A systematic evidence map for the evaluation of noncancer health effects and exposures to polychlorinated biphenyl mixtures.

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches. A protocol was developed that describes the literature search strategy and Populations, Exposures, Comparators, and Outcomes (PECO) criteria used to facilitate subsequent screening and categorization of literature into a systematic evidence map of PCB exposure and noncancer health endpoints across 15 organs/systems. A comprehensive literature search yielded 62,599 records. After electronic prioritization steps, 17,037 studies were manually screened at the title and abstract level. An additional 900 studies identified by experts or supplemental searches were also included. After full-text screening of 3889 references, 1586 studies met the PECO criteria. Relevant study details such as the endpoints assessed, exposure duration, and species were extracted into literature summary tables. This review compiles and organizes the human and mammalian studies from these tables into an evidence map for noncancer health endpoints and PCB mixture exposure to identify areas of robust research as well as areas of uncertainty that would benefit from future investigation. Summary data are available online as interactive visuals with downloadable metadata. Sufficient research is available to inform PCB hazard assessments for most organs/systems, but the amount of data to inform associations with specific endpoints differs. Furthermore, despite many years of research, sparse data exist for inhalation and dermal exposures, which are highly relevant human exposure routes. This evidence map provides a foundation for future systematic reviews and noncancer hazard assessments of PCB mixtures and for strategic planning of research to inform areas of greater uncertainty.

Pre-Glenn aorto-pulmonary collaterals in single-ventricle patients.

BACKGROUND: In single-ventricle patients undergoing staged-bidirectional Glenn, 36-59% have aorto-pulmonary collateral flow, but risk factors and clinical outcomes are unknown. We hypothesise that shunt type and catheter haemodynamics may predict pre-bidirectional Glenn aorto-pulmonary collateral burden, which may predict death/transplantation, pulmonary artery or aorto-pulmonary collateral intervention. METHODS: Retrospective cohort study of patients undergoing a Norwood procedure for single-ventricle anatomy. Covariates included clinical and haemodynamic characteristics up to/including pre-bidirectional Glenn catheterisation and aorto-pulmonary collateral burden at pre-bidirectional Glenn catheterisation. Multivariable models used to evaluate relationships between risk factors and outcomes. RESULTS: From January 2011 to March 2016, 104 patients underwent Norwood intervention. Male sex (odds ratio 3.36, 95% confidence interval 1.17-11.4), age at pre-bidirectional Glenn assessment (2.12, 1.33-3.39 per month), and pulmonary to systemic flow ratio (1.23, 1.08-1.41 per 0.1 unit) were associated with aorto-pulmonary collateral burden. Aorto-pulmonary collateral burden was not associated with death/transplantation (hazard ratio 1.19, 95% confidence interval 0.37-3.85), pulmonary artery (sub-hazard ratio 1.38, 0.32-2.61), or aorto-pulmonary collateral interventions (sub-hazard ratio 1.11, 0.21-5.76). Longer post-Norwood length of stay was associated with greater risk of death/transplantation (hazard ratio 1.22 per week, 95% confidence interval 1.08-1.38), but lower risk of aorto-pulmonary collateral intervention (sub-hazard ratio 0.86 per week, 95% confidence interval 0.75-0.98). Time to pre-bidirectional Glenn catheterisation was associated with lower risk of pulmonary artery (sub-hazard ratio 0.80 per month, 95% confidence interval 0.65-0.98) and aorto-pulmonary collateral intervention (sub-hazard ratio 0.79, 0.63-0.99). Probability of moderate/severe aorto-pulmonary collateral burden increased with left-to-right shunt (22.5% at <1.0, 57.6% at >1.4) and the age at pre-bidirectional Glenn catheterisation (10.6% at <2 months, 56.9% at >5 months). CONCLUSIONS: Aorto-pulmonary collateral burden is common after Norwood procedure and increases as age at bidirectional Glenn increases. As expected, higher pulmonary to systemic flow ratio is a marker for greater aorto-pulmonary collateral burden pre-bi-directional Glenn; aorto-pulmonary collateral burden does not confer risk of death/transplantation or pulmonary artery intervention.

