3-Year Outcomes for Degenerative Mitral Regurgitation Repair in a Medicare Population.

OBJECTIVE: Mitral valve repair (MVr) has become the standard therapy for degenerative mitral regurgitation (DMR), but real-world late mortality, reintervention, and readmission data are lacking. This study estimates MVr outcomes for DMR to 3 years in the Medicare fee-for-service population. METHODS: There were 4,219 DMR patients older than 65 years undergoing MVr within the Medicare 100% standard analytic file from October 2015 to December 2018 who were evaluated. Outcomes were analyzed for isolated MVr patients (n = 2,433) and patients undergoing MVr with certain concomitant procedures: MVr + tricuspid valve surgery (TVS; n = 619), MVr + cardiac ablation (CA; n = 540), and MVr + left atrial appendage closure (n = 627). Outcomes over a 3-year period included all-cause mortality, reintervention, rehospitalization, and common complications. All outcomes were modeled with adjustments for patient demographics and comorbid conditions. RESULTS: The average age for all patients was 71.9 ± 5.2 years. Adjusted all-cause mortality and MV reintervention (surgery or transcatheter) at 3 years for the primary cohort of isolated MVr was 3.5% and 1.6%, respectively. Directionally higher mortality at 3 years was observed in patients with concomitant TVS or CA. All-cause readmission and cardiac readmission for isolated MVr was 37.0% and 14.1%, with the highest rates for those with concomitant TVS or CA. Acute kidney injury and stroke/transient ischemic attack were the most common adverse events over 3 years for all patients. CONCLUSIONS: The 3-year mortality and reintervention rates in Medicare patients undergoing degenerative MVr are low. Those undergoing concomitant TVS or CA had directionally higher mortality and cardiac readmission rates. These results help refine outcome benchmarks as new transcatheter MVr procedures continue to emerge.

Effects of albiglutide on myocardial infarction and ischaemic heart disease outcomes in patients with type 2 diabetes and cardiovascular disease in the Harmony Outcomes trial.

AIMS: Large outcome trials have demonstrated cardiovascular benefits of selected glucagon-like peptide-1 (GLP-1) receptor agonists. We examined coronary disease outcomes in the Harmony Outcomes trial of the GLP-1 receptor agonist albiglutide. METHODS AND RESULTS: Harmony Outcomes was an event-driven, multicenter, double-blind, and placebo-controlled trial involving 9463 patients >40 years of age with type-2 diabetes and established atherosclerotic cardiovascular disease. It tested the effects of albiglutide on the occurrence of a composite primary endpoint, consisting of cardiovascular death, myocardial infarction (MI), or stroke. Within this post-hoc analysis, the effects of albiglutide on MI subtypes and other ischaemic endpoints were analysed.During the median-follow up of 1.6 years, a total of 421 patients (4.5%) experienced at least one MI, with 72 patients having more than one event. Treatment with albiglutide reduced both first events [hazard ratio (HR) 0.75 (0.62-0.91)] and overall events [HR 0.75 (0.61-0.91)] as well as first type 1 [HR 0.73 (0.57-0.92)] and type 2 myocardial infarctions [HR 0.65 (0.46-0.92)]. The effect of albiglutide treatment was consistent for ST-segment elevation [HR 0.69 (0.38-1.26)] and non-ST elevation (HR 0.86 (0.66-1.2) MI. CONCLUSION: Treatment with the GLP-1 receptor agonist albiglutide resulted in a 25% relative risk reduction in MI that was consistent for type of infarction and presence or absence of ST elevation. Our findings add novel information about the effects of GLP-1 receptor agonists on ischaemic events in patients with type 2 diabetes.

Investigating the effect of host plant identity on instar number in fall webworm, a common generalist herbivore.

