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Occurrences of alkaline and carbonatite rocks with high concentrations of rare earth elements (REE) are a defining feature of Precambrian geology in the Mojave Desert of southeastern California. The most economically important occurrence is the carbonatite stock at Mountain Pass, which constitutes the largest REE deposit in the United States. A central scientific goal is to understand the genesis of the carbonatite ore body in the context of widespread REE‐rich igneous activity. A swarm of mafic alkaline (shonkinite) dikes has been mapped and sampled at Bobcat Hills, 65 km southeast of the Mountain Pass mine. Whole‐rock geochemistry and zircon geochronology demonstrate a clear affinity to the ca. 1.4 Ga Mountain Pass intrusive system. Bobcat Hills dikes have comparably high REE concentrations (La ∼1,000× chondritic) and an error‐weighted mean 207Pb/206Pb zircon crystallization age of 1,426 ± 2 Ma (2σ). Unlike the alkaline intrusions at Mountain Pass, which have abundant inherited zircon from Paleoproterozoic basement rocks and crustally influenced oxygen isotope compositions (δ18Ozircon = 6.5–7.5‰), the Bobcat Hills dikes lack any evidence of crustal assimilation and have oxygen isotope values that overlap a mantle range (Bobcat Hills average δ18Ozircon = 5.6 ± 0.3‰). The dikes were a high‐temperature, early center of mafic alkaline magmatism in the Mojave Desert that serve as a snapshot of melt generation from a spatially extensive, metasomatized mantle source. We propose that modification of the crust over many tens of Myr at Mountain Pass created an environment that favored crustal assimilation and enabled ascent of late‐stage, REE‐rich carbonatite magmas. Key Points: The Bobcat Hills site expands the distribution of REE‐rich mafic alkaline magmatism 65 km southeast of the Mountain Pass mineShonkinite dikes at Bobcat Hills are physically and chemically similar to mafic intrusions at Mountain Pass and have comparably high REEBobcat Hills was an early center of REE‐rich magmatism in the Mojave Desert, with a zircon U‐Pb crystallization age of 1,426 ± 2 Ma [ABSTRACT FROM AUTHOR]

The Sulphide Queen carbonatite deposit at Mountain Pass in southeast California is a world class rare earth element (REE) resource. This study images electrical resistivity structure of the REE deposit and surrounding area to characterize resources under cover. An east-west elongated grid (35 × 15 km) of 65 wideband magnetotelluric stations spanning from eastern Shadow Valley to eastern Ivanpah Valley were collected and modeled in three-dimensions (3-D). Gravity, aeromagnetic, and geologic data are used to inform interpretation of structures in the resistivity model, including the following observations. Shadow Valley is filled with conductive sediment that locally dips southward to a depth of 1 km. The Kingston Range-Halloran Hills detachment fault dips westward at ~15 degrees. The REE deposit is a moderate low resistivity zone dipping southwest to a possible depth of ~1 km, and is bounded by the North and South faults and bisected by the Middle fault. Ivanpah Dry Lake is underlain by a north striking southward dipping sedimentary basin. Two possible zones of mineralization are observed in Ivanpah Valley, one along the western edge of Ivanpah Dry Lake and one on the western edge of valley along a new inferred fault. The brittle-ductile transition is imaged at ~10 km below mean sea level. No deep electrically conductive structures are imaged to be related to the REE deposit likely due to the complex geologic history of the Mojave terrane. Future studies should regional target Proterozoic rocks and search within for geophysical signatures similar to Mountain Pass. [ABSTRACT FROM AUTHOR]