Glycine betaine uptake and metabolism in marine microbial communities.

Glycine betaine (GBT) is a compatible solute in high concentrations in marine microorganisms. As a component of labile organic matter, GBT has complex biochemical potential as a substrate for microbial use that is unconstrained in the environment. Here we determine the uptake kinetics and metabolic fate of GBT in two natural microbial communities in the North Pacific characterized by different nitrate concentrations. Dissolved GBT had maximum uptake rates of 0.36 and 0.56 nM h-1 with half-saturation constants of 79 and 11 nM in the high nitrate and low nitrate stations respectively. During multiday incubations, most GBT taken into cells was retained as a compatible solute. Stable isotopes derived from the added GBT were also observed in other metabolites, including choline, carnitine and sarcosine, suggesting that GBT was used for biosynthesis and for catabolism to pyruvate and ammonium. Where nitrate was scarce, GBT was primarily metabolized via demethylation to glycine. Gene transcript data were consistent with SAR11 using GBT as a source of methyl groups to fuel the methionine cycle. Where nitrate concentrations were higher, more GBT was partitioned for lipid biosynthesis by both bacteria and eukaryotic phytoplankton. Our data highlight unexpected metabolic pathways and potential routes of microbial metabolite exchange.

Prochlorococcus extracellular vesicles: molecular composition and adsorption to diverse microbes.

Extracellular vesicles are small (~50-200 nm diameter) membrane-bound structures released by cells from all domains of life. While vesicles are abundant in the oceans, their functions, both for cells themselves and the emergent ecosystem, remain a mystery. To better characterize these particles - a prerequisite for determining function - we analysed the lipid, protein, and metabolite content of vesicles produced by the marine cyanobacterium Prochlorococcus. We show that Prochlorococcus exports a diverse array of cellular compounds into the surrounding seawater enclosed within discrete vesicles. Vesicles produced by two different strains contain some materials in common, but also display numerous strain-specific differences, reflecting functional complexity within vesicle populations. The vesicles contain active enzymes, indicating that they can mediate extracellular biogeochemical reactions in the ocean. We further demonstrate that vesicles from Prochlorococcus and other bacteria associate with diverse microbes including the most abundant marine bacterium, Pelagibacter. Together, our data point toward hypotheses concerning the functional roles of vesicles in marine ecosystems including, but not limited to, possibly mediating energy and nutrient transfers, catalysing extracellular biochemical reactions, and mitigating toxicity of reactive oxygen species.

Digital solution for follow-up in congenital cardiac surgery.

BACKGROUND: In this era of public scrutiny, there is an ongoing need for innovative methods for patient follow-up. OBJECTIVES: As part of a quality initiative, we developed an automated post-operative follow-up system for patients following discharge after cardiac surgery at Boston Children's Hospital. METHODS: Discharge Communication (DisCo) is a web-based system developed at Boston Children's Hospital. An automated text and e-mail with a link to a health status survey are sent at 30 days and 1 year post-discharge in English/Spanish. If there is no response, surveys are completed via phone calls to the patient/patient's physician or chart review. Responses are stored in the DisCo database and the patient's medical record. Patients who underwent cardiac surgery and survived to hospital discharge from October, 2016 received the surveys. RESULTS: Overall, 3345 30-day and 2563 1-year surveys were sent between October, 2016 and June, 2020. Of 3345 30-day surveys, there were 3191 responses (95%). Of 2563 1-year surveys, there were 1807 responses (71%). Most patients/families responded directly to the link at 30 days (65% for paediatrics/75% for adults) and at 1 year (72% for paediatrics/78% for adults). Multi-variable logistic regression revealed that higher complexity of cardiac lesion, presence of major non-cardiac anomalies and presence of major residua were associated with readmission and catheter/surgical reinterventions. Non-cardiac anomalies were associated with increased need for services for learning, development or behaviour. CONCLUSIONS: DisCo provides a successful web-based health status assessment of patients following congenital cardiac surgery. It helps to identify high-risk patients who need closer follow-up.