For herbivorous insects with a broad diet breadth, host plant identity can influence larval development by either accelerating or delaying growth. For some species of Lepidoptera, the number of larval instars varies depending on the host plant's identity. Fall webworm (Hyphantria cunea, Drury) is a polyphagous herbivore that feeds on over 450 host plants worldwide. Of the 2 morphotypes (red- and black-head) of fall webworm, the number of instars for the red-head fall webworms has not been characterized. Given its broad diet breadth, fall webworm developmental stages may vary with plant identity. We investigated whether host plant identity affected the number of instars observed during red-head fall webworm development. We measured the head capsules of over 6,000 fall webworm larvae reared on 6 different plants commonly eaten by fall webworms in Colorado. We modeled head capsule widths as Gaussian mixture models, with a Gaussian distribution that corresponded to each instar. We show that our red-head fall webworms varied in number of instars depending on the identity of their host plant upon which they fed. We found that red-head fall webworm exhibited 7 instars on 5 of the host plants and 8 instars on 1 host plant that we studied. Our results for the number of instars for red-head fall webworm are consistent with reports of the number of instars for black-head fall webworm. Our research provides insight into the influence of host plant identity on fall webworm development, which can be used to advance lab and field research of this species.

Standoff trace explosives vapor detection at meter distances.

Vapor detection is a noncontact sampling method, which is a less invasive means of explosives screening than physical swiping. Explosive vapor detection is a challenge due to the low levels of vapors available for detection. This study demonstrates that the parts-per-quadrillion sensitivity of atmospheric flow tube-mass spectrometry (AFT-MS) combined with a high-volume air sampler enables standoff detection of trace explosives vapor at distances of centimeters to meters. Standoff detection of explosives vapor was possible both upstream and downstream of the vapor source relative to room air currents. RDX vapor from a saturated source was detected at up to 2.5 m. Vapors from RDX residue and nitroglycerin residue were detected at distances up to 0.5 m. The sampling can be optimized by accounting for air movement in the room or environment, which could further extend standoff detection distances. Using AFT-MS with a high-volume sampler could also be effective for standoff vapor detection of drugs and additional chemical threats and could be useful for security screening applications such as at mail facilities, border crossings, and security checkpoints.

Does artificial light at night alter moth community composition?

Ecological studies investigating the effects of artificial light at night (ALAN) have primarily focused on single or a few species, and seldom on community-level dynamics. As ALAN is a potential cause of insect and biodiversity declines, community-level perspectives are essential. We empirically tested the hypothesis that moth species differentially respond to ALAN and that these responses can cause shifts in community composition. We sampled moths from prairie fragments in Colorado, USA. We tested whether local light sources, sky glow, site area and/or vegetation affected moth community diversity. We found that increased sky glow decreased moth abundance and species richness and shifted community composition. Increased sky glow shifted moth community composition when light and bait traps were combined; notably this result appears to be driven entirely by moths sampled at bait traps, which is an unbiased sampling technique. Our results show that ALAN has significant effects on moth communities and that local light sources have contrasting effects on moth community composition compared to sky glow. It is imperative that we better understand the contrasting effects of types of ALAN to comprehend the overall impacts of light pollution on biodiversity declines. This article is part of the theme issue 'Light pollution in complex ecological systems'.

Outpatient visits before and after Lyme disease diagnosis in a Maryland employer-based health plan.

