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OBJECTIVEGeographic and racial/ethnic disparities related to diabetes control and treatment have not previously been examined at the national level.RESEARCH DESIGN AND METHODSA retrospective cohort study was conducted in a national cohort of 1,140,634 veterans with diabetes, defined as two or more diabetes ICD-9 codes (250.xx) across inpatient and outpatient records. Main exposures of interest included 125 Veterans Administration Medical Center (VAMC) catchment areas as well as racial/ethnic group. The main outcome measure was HbA1c level dichotomized at ≥8.0% (≥64 mmol/mol).RESULTSAfter adjustment for age, sex, racial/ethnic group, service-connected disability, marital status, and the van Walraven Elixhauser comorbidity score, the prevalence of uncontrolled diabetes varied by VAMC catchment area, with values ranging from 19.1% to 29.2%. Moreover, these differences largely persisted after further adjusting for medication use and adherence as well as utilization and access metrics. Racial/ethnic differences in diabetes control were also noted. In our final models, compared with non-Hispanic Whites, non-Hispanic Blacks (odds ratio 1.11 [95% credible interval 1.09–1.14]) and Hispanics (1.36 [1.09–1.14]) had a higher odds of uncontrolled HBA1c level.CONCLUSIONSIn a national cohort of veterans with diabetes, we found geographic as well as racial/ethnic differences in diabetes control rates that were not explained by adjustment for demographics, comorbidity burden, use or type of diabetes medication, health care utilization, access metrics, or medication adherence. Moreover, disparities in suboptimal control appeared consistent across most, but not all, VAMC catchment areas, with non-Hispanic Black and Hispanic veterans having a higher odds of suboptimal diabetes control than non-Hispanic White veterans.

Purpose Previous studies investigating the association between anticholinergic burden (ACB) and health-related quality of life (HRQoL) showed conflicting results and focused on older adults or specific patient groups only. Methods Participants from the European Prospective Investigation of Cancer-Norfolk study were divided into three groups according to their ACB from medications at baseline, representing ACB scores of 0, 1 and ≥2. Outcomes of interest were the physical and mental component summary scores (PCS and MCS) of the Short Form-36, collected at 18 months from the baseline and again after a mean 13 years of follow-up. Linear regression and logistic regression for cross-sectional and longitudinal associations between ACB and HRQoL were constructed adjusting for potential confounders. Results A total of 16 675 participants, mean age 58.9 ± 9.1 years (55.6% female) and 7133 participants, mean age at follow-up 69.1 ± 8.7 years (56.8% female), were included in the cross-sectional and longitudinal analyses, respectively. In cross-sectional analysis, higher anticholinergic burden was associated with higher odds of being in the lowest quartile of PCS (ACB = 1; OR, 1.85[1.64, 2.09] and ACB ≥ 2:2.19[1.85, 2.58] and MCS (ACB = 1:1.47[1.30, 1.66] and ACB ≥ 2:1.68[1.42, 1.98]). In longitudinal analysis, higher anticholinergic burden was similarly associated with higher odds of being in the lowest quartile of PCS (ACB = 1:1.56[1.24, 1.95] and ACB ≥ 2:1.48[1.07, 2.03]) compared with ACB 0 group. The association with MCS scores did not reach statistical significance. Conclusion The use of anticholinergic medications is associated with both short and long-term poorer physical functions but association with mental functioning appears more short-term.

Methamphetamine (MA) use during pregnancy is a significant public health concern in the United States and affects long-term brain and behavioral development in children. We hypothesized that prenatal MA exposure would be related to greater DNA methylation of HSD11B2 and postnatal environmental stress.The Infant Development, Environment, and Lifestyle Study (IDEAL), a longitudinal study of prenatal MA exposure enrolled mother-infant dyads in California, Hawaii, Iowa, and Oklahoma. Prenatal exposure was defined by maternal self-report and/or meconium toxicology screening. At ages 10-11 years, 100 children were assessed for drug exposure and DNA methylation of HSD11B2. Hierarchical linear models were used to determine the association between prenatal MA exposure and methylation of HSD11B2 at four CpG sites.Prenatal MA exposure (1.4% vs 0.31%, P 0.01) and early childhood adversity (3.0 vs 2.0, P 0.01) were associated with greater DNA methylation of HSD11B2 at the CpG2 site. The statistically significant effects of early childhood adversity (B = 0.11, P 0.01) and prenatal MA exposure (B = 0.32, P = 0.03) on DNA methylation remained after adjusting for covariates.Prenatal MA exposure is related to postnatal childhood adversity and epigenetic alterations in HSD11B2, an important gene along the stress response pathway suggesting prenatal and postnatal programming effects.Prenatal methamphetamine exposure has been associated with developmental issues in newborns, yet little is known about the stress pathophysiology of methamphetamine on neurobehavior. This is the first evidence that prenatal methamphetamine exposure acts as a stressor, confirming the third pathophysiology of methamphetamine exposure.

