Moon-forming impactor as a source of Earth's basal mantle anomalies.

Seismic images of Earth's interior have revealed two continent-sized anomalies with low seismic velocities, known as the large low-velocity provinces (LLVPs), in the lowermost mantle1. The LLVPs are often interpreted as intrinsically dense heterogeneities that are compositionally distinct from the surrounding mantle2. Here we show that LLVPs may represent buried relics of Theia mantle material (TMM) that was preserved in proto-Earth's mantle after the Moon-forming giant impact3. Our canonical giant-impact simulations show that a fraction of Theia's mantle could have been delivered to proto-Earth's solid lower mantle. We find that TMM is intrinsically 2.0-3.5% denser than proto-Earth's mantle based on models of Theia's mantle and the observed higher FeO content of the Moon. Our mantle convection models show that dense TMM blobs with a size of tens of kilometres after the impact can later sink and accumulate into LLVP-like thermochemical piles atop Earth's core and survive to the present day. The LLVPs may, thus, be a natural consequence of the Moon-forming giant impact. Because giant impacts are common at the end stages of planet accretion, similar mantle heterogeneities caused by impacts may also exist in the interiors of other planetary bodies.

Compositionally and density stratified igneous terrain in Jezero crater, Mars.

Before Perseverance, Jezero crater's floor was variably hypothesized to have a lacustrine, lava, volcanic airfall, or aeolian origin. SuperCam observations in the first 286 Mars days on Mars revealed a volcanic and intrusive terrain with compositional and density stratification. The dominant lithology along the traverse is basaltic, with plagioclase enrichment in stratigraphically higher locations. Stratigraphically lower, layered rocks are richer in normative pyroxene. The lowest observed unit has the highest inferred density and is olivine-rich with coarse (1.5 millimeters) euhedral, relatively unweathered grains, suggesting a cumulate origin. This is the first martian cumulate and shows similarities to martian meteorites, which also express olivine disequilibrium. Alteration materials including carbonates, sulfates, perchlorates, hydrated silicates, and iron oxides are pervasive but low in abundance, suggesting relatively brief lacustrine conditions. Orbital observations link the Jezero floor lithology to the broader Nili-Syrtis region, suggesting that density-driven compositional stratification is a regional characteristic.

Gravity-dominated Collisions: A Model for the Largest Remnant Masses with Treatment for "Hit and Run" and Density Stratification.

We develop empirical relationships for the accretion and erosion of colliding gravity-dominated bodies of various compositions under conditions expected in late-stage solar system formation. These are fast, easily coded relationships based on a large database of smoothed particle hydrodynamics (SPH) simulations of collisions between bodies of different compositions, including those that are water rich. The accuracy of these relations is also comparable to the deviations of results between different SPH codes and initial thermal/rotational conditions. We illustrate the paucity of disruptive collisions between major bodies, as compared to collisions between less massive planetesimals in late-stage planet formation, and thus focus on more probable, low-velocity collisions, though our relations remain relevant to disruptive collisions as well. We also pay particular attention to the transition zone between merging collisions and those where the impactor does not merge with the target, but continues downrange, a "hit-and-run" collision. We find that hit-and-run collisions likely occur more often in density-stratified bodies and across a wider range of impact angles than suggested by the most commonly used analytic approximation. We also identify a possible transitional zone in gravity-dominated collisions where larger bodies may undergo more disruptive collisions when the impact velocity exceeds the sound speed, though understanding this transition warrants further study. Our results are contrary to the commonly assumed invariance of total mass (scale), density structure, and material composition on the largest remnants of giant impacts. We provide an algorithm for adopting our model into N-body planet formation simulations, so that the mass of growing planets and debris can be tracked.

Spontaneous central venous thrombosis and shunt occlusion following peritoneovenous shunt placement for intractable ascites.

A 43-year-old man had a peritoneovenous shunt inserted for the treatment of chylous ascites secondary to myelofibrosis. Despite being on anticoagulation for superior mesenteric vein thrombosis, he developed shunt dysfunction within two weeks of insertion. Superior venacavography showed multiple filling defects in the right axillary vein, no filling of the right brachiocephalic and right subclavian vein, and thrombotic occlusion of the internal jugular veins bilaterally. The shunt was removed 11 days after insertion, and there was extensive thrombosis of the venous end of the shunt and the compressible pump chamber. Shunt thrombosis is known to occur but remains a rare complication, with 87% of such obstructions being due to a thrombus at the tip of the venous end of the shunt. Extensive thrombosis of the shunt (as in the present case) is very rare.

