Characterisation, prevalence and severity of skin lesions caused by ophidiomycosis in a population of wild snakes.

Ophidiomycosis is an emerging infectious disease affecting wild snakes in the Northern Hemisphere. Recently confirmed in Great Britain, the prevalence, severity and significance of ophidiomycosis has yet to be characterised in free-living snakes at a population level in Europe. Therefore, a population of barred grass snakes (Natrix helvetica) in eastern England was monitored for three seasons (May 2019 to October 2021), to investigate the prevalence (25.5%; 191/750 snakes) and severity of skin lesions and their aetiology. The most frequently observed skin lesion characteristics were changes in scale colour, crusting, and scale margin erosion. The majority of such lesions (96.9%; 185/191 snakes) was observed on the ventral surface along the length of the body. The severity of skin lesions was considered mild in more than half of the cases (53.1%; 98/191 snakes). Predominantly, skin lesions were observed in adult snakes (72.8%; 139/191 snakes). Combined histological examinations and qPCR tests of skin lesions from N. helvetica sloughs and/or carcasses confirmed a diagnosis of ophidiomycosis. Further targeted surveillance, supported by molecular and histological examinations to confirm skin lesion aetiology, is required to determine the extent to which our findings reflect the occurrence of ophidiomycosis in populations within wider landscapes.

Standard Versus Modified Ipilimumab, in Combination With Nivolumab, in Advanced Renal Cell Carcinoma: A Randomized Phase II Trial (PRISM).

PURPOSE: Ipilimumab (IPI), in combination with nivolumab (NIVO), is an approved frontline treatment option for patients with intermediate- or poor-risk advanced renal cell carcinoma (aRCC). We conducted a randomized phase II trial to evaluate whether administering IPI once every 12 weeks (modified), instead of once every 3 weeks (standard), in combination with NIVO, is associated with a favorable toxicity profile. METHODS: Treatment-naïve patients with clear-cell aRCC were randomly assigned 2:1 to receive four doses of modified or standard IPI, 1 mg/kg, in combination with NIVO (3 mg/kg). The primary end point was the proportion of patients with a grade 3-5 treatment-related adverse event (trAE) among those who received at least one dose of therapy. The key secondary end point was 12-month progression-free survival (PFS) in the modified arm compared with historical sunitinib control. The study was not designed to formally compare arms for efficacy. RESULTS: Between March 2018 and January 2020, 192 patients (69.8% intermediate/poor-risk) were randomly assigned and received at least one dose of study drug. The incidence of grade 3-5 trAEs was significantly lower among participants receiving modified versus standard IPI (32.8% v 53.1%; odds ratio, 0.43 [90% CI, 0.25 to 0.72]; P = .0075). The 12-month PFS (90% CI) using modified IPI was 46.1% (38.6 to 53.2). At a median follow-up of 21 months, the overall response rate was 45.3% versus 35.9% and the median PFS was 10.8 months versus 9.8 months in the modified and standard IPI groups, respectively. CONCLUSION: Rates of grade 3-5 trAEs were significantly lower in patients receiving modified versus standard IPI. Although 12-month PFS did not meet the prespecified efficacy threshold compared with historical control, informal comparison of treatment groups did not suggest any reduction in efficacy with the modified schedule.

Temporary treatment cessation versus continuation of first-line tyrosine kinase inhibitor in patients with advanced clear cell renal cell carcinoma (STAR): an open-label, non-inferiority, randomised, controlled, phase 2/3 trial.

