Therapy for Hyperlipidemia.

Significant advances in atherosclerotic cardiovascular (ASCVD) risk stratification and treatment have occurred over the past 10 years. While the lipid panel continues to be the basis of risk estimation, imaging for coronary artery calcium is now widely used in estimating risk at the individual level. Statins remain first-line agents for ASCVD risk reduction but in high-risk patients, ezetimibe, proprotein convertase subtilisin kexin-9 inhibitors, and bempedoic acid can be added to further reduce individual cardiovascular risk based on results of cardiovascular outcomes trials. Results of randomized control trials do not support use of medications targeted at triglyceride lowering for ASCVD risk reduction, but icosapent ethyl can be considered.

Use of letermovir for cytomegalovirus primary prophylaxis in lung transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a driver of negative outcomes after lung transplant (LTX) and primary prophylaxis (PPX) with valganciclovir (VGC) is standard-of-care. VGC is associated with myelosuppression, prompting interest in letermovir (LTV). METHODS: Adults receiving LTX between April 1, 2015, and July 30, 2022, at our institution were evaluated. Patients were excluded if low CMV risk (D-/R-), survived <90 days post-LTX, or transferred care before PPX withdrawal. Primary outcomes were leukopenia (white blood cell count [WBC] ≤ 3.0 × 109/L), severe leukopenia (WBC ≤ 2.0 × 109/L), and neutropenia (absolute neutrophil count ≤ 1500 cells/µL) requiring granulocyte-colony stimulating factor (GCSF) on PPX. Secondary outcomes included breakthrough CMV infection and post-PPX CMV infection. RESULTS: 204 patients met inclusion criteria: 175 patients on VGC and 29 patients on LTV (after VGC conversion). Most patients received bilateral LTX (62.7%) with non-lymphocyte-depleting induction (96.6%) and moderate-risk serostatus (D+/R+, 48.5%). Patients transitioned from VGC to LTV after a mean of 178 days (SD 80.8 days) post-transplant. Patients on VGC experienced significantly more leukopenia (82.3% vs. 58.6%, p = 0.008), severe leukopenia (57.1% vs. 31.0%, p = 0.016), and neutropenia requiring GCSF (70.9% vs. 51.7%, p = 0.048). Breakthrough (5.7% vs. 3.4%, p = 0.955) and post-PPX (24.6% vs. 37.9%, p = 0.199) infections were similar. A subgroup analysis of patients with high-risk serostatus showed similar trends, though did not reach statistical significance. CONCLUSIONS: In this single-center study, the incidence of leukopenia and neutropenia requiring GCSF were reduced with LTV compared to VGC. Breakthrough and post-PPX infections were not significantly different. This evidence suggests that LTV has comparable efficacy with reduced myelosuppression compared to VGC in LTX recipients, and may be an appropriate alternative for PPX.

Microbially induced calcium carbonate precipitation through CO2 sequestration via an engineered Bacillus subtilis.

BACKGROUND: Microbially induced calcium carbonate precipitation has been extensively researched for geoengineering applications as well as diverse uses within the built environment. Bacteria play a crucial role in producing calcium carbonate minerals, via enzymes including carbonic anhydrase-an enzyme with the capability to hydrolyse CO2, commonly employed in carbon capture systems. This study describes previously uncharacterised carbonic anhydrase enzyme sequences capable of sequestering CO2 and subsequentially generating CaCO3 biominerals and suggests a route to produce carbon negative cementitious materials for the construction industry. RESULTS: Here, Bacillus subtilis was engineered to recombinantly express previously uncharacterised carbonic anhydrase enzymes from Bacillus megaterium and used as a whole cell catalyst allowing this novel bacterium to sequester CO2 and convert it to calcium carbonate. A significant decrease in CO2 was observed from 3800 PPM to 820 PPM upon induction of carbonic anhydrase and minerals recovered from these experiments were identified as calcite and vaterite using X-ray diffraction. Further experiments mixed the use of this enzyme (as a cell free extract) with Sporosarcina pasteurii to increase mineral production whilst maintaining a comparable level of CO2 sequestration. CONCLUSION: Recombinantly produced carbonic anhydrase successfully sequestered CO2 and converted it into calcium carbonate minerals using an engineered microbial system. Through this approach, a process to manufacture cementitious materials with carbon sequestration ability could be developed.

