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Sepsis-associated coagulopathy increases risk of mortality. Impairment of the anticoagulant protein C (PC) pathway may contribute to the thrombotic phenotype in coronavirus disease 2019 (COVID-19) sepsis. This study assessed the functionality of this pathway in COVID-19 and non-COVID sepsis by measuring its key enzymes, thrombin and activated PC (APC). The study population included 30 patients with COVID-19, 47 patients with non-COVID sepsis, and 40 healthy controls. In healthy controls, coagulation activation and subsequent APC formation was induced by 15 µg/kg recombinant activated factor VII one hour before blood sampling. APC and thrombin in plasma were measured using oligonucleotide-based enzyme capture assays. The indirect thrombin markers prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) were also measured. Compared with stimulated healthy controls, median thrombin, F1+2, and TAT levels were higher in patients with COVID-19 (up to 6-fold, p < 2 × 10−6) and non-COVID sepsis (up to 4.7-fold, p < 0.010). APC levels were 2.4-fold higher in patients with COVID-19 (7.44 pmol/L, p = 0.011) and 3.4-fold higher in non-COVID sepsis patients (10.45 pmol/L, p = 2 × 10−4) than in controls (3.08 pmol/L). Thrombin markers and APC showed correlation in both COVID-19 (r = 0.364–0.661) and non-COVID sepsis patients (r = 0.535–0.711). After adjustment for PC levels, median APC/thrombin, APC/F1+2, and APC/TAT ratios were 2-fold (p = 0.036), 6-fold (p = 3 × 10−7) and 3-fold (p = 8 × 10−4) lower in the COVID-19 group than in the non-COVID sepsis group, and the latter two were also lower in the COVID-19 group than in stimulated healthy controls. In conclusion, it was found that a comparatively lower anticoagulant APC response in COVID-19 patients as compared to non-COVID sepsis patients, potentially linked to endothelial dysfunction, contributes to the prothrombotic phenotype of COVID-19 sepsis.

Necroptosis, a pathway of regulated necrosis, involves recruitment and activation of RIPK1, RIPK3 and MLKL, leading to cell membrane rupture, cell death and release of intracellular contents causing further injury and inflammation. Necroptosis is believed to play an important role in the pathogenesis of kidney ischemia-reperfusion injury (IRI). However, the dynamics of necroptosis in kidney IRI is poorly understood, in part due to difficulties in detecting phosphorylated MLKL (pMLKL), the executioner of the necroptosis pathway. Here, we investigated the temporal and spatial activation of necroptosis in a mouse model of unilateral warm kidney IRI, using a robust method to stain pMLKL. We identified the period 3-12 hrs after reperfusion as a critical phase for the activation of necroptosis in proximal tubular cells. After 12 hrs, the predominant pattern of pMLKL staining shifted from cytoplasmic to membrane, indicating progression to the terminal phase of necroptotic cell death. Mlkl-ko mice exhibited reduced kidney inflammation at 12 hrs and lower serum creatinine and tubular injury at 24 hrs compared to wild-type littermates. Interestingly, we observed increased apoptosis in the injured kidneys of Mlkl-ko mice, suggesting a relationship between necroptosis and apoptosis in kidney IRI. Together, our findings confirm the role of necroptosis and necroinflammation in kidney IRI, and identify the first 3 hrs following reperfusion as a potential window for targeted treatments.

Highlights Substance use continues to contribute to significant morbidity and mortality in the United States. To reduce the public health burden attributable to substances, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism have identified that medication development for substance use disorder is a high priority research area. We reviewed major classes of abused substances (nicotine, alcohol, cocaine, cannabis, opioids) demonstrating that, sex and gender have not been well-considered in addiction medication development research. When adequate data on sex and gender differences have been evaluated (i.e., in tobacco cessation), clinically significant differences in response have been identified between women and men. However, these data are not at all considered in clinical care guidelines. We recommend improved access to publicly available sex-stratified data from medication development investigations, to inform clinical practice and to improve treatment provided to women with substance use disorders.