BACKGROUND: Insurance claims data have been used to inform an understanding of Lyme disease epidemiology and cost of care, however few such studies have incorporated post-treatment symptoms following diagnosis. Using longitudinal data from a private, employer-based health plan in an endemic US state, we compared outpatient care utilization pre- and post-Lyme disease diagnosis. We hypothesized that utilization would be higher in the post-diagnosis period, and that temporal trends would differ by age and gender. METHODS: Members with Lyme disease were required to have both a corresponding ICD-9 code and a fill of an antibiotic indicated for treatment of the infection within 30 days of diagnosis. A 2-year 'pre- diagnosis' period and a 2-year 'post-diagnosis period' were centered around the diagnosis month. Lyme disease-relevant outpatient care visits were defined as specific primary care, specialty care, or urgent care visits. Descriptive statistics examined visits during these pre- and post-diagnosis periods, and the association between these periods and the number of visits was explored using generalized linear mixed effects models adjusting for age, season of the year, and gender. RESULTS: The rate of outpatient visits increased 26% from the pre to the post-Lyme disease diagnosis periods among our 317-member sample (rate ratio = 1.26 [1.18, 1.36], p < 0.001). Descriptively, care utilization increases appeared to persist across months in the post-diagnosis period. Women's care utilization increased by 36% (1.36 [1.24, 1.50], p < 0.001), a significantly higher increase than the 14% increase found among men (1.14 [1.02, 1.27], p = 0.017). This gender difference was mainly driven by adult members. We found a borderline significant 17% increase in visits for children < 18 years, (1.17 [0.99, 1.38], p = 0.068), and a 31% increase for adults ≥ 18 years (1.31 [1.21, 1.42], p < 0.001). CONCLUSIONS: Although modest at the population level, the statistically significant increases in post-Lyme diagnosis outpatient care we observed were persistent and unevenly distributed across demographic and place of service categories. As Lyme disease cases continue to grow, so will the cumulative prevalence of persistent symptoms after treatment. Therefore, it will be important to confirm these findings and understand their significance for care utilization and cost, particularly against the backdrop of other post-acute infectious syndromes.

Direct detection of drug-resistant Mycobacterium tuberculosis using targeted next generation sequencing.

Mycobacterium tuberculosis complex (MTBC) infections are treated with combinations of antibiotics; however, these regimens are not as efficacious against multidrug and extensively drug resistant MTBC. Phenotypic (growth-based) drug susceptibility testing on slow growing bacteria like MTBC requires many weeks to months to complete, whereas sequencing-based approaches can predict drug resistance (DR) with reduced turnaround time. We sought to develop a multiplexed, targeted next generation sequencing (tNGS) assay that can predict DR and can be performed directly on clinical respiratory specimens. A multiplex PCR was designed to amplify a group of thirteen full-length genes and promoter regions with mutations known to be involved in resistance to first- and second-line MTBC drugs. Long-read amplicon libraries were sequenced with Oxford Nanopore Technologies platforms and high-confidence resistance mutations were identified in real-time using an in-house developed bioinformatics pipeline. Sensitivity, specificity, reproducibility, and accuracy of the tNGS assay was assessed as part of a clinical validation study. In total, tNGS was performed on 72 primary specimens and 55 MTBC-positive cultures and results were compared to clinical whole genome sequencing (WGS) performed on paired patient cultures. Complete or partial susceptibility profiles were generated from 82% of smear positive primary specimens and the resistance mutations identified by tNGS were 100% concordant with WGS. In addition to performing tNGS on primary clinical samples, this assay can be used to sequence MTBC cultures mixed with other mycobacterial species that would not yield WGS results. The assay can be effectively implemented in a clinical/diagnostic laboratory with a two to three day turnaround time and, even if batched weekly, tNGS results are available on average 15 days earlier than culture-derived WGS results. This study demonstrates that tNGS can reliably predict MTBC drug resistance directly from clinical specimens or cultures and provide critical information in a timely manner for the appropriate treatment of patients with DR tuberculosis.

Cost and Clinical Outcomes Evaluation Between the Endoaortic Balloon and External Aortic Clamp in Cardiac Surgery.

OBJECTIVE: Endoaortic balloon occlusion facilitates cardioplegic arrest during minimally invasive surgery (MIS). Studies have shown endoclamping to be as safe as traditional aortic clamping. We compared outcomes and hospital costs of endoclamping versus external aortic occlusion in a large administrative database. METHODS: There were 52,882 adults undergoing eligible cardiac surgery (October 2015 to March 2020) identified in the Premier Healthcare Database. Endoclamp procedures (n = 419) were 1:3 propensity score matched to similar procedures using external aortic occlusion (n = 1,244). Generalized linear modeling measured differences in in-hospital complications (major adverse renal and cardiac events, including mortality, new-onset atrial fibrillation, acute kidney injury [AKI], myocardial infarction [MI], postcardiotomy syndrome, stroke/transient ischemic attack [TIA], and aortic dissection) and length of stay (LOS). RESULTS: The mean age was 63 years, and 53% were male (n = 882). The majority (93%, n = 1,543) were mitral valve procedures, and 17% of procedures (n = 285) were robot-assisted. Total hospitalization costs were not statistically significantly different between the 2 groups ($52,158 vs $49,839, P = 0.06). The median LOS was significantly shorter in the endoclamp group (incident rate ratio = 0.87, P < 0.001). Mortality, atrial fibrillation, AKI, and stroke/TIA were similar between the 2 groups. MI and postcardiotomy syndrome were lower in the endoclamp group (odds ratio [OR] = 0.14, P = 0.006, and OR = 0.27, P = 0.005). There were no aortic dissections in the endoclamp group. CONCLUSIONS: Aortic endoclamping in MIS was associated with similar costs, shorter LOS, no dissections, and comparably low mortality and stroke rates when compared with external clamping in this hospital billing dataset. These results demonstrate the clinical safety and efficacy of endoaortic balloon clamping in a real-world setting. Further studies are warranted.