The Effect of Gastrointestinal Graft-Versus-Host Disease and Diarrhea on the Pharmacokinetic Profile of Sotrovimab in Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Monoclonal antibodies (mAbs) are utilized broadly to treat cancer and infectious diseases, and mAb exposure (serum concentration over time) is one predictor of overall treatment efficacy. Herein, we present findings from a clinical trial evaluating the pharmacokinetics of the long-acting mAb sotrovimab targeting severe acute respiratory syndrome coronavirus 2 in hematopoietic cell transplant (HCT) recipients. METHODS: All participants received an intravenous infusion of sotrovimab within 1 week prior to initiating the pretransplant preparative regimen. The serum concentration of sotrovimab was measured longitudinally for up to 24 weeks posttransplant. RESULTS: Compared to non-HCT participants, we found that mAb clearance was 10% and 26% higher in autologous and allogeneic HCT recipients, respectively. Overall sotrovimab exposure was approximately 15% lower in HCT recipients compared to non-HCT recipients. Exposure was significantly reduced in HCT recipients who developed diarrhea and lower gastrointestinal graft-versus-host disease (GVHD) posttransplant. CONCLUSIONS: These data show that sotrovimab exposure may be reduced in HCT recipients, possibly related to increased gastrointestinal clearance in patients with GVHD. This phenomenon has implications for dose selection and duration of efficacy with sotrovimab and potentially other mAbs in this vulnerable patient population. Thus, mAb dose regimens developed in non-HCT populations may have to be optimized when applied to HCT populations.

Neonatal morbidity and mortality in birth centers in the United States 2018-2021: An observational study of low-risk birthing individuals.

BACKGROUND: Many studies reporting neonatal outcomes in birth centers include births with risk factors not acceptable for birth center care using the evidence-based CABC criteria. Accurate comparisons of outcomes by birth setting for low-risk patients are needed. METHODS: Data from the public Natality Detailed File from 2018 to 2021 were used. Logistic regression, including adjusted and unadjusted odds ratios, compared neonatal outcomes (chorioamnionitis, Apgar scores, resuscitation, intensive care, seizures, and death) between centers and hospitals. Covariates included maternal diabetes, body mass index, age, parity, and demographic characteristics. RESULTS: The sample included 8,738,711 births (8,698,432 (99.53%) in hospitals and 40,279 (0.46%) in birth centers). There were no significant differences in neonatal deaths (aOR 1.037; 95% CI [0.515, 2.088]; p-value 0.918) or seizures (aOR 0.666; 95% CI [0.315, 1.411]; p-value 0.289). Measures of morbidity either not significantly different or less likely to occur in birth centers compared to hospitals included chorioamnionitis (aOR 0.032; 95% CI [0.020, 0.052]; p-value < 0.001), Apgar score < 4 (aOR 0.814, 95% CI [0.638, 1.039], p-value 0.099), Apgar score < 7 (aOR 1.075, 95% CI [0.979, 1.180], p-value 0.130), ventilation >6 h (aOR 0.349; [0.281,0.433], p-value < 0.001), and intensive care admission (aOR 0.356; 95% CI [0.328, 0.386], p-value < 0.001). Birth centers had higher odds of assisted neonatal ventilation for <6 h as compared to hospitals (aOR 1.373; 95% CI [1.293, 1.457], p-value < 0.001). CONCLUSION: Neonatal deaths and seizures were not significantly different between freestanding birth centers and hospitals. Chorioamnionitis, Apgar scores < 4, and intensive care admission were less likely to occur in birth centers.

Clinical Activity of Selpercatinib in RET-mutant Pheochromocytoma.

INTRODUCTION: Activating RET alterations have been reported in a variety of solid tumors, including pheochromocytoma where they occur both sporadically and as part of familial multiple endocrine neoplasia type 2 (MEN2) syndromes. Selpercatinib is a first-in-class, highly selective, and potent small molecule RET kinase inhibitor that has demonstrated marked and durable anti-tumor activity in diverse RET-activated solid tumors in the LIBRETTO-001 study (NCT03157128). METHODS: We describe the first six pheochromocytoma cases treated with selpercatinib in the LIBRETTO-001 study. RESULTS: Of the six patients (one sporadic and five reported as part of MEN2 syndromes) in this case report, four had a partial response/complete response and two had stable disease per independent review committee. Treatment duration ranged from 9.2 months to more than 56.4 months. The safety profile of treatment was consistent with selpercatinib in other indications. CONCLUSION: These data support selpercatinib as an effective therapy against RET-mutant pheochromocytoma, adding to the diversity of RET-activated tumor types that may benefit from targeted RET inhibition.