Abstract The complement system is a potent mediator of ischemia–reperfusion injury (IRI), which detrimentally affects the function and survival of transplanted kidneys. Human complement receptor 1 (HuCR1) is an integral membrane protein that inhibits complement activation by blocking the convertases that activate C3 and C5. We have previously reported that CSL040, a truncated form of recombinant soluble HuCR1 (sHuCR1), has enhanced complement inhibitory activity and improved pharmacokinetic properties compared to the parent molecule. Here, we compared the capacity of CSL040 and full-length sHuCR1 to suppress complement-mediated organ damage in a mouse model of warm renal IRI. Mice were treated with two doses of CSL040 or sHuCR1, given 1 h prior to 22 min unilateral renal ischemia and again 3 h later. 24 h after reperfusion, mice treated with CSL040 were protected against warm renal IRI in a dose-dependent manner, with the highest dose of 60 mg/kg significantly reducing renal dysfunction, tubular injury, complement activation, endothelial damage, and leukocyte infiltration. In contrast, treatment with sHuCR1 at a molar equivalent dose to 60 mg/kg CSL040 did not confer significant protection. Our results identify CSL040 as a promising therapeutic candidate to attenuate renal IRI and demonstrate its superior efficacy over full-length sHuCR1 in vivo.

Stress is a frequent precipitant of relapse to drug use. Pharmacotherapies targeting a diverse array of neural systems have been assayed for efficacy in attenuating stress-induced drug-seeking in both rodents and in humans, but none have shown enough evidence of utility to warrant routine use in the clinic. We posit that a critical barrier in effective translation is inattention to sex as a biological variable at all phases of the research process. In this review, we detail the neurobiological systems implicated in stress-induced relapse to cocaine, opioids, methamphetamine, and cannabis, as well as the pharmacotherapies that have been used to target these systems in rodent models, the human laboratory, and in clinical trials. In each of these areas we additionally describe the potential influences of biological sex on outcomes, and how inattention to fundamental sex differences can lead to biases during drug development that contribute to the limited success of large clinical trials. Based on these observations, we determine that of the pharmacotherapies discussed only α2-adrenergic receptor agonists and oxytocin have a body of research with sufficient consideration of biological sex to warrant further clinical evaluation. Pharmacotherapies that target β-adrenergic receptors, other neuroactive peptides, the hypothalamic-pituitary-adrenal axis, neuroactive steroids, and the endogenous opioid and cannabinoid systems require further assessment in females at the preclinical and human laboratory levels before progression to clinical trials can be recommended.

An on-chip asymmetric directional coupler (DC) can convert fundamental modes to higher-order modes and is one of the core components of mode-division multiplexing (MDM) technology. In this study, we propose that waveguides of the asymmetric DC can be trimmed by silicon ion implantation to tune the effective refractive index and facilitate mode conversion into higher-order modes. Through this method of tuning, transmission changes of up to 18 dB have been realized with one ion implantation step. In addition, adjusting the position of the ion implantation on the waveguide can provide a further degree of control over the transmission into the resulting mode. The results of this work present a promising new route for the development of high-efficiency, low-loss mode converters for integrated photonic platforms, and aim to facilitate the application of MDM technology in emerging photonic neuromorphic computing.

