Data quality assessment of the Dutch Breast Implant Registry by automated data verification using medical billing data.

BACKGROUND: The Dutch Breast Implant Registry (DBIR) provides real-time population-based data to monitor and improve the quality and safety of breast implants and to trace patients in the event of an (inter)national recall. To serve these main goals, the capture rate and percentage of implants that are actually registered should be known and data should be complete. This study aimed to describe an automated verification process for capture rates and data completeness using medical billing data as the external source. METHODS: DBIR-data on reconstructive permanent breast implants and tissue expanders (TEs) from 2019 were compared to medical billing data. At the hospital level, the capture rate of DBIR and accuracy of the selected data points were assessed. RESULTS: In total, 2389 implants (1420 patients) were included from 12 participating hospitals (11% of all healthcare institutions registering in DBIR). DBIR had capture rates of 99% to 114% for inserted permanent implants and TEs and 49% for explanted permanent implants and TEs. Among the 9015 data points analyzed in DBIR, 8861 (98%) matched the medical billing data. Mastopexy had the highest matching percentage (100%) and capsulectomy the lowest (86%). CONCLUSION: This study showed varying capture rates in DBIR depending on the intervention group, indicating that registration of DBIR-data and medical billing codes could be further optimized. Data accuracy was high as only 2% of data points did not correspond to medical billing data. For future data verification, other external data sources could be explored, including sources that enable verification of cosmetic implants.

Impact of Baseline Renal Insufficiency on Piflufolastat F-18 Performance and Investigation of Changes in Renal Function Following Piflufolastat F-18 Administration: Results From the OSPREY Trial.

INTRODUCTION: Piflufolastat F-18, a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, is predominantly eliminated via urinary excretion, and the kidneys have one of the highest absorbed doses. Therefore, this subgroup analysis aimed to investigate the impact of piflufolastat F-18 on renal function and its diagnostic performance in patients stratified by baseline renal function. PATIENTS AND METHODS: The OSPREY clinical trial enrolled 2 cohorts: A-high-risk patients undergoing radical prostatectomy with pelvic lymphadenectomy, and B-patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Baseline estimated glomerular filtration rates were calculated, and patients were stratified by baseline chronic kidney disease (CKD) stage. Changes in serum creatinine within 28 days postdose and diagnostic performance of piflufolastat F-18 were assessed for each CKD stage group in both cohorts. RESULTS: 385 patients (cohort A, n = 268; cohort B, n = 117) underwent piflufolastat F-18-PET/CT. Baseline and postpiflufolastat F-18 median creatinine levels (mg/dL) were similar for patients in cohort A (0.95 [n = 264] vs. 0.95 [n = 252], respectively) and cohort B (0.93 [n = 116] vs. 0.96 [n = 84], respectively). Among 332 men (cohort A, n = 249; cohort B, n = 83) with baseline and postpiflufolastat creatinine measurements, there were minimal changes in creatinine across all baseline CKD stage groups (median change ranged from -0.02 to 0.023 in groups with >1 patient). The diagnostic performance of piflufolastat F-18 showed no meaningful differences when stratified by baseline CKD stage. CONCLUSION: Piflufolastat F-18 appears to be safe and effective for imaging prostate cancer, including men with mild/moderate renal insufficiency.

Evaluation of gradient strip diffusion for susceptibility testing of aztreonam-avibactam in metallo-ß-lactamase-producing Enterobacterales.

