Changes in motor activity level in individuals with frontotemporal dementia.

Changes in motor activity are common in individuals with Frontotemporal dementia (FTD). Yet, it remains unclear why some individuals become motorically hyperactive, while others hypoactive even in early stages of the disease. This study aimed to examine the relationship between motor activity level and (1) FTD clinical subtype, and (2) cortical thickness and subcortical volumes. Eighty-two charts were retrospectively reviewed from patients meeting consensus criteria for one of the three main clinical subtypes of FTD: probable bvFTD, semantic variant Primary Progressive Aphasia (PPA), or non-fluent variant PPA. Participants were assigned to one of three groups: (1) hyperactive, (2) hypoactive, or (3) no record of change. Hyperactivity was prevalent among bvFTD (58.5%) and semantic PPA (68.8%) subtypes while hypoactivity was less common in both subtypes (29.3% and 18.8%, respectively). The majority of patients with non-fluent PPA showed no record of change in motor activity (66.7%). The analysis of cortical thickness and subcortical volumes did not identify significant associations with motor activity levels. In conclusion, increased motor activity is highly prevalent among individuals with FTD, especially bvFTD and svPPA subtypes. These findings may inform prognosis and prediction of changes in motor activity, and allow planning for appropriate environmental and behavioural interventions. Future studies with prospective, standardized longitudinal collection of information regarding the type and level of change in motor activity, including wearable measures of actigraphy, may help to further delineate the onset and progression of abnormal motor behaviours and determine neuroanatomic associations in FTD.

Pathophysiology of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia worldwide. While neuritic plaques consisting of aggregated amyloid-beta proteins and neurofibrillary tangles of accumulated tau proteins represent the pathophysiologic hallmarks of AD, numerous processes likely interact with risk and protective factors and one's culture to produce the cognitive loss, neuropsychiatric symptoms, and functional impairments that characterize AD dementia. Recent biomarker and neuroimaging research has revealed how the pathophysiology of AD may lead to symptoms, and as the pathophysiology of AD gains clarity, more potential treatments are emerging that aim to modify the disease and relieve its burden.

Pre-validation of SENS-IS assay for in vitro skin sensitization of medical devices.

According to ISO 10993-1:2018, the skin sensitization potential of all medical devices must be evaluated, and for this endpoint ISO 10993-10:2010 recommends the use of in vivo assays. The goal of the present study was to determine if the in vitro SENS-IS assay could be a suitable alternative to the current in vivo assays. The SENS-IS assay uses the Episkin Large and SkinEthic RHE reconstructed human epidermis models to evaluate marker genes. In our study, the SENS-IS assay correctly identified 13 sensitizers spiked in a non-polar solvent. In a subsequent analysis six medical device silicone samples previously impregnated with sensitizers were extracted with polar and non-polar solvents. The SENS-IS assay correctly identified five of these extracts, while a sixth extract, which contained the weak sensitizer phenyl benzoate, was classified as negative. However, when this extract was concentrated, or a longer exposure time was used, the assay was able to detect phenyl benzoate. The SENS-IS assay was transferred to a naïve laboratory which correctly identified sensitizers in six blinded silicone samples, including the one containing phenyl benzoate. In light of these results, we conclude that the SENS-IS assay is able to correctly identify the presence of sensitizers in medical devices extracts.

Reverse genetic approaches for the development of Zika vaccines and therapeutics.

In 2015-2016, the little known Zika virus (ZIKV) caused an epidemic, in which it became recognized as a unique human pathogen associated with a range of devastating congenital abnormalities collectively categorized as congenital Zika syndrome (CZS). In adults, the virus can trigger the autoimmune disorder Guillain-Barré syndrome (GBS), characterized by ascending paralysis. In February 2016, the World Health Organization (WHO) declared ZIKV to be a Public Health Emergency of International Concern. The global public health problem prompted academia, industry, and governments worldwide to initiate development of an effective vaccine to prevent another ZIKV epidemic that would put millions at risk. The development of reverse genetic systems for the study and manipulation of RNA viral genomes has revolutionized the field of virology, providing platforms for vaccine and antiviral development. In this review, we discuss the impact of reverse genetic systems on the rapid progress of ZIKV vaccines and antiviral therapeutics.