We report partition coefficients for Sr, Sc, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Y, and Th for plagioclase, pigeonite, and olivine experimentally grown from a lunar basaltic liquid at 1 bar and two different oxygen fugacities (fO2; fayalite-magnetite-quartz (FMQ) and the iron-wustite (IW) oxygen buffers) at temperatures (Ts) of 1100–1125 °C. These results expand the partitioning database for plagioclase-silicate melt partitioning at lunar relevant conditions and compositions. Variations of partition coefficients for rare earth elements (REEs) are highly systematic with respect to ionic radii, in agreement with lattice strain theory. We use the lattice strain model to evaluate partition coefficients for highly incompatible elements such as the light (or in the case of plagioclase, heavy) REEs, for which direct determinations are experimentally and analytically difficult. Our experiments suggest that within analytical and experimental uncertainty, over the range of explored fO2 (FMQ to IW), T (1100–1125 °C) and An# conditions (An# >94.5, where An#=Ca/(Ca + Na) × 100, in moles), fO2 exerts an important but secondary control on Eu partitioning in anorthitic plagioclase. In contrast, the global plagioclase-melt partitioning dataset highlights the first-order role of fO2 in determining plagioclase-melt Eu partition coefficients over a wide range of An#s. Using experimental results and predictive models for divalent and trivalent element plagioclase-melt partitioning in the plagioclase ring site, we parameterized an fO2-dependent plagioclase-melt Eu partitioning model. Within a factor of two, the model reproduces measured Eu partition coefficients for a wide range of experimental conditions (750–1400 °C) and compositional systems (basalts to dacites) over > 15 orders of magnitude variation in fO2. When equilibrium partitioning of Eu between plagioclase and melt can be established, the model may be applied as a plagioclase-melt oxybarometer. Preliminary application to plagioclase-hosted melt inclusions in mid-ocean ridge basalts suggests they equilibrated near the FMQ buffer. We used the new Eu partitioning model to evaluate the petrogenesis of a lunar anorthositic impactite that hosts plagioclase with both positive and negative Eu anomalies. Our investigation suggests the distribution of REEs and Eu in this sample is consistent with subsolidus reequilibration after impact-induced heating.

Significance Neuropeptide Y (NPY) is implicated in many pathological conditions including obesity, diabetes, and insulin resistance. However, a pathogenic role of NPY in kidney disease has not been described. We found that NPY is produced by the podocyte in the glomerulus, and this production decreases in renal disease, in contrast to an increase in circulating NPY levels. In the glomerulus, NPY signals via the NPY receptor 2 (NPY2R) and modulates PI3K, MAPK, and NFAT signaling, along with RNA processing and cell migration and, if prolonged, predicted nephrotoxicity. The pharmacological inhibition of NPY-NPY2R signaling also protected against albuminuria and kidney disease in a mouse model of glomerulosclerosis, suggesting that inhibiting this pathway may be therapeutically beneficial in the prevention of kidney disease., Albuminuria is an independent risk factor for the progression to end-stage kidney failure, cardiovascular morbidity, and premature death. As such, discovering signaling pathways that modulate albuminuria is desirable. Here, we studied the transcriptomes of podocytes, key cells in the prevention of albuminuria, under diabetic conditions. We found that Neuropeptide Y (NPY) was significantly down-regulated in insulin-resistant vs. insulin-sensitive mouse podocytes and in human glomeruli of patients with early and late-stage diabetic nephropathy, as well as other nondiabetic glomerular diseases. This contrasts with the increased plasma and urinary levels of NPY that are observed in such conditions. Studying NPY-knockout mice, we found that NPY deficiency in vivo surprisingly reduced the level of albuminuria and podocyte injury in models of both diabetic and nondiabetic kidney disease. In vitro, podocyte NPY signaling occurred via the NPY2 receptor (NPY2R), stimulating PI3K, MAPK, and NFAT activation. Additional unbiased proteomic analysis revealed that glomerular NPY-NPY2R signaling predicted nephrotoxicity, modulated RNA processing, and inhibited cell migration. Furthermore, pharmacologically inhibiting the NPY2R in vivo significantly reduced albuminuria in adriamycin-treated glomerulosclerotic mice. Our findings suggest a pathogenic role of excessive NPY-NPY2R signaling in the glomerulus and that inhibiting NPY-NPY2R signaling in albuminuric kidney disease has therapeutic potential.