Best Overall Response-Associated Signature to Doxorubicin in Soft Tissue Sarcomas: A Transcriptomic Analysis from ANNOUNCE.

PURPOSE: This exploratory analysis evaluated the tumor samples of the patients treated with doxorubicin (with or without olaratumab) in a negative phase III ANNOUNCE trial to better understand the complexity of advanced soft tissue sarcomas (STS) and to potentially identify its predictive markers. EXPERIMENTAL DESIGN: RNA sequencing was performed on pretreatment tumor samples (n = 273) from the ANNOUNCE trial to evaluate response patterns and identify potential predictive treatment markers for doxorubicin. A BOR-associated signature to doxorubicin (REDSARC) was created by evaluating tumors with radiographic response versus progression. An external cohort of doxorubicin-treated patients from the Spanish Group for Research on Sarcomas (GEIS) was used for refinement and validation. RESULTS: A total of 259 samples from the trial were considered for analysis. Comparative analyses by the treatment arm did not explain the negative trial. However, there was an association between the BOR signature and histologic subtype (χ2P = 2.0e-7) and grade (P = 0.002). There were no associations between the BOR signature and gender, age, ethnicity, or stage. Applied to survival outcomes, REDSARC was also predictive for progression-free survival (PFS) and overall survival (OS). Using the GEIS cohort, a refined 25-gene signature was identified and applied to the ANNOUNCE cohort, where it was predictive of PFS and OS in leiomyosarcoma, liposarcoma, and other sarcoma subtypes, but not in undifferentiated pleomorphic sarcoma. CONCLUSIONS: The refined REDSARC signature provides a potential tool to direct the application of doxorubicin in sarcomas and other malignancies. Validation and further refinement of the signature in other potentially subtype specific prospective cohorts is recommended.

Transcriptional profiling of peripheral blood mononuclear cells identifies inflammatory phenotypes in Ataxia Telangiectasia.

INTRODUCTION: Ataxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disease with widespread systemic manifestations and marked variability in clinical phenotypes. In this study, we sought to determine whether transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) defines subsets of individuals with A-T beyond mild and classic phenotypes, enabling identification of novel features for disease classification and treatment response to therapy. METHODS: Participants with classic A-T (n = 77), mild A-T (n = 13), and unaffected controls (n = 15) were recruited from two outpatient clinics. PBMCs were isolated and bulk RNAseq was performed. Plasma was also isolated in a subset of individuals. Affected individuals were designated mild or classic based on ATM mutations and clinical and laboratory features. RESULTS: People with classic A-T were more likely to be younger and IgA deficient and to have higher alpha-fetoprotein levels and lower % forced vital capacity compared to individuals with mild A-T. In classic A-T, the expression of genes required for V(D)J recombination was lower, and the expression of genes required for inflammatory activity was higher. We assigned inflammatory scores to study participants and found that inflammatory scores were highly variable among people with classic A-T and that higher scores were associated with lower ATM mRNA levels. Using a cell type deconvolution approach, we inferred that CD4 + T cells and CD8 + T cells were lower in number in people with classic A-T. Finally, we showed that individuals with classic A-T exhibit higher SERPINE1 (PAI-1) mRNA and plasma protein levels, irrespective of age, and higher FLT4 (VEGFR3) and IL6ST (GP130) plasma protein levels compared with mild A-T and controls. CONCLUSION: Using a transcriptomic approach, we identified novel features and developed an inflammatory score to identify subsets of individuals with different inflammatory phenotypes in A-T. Findings from this study could be used to help direct treatment and to track treatment response to therapy.

Sex differences in energy balance, body composition, and metabolic and endocrine markers during prolonged arduous military training.