Suitability for endovascular aneurysm repair in an unselected population.

BACKGROUND: Tertiary referral centres report that up to 60 per cent of patients may be suitable for endovascular repair of abdominal aortic aneurysm (EVAR). The aim of this study was to determine the percentage of abdominal aortic aneurysms (AAAs) presenting to a county-wide vascular service that were suitable for EVAR, and to examine the outcome of subsequent AAA repair in relation to aneurysm morphology. PATIENTS AND METHODS: All patients being assessed for AAA repair between January 1998 and December 1999 underwent spiral computed tomography angiography to determine aneurysm morphology and suitability for EVAR. Subsequent outcome for all patients in the study was recorded in a prospective vascular database. RESULTS: A total of 115 patients was assessed. Sixty-three aneurysms (55 per cent) had one or more absolute contraindications to EVAR, a further 13 (11 per cent) had at least one relative contraindication, and 39 (34 per cent) had no contraindication. Of patients with no absolute contraindication to EVAR, ten underwent successful EVAR, five did not meet recognized criteria for surgery, one awaits EVAR, four remain under observation, one awaits open repair, and 31 underwent open repair without death. CONCLUSION: Only 30 per cent of unselected AAAs presenting to a vascular service are entirely suitable for EVAR; most of these patients can safely undergo open AAA repair. These data suggest that increased use of EVAR is only possible by deploying devices in suboptimal morphology, and in treating patients who would not normally be considered for open AAA repair.

Intrarenal color duplex examination of aortic endograft patients with suprarenal stents.

PURPOSE: To report an experience using intrarenal color duplex ultrasonography (ICDU) to detect high-grade renal artery stenosis in patients who had endovascular repair of abdominal aortic aneurysm (AAA) with suprarenal stent fixation. METHODS: Twenty-eight patients (25 men; mean age 71 years, range 58-83) who had endovascular AAA repair with suprarenal stenting at least 3 months prior to commencement of this study were screened with ICDU. Acceleration time (AT), peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) were measured. The Doppler waveform was quantitatively scored on a scale from 0 to 4. AT >0.07 seconds, RI <0.45, or a Doppler waveform score of 0 or 1 (indicating loss of early systolic peak) were indicative of high-grade renal artery stenosis. RESULTS: Median follow-up was 15.5 months (range 3-34). ICDU was successful in 54 (98%) of 55 kidneys scanned. No AT values exceeded 0.07 seconds, all RIs were >0.45, and no waveforms had loss of early systolic peak, indicating that no patient had evidence of high-grade renal artery stenosis. CONCLUSIONS: ICDU is a simple and affordable method that seems well suited to periodic screening in patients with suprarenal stents. Longer follow-up with a larger number of patients is needed before definite conclusions can be drawn about the effect of suprarenal stenting on renal circulation.

Long-term follow-Up of percutaneous balloon angioplasty in adult aortic coarctation.

PURPOSE: To assess long-term outcomes following percutaneous transluminal angioplasty (PTA) of congenital aortic coarctation in adults. METHODS: Seventeen patients underwent PTA for symptomatic adult coarctation of the aorta. Sixteen patients, with a mean age of 28 years (range 15-60 years), were reviewed at a mean interval after angioplasty of 7.3 years (range 1.5-11 years). Assessment included magnetic resonance imaging (MRI), Doppler echocardiography, and clinical examination. Current clinical measurements were compared with pre- and immediate post-angioplasty measurements. RESULTS: At follow-up 16 patients were alive and well. The patient not included in follow-up had undergone surgical repair and excision of the coarctation segment following PTA. Mean brachial systolic blood pressure for the group decreased from 174 mmHg before angioplasty to 130 mmHg at follow-up (p = 0.0001). The mean gradient had fallen significantly from 50.9 to 17.8 at follow-up (p = 0.001). The average number of antihypertensive drugs required per patient decreased from 0.56 to 0.31 (p = 0.234). No significant residual stenoses or restenoses were seen at MRI. Small but clinically insignificant residual pressure gradients were recorded in all patients using Doppler echocardiography. Complications included one transient ischemic attack at 5 days, one external iliac dissection requiring stent insertion, and a further patient who developed a false aneurysm close to the coarctation site at 12 months which subsequently required surgical excision. CONCLUSION: PTA of adult coarctation is safe and effective in the long term. Although primary stenting has recently been advocated in the treatment of this condition, our results suggest that PTA remains the treatment of choice.