Outcomes following vagus nerve stimulation (VNS) improve over years after implantation in children with drug-resistant epilepsy. The added value of deep brain stimulation (DBS) instead of continued VNS optimization is unknown. In a prospective, non-blinded, randomized patient preference trial of 18 children (aged 8-17 years) who did not respond to VNS after at least 1 year, add-on DBS resulted in greater seizure reduction compared with an additional year of VNS optimization (51.9% vs. 12.3%, p = 0.047). Add-on DBS also resulted in less bothersome seizures (p = 0.03), but no change in quality of life. DBS may be considered earlier for childhood epilepsy after non-response to VNS. ANN NEUROL 2024;96:405-411., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Lead service lines (LSLs), when present, are the largest source of lead in drinking water, and their removal is necessary to reduce public exposure to lead from drinking water. Unfortunately, the composition of many service lines (SLs) is uncertain. The town of Bennington, Vermont, for example, has unreliable SL records, making it challenging to build an inventory and conduct an LSL replacement program. In 2017, Bennington commenced a project to identify SL materials and replace all LSLs. 159 control homes, consisting of 99 LSL and 60 non-LSL sites, were chosen for record reviews, visual SL observations, fully flushed (FF) and sequential profile water sampling, and test excavations to evaluate method accuracies. Of the 159 control homes, records for 90 % of the 99 known LSL homes were accurate. Whereas 3 % of the 60 non-lead SL homes' records accurately identified SL material. Fully flushed and sequential profile samples (SPSs) were 73 % and 95 % accurate for identifying LSLs and 95 % and 83 % accurate for identifying non-LSLs, respectively. Results were 100 % accurate when visual observations, FF samples, and test excavation were used in a stepwise approach. A stepwise approach consisting of visual SL observations, FF samples, and SPSs achieved a 98 % accuracy at identifying LSLs and a 67 % cost reduction compared to performing test excavations at each home. Findings from this control group study are critical for state, tribal, and local officials to inform their decisions about the selected approach to identify unknown SLs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Patrick Smart, MSK Engineers reports financial support was provided by Vermont Drinking Water State Revolving Fund, (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Protected areas (PAs) are the primary strategy for slowing terrestrial biodiversity loss. Although expansion of PA coverage is prioritized under the Convention on Biological Diversity, it remains unknown whether PAs mitigate declines across the tetrapod tree of life and to what extent land cover and climate change modify PA effectiveness 1,2 . Here we analysed rates of change in abundance of 2,239 terrestrial vertebrate populations across the globe. On average, vertebrate populations declined five times more slowly within PAs (-0.4% per year) than at similar sites lacking protection (-1.8% per year). The mitigating effects of PAs varied both within and across vertebrate classes, with amphibians and birds experiencing the greatest benefits. The benefits of PAs were lower for amphibians in areas with converted land cover and lower for reptiles in areas with rapid climate warming. By contrast, the mitigating impacts of PAs were consistently augmented by effective national governance. This study provides evidence for the effectiveness of PAs as a strategy for slowing tetrapod declines. However, optimizing the growing PA network requires targeted protection of sensitive clades and mitigation of threats beyond PA boundaries. Provided the conditions of targeted protection, adequate governance and well-managed landscapes are met, PAs can serve a critical role in safeguarding tetrapod biodiversity., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Most neonatal and infantile-onset epilepsies have presumed genetic aetiologies, and early genetic diagnoses have the potential to inform clinical management and improve outcomes. We therefore aimed to determine the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in this population., Methods: We conducted an international, multicentre, cohort study (Gene-STEPS), which is a pilot study of the International Precision Child Health Partnership (IPCHiP). IPCHiP is a consortium of four paediatric centres with tertiary-level subspecialty services in Australia, Canada, the UK, and the USA. We recruited infants with new-onset epilepsy or complex febrile seizures from IPCHiP centres, who were younger than 12 months at seizure onset. We excluded infants with simple febrile seizures, acute provoked seizures, known acquired cause, or known genetic cause. Blood samples were collected from probands and available biological parents. Clinical data were collected from medical records, treating clinicians, and parents. Trio genome sequencing was done when both parents were available, and duo or singleton genome sequencing was done when one or neither parent was available. Site-specific protocols were used for DNA extraction and library preparation. Rapid genome sequencing and analysis was done at clinically accredited laboratories, and results were returned to families. We analysed summary statistics for cohort demographic and clinical characteristics and the timing, diagnostic yield, and clinical impact of rapid genome sequencing., Findings: Between Sept 1, 2021, and Aug 31, 2022, we enrolled 100 infants with new-onset epilepsy, of whom 41 (41%) were girls and 59 (59%) were boys. Median age of seizure onset was 128 days (IQR 46-192). For 43 (43% [binomial distribution 95% CI 33-53]) of 100 infants, we identified genetic diagnoses, with a median time from seizure onset to rapid genome sequencing result of 37 days (IQR 25-59). Genetic diagnosis was associated with neonatal seizure onset versus infantile seizure onset (14 [74%] of 19 vs 29 [36%] of 81; p=0·0027), referral setting (12 [71%] of 17 for intensive care, 19 [44%] of 43 non-intensive care inpatient, and 12 [28%] of 40 outpatient; p=0·0178), and epilepsy syndrome (13 [87%] of 15 for self-limited epilepsies, 18 [35%] of 51 for developmental and epileptic encephalopathies, 12 [35%] of 34 for other syndromes; p=0·001). Rapid genome sequencing revealed genetic heterogeneity, with 34 unique genes or genomic regions implicated. Genetic diagnoses had immediate clinical utility, informing treatment (24 [56%] of 43), additional evaluation (28 [65%]), prognosis (37 [86%]), and recurrence risk counselling (all cases)., Interpretation: Our findings support the feasibility of implementation of rapid genome sequencing in the clinical care of infants with new-onset epilepsy. Longitudinal follow-up is needed to further assess the role of rapid genetic diagnosis in improving clinical, quality-of-life, and economic outcomes., Funding: American Academy of Pediatrics, Boston Children's Hospital Children's Rare Disease Cohorts Initiative, Canadian Institutes of Health Research, Epilepsy Canada, Feiga Bresver Academic Foundation, Great Ormond Street Hospital Charity, Medical Research Council, Murdoch Children's Research Institute, National Institute of Child Health and Human Development, National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, One8 Foundation, Ontario Brain Institute, Robinson Family Initiative for Transformational Research, The Royal Children's Hospital Foundation, University of Toronto McLaughlin Centre., Competing Interests: Declaration of interests APa is a current member of the National Institute of Health and Clinical excellence (NICE) technology appraisal committee B and has a financial interest in Genedrive PLC. KW has consulted for Stoke Therapeutics. JHC has received renumeration for lectures by GW pharma/Jazz, UCB/Zogenix, Biocodex, and Biogen; is a member of the Data Monitoring and Safety Committee for Admiral Trial (Stroke Therapeutics); and is Chair of the Medical Advisory Board for Matthews Friends, Dravet UK, and Hope for Hypothalamic Hamartoma. IES has served on scientific advisory boards for BioMarin, Chiesi, Eisai, Encoded Therapeutics, GlaxoSmithKline, Knopp Biosciences, Nutricia, Rogcon, Takeda Pharmaceuticals, UCB, and Xenon Pharmaceuticals; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex, Chiesi, Liva Nova, Nutricia, Zuellig Pharma, and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin, Encoded Therapeutics, and Eisai; has served as an investigator for Anavex Life Sciences, Cerecin, Cerevel Therapeutics, Eisai, Encoded Therapeutics, EpiMinder, Epygenyx, ES-Therapeutics, GW Pharma, Marinus, Neurocrine BioSciences, Ovid Therapeutics, Takeda Pharmaceuticals, UCB, Ultragenyx, Xenon Pharmaceuticals, Zogenix, and Zynerba; and has consulted for Care Beyond Diagnosis, Epilepsy Consortium, Atheneum Partners, Ovid Therapeutics, UCB, Zynerba Pharmaceuticals, BioMarin, Encoded Therapeutics, and Biohaven Pharmaceuticals; and is a Non-Executive Director of Bellberry and a Director of the Australian Academy of Health and Medical Sciences and the Australian Council of Learned Academies. IES might accrue future revenue on pending patent WO61/010176 (filed in 2008; therapeutic compound); has a patent for SCN1A testing held by Bionomics and licensed to various diagnostic companies; has a patent molecular diagnostic or theranostic target for benign familial infantile epilepsy (PRRT2; 2011904493, 2012900190, and PCT/AU2012/001321 [TECH ID:2012-009]). GC has received honorarium from CADTH and serves as the Co-Lead of the Can-GARD Initiative and on the SickKids Precision Child Health steering committee. APo serves on the scientific advisory boards for TevardBio and Syngap Research Fund, and on the American Epilepsy Society Board of Directors. KBH has received support from RogCon Biosciences and Praxis Precision Medicines. AM has received consulting fees from Rocket Pharmaceuticals; honorarium from Jazz Pharmaceuticals; support for attending conferences from Jazz Pharmaceuticals and European Paediatric Neurology Society; fees for participating on boards for Biogen and Biocodex; and serves unpaid roles on the ILAE Genetic Literacy Task Force, EPICARE, and Great Ormond Street Hospital National Institute for Health and Care Research Biomedical Research Centre Chair of Junior Faculty. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Global biodiversity is facing a crisis, which must be solved through effective policies and on-the-ground conservation. But governments, NGOs, and scientists need reliable indicators to guide research, conservation actions, and policy decisions. Developing reliable indicators is challenging because the data underlying those tools is incomplete and biased. For example, the Living Planet Index tracks the changing status of global vertebrate biodiversity, but taxonomic, geographic and temporal gaps and biases are present in the aggregated data used to calculate trends. However, without a basis for real-world comparison, there is no way to directly assess an indicator's accuracy or reliability. Instead, a modelling approach can be used. We developed a model of trend reliability, using simulated datasets as stand-ins for the "real world", degraded samples as stand-ins for indicator datasets (e.g., the Living Planet Database), and a distance measure to quantify reliability by comparing partially sampled to fully sampled trends. The model revealed that the proportion of species represented in the database is not always indicative of trend reliability. Important factors are the number and length of time series, as well as their mean growth rates and variance in their growth rates, both within and between time series. We found that many trends in the Living Planet Index need more data to be considered reliable, particularly trends across the global south. In general, bird trends are the most reliable, while reptile and amphibian trends are most in need of additional data. We simulated three different solutions for reducing data deficiency, and found that collating existing data (where available) is the most efficient way to improve trend reliability, whereas revisiting previously studied populations is a quick and efficient way to improve trend reliability until new long-term studies can be completed and made available., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

