre-pregnancy BMI was associated with offspring NAFLD, having accounted for shared parental confounding. We did not replicate previous work that found a strong association between breastfeeding and NAFLD. FUNDING: Medical Research Council UK, Alcohol Research UK, David Telling Charitable Trust.

Mechanisms underpinning nonadditivity of global change factor effects in the plant-soil system.

Plant-soil systems are key for understanding the effects of factors of global change. Recent work has highlighted the general importance of considering the simultaneous incidence of some factors or stressors. To help mechanistically dissect the possible interactions of such factors, we here propose three broad groups of mechanisms that may generally lead to nonadditivity of responses within a plant-soil system: direct factor interactions (that is one factor directly changing another), within-plant information processing and crosstalk, and effects of factors on groups of soil biota interacting with plants. Interactions are also possible within and across these groups. Factor interactions are very likely to be present in experiments, especially when dealing with an increasing number of factors. Identifying the nature of such interactions will be essential for understanding and predicting global change impacts on plants and soil.

Predictive factors for carboplatin hypersensitivity reactions in gynecologic cancers: Effect of BRCA status.

INTRODUCTION: Carboplatin hypersensitivity reactions have been reported to occur in up to 16% of patients with gynecologic cancers. Several predisposing factors have been suggested including presence of BRCA1/2 mutation, however, contribution of these mutations to reaction development has not been extensively studied. The purpose of this study was to determine if there is an association between BRCA1/2 mutation status and the development of carboplatin hypersensitivity reactions.Methodology: Eligible patients were women aged 18 years or older with a diagnosis of ovarian, fallopian tube, uterine, endometrial, or primary peritoneal cancer who attempted to receive at least one dose of carboplatin. The primary outcome was the effect of BRCA1/2 status on the development of carboplatin hypersensitivity reactions with regard to: reaction frequency, timing, and severity. Secondary outcomes included identification of additional risk factors that may help identify predisposition to carboplatin hypersensitivity reaction. RESULTS: A total of 44 patients were included in this study. Five patients (38%) in the reaction group and 4 patients (31%) in the no reaction group had a documented mutation in one or both BRCA genes (p = 1.00). No significant differences were found in terms of reaction severity or symptoms, and timing of reaction after dose administration. Incidence of thyroid disorder was significantly higher among patients who experienced a hypersensitivity reaction (1 (4%) vs 10 (45%); p = 0.004). CONCLUSION: BRCA mutation status was not associated with an increased risk of carboplatin hypersensitivity in our patient population. Further investigation into thyroid dysfunction as a risk factor for reaction development is warranted.

Towards a unified study of multiple stressors: divisions and common goals across research disciplines.

Anthropogenic environmental changes, or 'stressors', increasingly threaten biodiversity and ecosystem functioning worldwide. Multiple-stressor research is a rapidly expanding field of science that seeks to understand and ultimately predict the interactions between stressors. Reviews and meta-analyses of the primary scientific literature have largely been specific to either freshwater, marine or terrestrial ecology, or ecotoxicology. In this cross-disciplinary study, we review the state of knowledge within and among these disciplines to highlight commonality and division in multiple-stressor research. Our review goes beyond a description of previous research by using quantitative bibliometric analysis to identify the division between disciplines and link previously disconnected research communities. Towards a unified research framework, we discuss the shared goal of increased realism through both ecological and temporal complexity, with the overarching aim of improving predictive power. In a rapidly changing world, advancing our understanding of the cumulative ecological impacts of multiple stressors is critical for biodiversity conservation and ecosystem management. Identifying and overcoming the barriers to interdisciplinary knowledge exchange is necessary in rising to this challenge. Division between ecosystem types and disciplines is largely a human creation. Species and stressors cross these borders and so should the scientists who study them.