Treatment of murine candidiasis and cryptococcosis with amphotericin B incorporated into egg lecithin-bile salt mixed micelles.

Amphotericin B (AmB) with deoxycholate (Fungizone) and AmB incorporated into mixed micelles (AmB-mixMs) composed of egg lecithin with glycocholate, deoxycholate, or taurocholate were compared as treatments for murine infections. For mice infected with Candida albicans, treatment consisted of a single intravenous injection; for mice infected with Cryptococcus neoformans, treatment consisted of two intravenous injections. The maximal tolerated doses of AmB as Fungizone were 1.25 mg/kg of body weight in mice with candidiasis and 2.5 mg/kg of body weight in mice with cryptococcosis. The AmB-mixMs were nontoxic to mice at doses of 80 and 100 mg/kg of body weight and were therapeutically more active than the maximal tolerated dose of Fungizone in both models of infection. However, when Fungizone or AmB-mixMs were administered at equivalent doses of AmB, AmB-mixMs were more active in treating murine candidiasis, whereas Fungizone was more active in treating murine cryptococcosis.

4-oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus I.

Candida albicans and Cryptococcus neoformans are major causes of systemic fungal infections, particularly in patients with acquired immunodeficiency syndrome. Metabolic labeling studies revealed that these organisms synthesize a small number of N-myristoylproteins, the most prominent being 20-kDa ADP-ribosylation factors (Arfs). C. albicans Arf has approximately 80% identity with the essential Arf1 and Arf2 proteins of Saccharomyces cerevisiae. [3H]Myristic acid analogs with oxygen for -CH2- substitutions at C4, C6, C11, and C13 are incorporated into cellular N-myristoylproteins, phospholipids, and neutral lipids produced by these three yeasts during exponential growth at 30 degrees C in complex media. Analog- and organism-specific differences in the efficiency of labeling of proteins and lipid classes were observed. The effects of oxatetradecanoic acids with oxygen for -CH2- substitutions at C3-C13 on C. neoformans, C. albicans, and S. cerevisiae were assessed during mid-log phase growth at 30 degrees C. A single dose of 3-oxa-, 4-oxa-, 5-oxa- or 6-oxatetradecanoic acid (O3-O6, final concentration = 300 microM) was able to inhibit growth of C. neoformans in the order O4 greater than O5 greater than O3 approximately O6. The other compounds were inactive. 4-Oxatetradecanoic acid was fungicidal, producing a 10,000-fold reduction in viable cell number 1 h after administration and continued suppression of cell growth for 7 h. A clear dose response was observed over a concentration range of 100-300 microM. 4-Oxatridecanoic acid was 100-fold less potent in reducing cell viability than 4-oxatetradecanoic acid but more potent than 5-oxatridecanoic acid. O4 produced approximately 10-100-fold reductions in the viability of C. albicans and S. cerevisiae at 300-500 microM, respectively, whereas O5 and O6 were less active. Since N-myristoylation of the Pr55gag polyprotein precursor produced by human immunodeficiency virus I (HIV-I) is essential for its assembly, we also assessed the antiviral effects of 4-oxatetradecanoic acid. O4 is able to produce a 50% reduction in the replication of HIV-I in acutely infected human T-lymphocyte cell lines at a concentration of 18 microM. Together, these data suggest that (i) the position of the oxygen for methylene substitution is a critical determinant of the fungicidal activity of O4 and (ii) NMT may be an attractive therapeutic target for treating opportunistic fungal infections in patients infected with HIV-I.

Temperature-sensitive variants of Histoplasma capsulatum isolated from patients with acquired immunodeficiency syndrome.

Histoplasma capsulatum isolates from three St. Louis area AIDS patients with disseminated histoplasmosis were found to be closely related to the temperature-sensitive, previously unique, Downs strain based on growth phenotype and restriction fragment length polymorphisms (RFLP) involving mitochondrial DNA, ribosomal DNA, and the yps-3 gene. H. capsulatum isolates from five non-AIDS patients in the St. Louis area with disseminated histoplasmosis or chronic pulmonary histoplasmosis had the growth phenotype and RFLP pattern characteristic of most strains isolated from other regions of the USA.

In vitro and in vivo activities of Sch 39304, fluconazole, and amphotericin B against Histoplasma capsulatum.