As we enter the next phase of international policy commitments to halt biodiversity loss (e.g., Kunming-Montreal Global Biodiversity Framework), biodiversity indicators will play an important role in forming the robust basis upon which targeted, and time sensitive conservation actions are developed. Population trend indicators are one of the most powerful tools in biodiversity monitoring due to their responsiveness to changes over short timescales and their ability to aggregate species trends from global down to sub-national or even local scale. We consider how the project behind one of the foremost population level indicators - the Living Planet Index - has evolved over the last 25 years, its value to the field of biodiversity monitoring, and how its components have portrayed a compelling account of the changing status of global biodiversity through its application at policy, research and practice levels. We explore ways the project can develop to enhance our understanding of the state of biodiversity and share lessons learned to inform indicator development and mobilise action., (© 2023. The Author(s).)

To safeguard nature, we must understand the drivers of biodiversity loss. Time-delayed biodiversity responses to environmental changes (ecological lags) are often absent from models of biodiversity change, despite their well-documented existence. We quantify how lagged responses to climate and land-use change have influenced mammal and bird populations around the world, while incorporating effects of direct exploitation and conservation interventions. Ecological lag duration varies between drivers, vertebrate classes and body size groupings-e.g. lags linked to climate-change impacts are 13 years for small birds, rising to 40 years for larger species. Past warming and land conversion generally combine to predict population declines; however, such conditions are associated with population increases for small mammals. Positive effects of management ( > +4% annually for large mammals) and protected areas ( > +6% annually for large birds) on population trends contrast with the negative impact of exploitation ( < -7% annually for birds), highlighting the need to promote sustainable use. Model projections suggest a future with winners (e.g. large birds) and losers (e.g. medium-sized birds), with current/recent environmental change substantially influencing abundance trends to 2050. Without urgent action, including effective conservation interventions and promoting sustainable use, ambitious targets to stop declines by 2030 may already be slipping out of reach.

We model the post-hexaploidy evolution of four genomes from the Solanaceae, a group of flowering plants comprising tomatoes, potatoes and their relatives. The hexaploidy that these genomes descend from occurred through two sequential allopolyploidy events and was marked by the unequal losses of duplicated genes from the different progenitor subgenomes. In contrast with the hexaploid Brassiceae (broccoli and its relatives), where the subgenome with the most surviving genes arrived last in the hexaploidy, among the Solanaceae the most preserved subgenome descends from one of the original two tetraploid progenitors. In fact, the last-arriving subgenome in these plants actually has the fewest surviving genes in the modern genomes. We explore whether the distribution of repetitive elements (REs) in these genomes can explain the biases in gene losses, but while the signals we find are broadly consistent with a role for high RE density in driving gene losses, the REs turn over so quickly that little signal of the RE condition at the time of paleopolyploidy is extant in the modern genomes.

The wrinkle period and morphology of a metal thin film on an elastic substrate is typically controlled by modifying the substrate before carrying out additional metal deposition steps. Herein, we show that a simultaneously selective and reactive sputtering plasma that modifies the surface of a polydimethylsiloxane (PDMS) substrate while not reacting with the metal during the deposition process decreases the wrinkle wavelength and induces additional wrinkling components and features such as ripples or folds. The selective reaction of the nitrogen plasma with PDMS functionalizes the siloxane surface into silicon oxynitride. This hardens the immediate surface of PDMS, with a quadratic increase in the Young's modulus as a function of the sputtering flow ratio. The increase in the critical strain mismatch and the corresponding presence of folds in the nitrogen-modified wrinkled silver film form a suitable plasmonic platform for surface-enhanced Raman spectroscopy (SERS), yielding an enhancement factor of 4.8 × 10 5 for detecting lipids. This enhancement is linked to the emergence of electromagnetic hotspots from surface plasmon polariton coupling between the folds/wrinkles, which in turn enables the detection of low concentrations of organics using SERS. Furthermore, when strained, the nitrogen-modified wrinkles enhance electrical conductivity by a factor of 12 compared with unmodified films. Finally, the optical properties of the substrate can be tuned by altering the N 2 content. The simple addition of nonreactive nitrogen to silver sputtering enables simultaneous PDMS hardening and growth of the silver film and together provide a new avenue for tuning wrinkling parameters and enhancing the electrical conductivity of pliable surfaces., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