This study investigated sex differences in energy balance, body composition, and metabolic and endocrine markers during prolonged military training. Twenty-three trainees (14 women) completed 44-wk military training (three terms of 14 wk with 2-wk adventurous training). Dietary intake and total energy expenditure were measured over 10 days during each term by weighed food and doubly labeled water. Body composition was measured by dual-energy X-ray absorptiometry (DXA) at baseline and at the end of each term. Circulating metabolic and endocrine markers were measured at baseline and at the end of terms 2 and 3. Absolute energy intake and total energy expenditure were higher, and energy balance was lower, for men than women (P ≤ 0.008). Absolute energy intake and balance were lower, and total energy expenditure was higher, during term 2 than terms 1 and 3 (P < 0.001). Lean mass did not change with training (P = 0.081). Fat mass and body fat increased from term 1 to terms 2 and 3 (P ≤ 0.045). Leptin increased from baseline to terms 2 and 3 in women (P ≤ 0.002) but not in men (P ≥ 0.251). Testosterone and free androgen index increased from baseline to term 3 (P ≤ 0.018). Free thyroxine (T4) decreased and thyroid-stimulating hormone (TSH) increased from baseline to term 2 and term 3 (P ≤ 0.031). Cortisol decreased from baseline to term 3 (P = 0.030). IGF-I and total triiodothyronine (T3) did not change with training (P ≥ 0.148). Men experienced greater energy deficits than women during military training due to higher total energy expenditure.NEW & NOTEWORTHY Energy deficits are common in military training and can result in endocrine and metabolic disturbances. This study provides first investigation of sex differences in energy balance, body composition, and endocrine and metabolic markers in response to prolonged and arduous military training. Men experienced greater energy deficits than women due to higher energy expenditure, which was not compensated for by increased energy intake. These energy deficits were not associated with decreases in fat or lean mass or metabolic or endocrine function.

An alternative model of maternity care for low-risk birth: Maternal and neonatal outcomes utilizing the midwifery-based birth center model.

OBJECTIVE: To assess key birth outcomes in an alternative maternity care model, midwifery-based birth center care. DATA SOURCES: The American Association of Birth Centers Perinatal Data Registry and birth certificate files, using national data collected from 2009 to 2019. STUDY DESIGN: This observational cohort study compared key clinical birth outcomes of women at low risk for perinatal complications, comparing those who received care in the midwifery-based birth center model versus hospital-based usual care. Linear regression analysis was used to assess key clinical outcomes in the midwifery-based group as compared with hospital-based usual care. The hospital-based group was selected using nearest neighbor matching, and the primary linear regressions were weighted using propensity score weights (PSWs). The key clinical outcomes considered were cesarean delivery, low birth weight, neonatal intensive care unit admission, breastfeeding, and neonatal death. We performed sensitivity analyses using inverse probability weights and entropy balancing weights. We also assessed the remaining role of omitted variable bias using a bounding methodology. DATA COLLECTION: Women aged 16-45 with low-risk pregnancies, defined as a singleton fetus and no record of hypertension or cesarean section, were included. The sample was selected for records that overlapped in each year and state. Counties were included if there were at least 50 midwifery-based birth center births and 300 total births. After matching, the sample size of the birth center cohort was 85,842 and the hospital-based cohort was 261,439. PRINCIPAL FINDINGS: Women receiving midwifery-based birth center care experienced lower rates of cesarean section (-12.2 percentage points, p < 0.001), low birth weight (-3.2 percentage points, p < 0.001), NICU admission (-5.5 percentage points, p < 0.001), neonatal death (-0.1 percentage points, p < 0.001), and higher rates of breastfeeding (9.3 percentage points, p < 0.001). CONCLUSIONS: This analysis supports midwifery-based birth center care as a high-quality model that delivers optimal outcomes for low-risk maternal/newborn dyads.

Assessment of Obstructive Sleep Apnea Among Patients With Chronic Obstructive Pulmonary Disease in Primary Care.