The antifungal activities of amphotericin B and two triazoles, Sch 39304 and fluconazole, were tested against Histoplasma capsulatum. In this study Sch 39304 compared favorably with amphotericin B in treating histoplasmosis in normal and leukopenic mice, whereas fluconazole was much less active. The differences in the efficacies of the triazoles appeared to be due to differences in their pharmacokinetics and the dosage schedule that was used. For amphotericin B there was a good correlation between in vitro and in vivo efficacy, but this was not true of the triazole derivatives. These results further demonstrate that, with the methods used in this study, in vitro susceptibility testing of triazoles may not be predictive of in vivo activity against isolates of H. capsulatum.

Comparison of fluconazole with amphotericin B in treatment of histoplasmosis in normal and immunosuppressed mice.

The activities of fluconazole and amphotericin B against Histoplasma capsulatum were investigated. The minimum inhibitory concentrations ranged from 0.12 to 0.47 microgram/mL for amphotericin B and from 16 to 250 micrograms/mL for fluconazole. Fluconazole given orally twice a day for 6 consecutive days compared favorably with amphotericin B given intraperitoneally once every other day for a total of six doses in the treatment of histoplasmosis in normal and leukopenic mice.

DNA probe for the identification of Histoplasma capsulatum.

A 1.85-kilobase HindIII nuclear DNA probe from Histoplasma capsulatum G217B detected polymorphic restriction fragments within whole-cell DNA from different clinical isolates of H. capsulatum, consistent with the previous system of classification. The probe failed to hybridize to DNA from Blastomyces dermatitidis, Candida spp., Saccharomyces cerevisiae, Sepedonium chrysospermum, and Chrysosporium keratinophilum under low-stringency conditions and therefore may have value as a diagnostic reagent to identify H. capsulatum.

Use of mitochondrial and ribosomal DNA polymorphisms to classify clinical and soil isolates of Histoplasma capsulatum.

We have developed an improved scheme for the classification of environmental and clinical isolates of Histoplasma capsulatum that is based on analysis of mitochondrial DNA (mtDNA) and ribosomal DNA (rDNA). Strains were initially divided into mtDNA groups according to restriction digests of whole-cell DNA and Southern hybridization with cloned mtDNA probes. Strains within a mtDNA class could be further grouped by polymorphisms in rDNA. The majority of soil and clinical isolates from the United States had identical mtDNA patterns; however, rDNA polymorphisms were common in both types of isolates. The combination of mtDNA and rDNA typing described in this report will be useful in resolving questions concerning the epidemiology of H. capsulatum infections.

Effects of Histoplasma capsulatum on murine macrophage functions: inhibition of macrophage priming, oxidative burst, and antifungal activities.

Histoplasma capsulatum yeast cells fail to trigger an oxidative burst response in normal murine macrophages. The results of this study, in which an in vitro assay of macrophage antifungal effects was used, extend these findings. During 18 h of incubation, unprimed elicited murine macrophages inhibited H. capsulatum growth only when macrophages were present in great excess. Gamma interferon (IFN-gamma)-primed macrophages showed enhanced fungal growth inhibition but a similar requirement for an excess of phagocytes. Macrophages containing heat-killed H. capsulatum exhibited diminished antifungal effects toward viable H. capsulatum and Saccharomyces cerevisiae cells. Parallel experiments showed no comparable effect of ingested latex particles on macrophage antifungal activity. Using chemiluminescence as a measure of the oxidative burst, we found that macrophages primed in vitro with IFN-gamma alone failed to exhibit a significant response to triggering by H. capsulatum yeast cells unless a second priming agent (tumor necrosis factor alpha or bacterial lipopolysaccharide) was added to IFN-gamma. Furthermore, macrophage priming with single agents was blocked by the prior ingestion of heat-killed H. capsulatum. These studies provide evidence that ingestion of H. capsulatum yeast cells can induce a prompt and enduring deactivation of murine macrophages.

Comparative in vitro activity of LY121019 and amphotericin B against clinical isolates of Candida species.

LY121019 and amphotericin B were equally active in vitro against most clinical isolates of Candida albicans and Candida tropicalis. Higher concentrations of LY121019 were required for inhibition of Candida glabrata. Other Candida species were inhibited by amphotericin B but not by LY121019.

Comparison of fluconazole and amphotericin B in treating histoplasmosis in immunosuppressed mice.

Fluconazole (UK-49,858) was compared with amphotericin B in treating histoplasmosis in female AKR mice immunosuppressed with either cyclophosphamide or cortisone. Both drugs protected animals from a lethal challenge with Histoplasma capsulatum, but neither regimen resulted in cures since viable organisms were cultured from spleens of survivors.