Species monitoring, defined here as the repeated, systematic collection of data to detect long-term changes in the populations of wild species, is a vital component of conservation practice and policy. We created a database of nearly 1200 schemes, ranging in start date from 1800 to 2018, to review spatial, temporal, taxonomic, and methodological patterns in global species monitoring. We identified monitoring schemes through standardized web searches, an online survey of stakeholders, in-depth national searches in a sample of countries, and a review of global biodiversity databases. We estimated the total global number of monitoring schemes operating at 3300-15,000. Since 2000, there has been a sharp increase in the number of new schemes being initiated in lower- and middle-income countries and in megadiverse countries, but a decrease in high-income countries. The total number of monitoring schemes in a country and its per capita gross domestic product were strongly, positively correlated. Schemes that were active in 2018 had been running for an average of 21 years in high-income countries, compared with 13 years in middle-income countries and 10 years in low-income countries. In high-income countries, over one-half of monitoring schemes received government funding, but this was less than one-quarter in low-income countries. Data collection was undertaken partly or wholly by volunteers in 37% of schemes, and such schemes covered significantly more sites and species than those undertaken by professionals alone. Birds were by far the most widely monitored taxonomic group, accounting for around half of all schemes, but this bias declined over time. Monitoring in most taxonomic groups remains sparse and uncoordinated, and most of the data generated are elusive and unlikely to feed into wider biodiversity conservation processes. These shortcomings could be addressed by, for example, creating an open global meta-database of biodiversity monitoring schemes and enhancing capacity for species monitoring in countries with high biodiversity. Article impact statement: Species population monitoring for conservation purposes remains strongly biased toward a few vertebrate taxa in wealthier countries., (© 2021 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Maintaining the resilience of natural populations, their ability to resist and recover from disturbance, is crucial to prevent biodiversity loss. However, the lack of appropriate data and quantitative tools has hampered our understanding of the factors determining resilience on a global scale. Here, we quantified the temporal trends of two key components of resilience-resistance and recovery-in >2000 population time-series of >1000 vertebrate species globally. We show that the number of threats to which a population is exposed is the main driver of resilience decline in vertebrate populations. Such declines are driven by a non-uniform loss of different components of resilience (i.e. resistance and recovery). Increased anthropogenic threats accelerating resilience loss through a decline in the recovery ability-but not resistance-of vertebrate populations. These findings suggest we may be underestimating the impacts of global change, highlighting the need to account for the multiple components of resilience in global biodiversity assessments., (© 2021 The Authors. Ecology Letters published by John Wiley & Sons Ltd.)

Wet grassland populations of wading birds in the United Kingdom have declined severely since 1990. To help mitigate these declines, the Royal Society for the Protection of Birds has restored and managed lowland wet grassland nature reserves to benefit these and other species. However, the impact of these reserves on bird population trends has not been evaluated experimentally due to a lack of control populations. We compared population trends from 1994 to 2018 among 5 bird species of conservation concern that breed on these nature reserves with counterfactual trends created from matched breeding bird survey observations. We compared reserve trends with 3 different counterfactuals based on different scenarios of how reserve populations could have developed in the absence of conservation. Effects of conservation interventions were positive for all 4 targeted wading bird species: Lapwing (Vanellus vanellus), Redshank (Tringa totanus), Curlew (Numenius arquata), and Snipe (Gallinago gallinago). There was no positive effect of conservation interventions on reserves for the passerine, Yellow Wagtail (Motacilla flava). Our approach using monitoring data to produce valid counterfactual controls is a broadly applicable method allowing large-scale evaluation of conservation impact., (© 2021 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)