BACKGROUND: Temporary drug treatment cessation might alleviate toxicity without substantially compromising efficacy in patients with cancer. We aimed to determine if a tyrosine kinase inhibitor drug-free interval strategy was non-inferior to a conventional continuation strategy for first-line treatment of advanced clear cell renal cell carcinoma. METHODS: This open-label, non-inferiority, randomised, controlled, phase 2/3 trial was done at 60 hospital sites in the UK. Eligible patients (aged ≥18 years) had histologically confirmed clear cell renal cell carcinoma, inoperable loco-regional or metastatic disease, no previous systemic therapy for advanced disease, uni-dimensionally assessed Response Evaluation Criteria in Solid Tumours-defined measurable disease, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients were randomly assigned (1:1) at baseline to a conventional continuation strategy or drug-free interval strategy using a central computer-generated minimisation programme incorporating a random element. Stratification factors were Memorial Sloan Kettering Cancer Center prognostic group risk factor, sex, trial site, age, disease status, tyrosine kinase inhibitor, and previous nephrectomy. All patients received standard dosing schedules of oral sunitinib (50 mg per day) or oral pazopanib (800 mg per day) for 24 weeks before moving into their randomly allocated group. Patients allocated to the drug-free interval strategy group then had a treatment break until disease progression, when treatment was re-instated. Patients in the conventional continuation strategy group continued treatment. Patients, treating clinicians, and the study team were aware of treatment allocation. The co-primary endpoints were overall survival and quality-adjusted life-years (QALYs); non-inferiority was shown if the lower limit of the two-sided 95% CI for the overall survival hazard ratio (HR) was 0·812 or higher and if the lower limit of the two-sided 95% CI of the marginal difference in mean QALYs was -0·156 or higher. The co-primary endpoints were assessed in the intention-to-treat (ITT) population, which included all randomly assigned patients, and the per-protocol population, which excluded patients in the ITT population with major protocol violations and who did not begin their randomisation allocation as per the protocol. Non-inferiority was to be concluded if it was met for both endpoints in both analysis populations. Safety was assessed in all participants who received a tyrosine kinase inhibitor. The trial was registered with ISRCTN, 06473203, and EudraCT, 2011-001098-16. FINDINGS: Between Jan 13, 2012, and Sept 12, 2017, 2197 patients were screened for eligibility, of whom 920 were randomly assigned to the conventional continuation strategy (n=461) or the drug-free interval strategy (n=459; 668 [73%] male and 251 [27%] female; 885 [96%] White and 23 [3%] non-White). The median follow-up time was 58 months (IQR 46-73 months) in the ITT population and 58 months (46-72) in the per-protocol population. 488 patients continued on the trial after week 24. For overall survival, non-inferiority was demonstrated in the ITT population only (adjusted HR 0·97 [95% CI 0·83 to 1·12] in the ITT population; 0·94 [0·80 to 1·09] in the per-protocol population). Non-inferiority was demonstrated for QALYs in the ITT population (n=919) and per-protocol (n=871) population (marginal effect difference 0·06 [95% CI -0·11 to 0·23] for the ITT population; 0·04 [-0·14 to 0·21] for the per-protocol population). The most common grade 3 or worse adverse events were hypertension (124 [26%] of 485 patients in the conventional continuation strategy group vs 127 [29%] of 431 patients in the drug-free interval strategy group); hepatotoxicity (55 [11%] vs 48 [11%]); and fatigue (39 [8%] vs 63 [15%]). 192 (21%) of 920 participants had a serious adverse reaction. 12 treatment-related deaths were reported (three patients in the conventional continuation strategy group; nine patients in the drug-free interval strategy group) due to vascular (n=3), cardiac (n=3), hepatobiliary (n=3), gastrointestinal (n=1), or nervous system (n=1) disorders, and from infections and infestations (n=1). INTERPRETATION: Overall, non-inferiority between groups could not be concluded. However, there seemed to be no clinically meaningful reduction in life expectancy between the drug-free interval strategy and conventional continuation strategy groups and treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma. FUNDING: UK National Institute for Health and Care Research.

Activity patterns and reproductive behavior of the Critically Endangered Bermuda skink (Plestiodon longirostris).

The study of rare or cryptic species in zoos can provide insights into natural history and behavior that would be difficult to obtain in the field. Such information can then be used to refine population assessment protocols and conservation management. The Bermuda skink (Plestiodon longirostris) is an endemic Critically Endangered lizard. Chester Zoo's successful conservation breeding program is working to safeguard, increase and reinforce skink populations in the wild. A key aim of this program is to develop our understanding of the behavior of this species. In this study, using 24 h video recordings, we examined the daily activity patterns, basking behavior and food preferences of four pairs of Bermuda skinks. The skinks displayed a bimodal pattern of activity and basking, which may have evolved to avoid the strength of the midday sun in exposed habitats in Bermuda. Captive Bermuda skinks appear to prefer a fruit-based diet to orthopteran prey. We also documented their reproductive behavior and compared it against two closely related species. Although there were many similarities between the courtship and mating behaviors of the three species, there was a significantly shorter period of cloacal contact in the Bermuda skink. Oophagia was also documented for the first time in this species. This knowledge has enabled the evaluation of the current ex-situ management practices of this species, filled gaps in knowledge that would be challenging to obtain in the field, and enabled the enhancement of both animal husbandry and reproductive success for the conservation breeding program.

