Large sensory volumes enable Southern elephant seals to exploit sparse deep-sea prey.

The ability of echolocating toothed whales to detect and classify prey at long ranges enables efficient searching and stalking of sparse prey in these time-limited dives. However, nonecholocating deep-diving seals such as elephant seals appear to have much less sensory advantage over their prey. Both elephant seals and their prey rely on visual and hydrodynamic cues that may be detectable only at short ranges in the deep ocean, leading us to hypothesize that elephant seals must adopt a less efficient reactive mode of hunting that requires high prey densities. To test that hypothesis, we deployed high-resolution sonar and movement tags on 25 females to record simultaneous predator and prey behavior during foraging interactions. We demonstrate that elephant seals have a sensory advantage over their prey that allows them to potentially detect prey 5 to 10 s before striking. The corresponding prey detection ranges of 7 to 17 m enable stealthy approaches and prey-specific capture tactics. In comparison, prey react at a median range of 0.7 m, close to the neck extension range of striking elephant seals. Estimated search swathes of 150 to 900 m2 explain how elephant seals can locate up to 2,000 prey while swimming more than 100 km per day. This efficient search capability allows elephant seals to subsist on prey densities that are consonant with the deep scattering layer resources estimated by hydroacoustic surveys but which are two orders of magnitude lower than the prey densities needed by a reactive hunter.

Small reductions in cargo vessel speed substantially reduce noise impacts to marine mammals.

Global reductions in the underwater radiated noise levels from cargo vessels are needed to reduce increasing cumulative impacts to marine wildlife. We use a vessel exposure simulation model to examine how reducing vessel source levels through slowdowns and technological modifications can lessen impacts on marine mammals. We show that the area exposed to ship noise reduces markedly with moderate source-level reductions that can be readily achieved with small reductions in speed. Moreover, slowdowns reduce all impacts to marine mammals despite the longer time that a slower vessel takes to pass an animal. We conclude that cumulative noise impacts from the global fleet can be reduced immediately by slowdowns. This solution requires no modification to ships and is scalable from local speed reductions in sensitive areas to ocean basins. Speed reductions can be supplemented by routing vessels away from critical habitats and by technological modifications to reduce vessel noise.

Tuaimenals B-H, Merosesquiterpenes from the Irish Deep-Sea Soft Coral Duva florida with Bioactivity against Cervical Cancer Cell Lines.

Previous chemical investigation of the Irish deep-sea soft coral Duva florida led to the identification of tuaimenal A (10), a new merosesquiterpene containing a highly substituted chromene core and modest cytotoxicity against cervical cancer. Further MS/MS and NMR-guided investigation of this octocoral has resulted in the isolation and characterization of seven additional tuaimenal analogs, B-H (1-7), as well as two known A-ring aromatized steroids (8, 9), and additional tuaimenal A (10). Tuaimenals B, F, and G (1, 5, 6), bearing an oxygen at the C5 position, as well as monocyclic tuaimenal H (7), show increased cervical cancer inhibition profiles in comparison to that of 10. Tuaimenal G further displayed potent, selective cytotoxicity with an EC50 value of 0.04 µM against the C33A cell line compared to the CaSki cell line (EC50 20 µM). These data reveal the anticancer properties of tuaimenal analogs and suggest unique antiproliferation mechanisms across these secondary metabolites.

Low cost macroalgal canopy biomass monitoring using light attenuation.

Macroalgal canopies are productive and diverse habitats that export material to other marine ecosystems. Macroalgal canopy cover and composition are considered an Essential Ocean Variable by the research community. Although several techniques exist to both directly and remotely measure algal canopies, frequent measures of biomass are challenging. Presented here is a technique of using the relative attenuation of light inside and outside canopies to derive a proxy for algal biomass. If canopy attenuation coefficients are known, the proxy can be converted to an area of algal thallus per seabed area (thallus area index). An advantage of the approach is that light loggers are widely available and relatively inexpensive. Deployment for a year in the intertidal demonstrated that the method has the sensitivity to resolve summertime peaks in macroalgal biomass, despite the inherent variation in light measurements. Relative attenuation measurements can complement existing monitoring, providing point proxies for biomass and adding seasonal information to surveys that sample shores at less frequent intervals.