The Hayward fault in California's San Francisco Bay area produces large earthquakes, with the last occurring in 1868. We examine how physics‐based dynamic rupture modeling can be used to numerically simulate large earthquakes on not only the Hayward fault, but also its connected companions to the north and south, the Rodgers Creek and Calaveras faults. Equipped with a wealth of images of this fault system, including those of its 3D geology and 3D geometry, in addition to inferences about its interseismic creep‐rate pattern and rock‐friction behavior, we use a finite‐element computer code to perform 3D dynamic earthquake rupture simulations. We find that the rock properties affect the locations and amount of slip produced in our simulated large earthquakes. Crucial factors that control rupture behavior in our modeling are the earthquake nucleation locations, the fault geometry, and the data that reveal where the fault system is creeping or locked. Our findings suggest that large Rodgers Creek‐Hayward‐Calaveras‐Northern Calaveras (RC‐H‐C‐NC) fault‐system earthquakes may result from dynamic rupture that starts in a locked part of the fault system, but is then stopped by the creeping parts, leading to high‐magnitude‐6 earthquakes; or, from dynamic rupture that starts in a locked part of the fault system, then cascades through some of the creeping parts, leading to magnitude‐7 earthquakes. Plain Language Summary: The San Francisco Bay area has experienced large earthquakes in the past and is likely to experience large earthquakes in the future. Although the San Andreas fault is the best‐known earthquake generator, other San Francisco Bay area faults, including some that slowly move (creep) all of the time are also known to be hazardous. We use computer modeling to simulate large earthquakes on the Hayward fault, and its connected companions to the north and south, the Rodgers Creek and Calaveras faults. In our computer simulations, we include information about the rock properties, rock‐friction, and fault geometry, in addition to inferences about where the faults creep. We find that the earthquake nucleation location, the fault geometry, and the pattern of fault creep, are most important. Our findings suggest that large earthquakes on these faults may result from a fast‐slipping rupture that starts in a locked part of the faults, but is then stopped by the slowly slipping parts of the faults, leading to high‐magnitude‐6 earthquakes, or, from fast‐slipping rupture that starts in a locked part of the faults, then cascades through some of the creeping‐fault parts, leading to magnitude‐7 earthquakes. Key Points: We simulated large earthquakes on the Rodgers Creek‐Hayward‐Calaveras fault system, CaliforniaOur spontaneous rupture (dynamic rupture) simulations included the 3D fault geometry, 3D rock properties, and creeping‐fault patchesThe resulting earthquakes are most affected by which fault they start on, the fault geometry, and the pattern of interseismic fault creep [ABSTRACT FROM AUTHOR]

Summary: Cryptorchidism is one of the most common congenital disorders in boys, and several genetic, hormonal, and environmental factors have been proposed as possible causes for this genitourinary defect. Genetic factors have been intensively searched, but relatively few pathogenic variants have been described. Cryptorchidism is a frequent finding in patients with RASopathies, a group of syndrome caused by mutations in genes of the Ras/MAPK pathway. Our aim was to determine whether patients with isolated cryptorchidism (IC) exhibit Ras/MAPK pathway gene variants associated with RASopathies. Two hundred thirty‐nine patients with IC were recruited after orchidopexy. Determination of Ras/MAPK pathway gene variants was performed by high‐resolution melting (HRM) analysis followed by sequencing. Restriction or allele‐specific amplification assay was applied to (i) variant confirmation; (ii) search in healthy controls; and (iii) segregation analysis. Controls correspond to 100 healthy Chilean adults without a history of cryptorchidism. Molecular analysis showed one synonymous substitution (BRAF_p.Q456Q) in two patients and four missense substitutions (SOS1_ p.R497Q, BRAF_ p.F595L, NRAS_ p.T50I, and MAP2K2_ p.Y134C) in five patients. Our results suggest that some patients with isolated cryptorchidism, but with no evidence of dysmorphic features suggestive of RASopathies, may harbor Ras/MAPK pathway gene alterations. [ABSTRACT FROM AUTHOR]