Hip fracture specialists facilitate low-dose spinal anaesthesia in fractured neck of femur surgery.

Fractured neck of femur is a common but potentially devastating complication of frailty. In other surgical specialities, there is an inverse relationship between surgical experience and duration of surgery; however, this has not been quantified in hip trauma. In perioperative hip fracture care, prolonged surgery may be associated with increased morbidity and significantly impacts on the conduct of anaesthesia. Specifically, low-dose spinal anaesthesia, which is associated with improved haemodynamic stability, cannot be used if surgery is likely to be prolonged. We studied the duration of hip fracture surgery undertaken in our institution and compared this to surgical expertise. We retrospectively explored our theatre database to identify patients who underwent hip fracture surgery in our hospital over a 62-month period, recording duration of surgery and primary operating surgeon. Surgeons were classified into one of 3 groups: Consultant hip surgeon (specialist interest in hip surgery), Consultant orthopaedic surgeon but non-hip specialist, or Non-consultant (trainee or non-training grade). We identified 1426 hip fracture procedures. Consultant hip surgeons performed all types of hip fracture surgery faster, and with reduced variation in surgical duration, than did either non-hip specialist consultants or non-consultant grades. Consultant hip surgeons consistently performed hip fracture surgery in under 60 minutes. Specialist consultant hip surgeons make low-dose spinal anaesthesia (with shorter block duration but increased haemodynamic stability) feasible. Our data supports the development of dedicated hip fracture trauma lists where patients should be operated on by specialist hip surgeons or trainees directly under their supervision.

Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity.

Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.

Neurofibromatosis-associated Gastrointestinal Stromal Tumor Causing Small Bowel Obstruction.

Multiple gastrointestinal stromal tumors (GISTs) of the small intestine is an uncommon finding but can be a marker for underlying neurofibromatosis type 1 (NF1). We present the case of the 38-year-old male without prior NF1 diagnosis who presented with a small bowel obstruction. His physical exam was notable for cutaneous nodules and café-au-lait spots. He progressed to peritonitis and underwent an exploratory laparotomy, which revealed a 6-cm hemorrhagic mass along the antimesenteric border of the jejunum, causing obstruction and perforation. Pathology was consistent with GISTs. NF1-associated GISTs differ from wild-type GISTs in that they are unlikely to have C-KIT and PDGFRA mutations and therefore do not respond to imatinib. Treatment is largely limited to surgical resection; however, there is evidence that MEK inhibitors may prove an additional treatment strategy.

Reliability of environmental DNA surveys to detect pond occupancy by newts at a national scale.

The distribution assessment and monitoring of species is key to reliable environmental impact assessments and conservation interventions. Considerable effort is directed towards survey and monitoring of great crested newts (Triturus cristatus) in England. Surveys are increasingly undertaken using indirect methodologies, such as environmental DNA (eDNA). We used a large data set to estimate national pond occupancy rate, as well as false negative and false positive error rates, for commercial eDNA protocols. Additionally, we explored a range of habitat, landscape and climatic variables as predictors of pond occupancy. In England, 20% of ponds were estimated to be occupied by great crested newts. Pond sample collection error rates were estimated as 5.2% false negative and 1.5% false positive. Laboratory error indicated a negligible false negative rate when 12 qPCR replicates were used. Laboratory false positive error was estimated at 2% per qPCR replicate and is therefore exaggerated by high levels of laboratory replication. Including simple habitat suitability variables into the model revealed the importance of fish, plants and shading as predictors of newt presence. However, variables traditionally considered as important for newt presence may need more precise and consistent measurement if they are to be employed as reliable predictors in modelling exercises.

Survival of climate warming through niche shifts: Evidence from frogs on tropical islands.