Crannenols A-D, Sesquiterpenoids from the Irish Deep-Sea Soft Coral Acanella arbuscula.

Four undescribed sesquiterpenoids, crannenols A-D (1-4), have been isolated from CHCl2 and MeOH extracts of the deep-sea bamboo coral Acanella arbuscula. The corals were collected from a submarine canyon on the edge of Ireland's Porcupine Bank via a remotely operated vehicle. The structure elucidation of these (Z,E)-α-farnesene derivatives was achieved using a combination of 1D and 2D NMR, electron impact (1, 2), and electrospray ionization (3, 4) mass spectrometry.

Tuaimenal A, a Meroterpene from the Irish Deep-Sea Soft Coral Duva florida, Displays Inhibition of the SARS-CoV-2 3CLpro Enzyme.

Cold water benthic environments are a prolific source of structurally diverse molecules with a range of bioactivities against human disease. Specimens of a previously chemically unexplored soft coral, Duva florida, were collected during a deep-sea cruise that sampled marine invertebrates along the Irish continental margin in 2018. Tuaimenal A (1), a cyclized merosesquiterpenoid representing a new carbon scaffold with a highly substituted chromene core, was discovered through exploration of the soft coral secondary metabolome via NMR-guided fractionation. The absolute configuration was determined through vibrational circular dichroism. Functional biochemical assays and in silico docking experiments found tuaimenal A selectively inhibits the viral main protease (3CLpro) of SARS-CoV-2.

Not Drug-like, but Like Drugs: Cnidaria Natural Products.

Phylum Cnidaria has been an excellent source of natural products, with thousands of metabolites identified. Many of these have not been screened in bioassays. The aim of this study was to explore the potential of 5600 Cnidaria natural products (after excluding those known to derive from microbial symbionts), using a systematic approach based on chemical space, drug-likeness, predicted toxicity, and virtual screens. Previous drug-likeness measures: the rule-of-five, quantitative estimate of drug-likeness (QED), and relative drug likelihoods (RDL) are based on a relatively small number of molecular properties. We augmented this approach using reference drug and toxin data sets defined for 51 predicted molecular properties. Cnidaria natural products overlap with drugs and toxins in this chemical space, although a multivariate test suggests that there are some differences between the groups. In terms of the established drug-likeness measures, Cnidaria natural products have generally lower QED and RDL scores than drugs, with a higher prevalence of metabolites that exceed at least one rule-of-five threshold. An index of drug-likeness that includes predicted toxicity (ADMET-score), however, found that Cnidaria natural products were more favourable than drugs. A measure of the distance of individual Cnidaria natural products to the centre of the drug distribution in multivariate chemical space was related to RDL, ADMET-score, and the number of rule-of-five exceptions. This multivariate similarity measure was negatively correlated with the QED score for the same metabolite, suggesting that the different approaches capture different aspects of the drug-likeness of individual metabolites. The contrasting of different drug similarity measures can help summarise the range of drug potential in the Cnidaria natural product data set. The most favourable metabolites were around 210-265 Da, quite often sesquiterpenes, with a moderate degree of complexity. Virtual screening against cancer-relevant targets found wide evidence of affinities, with Glide scores <-7 in 19% of the Cnidaria natural products.

Open Fetal Surgical Outcomes for Myelomeningocele Closure Stratified by Maternal Body Mass Index in a Large Single-Center Cohort.