In-Hospital Outcomes of Heart Failure Patients with Valvular Heart Disease: Insights from Real-World Claims Data.

Purpose: Heart failure (HF) is a serious public health burden that is rapidly increasing in the aging population. Valvular heart disease (VHD) is a known etiology of heart failure (HF); however, the impact of VHD on outcomes of patients with HF has not been well-studied in Japan. This study aimed to determine the rates of VHD in Japanese patients admitted for HF and explore associations of VHD with in-hospital outcomes through a claim-based analysis. Patients and methods: We analyzed claims data from 86,763 HF hospitalizations (January 2017 through December 2019) from the Medical Data Vision database. Common etiologies of HF were examined, then hospitalizations were categorized into those with VHD and those without. Covariate-adjusted models were used to explore the association of VHD with in-hospital mortality, length of stay, and medical cost. Results: Of 86,763 hospitalizations for HF, 13,183 had VHD and 73,580 did not. VHD was the second most frequent etiology of HF (15.2%). The most frequent type of VHD was mitral regurgitation (36.4% of all hospitalizations with VHD), followed by aortic stenosis (33.7%) and aortic regurgitation (16.4%). There was no significant difference in in-hospital mortality between hospitalizations with VHD vs those without (9.0% vs 8.9%; odds ratio [95% CI]: 1.01 [0.95-1.08]; p=0.723). Hospitalizations with VHD were associated with significantly longer length of stay (26.1 vs 24.8 days; incident rate ratio [95% CI]: 1.05 [1.03-1.07]; p<0.001) and higher medical costs (1536 vs 1195 thousand yen; rate ratio [95% CI]: 1.29 [1.25-1.32]; p<0.001). Conclusion: VHD was a frequent etiology of HF that was associated with significant medical resource use. Future studies are needed to investigate whether timely VHD treatment could reduce HF progression and its associated healthcare resource utilization.

Valvular heart disease in Japan: Characteristics and treatment of patients in acute care hospitals in 2019.

BACKGROUND: Valvular heart disease (VHD) is one of the commonest causes of cardiovascular morbidity and mortality worldwide, with acquired VHD especially prevalent in countries with aging populations. The scope and pattern of disease are not well understood, as some patients are asymptomatic and available options for invasive treatment vary by affected valve. We sought to understand the burden of VHD in Japan including the distribution of patients by valve disease type and age, using administrative claims data from acute care hospitals. METHODS: This was a retrospective descriptive study of patients with VHD diagnosis and at least one record of echocardiography in 2019 documented in the Medical Data Vision database. Affected valve(s) and type of valve disease were characterized using ICD-10 codes; patients undergoing invasive treatment for VHD at the same facility and during the same year as their diagnosis were assessed using procedure codes. RESULTS: Of 203,398 patients with VHD diagnosis and a record of echocardiography in 2019, 49.0 % had a mitral valve disorder, 44.9 % aortic valve, 22.9 % tricuspid valve, and 2.2 % pulmonic valve (14.9 % of patients had more than one disordered valve). A total of 7201 patients (<4 % of the total diagnosed population) received invasive treatment for VHD in 2019 at the diagnosing hospital. Patients with aortic stenosis (AS) had the highest mean age, at 79 years. Although mitral regurgitation was the most common VHD among diagnosed patients, AS predominated in the cohort of treated patients. A substantial portion of patients undergoing treatment for AS were age 85 years or older (27.2 %). CONCLUSIONS: The cohort of treated patients in 2019 was a small fraction of the total population with a VHD diagnosis in that year. Wide availability of transcatheter treatment for AS in Japan may be allowing more elderly patients to receive intervention than in other types of VHD.