How will organisms cope when forced into warmer-than-preferred thermal environments? This is a key question facing our ability to monitor and manage biota as average annual temperatures increase, and is of particular concern for range-limited terrestrial species unable to track their preferred climatic envelope. Being ectothermic, desiccation prone, and often spatially restricted, island-inhabiting tropical amphibians exemplify this scenario. Pre-Anthropocene case studies of how insular amphibian populations responded to the enforced occupation of warmer-than-ancestral habitats may add a valuable, but currently lacking, perspective. We studied a population of frogs from the Seychelles endemic family Sooglossidae which, due to historic sea-level rise, have been forced to occupy a significantly warmer island (Praslin) than their ancestors and close living relatives. Evidence from thermal activity patterns, bioacoustics, body size distributions, and ancestral state estimations suggest that this population shifted its thermal niche in response to restricted opportunities for elevational dispersal. Relative to conspecifics, Praslin sooglossids also have divergent nuclear genotypes and call characters, a finding consistent with adaptation causing speciation in a novel thermal environment. Using an evolutionary perspective, our study reveals that some tropical amphibians have survived episodes of historic warming without the aid of dispersal and therefore may have the capacity to adapt to the currently warming climate. However, two otherwise co-distributed sooglossid species are absent from Praslin, and the deep evolutionary divergence between the frogs on Praslin and their closest extant relatives (~8 million years) may have allowed for gradual thermal adaptation and speciation. Thus, local extinction is still a likely outcome for tropical frogs experiencing warming climates in the absence of dispersal corridors to thermal refugia.

Concise Reporting of Benign Endometrial Biopsies is an Acceptable Alternative to Descriptive Reporting.

In the United Kingdom, endometrial biopsy reports traditionally consist of a morphologic description followed by a conclusion. Recently published consensus guidelines for reporting benign endometrial biopsies advocate the use of standardized terminology. In this project we aimed to assess the acceptability and benefits of this simplified "diagnosis only" format for reporting non-neoplastic endometrial biopsies. Two consultants reported consecutive endometrial biopsies using 1 of 3 possible formats: (i) diagnosis only, (ii) diagnosis plus an accompanying comment, and (iii) the traditional descriptive format. Service users were asked to provide feedback on this approach via an anonymized online survey. The reproducibility of this system was assessed on a set of 53 endometrial biopsies among consultants and senior histopathology trainees. Of 370 consecutive benign endometrial biopsies, 245 (66%) were reported as diagnosis only, 101 (27%) as diagnosis plus a brief comment, and 24 (7%) as diagnosis following a morphologic description. Of the 43 survey respondents (28 gynecologists, 11 pathologists, and 4 clinical nurse specialists), 40 (93%) preferred a diagnosis only, with 3 (7%) being against/uncertain about a diagnosis only report. Among 3 histopathology consultants and 4 senior trainees there was majority agreement on the reporting format in 53/53 (100%) and 52/53 (98%) biopsies. In summary, we found that reporting benign specimens within standardized, well-understood diagnostic categories is an acceptable alternative to traditional descriptive reporting, with the latter reserved for the minority of cases that do not fit into specific categories. This revised approach has the potential to improve reporting uniformity and reproducibility.

Daily activity profile of the golden mantella in the "Froggotron"-A replicated behavioral monitoring system for amphibians.

Research on threatened species in zoos can provide vital information to inform conservation planning and implementation in the field. This is particularly important for rare and cryptic species with behavior patterns that are difficult to observe in the wild. The Critically Endangered golden mantella (Mantella aurantiaca) is an iconic, endemic frog confined to mid-altitude subhumid forest in Moramanga District, Madagascar. Ecological and behavioral data for this highly threatened species are sparse, and conservation work will need to be informed by both in situ and ex situ research on behavior and habitat preferences. This study utilized environmental information gathered in the field to design a system where behavior and microhabitat use could be measured in captivity. Using replicated climatically controlled chambers (the "Froggotrons"), we analysed the 24-h activity profile of the golden mantella in relation to temperature and humidity. Golden mantellas showed a bimodal pattern of activity during the day with much less activity during the night. Frogs kept at warmer temperatures (20-25°C) were more active than those kept under cooler conditions (16-19°C). However, the bimodal pattern was retained under the different temperatures, although the second peak occurred slightly earlier under warmer conditions. Most activity was observed when humidity levels were above 85%, although less than half of the mantellas were active outside leaf microhabitats during peak periods. These findings can inform ongoing field surveys through determining the optimum times of day to either capture or count golden mantellas for further conservation actions.

Zoos and amphibian conservation: Evaluating the impact of "The Year of The Frog" Campaign.