The emergence of metallo-ß-lactamase (MBL)-producing Enterobacterales presents unique clinical treatment challenges. Recently developed ß-lactam/ ß-lactamase inhibitor combination agents, while effective against other carbapenemase-producing organisms, are notably ineffective against MBL producers. While MBLs do not hydrolyze monobactams (aztreonam), many MBL-producing organisms are resistant to aztreonam through alternate mechanisms, leaving cefiderocol as the sole monotherapy treatment option recommended for MBL producers. Recent guidelines for the treatment of MBL-harboring organisms have added combination therapy with aztreonam and ceftazidime-avibactam, using ceftazidime-avibactam as a source of the ß-lactamase inhibitor avibactam. Current laboratory testing options for the combination of aztreonam-avibactam are limited to broth microdilution (BMD) and broth disk elution (BDE) methods, which are not practical in most clinical laboratories. In this study, we evaluated the performance of aztreonam/avibactam gradient strips on 103 MBL-producing Enterobacterales patient isolates as well as an additional 31 isolates from the CDC AR Bank. All MBL Enterobacterales patient isolates included in this study harbored a New Delhi metallo-ß-lactamase (blaNDM) gene. Essential agreement of gradient strip minimal inhibitory concentrations (MICs) for patient isolates compared to BMD was 93.2%. While there are no established breakpoints for aztreonam-avibactam, category agreement (CA) for patient isolates was 97.1% when using the CLSI aztreonam breakpoints. There were no major or very major errors observed. There were three minor errors. Precision for aztreonam-avibactam gradient strip diffusion was 100%. These data demonstrate that the use of gradient strip diffusion for aztreonam-avibactam MIC determination in MBL-producing Enterobacterales is a viable option for clinical laboratories.

HLA-C Peptide Repertoires as Predictors of Clinical Response during Early SARS-CoV-2 Infection.

The human leukocyte antigen (HLA) system plays a pivotal role in the immune response to viral infections, mediating the presentation of viral peptides to T cells and influencing both the strength and specificity of the host immune response. Variations in HLA genotypes across individuals lead to differences in susceptibility to viral infection and severity of illness. This study uses observations from the early phase of the COVID-19 pandemic to explore how specific HLA class I molecules affect clinical responses to SARS-CoV-2 infection. By analyzing paired high-resolution HLA types and viral genomic sequences from 60 patients, we assess the relationship between predicted HLA class I peptide binding repertoires and infection severity as measured by the sequential organ failure assessment score. This approach leverages functional convergence across HLA-C alleles to identify relationships that may otherwise be inaccessible due to allelic diversity and limitations in sample size. Surprisingly, our findings show that severely symptomatic infection in this cohort is associated with disproportionately abundant binding of SARS-CoV-2 structural and non-structural protein epitopes by patient HLA-C molecules. In addition, the extent of overlap between a given patient's predicted HLA-C and HLA-A peptide binding repertoires correlates with worse prognoses in this cohort. The findings highlight immunologic mechanisms linking HLA-C molecules with the human response to viral pathogens that warrant further investigation.

Machine learning with multiple modalities of brain magnetic resonance imaging data to identify the presence of bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a chronic psychiatric mood disorder that is solely diagnosed based on clinical symptoms. These symptoms often overlap with other psychiatric disorders. Efforts to use machine learning (ML) to create predictive models for BD based on data from brain imaging are expanding but have often been limited using only a single modality and the exclusion of the cerebellum, which may be relevant in BD. METHODS: In this study, we sought to improve ML classification of BD by combining information from structural, functional, and diffusion-weighted imaging. Participants (108 BD I, 78 control) with BD type I and matched controls were recruited into an imaging study. This dataset was randomly divided into training and testing sets. For each of the three modalities, a separate ML model was selected, trained, and then used to generate a prediction of the class of each test subject. Majority voting was used to combine results from the three models to make a final prediction of whether a subject had BD. An independent replication sample was used to evaluate the ability of the ML classification to generalize to data collected at other sites. RESULTS: Combining the three machine learning models through majority voting resulted in an accuracy of 89.5 % for classification of the test subjects as being in the BD or control group. Bootstrapping resulted in a 95 % confidence interval of 78.9 %-97.4 % for test accuracy. Performance was reduced when only using 2 of the 3 modalities. Analysis of feature importance revealed that the cerebellum and nodes of the emotional control network were among the most important regions for classification. The machine learning model performed at chance on the independent replication sample. CONCLUSION: BD I could be identified with high accuracy in our relatively small sample by combining structural, functional, and diffusion-weighted imaging data within a single site but not generalize well to an independent replication sample. Future studies using harmonized imaging protocols may facilitate generalization of ML models.