The role of epidemiology studies in human health risk assessment of polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) are a public health concern given evidence that they persist and accumulate in the environment and can cause toxic effects in animals and humans. However, evaluating adverse effects of PCBs in epidemiologic studies is complicated by the characteristics of PCB exposure. PCBs exist as mixtures in the environment; the mixture changes over time due to degradation, and given physicochemical differences between specific PCB congeners, the mixture that an individual is exposed to (via food, air, or other sources) is likely different from that which can be measured in biological tissues. This is particularly problematic when evaluating toxicity of shorter-lived congeners that may not be measurable by the time biological samples are collected. We review these and other issues that arise when evaluating epidemiologic studies of PCBs and discuss how epidemiology data can still be used to inform both hazard identification and dose-response evaluation.

Management of Complex Left Ventricular Outflow Tract Obstruction: A Comparison of Konno and Modified Konno Techniques.

Management of complex left ventricular outflow tract obstruction (LVOTO) can be achieved with a Konno or Modified Konno procedure to enlarge the LVOT. We hypothesized that patients who undergo a Modified Konno procedure would have a higher rate of LVOT re-intervention compared to the Konno procedure. Patients who underwent a Konno or Modified Konno procedure for LVOTO at a single tertiary care center between 1990 and 2014 were retrospectively reviewed. The primary outcome was LVOT re-intervention post-discharge from index Konno or Modified Konno procedure. Cox regression and Kaplan-Meier estimates were used for time-to-event analysis of LVOT re-interventions, any unplanned re-interventions, and transplant-free survival. The study included 122 patients: 51 (41.8%) in the Konno group and 71 (58.2%) in the Modified Konno group. Median age at surgery was 8.2 (IQR 3-16) years in the Konno group and 3.9 (IQR 1.5-11) years in the Modified Konno group. Multiple left heart lesions were less prevalent in Modified Konno patients. There were 36 (29.5%) patients with LVOT re-interventions: 8 (16%) in the Konno group and 28 (39.4%) in the Modified Konno group (p = 0.01). Transplant-free survival at five years was 87.2% for the Konno group and 93.5% for the Modified Konno group. A higher rate of LVOT re-intervention was found in the Modified Konno group although the Konno and Modified Konno techniques were applied to different patient populations. This finding suggests that careful preoperative decision-making can direct therapy appropriately and that fundamental diagnosis affects procedure choice.

Characteristics and outcomes of gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices: A systematic review.

Gastrointestinal bleeding (GIB) is a common adverse event after continuous-flow left ventricular assist device (CF-LVAD) implantation. We sought to evaluate patterns of GIB development and related outcomes in CF-LVAD recipients. An electronic search was performed to identify all articles related to GIB in the setting of CF-LVAD implantation. A total of 34 studies involving 1087 patients were pooled for analysis. Mean patient age was 60 years (95% CI 57-64) and 24% (95% CI 21-28%) were female. The mean time from CF-LVAD implantation to the first GIB was 54 days (95% CI 24-84) with 40% (95% CI 34-45%) of patients having multiple episodes of GIB. Anemia was present in 75% (95% CI 41-93%) and the most common etiology of bleeding was arteriovenous malformations (36% [95% CI 24-50%]). The mean duration of follow-up was 14.6 months (95% CI 6.9-22.3) during which the all-cause mortality rate was 21% (95% CI 12-36%) and the mortality rate from GIB was 4% (95% CI 2-9%). Thromboembolic events occurred in 32% (95% CI 22-44%) of patients with an ischemic stroke rate of 16% (95% CI 3-51%) and a pump thrombosis rate of 8% (95%CI 3-22%). Heart transplantation was performed in 31% (95% CI 18-47%) of patients, after which 0% (95% CI 0-10%) experienced recurrent GIB. GIB is a major source of morbidity among CF-LVAD recipients. While death due to GIB is rare, cessation of anticoagulation during treatment increases the risk of subsequent thrombotic events. Heart transplant in these patients appears to reliably resolve the risk of future GIB.

Use of a novel computerized decision aid for aneuploidy screening: a randomized controlled trial.