Association of ACEI/ARB and statin prescribing patterns with mortality after Transcatheter Aortic Valve Replacement (TAVR): Findings from real-world claims data.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become the standard of care for most patients with severe aortic stenosis (AS), but the impact of medical therapy prescribing patterns on post-TAVR patients has not been thoroughly investigated. METHODS: We analyzed Optum claims data from 9,012 adults who received TAVR for AS (January 2014-December 2018). Pharmacy claims data were used to identify patients who filled ACEI/ARB and/or statin prescriptions during the study's 90-day landmark period post-TAVR. Kaplan-Meier and adjusted Cox Proportional Hazards models were used to evaluate the association of prescribing patterns with mortality during the 3-year follow-up period. Subgroup analyses were performed to examine the impact of 11 potential confounders on the observed associations. RESULTS: A significantly lower adjusted 3-year mortality was observed for patients with post-TAVR prescription for ACEI/ARBs (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.74-0.91, P = .0003) and statins (HR = 0.85, 95% CI 0.77-0.94, P = .0018) compared to patients who did not fill prescriptions for these medications post-TAVR. Subgroup analyses revealed that the survival benefit associated with ACEI/ARB prescription was not affected by any of the potential confounding variables, except preoperative ACEI/ARB prescription was associated with significantly lower risk of mortality vs postoperative prescription only. No other subgroup variables had significant interactions associated with survival benefits, including preoperative use of statins. CONCLUSIONS: In this large-scale, real-world analysis of patients undergoing TAVR, the prescription of ACEI/ARB and statins was associated with a significantly lower risk of mortality at 3-years, especially in those where the medications were initiated preoperatively.

Bottom-up and top-down pressures mediate competition between two generalist insects.

The effects of competition can have far-reaching consequences for individuals, populations, and communities and therefore we should strive toward a deeper understanding of competitive interactions. In some cases, dietary generalists may be predicted to experience weak competition effects because of their ability to use a wide range of host plants. However, competition between insects frequently occurs indirectly, which can hinder insects' abilities to avoid competitive interactions. Therefore, competition may be as strong among dietary generalists as among dietary specialists. Yet competition between insects that are dietary generalists is infrequently studied. We tested for evidence of competitive interactions between two common, temporally separated, generalist insects: the western tent caterpillar (Malacosoma californicum), which feeds early in the season, and the fall webworm (Hyphantria cunea), which feeds later in the season. Both species frequently use a common host plant species (chokecherry) as a preferred host at our field sites. We tested the relative strength of bottom-up effects resulting from competitive interactions between these two generalists with laboratory-rearing trials at the relevant time of year for each insect. We recorded three common fitness measures (development time, pupal mass, and survival) for caterpillars reared on chokecherry with no damage from either of our focal species, with tent caterpillar damage, and with fall webworm damage. To test the strength of top-down pressures on fall webworm larval fitness and any potential interactions with bottom-up effects, we reared larvae in the field either exposed to or protected from predators on host plants that either did or did not have tent caterpillars feeding on them earlier in the season. We found evidence of bottom-up fitness effects on tent caterpillars and top-down and bottom-up fitness effects on fall webworms confirming that tent caterpillars and fall webworms compete indirectly. Tent caterpillars had lower pupal mass when reared on leaves from shrubs damaged by fall webworms. Fall webworms had lower pupal mass and longer development time when reared on leaves from shrubs damaged by tent caterpillars. In field trials, fall webworms reared on shrubs damaged by tent caterpillars had a lower survival and pupal mass. We show evidence of indirect competition in temporally separated generalists through leaf quality (bottom-up effects) and natural enemies (top-down effects).