Exploring the therapeutic potential of prolinamides as multi-targeted agents for Alzheimer's disease treatment: molecular docking and molecular dynamic simulation studies.

Alzheimer's disease (AD) presents a significant global health challenge, with its prevalence expected to rise sharply in the coming years. Despite extensive research, effective treatments addressing the multifaceted pathophysiology of AD remain elusive. This study investigates the therapeutic potential of twenty-seven prolinamides (P1 - P27), with the focus on their interactions with key proteins implicated in AD pathogenesis. Four of the compounds, namely; 10-((4-nitrophenyl)prolyl)-10 H-phenothiazine (P14), 2-((4-nitrophenyl)prolyl)isoindoline (P19), 1-(4-formylphenyl)-N-(p-tolyl)pyrrolidine-2-carboxamide (P22), and N,1-bis(4-nitrophenyl)pyrrolidine-2-carboxamide (P27) showed promising potential as Alzheimer's drug. In-silico approaches including molecular docking, molecular dynamic (MD) simulation, post md study, physicochemical and drug-likeness parameters were employed to ascertain the potential of these compounds as inhibitors of certain proteins implicated in the pathophysiology of Alzheimer's disease. Molecular docking and dynamics simulations demonstrated that P14, P19, P22 and P27 exhibited promising binding affinities towards crucial AD-associated proteins, including Beta-Secretase 1 (BACE1), Butyrylcholinesterase (BuChE), and Tau-tubulin kinase 2 (TTBK2). Structural stability analyses revealed that prolinamides, particularly P22 and P27 for BACE1 and P14 and P19 for BuChE, exhibited greater stability than their reference ligands, indicated by lower RMSD, RoG, and RMSF values. For BuChE, Rivastigmine had a docking score of -7.0 kcal/mol, a binding free energy (ΔGbind) of -22.19 ± 2.44 kcal/mol, RMSD of 1.361 ± 0.162 Å, RMSF of 9.357 ± 3.212 Å, and RoG of 22.919 ± 0.064 Å, whereas P19 exhibited a superior docking score of -10.3 kcal/mol, a significantly better ΔGbind of -33.74 ± 2.84 kcal/mol, RMSD of 1.347 ± 0.132 Å, RMSF of 8.164 ± 2.748 Å, and RoG of 22.868 ± 0.070 Å. Physicochemical and pharmacokinetic assessments affirmed the drug-likeness and bioavailability of P19 notably capable of penetrating the blood-brain barrier. Compounds P19 and P22, emerged as multi-targeted ligands, offering the potential for simultaneous modulation of multiple AD-related pathways. These findings highlight the possibilities of these compounds to be explored as novel therapeutic agents for AD. They also highlight the need for further experimental validation to confirm their efficacy and safety profiles, advancing them toward clinical application in AD management. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00250-z.

Lead exposure of a fossorial rodent varies with the use of ammunition across the landscape.

Exposure to heavy metals has been documented in a wide range of wildlife species, but infrequently in ground squirrels. This is despite their tendency to be targets of recreational shooters and the accumulation of lead ammunition in the soil environments they inhabit. We analyzed lead and copper concentrations in liver (nPb = 116, nCu = 101) and femur (nPb = 116, nCu = 116) of Piute ground squirrels (Urocitellus mollis) and in soil (n = 75) on public lands in southwestern Idaho to understand how lead exposure may vary across a gradient of intensities and histories of shooting activity. The liver and femur of squirrels from areas used for recreational shooting for >30 years had elevated lead concentrations relative to areas where shooting was rare or did not occur (our negative control), but as expected, lower than areas used for military target training for >70 years (our positive control). Lead concentration in soils were higher in areas used for military target training than in those used for recreational shooting. There were no differences in copper concentrations in biological or soil samples among sites. These data suggest that ground squirrels can be influenced by the history of lead use in their local environment, and they illustrate another pathway by which human activity can influence toxicant exposure to wildlife.