Study Objectives: Observational studies link untreated obstructive sleep apnea (OSA) with adverse outcomes in chronic obstructive pulmonary disease (COPD). The first step in addressing OSA is a clinical assessment. However, given competing demands and a lack of high-quality evidence, it is unclear how often such assessments occur. We explored the documentation of OSA assessment among patients with COPD in primary care, and the patient and provider characteristics associated with these assessments. Methods: We conducted a cross-sectional study of patients with clinically diagnosed COPD at 2 primary care practices. We abstracted charts to determine whether providers assessed OSA, defined as documentation of symptoms, treatment, or a referral to sleep medicine. We performed multivariable mixed-effects logistic regression to assess the associations of patient and provider characteristics with OSA assessment. Results: Among 641 patients with clinically diagnosed COPD, 146 (23%) had OSA assessed over a 1-year period. Positive associations with OSA assessment included body mass index ≥ 30 (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-7.0), pulmonary subspecialist visits (OR 3.9, 95%CI 2.4-6.3), and a prior sleep study demonstrating OSA documented within the electronic medical record (OR 18.0, 95%CI 9.0-35.8). Notably, patients identifying as Black were less likely to have OSA assessed than those identifying as White (OR 0.5, 95%CI 0.2-0.9). Conclusions: Providers document an assessment of OSA among a quarter of patients with COPD. Our findings highlight the importance of future work to rigorously test the impact of assessment on important health outcomes. Our findings also reinforce that additional strategies are needed to improve the equitable delivery of care.

Race, ethnicity, and indications for primary cesarean birth: Associations within a national birth center registry.

BACKGROUND: Racial and ethnic disparities in cesarean rates in the United States are well documented. This study investigated whether cesarean inequities persist in midwife-led birth center care, including for individuals with the lowest medical risk. METHODS: National registry records of 174,230 childbearing people enrolled in care in 115 midwifery-led birth center practices between 2007 and 2022 were analyzed for primary cesarean rates and indications by race and ethnicity. The lowest medical risk subsample (n = 70,521) was analyzed for independent drivers of cesarean birth. RESULTS: Primary cesarean rates among nulliparas (15.5%) and multiparas (5.7%) were low for all enrollees. Among nulliparas in the lowest-risk subsample, non-Latinx Black (aOR = 1.37; 95% CI, 1.15-1.63), Latinx (aOR = 1.51; 95% CI, 1.32-1.73), and Asian participants (aOR = 1.48; 95% CI, 1.19-1.85) remained at higher risk for primary cesarean than White participants. Among multiparas, only Black participants experienced a higher primary cesarean risk (aOR = 1.49; 95% CI, 1.02-2.18). Intrapartum transfers from birth centers were equivalent or lower for Black (14.0%, p = 0.345) and Latinx (12.7%, p < 0.001) enrollees. Black participants experienced a higher proportion of primary cesareans attributed to non-reassuring fetal status, regardless of risk factors. Place of admission was a stronger predictor of primary cesarean than race or ethnicity. CONCLUSIONS: Place of first admission in labor was the strongest predictor of cesarean. Racism as a chronic stressor and a determinant of clinical decision-making reduces choice in birth settings and may increase cesarean rates. Research on components of birth settings that drive inequitable outcomes is warranted.

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer.

BACKGROUND: Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced RET-mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear. METHODS: We conducted a phase 3, randomized trial comparing selpercatinib as first-line therapy with the physician's choice of cabozantinib or vandetanib (control group). Eligible patients had progressive disease documented within 14 months before enrollment. The primary end point in the protocol-specified interim efficacy analysis was progression-free survival, assessed by blinded independent central review. Crossover to selpercatinib was permitted among patients in the control group after disease progression. Treatment failure-free survival, assessed by blinded independent central review, was a secondary, alpha-controlled end point that was to be tested only if progression-free survival was significant. Among the other secondary end points were overall response and safety. RESULTS: A total of 291 patients underwent randomization. At a median follow-up of 12 months, median progression-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 16.8 months (95% confidence interval [CI], 12.2 to 25.1) in the control group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.16 to 0.48; P<0.001). Progression-free survival at 12 months was 86.8% (95% CI, 79.8 to 91.6) in the selpercatinib group and 65.7% (95% CI, 51.9 to 76.4) in the control group. Median treatment failure-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 13.9 months in the control group (hazard ratio for disease progression, discontinuation due to treatment-related adverse events, or death, 0.25; 95% CI, 0.15 to 0.42; P<0.001). Treatment failure-free survival at 12 months was 86.2% (95% CI, 79.1 to 91.0) in the selpercatinib group and 62.1% (95% CI, 48.9 to 72.8) in the control group. The overall response was 69.4% (95% CI, 62.4 to 75.8) in the selpercatinib group and 38.8% (95% CI, 29.1 to 49.2) in the control group. Adverse events led to a dose reduction in 38.9% of the patients in the selpercatinib group, as compared with 77.3% in the control group, and to treatment discontinuation in 4.7% and 26.8%, respectively. CONCLUSIONS: Selpercatinib treatment resulted in superior progression-free survival and treatment failure-free survival as compared with cabozantinib or vandetanib in patients with RET-mutant medullary thyroid cancer. (Funded by Loxo Oncology, a subsidiary of Eli Lilly; LIBRETTO-531 ClinicalTrials.gov number, NCT04211337.).