In 2015, country singer Chris Stapleton, lauded for his allegiance to hard country music, stepped on stage at the Country Music Association annual awards show in Nashville, Tennessee, and knocked out a stunning performance of “Tennessee Whiskey.” The moment was heralded by critics and fans alike as a celebrated return to roots-oriented, traditional, hard country music. But Stapleton's cover version rewrote the song over a historically significant soul groove. In so doing, he presented a musical-political statement about the past and present of country music that challenged its acknowledged racial politics. The analyses presented here, centered on Stapleton and Sturgill Simpson, weave these threads together into a sonic explanation of country music's contradictory senses of genre identity, musical style, and racial politics. They propose a new historical perspective on the confluence of country and soul in the early 1960s, most memorably realized in the two Modern Sounds in Country and Western Music albums that Ray Charles released in 1962. What emerges in conclusion is a subversive narrative that reinvents modern hard country music through a lineage of R&B and soul.

The endothelial glycocalyx is a key component of the glomerular filtration barrier. We have shown that matrix metalloproteinase (MMP)-mediated syndecan 4 shedding is a mechanism of glomerular endothelial glycocalyx damage in vitro, resulting in increased albumin permeability. Here we sought to determine whether this mechanism is important in early diabetic kidney disease, by studying streptozotocin-induced type 1 diabetes in DBA2/J mice. Diabetic mice were albuminuric, had increased glomerular albumin permeability and endothelial glycocalyx damage. Syndecan 4 mRNA expression was found to be upregulated in isolated glomeruli and in flow cytometry-sorted glomerular endothelial cells. In contrast, glomerular endothelial luminal surface syndecan 4 and Marasmium oreades agglutinin lectin labelling measurements were reduced in the diabetic mice. Similarly, syndecan 4 protein expression was significantly decreased in isolated glomeruli but increased in plasma and urine, suggesting syndecan 4 shedding. Mmp-2, 9 and 14 mRNA expression were upregulated in isolated glomeruli, suggesting a possible mechanism of glycocalyx damage and albuminuria. We therefore characterised in detail the activity of MMP-2 and 9 and found significant increases in kidney cortex, plasma and urine. Treatment with MMP-2/9 inhibitor I for 21 days, started six weeks after diabetes induction, restored endothelial glycocalyx depth and coverage and attenuated diabetes-induced albuminuria and reduced glomerular albumin permeability. MMP inhibitor treatment significantly attenuated glomerular endothelial and plasma syndecan 4 shedding and inhibited plasma MMP activity. Thus, our studies confirm the importance of MMPs in endothelial glycocalyx damage and albuminuria in early diabetes and demonstrate that this pathway is amenable to therapeutic intervention. Hence, treatments targeted at glycocalyx protection by MMP inhibition may be of benefit in diabetic kidney disease.

Some insects, such as dragonflies, have evolved nanoprotrusions on their wings that rupture bacteria on contact. This has inspired the design of antibacterial implant surfaces with insect-wing mimetic nanopillars made of synthetic materials. Here, we characterise the physiological and morphological effects of mimetic titanium nanopillars on bacteria. The nanopillars induce deformation and penetration of the Gram-positive and Gram-negative bacterial cell envelope, but do not rupture or lyse bacteria. They can also inhibit bacterial cell division, and trigger production of reactive oxygen species and increased abundance of oxidative stress proteins. Our results indicate that nanopillars’ antibacterial activities may be mediated by oxidative stress, and do not necessarily require bacterial lysis., Synthetic nanopillars resembling the wing surface of certain insects display antibacterial activities. Here, Jenkins et al. show that these activities do not necessarily require bacterial lysis, and may be mediated by oxidative stress induced by deformation of the bacterial cell envelope.