One-food versus 4-food elimination diet for pediatric eosinophilic esophagitis: A multisite randomized trial.

BACKGROUND: A 6-food elimination diet in pediatric eosinophilic esophagitis (EoE) is difficult to implement and may negatively affect quality of life (QoL). Less restrictive elimination diets may balance QoL and efficacy. OBJECTIVE: We performed a multisite, randomized comparative efficacy trial of a 1-food (milk) elimination diet (1FED) versus 4-food (milk, egg, wheat, soy) elimination diet (4FED) in pediatric EoE. METHODS: Patients aged 6 to 17 years with histologically active and symptomatic EoE were randomized 1:1 to 1FED or 4FED for 12 weeks. Primary end point was symptom improvement by Pediatric Eosinophilic Esophagitis Symptom Score (PEESS). Secondary end points were proportion experiencing histologic remission (<15 eosinophils per high-power field); change in histologic features (histology scoring system), endoscopic severity (endoscopic reference score), transcriptome (EoE diagnostic panel), and QoL scores; and predictors of remission. RESULTS: Sixty-three patients were randomly assigned to 1FED (n = 38) and 4FED (n = 25). In 4FED versus 1FED, mean PEESS improved -25.0 versus -14.5 (P = .04), but remission rates (41% vs 44%; P = 1.00), histology scoring system (-0.25 vs -0.29; P = .77), endoscopic reference score (-1.10 vs -0.58; P = .47), and QoL scores were similar between groups. The EoE transcriptome normalized in those with histologic response to both diets. Baseline peak eosinophil count predicted remission (odds ratio, 0.975 [95% confidence interval, 0.953-0.999], P = .04; cutoff ≤42 eosinophils per high-power field). The 4FED withdrawal rate (32%) exceeded that of 1FED (11%) (P = .0496). CONCLUSIONS: Although 4FED moderately improved symptoms compared with 1FED, the histologic, endoscopic, QoL, and transcriptomic outcomes were similar in both groups. 1FED is a reasonable first-choice therapy for pediatric EoE, given its effects, tolerability, and relative simplicity.

Patterns of Immune Dysregulation in Bipolar Disorder.

Background: Bipolar disorder is a debilitating mood disorder associated with a high risk of suicide and characterized by immune dysregulation. In this study, we used a multi-faceted approach to better distinguish the pattern of dysregulation of immune profiles in individuals with BD. Methods: We analyzed peripheral blood mononuclear cells (bipolar disorder N=39, control N=30), serum cytokines (bipolar disorder N=86, control N=58), whole blood RNA (bipolar disorder N=25, control N=25), and whole blood DNA (bipolar disorder N=104, control N=66) to identify immune-related differences in participants diagnosed with bipolar disorder compared to controls. Results: Flow cytometry revealed a higher proportion of monocytes in participants with bipolar disorder together with a lower proportion of T helper cells. Additionally, the levels of 18 cytokines were significantly elevated, while two were reduced in participants with bipolar disorder. Most of the cytokines altered in individuals with bipolar disorder were proinflammatory. Forty-nine genes were differentially expressed in our bipolar disorder cohort and further analyses uncovered several immune-related pathways altered in these individuals. Genetic analysis indicated variants associated with inflammatory bowel disease also influences bipolar disorder risk. Discussion: Our findings indicate a significant immune component to bipolar disorder pathophysiology and genetic overlap with inflammatory bowel disease. This comprehensive study supports existing literature, whilst also highlighting novel immune targets altered in individuals with bipolar disorder. Specifically, multiple lines of evidence indicate differences in the peripheral representation of monocytes and T cells are hallmarks of bipolar disorder.

A closed 3D printed microfluidic device for automated growth and differentiation of cerebral organoids from single-cell suspension.