The global reach of zoos has enormous potential to raise awareness of conservation issues such as the amphibian extinction crisis. One mechanism of achieving this is through targeted, time-limited campaigns. However, the longer-term impact of such campaigns on conservation outcomes is rarely evaluated. The goal of this study is to evaluate how zoos view "The Year of The Frog," a campaign launched by zoos in 2008, with the aim of raising awareness of the global amphibian crisis and generating funds to support amphibian conservation initiatives. A questionnaire-based survey of 43 zoos from fourteen countries was used to evaluate how zoo practitioners believed the campaign influenced amphibian conservation some 10 years after its launch. Survey results showed that the campaign not only contributed to the improvement of research into amphibian husbandry in zoos but also increased support of in situ conservation of amphibians. Zoos focused on exotic species, but developed countries led most of the actions of the campaign. The campaign has inspired and encouraged some zoos and other ex situ conservation organizations to embrace amphibian conservation. The next step is to increase collaboration with more organizations through, for example, AArk and IUCN SSC/ASG, particularly in countries that have high amphibian biodiversity.

Mucocele-like lesions of the breast - A radiological and clinicopathological analysis.

INTRODUCTION: Mucocele-like lesions (MLL) of the breast are rare entities which are considered to harbor uncertain malignant potential. Current UK guidelines recommend vacuum assisted excision (VAE) of all such lesions regardless of whether they display epithelial atypia. This study sought to review the key histological and radiological features of MLLs and compare their differing outcomes based on the presence of epithelial atypia. METHODS: Pathology records of a single breast cancer screening center were retrospectively searched for all biopsy diagnosed MLLs over an 11-year period. Upgrade rates to malignancy (positive predictive values) were calculated by reviewing histology from the initial core biopsy and comparing with the corresponding excision specimen. Radiological images were simultaneously reviewed to provide radiological-pathological correlation. RESULTS: Three of 11 patients (27.3%) with atypical MLLs on biopsy had malignant outcomes at excision, compared with only 1 of 36 patients (2.8%) with non-atypical MLLs. The majority of MLLs (93%) were identified as microcalcifications on mammographic imaging. No specific radiological features were predictive of malignancy. CONCLUSIONS: Our data suggest that MLLs without atypia are potentially overtreated with current protocols and could be managed conservatively with radiological follow up. Radiological-pathological correlation is essential.

Optimising sampling and analysis protocols in environmental DNA studies.

Ecological surveys risk incurring false negative and false positive detections of the target species. With indirect survey methods, such as environmental DNA, such error can occur at two stages: sample collection and laboratory analysis. Here we analyse a large qPCR based eDNA data set using two occupancy models, one of which accounts for false positive error by Griffin et al. (J R Stat Soc Ser C Appl Stat 69: 377-392, 2020), and a second that assumes no false positive error by Stratton et al. (Methods Ecol Evol 11: 1113-1120, 2020). Additionally, we apply the Griffin et al. (2020) model to simulated data to determine optimal levels of replication at both sampling stages. The Stratton et al. (2020) model, which assumes no false positive results, consistently overestimated both overall and individual site occupancy compared to both the Griffin et al. (2020) model and to previous estimates of pond occupancy for the target species. The inclusion of replication at both stages of eDNA analysis (sample collection and in the laboratory) reduces both bias and credible interval width in estimates of both occupancy and detectability. Even the collection of > 1 sample from a site can improve parameter estimates more than having a high number of replicates only within the laboratory analysis.

Periprosthetic fractures: the next fragility fracture epidemic? A national observational study.