Background: Treatment for severe acute kidney injury (AKI) typically involves the use of acute kidney replacement therapy (AKRT) to prevent or reverse complications., Methodology: We aimed to determine the prevalence of successful discontinuation of AKRT and its predictive factors. A retrospective cohort study was performed with 316 patients hospitalized at a public Brazilian university hospital between January 2011 and June 2020., Results: Success and hospital discharge were achieved for most patients (85% and 74%, respectively). Multivariable logistic regression analysis showed that C-reactive protein (CRP), urine output, and need mechanical ventilation at the time of interruption were variable associated with discontinuation success (OR 0.969, CI 0.918-0.998, p = 0.031; OR 1.008, CI 1.001-1.012, p = 0.041 and OR 0.919, CI 0.901-0.991, p = 0.030; respectively), while the absence of comorbidities such as chronic kidney disease (OR 0.234, CI 0.08-0.683, p = 0.008), cardiovascular disease (OR 0.353, CI 0.134-0.929, p = 0.035) and hypertension (OR 0.278, CI 0.003-0.882, p = 0.009), as well as pH values at the time of AKRT indication (OR 1.273, CI 1.003-1.882, p = 0.041), mechanical ventilation at the time of interruption (OR 0.19, CI 0.19-0.954, p = 0.038) and successful discontinuation (OR 8.657, CI 3.135-23.906, p < 0.001) were identified as variables associated with hospital discharge., Conclusion: These results show that clinical conditions such as comorbidities, urine output, and mechanical ventilation, and laboratory variables such as pH and CRP are factors associated with hospital discharge and AKRT discontinuation success, requiring larger studies for confirmation., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Around 5% of coronavirus disease 2019 (COVID-19) patients develop critical disease, with severe pneumonia and acute respiratory distress syndrome (ARDS). In these cases, extracorporeal membrane oxygenation (ECMO) may be considered when conventional therapy fails. This study aimed to describe the clinical characteristics and in-hospital outcomes of COVID-19 patients with ARDS refractory to lung-protective ventilation and prone positioning on ECMO support, as well as to review the available literature on ECMO use and COVID-19 patients' outcome. Patients from this case series were selected from the Brazilian COVID-19 Registry. From the 7646 patients included in the registry, only eight received ECMO support (0.1%), in four hospitals. The median age of the entire sample was 59 (interquartile range 54.2-64.4) years old and 87.5% were male. Hypertension (50.0%), diabetes mellitus (50.0%) and obesity (37.5%) were the most frequent comorbidities. The indications for ECMO were PaO 2 /FiO 2 ratio <80 mm Hg for more than 6 h or PaO 2 /FiO 2 ratio <60 mm Hg for more than 3 h. The mortality rate was 87.5%. In conclusion, in this case series of COVID-19 patients with ARDS refractory to conventional therapy who received ECMO support, a very high mortality was observed. Our findings are not different from previous studies including a small number of patients; however, there is a huge difference from Extracorporeal Life Support Organization results, which encourages us to keep looking for improvement., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

We report the case of a 14 years and 8 months girl, who is the first child of nonconsanguineous parents, with short stature, obstructive hypertrophic cardiomyopathy, multiple facial lentigines, high and wide forehead, downslanting palpebral fissures, low-set ears, short neck, and pectus excavatum; all features suggestive of Noonan syndrome with multiple lentigines (NSML). In addition, the patient exhibited craniosynostosis. Molecular analysis of rats sarcoma (RAS)/mitogen-activated protein kinase (MAPK) pathway genes with high-resolution melting curve analysis followed by sequencing showed a RAF1 amino acid substitution of valine to glycine at position 263 (p.V263G). The present report provides clinical data regarding the first association of a RAF1 variant and craniosynostosis in a patient with clinical diagnosis of NSML., (© 2019 Wiley Periodicals, Inc.)