The development of 3D organoids has provided a valuable tool for studying human tissue and organ development in vitro. Cerebral organoids, in particular, offer a unique platform for investigating neural diseases. However, current methods for generating cerebral organoids suffer from limitations such as labor-intensive protocols and high heterogeneity among organoids. To address these challenges, we present a microfluidic device designed to automate and streamline the formation and differentiation of cerebral organoids. The device utilizes microwells with two different shapes to promote the formation of a single aggregate per well and incorporates continuous medium flow for optimal nutrient exchange. In silico simulations supported the effectiveness of the microfluidic chip in replicating cellular microenvironments. Our results demonstrate that the microfluidic chip enables uniform growth of cerebral organoids, significantly reducing the hands-on time required for maintenance. Importantly, the performance of the microfluidic system is comparable to the standard 96-well plate format even when using half the amount of culture medium, and the resulting organoids exhibit substantially developed neuroepithelial buds and cortical structures. This study highlights the potential of custom-designed microfluidic technology in improving the efficiency of cerebral organoid culture.

Understanding Older Adults' Experiences With a Digital Health Platform in General Practice: Qualitative Interview Study.

Background: In our aging population, primary care is under pressure to remain accessible to all. Effective use of digital health care could potentially lower general practitioners' (GPs) workload. Some general practices are already implementing a digital health platform as a primary method to contact their patients. However, it is unknown how older people experience this novel way to communicate with their GP. Objective: The aim of this study was to study the experiences of patients aged 65 years and older in general practices who use digital health as a primary communication tool. The secondary aims were to identify barriers and facilitators for the use of digital health care and whether a practice focus on digital health influences older patients' choice to enlist. Methods: We invited all patients aged 65 years and older at 2 general practices in Amsterdam that work with a novel digital health platform. We used purposive sampling to select a heterogeneous group of patients in terms of age, sex, level of education, digital literacy, and experiences with the digital app of their general practice. We conducted 18 semistructured interviews from May through July 2023. All interviews were audio-recorded, transcribed, coded, and thematically analyzed. Results: We generated three themes: (1) experiences of older people with digital health care in general practice, (2) impact of individual factors on digital health experiences, and (3) reasons for choosing a digitally oriented general practice. Participants reported both positive and negative experiences. The main perceived advantages of the digital health platform were increased accessibility, direct GP contact without an intermediary, and saving time through asynchronous communication. The disadvantages mentioned were log-in difficulties and problems with the automated explanatory questionnaire. Individual factors such as age, digital literacy, and expectations of general practice care seemed to impact people's experiences and could act as barriers or facilitators for using digital health. Reasons for older patients to enlist at a general practice were mainly practical. The digital orientation of the practice hardly played a role in this choice. Conclusions: Older patients in general practice see benefits to using a digital health platform that offers 2-way chat-based communication between the patient and GP. We found that individual factors such as skills, norms and values, attitudes toward digitalization, and expectations of general practice care impacted older patients' experiences with digital health care. For many older participants, the digital profile of the general practice did not play a role in their choice to enlist. Further improvement of digital health platforms will be necessary to ensure digital health for all in general practice.

Patch Testing to Mentha piperita (Peppermint) Oil: The North American Contact Dermatitis Group Experience (2009-2020).

Background: Mentha piperita (MP; peppermint) oil has many commercial uses. Objective: To characterize the epidemiology of contact allergy to MP oil 2% petrolatum. Methods: Retrospective analysis of North American Contact Dermatitis Group data (2009-2020). Results: Of 28,128 patients tested to MP, 161 (0.6%) had an allergic reaction. Most allergic patients were female (77.0%) and/or over 40 years of age (71.4%). The most common anatomical sites of dermatitis included face (31.7%; of these, one-third specified lips), hands (17.4%), and scattered/generalized (18.6%). Nearly one-third (30.4%) of reactions were strong (++)/extreme (+++), and 80.1% were considered currently relevant. Common sources included oral hygiene preparations, foods, and lip products. Co-reaction with at least 1 of the other 19 fragrance/plant-related screening test preparations occurred in 82.6% (133/161) of MP-allergic patients, most commonly Cananga odorata oil (42.9%), fragrance mix I (41.0%), hydroperoxides of linalool (35.7%), Compositae mix (35.4%), Jasminum officinale oil (31.9%), Myroxylon pereirae (31.7%), and propolis (28.1%). Co-reaction with at least 1 of the 3 most commonly used fragrance screening allergens (fragrance mix I, fragrance mix II, and/or Myroxylon pereirae) was 59.6%. Conclusions: Twelve-year prevalence of MP allergy was 0.6%. Approximately 40% of cases would have been missed if only fragrance screening allergens were tested.