BACKGROUND: Open maternal-fetal surgery for in utero closure of myelomeningocele (MMC) has become an accepted treatment option for prenatally diagnosed open neural tube defects. Historically, this option has been limited to women with BMI < 35 due to concern for increasing complications in patients with obesity. OBJECTIVE: The aim of this study was to evaluate maternal, obstetric, and fetal/neonatal outcomes stratified by maternal BMI classification in women who undergo open maternal-fetal surgery for fetal myelomeningocele (fMMC) closure. METHODS: A single-center fMMC closure registry was queried for maternal demographics, preoperative factors, fetal surgery outcomes, delivery outcomes, and neonatal outcomes. Data were stratified based on maternal BMI: <30, 30-34.99, and ≥35-40, corresponding to normal weight/overweight, obesity class I, and obesity class II. Statistical analysis was performed using statistical software SAS v.9.4 (SAS Institute Inc., Cary, NC, USA). RESULTS: A total of 264 patients were analyzed, including 196 (74.2%) with BMI <30, 54 (20.5%) with BMI 30-34.99, and 14 (5.3%) with BMI ≥ 35-40. Maternal demographics and preoperative characteristics were similar among the groups. Operative time increased with increasing BMI; otherwise, perioperative outcomes were similar among the groups. Obstetric and neonatal outcomes were similar among the groups. CONCLUSION: Increasing maternal BMI did not result in a negative impact on maternal, obstetric, and fetal/neonatal outcomes in a large cohort of patients undergoing open maternal-fetal surgery for fMMC closure. Further study is warranted to determine the generalizability of these results.

Estimating intertidal seaweed biomass at larger scales from quadrat surveys.

The amount of macroalgal biomass is an important ecosystem variable. Estimates can be made for a sampled area or values can be extrapolated to represent biomass over a larger region. Typically biomass is scaled-up using the area multiplied by the mean: a non-spatial method. Where algal biomass is patchy or shows gradients, non-spatial estimates for an area may be improved by spatial interpolation. A separate issue with scaling-up biomass estimates is that conventional confidence intervals based on the standard error (SE) of the sample may not be appropriate. The issues around interpolation and confidence intervals were examined for three fucoid species using data from 40 × 0.25 m-2 quadrats thrown in a 0.717 ha sampling plot on the shore of Galway Bay. Despite evidence of spatial autocorrelation, interpolation did not appear to improve estimates of the total plot biomass of Fucus serratus and F. vesiculosus. In contrast, interpolated estimates for Ascophyllum nodosum had less error than those based on the non-spatial method. Bootstrapped confidence intervals had several benefits over those based on the SE. These benefits include the avoidance of negative confidence limits at low sample sizes and no assumptions of normality in the data. If there is reason to expect strong patchiness or a gradient of biomass in the area of interest, interpolation is likely to produce more accurate estimates of biomass than non-spatial methods. Development of methodologies for biomass would benefit from more definition of local and regional gradients in biomass and their associated covariates.

Prenatal Repair of Myelomeningocele and School-age Functional Outcomes.

BACKGROUND AND OBJECTIVES: The Management of Myelomeningocele Study (MOMS), a randomized trial of prenatal versus postnatal repair for myelomeningocele, found that prenatal surgery resulted in reduced hindbrain herniation and need for shunt diversion at 12 months of age and better motor function at 30 months. In this study, we compared adaptive behavior and other outcomes at school age (5.9-10.3 years) between prenatal versus postnatal surgery groups. METHODS: Follow-up cohort study of 161 children enrolled in MOMS. Assessments included neuropsychological and physical evaluations. Children were evaluated at a MOMS center or at a home visit by trained blinded examiners. RESULTS: The Vineland composite score was not different between surgery groups (89.0 ± 9.6 in the prenatal group versus 87.5 ± 12.0 in the postnatal group; P = .35). Children in the prenatal group walked without orthotics or assistive devices more often (29% vs 11%; P = .06), had higher mean percentage scores on the Functional Rehabilitation Evaluation of Sensori-Neurologic Outcomes (92 ± 9 vs 85 ± 18; P < .001), lower rates of hindbrain herniation (60% vs 87%; P < .001), had fewer shunts placed for hydrocephalus (49% vs 85%; P < .001) and, among those with shunts, fewer shunt revisions (47% vs 70%; P = .02) than those in the postnatal group. Parents of children repaired prenatally reported higher mean quality of life z scores (0.15 ± 0.67 vs 0.11 ± 0.73; P = .008) and lower mean family impact scores (32.5 ± 7.8 vs 37.0 ± 8.9; P = .002). CONCLUSIONS: There was no significant difference between surgery groups in overall adaptive behavior. Long-term benefits of prenatal surgery included improved mobility and independent functioning and fewer surgeries for shunt placement and revision, with no strong evidence of improved cognitive functioning.