We have previously demonstrated that sickle cell disease (SCD) patients maintain normal global systemic and cerebral oxygen delivery by increasing cardiac output. However, ischemic end-organ injury remains common suggesting that tissue oxygen delivery may be impaired by microvascular dysregulation or damage. To test this hypothesis, we performed fingertip laser Doppler flowmetry measurements at the base of the nailbed and regional oxygen saturation (rSO 2 ) on the dorsal surface of the same hand. This was done during flow mediated dilation (FMD) studies in 26 chronically transfused SCD, 75 non-transfused SCD, and 18 control subjects. Chronically transfused SCD patients were studied prior to and following a single transfusion and there was no acute change in rSO 2 or perfusion. Laser Doppler estimates of resting perfusion were 76% higher in non-transfused and 110% higher in transfused SCD patients, compared to control subjects. In contrast, rSO 2 was 12 saturation points lower in non-transfused SCD patients, but normal in the transfused SCD patients. During cuff occlusion, rSO 2 declined at the same rate in all subjects suggesting similar intrinsic oxygen consumption rates. Upon cuff release, laser doppler post occlusive hyperemia was blunted in SCD patients in proportion to their resting perfusion values. Transfusion therapy did not improve the hyperemia response. FMD was impaired in SCD subjects but partially ameliorated in transfused SCD subjects. Taken together, non-transfused SCD subjects demonstrate impaired conduit artery FMD, impaired microcirculatory post-occlusive hyperemia, and resting hypoxia in the hand despite compensated oxygen delivery, suggesting impaired oxygen supply-demand matching. Transfusion improves FMD and oxygen supply-demand matching but not microcirculation hyperemic response., (© 2019 Wiley Periodicals, Inc.)

Vancomycin is an antibiotic used in the treatment of infections caused by multidrug-resistant Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus. In the last decades, vancomycin has been widely used in hospital environments due to the increasing incidence of sepsis and septic shock. Sepsis may lead to multiple organ failure; it is considered a risk factor for the development of acute kidney injury (AKI), with an overall mortality rate of around 45%, which can reach the surprising rate of 70% with the combination of AKI and sepsis. Considering the high mortality rate of sepsis and its related costs of hospitalization and treatment, specific measures should be adopted, such as early-goal treatment protocols: proper and early administration of antimicrobials, fluids, vasoactive drugs and transfusion support. Besides the careful selection of the antimicrobial, another concern related to critically ill patients is the proper dose of the antimicrobial, since pharmacokinetic changes are observed due to drug absorption, distribution, metabolism and elimination. Gram-positive pathogens are very common in hospitalized patients with septic shock, so vancomycin has been the antimicrobial of choice for more than 60 years. However, discussions about its dosage, administration and monitoring are extremely important, considering the risk of nephrotoxicity and the emergence of resistant S. aureus. This narrative review aims to discuss controversial aspects related to the efficacy and safety of vancomycin, correlating them with data available in the literature and identifying knowledge gaps in guide future lines of research., (© 2019 John Wiley & Sons Australia, Ltd.)

Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. This study aimed to evaluate the incidence of thrombotic obstruction of tunneled CVC in HD patients and the efficacy of occlusion treatment with alteplase use, and identify factors associated with thrombotic occlusion. It was a prospective cohort study performed in two centers which evaluated the diagnosis and treatment of thrombotic occlusion of CVC in HD patients for 24 consecutive months. The catheter occlusion was defined as the difficulty infusing or withdrawing fluid from their paths. Alteplase dose was infused to fill the lumen of the occluded catheter and remained for 50 min. As there was no obstruction of the catheter, the procedure was repeated. Three hundred and thirty-nine CVC in 247 patients were evaluated and followed, totalling 67,244 CVC-days. One hundred fifty-seven patients had only one CVC, 88 patients had two CVC during the study, and two patients had three CVC. The median age was 58 (47-66) years, patients were predominantly men (54%), with diabetic nephropathy as the main cause of chronic kidney disease (44%), the internal jugular vein as the main site of implantation (82%), and duration of dialysis before CVC implantation of 