Species loss and nitrogen pollution alter litter decomposition dynamics in coastal salt marshes.

Litter decomposition is a central ecosystem function because dead plant biomass plays a critical role in carbon storage, the nitrogen (N) cycle, and as food/habitat for animals and microorganisms. In the face of global change, interactions between organisms that participate in litter decomposition are likely to change due to species loss and N pollution. To understand how these global change factors may interact to alter litter decomposition, we manipulated the detritivore community and N concentrations in a coastal salt marsh for 2 years. We chose to manipulate densities of a dominant, detritivorous snail (Melampus bidentatus) because its population size is expected to decline due to climate change, yet its impact on litter decomposition has not been tested in the field. We measured litter decomposition rates, detritivore densities, and the N concentrations of sediment and litter. We found that endogenous N enrichment (N added live plants before decomposition), exogenous N enrichment (N added to decomposing plants) and higher densities of Melampus increased litter decomposition rates. Linear mixed models further revealed that snails, other detritivores, and soil NH4+ were the best predictors of litter mass loss in the middle stages of decomposition. Notably, exogenous N added to litter already enriched with N further increased mass loss but did not increase litter %N. Our study reveals how global change in the form species loss and N pollution can have palpable impacts on carbon cycling and ecosystem function.

Positive feedback drives a secondary nonlinear product burst during a biphasic DNA amplification reaction.

Isothermal DNA amplification reactions are used in a broad variety of applications, from diagnostic assays to DNA circuits, with greater speed and less complexity than established PCR technologies. We recently reported a unique, high gain, biphasic isothermal DNA amplification reaction, called the Ultrasensitive DNA Amplification Reaction (UDAR). Here we present a detailed analysis of the UDAR reaction pathways that initiates with a first phase followed by a nonlinear product burst, which is caused by an autocatalytic secondary reaction. The experimental reaction output was reproduced using an ordinary differential equation model based on detailed reaction mechanisms. This model provides insight on the relative importance of each reaction mechanism during both phases, which could aid in the design of product output during DNA amplification reactions.

Metabolomics-based mass spectrometry methods to analyze the chemical content of 3D organoid models.

Metabolomics, the study of metabolites present in biological samples, can provide a global view of sample state as well as insights into biological changes caused by disease or environmental interactions. Mass spectrometry (MS) is commonly used for metabolomics analysis given its high-throughput capabilities, high sensitivity, and capacity to identify multiple compounds in complex samples simultaneously. MS can be coupled to separation methods that can handle small volumes, making it well suited for analyzing the metabolome of organoids, miniaturized three-dimensional aggregates of stem cells that model in vivo organs. Organoids are being used in research efforts to study human disease and development, and in the design of personalized drug treatments. For organoid models to be useful, they need to recapitulate morphological and chemical aspects, such as the metabolome, of the parent tissue. This review highlights the separation- and imaging-based MS-based metabolomics methods that have been used to analyze the chemical contents of organoids. Future perspectives on how MS techniques can be optimized to determine the accuracy of organoid models and expand the field of organoid research are also discussed.

Impact of Managing Provider Type on Severe Aortic Stenosis Management and Mortality.