Density-dependent growth in 'catch-and-wait' fisheries has implications for fisheries management and Marine Protected Areas.

Stock enhancement activities provide an opportunity to examine density-dependent suppression of population biomass which is a fundamental issue for resource management and design of no-take-zones. We document 'catch-and-wait' fisheries enhancement where all but the largest lobsters are thrown back, recapturing them later after they have grown to a larger size. The residency, rate of return, and potential negative density-dependent effects of this activity are described using a combination of tagging and v-notching and by relating spatial growth patterns to population density defined with Catch Per Unit Effort. The results successfully demonstrated the concept of catch-and-wait practices. However, a density-dependent suppression of growth (in body size) was observed in male lobsters. This demonstrates a mechanism to explain differences in lobster sizes previously observed across EU fishing grounds with different stock densities. This negative effect of density could also affect individual biomass production in marine reserve or no-take zones.

Pediatric neurosurgeons' views regarding prenatal surgery for myelomeningocele and the management of hydrocephalus: a national survey.

OBJECTIVE: The Management of Myelomeningocele Study (MOMS) compared prenatal with postnatal surgery for myelomeningocele (MMC). The present study sought to determine how MOMS influenced the clinical recommendations of pediatric neurosurgeons, how surgeons' risk tolerance affected their views, how their views compare to those of their colleagues in other specialties, and how their management of hydrocephalus compares to the guidelines used in the MOMS trial. METHODS: A cross-sectional survey was sent to all 154 pediatric neurosurgeons in the American Society of Pediatric Neurosurgeons. The effect of surgeons' risk tolerance on opinions and counseling of prenatal closure was determined by using ordered logistic regression. RESULTS: Compared to postnatal closure, 71% of responding pediatric neurosurgeons viewed prenatal closure as either "very favorable" or "somewhat favorable," and 51% reported being more likely to recommend prenatal surgery in light of MOMS. Compared to pediatric surgeons, neonatologists, and maternal-fetal medicine specialists, pediatric neurosurgeons viewed prenatal MMC repair less favorably (p < 0.001). Responders who believed the surgical risks were high were less likely to view prenatal surgery favorably and were also less likely to recommend prenatal surgery (p < 0.001). The management of hydrocephalus was variable, with 60% of responders using endoscopic third ventriculostomy in addition to ventriculoperitoneal shunts. CONCLUSIONS: The majority of pediatric neurosurgeons have a favorable view of prenatal surgery for MMC following MOMS, although less so than in other specialties. The reported acceptability of surgical risks was strongly predictive of prenatal counseling. Variation in the management of hydrocephalus may impact outcomes following prenatal closure.

Effect of parental origin of damaging variants in pro-angiogenic genes on fetal growth in patients with congenital heart defects: Data and analyses.

The placenta is a highly vascular structure composed of both maternal and fetal elements. We have determined that damaging variants in genes responsible for the positive regulation of angiogenesis (PRA) (GO:0045766) that are inherited by the fetus impair fetal growth and placental function in pregnancies involving critical congenital cardiac defects (Russell et al., 2019). In this dataset, we present the specific genetic variants identified, describe the parental origin of each variant where possible and present the analyses regarding the potential effects of parental origin of the variant on placental function and fetal growth. The data presented are related to the research article "Damaging variants in pro-angiogenic genes impair growth in fetuses with cardiac defects" (Russell et al., 2019).

Damaging Variants in Proangiogenic Genes Impair Growth in Fetuses with Cardiac Defects.