PURPOSE: To assess whether knowledge following use of a decision aid (DA) for aneuploidy screening and testing is inferior to knowledge in women who saw a genetic counselor (GC) only. METHODS: This is a randomized controlled noninferiority trial of pregnant women at ≤22 weeks. Women who were scheduled for GC were randomly allocated to use a DA before GC or to GC alone. The primary outcome was knowledge score, comparing women who had used the DA only to those who saw GC alone. Analysis was by intent to treat. RESULTS: Between January and October 2017, 197 women were randomized, 105 to GC only and 92 to DA use before GC. Demographics and baseline knowledge were similar between groups. Mean knowledge score following DA use was not inferior to mean knowledge score following GC only (10.4 vs. 10.6, p = 0.306). Decisional conflict was similar following completion of the DA to following GC only, but was reduced following completion of both the DA and GC compared with GC only (0.22 vs. 1.74, p = 0.003). CONCLUSION: Knowledge surrounding aneuploidy screening in women who used a DA was not inferior to knowledge in women who underwent GC. Use of the DA in addition to GC reduced decisional conflict.

Use of exogenous glycine betaine and its precursor choline as osmoprotectants in Antarctic sea-ice diatoms1.

Wide salinity ranges experienced during the seasonal freeze and melt of sea ice likely constrain many biological processes. Microorganisms generally protect against fluctuating salinities through the uptake, production, and release of compatible solutes. Little is known, however, about the use or fate of glycine betaine (GBT hereafter), one of the most common compatible solutes, in sea-ice diatoms confronted with shifts in salinity. We quantified intracellular concentrations and used [14 C]-labeled compounds to track the uptake and fate of the nitrogen-containing osmolyte GBT and its precursor choline in three Antarctic sea-ice diatoms Nitzschia lecointei, Navicula cf. perminuta, and Fragilariopsis cylindrus at -1°C. Experiments show that these diatoms have effective transporters for GBT, but take up lesser amounts of choline. Neither compound was respired. Uptake of GBT protected cells against hyperosmotic shock and corresponded with reduced production of extracellular polysaccharides in N. lecointei cells, which released 85% of the retained GBT following hypoosmotic shock. The ability of sea-ice diatoms to rapidly scavenge and release compatible solutes is likely an important strategy for survival during steep fluctuations in salinity. The release and recycling of compatible solutes may play an important role in algal-bacterial interactions and nitrogen cycling within the semi-enclosed brines of sea ice.

Integrating data gap filling techniques: A case study predicting TEFs for neurotoxicity TEQs to facilitate the hazard assessment of polychlorinated biphenyls.

The application of toxic equivalency factors (TEFs) or toxic units to estimate toxic potencies for mixtures of chemicals which contribute to a biological effect through a common mechanism is one approach for filling data gaps. Toxic Equivalents (TEQ) have been used to express the toxicity of dioxin-like compounds (i.e., dioxins, furans, and dioxin-like polychlorinated biphenyls (PCBs)) in terms of the most toxic form of dioxin: 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). This study sought to integrate two data gap filling techniques, quantitative structure-activity relationships (QSARs) and TEFs, to predict neurotoxicity TEQs for PCBs. Simon et al. (2007) previously derived neurotoxic equivalent (NEQ) values for a dataset of 87 PCB congeners, of which 83 congeners had experimental data. These data were taken from a set of four different studies measuring different effects related to neurotoxicity, each of which tested overlapping subsets of the 83 PCB congeners. The goals of the current study were to: (i) evaluate an alternative neurotoxic equivalent factor (NEF) derivations from an expanded dataset, relative to those derived by Simon et al. and (ii) develop QSAR models to provide NEF estimates for the large number of untested PCB congeners. The models used multiple linear regression, support vector regression, k-nearest neighbor and random forest algorithms within a 5-fold cross validation scheme and position-specific chlorine substitution patterns on the biphenyl scaffold as descriptors. Alternative NEF values were derived but the resulting QSAR models had relatively low predictivity (RMSE ∼0.24). This was mostly driven by the large uncertainties in the underlying data and NEF values. The derived NEFs and the QSAR predicted NEFs to fill data gaps should be applied with caution.

Best-Matched Internal Standard Normalization in Liquid Chromatography-Mass Spectrometry Metabolomics Applied to Environmental Samples.