Mutant Huntingtin Drives Development of an Advantageous Brain Early in Life: Evidence in Support of Antagonistic Pleiotropy.

OBJECTIVE: Huntington's disease (HD) is a neurodegenerative disease caused by a triplet repeat expansion within the gene huntingtin (HTT). Antagonistic pleiotropy is a theory of aging that posits that some genes, facilitating individual fitness early in life through adaptive evolutionary changes, also augment detrimental aging-related processes. Antagonistic pleiotropy theory may explain a positive evolutionary pressure toward functionally advantageous brain development that is vulnerable to rapid degeneration. The current study investigated antagonistic pleiotropy in HD using a years-to-onset paradigm in a unique sample of children and young adults at risk for HD. METHODS: Cognitive, behavioral, motor, and brain structural measures from premanifest gene-expanded (n = 79) and gene nonexpanded (n = 112) participants (6-21 years) in the Kids-HD study were examined. All measures in the gene-expanded group were modeled using a mixed-effects regression approach to assess years-to-onset-based changes while controlling for normal growth. Simultaneously, structure-function associations were also examined. RESULTS: Decades from motor onset, gene-expanded participants showed significantly better cognitive, behavioral, and motor scores versus gene nonexpanded controls, along with larger cerebral volumes and cortical features. After this initial peak, a prolonged deterioration was observed in both functional and structural measures. Far from onset, brain measures were positively correlated with functional measures, supporting the view that functional advantages were mediated by structural differences. INTERPRETATION: Mutant HTT may drive the development of a larger than normal brain that subserves superior early-life function. These findings support the antagonistic pleiotropy theory of HTT in HD, where this gene drives early advantage followed by accelerated aging processes. ANN NEUROL 2024.

TH2 cell compensatory effect following benralizumab treatment for eosinophilic gastritis.

BACKGROUND: Eosinophil accumulation is a main feature of eosinophilic gastritis (EoG) and is associated with its histologic diagnosis and pathology. However, a recent clinical trial has demonstrated that EoG endoscopic, noneosinophil histologic, and clinical features remain persistent despite complete eosinophil depletion. OBJECTIVE: Our aim was to examine gastric T-cell composition and associated cytokine levels of patients with EoG following benralizumab-induced eosinophil depletion versus following administration of placebo. METHODS: A cohort of subjects with EoG from a subset of subjects who participated in a recent phase 2 benralizumab trial was treated for 12 weeks with administration of 3 doses of benralizumab (anti-IL-5 receptor α antibody [n = 5]) or placebo (n = 4). Single-cell suspensions obtained by gastric biopsy were stimulated with phorbol 12,13-dibutyrate and ionomycin in the presence of brefeldin A and monensin. Harvested cells were fixed, stained, and analyzed by flow cytometry to examine T-cell populations and associated cytokines. RESULTS: Following benralizumab treatment but not placebo, blood and gastric eosinophil levels decreased 16-fold and 10-fold, respectively. Whereas histologic score and features were significantly decreased, no change was observed in endoscopic score and features. Following complete eosinophil depletion with benralizumab, gastric TH2 cell levels were 3-fold higher than the levels in the patients with EoG who were given placebo; and the levels of associated type 2 cytokine production of IL-4, IL-5, and IL-13 in the benralizumab-treated patients were, respectively, 4-, 5.5-, and 2.5-fold, higher than those in the placebo-treated patients. CONCLUSION: We have identified a putative positive feedback loop whereby eosinophil depletion results in a paradoxic increase in levels of TH2 cells and derived cytokines; this finding suggests an explanation for the limited success of eosinophil depletion as monotherapy in eosinophil-associated gastrointestinal disorders.