A review of general surgery resident experience in common bile duct exploration in the ERCP era.

BACKGROUND: Use of minimally invasive techniques for management of common bile duct (CBD) stones has led to declining number of CBD explorations (CBDE) performed at teaching and non-teaching institutions. We evaluate the impact of this decline on surgery training in bile duct procedures. STUDY DESIGN: National operative data for general surgery residents (GSR) were examined from 2000 to 2018. Biliary operations including, cholecystectomy open and laparoscopic, and CBDE open and laparoscopic were evaluated for mean number of cases per graduating GSR. RESULTS: Despite increases in number of GSR, case numbers for laparoscopic cholecystectomy increased 39% from 84 to 117, p < .00001, per GSR. Mean number of cases for open CBDE, however, decreased 74% from 2.7 to 0.7, p < .00001, per GSR and laparoscopic CBDE declined 22% from 0.9 to 0.7 per resident. CONCLUSION: GSR operative case volume in CBDE has declined significantly creating a training deficiency for this complex skill. Novel simulation, including fresh cadavers, may offer the best option with high-fidelity, dynamic training to mitigate the loss of low volume, high acuity procedures.

Sources of viral respiratory infections in Canadian acute care hospital healthcare personnel.

BACKGROUND: Viral respiratory illnesses are common causes of outbreaks and can be fatal to some patients. AIM: To investigate the association between laboratory-confirmed viral respiratory infections and potential sources of exposure during the previous 7 days. METHODS: In this nested case-control analysis, healthcare personnel from nine Canadian hospitals who developed acute respiratory illnesses during the winters of 2010/11-2013/14 submitted swabs that were tested for viral pathogens. Associated illness diaries and the weekly diaries of non-ill participants provided information on contact with people displaying symptoms of acute respiratory illness in the previous week. Conditional logistic regression assessed the association between cases, who were matched by study week and site with controls with no respiratory symptoms. FINDINGS: There were 814 laboratory-confirmed viral respiratory illnesses. The adjusted odds ratio (aOR) of a viral illness was higher for healthcare personnel reporting exposures to ill household members [7.0, 95% confidence interval (CI) 5.4-9.1], co-workers (3.4, 95% CI 2.4-4.7) or other social contacts (5.1, 95% CI 3.6-7.1). Exposures to patients with respiratory illness were not associated with infection (aOR 0.9, 95% CI 0.7-1.2); however, healthcare personnel with direct patient contact did have higher odds (aOR 1.3, 95% CI 1.1-1.6). The aORs for exposure and for direct patient contact were similar for illnesses caused by influenza. CONCLUSION: Community and co-worker contacts are important sources of viral respiratory illness in healthcare personnel, while exposure to patients with recognized respiratory infections is not associated. The comparatively low risk associated with direct patient contact may reflect transmission related to asymptomatic patients or unrecognized infections.

Exploring the Interface of Oncology and Palliative Care in Ireland

Aims To explore the integration and delivery of oncology led referrals to palliative care (PC) by examining physician attitudes and referral practices. Methods An online survey was circulated to oncologists and PC physicians in Ireland. Results The study (N = 100) comprised sixty-nine oncologists (69%) and thirty-one PC physicians (31%). Ninety-two(92%) believe patients with advanced cancer should receive concurrent treatment, however only 53% of oncologists(N = 37) routinely refer. Regarding end-of-life (EOL) care: 81% of oncologists (N = 55) are directly involved in its administration, despite 84% (N = 53) agreeing patients benefit when PC specialists coordinate EOL care. Conclusion The gulf between positive attitudes and limited implementation suggests the need for interdisciplinary changes to facilitate integration of PC in clinical practice in Ireland.