BACKGROUND: Clinically suspected and laboratory-confirmed bloodstream infections are frequent causes of morbidity and mortality during neonatal care. The most effective infection prevention and control interventions for neonates in low- and middle-income countries (LMIC) are unknown. AIM: To identify effective interventions in the prevention of hospital-acquired bloodstream infections in LMIC neonatal units. METHODS: Medline, PUBMED, the Cochrane Database of Systematic Reviews, EMBASE and PsychInfo (January 2003 to October 2020) were searched to identify studies reporting single or bundled interventions for prevention of bloodstream infections in LMIC neonatal units. RESULTS: Our initial search identified 5206 articles; following application of filters, 27 publications met the inclusion and Integrated Quality Criteria for the Review of Multiple Study Designs assessment criteria and were summarized in the final analysis. No studies were carried out in low-income countries, only 1 in Sub-Saharan Africa and just 2 in multiple countries. Of the 18 single-intervention studies, most targeted skin (n = 4) and gastrointestinal mucosal integrity (n = 5). Whereas emollient therapy and lactoferrin achieved significant reductions in proven neonatal infection, glutamine and mixed probiotics showed no benefit. Chlorhexidine gluconate for cord care and kangaroo mother care reduced infection in individual single-center studies. Of the 9 studies evaluating bundles, most focused on prevention of device-associated infections and achieved significant reductions in catheter- and ventilator-associated infections. CONCLUSIONS: There is a limited evidence base for the effectiveness of infection prevention and control interventions in LMIC neonatal units; bundled interventions targeting device-associated infections were most effective. More multisite studies with robust study designs are needed to inform infection prevention and control intervention strategies in low-resource neonatal units.

BackgroundNon-invasive biomarkers of immune checkpoint inhibitor-associated acute tubulointerstitial nephritis (ICI-nephritis) are urgently needed. Because ICIs block immune checkpoint pathways that include cytotoxic T lymphocyte antigen 4 (CTLA4), we hypothesized that biomarkers of immune dysregulationpreviously defined in patients with congenital CTLA4 deficiency, including elevated soluble interleukin-2 receptor alpha (sIL-2R) and flow cytometric cell-based markers of B and T cell dysregulation in peripheral blood may aid the diagnosis of ICI-nephritis.MethodsA retrospective cohort of patients diagnosed with ICI-nephritis was compared with three prospectively enrolled control cohorts: ICI-treated controls without immune-related adverse events, patients not on ICIs with hemodynamic acute kidney injury (hemodynamic AKI), and patients not on ICIs with biopsy proven acute interstitial nephritis from other causes (non-ICI-nephritis). sIL-2R level and flow cytometric parameters were compared between groups using Wilcoxon rank sum test or Kruskal-Wallis test. Receiver operating characteristic curves were generated to define the accuracy of sIL-2R and flow cytometric biomarkers in diagnosing ICI-nephritis. The downstream impact of T cell activation in the affected kidney was investigated using archived biopsy samples to evaluate the gene expression ofIL2RA,IL-2 signaling, and T cell receptor signaling in patients with ICI-nephritis compared with other causes of drug-induced nephritis, acute tubular injury, and histologically normal controls.ResultssIL-2R level in peripheral blood was significantly higher in patients with ICI-nephritis (N=24) (median 2.5-fold upper limit of normal (ULN), IQR 1.9–3.3), compared with ICI-treated controls (N=10) (median 0.8-fold ULN, IQR 0.5–0.9, p96%) when compared with either ICI-treated or hemodynamic AKI controls. By peripheral blood flow cytometry analysis, lower absolute CD8+T cells, CD45RA+CD8+ T cells, memory CD27+B cells, and expansion of plasmablasts were prominent features of ICI-nephritis compared with ICI-treated controls. Gene expressions forIL2RA, IL-2 signaling, and T cell receptor signaling in the kidney tissue with ICI-nephritis were significantly higher compared with controls.ConclusionElevated sIL-2R level and flow cytometric markers of both B and T cell dysregulation may aid the diagnosis of ICI-nephritis.