119 (41.5 to 585.5) days. Eight hundred and fifteen occlusion episodes were diagnosed (12 episodes/1000 CVC-days), with primary success with alteplase in 596 episodes (77%) and secondary in 81 cases (10%). In 99 episodes (13%), success was not achieved after the second dose of alteplase. Two hundred and thirty CVC were removed during the study and the removal causes were arteriovenous fistula use in 88 patients (38.3%), infectious and mechanical complications in 89 (38.7%) and 21 (9.1%), respectively, and others (transplantation, transfer, or death) in 32 patients (13.9%). Adverse effects were also not observed. In the multivariate analysis, we identified the greatest number of days with CVC (OR = 1.02, CI = 1.01-1.04, P = 0.004), the presence of diabetes (OR = 1.560, CI = 1.351-1.894, P = 0.015), and exit site infection (ESI) (OR = 1.567 CI = 1347-1926, P = 0.023) as factors associated with obstruction. Thrombotic occlusion showed frequent mechanical complication in CVC of HD patients. We observed 12 episodes of obstruction per 1000 CVC-days, with a high success rate after alteplase use (87%). In the multivariate analysis, the time with CVC, the presence of diabetes, and ESI were identified as variables associated with thrombotic obstruction., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Prolonged intermittent renal replacement therapy (PIRRT) has emerged as an alternative to continuous renal replacement therapy in the management of acute kidney injury (AKI) patients. This trial aimed to compare the dialysis complications occurring during different durations of PIRRT sessions in critically ill AKI patients. We included patients older than 18 years with AKI associated with sepsis admitted to the intensive care unit and using noradrenaline doses ranging from 0.3 to 0.7 µg/kg/min. Patients were divided into two groups randomly: in G1, 6-h sessions were performed, and in G2, 10-h sessions were performed. Seventy-five patients were treated with 195 PIRRT sessions for 18 consecutive months. The prevalence of hypotension, filter clotting, hypokalemia, and hypophosphatemia was 82.6, 25.3, 20, and 10.6%, respectively. G1 was composed of 38 patients treated with 100 sessions, whereas G2 consisted of 37 patients treated with 95 sessions. G1 and G2 were similar in male predominance (65.7 vs. 75.6%, P = 0.34), age (63.6 ± 14 vs. 59.9 ± 15.5 years, P = 0.28) and Sequential Organ Failure Assessment score (SOFA; 13.1 ± 2.4 vs. 14.2 ± 3.0, P = 0.2). There was no significant difference between the two groups in hypotension (81.5 vs. 83.7%, P = 0.8), filter clotting (23.6 vs. 27%, P = 0.73), hypokalemia (13.1 vs. 8.1%, P = 0.71), and hypophosphatemia (18.4 vs. 21.6%, P = 0.72). However, the group treated with sessions of 10 h were refractory to clinical measures for hypotension, and dialysis sessions were interrupted more often (9.5 vs. 30.1%, P = 0.03). Metabolic control and fluid balance were similar between G1 and G2 (blood urea nitrogen [BUN]: 81 ± 30 vs. 73 ± 33 mg/dL, P = 1.0; delivered Kt/V: 1.09 ± 0.24 vs. 1.26 ± 0.26, P = 0.09; actual ultrafiltration: 1731 ± 818 vs. 2332 ± 947 mL, P = 0.13) and fluid balance (-731 ± 125 vs. -652 ± 141 mL, respectively) . In conclusion, intradialysis hypotension was common in AKI patients treated with PIRRT. There was no difference in the prevalence of dialysis complications in patients undergoing different durations of PIRRT., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Despite their propensity for significant infectious and mechanical complications, tunneled central venous catheters (CVCs) have become a common means of vascular access in the world for patients requiring chronic hemodialysis for end-stage renal disease. The objective of this study was to explore if cryopreserved solutions of the thrombolytic agent alteplase could be used as an effective, safe, and economically reasonable alternative in hemodialysis patients with occluded tunneled CVC. Patients requiring chronic hemodialysis and presenting with occluded tunneled CVC received a sufficient volume of the alteplase solution to fill the occluded catheter. To make alteplase economically feasible, it was diluted to 1-mg/mL aliquots and they were stored at -20°C until use. Eighty-one patients accounting for 179 attempted clearances were assessable for efficacy. One hundred forty-seven (82.1%) of the 179 catheter clearance attempts resulted in successful catheter clearance after one dose. Twenty-seven (15.1%) of all occluded CVCs were successful after two doses whereas five (2.8%) were not. No adverse events were reported. Cryopreserved 1-mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVC for hemodialysis patients., (Copyright © 2013 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)