Evaluation of gastric motility in nine dogs before and after prophylactic laparoscopic gastropexy: a pilot study.

BACKGROUND: The purpose of this study was to evaluate the effect of a prophylactic laparoscopic gastropexy on gastric motility in healthy large-breed dogs. METHODS: This was a prospective pilot study with nine healthy client-owned dogs. Each dog was its own control. Gastric motility was evaluated before and after laparoscopic gastropexy. Dogs were fed a standard diet three weeks before and after surgery. Gastric motility was measured before and 3 weeks after surgery. A wireless motility capsule (WMC) was used to measure gastric pH, intragastric pressure, temperature, frequency of contractions, motility index (MI) and transit time. Non-parametric statistical analysis was used to compare the paired data. Clients were contacted for follow-up information 2 years postoperatively. RESULTS: Median frequency of gastric contractions was 1.3 (range, 0.6-1.9 contractions/min) before gastropexy and 1.0 (range, 0.3-2.6 contractions/min) after gastropexy (P = 0.820). Median MI was 49.2 (range, 23.7-96.6) before gastropexy and 28.1 (range, 12.2-148.9) after gastropexy (P = 0.652). Median gastric emptying time was 1140 (range, 486-1230 min) before gastropexy and 1110 (range, 306-2610 min) after gastropexy (P = 0.570). During the hour before the WMC passed through the pylorus, median MI was 72.2 (range, 48.2-549.3) before gastropexy and 52.9 (range, 15.20-322.8) after gastropexy (P = 0.734), and frequency of contractions was 1.1 (range, 0.9-4.1 contractions/min) before gastropexy and 1.2 (range, 0.5-3.0 contractions/min) after gastropexy (P = 0.652). CONCLUSION: Motility in the stomach did not change in healthy dogs after prophylactic laparoscopic gastropexy. We conclude that preventive laparoscopic gastropexy does not induce gastroparesis.

Modelling the effect of spatially variable soil properties on the distribution of weeds.

The patch spraying of weeds is an area of precision agriculture that has had limited uptake. This is in part due to the perceived risks associated with not controlling individual weeds. Nevertheless, the inherent patchiness of weeds makes them ideal targets for site-specific management. We propose using a mechanistic model to identify areas of a field vulnerable to invasion by weeds, allowing the creation of treatment maps that are risk averse. We developed a spatially-explicit mechanistic model of the life-cycle of Alopecurus myosuroides, a particularly problematic weed of cereal crops in the UK. In the model, soil conditions which vary across the field, affect the life-cycle of A. myosuroides. The model was validated using data on the within-field distribution of A. myosuroides on commercial farms and its co-location with soil properties. We demonstrate the important role played by soil properties in determining the within-field distribution of A. myosuroides. We also show that scale-dependent correlations between A. myosuroides and soil properties observed in the field are an emergent property of the modelled dynamics of the A. myosuroides life-cycle. Our model could therefore support effective site-specific management of A. myosuroides within fields by predicting areas that are vulnerable to A. myosuroides. The usefulness of this model in its ability to predict patch locations for A. myosuroides highlights the possibility of using similar models for other species where data are available on the response of the species to various soil properties.

Ambroxol as a novel disease-modifying treatment for Parkinson's disease dementia: protocol for a single-centre, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for ß-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The aims of this trial are to determine if Ambroxol is safe and well-tolerated by individuals with PDD and if Ambroxol affects cognitive, biochemical, and neuroimaging measures. METHODS: This is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician's Global Impression of Change (CGIC). Secondary measures will include the Parkinson's disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson's disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes. DISCUSSION: If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.

An Exploration of the Relationships Among Facial Dimensions, Age, Sex, Dominance Status, and Personality in Rhesus Macaques (Macaca mulatta).