The goal of metabolomics is to measure the entire range of small organic molecules in biological samples. In liquid chromatography-mass spectrometry-based metabolomics, formidable analytical challenges remain in removing the nonbiological factors that affect chromatographic peak areas. These factors include sample matrix-induced ion suppression, chromatographic quality, and analytical drift. The combination of these factors is referred to as obscuring variation. Some metabolomics samples can exhibit intense obscuring variation due to matrix-induced ion suppression, rendering large amounts of data unreliable and difficult to interpret. Existing normalization techniques have limited applicability to these sample types. Here we present a data normalization method to minimize the effects of obscuring variation. We normalize peak areas using a batch-specific normalization process, which matches measured metabolites with isotope-labeled internal standards that behave similarly during the analysis. This method, called best-matched internal standard (B-MIS) normalization, can be applied to targeted or untargeted metabolomics data sets and yields relative concentrations. We evaluate and demonstrate the utility of B-MIS normalization using marine environmental samples and laboratory grown cultures of phytoplankton. In untargeted analyses, B-MIS normalization allowed for inclusion of mass features in downstream analyses that would have been considered unreliable without normalization due to obscuring variation. B-MIS normalization for targeted or untargeted metabolomics is freely available at https://github.com/IngallsLabUW/B-MIS-normalization .

How the physicality of space affects how we think about time.

Time is an abstract concept that may be better understood when mapped onto space. For English speakers, typically a timeline is used that runs horizontally from left (past) to right (future) (Boroditsky, Fuhrman, & McCormick, 2011) and can be separated into regions, past and future. However, it is unclear from prior research how these regions along the timeline are differentiated. In addition, although for English speakers time is typically thought of in terms of a left-right axis, gestures and metaphors that conceptualize the past as behind and the future as ahead are prevalent, implicating the use of a front-back axis. In three experiments, participants made temporal judgments of pictures while holding their hands in various positions around their bodies, to assess whether the body or hands or both are used as anchors to differentiate regions and whether the front-back axis can be used as a timeline. In Experiment 1 we found independent influences of the body and the hands in anchoring the left-right axis. In Experiment 2 we found support for the use of the front-back axis to map time, with independent influences of the body and the hands in anchoring this axis as well. In Experiment 3 we demonstrated that the timeline must be configured in a way that is consistent with underlying conceptualizations of time, by showing that the above-below axis is not used for English speakers. Together, these results indicate that time is mapped onto space, with this mapping being constrained by underlying conceptualizations of time.

Confounding effects of oxygen and temperature on the TEX86 signature of marine Thaumarchaeota.

Marine ammonia-oxidizing archaea (AOA) are among the most abundant of marine microorganisms, spanning nearly the entire water column of diverse oceanic provinces. Historical patterns of abundance are preserved in sediments in the form of their distinctive glycerol dibiphytanyl glycerol tetraether (GDGT) membrane lipids. The correlation between the composition of GDGTs in surface sediment and the overlying annual average sea surface temperature forms the basis for a paleotemperature proxy (TEX86) that is used to reconstruct surface ocean temperature as far back as the Middle Jurassic. However, mounting evidence suggests that factors other than temperature could also play an important role in determining GDGT distributions. We here use a study set of four marine AOA isolates to demonstrate that these closely related strains generate different TEX86-temperature relationships and that oxygen (O2) concentration is at least as important as temperature in controlling TEX86 values in culture. All of the four strains characterized showed a unique membrane compositional response to temperature, with TEX86-inferred temperatures varying as much as 12 °C from the incubation temperatures. In addition, both linear and nonlinear TEX86-temperature relationships were characteristic of individual strains. Increasing relative abundance of GDGT-2 and GDGT-3 with increasing O2 limitation, at the expense of GDGT-1, led to significant elevations in TEX86-derived temperature. Although the adaptive significance of GDGT compositional changes in response to both temperature and O2 is unclear, this observation necessitates a reassessment of archaeal lipid-based paleotemperature proxies, particularly in records that span low-oxygen events or underlie oxygen minimum zones.

Transabdominal ultrasound is appropriate.