OBJECTIVE: To determine the impact of damaging genetic variation in proangiogenic pathways on placental function, complications of pregnancy, fetal growth, and clinical outcomes in pregnancies with fetal congenital heart defect. STUDY DESIGN: Families delivering a baby with a congenital heart defect requiring surgical repair in infancy were recruited. The placenta and neonate were weighed and measured. Hemodynamic variables were recorded from a third trimester (36.4 ± 1.7 weeks) fetal echocardiogram. Exome sequencing was performed on the probands (N = 133) and consented parents (114 parent-child trios, and 15 parent-child duos) and the GeneVetter analysis tool used to identify damaging coding sequence variants in 163 genes associated with the positive regulation of angiogenesis (PRA) (GO:0045766). RESULTS: In total, 117 damaging variants were identified in PRA genes in 133 congenital heart defect probands with 73 subjects having at least 1 variant. Presence of a damaging PRA variant was associated with increased umbilical artery pulsatility index (mean 1.11 with variant vs 1.00 without; P = .01). The presence of a damaging PRA variant was also associated with lower neonatal length and head circumference for age z score at birth (mean -0.44 and -0.47 with variant vs 0.23 and -0.05 without; P = .01 and .04, respectively). During median 3.1 years (IQR 2.0-4.1 years) of follow-up, deaths occurred in 2 of 60 (3.3%) subjects with no PRA variant and in 9 of 73 (12.3%) subjects with 1 or more PRA variants (P = .06). CONCLUSIONS: Damaging variants in proangiogenic genes may impact placental function and are associated with impaired fetal growth in pregnancies involving a fetus with congenital heart defect.

Field-recorded data on habitat, density, growth and movement of Nephrops norvegicus.

The availability of growth data in N. norvegicus is important for management purposes due to a lack of aging criteria and the commercial importance of fisheries in this species. Growth varies as a function of stock density, hence comparisons of growth rates between stocks at known density is particularly valuable. Growth is also related to starting size in males, making raw data on size-specific growth rates more valuable. Internally injected passive tags allowed us to track the growth of male and female individuals over one or two years. The spatial position of tagged recaptures was recorded to measure site fidelity of tagged releases. A total of 3300 pots were fished and their spatial positions were recorded to enable Catch Per Unit Effort calculations. Similarly, spatially geo-referenced v-notching and notched recovery enables spatially gridded densities to be calculated. Finally, acoustic mapping was carried out both on and off the fishing ground and was ground-truthed with sedimentology from grabs at 22 stations. These data are useful for fisheries and macroecological studies.

Fetal cardiomyopathy in neurofibromatosis type I: Novel phenotype and review of the literature.

Neurofibromatosis type I (NF1) is a relatively common genetic disorder characterized by neurocutaneous lesions, neurofibromas, skeletal anomalies, iris hamartomas, and predisposition to other tumors. NF1 results from heterozygous loss-of-function mutations in neurofibromin (NF1), and diagnosis is most often made using clinical diagnostic criteria. Cardiac manifestations of NF1 include congenital heart disease (such as valvar pulmonary stenosis), left ventricular hypertrophy, and adult-onset pulmonary hypertension. Prenatal features of NF1 are often nonspecific and diagnoses are infrequently made prenatally without a known family history. Herein, we report the first case, to the best of our knowledge, of fetal cardiomyopathy as the presenting feature in NF1 and review NF1-related left ventricular hypertrophy. NF1 should be considered in the differential diagnosis for fetuses with cardiomyopathy, even in the absence of a known family history of the condition.

High Tumor Volume to Fetal Weight Ratio Is Associated with Worse Fetal Outcomes and Increased Maternal Risk in Fetuses with Sacrococcygeal Teratoma.

OBJECTIVE: Tumor volume to fetal weight ratio (TFR) > 0.12 before 24 weeks has been associated with poor outcome in fetuses with sacrococcygeal teratoma (SCT). We evaluated TFR in predicting poor fetal outcome and increased maternal operative risk in our cohort of SCT pregnancies. METHODS: This is a retrospective, single-center review of fetuses seen with SCT from 1997 to 2015. Patients who chose termination of pregnancy (TOP), delivered elsewhere, or had initial evaluation at > 24 weeks were excluded. Receiver operating characteristic (ROC) analysis determined the optimal TFR to predict poor fetal outcome and increased maternal operative risk. Poor fetal outcome included fetal demise, neonatal demise, or fetal deterioration warranting open fetal surgery or delivery < 32 weeks. Increased maternal operative risk included cases necessitating open fetal surgery, classical cesarean delivery, or ex utero intrapartum treatment (EXIT). RESULTS: Of 139 pregnancies with SCT, 27 chose TOP, 14 delivered elsewhere, and 40 had initial evaluation at > 24 weeks. Thus, 58 fetuses were reviewed. ROC analysis revealed that at ≤24 weeks, TFR > 0.095 was predictive of poor fetal outcome and TFR > 0.12 was predictive of increased maternal operative risk. CONCLUSION: This study supports the use of TFR at ≤24 weeks for risk stratification of pregnancies with SCT.