Photopatch testing: Clinical characteristics, test results, and final diagnoses from the North American Contact Dermatitis Group, 2009-2020.

BACKGROUND: Photoallergic contact dermatitis (PACD) is a delayed hypersensitivity reaction to allergens only in the presence of ultraviolet radiation in sunlight. Photopatch testing (PhotoPT) is necessary to confirm the diagnosis of PACD. There are few published studies of PhotoPT in North America. OBJECTIVE: To summarise the results of patients photopatch tested by members of the North American Contact Dermatitis Group (NACDG), 2009-2020. METHODS: Retrospective analysis of patient characteristics and PhotoPT results to 32 allergens on the NACDG Photopatch Test Series. RESULTS: Most of the 454 tested patients were female (70.3%), 21-60 years old (66.7%) and White (66.7%). There were a total of 119 positive photopatch tests. Sunscreen agents comprised 88.2% of those, with benzophenones responsible for over half of them. Final diagnoses included PACD in 17.2%, allergic contact dermatitis (ACD) in 44.5%, polymorphous light eruption (PMLE) in 18.9% and chronic actinic dermatitis (CAD) in 9.0% of patients. CONCLUSIONS: In 454 patients with suspected photosensitivity referred for photopatch testing in North America, approximately one-fifth had PACD. Sunscreen agents, especially benzophenones, were the most common photoallergens. Other common diagnoses included ACD, PMLE and CAD. Photopatch testing is an important tool for differentiating these conditions.

Social, not genetic, programming of development and stress physiology of a colonial seabird.

Phenotypic differences often stem from genetic/maternal differences and/or early-life adaptations to local environmental conditions. In colonial animals, little is known on how variation in the social environment is embedded into individual phenotypes, nor what the consequences are on individual fitness. We conducted an experimental cross-fostering study on king penguins (Aptenodytes patagonicus), exchanging eggs among 134 pairs breeding in high-density (67 pairs) or low-density (67 pairs) areas of the same breeding colony. We investigated differences in parent and chick phenotypes and survival in relation to the density of their origin and foster environment. Adults breeding in colony areas of high density exhibited decreased resting behaviour and increased aggression and vigilance, increased hypometabolism during incubation fasts, and more moderate corticosterone responses shaped by exposure to chronic stressors (e.g. constant aggression by neighbours). Chick phenotypes were more influenced by the environment in which they were raised than their genetic/maternal origin. Chicks raised in high-density colonial environments showed enhanced weight gain and survival rates regardless of the density of their genetic parents' breeding areas. Our study experimentally shows advantages to breeding in colonial areas of higher breeder densities in king penguins, and highlights the importance of social settings in shaping phenotype expression in colonial seabirds.

Population density and vegetation resources influence demography in a hibernating herbivorous mammal.

Demography of herbivorous mammal populations may be affected by changes in predation, population density, harvesting, and climate. Whereas numerous studies have focused on the effect of single environmental variables on individual demographic processes, attempts to integrate the consequences of several environmental variables on numerous functional traits and demographic rates are rare. Over a 32-year period, we examined how forage availability (vegetation assessed through NDVI) and population density affected the functional traits and demographic rates of a population of Columbian ground squirrels (Urocitellus columbianus), a herbivorous hibernating rodent. We focused on mean population phenology, body mass, breeding success, and survival. We found a negative effect of population density on demographic rates, including on breeding success and pup and adult survival to the next year. We found diverging effects of vegetation phenology on demographic rates: positive effects of a later start of the growing season on adult and yearling female survival, and juvenile survival, but no clear effect on male survival. Interestingly, neither population density nor vegetation affected population phenology or body condition in the following year. Vegetative growth rate had a positive influence on female mass gain (somatic investment) over a season, but both vegetative growth rate and biomass, surprisingly, had negative effects on the survival of young through their first hibernation. Thus, ground squirrels appeared to benefit more from later timing of vegetation than increases in vegetative biomass per se. Our study provides evidence for complex ecological effects of vegetation and population density on functional traits and demographic rates of small mammal populations.