OBJECTIVES: Periprosthetic fractures have considerable clinical implications for patients and financial implications for healthcare systems. This study aims to determine the burden of periprosthetic fractures of the lower and upper limbs in England and identify any factors associated with differences in treatment and outcome. DESIGN: A national, observational study. SETTING: England. PARTICIPANTS: All individuals admitted to hospital with periprosthetic fractures between 1 April 2015 and 31 December 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: Mortality, length of stay, change in rate of admissions. METHODS: We analysed Hospital Episode Statistics data using the International Classification of Diseases 10th Revision code M96.6 (Fracture of bone following insertion of orthopaedic implant, joint prosthesis, or bone plate) to identify periprosthetic fractures recorded between April 2013 and December 2018. We determined the demographics, procedures performed, mortality rates and discharge destinations. Patient characteristics associated with having a procedure during the index admission were estimated using logistic regression. The annual rate of increase in admissions was estimated using Poisson regression. RESULTS: Between 1 April 2015 and 31 December 2018, there were 13 565 patients who had 18 888 admissions (89.5% emergency) with M96.6 in the primary diagnosis field. There was a 13% year-on-year increase in admissions for periprosthetic fracture in England during that period. Older people, people living in deprived areas and those with heart failure or neurological disorders were less likely to receive an operation. 14.4% of patients did not return home after hospital discharge. The overall inpatient mortality was 4.3% and total 30-day mortality was 3.3%. CONCLUSIONS: The clinical and operational burden of periprosthetic fractures is considerable and increasing rapidly. We suggest that the management of people with periprosthetic fractures should be undertaken and funded in a similar manner to that successfully employed for people sustaining hip fractures, using national standards and data collection to monitor and improve performance.

Using GPS-enabled decoy turtle eggs to track illegal trade.

The insatiable human appetite for wildlife products drives species to extinction, spreads disease and has negative consequences for the economies of source countries [1,2]. As a major transnational enterprise, illegal wildlife trade is valued between eight and 26.5 billion US dollars annually [3,4]. Because law enforcement is often only reactive, information on trafficking routes is key to disrupting trade and curtailing wildlife crime. In our efforts to uncover trade routes of trafficked sea turtle eggs, we developed and field-tested the InvestEGGator, a 3D-printed decoy turtle egg embedded with a GPS-GSM transmitter (Supplemental Information). Illegally collected clutches of turtle eggs containing a decoy transmitter enabled us to track the movements of traffickers, and thus gain a better understanding of illegal trade routes. The decoys, set to emit a signal once an hour, provided five tracks, the most detailed of which identified an entire trade chain, covering 137 km. Using data provided by the decoys, we identified trafficking routes and on two occasions properties of potential interest to law enforcement. Decoys also yielded anecdotal information, furthering our understanding of trafficking routes.

Horizon Scan of the Belt and Road Initiative.

The Belt and Road Initiative (BRI) represents the largest infrastructure and development project in human history, and presents risks and opportunities for ecosystems, economies, and communities. Some risks (habitat fragmentation, roadkill) are obvious, however, many of the BRI's largest challenges for development and conservation are not obvious and require extensive consideration to identify. In this first BRI Horizon Scan, we identify 11 frontier issues that may have large environmental and social impacts but are not yet recognised. More generally, the BRI will increase China's participation in international environmental governance. Thus, new cooperative modes of governance are needed to balance geopolitical, societal, and environmental interests. Upgrading and standardising global environmental standards is essential to safeguard ecological systems and human societies.

Drivers of amphibian population dynamics and asynchrony at local and regional scales.

Identifying the drivers of population fluctuations in spatially distinct populations remains a significant challenge for ecologists. Whereas regional climatic factors may generate population synchrony (i.e. the Moran effect), local factors including the level of density dependence may reduce the level of synchrony. Although divergences in the scaling of population synchrony and spatial environmental variation have been observed, the regulatory factors that underlie such mismatches are poorly understood. Few previous studies have investigated how density-dependent processes and population-specific responses to weather variation influence spatial synchrony at both local and regional scales. We addressed this issue in a pond-breeding amphibian, the great crested newt Triturus cristatus. We used capture-recapture data collected through long-term surveys in five T. cristatus populations in Western Europe. In all populations-and subpopulations within metapopulations-population size, annual survival and recruitment fluctuated over time. Likewise, there was considerable variation in these demographic rates between populations and within metapopulations. These fluctuations and variations appear to be context-dependent and more related to site-specific characteristics than local or regional climatic drivers. We found a low level of demographic synchrony at both local and regional levels. Weather has weak and spatially variable effects on survival, recruitment and population growth rate. In contrast, density dependence was a common phenomenon (at least for population growth) in almost all populations and subpopulations. Our findings support the idea that the Moran effect is low in species where the population dynamics more closely depends on local factors (e.g. population density and habitat characteristics) than on large-scale environmental fluctuation (e.g. regional climatic variation). Such responses may have far-reaching consequences for the long-term viability of spatially structured populations and their ability to respond to large-scale climatic anomalies.