Neonatal encephalopathy (NE) accounts for ~23% of the 2.4 million annual global neonatal deaths. Approximately 99% of global neonatal deaths occur in low-resource settings, however, accurate data from these low-resource settings are scarce. We reviewed risk factors of neonatal mortality in neonates admitted with neonatal encephalopathy from a tertiary neonatal unit in Zimbabwe. A retrospective review of risk factors of short-term neonatal encephalopathy mortality was conducted at Sally Mugabe Central Hospital (SMCH) (November 2018 –October 2019). Data were gathered using a tablet-based data capture and quality improvement newborn care application (Neotree). Analyses were performed on data from all admitted neonates with a diagnosis of neonatal encephalopathy, incorporating maternal, intrapartum, and neonatal risk predictors of the primary outcome: mortality. 494/2894 neonates had neonatal encephalopathy on admission and were included. Of these, 94 died giving a neonatal encephalopathy-case fatality rate (CFR) of 190 per 1000 admitted neonates. Caesarean section (odds ratio (OR) 2.95(95% confidence interval (CI) 1.39–6.25), convulsions (OR 7.13 (1.41–36.1)), lethargy (OR 3.13 (1.24–7.91)), Thompson score “11–14” (OR 2.98 (1.08–8.22)) or “15–22” (OR 17.61 (1.74–178.0)) were significantly associated with neonatal death. No maternal risk factors were associated with mortality. Nearly 1 in 5 neonates diagnosed with neonatal encephalopathy died before discharge, similar to other low-resource settings but more than in typical high-resource centres. The Thompson score, a validated, sensitive and specific tool for diagnosing neonates with neonatal encephalopathy was an appropriate predictive clinical scoring system to identify at risk neonates in this setting. On univariable analysis time-period, specifically a period of staff shortages due to industrial action, had a significant impact on neonatal encephalopathy mortality. Emergency caesarean section was associated with increased mortality, suggesting perinatal care is likely to be a key moment for future interventions.

Sample return shows late lunar volcanism Measuring physical samples of Solar System bodies in the laboratory provides more information than is possible from remote sensing alone. In December 2020, the Chang’e-5 mission landed on the Moon, collected samples, and returned them to Earth. Che et al . analyze two fragments of volcanic lunar basalt collected by Chang’e-5. Radiometric dating using lead isotopes indicated that the rocks formed from magma that erupted about 2 billion years ago, later than other volcanic lunar samples. The abundance of extinct radioactive elements in the rock is too low for radioactive heating to have produced the magma. Another, thus far unknown, source must be responsible for the late lunar volcanism. —KTS

We conducted a thorough analysis of the feldspathic breccia meteorite Dhofar 1428 with the aim of better understanding the composition and evolution of lunar crust. This sample comprises a heterogeneous array of lithic fragments including magnesian and ferroan anorthositic granulites, mafic granulites/granulitic breccia, basalts, and different kinds of impact melt rocks. In which, a high-Ti basalt clast comprising large zoned pyroxene was observed. Based on equilibrium melt calculations of mineral zonations from this basalt, Mg-pyroxene cores were interpreted to be formed from a light rare earth element (LREE) enriched liquid, whereas the Fe-pyroxene rims grew from an LREE-depleted magma. We propose that LREE-depleted signature of Fe-pyroxene results from co-crystallization with apatite. The Mg-pyroxenes suggest that enriched liquids with higher REE contents and different REE patterns relative to KREEP existed within lunar interior. Oscillating Ti/Al ratios across pyroxene in this basalt may indicate several magma recharge events or crystal movement within a zoned magma chamber. This feature illustrates that magmas were derived from a variety of sources around the time of formation of this basalt. In situ U-Pb dating was conducted on apatite grains within this basalt, the excellent consistence between the U-Pb Concordia age (3941 ± 24 Ma, 2σ) and 207Pb/206Pb isochron age (3934 ± 24 Ma, 2σ) indicates the most likely crystallization age of this high-Ti basalt at ∼3940 Myr, making it one of the oldest high-Ti basalts formed on the Moon. Magnesian anorthositic granulites are mineralogically and geochemically similar to those trace element-poor magnesian anorthositic granulites in many lunar meteorites. These magnesian granulites cannot form from simple mixing of pristine Ferroan Anorthosite and lithologies from the Mg-Suite, and do not have any affinities with KREEP or the Procellarum KREEP Terrane, and they could be important components of farside highlands.