Preterm birth remains a major cause of perinatal morbidity and mortality. A short cervix is strongly associated with spontaneous preterm birth. Professional organizations support cervical length screening for singleton gestations with a prior spontaneous preterm birth and second-trimester cervical length measurements between 16-24 weeks. All interventions used to decrease the risk of preterm birth in women with a short cervix are based on clinical trials that used transvaginal cervical length measurement, but transabdominal ultrasound has been shown to correlate well with transvaginal measurement in some observational studies. Transvaginal cervical length measurement is more accurate and more reliably obtained than the transabdominal approach. Conversely, transabdominal ultrasound could have the advantage of ease of implementation and, in general, is perceived by patients to be associated with less discomfort. Currently, there is no randomized clinical study that compares head-to-head the effectiveness of transvaginal vs transabdominal ultrasound for preterm birth risk screening. This point/counterpoint article summarizes the pros and cons of the 2 ultrasound approaches and debates whether transvaginal ultrasound should be used exclusively or if transabdominal ultrasound can be incorporated in cervical length screening for prevention of preterm birth.

Predicting neonatal respiratory morbidity by lamellar body count and gestational age.

AIMS: To develop a predictive model for assessing the risk of developing neonatal respiratory morbidity using lamellar body counts (LBCs) and gestational age (GA) to provide a more patient-specific assessment. METHODS: Retrospective cohort study of patients' ≥32 weeks' gestation who received amniocentesis with LBC analysis over a 9-year period. Respiratory morbidity was defined as respiratory distress syndrome, transient tachypnea of the newborn or oxygen requirement for >24 h. Logistic regression analyses were used to predict the absolute risk and odds of respiratory morbidity as a function of GA and lamellar body count. RESULTS: Two hundred and sixty-seven mother-infant pairs included in the analysis with 32 cases (12.0%) of respiratory morbidity. When compared to those without respiratory morbidity, neonates with respiratory morbidity had amniocentesis performed at an earlier median GA, had lower mean birthweight and had lower median LBC (P<0.01). The GA specific absolute risks and odds ratios for the presence of respiratory morbidity were calculated. The predicted absolute risks of neonatal respiratory morbidity ranged from 38% at 32 weeks to 6% at 40 weeks when LBC were 35,000/µL. CONCLUSION: GA specific predicted risk of neonatal respiratory morbidity using LBC provides a statistical model, which can aid clinicians in individually counseling patients regarding the absolute risk of their neonate developing respiratory morbidity.

Management of Pregnancy and Survival of Infants with Trisomy 13 or Trisomy 18.

Objective The objective of this study was to describe antenatal/intrapartum management and survival of liveborn infants with known trisomy 13 (T13) or trisomy 18 (T18) based on planned neonatal care. Study Design This is a retrospective cohort study of singleton pregnancies complicated by T13/T18 at a tertiary center from 2004 to 2015. We included pregnancies with antenatal or neonatal cytogenetic T13/T18 diagnosis and excluded those which were terminated or had a fetal demise < 20 weeks. We compared antenatal/intrapartum management and neonatal survival by planned neonatal care, defined as either neonatal intervention (INT), including neonatal cardiopulmonary resuscitative measures or comfort care (CC) without resuscitative measures. Results In this study, 32 women (10 with T13 and 22 with T18) met study criteria; 12 (38%) elected INT and 20 (62%) CC. Compared with those who elected INT, women who elected CC were more likely to undergo elective induction (40 vs. 0%, p = 0.01), have an intrapartum stillbirth (0 vs. 32%, p = 0.14), and deliver vaginally (25 vs. 63%, p < 0.01). In neonatal survival analysis (n = 26), median survival was longer in the INT group compared with CC group (64 days [interquartile range, IQR: 2, 155) vs. 3 days [IQR]: 0.3, 42), p = 0.28), but survival to hospital discharge was similar (53 vs. 57%, p = 0.95). Conclusion Regardless of desired level of neonatal INT, many women who continue pregnancies complicated by T13/18 have infants who survive beyond hospital discharge.

Determination of four forms of vitamin B12 and other B vitamins in seawater by liquid chromatography/tandem mass spectrometry.