Aspects of personality in nonhuman primates have been linked to health, social relationships, and life history outcomes. In humans as well as nonhuman primates, facial morphology is associated with assertiveness, aggression, and measures of dominance status. In this study we aimed to examine the relationship among facial morphology, age, sex, dominance status, and ratings on the personality dimensions Confidence, Openness, Assertiveness, Friendliness, Activity, and Anxiety in rhesus macaques (Macaca mulatta). We measured facial width-to-height ratio (fWHR) and lower-height/full-height ratio (fLHFH) using photographs from 109 captive rhesus macaques, which observers also assessed for dominance status and personality, and explored the associations among facial morphology, age, sex, dominance status, and personality. fWHR and fLHFH personality associations depended on age category: Assertiveness was associated with higher fWHR and fLHFH, and Confidence was associated with lower fWHR and fLHFH, but all these associations were consistent only in individuals <8 yr. of age. We found fWHR and fLHFH to not be consistently associated with sex or dominance status; compared to younger individuals, we found few associations with fWHR and fLHFH for individuals older than 8 yr., which may be due to limited sample size. Our results indicate that in macaques <8 yr. old, facial morphology is associated with the Assertiveness and Confidence personality dimensions, which is consistent with results suggesting a relationship between fWHR and trait aggression in humans and assertiveness in brown capuchins, all of which implies that fWHR might be a cue to assertive and aggressive traits.

Fragile X mental retardation protein is a Zika virus restriction factor that is antagonized by subgenomic flaviviral RNA.

Subgenomic flaviviral RNA (sfRNA) accumulates during infection due to incomplete degradation of viral genomes and interacts with cellular proteins to promote infection. Here we identify host proteins that bind the Zika virus (ZIKV) sfRNA. We identified fragile X mental retardation protein (FMRP) as a ZIKV sfRNA-binding protein and confirmed this interaction in cultured cells and mouse testes. Depletion of FMRP elevated viral translation and enhanced ZIKV infection, indicating that FMRP is a ZIKV restriction factor. We further observed that an attenuated ZIKV strain compromised for sfRNA production was disproportionately stimulated by FMRP knockdown, suggesting that ZIKV sfRNA antagonizes FMRP activity. Importantly, ZIKV infection and expression of ZIKV sfRNA upregulated endogenous FMRP target genes in cell culture and ZIKV-infected mice. Together, our observations identify FMRP as a ZIKV restriction factor whose activity is antagonized by the sfRNA. Interaction between ZIKV and FMRP has significant implications for the pathogenesis of ZIKV infections.

Pemetrexed Continuation Maintenance Phase 3 Trials in Nonsquamous, Non-Small-Cell Lung Cancer: Focus on 2-Year Overall Survival and Continuum of Care.

Although lung cancer prognosis remains poor for most patients, treatments developed in the past 2 decades have extended survival for many. For those with disease that responded to or those with stable disease after receipt of platinum-based chemotherapy, maintenance regimens enable continued targeting of tumors beyond the induction phase, which is limited by toxicity. This overview summarizes completed phase 3 trials of pemetrexed continuation maintenance treatment in nonsquamous, non-small-cell lung cancer with a focus on 2-year survival, and highlights similar ongoing trials. Some studies showed survival benefits of pemetrexed maintenance treatment versus control arms, with the potential for added benefit when combined with bevacizumab. Two-year survival rates underscore the value of maintenance therapy and suggest progress toward a clinical goal of managing non-small-cell lung cancer as a treatable chronic disease.

Rash management and treatment persistence of cancer patients treated with epidermal growth factor receptor inhibitors in the Truven MarketScan® research database.