Background Many patients with symptomatic severe aortic stenosis do not undergo aortic valve replacement (AVR) despite clinical guidelines. This study analyzed the association of managing provider type with cardiac specialist follow-up, AVR, and mortality for patients with newly diagnosed severe aortic stenosis (sAS). Methods and Results We identified adults with newly diagnosed sAS per echocardiography performed between January 2017 and March 2019 using Optum electronic health record data. We then selected from those meeting all eligibility criteria patients managed by a primary care provider (n=1707 [25%]) or cardiac specialist (n=5039 [75%]). We evaluated the association of managing provider type with cardiac specialist follow-up, AVR, and mortality, as well as the independent association of cardiac specialist follow-up and AVR with mortality, within 1 year of echocardiography detecting sAS. A subgroup analysis was limited to patients with symptomatic sAS. Patient characteristics and comorbidities at baseline were used for covariate-adjusted cause-specific and multivariable Cox proportional hazard models assessing group differences in outcomes by managing provider type. An adjusted Cox proportional hazard model with additional time-dependent covariates for follow-up and AVR was used to assess these practices' association with mortality. Within 1 year of echocardiography detecting sAS, data revealed that primary care provider management was associated with lower rates of cardiac specialist follow-up (hazard ratio [HR], 0.47 [95% CI, 0.43-0.50], P<0.0001) and AVR (HR, 0.58 [95% CI, 0.53-0.64], P<0.0001) and with higher 1-year mortality (HR, 1.45 [95% CI, 1.26-1.66], P<0.0001). Cardiac specialist follow-up and AVR were independently associated with lower mortality (follow-up: HR, 0.55 [95% CI, 0.48-0.63], P<0.0001; AVR: HR, 0.70 [95% CI, 0.60-0.83], P<0.0001). Results were similar for patients with symptomatic sAS. All analyses were adjusted for baseline patient characteristics and comorbidities. Conclusions For patients newly diagnosed with sAS, we observed differences in rates of cardiac specialist follow-up and AVR and risk of mortality between primary care provider- versus cardiologist-managed patients with sAS. In addition, a lower likelihood of receiving follow-up and AVR was independently associated with higher mortality.

Genetic divergence among threespine stickleback that differ in nuptial coloration.

Sexual signals are shaped by their intended and unintended receivers as well as the signalling environment. This interplay between sexual and natural selection can lead to divergence in signals in heterogeneous environments. Yet, the extent to which gene flow is restricted when signalling phenotypes vary across environments and over what spatial scales remains an outstanding question. In this study, we quantify gene flow between two colour morphs, red and black, of freshwater threespine stickleback fish (Gasterosteus aculeatus). We capitalize on the very recent divergence of signalling phenotypes in this system to characterize within-species and among-morph genetic variation and to test for levels of gene flow between colour morphs in Oregon and Washington. Despite limited evidence for assortative mating between allopatric red and black populations, we found that black populations are genetically distinct from nearby red populations and that the black morph appears to have evolved independently at least twice in Oregon and Washington. Surprisingly, we uncovered a group of stickleback in one small coastal stream, Connor Creek, which is genetically and morphologically distinct from the red and black colour morphs and from marine stickleback. Historically, both colour morphs have coexisted in this location and sometimes hybridized, raising new questions about the origins and history of these fish, which were first described as anadromous-black hybrids >50 years ago. Understanding how genetic variation is currently partitioned within and among populations and colour morphs in this system should prompt future studies to assess the relative roles of habitat, ecological and pre- and post-reproductive barriers in the genetic divergence and phenotypic patterns we observe in nature.

Infection and higher cortisol during pregnancy and risk for depressive symptoms in adolescent offspring.

Prenatal infection, particularly at mid-gestation, has been associated with various psychopathological outcomes in offspring; however, findings linking prenatal infection to offspring depression outcomes have been mixed. Previous research indicates that it may be the co-occurrence of prenatal adversities (e.g., infection and stress) that are associated with depression outcomes in offspring. Nevertheless, no study to date has investigated whether higher levels of biomarkers linked to prenatal stress (e.g., cortisol) in the presence of infection may account for these outcomes. Participants were drawn from the Child Health and Development Studies (CHDS), a prospective, longitudinal study of pregnant women and their offspring. The present study included mother-offspring dyads from the Adolescent Study, a subsample of the CHDS cohort, whose offspring were assessed in adolescence and whose mothers also provided sera to be assayed for cortisol (n = 695). Hierarchical multivariable regressions were conducted to examine whether maternal cortisol during the first and second trimesters of pregnancy interacted with maternal infection to predict increased risk for symptoms of depression in adolescent offspring. There was a significant interaction of second trimester infection and higher cortisol on offspring depression scores during adolescence, controlling for maternal education (p = 0.04). Findings suggest that higher maternal cortisol may sensitize mothers and their offspring to the disruptive influences of infection during mid-pregnancy, conferring greater risk of depressive symptomatology in offspring.