2023 HRS expert consensus statement on the management of arrhythmias during pregnancy

The Heart Rhythm Society (HRS) has developed expert consensus documents that have guided clinical care in the management of cardiac arrhythmias since 1996. This HRSled expert consensus statement was developed in collaboration with the American College of Cardiology (ACC), the American College of Obstetricians and Gynecologists (ACOG), the American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), the European Heart Rhythm Association (EHRA), the Latin American Heart Rhythm Society (LAHRS), the Pediatric and Congenital Electrophysiology Society (PACES), and the Society for Maternal-Fetal Medicine (SMFM). This clinical practice document is intended to provide comprehensive guidance to cardiac electrophysiologists, cardiologists, and other health care professionals on the management of cardiac arrhythmias in pregnant patients, including arrhythmias that occur in the mother and in the fetus.

The birth center model of care: Staffing, business characteristics, and core clinical outcomes.

OBJECTIVES: Interest in expanding access to the birth center model is growing. The purpose of this research is to describe birth center staffing models and business characteristics and explore relationships to perinatal outcomes. METHODS: This descriptive analysis includes a convenience sample of all 84 birth center sites that participated in the AABC Site Survey and AABC Perinatal Data Registry between 2012 and 2020. Selected independent variables include staffing model (CNM/CM or CPM/LM), legal entity status, birth volume/year, and hours of midwifery call/week. Perinatal outcomes include rates of induction of labor, cesarean birth, exclusive breastfeeding, birthweight in pounds, low APGAR scores, and neonatal intensive care admission. RESULTS: The birth center model of care is demonstrated to be safe and effective, across a variety of staffing and business models. Outcomes for both CNM/CM and CPM/LM models of care exceed national benchmarks for perinatal quality with low induction, cesarean, NICU admission, and high rates of breastfeeding. Within the sample of medically low-risk multiparas, variations in clinical outcomes were correlated with business characteristics of the birth center, specifically annual birth volume. Increased induction of labor and cesarean birth, with decreased success breastfeeding, were present within practices characterized as high volume (>200 births/year). The research demonstrates decreased access to the birth center model of care for Black and Hispanic populations. CONCLUSIONS FOR PRACTICE: Between 2012 and 2020, 84 birth centers across the United States engaged in 90,580 episodes of perinatal care. Continued policy development is necessary to provide risk-appropriate care for populations of healthy, medically low-risk consumers.

2023 HRS expert consensus statement on the management of arrhythmias during pregnancy.

This international multidisciplinary expert consensus statement is intended to provide comprehensive guidance that can be referenced at the point of care to cardiac electrophysiologists, cardiologists, and other health care professionals, on the management of cardiac arrhythmias in pregnant patients and in fetuses. This document covers general concepts related to arrhythmias, including both brady- and tachyarrhythmias, in both the patient and the fetus during pregnancy. Recommendations are provided for optimal approaches to diagnosis and evaluation of arrhythmias; selection of invasive and noninvasive options for treatment of arrhythmias; and disease- and patient-specific considerations when risk stratifying, diagnosing, and treating arrhythmias in pregnant patients and fetuses. Gaps in knowledge and new directions for future research are also identified.

Implicit Metaethical Intuitions: Validating and Employing a New IAT Procedure.

Philosophical arguments often assume that the folk tends towards moral objectivism. Although recent psychological studies have indicated that lay persons' attitudes to morality are best characterized in terms of non-objectivism-leaning pluralism, it has been maintained that the folk may be committed to moral objectivism implicitly. Since the studies conducted so far almost exclusively assessed subjects' metaethical attitudes via explicit cognitions, the strength of this rebuttal remains unclear. The current study attempts to test the folk's implicit metaethical commitments. We present results of a newly developed Implicit Association Test (IAT) for metaethical attitudes which indicate that the folk generally tend towards moral non-objectivism on the implicit level as well. We discuss implications of this finding for the philosophical debate.