PURPOSE: Rash toxicity is a common, expected class effect of epidermal growth factor receptor (EGFR) inhibitors. Although rash management is practiced, it is not well characterized in the real-world setting. We describe the management of rash that developed while receiving EGFR-inhibitor therapy and how rash affects treatment duration, using Truven MarketScan® Research Database, a US medical claims database. METHODS: Adult patients who received EGFR-inhibitor treatment between 2004 and 2015 after a diagnosis of colon, head and neck, lung, breast, or thyroid cancer were identified. Descriptive analyses were conducted to describe occurrence of rash during the EGFR-inhibitor treatment period, EGFR-inhibitor treatment persistence and management of rash, including treatment and cost. RESULTS: Of 44,533 eligible patients, 4649 (10.4%) had records of rash during the EGFR-inhibitor treatment period, and of patients experiencing rash, 2891 (62.2%) received prescription drugs for rash treatment. Treatment persistence with an EGFR inhibitor was longer among patients experiencing rash compared with no rash (median 178 vs. 80 days for EGFR-TKIs, 85 vs. 57 days for EGFR-monoclonal antibodies), especially among patients with rash who were treated for rash (208 days for EGFR-tyrosine kinase inhibitors, 104 days for EGFR- monoclonal antibodies). Annualized cost during EGFR-inhibitor treatment was lowest among patients not experiencing rash (US$185,619), followed by rash patients receiving drugs for rash management (US$215,561), and highest among rash patients not treated for rash (US$267,105). CONCLUSION: Our findings suggest that management of EGFR inhibitor-associated rash could be important for EGFR-inhibitor treatment persistence.

BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells.

Bromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and nuclear factor-κB (NF-κB) target genes that undermines the growth and survival of mantle cell lymphoma (MCL) cells. However, BET bromodomain inhibitor (BETi) treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4 that potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells. BET-PROTACs induce more apoptosis than BETi of MCL cells, including those resistant to ibrutinib. BET-PROTAC treatment induced more perturbations in the mRNA and protein expressions than BETi, with depletion of c-Myc, CDK4, cyclin D1 and the NF-κB transcriptional targets Bcl-xL, XIAP and BTK, while inducing the levels of HEXIM1, NOXA and CDKN1A/p21. Treatment with ARV-771, which possesses superior pharmacological properties compared with ARV-825, inhibited the in vivo growth and induced greater survival improvement than the BETi OTX015 of immune-depleted mice engrafted with MCL cells. Cotreatment of ARV-771 with ibrutinib or the BCL2 antagonist venetoclax or CDK4/6 inhibitor palbociclib synergistically induced apoptosis of MCL cells. These studies highlight promising and superior preclinical activity of BET-PROTAC than BETi, requiring further in vivo evaluation of BET-PROTAC as a therapy for ibrutinib-sensitive or -resistant MCL.

Changes in soil organic matter over 70 years in continuous arable and ley-arable rotations on a sandy loam soil in England.

The sequestration in soil of organic carbon (SOC) derived from atmospheric carbon dioxide (CO2) by replacing arable crops with leys, has been measured over 70 years on a sandy loam soil. The experiment was designed initially to test the effect of leys on the yields of arable crops. A 3-year grazed grass with clover (grass + clover) ley in a 5-year rotation with arable crops increased percentage organic carbon (%OC) in the top 25 cm of the soil from 0.98 to 1.23 in 28 years, but with little further increase during the next 40 years with all-grass leys given fertilizer nitrogen (N). In this second period, OC inputs were balanced by losses, suggesting that about 1.3% OC might be near the equilibrium content for this rotation. Including 3-year lucerne (Medicago sativa) leys had little effect on %OC over 28 years, but after changing to grass + clover leys, %OC increased to 1.24 during the next 40 years. Eight-year leys (all grass with N or grass + clover) in 10-year rotations with arable crops were started in the 1970s, and after three rotations %OC had increased to ca. 1.40 in 2000-2009. Over 70 years, %OC declined from 0.98 to 0.94 in an all-arable rotation with mainly cereals and to 0.82 with more root crops. Applications of 38 t ha-1 farmyard manure (FYM) every fifth year increased %OC by 0.13% by the mid-1960s when applications ceased. Soil treated with FYM still contained 0.10% more OC in 2000-2009. Changes in the amount of OC have been modelled with RothC-26.3 and estimated inputs of C for selected rotations. Little of the OC input during the 70 years has been retained; most was retained in the grazed ley rotation, but 9 t ha-1 only of a total input of 189 t ha-1. In other rotations more than 98% of the total OC input was lost. Despite large losses of C, annual increases in OC of 4‰ are possible on this soil type with the inclusion of grass or grass + clover leys or the application of FYM, but only for a limited period. Such increases in SOC might help to limit increases in atmospheric CO2. HIGHLIGHTS: Can leys sequester significant amounts of atmospheric CO 2 in SOM and contribute to the 4‰ initiative?Changes in the percentage and amount of OC were measured and modelled over 70 years and OC losses estimated.Three-year grass or grass + clover leys increased %OC, but only to an equilibrium level that was then maintained.Despite large losses, sequestering CO 2-C at 4‰ year-1 by growing grass or grass + clover leys is possible.

Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells.

The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reverse Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in messenger RNA (mRNA) and protein expressions than OTX015 in sAML cells. Specifically, compared with OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, p-STAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared with OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.

Antenatal Pertussis Vaccination: Why are General Practitioners Reluctant? A Mixed Methods StudySetting.

Pertussis has a disproportionately higher morbidity and mortality in infants less than 3 months of age. International and national guidelines recommend pertussis vaccination during pregnancy, as a safe and effective way to protect these infants. Antenatal pertussis vaccination uptake rates remain suboptimal, with many health care professionals (HCPs) still not recommending it. The reasons underlying this reluctance on behalf of HCPs have not been fully established. This study aims to evaluate the current practice and attitudes of General Practitioners (GPs) with regard to antenatal pertussis vaccination. An embedded mixed method design was used. The response rate was 41% (n=109). 54% of GPs who responded (n=59) routinely recommend antenatal pertussis vaccination. Safety concerns and a sense of isolation emerged as the major qualitative themes. More safety data, adequate funding from the Health Service Executive (HSE) and support from secondary care may help to increase the GP recommendation rate and enhance vaccination uptake in pregnancy.

Cliff-nesting seabirds influence production and sediment chemistry of lakes situated above their colony.

Seabirds that congregate in large numbers during the breeding season concentrate marine-derived nutrients to their terrestrial nesting sites, and these nutrients disperse and enhance production in nearby terrestrial, freshwater and marine ecosystems. In the Canadian Arctic, large seabird colonies (>100,000 breeding pairs) nest on cliff faces that drain directly in the ocean, ultimately returning the nutrients back to the marine environment from which they were derived. However, strong winds blowing up cliff faces could transport nutrients up in elevation and onto surrounding terrestrial and aquatic environments. Here, we assess the degree to which seabird nutrients and metals have been delivered to coastal lakes near Hudson Strait (Nunavut, Canada) over the past century. Three lakes located at a higher elevation and increasing distance from a thick-billed murre (Uria lomvia) colony (~400,000 breeding pairs) were sampled for surface water chemistry. In addition, algal assemblages, nitrogen isotopes, and metal/metalloids were analyzed in four dated sediment cores. Elevated nutrients and major ions, as well as an enriched δ15N signature in the sediment cores, were measured in the lake <100m from the cliff, whilst no comparable changes were recorded in lakes >1km from the seabird colony. In contrast, similar oligotrophic and benthic diatom assemblages were identified in all three lakes, suggesting that diatoms were not influenced by enhanced nutrient inputs in this Arctic environment. Chemical tracers (e.g., total mercury) and algal assemblages in the lake near the colony suggest climate warming since ~1950 was the most likely driver of limnological changes, but this effect was muted in the more distant lakes. These pronounced changes in the seabird-impacted lake suggest that, with warming air temperatures and diminished lake ice cover, longer growing seasons may allow for aquatic organisms to more fully exploit the seabird nutrient subsidies.