Preemptive Delivery and Immediate Resection for Fetuses with High-Risk Sacrococcygeal Teratomas.

INTRODUCTION: Fetuses with "high-risk" sacrococcygeal teratoma (SCT) have a mortality rate of 40-50%. While fetal surgery may benefit select fetuses prior to 27 weeks' gestation, many fetuses die due to consequences of rapid tumor growth after 27 weeks. Here we report our experience applying "preemptive" delivery to fetuses who manifest signs of decompensation between 27 and 32 weeks. METHODS: A retrospective review of SCT fetuses delivered between 2010 and 2016 at ≤32 weeks' gestation was performed. Patients who decompensated prior to 27 weeks and were treated with fetal surgery or neonatal palliation were excluded. RESULTS: Forty-two SCT fetuses were evaluated, and 11 were preemptively delivered in response to impending fetal or maternal decompensation. Nine (81.8%) survived. One death was due to pulmonary hypoplasia in a neonate with significant intra-abdominal tumor burden, and the other was due to in utero tumor rupture. There were no deaths related to prematurity in this cohort. CONCLUSIONS: Many fetuses with SCT manifest signs of decompensation between 27 and 32 weeks. In the absence of fetal hydrops prior to 27 weeks or tumor rupture in utero, early delivery is associated with favorable outcomes. Our single-center experience supports a management algorithm change to incorporate "preemptive" delivery for selected cases.

Convection-Enhanced Delivery in the Treatment of Glioblastoma.

OBJECTIVE: To describe the indications for convection-enhanced delivery in the treatment of glioblastoma, highlighting candidates for the delivery method, mechanics of drug delivery, and management of acute and long-term complications. DATA SOURCES: A conceptual framework drawn from published literature as well as author's expert experiences. CONCLUSION: Convection-enhanced delivery is an established method of delivering new therapies to patients with glioblastoma. Management of both acute and long-term complications is often drug dependent. IMPLICATIONS FOR NURSING PRACTICE: Nurses should be able to recognize and manage potential complications during the infusion of agents delivered via convection-enhanced delivery. Post-infusion symptoms may worsen because of immunologic responses related to the drug and management should be directed toward symptom relief and support without interference on the immunologic response.

Limited congruence exhibited across microbial, meiofaunal and macrofaunal benthic assemblages in a heterogeneous coastal environment.

One of the most common approaches for investigating the ecology of spatially complex environments is to examine a single biotic assemblage present, such as macroinvertebrates. Underlying this approach are assumptions that sampled and unsampled taxa respond similarly to environmental gradients and exhibit congruence across different sites. These assumptions were tested for five benthic groups of various sizes (archaea, bacteria, microbial eukaryotes/protists, meiofauna and macrofauna) in Plymouth Sound, a harbour with many different pollution sources. Sediments varied in granulometry, hydrocarbon and trace metal concentrations. Following variable reduction, canonical correspondence analysis did not identify any associations between sediment characteristics and assemblage composition of archaea or macrofauna. In contrast, variation in bacteria was associated with granulometry, trace metal variations and bioturbation (e.g. community bioturbation potential). Protists varied with granulometry, hydrocarbon and trace metal predictors. Meiofaunal variation was associated with hydrocarbon and bioturbation predictors. Taxon turnover between sites varied with only three out of 10 group pairs showing congruence (meiofauna-protists, meiofauna-macrofauna and protists-macrofauna). While our results support using eukaryotic taxa as proxies for others, the lack of congruence suggests caution should be applied to inferring wider indicator or functional interpretations from studies of a single biotic assemblage.