RATIONALE: Vitamin B(12) is an essential nutrient for more than half of surveyed marine algae species, but methods for directly measuring this important cofactor in seawater are limited. Current mass spectrometry methods do not quantify all forms of B(12), potentially missing a significant portion of the B(12) pool. METHODS: We present a method to measure vitamins B(1), B(2), B(6), B(7) and four forms of B(12) dissolved in seawater. The method entails solid-phase extraction, separation by ultra-performance liquid chromatography, and detection by triple-quadrupole tandem mass spectrometry using stable-isotope-labeled internal standards. We demonstrated the use of this method in the environment by analyzing B(12) concentrations at different depths in the Hood Canal, part of the Puget Sound estuarine system in Washington State. RESULTS: Recovery of vitamin B(12) forms during the preconcentration steps was >71% and the limits of detection were <0.275 pM in seawater. Standard addition calibration curves in three different seawater matrices were used to determine analytical response and to quantify samples from the environment. Hydroxocobalamin was the main form of B(12) in seawater at our field site. CONCLUSIONS: We developed a method for quantifying four forms of B(12) in seawater by liquid chromatography/mass spectrometry with the option of simultaneous analysis of vitamins B(1), B(2), B(6), and B(7). We validated the method and demonstrated its application in the field.

Expanded Systematic Evidence Map for Hundreds of Per- and Polyfluoroalkyl Substances (PFAS) and Comprehensive PFAS Human Health Dashboard.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) encompass a class of chemically and structurally diverse compounds that are extensively used in industry and detected in the environment. The US Environmental Protection Agency (US EPA) 2021 PFAS Strategic Roadmap describes national research plans to address the challenge of PFAS. OBJECTIVES: Systematic Evidence Map (SEM) methods were used to survey and summarize available epidemiological and mammalian bioassay evidence that could inform human health hazard identification for a set of 345 PFAS that were identified by the US EPA's Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing and through interagency discussions on PFAS of interest. This work builds from the 2022 evidence map that collated evidence on a separate set of ∼150 PFAS. Like our previous work, this SEM does not include PFAS that are the subject of ongoing or completed assessments at the US EPA. METHODS: SEM methods were used to search, screen, and inventory mammalian bioassay and epidemiological literature from peer-reviewed and gray literature sources using manual review and machine-learning software. For each included study, study design details and health end points examined were summarized in interactive web-based literature inventories. Some included studies also underwent study evaluation and detailed extraction of health end point data. All underlying data is publicly available online as interactive visuals with downloadable metadata. RESULTS: More than 13,000 studies were identified from scientific databases. Screening processes identified 121 mammalian bioassay and 111 epidemiological studies that met screening criteria. Epidemiological evidence (available for 12 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Mammalian bioassay evidence (available for 30 PFAS) commonly assessed effects in the reproductive, whole-body, nervous, and hepatic systems. Overall, 41 PFAS had evidence across mammalian bioassay and epidemiology data streams (roughly 11% of searched chemicals). DISCUSSION: No epidemiological and/or mammalian bioassay evidence were identified for most of the PFAS included in our search. Results from this SEM, our 2022 SEM on ∼150 PFAS, and other PFAS assessment products from the US EPA are compiled into a comprehensive PFAS dashboard that provides researchers and regulators an overview of the current PFAS human health landscape including data gaps and can serve as a scoping tool to facilitate prioritization of PFAS-related research and/or risk assessment activities. https://doi.org/10.1289/EHP13423.

When what you hear influences when you see: listening to an auditory rhythm influences the temporal allocation of visual attention.

The three experiments reported here demonstrated a cross-modal influence of an auditory rhythm on the temporal allocation of visual attention. In Experiment 1, participants moved their eyes to a test dot with a temporal onset that was either synchronous or asynchronous with a preceding auditory rhythm. Saccadic latencies were faster for the synchronous condition than for the asynchronous conditions. In Experiment 2, the effect was replicated in a condition in which the auditory context stopped prior to the onset of the test dot, and the effect did not occur in a condition in which auditory tones were presented at irregular intervals. Experiment 3 replicated the effect using an accuracy measure within a nontimed visual task. Together, the experiments' findings support a general entrainment perspective on attention to events over time.