Very high potassium or VHK basalts have been described from the Apollo 14 landing site at Fra Mauro on the lunar near side. Many of the known samples are clasts in polymict breccias with a few as New work completed on fourteen VHK basalts include Crystal Size Distributions (CSDs) and in-situ chemical analyses and element maps collected by electron probe microanalysis (EPMA). CSDs completed on three VHK basalt samples indicate that these basalts are not impact melts and represent endogenous melts of the lunar interior. Potassium Kα element maps reveal the spatial relationship between the K-rich material and the basalt clasts with attached breccia matrix if present. In-situ EPMA analyses have identified two distinct types of K-rich material: K-feldspar and K-rich glass. With these new data, an additional mechanism for an exogenic petrogenesis of VHK basalts is proposed that involves the impact process. VHK basalts can be divided into two groups based on density and viscosity. VHK-1 basalts formed when a hot impact ejecta covered the granite/felsite-rich matrix material containing high-Al basalt clasts. Heat from the impact ejecta partially melted and possibly evaporated nearby K-bearing materials, which then infiltrated and contaminated the high-Al clasts. VHK-2 basalts are consistent with the hypothesis of granite assimilation by a high-Al magma, as seen in the higher abundances of network-forming elements.

The Joint Workshop on Induced Special Regions convened scientists and planetary protection experts to assess the potential of inducing special regions through lander or rover activity. An Induced Special Region is defined as a place where the presence of the spacecraft could induce water activity and temperature to be sufficiently high and persist for long enough to plausibly harbor life. The questions the workshop participants addressed were: (1) What is a safe stand-off distance, or formula to derive a safe distance, to a purported special region? (2) Questions about RTGs (Radioisotope Thermoelectric Generator), other heat sources, and their ability to induce special regions. (3) Is it possible to have an infected area on Mars that does not contaminate the rest of Mars? The workshop participants reached a general consensus addressing the posed questions, in summary: (1) While a spacecraft on the surface of Mars may not be able to explore a special region during the prime mission, the safe stand-off distance would decrease with time because the sterilizing environment, that is the martian surface would progressively clean the exposed surfaces. However, the analysis supporting such an exploration should ensure that the risk to exposing interior portions of the spacecraft (i.e., essentially unsterilized) to the martian surface is minimized. (2) An RTG at the surface of Mars would not create a Special Region but the short-term result depends on kinetics of melting, freezing, deliquescence, and desiccation. While a buried RTG could induce a Special Region, it would not pose a long-term contamination threat to Mars, with the possible exception of a migrating RTG in an icy deposit. (3) Induced Special Regions can allow microbial replication to occur (by definition), but such replication at the surface is unlikely to globally contaminate Mars. An induced subsurface Special Region would be isolated and microbial transport away from subsurface site is highly improbable.

BACKGROUND Psychosocial adversity escalates medical risk for poor outcomes in infants born

The Ontong Java Plateau (OJP), Shatsky Rise (SR), and Kerguelen Plateau/Broken Ridge (KP/BR) represent three large igneous provinces (LIPs) located in oceanic settings. The basement lavas have been investigated through scientific ocean drilling and, in the case of the OJP, fieldwork on the emergent obducted portions of the plateau in the Solomon Islands. Such studies show that these three LIPs have very different characteristics. For example, the KP/BR still has an active hotspot, whereas the OJP and the SR do not. The OJP is remarkable in its compositional monotony across the plateau (the Kwaimbaita geochemical type), with minor compositional variation found at the margins (the Kroenke, Singgalo, and Wairahito types). Shatsky Rise shows more compositional variation and, like the OJP, has a dominant lava type (termed the "normal" type) in the early stages (Tamu Massif), but subsequent eruptions at the Ori and Shirshov massifs comprise isotopically and trace element enriched lavas, likely reflecting a change in mantle source over time. The KP/BR has highly variable basement lava compositions, ranging from lavas slightly enriched above that of normal mid-ocean ridge basalt in the northern portion (close to the South East Indian Ridge) to more enriched varieties to the south and on Broken Ridge, with a continental crust signature present in lavas from the southern and central KP/BR. The OJP and the KP/BR appear to have formed through punctuated magmatic events, whereas the SR was formed by one relatively long, drawn out event. The formation of oceanic LIPs has in many (but not all) cases been synchronous with oceanic anoxic events. This paper focuses on three oceanic plateaus to emphasize the debate surrounding the environmental impact such LIPs may have had, and also highlights the contributions of scientific ocean drilling to our knowledge of oceanic LIP formation and evolution. This new knowledge allows planning for future oceanic LIP drilling.